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 Antiviral Agents - Antimicrobial Chemotherapy, 5th Edition

Antimicrobial Chemotherapy, 5th Edition

Part 1 - General Properties of Antimicrobial Agents

Chapter 6

Antiviral Agents

Viruses are almost as versatile as bacteria in the range of diseases they can cause. Vertebrates, insects, plants, and even bacteria are all open to attack. Some viruses of vertebrates (arboviruses) develop in and are transmitted by mosquitoes or other arthropods; others—rabies is a good example—can infect a wide range of mammalian hosts. In general, however, viruses are highly specific in their host range.

All viruses are obligate intracellular parasites; that is, they replicate only within living cells and cannot usually survive for long outside the host cell. Selectivity usually extends not only to the host, but also to the type of cell within the host, as viruses only infect cells that express appropriate receptors on their surface. The preference of a virus for certain types of cell is known as the tropism of the virus, and this often accounts for the characteristic clinical manifestations of particular viral infections. Thus, some viruses preferentially infect liver cells, giving rise to hepatitis.

Most viruses that infect man gain entry to the body by adsorption to superficial cells of the mucous membranes of the respiratory, intestinal, and genital tracts, or of the conjunctivae. Others find their way in through damaged skin, insect bites, or direct inoculation. Intact skin is normally impermeable to viruses, although wart virus is an exception.

The principal types of virus causing human disease are listed in Table 6.1.

Properties of viruses

Viruses are deceptively simple. Sizes range from about 20 nm (parvovirus) to 300 nm (poxvirus); consequently, even the biggest viruses fall barely within the limits of resolution of conventional light microscopy and the electron microscope must be used to visualize them.

Complete virus particles (virions) consist of a nucleic acid core (the viral genome), surrounded by a few proteins, and possibly a lipid envelope. The nucleic acid may be DNA or RNA (never both), single or double stranded, circular or linear, continuous or segmented. This provides all the information needed for viral replication once it is released within the host cell. The proteins serve a number of functions. The capsid, or protein coat surrounding the nucleic acid consists of repeating structural units made up of one to three different protein molecules that are generally arranged in helical or icosahedral symmetry. The nucleic acid surrounded by its capsid is referred to as the nucleocapsid of the virus. Many viral proteins have enzymatic properties. These include polymerases and proteases that are necessary for replication and assembly of viral particles. Proteins protruding from the surface coat of the virus act as ligands that will bind to cellular receptors during the first stage of infection of a cell. The lipid envelope possessed by some viruses is derived from membranes of the host cell.

Table 6.1 Principal types of virus causing human disease

Mode of transmission

RNA Viruses

Influenza A and B viruses

Mumps virus

Measles virus

Respiratory syncytial virus

Bronchiolitis (especially babies)

Human metapneumovirus

Bronchiolitis (especially babies)

Parainfluenza viruses

Croup; bronchiolitis (especially babies)

Rabies virus

Bite of rabid animal

Lassa virus

Lassa fever

Respiratory/rodent reservoir

Rubella virus

German measles (rubella)

Many arboviruses

Yellow fever

Arthropod vectors

Hepatitis C virus

Enteroviruses: polio

Meningitis; paralysis

Coxsackie A and B

Hepatitis A virus

Infectious hepatitis

Human immunodeficiency viruses

Human T-cell lymphotropic viruses

T-cell leukaemia; lymphoma

Infantile diarrhoea

Norovirus (Norwalk virus)

Human coronavirus

Severe acute respiratory syndrome (SARS)

DNA Viruses

Smallpox (now eradicated)

Mainly respiratory

Smallpox vaccine

Molluscum contagiosum

Skin disease

Skin disease

Contact with sheep

Herpes simplex virus types 1 and 2

Cold sores; genital herpes

Varicella zoster

Chickenpox; shingles

Non-specific illness

Close contact/kissing

Epstein-Barr virus

Glandular fever

Saliva, e.g. kissing

Human herpesvirus type 6

Roseola infantum (sixth disease)

Human herpesvirus type 7

Not known

Human herpesvirus type 8

Kaposi's sarcoma

Many serotypes

Conjunctivitis; pharyngitis; infantile diarrhoea

Cervical cancer; Warts

Hepatitis B virus

Serum hepatitis

Parvovirus B19

Erythema infectiosum (fifth disease)

Targets for antiviral drugs

Virus infection of and replication within cells proceeds via a number of distinct steps, each of which, theoretically, provides a possible target for attack (Fig. 6.1). Although the exact details of these steps vary between different viruses, they can be broadly summarized as follows:

  • Adsorption to the cell surface.This involves a specific interaction between proteins (ligands) on the surface of the virus, with receptors on the surface of the cell. The nature of the viral ligands and cellular receptors is known in great detail for some viruses (e.g. the gp120 of human immunodeficiency virus (HIV) and the CD4 molecule on T lymphocytes), but not at all for others.
  • Uptake into the host cell.Some viruses can enter cells by fusion of their own outer lipid membrane with the plasma membrane of the cell, resulting in release of viral nucleocapsid into the cell cytoplasm. In other cases, the process of translocation of the viral particle from the outside of the cell to the inside is very poorly understood.
  • Uncoating of the viral genome.The viral nucleic acid must be released from its capsid before replication. This process may be mediated by cellular lysosomal enzymes.
  • Macromolecular synthesis.Within the cell, multiple copies of the viral genome are made, and mRNA derived from the virus is translated into multiple copies of the proteins encoded by the viral genome. Many viruses use enzymes present within the host cell to perform these activities, but some carry their own enzymes for certain synthetic processes that are not present within the host cell. A good example is HIV, which copies its RNA genome into a DNA intermediate. Since host cells are not able to convert RNA into DNA, the necessary reverse transcriptase must be encoded by the HIV genome itself.
  • Assembly.Before final assembly into new viral particles, viral proteins may be modified by host cell processes such as glycosylation or phosphorylation.
  • Release.The infected cell has by now become little more than a viral factory and complete viral particles may be released by destruction of the cell, or by continuous export through the cell membrane.

Fig. 6.1 Schematic representation of the virus replication cycle within the host cell, showing the stages that are theoretically open to inhibition by antiviral agents.

Virus-cell interactions

The viral replication cycle described above is representative of an acute viral infection: virus enters the cell, replicates, disrupts normal cellular function, and is released, often resulting in cell death. However, viruses may interact with cells in other ways. Some viruses can undergo latency within cells: the viral genome is present within the cell, and may even become incorporated into the host cell chromosomes, but no replication of the genome occurs, and few, if any, viral proteins are synthesized. The latent virus may cause the cell no harm, but it has the propensity, under certain conditions, to become reactivated, with consequent viral replication and damage to the cell.

Another form of virus-cell interaction is chronic or persistent infection. In this, there is a steady but low-level production and release of virus, but the host cell is able to survive. However, host cell function may be impaired, and the expression of viral antigens on the cell surface can lead to a chronic inflammatory state as in chronic infection of hepatocytes with hepatitis B virus leading to chronic active hepatitis.

A further potential consequence of virus-cell interaction is transformation, whereby virus infection leads to uncontrolled cell division, resulting in an immortal cell line. For example, Epstein-Barr virus infection of B lymphocytes in vitro results in stimulation of cell division, and the establishment of a continuous lymphoblastoid cell line. The molecular mechanisms underlying this process, and possible means of interfering with them, are of great interest, since several viruses, including Epstein-Barr virus, have been implicated in initiating malignant change in vivo.

Limitations of antiviral therapy

Although all stages of the cycle of virus replication are potential targets for antiviral drugs, the intimate relationship between the virus and its host cell means that the design or discovery of compounds that are selectively toxic for the virus is beset with considerable problems. Moreover, antiviral therapy may be at a disadvantage for quite a different reason: in many viral diseases initial infection and spread is commonly asymptomatic and the onset of illness, often at the peak of viral multiplication, occurs when the host defences have been fully mobilized. Unless the patient is immunodeficient in some way, these defences are usually quite able to deal with the infection unassisted. Consequently, initiation of antiviral therapy at the onset of symptoms may have little influence on the course of the disease.

Viruses that undergo latency pose a further problem. Unless the latently infected cells can be killed or removed, the virus cannot be eliminated from the patient. Achieving such elimination by therapeutic intervention is a daunting task, as there are no virus-specific metabolic processes occurring in those cells, and there is no expression of viral antigens on the cell surface against which an immune response could be mounted.

Despite these discouraging considerations, significant progress has been achieved in the development of antiviral compounds and an increasing number of antiviral agents is now in regular use (Table 6.2). Many are nucleoside analogues that interfere with viral replication, but other targets have been successfully exploited. Much research emphasis has been concentrated on agents that act to inhibit the replication of HIV (see Chapter 7).

Table 6.2 Principal antiviral agents (other than anti-HIV agents) in present use

Mode of action

Route of administration

Herpes simplex;

Nucleoside analogue

Oral; topical; intravenous

Adefovir dipivoxil

Hepatitis B

Nucleotide analoguea

Influenza A

Uncoating of virus

Nucleotide analogue

Hepatitis B

Nucleoside analogue

Herpes simplex Varicella-zoster

Nucleoside analoguea

Anti-sense oligonucleoside

DNA polymerase inhibitor

Nucleoside analogue

Chronic hepatitis

Chronic hepatitis

Nucleoside analogue; reverse transcriptase inhibitor

Respiratory syncytial virus
Chronic hepatitis

Nucleoside analogue

Herpes simplex;

Nucleoside analoguea

Nucleoside analoguea

Neuraminidase inhibitor

Neuraminidase inhibitor

Pro-drug formulation.

Properties of antiviral agents

Aciclovir was the first antiviral drug with selective toxicity: it inhibits the replication of certain viruses while exhibiting virtually no toxic side effects on host cells. Structurally, it is acycloguanosine (Fig. 6.2), an analogue of the purine nucleoside, guanosine, in which the deoxyribose moiety has lost its cyclic configuration. Aciclovir itself is inactive; in order to achieve its antiviral effect, it must first be phosphorylated to the triphosphate form within the infected cell. Although the second and third phosphate groups are added by cellular enzymes, the initial phosphorylation step is accomplished by a viral thymidine kinase, specified by herpes simplex and varicella zoster viruses; the cellular form of this enzyme is much less efficient in producing aciclovir monophosphate. This unique feature is the basis for the selective toxicity of aciclovir, for two reasons: first, it means that the active form of the drug is produced only in virally infected cells; secondly, by the law of mass action, once the equilibrium

Fig. 6.2 Structures of deoxyguanosine and three antiviral agents that act as analogues of the nucleoside: aciclovir, ganciclovir, and penciclovir.

aciclovir [left harpoon over right harpoon] aciclovir monophosphate

is shifted to the right within an infected cell, more free aciclovir will enter the cell from the extracellular space, thus resulting in concentration of the drug precisely where it is needed: in the infected cell.

Mode of action

As an analogue of guanosine triphosphate, aciclovir triphosphate is incorporated into the growing DNA chain and causes chain termination, since it lacks the 3′-hydroxyl group necessary to form the 5′-3′ phosphodiester

linkage with the next base. Aciclovir triphosphate is also a direct inhibitor of viral DNA polymerase.

It is theoretically possible for a virus to become resistant to aciclovir in several ways:

  • Strains of virus that lack the thymidine kinase enzyme, known as TK-mutants, are inherently resistant to the drug, as they cannot generate the active form.
  • Mutations in the TKgene may alter the thymidine kinase molecule, such that it becomes unable to perform the first phosphorylation step.
  • Alterations in viral DNA polymerase may reduce the ability of the enzyme to bind aciclovir triphosphate, and thereby to escape the inhibitory properties of the drug.

All these mechanisms occur in the laboratory and in nature. However, TK- strains, and those with altered thymidine kinases appear to exhibit reduced virulence, and DNA polymerase mutants are the ones that cause most clinical difficulties. These emerge particularly in immunocompromised patients including those with HIV infection, in whom recurrent herpes simplex virus infections cause frequent and extensive disease necessitating prolonged treatment with aciclovir.

Aciclovir represents a prime example of what a good antiviral drug should be. It has potent antiviral activity, but is virtually free of toxic side effects. It can be life saving in certain infections, and in others can significantly decrease morbidity (see Chapter 27). However, it is relatively poorly absorbed when given orally, and in life-threatening infection it must be given intravenously.

Analogues of aciclovir

Several structural analogues of aciclovir have been developed. Valaciclovir, the L-valyl ester of aciclovir, is an oral pro-drug that is well absorbed when given by mouth to release aciclovir into the bloodstream. A similar relationship exists between famciclovir and penciclovir; the former is metabolized into the latter after oral administration. Penciclovir (Fig. 6.2) exhibits antiviral activity very similar to that of aciclovir, but the half-life within cells is considerably longer, so fewer doses are necessary to achieve an antiviral effect.

Although aciclovir and its analogues are undoubtedly successful antiviral drugs, their clinical usefulness is limited by their narrow spectrum of activity. They are active only against a subgroup of herpesviruses—herpes simplex and varicella zoster viruses—that can perform the first phosphorylation step. It is particularly disappointing that these otherwise excellent drugs have no activity against cytomegalovirus, a herpesvirus that does not encode its own thymidine kinase enzyme.

Ganciclovir (dihydroxypropoxymethylguanine, DHPG, Fig. 6.2) is a derivative of aciclovir that shows useful activity against cytomegalovirus, an opportunist pathogen that causes severe and even life-threatening disease in immunosuppressed patients such as transplant recipients and HIV-infected individuals. Ganciclovir must be activated by phosphorylation, but cytomegalovirus uses a virally encoded phosphotransferase that differs from thymidine kinase of herpes simplex or varicella zoster. Subsequent phosphorylation to the triphosphate generates a compound that acts as a viral DNA polymerase inhibitor. Unfortunately, cellular enzymes also phosphorylate ganciclovir, so that active drug is generated in uninfected cells. Thus the toxicity of ganciclovir is considerably greater than that of aciclovir. The most frequent unwanted effects, leucopenia and thrombocytopenia, arise from a toxic effect on the function of the bone marrow, particularly affecting the production of neutrophils. Ganciclovir treatment can also result in a rise in serum creatinine. It is poorly absorbed (<10%) when given orally, and has to be administered intravenously. The valyl ester of ganciclovir, valganciclovir, is much better absorbed orally (40%), and serum concentrations are close to those arising from intravenous ganciclovir therapy. Despite its drawbacks, ganciclovir can be sight or life saving in immunosuppressed patients with severe cytomegalovirus infections (see Chapter 27).

Resistance to ganciclovir through point mutations in the phosphotransferase gene arises fairly commonly in clinical practice. Fortunately, the viral mutants remain sensitive to foscarnet (see below). Mutations in the cytomegalovirus DNA polymerase gene may also confer resistance.

Cidofovir and adefovir

The difficulty in achieving the first phosphorylation step of aciclovir-like compounds is avoided by acyclic nucleoside phosphonates, a class of compounds of which cidofovir (Fig. 6.3) and adefovir belong. The phosphonate group acts as a phosphate mimetic, and is attached to the acyclic nucleoside moiety through a stable P-C bond that cannot be split by cellular hydrolases. These agents need only two phosphorylation steps to reach the active triphosphate form, and cellular enzymes perform these steps. Thus, active drug may arise in both infected and uninfected cells, but a selective antiviral activity is maintained since the triphosphate exhibits a higher affinity for viral

DNA polymerases than for the corresponding cellular enzymes. Like aciclovir triphosphate, the drugs act as chain terminators and competitive inhibitors.

Fig. 6.3 Structure of cidofovir.

Given the mechanism of action of these drugs they would be expected to have a broad antiviral spectrum against all viruses with a DNA polymerase. Cidofovir is indeed active against all herpesviruses, as well as adeno-, polyoma-, papilloma-, and poxviruses. In addition, adefovir inhibits replication of hepatitis B virus (as does another nucleotide analogue, tenofovir, which also has useful antretroviral activity; see p. 111). This class of drugs thus offers great promise for the treatment of a wide range of virus infections, though toxicity has limited the value of presently available compounds.

Cidofovir is an acyclic cytosine analogue, administered by intravenous infusion in the treatment of cytomegalovirus retinitis. It has a prolonged antiviral effect such that dosing is required only once a week or less. It is, however, nephrotoxic in a dose-dependent manner, and must be administered with probenecid to prevent irreversible renal damage. Adefovir, an acyclic adenine analogue, is formulated as the dipivoxil ester for the oral treatment of chronic hepatitis B infection.

In theory, resistance to cidofovir and its congeners may arise through mutations in the viral DNA polymerases and time will tell how much of a problem this will become. Resistance to adefovir in hepatitis B is already well documented.

Unlike the drugs discussed so far, foscarnet (Fig. 6.4) is not a nucleoside analogue; it is trisodium phosphonoformate, a derivative of phosphonoacetic acid, and is therefore a pyrophosphate analogue. It does not require phosphorylation. It forms complexes with DNA polymerases, and prevents cleavage of pyrophosphate from nucleoside triphosphates, resulting in inhibition of further DNA synthesis. It shows some selective toxicity for viral rather than host cell enzymes, and is active against all the herpesviruses, including cytomegalovirus. It is used as an alternative to ganciclovir in the treatment of serious cytomegalovirus infection, as well as in the treatment of aciclovir-resistant herpes simplex infection. Like ganciclovir, oral bioavailability is poor, and it has to be administered by intravenous injection. It is nephrotoxic, and can cause acute renal failure. Other side effects include symptomatic hypocalcaemia, and penile ulceration.

Fig. 6.4 Structure of foscarnet.

Fomivirsen is an oligonucleotide, 21 bases in length. It is not marketed in the European Union, but is available in some countries for the treatment of cytomegalovirus retinitis by intravitreous injection. It is an anti-sense molecule: the mirror image of a section of cytomegalovirus-derived mRNA encoding regulatory proteins. Binding of the drug to this region prevents translation of the RNA into protein.

This nucleoside analogue, 3-thiacytidine, is an inhibitor of reverse transcriptase developed for the treatment of HIV infection (see Chapter 7). However, it is also active against hepatitis B virus. Although this is not a retrovirus (it has a DNA genome), there is a step in the viral replication cycle in which a viral DNA polymerase converts RNA into a DNA copy by reverse transcription. Lamivudine is triphosphorylated in the cell by cellular enzymes, and the triphosphate acts as a chain terminator and DNA polymerase inhibitor. Resistance to lamivudine has emerged as a major problem: after 5 years of therapy over 80% of patients with hepatitis B harbour resistant virus. An analogue, telbivudine is under development.

Entecavir is the latest addition to a range of drugs used in the treatment of hepatitis B. It is a nucleoside analogue based on guanosine, but differs from aciclovir and ganciclovir in that carbon replaces oxygen in the modified ribose substituent, which retains a cyclic arrangement. It inhibits the replication of hepatitis B virus and appears to have better activity than lamivudine. Importantly it retains activity against lamivudine-resistant virus. It is administered orally.

Ribavirin is a synthetic nucleoside in which ribose is linked to a triazole derivative (Fig. 6.5). Like other nucleoside analogues it has to be activated intracellularly by phosphorylation. The precise mode of action has proved elusive, though there are several theories including the possibility that it causes lethal mutations in viral nucleotides.

Fig. 6.5 Structure of ribavirin.

Ribavirin has an unusually broad spectrum of activity, against both RNA and DNA viruses, at least in vitro. Its main use is in the treatment of severe lower respiratory tract infection in young children, caused by respiratory syncytial virus. The compound is administered by inhalation of an aerosolized solution. Oral ribavirin has also been used successfully in the treatment of Lassa fever.

Although ribavirin itself is ineffective in the treatment of chronic hepatitis C, combination therapy with interferon (especially peginterferon; see below) produces a considerable improvement in response rates compared with the use of interferon alone.

The most commonly encountered serious side effect of prolonged ribavirin use is macrocytic anaemia. It may also cause a rise in serum bilirubin levels.

Older nucleoside analogues

Nucleoside analogues have been used for many years as antiviral agents, but the older ones are very toxic and have been eclipsed by later developments. Idoxuridine and trifluridine are still available in many countries for topical application in recurrent herpes simplex infections, but are no longer recommended. Cytarabine (cytosine arabinoside; ara-C) and vidarabine (adenine arabinoside; ara-A) are cytotoxic drugs of limited availability that are sometimes used as agents of last resort in life-threatening and otherwise untreatable viral infections.

Amantadine and rimantadine

Amantadine (Fig. 6.6) is a tricyclic amine derivative of adamantane, a compound that originally aroused interest because of its symmetrical three-dimensional structure, which is composed entirely of carbon atoms and is thus related to the crystalline array of natural diamonds. The antiviral activity of amantadine was first described in 1964. Rimantadine is a closely related substance that is available in some countries.

Fig. 6.6 Structure of amantadine.

The activity of both amantadine and rimantadine is restricted to influenza A virus. Other influenza viruses are virtually unaffected at therapeutically achievable concentrations. These compounds block a viral matrix protein ion channel, thereby interfering with uncoating of the viral nucleic acid within the infected cell. Resistance readily arises by mutation in the matrix protein, which is then unable to bind the drugs.

Amantadine has dopaminergic effects and may cause restlessness, insomnia, agitation, and confusion, especially in the elderly, one of the groups who stand to benefit most from an effective anti-influenza drug. Rimantadine gives rise to fewer side effects and is generally favoured in countries where it is available.

Combination therapy of amantadine with interferon has been used in patients with chronic hepatitis C virus infection, but ribavirin plus interferon is more effective and is now preferred. Amantadine is also licensed in the UK for use in shingles, but this has few advocates.

Oseltamivir and zanamivir

These drugs belong to a class of anti-influenza compounds that selectively inhibit viral neuraminidase, one of the two proteins (the other being haemagglutinin) present on the surface of all types of influenza viruses.

Viral neuraminidase enables budding influenza virus particles to break away from an infected cell. It may also facilitate the passage of virus particles through mucus to reach epithelial cell surfaces, thereby aiding infection of new cells. Oseltamivir and zanamivir act extracellularly to inhibit the release and propagation of infectious influenza viruses from the epithelial cells of the respiratory tract. Unlike amantadine, they act against both influenza A and B viruses, and inhibit all the known neuraminidase subtypes of influenza A viruses. Oseltamivir is administered by mouth, while zanamivir is formulated for oral inhalation. They appear to be generally safe, but zanamivir occasionally causes bronchospasm in patients with underlying lung disease.

These drugs bind to the active site of neuraminidase, which is highly conserved among different strains of influenza virus. This gave rise to hopes that resistance to the drug through mutation at the target site would be uncommon. However, high-level resistance has already been described in patients receiving oseltamivir and may increase with widespread use.

Interferon (IFN) was described in 1957 as an antiviral compound in chick embryo cells. It turns out that the activity is associated with a family of species-specific glycosylated proteins produced in vivo in response to viral or antigenic challenge. There are three types of human IFN: IFN-α, produced by many cell types; IFN-β, produced by fibroblasts; and IFN-γ (sometimes referred to as immune interferon) produced by T lymphocytes. IFN-α and IFN-β share 30% structural homology, but they are quite distinct from IFN-γ, which shares only about 10% homology in its amino acid sequence. Moreover, there are over 15 different forms of IFN-α, each differing by a few amino acids, and, possibly, two forms of IFN-β.

Interferons have a wide range of biological effects. They activate several different biochemical pathways within a cell, with the result that the cell is rendered resistant to virus infection. The relative importance of each of these pathways differs between different IFNs, and indeed between different cells stimulated by the same IFN. One pathway results in the activation of a ribonuclease that digests viral RNA. Another results in phosphorylation of a protein known as an initiation factor; phosphorylation of this factor, the normal function of which is to assist in the initiation of transcription of mRNA into protein, effectively prevents production of viral proteins.

IFNs also have various effects on cells of the immune system. As with their antiviral properties, these immunomodulatory effects vary in detail between different IFNs, but they include stimulation of natural killer cells, induction or suppression of antibody production, stimulation of T-cell activity, and stimulation of expression of HLA class I and II molecules on the surface of cells. Finally, IFNs affect cell proliferation, which has led to their successful use in the management of certain malignant tumours.

When IFNs were discovered, they were hailed as the antiviral equivalent of penicillin. As these substances were produced by cells as a natural defence in response to a wide range of virus infections, it seemed reasonable to imagine that when used as therapeutic agents, they would exhibit a broad antiviral spectrum, and that their toxic effects on host cells would be minimal. Early studies were hampered by difficulties in obtaining sufficient quantities of IFNs to conduct clinical trials. This problem has been solved by recombinant DNA technology, which has allowed cloning and expression of the relevant genes, and by the use of Sendai virus to induce IFN production by a lymphoblastoid cell line (so-called lymphoblastoid IFN). Unexpectedly, clinical trials revealed that patients receiving IFN experienced flu-like side effects: fever, headache, and myalgia. This led to the realization that individuals suffering from influenza complain of flu-like symptoms precisely because of the induction of IFNs by the virus. Most patients become tolerant to these effects after the first few doses.

IFN-α is successfully used in the management of patients with chronic viral hepatitis, but the therapeutic effect may be due to its immunomodulatory rather than antiviral properties. A formulation in which a polyethylene glycol unit has been linked to IFN-α (peginterferon) has an extended half-life, is better tolerated and, most importantly, produces a much superior virological response.

Prevention of virus infections

Prevention rather than cure plays such an important part in the control of viral diseases that an appreciation of the methods used is essential to understanding the complementary role of antiviral agents. The scourge of smallpox has been removed by appropriate use of vaccinia vaccine and certain other viral infections may be similarly eradicated. The World Health Organization campaign to eliminate polio is progressing towards a successful conclusion, and in many developed countries measles, mumps, and rubella are becoming rare.

Passive immunization

Immune globulin

The transfer of preformed antibodies from one individual to another can be achieved with human gammaglobulin derived from the blood of healthy individuals known to have high antibody titres. In the days before an effective vaccine against hepatitis A became available, normal human immunoglobulin obtained from pooled routine blood donations was widely used for the protection of individuals visiting countries where the virus is common. Other types of immunoglobulin are obtained specifically from known hyperimmune individuals. Those in current use include immunoglobulin preparations against: hepatitis B, varicella zoster, rabies, vaccinia, and tetanus.

Monoclonal antibody

Techniques allowing the production of monoclonal antibodies with their exceptional intrinsic specificity have led to investigation of such compounds in the prevention of viral infection. The only one presently available, palivizumab, is a monoclonal antibody directed against respiratory syncytial virus. It is administered by intramuscular injection to vulnerable infants at monthly intervals during the autumn and winter—seasons of greatest risk of infection with the virus.

Active immunization

The host can be stimulated to produce a protective immune response by vaccination with a form of the infectious agent that does not cause disease. Vaccines can be alive or dead. Live vaccines consist of attenuated forms of the infectious agent. Examples include measles, mumps, rubella, and live poliovirus (Sabin) vaccines.

Dead vaccines may consist of the whole agent, grown in the laboratory and subsequently killed by some means, or of a subunit of the agent, usually prepared by recombinant DNA technology. Dead vaccines have the advantage that there is no risk of reversion to virulence. However, they are less immunogenic than live vaccines, and therefore more doses need to be given to achieve a satisfactory response. Examples of such vaccines include the Salk polio vaccine (now generally preferred to the live Sabin vaccine), rabies virus, hepatitis A and hepatitis B virus vaccines; the latter is a subunit vaccine, consisting only of the surface protein (HBsAg), prepared by cloning and expressing the appropriate gene in yeast cells.

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Thursday, March 16, 2006

Thursday Thirteen revived!

Thirteen things that make me Me

1. My favourite drink is tea (with two sugars), I’ll take this over anything else, – unless it’s fancy, Earl Grey is too smelly (and I have a poor sense of smell!)

2. I have a problem with shoes, I don’t like them and thus have trouble choosing them. As I child I lived barefoot, but this doesn’t work so well as an adult (though I still have feet of leather and can walk on anything), stable 3” heeled boots are acceptable as they make me feel sexy (stable, because my sense of balance is squiffy – but not clumpy, as I also dislike clumpy), but you’re most likely to find me in walking boots.

3. Most mornings I wake confused. Some days it can take me a full six seconds to work out what day of the week it is, and when it is. And I’m not one for lying in bed. Once I’m awake, I like to get up as lying around just makes me tired again, and I don’t like drowsing as I get even more confused!

4. I like to see the moon as I fall asleep. At night if the moon is up but not in view of the window, I’ll angle the mirror so I can at least see the reflection.

5. I don’t eat breakfast as I don’t get hungry before lunchtime (probably due to all the tea and sugar ;o))

6. I twiddle my hair a lot, hard to say if it relaxes me or whether I do it when relaxed.

7. When nervous I either pull on a pendant (if wearing one, see next comment) or flick my nails off of each other.

8. I rarely wear jewellery, excepting my wedding and eternity rings.

9. I detest being called ‘Love’ or ‘Darling’ by strangers.

10. I rarely find men attractive based solely upon their looks, I need the interaction of a good personality before thinking a man gorgeous.

11. I cannot drive forwards into a parking space without mucking it up, but can reverse into the tightest, most awkward, near impossible, parking space with no problems at all!

12. The sound of someone brushing their teeth brings me out in goose-bumps and makes my toes curl, though I’m okay when doing my own.

13. I believe some essence of me has lived before, however I don’t believe in reincarnation as in the generally used term.

Links to other Thursday Thirteens!
Undercover Angel
Helen's world

Get the Thursday Thirteen code here!

The purpose of the meme is to get to know everyone who participates a little bit better every Thursday. Visiting fellow Thirteeners is encouraged! If you participate, leave the link to your Thirteen in others comments. It’s easy, and fun! Be sure to update your Thirteen with links that are left for you, as well! I will link to everyone who participates and leaves a link to their 13 things. Trackbacks, pings, comment links accepted!

Blogger Undercover Angel said...

Great list! My Thursday 13 is up.

Thursday, March 16, 2006 3:24:00 pm
Blogger Who is this Dave? said...

You're OK, if you drop in for a cuppa, as I keep some ordinary tea in too, for fussy people, so I can keep the Earl Grey to myself.

Thursday, March 16, 2006 4:33:00 pm
Blogger Amanda Matilda said...

Brushing teeth, really? Is your hearing hypersensative to compensate for your failing sense of smell and balance? Hmmm...

Thursday, March 16, 2006 5:23:00 pm
Blogger rdl said...

Funny :)

Thursday, March 16, 2006 6:41:00 pm
Blogger Tim-tambolini said...

Those are some unique idiocycracies. My boyfriend twiddles his hair too and it drives me crazy...nothing more distracting than sitting next to, or having a conversation with someone who is doing that.

I forgot about TT last week, and almost again this week, so I must put my thinking cap on.

Thursday, March 16, 2006 9:58:00 pm
Blogger Helen said...

Nice list. I`m also a tea-drinker.
Have just wrot my first TT.

Friday, March 17, 2006 8:49:00 am

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Sunday, September 20, 2015

Miro style tissue paintings, 2nd grade

Second graders began the year with the story Ish, which inspired us to be loose, expressive, and worry-free in our drawing. Next, we looked at the art of Joan Miro, who definitely had that same idea for his art - it is called abstract. We examined one of his well- known works and guessed what was happening - then we read the title and it cleared up a few questions. Reading the title of a work can often be helpful in understanding it better.
      People and Dog in Front of the Sun

We drew characters in a setting using abstract lines and shapes inspired by Miro, then we added random color by tissue painting, or wetting the paper and arranging colorful tissue squares. When dry, we peeled the squares off and created a descriptive title for our work. These artwork info forms are available on my Teachers pay Teachers page,

  1. Beautiful! Don't you just LOVE tissue paper staining?! My seconds do a Jack-'O-Lantern project with the tissue paper stained background! They have already been asking when we are going to do it! They remember seeing last year's and can't wait! I save all of the dried tissue paper squares in a box and we use them for other projects during the year! They become these AMAZING tie-dyed papers! The kids also like to use them during a free activity time and glue them down in a collage!

  2. How is class dojo working for you? I meant to ask you when you were here! Loved having you come by, by the way--fun to spend some time sharing.

    1. I love Class Dojo - this week I am giving my rewards for the highest points in each grade and my art stars for those who earned 10 points so far. I am also using their Class Story feature to share pics from class with the families - it is really cool!

    2. Oh and yes - it was great being in your classroom - we should do that more often! Thanks for letting me come visit.

Comments are very appreciated - thanks for stopping by!


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Sunday, June 16, 2013

Happy Father's Day

Happy Father's Day to some amazing dads out there.
But today I'm thankful for my husband who is an amazing dad to our sweet kids
and for my daddy who has influenced me so much.

I've said it a million times, so I'm just going to show you some of my favorite pictures of them both.

My dad!

These pictures are old, but I love what they say.
They say my dad loves his grandchildren and loves to play with them.
He's always making up funny things to call them, telling them jokes and getting them to say funny new sounds. Even when he's exhausted he'll still get down on the floor to play. Or be up for one more game of hide and seek. I love my daddy, so it's extra special when he views my kids with the same love that he had for me as a child.

My husband

 When I went to pick out pictures for this post I couldn't decide which ones to choose. There are tons of pictures of Jon playing with the kids, letting them "help" him with work around the house, or reading stories to them.
 He clearly adores them and the feeling is mutual.
 He tucks them in at night, regardless of how small the bed is. =)
 He plays with them.
 It warms my heart that the man of my dreams loves our kids so much.
Every time I see something like this I fall even more in love with this wonderful guy!
Happy Father's day to two very special men!

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Sunday, May 10, 2009

More Sunday Sweets...from Saturday

I think when I got married, I envisioned having days like yesterday.

Joel and I went to the gym (separately) but met up at the park near our house. We shot baskets (well, Joel shot baskets. I laid down on the court and got some sun.) Then we took a walk! This may not sound exciting, but it's been months since we've been able to take a walk together. I am SO thankful that his knee is better. We always have our best conversations when we're running or walking outside.

We cleaned our house (not fun, but necessary) and Joel was AWESOME and cleaned the bathroom. What a sweetie. That's like the same as flowers for me.

We went grocery shopping at Whole Foods (a splurge).

Then we saw Star Trek, which was a really good movie. I'm not going to lie. I was thoroughly entertained.

We bought Mother's Day presents at the mall and went home to eat our Whole Foods dinner of pita, mozzarella, salad, and wine.

One thing we struggle with is having quiet times together. It seems like we can always fill our time with something else, but we've tried recently to read the Bible together more often. We knew going into marriage that we can have quiet times alone, but setting aside time together for this is something we have to do intentionally. We read Proverbs yesterday and I loved learning from him.

Anyway, it was a perfect day.

I got to have lunch with my mom today. Happy Mother's Day to moms out there! You are fabulous!

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Wednesday, December 09, 2015

The Partisan Budget And Connecticut’s Destiny

Demography, it is said, is destiny. If so, the most current report from the U.S. Census should serve as a splash of cold water in the face of Connecticut legislators.

Marriage in Connecticut during the period surveyed, 2010-2014, has taken a massive hit. Experts say that young adults usually delay marriage because of the burdens of college debt, the high cost of rental housing and anemic salary growth. The high cost of rentals is a measure, in part, of the scarcity of rental housing; through budget mismanagement and a disinclination on the part of the dominant Democrats in the General Assembly to attack spending, Connecticut is still resting somnolently in the lap of a recession that disappeared years ago in the rest of the country; and UConn has just announced plans to boost tuition by thirty one percent.

According to a story in the Hartford Courant, “The number of never-married men in Connecticut jumped by 10.6 percent from 2010, and the number of never-married women jumped 9.3 percent. Nearly 37 percent of all males older than 15 in Connecticut have never married, up from 34.2 percent, the largest increase in the nation.”

An assistant professor of sociology at Quinnipiac University, Lauren Sardi, offered an additional reason for the spike: “People who are at the age now of being married may have come from a broken family, or grown up with divorced parents, and they’re just not interested in growing up and being a part of that.” Other variables account for Connecticut’s poor showing, according to Ms. Sardi: “It also has to do with fewer jobs for people without advanced degrees. People need to put career first before they can afford to get married and have kids. And Connecticut is very expensive, with very high taxes and not as many job opportunities.” If awards were given out to states with the most disappointing “first in the nation” scores, Connecticut’s trophy case would be full.

Last week, Republicans in the General Assembly backed away from a joint Democrat-Republican meeting on the budget – the very first in Connecticut since Governor Dannel Malloy decided to bar Republicans from formal budget negotiations – because Democrats showed no interest in attacking recurring deficits by biting the bullet and accepting proposals that would reduce long-term spending. One need hardly mention that effective spending reduction proposals would not be looked upon favorably by the Democrat’s usual pampered special interests, principally state worker unions, Connecticut’s fourth branch of government. The ship of state appears to be heading at full speed towards the usual iceberg; this time Republicans have refused to accommodate their Democratic brothers and sisters in the General Assembly by shifting the chairs on deck so that no one aboard will see the approaching calamity. Republicans declined to vote in favor of the imposture.

Democrats in the General Assembly have hiked taxes and then reduced a portion of the hikes. They have moved a huge hunk of pension costs from the state budget cap, raising the roof on spending. Attorney General George Jepsen, once Chairman of the Democratic Party, has relieved spendthrift Democrats from laboring under the imagined constraint of the cap by ruling that Connecticut’s constitutional cap on spending has no legal force. The same General Assembly that instituted the cap as an inducement to legislators wavering on voting in favor of then Governor Lowell Wicker’s income tax neglected to supply necessary definitions that would have made the cap operative. In their abbreviated discussion with Democrats, Republicans insisted that the Democrat dominated legislature should in special session enact enabling legislation so the cap could be enforced. No dice said Democrats, new spending projects dancing devilishly in their eyes. The upcoming special spending session will not feature Mr. Malloy’s favored constitutional “lockbox” (read: plunderable slush fund) in which $100 billion was to be deposited over a thirty year period to pay for Mr. Malloy’s extravagant legacy transportation infrastructure program. The “lockbox,” very similar to the faux constitutional cap, fell short of the 114 votes on Tuesday to present the question to state voters next year.

Following summary rejection by leading Democrats of a Republican deficit mitigation amendment that included, in the words of no-nonsense Republican legislator Gail Lavielle, “a list of long-term structural reforms that would end the ongoing deficit cycle, reduce the tax pressure on people and businesses, and protect necessary services for the most vulnerable,” Ms. Lavielle correctly characterized the upcoming business-as-usual prospective Democratic bill: “Their bill, which is like putting a bucket under a leaky roof without fixing the roof, will pass in a bit. What a shame for Connecticut, and how disingenuous.”

Bottom line: Connecticut is back to riotous spending and disingenuous deficit mitigation, nearly all the important locks on excessive spending having been removed by a one-party state that fiddles while everyone who has not fled Connecticut seeking prosperity elsewhere, with the possible exception of gimme-more unions, burns with barely suppressed indignation.
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Kamis, 01 Maret 2012

Deliciously tense historical fiction!

The Turncoat Renegades Revolution

The Turncoat Renegades Revolution

I am going to start this review off by saying this isn't a Romance, even though it is being reviewed on several Romance sites. I am usually a reader of historical romance, because straight historical fiction tends to bore me to tears. Nothing about this book even approximates boring. It held me riveted... I mean, "take a long lunch break" kind of riveted, because I couldn't bear to put it down and return to my desk.

Thorland masterfully crafts Kate Grey as a Quaker woman turned Rebel spy, who remains true to herself even as she changes into someone she doesn't recognize. The Revolutionay War was heart-wrenching and harrowing, and Thorland shows it in all its unsentimental detail. She doesn't need to embellish it - her scenes suggesting rape or worse don't need details to shock, even as we understand and abhor that such things happen in war. There is a hero and an anti-hero whom both tug at Kate's heart, and enough historical detail to keep the time period front and center without losing a reader with a short attention span.

My favorite part of this book, however, was the writing. The prose is breathtaking without being florid. Thorland writes like Ken Follett, at his best. High praise, as Follet is one of my all-time favorite authors.

My only criticism of the book is the ending, and I actually have to give kudos to Ms. Thorland for not giving into what was surely an urge to gift the protagonists with a story-book ending. I wanted a happily ever after (must be the romance reader in me). I didn't get it. Nor did I get clear closure on why the anti-hero made the choices he did in the end, against what seemed to be clear motivating factors on his part. However, I am adult enough to acknowledge that doesn't make the ending wrong.

Wonderful job, and I can't wait to see what Ms. Thorland produces next!

Get your The Turncoat Renegades Revolution Now!

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Like the Feathers of an Arrow (affectionately known as LFA).

...don't open...don't throw away... is not disappearing completely (not yet),
but postings here will be limited.

Friday, May 27, 2011

1 photo array

Blushing Bloom
(image by rmp, that's me)

this is my attempt to make up for slacking on the fifth rule for this blog, "Must include at least one image per week within a post."  so i walked around and snapped a photo or two or three or...

(image by rmp, that's me)

this watering can is like me...empty, abandoned, and alone...but pretty in pink!

Follow the Leader
(image by rmp, that's me)

the bottom of each of these turtles has a name on in it.  one for each of my nieces and nephews.  i wonder who the leader is?

Silent Roar
(image by rmp, that's me)

i should have turned the fountain on before snapping this image.  my dad always wanted a pair of lion statues to sit on either side of the drive...but the driveway's U-shaped and four would be over kill (ha ha...kill...).  then we thought maybe on either side of the walkway leading to the front of the house, but it is kind of narrow and the lions would have been too big for the space.  i thought he'd never get his lions...but as you can see i was wrong.

Safely Tucked In
(image by rmp, that's me)

i love the way this little tree drapes over the flowers...almost like it is sheltering them...gathering the close in its arms and keeping them safe.

Sprinkled in Pinks
(image by rmp, that's me)

i admit...when it comes to flowers...i have a thing for pink.  i can appreciate flowers in general, but pinks (and purples) have a way of bringing a smile to my face...brightening my day...lifting my spirits...touching my heart....

Dopey Grin
(image by rmp, that's me)
he's always been my favorite of the seven.  the goofiness...the lack of verbal communication...the over sized clothes...that broad grin.  sometimes i wonder what it would be like to not have to communicate through gestures and expressions.  it would probably get frustrating after awhile.  i admit that in the past when the incessant talking of my students was too much to handle, i'd go into mute mode.  it is amazing how their focus changes and their questions become more direct and inquisitive.  luckily math is a relatively easy subject to do that with.

1 comment:

  1. ...empty, abandoned and alone! The rest of your post doesn't reflect such saddness. Thank you for the email on adding sound. I will try to figure it out next week. WHY do computers have to be so difficult?


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Footy Golf

Strike the ball across wacky courses in a unique cross between SOCCER and GOLF.

Micro Battles

Play HEAD TO HEAD mini-games against your friends, wife, husband, cat, dog or anyone with a sense of humor.
Presented in adorable 8-bit gfx!

Sunday Lawn Seasons

The sequel to fan favorite Sunday Lawn is here. Better than ever and with THREE new seasons: Autumn, Winter and Spring.

Traffic Rush 2

Flick rushing cars across the intersection... without CRASHING! The long-awaited sequel is here, this time in charming 3D VOXELS and supercharged with truckloads of unlockable vehicles!

Traps n' Gemstones

## Voted GAME OF THE YEAR by GameZebo ##

Solve the mystery of the disappearing relics in our all-new "Metroidvania"-style explorer game!

Micro Battles 3

Battle your friends in 8-bit mini-games, 1980s style!

We're bringing back the golden era where SNAKES, CARS, ROBOTS and SAMURAIS settled the score in video games. 1 device, 1 friend required.
Vulture Island

Micro Battles 2

Monkey Flight 2

Beach Games

All Android Games

Lucky Coins

Castle Smasher

Monkey Flight

Sunday Lawn

Jungle Crash Land

Bricks of Camelot

Rat on the Run

Traffic Rush

Donut Merchandise

A cool selection of mousepads, T-shirts, keychains and other merch available from Zazzle.

Released: Footy Golf

April 12, 2017 - all
Strike the ball across wacky courses in a unique cross between SOCCER and GOLF.
Our new game Footy Golf is now available as a free download on App Store and Google Play.

Released: Vulture Island

November 21, 2016 - all
Exploration, puzzle solving and retro graphics. Three things that sum up our new platform adventure Vulture Island.
Download it from App Store or Google Play.

Released: Micro Battles 3

March 12, 2015 - all
We're turning back the clock again. Micro Battles 3 gives a new generation of gamers the chance to play the hilarous head-to-head battles of 1980s video games that many developers of today grew up with. Check out the video here.

Released: Micro Battles 2

December 15, 2014 - all
The sequel to our much appreciated battle game is here with all-new themes: Space, frogs, tanks and pirates. Grab a friend and start battling right away. Not familiar with the concept? See the YouTube video here.

Released: Micro Battles

October 22, 2014 - all
1 Device + 2 Players = Loads of fun!
Finally, a game where you can battle a friend sitting next to you in a bunch of 8-bit style mini games. Just like in the old days of the Atari 2600. Click here to see a video.

Released: Traps n' Gemstones

July 23, 2014 - all
Already considered the "#1 Hot Game" at Touch Arcade just hours after release, we're proud to announce our biggest adventure yet. This "Metroidvania"-style master piece is available on iPhone/iPad, Android and Windows 8.

Released: Monkey Flight 2

April 1, 2014 - all
Years have passed since our classic Monkey Flight was released and fans are STILL asking for more levels. We decided to go further. With Monkey Flight 2 you get all-new themes, graphics, features and lots of levels. For iOS, Android and Windows 8. Hooray!

Android: 3 New Releases

February 25, 2014 - Android
Our adrenaline packed runner Action Hero is now out on Android, along with the awesome platformer Bubble Pig and crazy cartoon puzzler Titanic Rescue.

Android: Urban Ninja

February 14, 2014 - Android
Francois, the chubby ninja, is ready to rock your Android device. Download now on Google Play.

Huge Update: Monkey Flight

February 12, 2014 - all
You favorite monkeys get an ALL-NEW game mode, 60 more levels, lifesavers and a score summary page. Download it for iOS or Android now.

Android: 3 Difficult Releases

February 11, 2014 - Android
Three ANNOYINGLY DIFFICULT games launch on Android. Can you beat your bf / gf's score? ;)
Try now: Monkey Ninja, Fishbowl Racer and Frogbert.

Android: 2 Snowy Releases

December 20, 2013 - Android
Android gets TWO new releases this december: Rat On A Snowboard and Ruberth's Kick n Fly. Happy holidays! :)

Released: Sunday Lawn Seasons

November 13, 2013 - all
You spoke, we listened. The sequel to Sunday Lawn is here, with THREE new seasons and lots of levels and extras.
Download for iPhone, iPad or Android.

New Levels: Rat on a Jet Ski

October 31, 2013 - all
20 New levels PLUS a new game mode on iOS. And to top it off, the game is now also available on Google Play.

Released: Beach Games

September 10, 2013 - all
Extend summer with Beach Games. Fast, frantic sports with a touch of retro-style NES and C64 gaming fun. Available for iOS, Android and Windows 8.

Android: Spikey's Bounce Around

June 7, 2013 - Android
Spikey bounces into the world of Android today. Download Spikey's Bounce Around on Google Play right away.

Android: Bricks of Camelot

May 24, 2013 - Android
Experience the epic adventures of Camelot in this action packed bricks breaker. Now on Android, available on Google Play.

Android: Icy Escort

May 16, 2013 - Android
Find scattered baby penguins in this puzzle-oriented platformer! Download Icy Escort on Google Play now.

Android: Rat On The Run

April 24, 2013 - Android
The game that started it all, the first in the Rat series, is now out on Android. Get Rat On The Run on Google Play.

Android: Traffic Rush

April 18, 2013 - Android
One of Donut's all-time favoirites, Traffic Rush, is now available for Android, hooray! Get Traffic Rush on Google Play now.

Android: Rat On A Scooter XL

April 16, 2013 - Android
Ratty hits the Android with today's release Rat On A Scooter XL on Google Play. Grab it now, tell your friends and let the fun begin.

Android: Jungle Crash Land

April 11, 2013 - Android
Open the bomb doors and clear the rocky pathway beneath you in Jungle Crash Land. Now on Google Play, yay!


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Saturday, January 12, 2013

Air Bagging a MK6 GLI Red and Gold (Airlift+Ridetech)

A year has passed since we moved in to the new shop and we got a call that Aj had picked up a new toy and was ready to get it on the ground.  Aj's old GTI was the first car I had the opportunity of bagging other than my own. It was a honor to get this chance again to get our hands on another car of his.
The new canvas was a VW MK6 red GLI, paired with his gold finished CCW's Classics this was going to be a looker.
The suspension set-up consist of Airlift slam series struts up front, shortened sway bar end links and Dorbritz Designs sway bar brackets. The rear was set-up using Slam Specialties re-5's along with Dorbritz Designs D-cups and Koni shocks.
Using his old management, the Ridetech Pod was mounted in the spare tire well to keep it discret and out of the way. A pod was then made to hold the E2 controller in the ashtray cubby.
One last cosmetic addition was made to the front upper and lower grilles. The honeycomb was ditched and was replaced with the Hybrid Jetta upper grille. The lower grille took a little bit more modifying. Using a Golf grill and the factory grill as a base, both were fused and blended together to create a one off lower grille.
The simplicity and subtle mods to the car already make it stunning. We can't wait to see where it goes from here.


WARC-Truncated: length

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Reviews | Doug Addison
Doug Addison

The Realm: The Awakening Begins

Posted on

The Realm: The Awakening Begins Book review by Doug Addison My ministry, InLight Connection, used to be located in Los Angeles. For over three years we trained outreach teams and helped establish a church there. Our first ministry intern was K.L. Glanville who was doing her graduate work at Fuller Seminary for her Masters in   …Read Full Post


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Tuesday, September 20, 2011

A Short Work of Fiction (Tilt-A-Whirl)

Photo courtesy of Wikipedia...with some alterations.
It wouldn’t be long before they got here.  In a small town a death is reason for hurry; a murder assures great speed. And they would all come, even the ones off-duty and the ones who wish they were cops.  Certainly the radios were humming now.  That city woman killed someone.  The man had meant to do me harm, of that I have no doubt, but how would they know that?  My ties here are thin, though I’ve lived here for more than ten years.  I’ve kept to the outskirts.  I came from elsewhere.

As I sit waiting for them I know I should be planning for the critical moments to come – a resolute silence, a lawyer and then a calm and clear statement of what had happened – but my mind keeps pulling my thoughts back to the summer after college when a friend and I went together to a carnival near my hometown.  It was raining lightly but not enough to have brought the rides to a halt and we gave the tall and too-thin, bearded man our tickets to ride the Tilt-A-Whirl.  The yellow clowns painted on the sides of the cars were vaguely sinister yet alluring, the deep red metal of the clam-shaped cars shiny with rain.  As the ride began we moved ourselves from side to side, urging the car to spin.  Before long the ride was in full motion and we pressed together and clutched at the wheel in the center.  When it would spin crazily tears of laughter poured down our faces.  We laughed so hard there was no sound to it.  Our grins flashing by must’ve looked maniacal to the spectators standing around the outside of the ride.  To us they were merely colorful blurs.  The tall carny, seeing our efforts, worked his way towards us on the slick and undulating surface until he was standing in front of our car.  He grabbed the side and shoved it, sending us into a blissful spiral, but then suddenly he was gone, his footing lost in the rain.  He had slipped over the edge of the ride.  For a few moments more the ride continued, mechanically oblivious to what had happened.  My friend and I strained to see him, hoped to see him standing, unharmed.  Later we’d learned he’d broken an arm and was bruised and cut.  The joy in the day was gone, our thoughts playing over and over the image of the man disappearing over the side of the ride.  We’d done it to him with our quest for the sensation of spinning.

The afternoon light is soft and gray coming into the window.  The house is so quiet.  Soon it will be filled with strangers and the sounds that strangers make.  I rest my hands on the table and study the fingers.  They’re thin and white.  They’re mine and they pulled the trigger.

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Friday, April 15, 2011

Pre-work ride

Things just all worked out to allow me to get a quick ride in before work today.  Not to bad, cool and sunny, 14 miles.  Makes the whole rest of the day nicer!

Really liking my new bike.  I have picked up a couple MPH over the same out and back I ride all the time.  Some surely is due to fitness, but some is due to the equipment.  Not sure I am super crazy about the OEM seat though.
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 Rayman Origins PC Download Free | PC Games Full Version
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Posted by admin on Mar 24, 2012
Rayman Origins PC

Rayman Origins PC

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Rayman Origins PC Download Free

Rayman Origins is a 2D platform game by Ubisoft, full version of this game is available for free download for PC from the direct link given at the bottom of this page. The game has been released already for PlayStation 3, Xbox 360, PlayStation Vita and Nintendo 3DS. The PC version of Rayman Origins is finally released in March 2012.

Rayman Origins, a classic game and a real gem which has been around for a long time. The game was a difficult one in the past without the use of checkpoints or saves but this time around the job has been done easier with checkpoints and also with the infinite number of lives that you get. Rayman Origins free download for PC is given at the bottom of this article.

The environment shown in this game are just terrific, no words for it. You will always want to scroll through the game no matter how many challenges are thrown at you or even after you have completed the game. This 2D game shows you a true artistic style that the new 2D platform games are bringing to the table and they look a lot better than their 3D counterparts. The game features landscapes on which you will see hand drawn details like lush jungles, snowfalls and many other things. Rayman Origins is truly one artistic looking game which leaves nothing to be achieved in that department. Rayman Origins PC download free is given below, skip directly to it or keep reading to know more about it.

There are many characters that you can play the game with but be these characters or the enemies that you encounter all look great with superb animation accompanying them. Movement in the game is the main character foe the game you will always be moving and the developers have designed the game keeping this in mind. All the levels you will see are designed for you to move quickly with things crumbling around you, enemies that are stronger if you stay in one place for long time. With the speedy gameplay you need good controls, fortunately for us the game does feature a good set of controls and the characters respond immediately. Free Rayman Origins PC download is given at the bottom of this page.

At the beginning of Rayman Origins you only have the abilities to jump and sprint but as you progress through the game new abilities will be unlocked. These abilities include gliding through air and running towards and up the walls and ceilings. Even though there might be a lot of moves that you need to keep track of but all the moves will be performed perfectly if you press the controlling buttons which are very responsive. Responsive controls are a good thing for this game, as even though the game might seem simple and easy at the beginning but take it from us it gets difficult. Death traps, swings and monsters are a common thing and they get trickier and trickier as time goes on. Rayman Origins PC download free is given from the link at the bottom.

None of the effects or traps or the monsters feel like they were done in a rush or look cheap. The experience of getting through all the levels that pose a great threat to your character is very rewarding in itself. Sometimes the problem with games is that they become repetitive because you have to play the entire level again and again in case you die; this is not the case with Rayman Origins. Rayman Origins features a lot of checkpoints which ensures that you don’t repeat the levels too much if you die. Even with the checkpoint system present the game gives you enough challenges to keep you interested. Rayman Origins free download for PC is given below.

Boss fights in the game are a little inconsistent with one fight being too difficult but the next one will be too easy, fortunately these not the only things that keep you in the game. The collectible items that have been scattered across are enormous and wherever you go you will see these items. Hidden challenges, lums, rewards are all scattered on the landscapes. After some point in the game collecting these items becomes impossible as you need to move fast to get to your objective. Only way to get the collectible items is to backtrack though previous levels after you have completed a challenge. Free download of Rayman Origins PC is given below.

No matter how you play the game or how many times you die during it, you will enjoy every bit of it. Rayman Origins is a gorgeous looking game with plenty of things to do with entertainment at its best. The game feels like a breath of fresh air where the PC gaming scene has become dull with the same kinds of games being released. Rayman Origins is a worth game to play no matter what age group you belong to. Following link will give you free Rayman Origins PC download.

Download Rayman Origins for PC Free

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  1. admin says:

    Install Instructions

    1. Download all parts from one box and use Winrar or 7zip to extract them. You will get a ISO file.
    2. Use Daemon tools lite to mount the ISO or Burn it on a DVD
    3. Install the game.
    4. Copy everything from the Crack folder (DVD) to installation folder in Program files (Hard Disk)
    5. Start the game as admin (Right click on the game shortcut and select Run as administrator)
    6. Play the game.

  2. Xfade says:

    Thanks for the upload

  3. finally says:

    the game looks just fantastic surreal.

  4. MaddR says:

    was waiting for this to come to PC. what a game!!!!

  5. US says:

    simply great!! works without a hitch and the game as said before looks gorgeous.

  6. SonofaGun says:

    thanks you for a great game. loving it on my 56 inch TV

  7. maraa says:

    nothing beats the classic games. thanks

  8. peaches says:

    worked. first time downloader had a good experience downloading. will come back for more games later on. cheers!!!!

  9. arman says:

  10. Jolt says:

  11. Jolt says:

    thanks guys good job. adding game for download before the launch and its not fake.

    Super thanks

    • Dawg says:

      yepp the official release is on 29th March but this game is as real as it gets. someone might have got their hands on the release.

      anyways thanks for it will probably finish the game before its even released officially LOL!!

  12. epic says:

    very good. thnk you

  13. confused says:

    don’t understand the 4th step given above.

    • admin says:

      after you install the game, open the DVD you will see a folder named Crack. Open the Crack folder and select everything in it. Now copy the files you selected and go to the folder where you installed the game and hit paste.

      You will be asked if you want to replace the files already present say yes to all and you are done. Follow the next step to start the game

  14. reggae says:

  15. rock says:

    no problems here. thanks

  16. Hitman says:

    finished download in record time and installed the game. been playing it since then

  17. lopez says:

    thanks very much

  18. atkinsons says:

    workd great. thnx

  19. Paulcool says:

    Works fine for me.

  20. Paully says:

    Thx, but how do I get rid of “Failed to Authorize Disc”

    Comment muchly appreciated

    • stue says:

      follow step 4 given by admin in first comment exactly.

      • Paully says:

        oops forgot to do that. everything is working now.

        To everyone who wants to know if this site is legit, i have the answer.

        All games given here are legit and full version, i have first hand experience of downloading

  21. tspanieli says:

    this game worked

  22. bopa says:

    Thanks for advice

  23. Thieutje says:

    Awesomenessfactor x10.000 :0))))) !!! THANKS !!!!

  24. mickeyblue says:

    many thx , loved the original on the ps1 so looking 4ward to this. Cheers uploader 🙂

  25. egalpr says:

    thank you

  26. stonecold says:

    thanks mate

  27. admin says:

    Antivirus programs block you from downloading games for free. So in order to download you need to use a antivirus program that doesn’t block or disable the AV software while downloading (Not Recommended)

    • jinchuriki4596 says:

      i finally downloaded all the files from one box and whenever i open a part …..it gives me an iso file….but when i try 2 extract it it says the file is corrupt and volume is corrupt.. HELP NEEDED

      • admin says:

        try using the latest Winrar or download the first part again.

  28. newbi says:

    Do i need to buy one of this Abos?
    Or how else can i download?

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Tagged:  Monster Hunter XX WiiU torrent download

By Games Torrents 1 Nintendo Wii U

Monster Hunter Generations is an action role-playing video game developed and published by Capcom for the Nintendo 3DS. Announced in May 2015, the game was released in Japan in November 2015, under the title Monster Hunter X (モンスターハンタークロス Monsutā Hantā… Read More »


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Dear All

I assume that you are here because you have a sibling or relative, or your relative has a relative that has an extra chromosome.
Maybe you are here because you just found out you are carrying a baby with 47 chromosomes.
 Maybe you have just delivered and find out about Down Syndrome.
 Maybe you are just one of my friends, or Leyla's friends.
Maybe you are just curious.
In any case let me introduce you, by means of little windows, into a not so well known world of DS.
I hope you find what you are looking for here and may it help you to keep the dreams you have for your children alive.
In Love.
Rosa Davila

About Me

My photo
I am a Therapeutic Massage Practitioner, highly trained in Aromatherapy. I have studied Natural Nutrition and Iridiology. I threw my Naturopathic studies to the side in order to follow my other half to the USA. I gave birth to my beautiful girl In April 2009. She was born with Down Syndrome. I am know aplying all my knowledge to researching T21 and how to best help her naturally and holistically. What a journey! During the first weeks after learning of my daughters diagnosis I spent hours on the internet searching for a modern image of Down Syndrome. I found it, and with it the hope, courage and calm that allowed me to keep dreaming for my baby. With this blog I hope to gather information about people with DS, their lives, epics and struggles. I hope to bring people closer to their hearts, warm them up about DS. There is so much misinformation, outdated research and prejudice. If you have something you think is worth for me to post here, please do not hesitate to let me know. Thanks. Have a great journey into Wonderland.

Thursday, August 27, 2009

365 project Video

This little video did wonders for me when we first heard of Leyla's T21. I thought I should share it.
Thanks to Dr. D. for the help in getting it here!

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Dillo Hills 2
Welcome to Dillo Hills 2! Join the fun and race against friends and players from all over the world in this free online racing game! Slide, swim, surf, and soar your way across crazy terrain, unlock and upgrade awesome racers, collect hundreds of accessories, and conquer your foes with powerups and items! Dillo Hills 2 is a multiplayer racing game that can be played on iOS, Android, or here in your browser. Race in real time with up to 8 players from all around the world, including players using different platforms!
Multiplayer Racing Game
Get Adobe Flash player


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BlockBase is BACK! We’ve republished* BlockBase and now we’re ready to have some sew along fun along with all of you!

(*This product has been republished. It is not a new version. Those who already own BlockBase should not purchase this again. The product is the same. But you can still sew along with all the BlockBase newbies!)

About BlockBase
BlockBase is the CD-ROM version of Barbara Brackman’sEncyclopedia of Pieced Quilt Patterns and it’s jam packed with over 4300 block patterns. And the best part is you can print the patterns for these blocks at any size you want!

BlockBase also includes a wealth of historical information for each block. You may find that the beautiful modern block you saw on a blog recently was actually first published in the 1930’s! As the saying goes, “Everything old is new again,” and quilting is no exception!

How the Sew Along Works
You will need to have the BlockBase software installed on your computer so you can print the sew along patterns. You can purchase BlockBase from our secure website, or from your local quilt shop.

Starting on October 1, we will feature a block to sew from BlockBase every two weeks. At the end of each two week period there will be a link up so you can share a photo of your finished block and we can all oohh and aahh over each other’s beautiful blocks!

Pick Your Size
Because the patterns in BlockBase can be printed at any size, YOU get to choose how big to make your blocks. You may want to make your decisions about block size before you get started with the sew along. Do you want to make all your blocks the same size? Or a variety of sizes that work well together, such as 6”, 9”, and 12”? Or maybe you just want to choose your block sizes randomly, and you’ll figure out how to fit them together at the end. It’s up to you!

We’ll be choosing blocks from many different categories, so in rotary cutting terms some blocks may be better suited to a specific size. For example, a block based on a 3×3 grid would be easiest to rotary cut if using a size that’s a multiple of 3 (6″, 9″, 12″, etc.). But never fear, because you can always choose to print the templates for a block (and the templates are always accurate!).

To get things kicked off right, we’ll be giving away five copies of BlockBase! To enter, visit our contest page and fill out the entry form. Entries must be received by Wednesday, September 19th at 9am EST. We’ll randomly choose five winners from all the entries.

So grab a blog badge and spread the word! We start sewing on October 1!


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Welcome to Drake Dairy Incorporated

Our Milk

On average, Drake Dairy produces over 126,000 pounds of milk per day.

Learn More

Our Herd

Drake Dairy’s herd consists of mostly the black and white Holstein breed with a very small percentage of red Holsteins.

Learn More

Our Facility

Our milking facility is a parallel parlor that currently milks 72 cows at a time.

Learn More

Support your local dairy farm

Drake Dairy Incorporated is a 3rd and 4th generation family run dairy farm business located in Elkhart Lake, Wisconsin.

We are very proud to carry on our family heritage and to help sustain the dairy industry in Wisconsin.

Our mission is to provide high quality dairy products, to be great stewards of the land and to support the local economy, the community and the dairy industry by maintaining an efficient, honest and profitable business.

We love farming and spread that happiness to each and every person we meet. Our cattle and employees are treated like family. We take great pride in our crops and strive for the very best production. We support fellow farmers and are always willing to lend a helping hand. We highly value landowners; in appreciation we pay very competitive rates.

Tours are available, contact us for more information.

Attention Land Owners

Do you have farm land available for rent in Calumet, Fond du Lac, Manitowoc or Sheboygan County? Drake Dairy pays a competitive rate with added benefits.


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Posts Tagged ‘independent thinking’

Solitude and Leadership: If you want others to follow, learn to be alone with your thoughts.

21 Jan

The Guiding Tenet: "Whenever you find yourself on the side of the majority, it's time to pause and reflect." - Mark Twain

Amy, my partner here at Drawing Down the Vision, shared a fantastic read with me this week: Solitude and Leadership. I’d like to share a taste here with you, but would greatly prefer if you read it in its entirety. I do it no justice.

William Deresiewicz, a former Yale professor, addressed the Plebe (Freshman) class at West Point Military Academy in October of 2010. He spoke about the crucial and difficult role of solitude in developing as a leader.

Mr. Deresiewicz derided the false image of the conservative, robotic West Point grads to ensure that is what they do not become. They are training to enter one of the largest bureaucracies there is. He exalted how in order to be successful leaders on the world stage, they must be true independent thinkers who know what they stand for, and fight for it. In essence, the larger the bureaucracy you enter, the more of an independent thinker it is your responsibility to become.

It seems counter-intuitive. Solitude and Leadership? It flies in the face of the common phrase, ‘a leader is nothing without followers.’ But flying in the face of the ‘common’ and accepted when appropriate is exactly what Mr. Deresiewicz advocates we must learn. We must not become expert hoop-jumpers. We must become confident, focused leaders. We must learn what we stand for. This is a lonesome journey if done right.

But how can they, and how can we, become those independent thinkers and successful leaders? For starters…

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Tuesday, 23 June 2015

Top 6 | Books I Have Read So Far In 2015

The top ten books you have read so far this year is the topic of next week's Top Ten Tuesday. However, I won't be around next week as I will be busy running about after about a group of 8-12 year olds (I'm a leader at a summer camp, it's not as weird as it sounds!), so I decided to do this list this week instead. I decided to narrow it down to the top 5, as some books I would be including in my top ten were just reasonably good, rather than great. As I expected, though, I couldn't choose between two so ended up picking my top 6.

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1. Allegiant by Veronica Roth
I didn't intend for these to be in any kind of order but this is probably my favourite book I have read so far this year. I put off finishing this series as I had heard so many mixed reviews of Allegiant; some people completely loved it, while others hated it so much they refuse to keep it on their shelf. I was, obviously, one of those who loved it. I thought it was a great ending to the series and, despite the controversy surrounding the way the book ended, I think Veronica Roth did a fantastic job of concluding the series. I have a full review of this book here where you can read more of my raving.

2. The Selection series by Kiera Casss
I decided to include the first three books in The Selection series - The Selection, The Elite and The One - as one, because collectively they are definitely next in line after Allegiant when it comes to favourites of the year. I absolutely loved the first three books in the series, despite hearing many mixed review, and though I wouldn't consider the fourth book, The Heir, as a favourite of the year, I did still enjoy it. I have a review of all three books - The Selection, The Elite and The One - if you want to know more of my thoughts.

3. How To Fall In Love by Cecelia Ahern
This is the last of my five star books I have read so far this year. This is only the second book I have read by Cecelia Ahern, with the first being my beloved Where Rainbows End, and I was very impressed. I really wanted to love this book, considering how much I loved my first of her books, and I was so relieved when I loved it. Cecelia Ahern has this incredible talent of taking something as serious and solemn as suicide and making it light-hearted and funny, while still being sensitive and respectful of the subject matter. I don't have a review of this one yet but it will be coming soon.

4. Ignite by Lily Paradis
This may have been a four star read from me but it was still great. This was my first experience of the New Adult genre and it has definitely made me want to read more. I loved this story, particularly the aspect of the main character suddenly becoming responsible for three children, but also the romance aspect. The characters were great and I became so immersed in their story. I have a full review of this one here if you want to know more.

5. I Was Here by Gayle Forman
This is another book relating to suicide, but it is completely different from How To Fall In Love. This was definitely a more serious take on the subject but it was still very enjoyable. The characters are very relatable and I enjoyed reading about them. More importantly, this was a great story of friendship and family and it really touched me. I don't have a full review of this one yet but I will have very soon.

6. The Distance Between Us by Kasie West
This is the only 'light and fluffy' contemporary I have amongst my favourite books of the year so far because, surprisingly for me, I haven't read that many. This was a very quirky take on the usual contemporary love story. The main character was very different from the usual, though great, and even the setting was quite unusual. There wasn't really anything particularly stand out about this book but I did really enjoy it. I will have a full review of this coming soon.

So those are my top 6 books of 2015 so far. Have you read any of them? What have your favourites been so far?

Sophie :)

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Wednesday, 4 May 2016

Wrap Up | April 2016

April has been a blur! How can a month go so fast? I have had a super busy month, involving a lot of concerts (6 to be exact) and a little holiday, but I also finally managed to read more. I think I may finally be out of my reading slump and while I didn't read a huge amount I am definitely getting back on track.

My Life In April...
- I started the month with my last date of the Collabro tour which involved a trip to Grimsby.
- Staying a bit nearer home I then went to see Little Mix, supported by my fave Nathan Sykes.
- Having been rejected from the last uni to respond, I accepted my offer for my first choice university.
- My mum started her chemotherapy treatment, which has been a bit of a rollercoaster.
- I got the chance to meet one of my favourite boybands, Hometown, at a meet-up.
- I then went to see then support my other faves, The Vamps, with one of my best friends.
- The very next day I was lucky enough to meet Hometown again while having lunch in a hotel.
- That same evening I got to meet The Vamps as I had M&G tickets for a second show.
- I then travelled to Manchester with my cousin and met Hometown again at a meet-up there.
- And the main reason for travelling to Manchester, we got the chance to see The Vamps again on their final night of tour.
- Back closer to home again I went to see the amazing 5SOS.
- I ended the month with a little family trip away for the week.

Watched In April...
- Teen Mom OG Season 2 - 3/5
- Pretty Little Liars Season 6B - 4/5
- Grease 3/5

Read In April...

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Sea Of Monsters by Rick Riordan -
I read the first book in the Percy Jackson series back in December 2014 so it really was about time I continued on with the series. I really enjoyed the first book and while I did also enjoy the second, I didn't think it was as good. There's never a dull moment in these books and the characters are great. I also really love the Greek mythology aspect. This was a really fun, quick read, just not quite as good as the first in the series. 3/5

Hello, Goodbye And Everything In Between by Jennifer E Smith -
This book follows a couple, Clare and Aidan, on the night before they are separated for college, during which they must decide whether or not to stay together. I loved my first Jennifer E Smith read, but wasn't a huge fan of my second so I wasn't sure what to expect from this. I love books set in one day/night, so that was a huge bonus for this book. I related to this story and to the characters, I really felt for them in this decision and, despite having seen negative comments in various reviews, I completely understand why this was such a big decision that needed to be made. I did have a few issues with this book but overall, I enjoyed it. 3.75/5

The Grownup by Gillian Flynn -
This was a short story written initially for George RR Martin's Rogues anthology, but released alone in 2015. This was very strange, as expected from Gillian Flynn, but upon finishing it felt a little like I had wasted the half hour I spend reading it. The story is extremely odd and the twists are unexpected but I was really a bit bored reading it. Also, I hate open endings to that was a disappointment. 2/5

UnStrung by Neal Shusterman -
This novella is #1.5 in the UnWind series and follows Lev during the time he was separated from the others. Though it had been some time since I read the first book, I did manage to keep up with what was going on (thanks Recaptains for helping me out there). I found this novella quite interesting as it introduced a whole new culture into the UnWind world and, despite the limited number of pages, this was done very well. Neal Shusterman managed to fit a lot into this novella and somehow just 60 pages managed to tug at my heart strings. This isn't a necessary read, I don't think, but I would definitely recommend it if you enjoy the series. 3/5

The Girl On The Train by Paula Hawkins -
This has been raved about since way before it was even published last year and has already been turned into a movie, to be released later this year. With all this hype I was quite scared to pick this up but I was so intrigued that I finally gave in. This took me a little while to get into, but once it got into the action I could not put it down. I loved the mystery and how unreliable our main character was, you didn't know what to believe. I really enjoyed this book, there is no question as to why there is so much hype, it is definitely well deserved. 4/5

Blogged In April...
- I wrapped up February & March.
- I hauled the books I accumulated during February & March.

What did you get up to in the month of April? Did you read any great books?

Sophie :)

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How to Make Pok Pok's Hunny at Home

[Photographs: Allan Zepeda]

"A lot of New York restaurants will have this amazing food list and an amazing drink list, but they just don't go together," laments Alex Mirkin, bar manager at Pok Pok Ny in Brooklyn. "Drinks and food can make each other tasteless. Our drinks are geared to work well with our food. If a drink works with the spiciest thing on the menu, then it works."

Pok Pok's food is mostly Thai (a few items, like Ike's Wings, are Vietnamese) and considerably spicy. The drinks are their own beasts: "Our drinks are a little bit sweeter, a little more citrus-forward, to play off that Thai chili spice," says Mirkin. "There isn't much of a cocktail scene in Thailand to draw from...but our cocktails are reminiscent of flavor profiles you would find in Southeast Asia."

When Mirkin is jonesing for something citrusy, he shakes up a Hunny. Though he likes to steer clear of references to the classics, once its vinegary froth settles, the Hunny's not a far cry from a margarita; a bittersweet margarita with a subtle X factor.

The X factor: Som honey vinegar. With the exception of the apple flavor, Pok Pok's line of vinegars are cane sugar vinegars, sweeter than you might expect. "The honey vinegar is more subdued than the others. It has almost a sherry quality...a mellow, sweet silkiness. You get the brightness of vinegar without that tannic level of lemon juice," Mirkin notes. "The citrusy honey plays really well off of fresh grapefruit and lime. It supplements rather than drowns out the spice factor. The grapefruit gives it this backend duskiness, and the tequila kind of grounds it."

In the Hunny, Mirkin uses affordable gold tequila, for what he calls its "fresh, citrus edge," but he's open to experimenting: "It could be fun to make it with a nice smoky mezcal, a Del Maguey."

Pok Pok runs a tight ship, with one tiny bar churning out drinks for the always-packed shack. "We're big on systems that make life easier," says Mirkin, pointing to the pumps they made for the vinegar (one pump equals half an ounce). In keeping with this, Pok Pok drinks are designed for quick and easy bartending, which means they're also easy to whip up at home. Just be sure to shake well (the vinegar needs it) and pair with something spicy if you want this sweetie of a cocktail to shine.

Get the Recipe

Pok Pok's Hunny »

About the author: Jaclyn Einis is a Boston-bred, Brooklyn-based writer. No matter where she wanders, it always comes back to food and drink. It's been that way since the day she was born (some got pilgrim hats; she was a turkey baby). You can find her cleaning plates here.


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2013 Nissan Altima – Dubbed by Nissan as their “Most Innovative Altima Ever”

2013 Nissan Altima Coupe

This new 2013 Nissan Altima is shocking all car enthusiasts with its hot new look. Nissan took a more efficient take on excitement with this new ride. Its exceptional performance and better acceleration has made for improved responsiveness.

This quiet and comfortable Altima has a 38mpg of best-in-class fuel economy. It is also ranked 6 out of 18 for the most affordable midsize cars. And to top it off, this midsize car is perfect for shoppers who need a practical family sedan but want a sporty and fun feel!

You will be impressed with the interior of this Altima with its NASA inspired “zero gravity” front bucket seats. These provide for the best comfortable drive along with a spicy new exterior. The 2013 model sits on the same wheelbase but with much larger wheels that give this sedan a noticeably stronger and athletic attitude.

This Nissan is built with the most advanced technology made to minimize distraction. The most exceptional feature is the multifunction rearview camera. It provides blind spot warning, lane departure warning and moving object detection. Typically the more expensive vehicles are the ones which have this high-tech feature!

If the all-new 2013 Nissan Altima sounds like something you’d like to see first hand… Then find your nearest Nissan dealer at http://www.mileone.com  and take this baby for a test drive!

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