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Biomedical subjects

S Carpenter

Publications and source records attributed to S Carpenter.

At least 19 recordsLinked to original sources

Spatial and temporal distribution of bluetongue and its Culicoides vectors in Bulgaria.

Surveillance of Culicoides (Diptera: Ceratopogonidae) biting midges was carried out between 2001 and 2003, at 119 sites within a 50 x 50-km grid distributed across Bulgaria, using light trap collections around the time of peak adult midge abundance. Sentinel and ad hoc serum surveillance of hosts susceptible to bluetongue infection was carried out at around 300 sites between 1999 and 2003. Following the initial incursion of bluetongue virus 9 (BTV-9) into Bourgas province in 1999, affecting 85 villages along the southern border, a further 76 villages were affected along the western border in 2001, with outbreaks extending as far north as 43.6 degrees N. The BTV-9 strain in circulation was found to have a low pathogenicity for Bulgarian sheep populations, with less than 2% of susceptible individuals becoming sick and seroconversions detected up to 30 km from recorded outbreaks in the south. The major Old World vector Culicoides imicola Kieffer was not detected among over 70,000 Culicoides identified in summer collections, suggesting that BTV-9 transmission in Bulgaria was primarily carried out by indigenous European vectors. The most likely candidates, the Palaearctic species complexes - the Culicoides obsoletus Meigen and C. pulicaris L. complexes - were widespread and abundant across the whole country. The C. obsoletus complex represented 75% of all individuals trapped in summer and occurred in high catch sizes (up to 15,000 individuals per night) but was not found across all outbreak sites, indicating that both Palearctic complexes probably played a role in transmission. Within the C. pulicaris complex, only C. pulicaris s.s., C. punctatus Meigen and C. newsteadi Austen were sufficiently abundant and prevalent to have been widely involved in transmission, whilst within the C. obsoletus complex most trapped males were C. obsoletus s.s. Adult vectors were found to be largely absent from sites in west Bulgaria for a period of at least 3 months over winter, which, taken along with the spatiotemporal pattern of outbreaks in the region between years, indicates the virus may be overwintering here by an alternative mechanism - either by covert persistence in the vertebrate host or possibly by persistence in larval stages of the vector.

Animals↗

An alternative method of blood-feeding Culicoides imicola and other haematophagous Culicoides species for vector competence studies.

The use of cotton wool pads saturated with blood/virus mixture for oral infection attempts was compared to membrane feeding for the assessment of vector competence in C. imicola Kieffer and C. bolitinos Meiswinkel (Diptera, Ceratopogonidae). Although lower infection rates were obtained using pad feeding, it was possible to clearly distinguish the levels of competence between species as well as differences in virus infection rates for various serotypes of bluetongue virus. Reduced infection rates with cotton pad feeding was partly due to a smaller volume of blood meals taken up. However, the method described is likely to be useful in situations where membrane feeding is not viable to separate populations with significant differences in vector competence.

Animals↗

Mathematical simulation of the diel O, S, and C biogeochemistry of a hypersaline microbial mat.

The creation of a mathematical simulation model of photosynthetic microbial mats is important to our understanding of key biogeochemical cycles that may have altered the atmospheres and lithospheres of early Earth. A model is presented here as a tool to integrate empirical results from research on hypersaline mats from Baja California Sur (BCS), Mexico into a computational system that can be used to simulate biospheric inputs of trace gases to the atmosphere. The first version of our model, presented here, calculates fluxes and cycling of O(2), sulfide, and dissolved inorganic carbon (DIC) via abiotic components and via four major microbial guilds: cyanobacteria (CYA), sulfate reducing bacteria (SRB), purple sulfur bacteria (PSB) and colorless sulfur bacteria (CSB). We used generalized Monod-type equations that incorporate substrate and energy limits upon maximum rates of metabolic processes such as photosynthesis and sulfate reduction. We ran a simulation using temperature and irradiance inputs from data collected from a microbial mat in Guerrero Negro in BCS (Mexico). Model O(2), sulfide, and DIC concentration profiles and fluxes compared well with data collected in the field mats. There were some model-predicted features of biogeochemical cycling not observed in our actual measurements. For instance, large influxes and effluxes of DIC across the MBGC mat boundary may reveal previously unrecognized, but real, in situ limits on rates of biogeochemical processes. Some of the short-term variation in field-collected mat O(2) was not predicted by MBGC. This suggests a need both for more model sensitivity to small environmental fluctuations for the incorporation of a photorespiration function into the model.

Carbon↗

Clotiapine for acute psychotic illnesses.

BACKGROUND: Acute psychotic illnesses, especially when associated with agitated or violent behaviour, require urgent pharmacological tranquillisation or sedation. Clotiapine, a dibenzothiazepine neuroleptic, is being used for this purpose in several countries. OBJECTIVES: To estimate the effects of clotiapine when compared to other 'standard' or 'non-standard' treatments for acute psychotic illnesses in controlling disturbed behaviour and reducing psychotic symptoms. SEARCH STRATEGY: We updated previous searches by searching the Cochrane Schizophrenia Group Register (April 2004) SELECTION CRITERIA: The review included randomised clinical trials comparing clotiapine with any other treatment for people with acute psychotic illnesses. DATA COLLECTION AND ANALYSIS: Relevant studies were selected for inclusion, their quality was assessed and data extracted. Data were excluded where more than 50% of participants in any group were lost to follow up. For binary outcomes we calculated a standard estimation of the risk ratio (RR) and its 95% confidence interval (CI). For continuous outcomes, endpoint data were preferred to change data. Non-skewed data from valid scales were summated using a weighted mean difference (WMD). MAIN RESULTS: We identified five relevant trials. None compared clotiapine with placebo, but control drugs were either antipsychotics (chlorpromazine, perphenazine, trifluoperazine and zuclopenthixol acetate) or benzodiazepines (lorazepam). Versus the antipsychotics, the results for 'no important global improvement' did not suggest clotiapine to be superior, or inferior, to chlorpromazine, perphenazine, or trifluoperazine (n = 83, 3 RCTs, RR 0.82 CI 0.22 to 3.05, I-squared 58%). Use of clotiapine when compared with chlorpromazine did change the proportion of people ready for hospital discharge by the end of the study (n = 49, 1 RCT, RR 1.04 95%CI 0.96 to 2.12). Overall, attrition rates were low. No significant difference was found for those allocated to clotiapine compared with people randomised to other antipsychotics (n = 121, RR 2.26 95%CI 0.40 to 13). Weak data suggests that clotiapine may result in less need for antiparkinsonian treatment compared with zuclopenthixol acetate (n = 38, RR 0.43 95%CI 0.02 to 0.98). Compared with lorazepam, clotiapine, when used to control aggressive/violent outbursts for people already treated with haloperidol, did not significantly improve mental state (WMD -3.36 95%CI -8.09 to 1.37). We could not pool much data due to skew or inadequate presentation of results. Economic outcomes and satisfaction with care were not addressed. REVIEWERS' CONCLUSIONS: We found no evidence to support the use of clotiapine in preference to other 'standard' or 'non-standard' treatments for management of people with acute psychotic illness. All trials in this review have important methodological problems. We do not wish to discourage clinicians from using clotiapine in the psychiatric emergency, but well-designed, conducted and reported trials are needed to properly determine the efficacy of this drug.

Acute Disease↗

Droperidol for acute psychosis.

BACKGROUND: People suffering from acute psychotic illnesses, especially those associated with agitated or violent behaviour, may require urgent pharmacological tranquillisation or sedation. Droperidol, a butyrophenone neuroleptic, has been used for this purpose in several countries. OBJECTIVES: To estimate the effects of droperidol compared to other treatments for controlling disturbed behaviour and reducing psychotic symptoms for people with suspected acute psychotic illnesses. SEARCH STRATEGY: We updated previous searches by searching the Cochrane Schizophrenia Group Register (September 2003). References of all identified studies were searched for further trial citations and authors of trials were contacted. Twenty-one other databases were also searched as part of a broader project and this composite database was searched for this review. This was supplemented by hand searching reference lists and contacting both the pharmacological industry and relevant authors. SELECTION CRITERIA: The review included randomised controlled trials comparing droperidol to any other treatment for people with suspected acute psychotic illnesses, including schizophrenia, schizoaffective disorder, mixed affective disorders, the manic phase of bipolar disorder or a brief psychotic episode. DATA COLLECTION AND ANALYSIS: Relevant studies were selected for inclusion, their quality was assessed and data extracted. Data were excluded when more than 50% of participants were lost to follow up. For binary outcomes, standard estimates of risk ratio (RR) and the corresponding 95% confidence intervals (CI) were calculated. Where possible, weighted number needed to treat or harm statistics (NNT, NNH), and the corresponding 95% confidence intervals (CI), were calculated. MAIN RESULTS: We identified only two relevant trials. One additional study focused on outcomes at 30 days rather than at a few hours. One small (n = 41) randomised trial compared intravenous (iv) droperidol (10 mg) with iv placebo and found that people allocated to droperidol were significantly less likely to need additional injections of another drug, haloperidol, in the first few minutes (n = 41, RR 0.37 CI 0.2 to 0.7, NNT 2 CI 1 to 10) compared to those given placebo. By 90 minutes this difference was still evident but not statistically significant (RR 0.46 CI 0.2 to 1.2). When 5 mg intramuscular (im) droperidol was compared with 5 mg im haloperidol, those given droperidol were also less likely to need additional injections by 30 minutes, than those given haloperidol, but this result was not statistically significant (n = 27, RR 0.45 CI 0.2 to 1.01). One person out of the 16 given haloperidol experienced a mild dystonic reaction (muscle spasms or abnormal contractions), while none of the 11 people allocated to droperidol were reported to have experienced adverse effects. REVIEWERS' CONCLUSIONS: This is an important, and surprisingly under-researched, area. To date, use of droperidol for emergency situations has been justified by experience rather than evidence from well conducted and reported randomised trials, but, as world reserves diminish, droperidol will no longer be a treatment option.

Acute Disease↗

FTIR spectroscopy demonstrates biochemical differences in mammalian cell cultures at different growth stages.

We have observed differences in the infrared spectra of viable fibroblast cells depending on whether the cells were in the exponential (proliferating) or plateau (nonproliferating) phase of growth. The spectral changes were observed even after correcting for cell number and volume, ruling out these trivial explanations. Several of the changes occurred for both transformed and normal cell lines and were greater for the normal cell line. The biochemical basis of the spectral changes was estimated by fitting the cell spectra to a linear superposition of spectra for the major biochemical components of mammalian cells (DNA, RNA, protein, lipids, and glycogen). The ratios of RNA/lipid and protein/lipid increased when the cells were in the exponential phase compared to the plateau phase of growth. The fits of cell spectra to individual biochemical components also demonstrated that DNA is a relatively minor spectroscopic component as would be expected biochemically. Contrary to other reports in the literature, our data demonstrate that determining DNA content or structure using Fourier transform infrared spectroscopy data is difficult due to the relatively small amount of DNA and the overlap of DNA bands with the absorption bands of other biochemical components.

Animals↗

Surveillance of individuals at intermediate risk of colorectal cancer--the impact of new guidelines.

OBJECTIVE: Individuals with two first degree relatives, or one diagnosed at age < 45 years, with colorectal cancer are at sufficient risk to merit surveillance. Most undergo colonoscopy four to five yearly, starting 10 years before the youngest case. The aim of this study was to assess the impact of a proposed new surveillance protocol. SUBJECTS AND METHODS: We identified individuals with these risk criteria seen in our clinic from 1989 to 2001 and reviewed their notes with respect to colonoscopy. RESULTS: Colonoscopy (n = 295) was performed on 186 patients in accordance with current recommendations. Cancer was detected in three and adenoma in 21 individuals. Applying the proposed protocol, 123 (42%) fewer colonoscopies would have been performed. No cancers would have been missed, but in five cases a small adenoma would not have been detected. CONCLUSIONS: Proposed new guidelines for surveillance of those at intermediate risk reduce the burden of colonoscopy without compromising identification of significant neoplasia.

Adenoma↗

Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures.

An understanding of the relationship between tissue structures and light scattering from tissue will help facilitate the development and acceptance of noninvasive optical diagnostics including elastic scattering spectroscopy, diffuse reflectance, and optical coherence tomography. For example, a quantitative model of the structures that scatter light in epithelial cells would allow determination of what structures control the characteristics of in vivo light transport measurements and subsequently could provide a detailed relationship between cellular structures and optical measurements. We have determined the size distribution of refractive index structure variations in epithelial cells as well as in nuclei isolated from epithelial cells from measurements of the angular dependence of polarized light scattering. The quantitative size distributions we obtained for both whole cells and isolated nuclei include particles with effective radii of 2 microm to 10 nm or less and contain orders of magnitude more small particles than large particles. These results demonstrate that not only are biological cells very heterogeneous, but so are the nuclei within them. Light scattering is likely sensitive to structures smaller than those commonly investigated by standard pathology methods.

Animals↗

Toward the molecular flashlight: preparation, properties, and photophysics of a hypericin-luciferin tethered molecule.

The synthesis of a molecule containing hypericin and luciferin moieties joined by a tether is reported. The light-induced (in vitro) antiviral activity as well as the photophysical properties of this new compound are measured and compared with those of the parent compounds, hypericin and pseudohypericin. This tethered molecule exhibits excited-state behavior that is very similar to that of its parent compounds and antiviral activity that is identical, within experimental error, to that of its more closely related parent compound, pseudohypericin. The implications for a photodynamic therapy that is independent of external light sources are discussed.

Anthracenes↗

Prevalence of pre-cancerous lesions and cervical cancer in South Africa--a multicentre study.

OBJECTIVES: To describe the age-specific prevalence rates of cancer of the cervix in South African women presenting for screening. DESIGN: A multicentre prevalence survey in 10 geographically defined areas following a common core protocol. Services were located in existing service sites, with the exception of KwaZulu-Natal which used a mobile service. Women aged 20 years and above were eligible for inclusion. OUTCOME MEASURES: Age-specific cervical cytologically diagnosed abnormality rates according to the Bethesda classification. RESULTS: During the study 20,603 women participated. Eighty per cent of the sample had never had a Pap smear before and just over 91% had not had a Pap smear in the last 5 years. In this study population 468 women screened (2.42%) were found to have low-grade squamous intra-epithelial lesions (LSIL) and the average age of these women was 33.1 years; 366 (1.8%) had high-grade SIL (HSIL) and these women were statistically significantly older at 37.97 years of age; and 92 women (0.47%) were found to have cytologically diagnosed invasive cancer. These women were significantly older, with an average age of 51.3 years. A clear relationship was found between age and LSIL, with younger women having a high rate of LSIL which decreases with increasing age. A similar but inverse relationship between age and invasive cancer is described, with the rate being low in young women and increasing with increasing age. A clear relationship between HSIL and age is not described in these data. The adequacy rate (satisfactory and satisfactory but limited) of the slides was 95%, and just under 92% of the study sample received their results. Not all women were appropriately referred and it was not possible to assess if women referred for treatment received it. CONCLUSIONS: These data indicate that cancer of the cervix is a common disease and that, similar to other countries, it is a disease of older women. These data give some positive indicators for future screening--older women will present for screening and the majority of women received their results. However, improvements in health system functioning are needed. A uniform national cytology reporting system is required as well as clear guidelines for providers on what action to take based on cytology reports. Linkage between the site of screening and treatment centre is inadequate and requires urgent attention in order to decrease cervical cancer mortality.

Adult↗

Molecular and functional characterization of genes encoding horse MHC class I antigens.

Sequence and functional analyses were undertaken on two cDNAs and a genomic clone encoding horse major histocompatibility complex (MHC) class I molecules. All of the clones were isolated from a single horse that is homozygous for all known horse MHC class I and class II antigens. The two cDNAs (clones 8-9 and 1-29) were isolated from a lymphocyte library and encode polymorphic MHC antigens from two loci. The genomic cosmid clone, isolated from a sperm library, contains the 8-9 gene. All three genes were expressed in mouse L-cells and were recognized by alloantisera and, for the cDNAs, by alloreactive cytotoxic T lymphocytes. A total of 3815 bp of the genomic clone were sequenced, extending from 429 bp upstream (5') of the leader peptide through the 3' untranslated region. Promoter region motifs and an intron-exon structure characteristic of MHC class I genes of other species were found. A subclone containing 407 bp of the promoter region was inserted into a chloramphenicol acetyl transferase reporter plasmid, tested in transient transfection assays, and found to have promoter activity in heterologous cells. This genomic clone will enable detailed studies of MHC class I gene regulation in horse trophoblasts, and in horse retroviral infections.

Amino Acid Sequence↗

Catastrophic shifts in ecosystems.

All ecosystems are exposed to gradual changes in climate, nutrient loading, habitat fragmentation or biotic exploitation. Nature is usually assumed to respond to gradual change in a smooth way. However, studies on lakes, coral reefs, oceans, forests and arid lands have shown that smooth change can be interrupted by sudden drastic switches to a contrasting state. Although diverse events can trigger such shifts, recent studies show that a loss of resilience usually paves the way for a switch to an alternative state. This suggests that strategies for sustainable management of such ecosystems should focus on maintaining resilience.

Animals↗

Genetic and biological variation in equine infectious anemia virus Rev correlates with variable stages of clinical disease in an experimentally infected pony.

Genetic and biological variation in the regulatory protein Rev of equine infectious anemia virus (EIAV) were examined throughout a clinically dynamic disease course of an experimentally infected pony. Following infection with the virulent EIAV(Wyo), the pony underwent a variable disease course, including an acute fever episode at 12 days postinfection (DPI), multiple recurrent fever episodes until 135 DPI, a prolonged subclinical period, and two late fever episodes. Viral RNA was isolated from the inoculum and sequential sera samples, and the rev exon 2/gp45 overlapping ORFs were amplified, cloned, and sequenced. Novel variants were found throughout infection, and genetic analyses indicated that both the Rev and gp45 ORFs were under selective pressure. The Rev variant predominant in the inoculum, R1, remained predominant during the early periods following infection (until 35 DPI); however, R1 was replaced by new predominant variants during the recurrent fever period (67-135 DPI). R1 reemerged as the predominant variant during the afebrile period, but a new predominant variant, R93, was associated with the late fever episodes. Rev variants predominant during recurrent febrile and late-febrile periods had significantly higher Rev-mediated nuclear export activity than the variants predominant during the acute and afebrile periods. Statistical correlation was found between Rev activity and different stages of clinical disease. Together, these results suggest that genetic and biological variation in rev may be a contributing factor in EIAV disease progression.

Amino Acid Sequence↗

Clotiapine for acute psychotic illnesses.

BACKGROUND: Acute psychotic illness, especially when associated with agitated or violent behaviour, requires urgent pharmacological tranquillisation or sedation. Clotiapine, a dibenzothiazepine neuroleptic, is being used for this purpose in several countries. OBJECTIVES: To estimate the effects of clotiapine when compared to other 'standard' or 'non-standard' treatments of acute psychotic illness in controlling disturbed behaviour and reducing psychotic symptoms. SEARCH STRATEGY: The Cochrane Controlled Trials Register (Issue 2, 2000), The Cochrane Schizophrenia Group's Register (May 2000), EMBASE (1980-2000), MEDLINE (1966-2000), PASCAL (1973-2000) and PsycLIT (1970-2000) were methodically searched. This was supplemented by hand searching reference lists, contacting industry and relevant authors. SELECTION CRITERIA: Randomised clinical trials comparing clotiapine to any treatment, for people with acute psychotic illnesses such as in schizophrenia, schizoaffective disorder, mixed affective disorders, manic phase of bipolar disorder, brief psychotic episode or organic psychosis following substance abuse. DATA COLLECTION AND ANALYSIS: Studies were reliably selected, quality assessed and data extracted. Data were excluded where more than 50% of participants in any group were lost to follow up. For binary outcomes a standard estimation of the risk ratio (RR) and its 95% confidence interval (CI) was calculated. Where possible, the weighted number needed to treat statistic (NNT), and its 95% confidence interval (CI), was also calculated. If heterogeneity was found, a random effects model was used. For continuous outcomes, endpoint data were preferred to change data. Non-skewed data from valid scales were summated using a weighted mean difference (WMD). Again, if heterogeneity was found a random effects model was used. A Mantel-Haenszel chi-square test was used to investigate the possibility of heterogeneity. MAIN RESULTS: Five trials were included. None compared clotiapine with placebo, but control drugs were either antipsychotics (chlorpromazine, perphenazine, trifluoperazine and zuclopenthixol acetate) or benzodiazepines (lorazepam). Versus antipsychotics: results for global clinical outcome were heterogeneous (p=0.09) but did not suggest clotiapine to be superior, or inferior, to chlorpromazine, perphenazine, or trifluoperazine (total randomised = 83). Use of clotiapine did change the proportion of people ready for hospital discharge by the end of the study in one small trial (n=49, RR 1.04 95%CI 0.96 to 2.12). Overall, attrition rates were low. No significant difference was found for those allocated to clotiapine compared with people randomised to other antipsychotics (n=121, RR 2.26 95%CI 0.40 to 13). Weak data suggests that clotiapine may result in less need for antiparkinsonian treatment compared with zuclopenthixol acetate (n=38, RR 0.43 95%CI 0.02 to 0.98). Versus lorazepam: when used to control aggressive/violent outbursts for people already treated with haloperidol, clotiapine did not significantly improve mental state compared to lorazepam (WMD -3.36 95%CI -8.09 to 1.37). Much data could not be pooled due to skew or inadequate presentation of results. Economic outcomes and satisfaction with care were not addressed. REVIEWER'S CONCLUSIONS: We found no significant evidence to support the use of clotiapine rather than other 'standard' or 'non-standard' treatments for the management of acute psychotic illness. The trials included in this review all present important methodological flaws. We do not wish to discourage clinicians from using clotiapine in the psychiatric emergency, we would just like to point out the fact that good quality controlled trials are needed on this subject.

Antipsychotic Agents↗

Droperidol for acute psychosis.

BACKGROUND: People with acute psychotic illnesses, especially when associated with agitated or violent behaviour, may require urgent pharmacological tranquillisation or sedation. Droperidol, a butyrophenone neuroleptic, is used for this purpose in several countries. OBJECTIVES: To estimate the effects of droperidol when compared to other treatments for controlling disturbed behaviour and reducing psychotic symptoms for people with suspected acute psychotic illnesses. SEARCH STRATEGY: The Cochrane Controlled Trials Register (Issue 2, 2000), The Cochrane Schizophrenia Group's Register (May 2000), EMBASE (1980-2000), MEDLINE (1966-2000), PASCAL (1973-2000) and PsycLIT (1970-2000) were methodically searched. Twenty-one other databases were also searched as part of a broader project and this composite database was searched for this review. This was supplemented by hand searching reference lists, contacting industry and relevant authors. SELECTION CRITERIA: Randomised clinical trials comparing droperidol to any treatment, for people with suspected acute psychotic illnesses, such as schizophrenia, schizoaffective disorder, mixed affective disorders, manic phase of bipolar disorder or brief psychotic episode. DATA COLLECTION AND ANALYSIS: Studies were reliably selected, quality assessed and data extracted. Data were excluded where more than 50% of participants were lost to follow up. For binary outcomes, standard estimations of risk ratio (RR) and their 95% confidence intervals (CI) were calculated. Where possible, weighted number needed to treat or harm statistics (NNT, NNH), and their 95% confidence intervals (CI), were also calculated. MAIN RESULTS: Only two clearly relevant randomised trials with usable data were identified. One additional study was included but focused on outcomes at 30 days rather than a few hours. One small (n=41) randomised trial compared droperidol (10mg IV) with placebo IV and found that people allocated to droperidol were significantly less likely to need additional haloperidol injections in the first few minutes (n=41, RR 0.37 CI 0.2 to 0.7, NNT 2 CI 1 to 10) than those given placebo. By 90 minutes this difference was still evident but not statistically significant (RR 0.46 CI 0.2 to 1.2). When 5mg IM droperidol was compared to 5mg IM haloperidol people given droperidol were again less likely to need additional injections by 30 minutes, than those given haloperidol, but this result did not quite reach conventional levels of statistical significance (n=27, RR 0.45 CI 0.2 to 1.01). One person out of 16 given haloperidol experienced a mild dystonic reaction, and none of the 11 people allocated to droperidol were reported to have experienced adverse effects. REVIEWER'S CONCLUSIONS: This is an important and surprisingly under-researched area. Use of droperidol for the emergency situation is currently justified on experience rather than evidence from well conducted and reported randomised trials.

Acute Disease↗

PAQ: Partition Analysis of Quasispecies.

MOTIVATION: The complexities of genetic data may not be accurately described by any single analytical tool. Phylogenetic analysis is often used to study the genetic relationship among different sequences. Evolutionary models and assumptions are invoked to reconstruct trees that describe the phylogenetic relationship among sequences. Genetic databases are rapidly accumulating large amounts of sequences. Newly acquired sequences, which have not yet been characterized, may require preliminary genetic exploration in order to build models describing the evolutionary relationship among sequences. There are clustering techniques that rely less on models of evolution, and thus may provide nice exploratory tools for identifying genetic similarities. Some of the more commonly used clustering methods perform better when data can be grouped into mutually exclusive groups. Genetic data from viral quasispecies, which consist of closely related variants that differ by small changes, however, may best be partitioned by overlapping groups. RESULTS: We have developed an intuitive exploratory program, Partition Analysis of Quasispecies (PAQ), which utilizes a non-hierarchical technique to partition sequences that are genetically similar. PAQ was used to analyze a data set of human immunodeficiency virus type 1 (HIV-1) envelope sequences isolated from different regions of the brain and another data set consisting of the equine infectious anemia virus (EIAV) regulatory gene rev. Analysis of the HIV-1 data set by PAQ was consistent with phylogenetic analysis of the same data, and the EIAV rev variants were partitioned into two overlapping groups. PAQ provides an additional tool which can be used to glean information from genetic data and can be used in conjunction with other tools to study genetic similarities and genetic evolution of viral quasispecies.

Algorithms↗

Tumor cell toxicity of hypericin and related analogs.

A series of hypericin analogs were found to differ in their cytotoxic activity induced by ambient light levels. These analogs vary in their ability to partition into cells, to generate singlet oxygen as well as in other photophysical properties. The data suggest that the biological activity of hypericin is due to a combination of factors whose roles may vary under different circumstances.

Anthracenes↗