Materials studies related to the Cu₂S/ZnCdS heterojunction : first quarterly report for period March 15 - June 15, 1980 /

"Work Performed Under Contract No. AC02-77CH00178."

A few lives; a report of Dosoris, study and treatment home for adolescent girls, 1945-1947.

Mode of access: Internet.

Factors influencing the number needed to excise: excision rates of pigmented lesions by general practitioners

Objective: To identify doctor and patient characteristics associated with excision of benign versus malignant pigmented skin lesions. Design, setting and participants: Retrospective audit of data on 4741 pigmented skin lesions excised from November 1998 to February 2000 by 468 general practitioners (39% response rate) from 223 practices in Perth, WA. (The data used were from the baseline period of a randomised controlled trial of a diagnostic aid for pigmented skin lesions.) Main outcome measure: The number needed to treat (NNT), defined as the number of pigmented lesions needed to be excised to identify one melanoma, in relation to demographic characteristics of GPs and patients. Results: Relatively more benign lesions were excised per melanoma (NNT = 83) in the youngest patients (aged 10-19 years) compared with the oldest (aged greater than or equal to 70) (NNT = 11) (P [trend]

Smoking and schizophrenia: is symptom profile related to smoking and which antipsychotic medication is of benefit in reducing cigarette use?

Smoking rate is disproportionately high among patients with schizophrenia, resulting in significant morbidity and mortality. However, cigarette smoking has been reported to have beneficial effects on negative symptoms, extrapyramidal symptoms, cognitive functioning and mood symptoms. Therefore, smoking cessation may worsen disability in schizophrenia. The association between smoking and these key clinical parameters was examined. Additionally, severity of smoking across four different antipsychotic treatment groups was explored. One hundred and forty-six patients with schizophrenia were assessed for smoking using expired carbon monoxide and smoking history. They were administered the Positive and Negative Symptom Scale, The Extrapyramidal Symptom Rating Scale, the Barnes Akathisia Rating Scale, Reitans Trail-making Test (A and B) and General Health Questionnaire-28. There was no difference in the chlorpromazine equivalent dose of any of the medications studied. Atypical agents were associated with significantly lower levels of smoking when compared with typical medications. There was no difference in smoking severity between the individual atypical medications examined. Similarly, there were no significant differences between smoking and non-smoking groups with regard to Positive and Negative Symptom Scale, Extrapyramidal Symptom Rating Scale, Trail-making Test and General Health Questionnaire-28. However, there was a significant difference between these groups with the smoking group demonstrating less akathisia. Smoking is not associated with positive, negative cognitive and mood symptoms in schizophrenia. Smoking is associated with lower levels of antipsychotic induced akathisia. Clinicians should not be discouraged from helping patients stop smoking for fear of worsening symptoms. However, akathisia may emerge upon cessation of smoking. Switching patients from typical to atypical antipsychotics may assist patients with schizophrenia to give up smoking.

Primary data sets of the hydrographic atlas of the Southern Ocean

The general knowledge of the hydrographic structure of the Southern Ocean is still rather incomplete since observations particularly in the ice covered regions are cumbersome to be carried out. But we know from the available information that thermohaline processes have large amplitudes and cover a wide range of scales in this part of the world ocean. The modification of water masses around Antarctica have indeed a worldwide impact, these processes ultimately determine the cold state of the present climate in the world ocean. We have converted efforts of the German and Russian polar research institutions to collect and validate the presently available temperature, salinity and oxygen data of the ocean south of 30°S latitude. We have carried out this work in spite of the fact that the hydrographic programme of the World Ocean Circulation Experiment (WOCE) will provide more new information in due time, but its contribution to the high latitudes of the Southern Ocean is quite sparse. The modified picture of the hydrographic structure of the Southern Ocean presented in this atlas may serve the oceanographic community in many ways and help to unravel the role of this ocean in the global climate system. This atlas could only be prepared with the altruistic assistance of many colleagues from various institutions worldwide who have provided us with their data and their advice. Their generous help is gratefully acknowledged. During two years scientists from the Arctic and Antarctic Research Institute in St. Petersburg and the Alfred Wegener Institute for Polar and Marine Research in Bremerhaven have cooperated in a fruitful way to establish the atlas and the archive of about 38749 validated hydrographic stations. We hope that both sources of information will be widely applied for future ocean studies and will serve as a reference state for global change considerations.

DRD2/ANKK1 Taq1A (rs 1800497 C>T) genotypes are associated with susceptibility to second generation antipsychotic-induced akathisia

Rationale Although the advent of atypical, second-generation antipsychotics (SGAs) has resulted in reduced likelihood of akathisia, this adverse effect remains a problem. Extrapyramidal adverse effects are associated with increased drug occupancy of dopamine 2 receptors (DRD2). The A1 allele of the DRD2/ANKK1,rs1800497, is associated with decreased striatal DRD2 density. Objectives The aim of this study was to identify whether the A1(T) allele of the DRD2/ANKK1 was associated with akathisia (measured with the Barnes Akathisia Rating Scale) in a clinical sample of 234 patients treated with antipsychotics. Results Definite akathisia (a score≥ 2 for the global clinical assessment of akathisia) was significantly less common in subjects prescribed SGAs (16.8 %) than those prescribed FGAs (47.6%), p<0.0001. Overall, 24.1% of A1+ (A1A2/A1A1) patients treated with SGAs had akathisia compared to 10.8% of A1- (A2A2) patients. A1+ (A1A2/A1A1) patients administered SGAs also had higher global clinical assessment of akathisia scores than A1- subjects (p=0.01). SGAs maintained their advantage over FGAs regarding akathisia even in A1+ patients treated with SGAs. Conclusions These results strongly suggest that A1+ variants of the DRD2/ANKK1 Taq1A allele confer risk for akathisia in patients treated with SGAs and may explain inconsistencies across prior studies comparing FGAs and SGAs.

Infection of monkeys by simian-human immunodeficiency viruses with transmitted/founder clade C HIV-1 envelopes.

Simian-human immunodeficiency viruses (SHIVs) that mirror natural transmitted/founder (T/F) viruses in man are needed for evaluation of HIV-1 vaccine candidates in nonhuman primates. Currently available SHIVs contain HIV-1 env genes from chronically-infected individuals and do not reflect the characteristics of biologically relevant HIV-1 strains that mediate human transmission. We chose to develop clade C SHIVs, as clade C is the major infecting subtype of HIV-1 in the world. We constructed 10 clade C SHIVs expressing Env proteins from T/F viruses. Three of these ten clade C SHIVs (SHIV KB9 C3, SHIV KB9 C4 and SHIV KB9 C5) replicated in naïve rhesus monkeys. These three SHIVs are mucosally transmissible and are neutralized by sCD4 and several HIV-1 broadly neutralizing antibodies. However, like natural T/F viruses, they exhibit low Env reactivity and a Tier 2 neutralization sensitivity. Of note, none of the clade C T/F SHIVs elicited detectable autologous neutralizing antibodies in the infected monkeys, even though antibodies that neutralized a heterologous Tier 1 HIV-1 were generated. Challenge with these three new clade C SHIVs will provide biologically relevant tests for vaccine protection in rhesus macaques.

Optimization of novel acyl pyrrolidine inhibitors of hepatitis C virus RNA-dependent RNA polymerase leading to a development candidate

Optimization of a pyrrolidine-based template using structure-based design and physicochemical considerations has provided a development candidate 20b (3082) with submicromolar potency in the HCV replicon and good pharmacokinetic properties.

Estudio de prevalencia de dificultades de aprendizaje en el c??lculo aritm??tico

Resumen tomado de la publicaci??n

Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge

A major problem in hepatitis C virus (HCV) immunotherapy or vaccine design is the extreme variability of the virus. We identified human monoclonal antibodies (mAbs) that neutralize genetically diverse HCV isolates and protect against heterologous HCV quasispecies challenge in a human liver-chimeric mouse model. The results provide evidence that broadly neutralizing antibodies to HCV protect against heterologous viral infection and suggest that a prophylactic vaccine against HCV may be achievable.

Heterogeneously catalyzed asymmetric hydrogenation of C = C bonds directed by surface-tethered chiral modifiers

Asymmetric hydrogenation of C=C bonds is of the highest importance in organic synthesis, and such reactions are currently carried out with organometallic homogeneous catalysts. Achieving heterogeneous metal-catalyzed hydrogenation, a highly desirable goal, necessitates forcing the crucial enantiodifferentiating step to take place at the metal surface. By synthesis and application of six chiral sulfide ligands that anchor robustly to Pd nanoparticles and resist displacement, we have for the first time accomplished heterogeneous enantioselective catalytic hydrogenation of isophorone. High resolution XPS data established that ligand adsorption from solution occurred exclusively on the Pd nanoparticles and not on the carbon support. All ligands contained a pyrrolidine nitrogen to enable their interaction with the isophorone substrate while the sulfide functionality provided the required interaction with the Pd surface. Enantioselective turnover numbers of up to similar to 100 product molecules per ligand molecule were found with a very large variation in asymmetric induction between ligands: observed enantiomeric excesses increased with increasing size of the alkyl group in the sulfide. This likely reflects varying degrees of ligand dispersion on the surface: bulky substituent groups hinder close approach of ligand molecules to each other, inhibiting close-packed island formation, favoring dispersion as separate molecules, and leading to effective asymmetric induction. Conversely, small substituents favor island formation leading to very low asymmetric induction. Enantioselective reaction most likely involves initial formation of an enamine or iminium species, confirmed by use of an analogous tertiary amine, which leads to racemic product. Ligand rigidity and resistance to self-assembled monolayer formation are important attributes that should be designed into improved chiral modifiers.

Burton Memorial Tower

Albert Kahn, architect. Built 1936. On verso: The 10-story Burton Memorial Tower has been a landmark on the University of Michigan Ann Arbor campus since the tower's 1936 dedication ... The largest bell in the carillon, "Big Baird," weighs 12 tons and sounds E-flat below middle C at the stroke of its 350-pound clapper. The smallest bell weighs four pounds and sounds A-sharp, four and one-half octaves higher. University of Michigan News and Information Services, 412 Maynard, Ann Arbor, MI. 48109-1399. Negative #5546. Frame 17