Aliphatic Ketone Claisen Rearrangement: Troubleshooting the Transetherification Step by Identifying a Stable Acid Catalyst.

After optimization for retention of catalytic activity, 4-chlorobenzoic acid emerged as the optimal catalyst for the aliphatic ketone Claisen rearrangement. The optimal catalyst enables a one-pot, metal-free, catalytic protocol from allylic alcohols to γ,δ-unsaturated ketones. The optimized process tolerates a range of substrates, including substituents with acid-labile protecting groups.

Quantitative assessment of the impact of standard agreement templates on multisite clinical trial start up time.

Contracting delays remain a challenge to the successful initiation of multisite clinical research in the US. The Clinical and Translational Science Awards (CTSA) Contracts Processing Study showed average contract negotiation duration of > 100 days for industry-sponsored or investigator-initiated contracts. Such delays create enormous costs to sponsors and to patients waiting to use new evidence-based treatments.

Antibody avidity-based approach to estimate population-level incidence of hepatitis C.

Background & Aims: Accurate HCV incidence estimates are critical for monitoring progress towards HCV elimination goals, including an 80% reduction in HCV incidence by 2030. Moreover, incidence estimates can help guide prevention and treatment programming, particularly in the context of the US opioid epidemic.

Methods: An inexpensive, Genedia-based HCV IgG antibody avidity assay was evaluated as a platform to estimate cross-sectional, population-level primary HCV incidence using 1,840 HCV antibody and RNA-positive samples from 875 individuals enrolled in 5 cohort studies in the US and India.

Hepatitis C Virus Infection in Indigenous Populations in the United States and Canada.

American Indian/Alaska Native (AI/AN) and Canadian Indigenous people are disproportionally affected by hepatitis C virus (HCV) infection yet are frequently underrepresented in epidemiologic studies and surveys often used to inform public health efforts. We performed a systematic review of published and unpublished literature and summarized our findings on HCV prevalence in these Indigenous populations. We found a disparity of epidemiologic literature of HCV prevalence among AI/AN in the United States and Indigenous people in Canada.

Talking About Hepatitis C: FAQs From Young Adults Who Inject Drugs.

Introduction: Young adults who inject drugs and live in rural communities are at high risk for hepatitis C virus (HCV) infection. Recent changes in HCV treatment must be communicated within these communities to improve access to care and reduce HCV transmission.

Methods: Field workers in the ¡VÁLE! Hepatitis Treatment and Integrated Prevention Services study identified frequently asked questions (FAQs) posed by young-adult participants at high risk for HCV during screening and educational sessions.

Use-inspired basic research on individual differences in face identification: implications for criminal investigation and security.

This journal is dedicated to "use-inspired basic research" where a problem in the world shapes the hypotheses for study in the laboratory. This review considers the role of individual variation in face identification and the challenges and opportunities this presents in security and criminal investigations. We show how theoretical work conducted on individual variation in face identification has, in part, been stimulated by situations presented in the real world.

The effect of arousal and eye gaze direction on trust evaluations of stranger's faces: A potential pathway to paranoid thinking.

Background And Objectives: When asked to evaluate faces of strangers, people with paranoia show a tendency to rate others as less trustworthy. The present study investigated the impact of arousal on this interpersonal bias, and whether this bias was specific to evaluations of trust or additionally affected other trait judgements. The study also examined the impact of eye gaze direction, as direct eye gaze has been shown to heighten arousal.

Transforming the Activation of Clinical Trials.

The Institute of Medicine and US Food and Drug Administration (FDA) recognize that activating clinical trials in the United States is lengthy and inefficient. Downstream consequences include increased expense, suboptimal accrual, move of clinical trials overseas, and delayed availability of treatments for patients. An in-tandem processing initiative is here highlighted that transformed the activation of clinical trials (TACT), reduced the activation time by 70%, and offers a paradigm for enhanced translational readiness.

Inside Job: Methods for Delivering Proteins to the Interior of Mammalian Cells.

Currently, 7 of the top 10 selling drugs are biologics, and all of them are proteins. Their large size, structural complexity, and molecular diversity often results in surfaces capable of potent and selective recognition of receptors that challenge, or evade, traditional small molecules. However, most proteins do not penetrate the lipid bilayer exterior of mammalian cells.

Compensatory shifts in visual perception are associated with hallucinations in Lewy body disorders.

Visual hallucinations are a common, distressing, and disabling symptom of Lewy body and other diseases. Current models suggest that interactions in internal cognitive processes generate hallucinations. However, these neglect external factors.

Evaluation of Nanobody Conjugates and Protein Fusions as Bioanalytical Reagents.

Enzyme-linked immunosorbent assay (ELISA), flow cytometry, and Western blot are common bioanalytical techniques. Successful execution traditionally requires the use of one or more commercially available antibody-small-molecule dyes or antibody-reporter protein conjugates that recognize relatively short peptide tags (<15 amino acids). However, the size of antibodies and their molecular complexity (by virtue of post-translational disulfide formation and glycosylation) typically require either expression in mammalian cells or purification from immunized mammals.

Minimalist Antibodies and Mimetics: An Update and Recent Applications.

The immune system utilizes antibodies to recognize foreign or disease-relevant receptors, initiating an immune response to destroy unwelcomed guests. Because researchers can evolve antibodies to bind virtually any target, it is perhaps unsurprising that these reagents, and their small-molecule conjugates, are used extensively in clinical and basic research environments. However, virtues of antibodies are countered by significant challenges.

Resurfaced cell-penetrating nanobodies: A potentially general scaffold for intracellularly targeted protein discovery.

By virtue of their size, functional group diversity, and complex structure, proteins can often recognize and modulate disease-relevant macromolecules that present a challenge to small-molecule reagents. Additionally, high-throughput screening and evolution-based methods often make the discovery of new protein binders simpler than the analogous small-molecule discovery process. However, most proteins do not cross the lipid bilayer membrane of mammalian cells.

Visual Hallucinations in Older People: Appraisals but not Content or Phenomenology Influence Distress.

Background: A previous study (Gauntlett-Gilbert and Kuipers, 2005) has suggested that distress associated with complex visual hallucinations (CVHs) in younger adults with psychosis may more strongly relate to appraisals of meaning than to the content of the hallucination. However, visual hallucinations are most commonly seen in the disorders of later life, where this relationship has not been investigated.

Aim: To establish if there is a relationship between appraisals of CVHs and distress in older, non-psychotic people with CVHs.

Visual Priming and Visual Hallucinations in Parkinson's Disease. Evidence for Normal Top-Down Processes.

Background: Visual hallucinations (VH) are common in Parkinson's disease (PD) and are associated with increased morbidity and mortality. Current explanations for VH in PD suggest combined impairments in top-down attentional and bottom-up perceptual processes, which allow the passive "release" of stored images. Alternative models in other disorders have suggested that top-down factors may actively encourage hallucinations.

Mutagenesis modulates the uptake efficiency, cell-selectivity, and functional enzyme delivery of a protein transduction domain.

Alanine scanning mutagenesis of a recently reported prostate cancer cell-selective Protein Transduction Domain (PTD) was used to assess the specific contribution each residue plays in cell uptake efficiency and cell-selectivity. These studies resulted in the identification of two key residues. Extensive mutagenesis at these key residues generated multiple mutants with significantly improved uptake efficiency and cell-selectivity profiles for targeted cells.

A preliminary investigation into the existence of a hypervigilance subtype of auditory hallucination in people with psychosis.

Background: The phenomenological heterogeneity of auditory hallucinations (AHs) means individual models struggle to account for all aspects of the experience. One alternative is that distinct subtypes of AHs exist, with each requiring their own unique explanatory model and tailored cognitive behavioural intervention strategies.

Aims: This exploratory study tested for the presence of one specific potential AH-subtype, hypervigilance hallucinations (HV-AHs).

Small γ-Ray Doses Prevent Rather than Increase Lung Tumors in Mice.

We show evidence for low doses of γ rays preventing spontaneous hyperplastic foci and adenomas in the lungs of mice, presumably via activating natural anticancer defenses. The evidence partly relates to a new study we conducted whereby a small number of female A/J mice received 6 biweekly dose fractions (100 mGy per fraction) of γ rays to the total body which prevented the occurrence of spontaneous hyperplastic foci in the lung. We also analyzed data from a much earlier Oak Ridge National Laboratory study involving more than 10,000 female RFMf/Un mice whereby single γ-ray doses from 100 to 1,000 mGy prevented spontaneous lung adenomas.

Low-dose gamma-radiation inhibits benzo[a]pyrene-induced lung adenoma development in a/j mice.

Low-dose ionizing radiation (LDR) may lead to suppression of smoking-related lung cancer. We examined the effects of a known cigarette smoke carcinogen Benzo[a]pyrene (B[a]P) alone or in combination with fractionated low-dose gamma radiation (60 - 600 mGy total dose) on the induction of lung neoplasms in the A/J mouse. Our results show that 600 mGy of gamma radiation delivered in six biweekly fractions of 100 mGy starting 1 month after B[a]P injection significantly inhibits the development of lung adenomas per animal induced by B[a]P.

Dynamic properties influence the perception of facial expressions.

Two experiments were conducted to investigate the role played by dynamic information in identifying facial expressions of emotion. Dynamic expression sequences were created by generating and displaying morph sequences which changed the face from neutral to a peak expression in different numbers of intervening intermediate stages, to create fast (6 frames), medium (26 frames), and slow (101 frames) sequences. In experiment 1, participants were asked to describe what the person shown in each sequence was feeling.

Recognising facial surfaces.

The extent to which faces depicted as surfaces devoid of pigmentation and with minimal texture cues ('head models') could be matched with photographs (when unfamiliar) and identified (when familiar) was examined in three experiments. The head models were obtained by scanning the three-dimensional surface of the face with a laser, and by displaying the surface measured in this way by using standard computer-aided design techniques. Performance in all tasks was above chance but far from ceiling.