bluuebunny/crossref_metadata_2025 huggingface dataset:
Retracted: ‘Clinical trials in Alzheimer’s disease’: immunotherapy approaches
Authors: Delrieu Julien , Ousset Pierre Jean , Caillaud Céline , Vellas Bruno
Published: September 2011

J. Neurochem. (2012) 120 (Suppl. 1), 186–193.

Recent advances in the understanding of Alzheimer’s disease pathogenesis have led to the development of numerous compounds that might modify the disease process. Amyloid β (Aβ) peptide represents an important molecular target for intervention in Alzheimer’s disease. Several types of Aβ peptide immunotherapy for Alzheimer’s disease are under investigation, direct immunization with synthetic intact Aβ42, active immunization involving the administration of synthetic fragments of Aβ peptide conjugated to a carrier protein and passive administration with monoclonal antibodies directed against Aβ peptide. Pre‐clinical studies showed that immunization against Aβ peptide can provide protection and reversal of the pathology of Alzheimer’s disease in animal models. Indeed, several adverse events have been described like meningoencephalitis with AN1792, vasogenic edema and microhemorrhages with bapineuzumab. Although immunotherapy approaches resulted in clearance of amyloid plaques in patients with Alzheimer’s disease, this clearance did not show significant cognitive effect for the moment. Currently, several Aβ peptide immunotherapy approaches are under investigation but also against tau pathology.
Shared space, distant lives? Understanding family and intimacy at home through the lens of internet gambling
Authors: Valentine Gill , Hughes Kahryn
Published: September 2011

This paper explores how space helps us to understand the ways that people relate to each other and manage the boundary between the personal and the social/familial by using original empirical material from a study of problem internet gamblers and their families. Here, we conceptualise intimacy in terms of the interiority of ‘family’ life, and as experienced particularly, though not exclusively, through the affective space of the home. The disclosure of an individual’s previously hidden problem gambling provides an important lens through which to understand the concepts of personal relationships, family and intimacy because it provides a rupture in ‘normal’ taken‐for‐granted domestic life in which individual family members are forced to reflect on: their relationships with the problem gambler and he/she with the family from whom they have concealed their gambling; the extent of their intimacy and togetherness (in terms of both space and time) in the light of the exposure of the gambler’s secrecy and lies; the degree of their responsibilities for, and emotional commitments to, each other; and how they might develop new ways of relating to each other in, and beyond, the home.
Structure‐activity relationships of vanilloid receptor agonists for arteriolar TRPV1
Authors: Czikora Á , Lizanecz E , Bakó P , Rutkai I , Ruzsnavszky F , Magyar J , Pórszász R , Kark T , Facskó A , Papp Z , Édes I , Tóth A
Published: September 2011

BACKGROUND AND PURPOSE The transient receptor potential vanilloid 1 (TRPV1) plays a role in the activation of sensory neurons by various painful stimuli and is a therapeutic target. However, functional TRPV1 that affect microvascular diameter are also expressed in peripheral arteries and we attempted to characterize this receptor.

EXPERIMENTAL APPROACH Sensory TRPV1 activation was measured in rats by use of an eye wiping assay. Arteriolar TRPV1‐mediated smooth muscle specific responses (arteriolar diameter, changes in intracellular Ca2+) were determined in isolated, pressurized skeletal muscle arterioles obtained from the rat and wild‐type or TRPV1−/− mice and in canine isolated smooth muscle cells. The vascular pharmacology of the TRPV1 agonists (potency, efficacy, kinetics of action and receptor desensitization) was determined in rat isolated skeletal muscle arteries.

KEY RESULTS Capsaicin evoked a constrictor response in isolated arteries similar to that mediated by noradrenaline, this was absent in arteries from TRPV1 knockout mice and competitively inhibited by TRPV1 antagonist AMG9810. Capsaicin increased intracellular Ca2+ in the arteriolar wall and in isolated smooth muscle cells. The TRPV1 agonists evoked similar vascular constrictions (MSK‐195 and JYL‐79) or were without effect (resiniferatoxin and JYL‐273), although all increased the number of responses (sensory activation) in the eye wiping assay. Maximal doses of all agonists induced complete desensitization (tachyphylaxis) of arteriolar TRPV1 (with the exception of capsaicin). Responses to the partial agonist JYL‐1511 suggested 10% TRPV1 activation is sufficient to evoke vascular tachyphylaxis without sensory activation.

CONCLUSIONS AND IMPLICATIONS Arteriolar TRPV1 have different pharmacological properties from those located on sensory neurons in the rat.
National Study of Emergency Department Observation Services
Authors: Wiler Jennifer L. , Ross Michael A. , Ginde Adit A.
Published: September 2011

ACADEMIC EMERGENCY MEDICINE 2011; 18:959–965 © 2011 by the Society for Academic Emergency Medicine

Objectives:  The objective was to describe patient and facility characteristics of emergency department (ED) observation services in the United States.

Methods:  The authors analyzed the 2007 National Hospital Ambulatory Medical Care Survey (NHAMCS). Characteristics of EDs with observation units (OUs) were compared to those without, and patients with a disposition of ED observation were compared to those with a “short‐stay” (<48 hour) hospital admission. Results are descriptive and without formal statistical comparisons for this observational analysis.

Results:  An estimated 1,746 U.S. EDs (36%) reported having OUs, of which 56% are administratively managed by ED staff. Fifty‐two percent of hospitals with ED‐managed OUs are in an urban location, and 89% report ED boarding, compared to 29 and 65% of those that do not have an OU. The admission rate is 38% at those with ED‐managed OUs and 15% at those without OUs. Of the 15.1% of all ED patients who are kept in the hospital following an ED visit, one‐quarter are kept for either a short‐stay admission (1.8%) or an ED observation admission (2.1%). Most (82%) ED observation patients were discharged from the ED. ED observation patients were similar to short‐stay admission patients in terms of age (median = 52 years for both, interquartile range = 36 to 70 years), self‐pay (12% vs. 10%), ambulance arrival (37% vs. 36%), urgent/emergent triage acuity (77% vs. 74%), use of ≥1 ED medication (64% vs.76%), and the most common primary chief complaints and primary diagnoses.

Conclusions:  Over one‐third of U.S. EDs have an OU. Short‐stay admission patients have similar characteristics as ED observation patients and may represent an opportunity for the growth of OUs.
Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation
Authors: Pinto Rita , Carvalho Ana S. , Conze Tim , Magalhães Ana , Picco Gianfranco , Burchell Joy M. , Taylor‐Papadimitriou Joyce , Reis Celso A. , Almeida Raquel , Mandel Ulla , Clausen Henrik , Söderberg Ola , David Leonor
Published: September 2011

Mucin glycoproteins are major secreted or membrane‐bound molecules that, in cancer, show modifications in both the mucin proteins expression and in the O‐glycosylation profile, generating some of the most relevant tumour markers in clinical use for decades. Thus far, the identification of these biomarkers has been based on the detection of either the protein or the O‐glycan modifications. We therefore aimed to identify the combined mucin and O‐glycan features, that is, specific glycoforms, in an attempt to increase specificity of these cancer biomarkers. Using in situ proximity ligation assays (PLA) based on existing monoclonal antibodies directed to MUC1, MUC2, MUC5AC and MUC6 mucins and to cancer‐associated carbohydrate antigens Tn, Sialyl‐Tn (STn), T, Sialyl‐Lea (SLea) and Sialyl‐Lex (SLex) we screened a series of 28 mucinous adenocarcinomas from different locations (stomach, ampulla of Vater, colon, lung, breast and ovary) to detect specific mucin glycoforms. We detected Tn/STn/SLea/SLex‐MUC1 and STn/SLea/SLex‐MUC2 glycoforms in $50% of the cases, with a variable distribution among organs. Some new glycoforms‐T/SLea‐MUC2, STn/T/SLea/SLex‐MUC5AC and STn/T/SLea/SLex‐MUC6‐were identified for the first time in the present study in a variable percentage of cases from different organs. In conclusion, application of the PLA technique allowed sensitive detection of specific aberrant mucin glycoforms in cancer, increasing specificity to the use of antibodies either to the mucin protein backbone or to the O‐glycan haptens alone.
Use of an antispasmodic (rociverine) to shorten the length of labor: a randomized, placebo‐controlled trial
Authors: CROMI ANTONELLA , GHEZZI FABIO , AGOSTI MASSIMO , UCCELLA STEFANO , PIAZZA NICOLETTA , SERATI MAURIZIO , BOLIS PIERFRANCESCO
Published: September 2011

Objective. To determine the effectiveness of rociverine, an antispasmodic drug, for reducing the duration of labor among nulliparous women managed according to a standard intrapartum protocol. Design. Randomized controlled trial. Setting. An academic tertiary care hospital. Population. Nulliparae in spontaneous active labor, with cervical dilatation between 3 and 5cm. Methods. Participants were randomly assigned to receive either an intramuscular injection of 20mg rociverine (n=55) or the same volume of saline (n=56). Main Outcome Measure. Cervical dilatation rate (from administration of study drug to full dilatation). Results. Laboring women who received rociverine had faster cervical dilatation than those assigned to placebo (2.43±1.84 vs. 1.85±1.38cm/hour, p=0.03). The time interval from treatment administration to full cervical dilatation was shorter in the rociverine group than in the placebo group (220±125 vs. 278±129min, p=0.04). No difference was found in any other obstetric outcome. No adverse effects have been recorded from rociverine administration. Conclusions. Intrapartum administration of rociverine to nulliparous women may help to reduce the duration of the first stage of labor in a context of uniform labor management.
Hydration measurements of the stratum corneum: comparison between the capacitance method (digital version of the Corneometer CM 825®) and the impedance method (Skicon‐200EX®)
Authors: Clarys Peter , Clijsen Ron , Taeymans Jan , Barel André O.
Published: September 2011

Background

Measurement of stratum corneum (SC) hydration often involves the use of commercial instruments. The aim of this study was to compare and validate two recent instruments: the Corneometer 825® (digital probe) and the Skicon‐200 EX®.

Methods

In vitro calibration was carried out on filter pads using different solvents, measurements over different layers of plastic foils, and evaluation of desorption kinetics. In vivo measurements were carried out on skin sites covering a range of very dry to well‐hydrated skin areas.

Results

Conductance measurements are influenced by electrolytes while capacitance measurements are not. Dielectric constant of the solvents influences the values of both instruments (r respectively 0.92 and 0.99). The capacitance method carries information from deeper layers (up to 45 μm) compared with the conductance instrument (up to 15 μm). Desorption experiments show a strong relation between the amount of water and respectively the capacitance and the conductance values. The in vivo experiments revealed a strong relation between the two methods (r = 0.97). Sensitivity of the capacitance method is limited for the highest hydration values.

Conclusions

Both instruments allow a certain calibration and both give good estimates of the SC hydration.
Satisfying Sexual Events as Outcome Measures in Clinical Trial of Female Sexual Dysfunction
Authors: Kingsberg Sheryl A. , Althof Stanley E.
Published: September 2011

Introduction

Assessing the sexual response in women with female sexual dysfunctions (FSDs) in clinical trials remains difficult. Part of the challenge is the development of meaningful and valid end points that capture the complexity of women’s sexual response.

Aim

The purpose of this review is to highlight the shortcomings of daily diaries and the limitations of satisfying sexual events (SSEs) as primary end points in clinical trials of women with hypoactive sexual desire disorder (HSDD) as recommended by the Food and Drug Administration (FDA) in their draft guidance on standards for clinical trials in women with FSD.

Methods

Clinical trials in women with HSDD using SSEs as primary end points were reviewed.

Main Outcome Measures

The agreement between three outcome measures (SSEs, desire, and distress) was assessed to illustrate to what degree improvements in SSEs were in agreement with improvements in sexual desire and/or personal distress.

Results

Nine placebo-controlled randomized trials in women with HSDD were reviewed: seven with transdermal testosterone and two with flibanserin. In four trials, all using transdermal testosterone 300 µg/day had agreement between changes in SSEs, desire, and distress. In five studies (testosterone 300 µg/day, n = 2; testosterone 150 µg/day, n = 1; flibanserin n = 2), changes in SSEs did not correlate with changes in desire and/or distress and vice versa. It should be noted that in the flibanserin trials, SSEs did correlate with desire assessed using the Female Sexual Function Index but not when it was assessed using the eDiary.

Conclusions

Findings in the literature do not uniformly support the recommendations from the FDA draft guidance to use diary measures in clinical trials of HSDD as primary end points. Patient-reported outcomes appear to be better suited to capture the multidimensional and more subjective information collected in trials of FSD.
DNA barcoding meets molecular scatology: short mtDNA sequences for standardized species assignment of carnivore noninvasive samples
Authors: CHAVES PAULO B. , GRAEFF VANESSA G. , LION MARÍLIA B. , OLIVEIRA LARISSA R. , EIZIRIK EDUARDO
Published: September 2011

Although species assignment of scats is important to study carnivore biology, there is still no standardized assay for the identification of carnivores worldwide, which would allow large‐scale routine assessments and reliable cross‐comparison of results. Here, we evaluate the potential of two short mtDNA fragments [ATP6 (126 bp) and cytochrome oxidase I gene (COI) (187 bp)] to serve as standard markers for the Carnivora. Samples of 66 species were sequenced for one or both of these segments. Alignments were complemented with archival sequences and analysed with three approaches (tree‐based, distance‐based and character‐based). Intraspecific genetic distances were generally lower than between‐species distances, resulting in diagnosable clusters for 86% (ATP6) and 85% (COI) of the species. Notable exceptions were recently diverged species, most of which could still be identified using diagnostic characters and uniqueness of haplotypes or by reducing the geographic scope of the comparison. In silico analyses were also performed for a 110‐bp cytochrome b (cytb) segment, whose identification success was lower (70%), possibly due to the smaller number of informative sites and/or the influence of misidentified sequences obtained from GenBank. Finally, we performed case studies with faecal samples, which supported the suitability of our two focal markers for poor‐quality DNA and allowed an assessment of prey DNA co‐amplification. No evidence of prey DNA contamination was found for ATP6, while some cases were observed for COI and subsequently eliminated by the design of more specific primers. Overall, our results indicate that these segments hold good potential as standard markers for accurate species‐level identification in the Carnivora.
Involvement of poly(3‐hydroxybutyrate) synthesis in catabolite repression of tetralin biodegradation genes in Sphingomonas macrogolitabida strain TFA
Authors: Martín‐Cabello Guadalupe , Moreno‐Ruiz Emilia , Morales Valle , Floriano Belén , Santero Eduardo
Published: August 2011

The tetralin biodegradation genes of Sphingomonas macrogolitabida strain TFA are repressed by catabolite. Insertion mutants in which thn genes are transcribed in the presence of a preferential carbon source and tetralin, bear the insertion in phaC, encoding a poly(3‐hydroxybutyrate) (PHB) synthase, a key enzyme in PHB synthesis. Mutant complementation with phaC genes from either Ralstonia euthropha or TFA restored PHB accumulation and the wild‐type regulatory pattern of thn genes, thus indicating that this accumulation is a signal for carbon sufficient conditions that prevents expression of thn catabolic genes in this α‐proteobacteria.
Characterization of hepatocellular adenoma based on the phenotypic classification: The Kanazawa experience
Authors: Sasaki Motoko , Yoneda Norihide , Kitamura Seiko , Sato Yasunori , Nakanuma Yasuni
Published: September 2011

Aim:  Hepatocellular adenoma (HCA) represents a heterogeneous entity, and recently four major subgroups were identified based on genotype and phenotype classification from Europe. HCA is rare in Asian countries including Japan and there has been no study regarding the subgroups of HCA in Japan.

Methods:  We took advantage of the reported genotype/phenotype classification to analyze 14 HCA (seven women) in Japan.

Results:  We identified one hepatocyte nuclear factor (HNF)1α‐inactivated HCA (one woman), two β‐catenin‐activated HCA (one woman), seven inflammatory HCA (IHCA, two women); four additional cases (three women) had no known phenotypic marker (unclassified HCA). The use of oral contraceptives was found only in two unclassified HCA (29%) cases. Fatty change of the background liver was seen in one β‐catenin‐activated HCA cases, four IHCA (57%) and two unclassified HCA (50%). Hepatic fibrosis was seen in five IHCA (71%) and two unclassified HCA (50%) cases. Four IHCA patients (one woman) were alcohol drinkers and one had alcoholic steatofibrosis and three had alcoholic cirrhosis. Eight HCA (57%) were multiple; one HNF1α‐inactivated HCA (100%), four IHCA (57%) and three unclassified HCA (75%). The tumor was significantly larger in β‐catenin‐activated HCA than in other subgroups. The association of hepatocellular carcinoma was seen only in one case of unclassified HCA.

Conclusion:  This study suggests that IHCA arising in men with alcoholic liver disease may be a major subtype of HCA in Japan.
IQ as a predictor of clinician‐rated mental health problems in children and adolescents
Authors: Mathiassen Børge , Brøndbo Per Håkan , Waterloo Knut , Martinussen Monica , Eriksen Mads , Hanssen‐Bauer Ketil , Kvernmo Siv
Published: September 2011

Objective. Previous studies indicate that low IQ is a substantial risk factor for developing mental health problems. Based on these results, we hypothesized that IQ may predict some of the variance in clinician‐rated severity of children's mental health problems measured with the Children's Global Assessment Scale (CGAS) and Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA). The other aims of this study were to examine if there was any difference in the predictive ability of the different IQ scores of the Wechsler Intelligence Scale for Children, Third edition (WISC‐III) and to examine if parent‐rated measure of child mental health problems could predict the scores on CGAS and HoNOSCA after controlling for IQ, age, and gender.

Methods. In this study, 132 patients at three outpatient clinics in North Norway were assessed with the parent version of the Strength and Difficulties Questionnaire (SDQ), HoNOSCA, CGAS, and with the WISC‐III.

Results. Hierarchical regression analyses were conducted with HoNOSCA and CGAS as dependent variables. Demographics, WISC‐III IQ scores, and SDQ were entered as independent variables. The model with HoNOSCA as the dependent variable predicted 25% of the total variance. The WISC‐III full‐scale IQ predicted an additional 6% of the variance. The analyses with CGAS as the dependent variable gave no significant results.

Conclusion. When a patient has a high HoNOSCA score, an intelligence test in addition to an evaluation of symptoms on mental health should be considered. Future research ought to examine whether HoNOSCA's ability to detect change might be affected by patients IQ.
Stabilité de l’holonomie sur les variétés quasi-projectives
Authors: Caro Daniel
Published: August 2011

Let 𝒱 be a mixed characteristic complete discrete valuation ring with perfect residue field k. We solve Berthelot’s conjectures on the stability of the holonomicity over smooth projective formal 𝒱-schemes. Then we build a category of F-complexes of arithmetic 𝒟-modules over quasi-projective k-varieties with bounded and holonomic cohomology. We obtain its stability under Grothendieck’s six operations.
The Relation Between Helical Spring Compliances With Free and Fixed End Rotations
Authors: Burns S. J.
Published: August 2011

A helical spring that is constrained to no rotation has a compliance that is typically more than 95% of the compliance of springs constrained to free rotation when restricted to symmetric wires made from materials with Poisson’s ratio between 0 and 1/2. It is shown that the shape of the spring wire can be designed so the spring will not twist when it is extended nor extend when it is twisted. The constrained spring versus a freely rotating spring with the helix angle equal to π/4 has the largest reduction in compliance in the limits of beam theory. Spring compliances for torsion and extension with quite complex helical spring geometries are found to be related by a dimensionless ratio of compliances in a very simple equation that only depends on Poisson’s ratio and the helical, spring angle, ψ. Springs made from materials with negative Poisson’s ratio, however, can have a very substantial reduction in compliance; the no rotation compliance is zero when Poisson’s ratio is −1. There are large changes in spring compliances for springs with geometric coils that are elongated rectangles or flattened ellipses.
Physics From the News — Fukushima Daiichi: Radiation Doses and Dose Rates
Authors: Bartlett A. A.
Published: August 2011

The nuclear disaster that was triggered by the Japanese earthquake and the following tsunami of March 11, 2011, continues to be the subject of a great deal of news coverage. The tsunami caused severe damage to the nuclear power reactors at Fukushima Daiichi, and this led to the escape of unknown quantities of radioactive material from the damaged fuel rods in the reactors and from the associated storage facilities for the fuel rods that had been removed from the reactors.
Ring Falling into a Chain: No Magic — Just Physics
Authors: Vollmer Michael , Möllmann Klaus-Peter
Published: August 2011

Magic tricks are very popular, and they can and should be used in teaching when the underlying principle is easily explained by physics. Such tricks often fall in the realm of hands-on experiments, which are considered to be potentially very effective in raising interest and motivating students.1 Unfortunately, many hands-on experiments are easy to do, but more difficult to explain. One of the reasons is that they often happen so fast that the underlying principle can only be guessed. Also, a magic trick can be disguised so that an observer cannot solve the puzzle with the naked eye. Quite often even regular camcorders do not provide the necessary time resolution. Fortunately, however, huge advances in microsystem technologies have recently led to the development of commercially available high-speed cameras that are relatively inexpensive. The low end of the price range is now at or below $300.2 Some models of the Casio Exilim series provide up to 1200 frames per second for reduced image size. The technology of such cameras has been extensively summarized elsewhere,3 and many nice examples of experiments recorded with high-speed imaging are under way.4 Here we present one example of a physics “magic trick” that is extremely easy to perform while giving stunning results. High-speed images (snapshots and movies) can nicely reveal the physics behind the trick.
Special Relativity in Week One: 4) Lack of Simultaneity
Authors: Huggins Elisha
Published: August 2011

This is our final article on teaching special relativity in the first week of an introductory physics course.1–3 One of the profound changes in our view of the world was Einstein's discovery of the lack of simultaneity. He illustrated this result with a thought experiment in which we observe a railroad car passing by us. We see the two ends of the car struck simultaneously by lightning bolts, but to someone riding inside the car, the lightning strikes were not simultaneous. My difficulty with this thought experiment is that while doing calculations, I have to go back and forth between two imagined points of view. To avoid this, I actually perform an experiment that involves two simultaneous events. then all we have to imagine is how the experiment looks to someone moving by us. Not only does the order of the two events depend on the direction of motion of the observer, but we can demonstrate that if information could travel faster than the speed of light, we could get answers to questions that have not yet been thought of.
Racial and Gender Issues with Physics in the Pacific Region
Authors: Aung Than , Singh Awnesh , Prasad Uma
Published: August 2011

This paper examines the state of physics teaching and learning in the Pacific Island nations. How have things changed in teaching physics? We believe that some of the goals and many of the challenges faced today have changed very little over the years. This paper is purely based upon the authors' experiences in teaching physics at the first-year level at the University of the South Pacific (USP). USP is a typical medium-sized teaching and research university as compared to universities internationally. In the Pacific, it is the biggest university and is effectively serving the 12 Pacific Island nations. Consequently, the findings described here should represent the overall situation for the Pacific region. Perhaps some of our results will resonate with readers in other locations as well. Worldwide, university students often find studying physics to be very challenging, and only a small fraction of them choose physics as a major for their degree or as a career.1 Students at USP are not an exception, and here we describe the severity of the problem.
Infrared Imaging for Inquiry-Based Learning
Authors: Xie Charles , Hazzard Edmund
Published: August 2011

Based on detecting long-wavelength infrared (IR) radiation emitted by the subject, IR imaging shows temperature distribution instantaneously and heat flow dynamically. As a picture is worth a thousand words, an IR camera has great potential in teaching heat transfer, which is otherwise invisible. The idea of using IR imaging in teaching was first discussed by Vollmer et al. in 2001.1–3 IR cameras were then too expensive for most schools. Thanks to the growing need of home energy inspection using IR thermography, the price of IR cameras has plummeted and they have become easy to use. As of 2011, the price of an entry-level handheld IR camera such as the FLIR I3 has fallen below $900 for educators. A slightly better version, FLIR I5, was used to take the IR images in this paper. As easy to use as a digital camera, the I5 camera automatically generates IR images of satisfactory quality with a temperature sensitivity of 0.1°C. The purpose of this paper is to demonstrate how these affordable IR cameras can be used as a visualization, inquiry, and discovery tool. As the prices of IR cameras continue to drop, it is time to give teachers an update about the educational power of this fascinating tool, especially in supporting inquiry-based learning.
Single-Concept Clicker Question Sequences
Authors: Lee Albert , Ding Lin , Reay Neville W. , Bao Lei
Published: August 2011

Students typically use electronic polling systems, or clickers, to answer individual questions. Differing from this tradition, we have developed a new clicker methodology in which multiple clicker questions targeting the same underlying concept but with different surface features are grouped into a sequence. Here we present the creation, validation, and evaluation of clicker question sequences sufficient in number to populate a year of calculus-based introductory physics.
Notes on Discussion: Using physics to teach ninth-graders to take effective notes in a science class
Authors: Kremer Joe
Published: August 2011

Taking conscientious notes in a science class is a skill that's crucial for a students success, yet students rarely receive direct instruction on how to do this. Many younger students learn to take notes by simply copying anything that's written on the blackboard down onto a sheet of paper. In a physics class, this can mean that a student's notes contain mostly diagrams and calculations, without context or explanation. Physics First provides an opportunity to use physics to teach conscientious note taking explicitly early on in a student's science career.
Chemical and Genetic Engineering of Selective Ion Channel–Ligand Interactions
Authors: Magnus Christopher J. , Lee Peter H. , Atasoy Deniz , Su Helen H. , Looger Loren L. , Sternson Scott M.
Published: September 2011

Engineered ion channels enable manipulation of cellular function by selective chemical control of ionic conductance.
Reconciling Food Production and Biodiversity Conservation: Land Sharing and Land Sparing Compared
Authors: Phalan Ben , Onial Malvika , Balmford Andrew , Green Rhys E.
Published: September 2011

Protecting the largest possible area of natural habitats while growing food on the smallest area can reconcile food production with conservation.
Algae's Second Try
Authors: Service Robert F.
Published: September 2011

Fifteen years ago, the United States gave up on algae-based biofuels. Now synthetic biology has helped revitalize the field.
Noninvasive Electroanatomic Mapping of Human Ventricular Arrhythmias with Electrocardiographic Imaging
Authors: Wang Yong , Cuculich Phillip S. , Zhang Junjie , Desouza Kavit A. , Vijayakumar Ramya , Chen Jane , Faddis Mitchell N. , Lindsay Bruce D. , Smith Timothy W. , Rudy Yoram
Published: September 2011

Noninvasive imaging of cardiac electrical activity during ventricular arrhythmias enables superior diagnosis and treatment.
Long-Term Persistence of a Polyclonal T Cell Repertoire After Gene Therapy for X-Linked Severe Combined Immunodeficiency
Authors: Gaspar H. Bobby , Cooray Samantha , Gilmour Kimberly C. , Parsley Kathryn L. , Adams Stuart , Howe Steven J. , Al Ghonaium Abdulaziz , Bayford Jinhua , Brown Lucinda , Davies E. Graham , Kinnon Christine , Thrasher Adrian J.
Published: August 2011

Gene therapy results in long-term persistence of T cells in immunodeficient patients.
A Picture Is Worth a Thousand Dollars?
Authors: Hong David S.
Published: August 2011

Screening for lung cancer with low-dose CT scans reduces mortality, but may cost significantly more than current methods.
Compensatory Mutations Restore the Replication Defects Caused by Cytotoxic T Lymphocyte Escape Mutations in Hepatitis C Virus Polymerase
Authors: Oniangue-Ndza Cesar , Kuntzen Thomas , Kemper Michael , Berical Andrew , Wang Yaoyu E. , Neumann-Haefelin Christoph , Foote Peter Kristian , Hills-Evans Kelsey , Reyor Laura L. , Kane Katherine , Gladden Adrianne D. , Bloom Allyson K. , Power Karen A. , Thimme Robert , Lauer Georg M. , Henn Matthew R. , Kim Arthur Y. , Allen Todd M.
Published: September 2011

While human leukocyte antigen B57 (HLA-B57) is associated with the spontaneous clearance of hepatitis C virus (HCV), the mechanisms behind this control remain unclear. Immunodominant CD8
+
T cell responses against the B57-restricted epitopes comprised of residues 2629 to 2637 of nonstructural protein 5B (NS5B
2629–2637
) (KSKKTPMGF) and E2
541–549
(NTRPPLGNW) were recently shown to be crucial in the control of HCV infection. Here, we investigated whether the selection of deleterious cytotoxic T lymphocyte (CTL) escape mutations in the NS5B KSKKTPMGF epitope might impair viral replication and contribute to the B57-mediated control of HCV. Common CTL escape mutations in this epitope were identified from a cohort of 374 HCV genotype 1a-infected subjects, and their impact on HCV replication assessed using a transient HCV replicon system. We demonstrate that while escape mutations at residue 2633 (position 5) of the epitope had little or no impact on HCV replication
in vitro
, mutations at residue 2629 (position 1) substantially impaired replication. Notably, the deleterious mutations at position 2629 were tightly linked
in vivo
to upstream mutations at residue 2626, which functioned to restore the replicative defects imparted by the deleterious escape mutations. These data suggest that the selection of costly escape mutations within the immunodominant NS5B KSKKTPMGF epitope may contribute in part to the control of HCV replication in B57-positive individuals and that persistence of HCV in B57-positive individuals may involve the development of specific secondary compensatory mutations. These findings are reminiscent of the selection of deleterious CTL escape and compensatory mutations by HLA-B57 in HIV-1 infection and, thus, may suggest a common mechanism by which alleles like HLA-B57 mediate protection against these highly variable pathogens.
Direct Sequencing and Characterization of a Clinical Isolate of Epstein-Barr Virus from Nasopharyngeal Carcinoma Tissue by Using Next-Generation Sequencing Technology
Authors: Liu Pan , Fang Xiaodong , Feng Zizhen , Guo Yun-Miao , Peng Rou-Jun , Liu Tengfei , Huang Zhiyong , Feng Yue , Sun Xiaoqing , Xiong Zhiqiang , Guo Xiaosen , Pang Sha-Sha , Wang Bo , Lv Xiaojuan , Feng Fu-Tuo , Li Da-Jiang , Chen Li-Zhen , Feng Qi-Sheng , Huang Wen-Lin , Zeng Mu-Sheng , Bei Jin-Xin , Zhang Yong , Zeng Yi-Xin
Published: September 2011

Epstein-Barr virus (EBV)-encoded molecules have been detected in the tumor tissues of several cancers, including nasopharyngeal carcinoma (NPC), suggesting that EBV plays an important role in tumorigenesis. However, the nature of EBV with respect to genome width
in vivo
and whether EBV undergoes clonal expansion in the tumor tissues are still poorly understood. In this study, next-generation sequencing (NGS) was used to sequence DNA extracted directly from the tumor tissue of a patient with NPC. Apart from the human sequences, a clinically isolated EBV genome 164.7 kb in size was successfully assembled and named GD2 (GenBank accession number
HQ020558
). Sequence and phylogenetic analyses showed that GD2 was closely related to GD1, a previously assembled variant derived from a patient with NPC. GD2 contains the most prevalent EBV variants reported in Cantonese patients with NPC, suggesting that it might be the prevalent strain in this population. Furthermore, GD2 could be grouped into a single subtype according to common classification criteria and contains only 6 heterozygous point mutations, suggesting the monoclonal expansion of GD2 in NPC. This study represents the first genome-wide analysis of a clinical isolate of EBV directly extracted from NPC tissue. Our study reveals that NGS allows the characterization of genome-wide variations of EBV in clinical tumors and provides evidence of monoclonal expansion of EBV
in vivo
. The pipeline could also be applied to the study of other pathogen-related malignancies. With additional NGS studies of NPC, it might be possible to uncover the potential causative EBV variant involved in NPC.
Annual Vaccination against Influenza Virus Hampers Development of Virus-Specific CD8+T Cell Immunity in Children
Authors: Bodewes Rogier , Fraaij Pieter L. A. , Geelhoed-Mieras Martina M. , van Baalen Carel A. , Tiddens Harm A. W. M. , van Rossum Annemarie M. C. , van der Klis Fiona R. , Fouchier Ron A. M. , Osterhaus Albert D. M. E. , Rimmelzwaan Guus F.
Published: September 2011

Infection with seasonal influenza A viruses induces immunity to potentially pandemic influenza A viruses of other subtypes (heterosubtypic immunity). We recently demonstrated that vaccination against seasonal influenza prevented the induction of heterosubtypic immunity against influenza A/H5N1 virus induced by infection with seasonal influenza in animal models, which correlated with the absence of virus-specific CD8+T cell responses. Annual vaccination of all healthy children against influenza has been recommended, but the impact of vaccination on the development of the virus-specific CD8+T cell immunity in children is currently unknown. Here we compared the virus-specific CD8+T cell immunity in children vaccinated annually with that in unvaccinated children. In the present study, we compared influenza A virus-specific cellular and humoral responses of unvaccinated healthy control children with those of children with cystic fibrosis (CF) who were vaccinated annually. Similar virus-specific CD4+T cell and antibody responses were observed, while an age-dependent increase of the virus-specific CD8+T cell response that was absent in vaccinated CF children was observed in unvaccinated healthy control children. Our results indicate that annual influenza vaccination is effective against seasonal influenza but hampers the development of virus-specific CD8+T cell responses. The consequences of these findings are discussed in the light of the development of protective immunity to seasonal and future pandemic influenza viruses.
A Fusion-Loop Antibody Enhances the Infectious Properties of Immature Flavivirus Particles
Authors: Rodenhuis-Zybert Izabela A. , Moesker Bastiaan , da Silva Voorham Júlia M. , van der Ende-Metselaar Heidi , Diamond Michael S. , Wilschut Jan , Smit Jolanda M.
Published: September 2011

Flavivirus-infected cells secrete a mixture of mature, partially immature, and fully immature particles into the extracellular space. Although mature virions are highly infectious, prM-containing fully immature virions are noninfectious largely because the prM protein inhibits the cell attachment and fusogenic properties of the virus. If, however, cell attachment and entry are facilitated by anti-prM antibodies, immature flavivirus becomes infectious after efficient processing of the prM protein by the endosomal protease furin. A recent study demonstrated that E53, a cross-reactive monoclonal antibody (MAb) that engages the highly conserved fusion-loop peptide within the flavivirus envelope glycoprotein, preferentially binds to immature flavivirus particles. We investigated here the infectious potential of fully immature West Nile virus (WNV) and dengue virus (DENV) particles opsonized with E53 MAb and observed that, like anti-prM antibodies, this anti-E antibody also has the capacity to render fully immature flaviviruses infectious. E53-mediated enhancement of both immature WNV and DENV depended on efficient cell entry and the enzymatic activity of the endosomal furin. Furthermore, we also observed that E53-opsonized immature DENV particles but not WNV particles required a more acidic pH for efficient cleavage of prM by furin, adding greater complexity to the dynamics of antibody-mediated infection of immature flavivirus virions.
Synthesis of pregnane 3-carboxylic acids via Pd-catalyzed alkoxycarbonylation and their effect on NMDA receptor activity
Authors: Šťastná Eva , Chodounská Hana , Pouzar Vladimír , Borovská Jiřina , Vyklický Ladislav
Published: September 2011

We have prepared 20-oxo-5α- and 20-oxo-5β-pregnane-3-carboxylic acids by palladium catalyzed alkoxycarbonylation using triflate and nonaflate as the leaving groups in this substitution reaction. The activity of the synthesized compounds was studied in cultured rat hippocampal neurons under voltage-clamp conditions. The 5β-carboxylic acid derivatives were found to diminish NMDA-induced responses, whereas the 5α-derivative potentiated the response.
Effects of parenteral amoxicillin on recovery rates and new infection rates for contagious ovine digital dermatitis in sheep
Authors: Duncan J. S. , Grove‐White D. , Oultram J. W. H. , Phythian C. J. , van Dijk J. , Carter S. D. , Cripps P. J. , Williams H. J.
Published: September 2011

The present study is a randomised split‐flock treatment trial, which compared the effect of foot bathing in a 1 per cent solution of chlortetracycline alone with a treatment protocol that added a single injection of a long‐acting amoxicillin. Overall, the prevalence of contagious ovine digital dermatitis in the examined flock was 22 per cent, while 45.7 per cent of affected sheep had infections in two or more feet. Parenteral antibiotic treatment increased the odds of a recovery by 3.8 times (95 per cent confidence interval 1.05 to 14.0) (P=0.008). Moreover, the amoxicillin injection may also have had a preventative effect, reducing the rate of establishment of new infections from 2.5 per cent for foot bathing alone compared with 1.0 per cent with the addition of parenteral amoxicillin.
Effects of transportation on expression of Hsp90, Hsp70, Hsp27 and αB‐crystallin in the pig stomach
Authors: Zhang M. , Lv Y. , Yue Z. , Islam A. , Rehana B. , Bao E. , Hartung J.
Published: August 2011

Twenty pigs were randomly divided into four groups based on the amount of time spent in transport (zero, one, two or four hours). Pathological examination of all transported pigs showed that exfoliation of chief cells from the gastric surface occurred in pigs during transportation. These results imply that integrity of the gastric mucosa was compromised by damage occurring during the four‐hour transportation, despite the fact that gastric ulcers were not present. Levels of Hsp90 expression in stomach tissues were significantly decreased (P<0.01) after two‐hour transportation, but Hsp70 levels increased significantly (P<0.05) after one, two and four hours of transportation. Hsp27 levels remained relatively stable independent of the length of transport. Levels of αB‐crystallin expression in the stomach were significantly increased (P<0.05) after four hours of transportation. Variations in Hsp90, Hsp70, Hsp27 and αB‐crystallin levels suggest that distinct protective functions are modulated by different Hsps in stomach tissues during transportation. Alterations in Hsp70 and αB‐crystallin expression appear to be associated with protective functions, as no apparent gastric ulcers were present in pigs that underwent four hours of transportation. Levels of heat shock transcription factor‐1, which regulate the expression of Hsps, remained relatively stable independent of the transportation period.
Strigolactones: a cry for help in the rhizosphere
Authors: López-Ráez Juan A. , Pozo María J. , García-Garrido José M.
Published: September 2011

Arbuscular mycorrhizal (AM) symbiosis is a beneficial symbiosis established between fungi of the phylum Glomeromycota and over 80% of terrestrial plants, including most agricultural and horticultural crop species. AM symbiosis improves the nutritional status and fitness of the host plant and enables the plant to perform better under stressful conditions. As a result, when plants are growing under unfavourable conditions, they try to recruit their AM fungal partner in the soil. Symbiosis establishment requires a complex chemical dialogue between the two partners, in which signalling molecules such as the strigolactones play a key role. Under deficient nutrient conditions, the host plant increases the production of strigolactones to promote fungal development and symbiosis establishment (a “cry for help”). As a clue to host presence in the rhizosphere, strigolactones are also detected by other organisms, particularly root parasitic plants, and therefore promote a parasitic interaction. We review here the role of strigolactones and their interaction with other phytohormones during AM symbiosis, paying special attention to the implications of the chemical communication that takes place in the rhizosphere. Finally, we point out the potential use of this molecular dialogue as a target for developing new biological control strategies against deleterious organisms such as root parasitic weeds.
Undrained stability of a circular tunnel where the shear strength increases linearly with depth
Authors: Wilson Daniel W. , Abbo Andrew J. , Sloan Scott W. , Lyamin Andrei V.
Published: September 2011

This paper investigates the undrained stability of a plane strain circular tunnel in clay, where the shear strength profile is assumed to increase linearly with depth. Stability solutions for a variety of geometries and soil conditions are found using rigid-block upper bound methods as well as finite element limit analysis (which gives both upper and lower bounds). The latter procedures employ a discrete form of the bound theorems of classical plasticity, use a bespoke conic programming scheme to solve the resulting optimization problems, and bracket the true collapse load to within 5% for all the cases considered. Results from the study are summarized in the form of stability charts as well as an approximate closed-form expression that can be used by practising engineers.
Potential adverse effects of oseltamivir in rats: males are more vulnerable than females
Authors: El-Sayed Wael M. , Al-Kahtani Mohamed Ali
Published: August 2011

Oseltamivir is the most widely used antiviral drug for the treatment and prophylaxis of influenza. However, not much is known about its adverse effects. The potential side effects were investigated in male and female rats (140–170 g). Oseltamivir was administered at 2.2 mg·kg–1·day–1for 5 days. For both genders, treatment with oseltamivir resulted in significant reductions in the hepatic activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase. Also for both genders, oseltamivir produced modest reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic glutathione content. For both genders, neither the kidney functions nor protein profile was affected by oseltamivir. Oseltamivir also caused significant elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the activity of γ-glutamyl transpeptidase, in both genders. For male animals only, oseltamivir treatment elevated the serum level of total cholesterol as well as the activity of serum alanine aminotransferase, and reduced the hepatic activities of superoxide dismutase and catalase. Oseltamivir caused oxidative stress and acute toxicity in the liver, and disrupted the cholesterol and lipid metabolism but was less likely to cause serious drug interactions. There was a sexual differentiation in these adverse effects, with adverse effects being more evident in male rats.
In vitro kinetics of oxygen transport in erythrocyte suspension or unmodified hemoglobin solution from human and other animals
Authors: Peng Weiyan , Wang Xiang , Gao Wei , Lan Ke
Published: August 2011

Oxygen transport behavior in erythrocyte suspension or in hemoglobin solution was studied as a potential therapeutic model for the clinical treatment of blood loss, and this can also provide physiological data with which to evaluate blood substitutes. In the present project, we examined the in vitro kinetics of hemoglobin binding to and releasing oxygen, to provide detailed oxygen-flux measurements for unmodified hemoglobin solutions and erythrocyte suspensions in human, as well as other vertebrates. An in vitro method was used, based on a widely used artificial system, with the oxygen saturation level being detected in real time. Results from this study indicated that the kinetic curves of human erythrocyte suspensions and hemoglobin solutions were either S-shaped or hyperbolic, respectively. Based on these curves, the significance of T50emerged in our investigation, where T50is defined as the time needed for 50% hemoglobin to be saturated with oxygen, and reflects the efficiency with which hemoglobin carries oxygen. This parameter may be used to diagnose blood diseases, and could be a standard for evaluating blood substitutes. In this study, we also compared the T50of 4 species of vertebrates, and found that it shows a distinct efficiency of oxygen binding related to species, and potentially reveals the evolutionary function of hemoglobin and its possible adaptation to the environment.