bluuebunny/crossref_metadata_2025 huggingface dataset:
MAPPING AFRICAN ETHICAL REVIEW COMMITTEE ACTIVITY ONTO CAPACITY NEEDS: THE MARC INITIATIVE AND HRWEB'S INTERACTIVE DATABASE OF RECS IN AFRICA
Authors: IJSSELMUIDEN CAREL , MARAIS DEBBIE , WASSENAAR DOUGLAS , MOKGATLA‐MOIPOLAI BOITUMELO
Published: April 2012

Health research initiatives worldwide are growing in scope and complexity, particularly as they move into the developing world. Expanding health research activity in low‐ and middle‐income countries has resulted in a commensurate rise in the need for sound ethical review structures and functions in the form of Research Ethics Committees (RECs). Yet these seem to be lagging behind as a result of the enormous challenges facing these countries, including poor resource availability and lack of capacity. There is thus an urgent need for ongoing capacity and resource development in these regions in general, and in Africa in particular. Similarly, there is a need for research and initiatives that can identify existing capacity and funding and indicate the areas where this needs to be developed.

This discussion paper argues that the Mapping African Research Ethics Capacity (MARC) project is a timely initiative aimed at identifying existing capacity. MARC provides a platform and tool on the Council on Health Research for Development's (COHRED) Health Research website (HRWeb), which can be used by RECs and key stakeholders in health research in Africa to identify capacity, constraints and development needs. MARC intends to provide the first comprehensive interactive database of RECs in Africa, which will allow for the identification of key relationships and analyses of capacity. The potential of MARC lies in the mapping of current ethical review activity onto capacity needs. This paper serves as a starting point by providing a descriptive illustration of the current state of RECs in Africa.
PROGRESSIVITY AND REDISTRIBUTION IN NON‐REVENUE NEUTRAL TAX REFORMS: THE LEVEL AND DISTANCE EFFECTS
Authors: DE SARRALDE SANTIAGO DÍAZ , GARCIMARTÍN CARLOS , RUIZ‐HUERTA JESÚS
Published: April 2012

Kakwani and Reynolds–Smolensky indices are used in the literature to measure the progressivity and redistributive capacity of taxes. These indices may, however, show some limits when used to make normative assessments about non‐revenue neutral tax reforms. Two approaches have traditionally been taken to overcome this problem. The first of these consists of comparing after‐tax income distributions through generalized Lorenz (concentration) curves. The second approach is based on the decomposition of changes in the Reynolds–Smolensky index into changes in the average tax rate and variations in progressivity. Nonetheless, this decomposition between the average tax rate and progressivity may be further exploited to obtain some information that can be relevant to assess tax reforms. The main aim of this study is to draw up some indicators that can be useful to quantify the effects of non‐revenue neutral tax reforms. These indicators are used to investigate the last personal income tax reforms that have taken place in Spain.
Nutritional status assessment in complete denture wearers
Authors: Prakash Nagaranjani , Kalavathy Natarajan , Sridevi Janakiramareddy , Premnath Kumareshan
Published: April 2012

doi: 10.1111/j.1741‐2358.2011.00620.x

Nutritional status assessment in complete denture wearers

Background and objectives:  The relationship between oral health and the nutritional status in the elderly is complex and controversial. It has been suggested that poor oral health and a decreased ability to chew have a profound influence on food selection, diet and thereby the nutritional status of the individual. This study aimed to evaluate the effect of edentulousness and prosthetic treatment on the nutritional status of the individual.

Methods:  A total of 94 patients were selected for the study, which was conducted over a period of 16 months. The nutritional status was assessed using the Mini Nutritional Assessment Form (MNA) before the complete denture treatment and after an interval of 6 months and 9 months following the treatment. The individual scores obtained for each question and the total scores at the baseline study were compared with those obtained after 6 and 9 months. Proportions were compared using chi‐squared test of significance.

Results:  The results showed statistically significant differences in the total MNA scores between the baseline study and after 6 and 9 months. The edentulous patients without complete dentures had significantly lower MNA scores.

Conclusion:  Prosthetic rehabilitation of the edentulous patients with complete dentures, along with the dietary counselling, improved the nutritional status of these patients.
Barriers and Facilitators to Implementation of the Institute of Medicine Recommendations on Preventing Mental, Emotional, and Behavioral Disorders Among Young People
Authors: Evans Mary E.
Published: April 2012

PROBLEM:  The purpose of this study was to gain an understanding of the barriers and facilitators to implementation of the five overarching recommendations of the Institute of Medicine report and to consider the implications for nursing.

METHODS:  Data were collected through use of a semi‐structured interview of purposive sample of 22 key informants regarding the barriers and facilitators to implementation of the report's five major recommendations.

FINDINGS:  The major barriers were competing priorities, lack of infrastructure for implementation, lack of public education regarding mental health and the effectiveness of prevention, stigma, and a paucity of facilitating factors. The facilitators were leadership, flexible resources, linkage to healthcare reform or other legislation, coordination across agencies and governmental levels, and additional research.

CONCLUSIONS:  The discussion focuses on ways of promoting facilitating factors and consideration of nursing's potential contributions in the areas of education, practice, and research.
A Comparative Assessment of Early Adult Life Status of Graduates of the North Carolina Adolescent Parenting Program
Authors: Gruber Kenneth J.
Published: April 2012

PROBLEM:  What is the comparative impact of a second pregnancy prevention program for teen mothers on those who graduate from the program compared with a sample of young mothers of similar age and social circumstances who did not participate in the program?

METHODS:  Fifteen program graduates and 20 nonprogram cohorts were surveyed regarding a range of life domains.

FINDINGS:  Data indicated that program graduates were on a more positive life course: greater primary responsibility for housing and utilities, greater higher education enrollment, more job stability, and greater focus on career goals.

CONCLUSION:  The differences demonstrate the value of programs designed to assist teen mothers through the challenges of parenting and their own adolescent development. Teen mothers who received these resources became more capable, happier, and confident, which in turn will make them better parents and more empowered to pursue their own personal development.
Investigation of Autism Comorbidities and Associations in a School‐Based Community Sample
Authors: Memari AmirHossein , Ziaee Vahid , Mirfazeli FatemehSadat , Kordi Ramin
Published: April 2012

PROBLEM:  Individuals with autism spectrum disorders (ASDs) have at least as many comorbidities as individuals with typical development may show, but sometimes with different presentations.

METHODS:  The study used a school‐based health survey related to children diagnosed with ASD in Tehran to determine the possibility of comorbid conditions. Ninety‐one children and adolescents with ASD between the ages of 6 and 14 years were included in the study, all from five schools of different districts of the city, using stratified random sampling. All of the subjects had received a clinical diagnosis of ASD (autism, Asperger, and pervasive developmental disorder‐not otherwise specified) by a child neurologist or psychiatrist. All of the schools had registered the subjects and were restricted to those with high‐functioning forms of ASD, and none were identified with co‐occurring mental retardation.

FINDINGS:  Results indicated that 72.5% had at least one comorbid condition. There was a trend of higher severity in autism symptoms in subjects with comorbidity. Results showed that attention‐deficit/hyperactivity disorder and epileptic disorders were the leading comorbidity in respective categories.

CONCLUSION:  Autistic individuals should be monitored regarding their comorbid profiles, with an emphasis on female subjects and those with more severe symptoms. Clinically, the current study has implications for school healthcare providers, including nurses, in addition to researchers and practitioners working with children diagnosed with ASDs.
Generation of Receptor Structural Ensembles for Virtual Screening Using Binding Site Shape Analysis and Clustering
Authors: Osguthorpe David J. , Sherman Woody , Hagler Arnold T.
Published: April 2012

Accounting for protein flexibility is an essential yet challenging component of structure‐based virtual screening. Whereas an ideal approach would account for full protein and ligand flexibility during the virtual screening process, this is currently intractable using available computational resources. An alternative is ensemble docking, where calculations are performed on a set of individual rigid receptor conformations and the results combined. The primary challenge associated with this approach is the choice of receptor structures to use for the docking calculations. In this work, we show that selection of a small set of structures based on clustering on binding site volume overlaps provides an efficient and effective way to account for protein flexibility in virtual screening. We first apply the method to crystal structures of cyclin‐dependent kinase 2 and HIV protease and show that virtual screening for ensembles of four cluster representative structures yields consistently high enrichments and diverse actives. We then apply the method to a structural ensemble of the androgen receptor generated with molecular dynamics and obtain results that are in agreement with those from the crystal structures of cyclin‐dependent kinase 2 and HIV protease. This work provides a step forward in the incorporation of protein flexibility into structure‐based virtual screening.
The principle of parliamentary sovereignty
Authors: McGarry John
Published: April 2012

In this paper, I use Dworkin's distinction between rules and principles to analyse the doctrine of parliamentary sovereignty. I argue that, inherent in many conceptions of the doctrine, is an assumption that it operates in the conclusive manner of a Dworkinian rule. I then submit that the doctrine actually functions in the flexible way characteristic of a Dworkinian principle. In support of this contention, I argue that Acts of Parliament may be balanced against competing principles or statutes; that they possess the dimension of weight or importance; and that the degree to which they will be adhered in any particular case will be contingent upon the importance attributed to any competing principle or statute. I finish the paper with an evaluation of my arguments and an attempt to anticipate potential counter-arguments.
Establishment and Optimization of Monoclonal Antibody‐based Heterologous dcELISA for 19‐Nortestosterone Residue in Bovine Edible Tissue
Authors: Jiang Jinqing , Zhang Haitang , Li Guangling , Yang Xuefeng , Li Renfeng , Wang Ziliang , Wang Jianhua
Published: April 2012

Abstract:  This paper presents the generation of monoclonal antibodies (mAbs) with high specificity against 19‐nortestosterone (NT) through cell fusion procedures, and the development of mAb‐based heterologous direct competitive enzyme‐linked immunoabsorbent assay (dcELISA) methods to detect NT residue using one of these hybridomas (clone 3B8‐E6). Under optimal experimental conditions, this assay exhibited a working range of 0.004 to 19 ng/mL with IC50 and limit of detection values of 0.28 and 0.002 ng/mL, respectively, when it was run in 0.01M phosphate‐buffered saline (pH 7.4). Except for minor cross‐reactivity with β‐boldenone (6.9%) and trenbolone (1.2%), other interference to the assay was negligible (<0.05%). No significant differences (P > 0.05) were found for IC50 values when the pH of the assay buffer ranged from 6 to 8 and phosphate ion concentration was less than 20 mM. The dcELISA can tolerate higher concentrations of methanol than other organic solvents tested. When applied to bovine sample, the correlation coefficients (R) of the dcELISA and GC‐MS data were 0.9918 in muscle, 0.9834 in liver, and 0.9976 in kidney. Therefore, this assay has the potential to be incorporated into a quantitative monitoring program for the rapid screening of NT residue in food.
Application of Proanthocyanidins from Peanut Skins as a Natural Yeast Inhibitory Agent
Authors: Sarnoski Paul J. , Boyer Renee R. , O’Keefe Sean F.
Published: April 2012

Abstract:  Proanthocyanidins were extracted from peanut skins and investigated for their antimicrobial activity against Saccharomyces cerevisiae, Zygosaccharomyces bailii, and Zygosaccharomyces bisporus in traditional growth media (Sabouraud Dextrose and Maltose broth) and a simulated apple juice beverage. Peanut skins extracts (PSE) were prepared through a multisolvent extraction procedure. The PSE extended the lag phase growth of the 3 yeasts studied at a concentration of 1 mg/mL and at 10 mg/mL yeast growth was totally inhibited for 120 h. PSE was fractionated by normal phase high performance liquid chromatography and the active components/fractions were determined. Compounds present in the fractions were identified by liquid chromatography‐mass spectrometry to determine the compounds responsible for inhibition. Fractions consisting mostly of A‐type proanthocyanidin dimers, trimers, and tetramers showed the highest percent inhibition toward the yeasts tested in this study. Both optical density (OD) and standard enumeration plating methods were performed in this study. The OD method led to an overestimation of the inhibitory effects of PSE, the 2 methods agreed in respect to treatment effects but not the severity of the inhibition.

Practical Application:  There is a growing consumer demand for “fresh like” products containing reduced amounts of chemical preservatives without compromising food safety and quality. Therefore, the goal of this study was to determine if an extract of peanut skins containing flavonoid rich compounds could function as a natural antimicrobial in a model beverage system. Proteins were removed through the process of producing the peanut skin extract, thus it is unlikely to contain peanut allergens. The antimicrobial compounds mentioned in this study were successfully integrated into a model beverage system, and were found to have antimicrobial effect. However, the incorporation of these compounds would likely lead to negative sensory attributes at the concentration needed to achieve an appreciable antimicrobial effect alone.
Suspected poisoning of cattle by scarlet pimpernel (Lysimachia arvensis L.)
Authors: Roche MJ , McCowan CI , Kelly JC
Published: April 2012

The ingestion of scarlet pimpernel (Lysimachia arvensis L.), also known as red chickweed, has been reported as a cause of death of cattle in Uruguay, and as the suspected cause of deaths of sheep in Australia. It has not previously been reported in association with deaths of cattle in Australia. We report the clinical and pathological findings from four cattle in western Victoria that died with a nephrosis suspected to be secondary to intoxication with scarlet pimpernel.
Influence of Helium‐Neon Laser Irradiation on Seed Germination In Vitro and Physico‐Biochemical Characters in Seedlings of Brinjal (Solanum melongena L.) var. Mattu Gulla
Authors: Muthusamy Annamalai , Kudwa Prathibha P. , Prabhu Vijendra , Mahato Krishna K. , Babu Vidhu Sankar , Rao Mattu Radhakrishna , Gopinath Puthiya Mandyat , Satyamoorthy Kapaettu
Published: April 2012

In the present study, the seeds of brinjal (Solanum melongena L.) var. Mattu Gulla were irradiated with single exposure of He–Ne laser at different doses of 5–40 J cm−2 and germinated aseptically. Thirty day old seedlings were harvested and the germination, growth, physiological and biochemical parameters were estimated and compared with un‐irradiated control seedlings. A significant enhancement in growth characters were noted with respect to length, fresh and dry weight of shoots and roots. In addition, chlorophyll (a and b), carotenoid content, anthocyanin and amylases (α and β) activities were found to be altered. Significant alterations in percentage of seed germination (P < 0.001) and time to 50% germination (P < 0.001) were observed in the irradiated seeds compared with the un‐irradiated controls. In conclusion, the results of the present study demonstrated that low dose (5–30 J cm−2) of He–Ne laser irradiation enhanced the germination process and altered growth, by positively influencing physiological and biochemical parameters of the brinjal seedlings compared with un‐irradiated control under in vitro conditions.
Lung cancer associated with an azygos lobe successfully treated with video‐assisted thoracoscopic surgery
Authors: Arai H , Inui K , Kano K , Nishii T , Kaneko T , Mano H , Sasaki T , Masuda M
Published: April 2012

Primary lung cancer associated with an azygos lobe is extremely rare. Herein, we report the case of a 64‐year‐old woman with lung adenocarcinoma arising in the right upper lobe with an azygos lobe. The patient underwent a right upper lobectomy and lymph node dissection with video‐assisted thoracoscopic surgery. Video‐assisted thoracoscopic surgery lobectomy for lung cancer of this variant has yet to be reported. We demonstrate the intraoperative findings and the resected pulmonary lobe. This is the first case of primary lung cancer associated with the azygos lobe treated by lobectomy with video‐assisted thoracoscopic surgery.
Assembly Bonded at the Ends: Could Thinner and Longer Legs Result in a Lower Thermal Stress in a Thermoelectric Module Design?
Authors: Suhir E. , Shakouri A.
Published: April 2012

An analytical (mathematical) thermal stress model has been developed for an electronic assembly comprised of identical components bonded at their end portions and subjected to different temperatures. The model is used to assess the effect of the size (dimension in the x-direction) and compliance of the bonded regions (legs) on the maximum interfacial shearing stress that is supposedly responsible for the mechanical robustness of the assembly. The numerical example is carried out for a simplified two-legged Bismuth-Telluride-Alloy (BTA)-based thermoelectric module (TEM) design. It has been determined that thinner (dimension in the horizontal, x-direction) and longer (dimension in the vertical, y-direction) bonds (legs) could result in a considerable relief in the interfacial stress. In the numerical example carried out for a 10 mm long (dimension in the x-direction) TEM assembly with two peripheral 1 mm thick (dimension in the x-direction) legs, the predicted maximum interfacial shearing stress is only about 40% of the maximum stress in the corresponding homogeneously bonded assembly, when the bond occupies the entire interface between the assembly components. It has been determined also that if thick-and-short legs are employed, the maximum interfacial shearing stress might not be very much different from the stress in a homogeneously bonded assembly, so that there is no need, as far as physical design and robustness of the assembly is concerned, to use a homogeneous bond or a multileg system. The application of such a system might be needed, however, for the satisfactory functional (thermo-electrical) performance of the device. In any event, it is imperative that sufficient bonding strength is assured in the assembly. If very thin legs are considered for lower stresses, the minimum acceptable size (real estate) of the interfaces (in the horizontal plane) should be experimentally determined (say, by shear-off testing) so that this strength is not compromised. On the other hand, owing to a lower stress level in an assembly with thin-and-long legs, assurance of its interfacial strength is less of a challenge than for an assembly with a homogeneous bond or with stiff thick-and-short legs. The obtained results could be used particularly for considering, based on the suggested predictive model, an alternative to the existing TEM designs, which are characterized by multiple big (thick-and-long) legs. In our novel design, fewer small (thin-and-short) legs could be employed, so that the size and thickness of the TEM is reduced for the acceptable stress level.
Response to Comment on “Detection of Emerging Sunspot Regions in the Solar Interior”
Authors: Ilonidis Stathis , Zhao Junwei , Kosovichev Alexander
Published: April 2012

Braun claims that his analysis using helioseismic holography does not confirm the detection of emerging sunspot regions. We examine his measurement procedure and explain why his method has different sensitivity than our method. We also discuss possible physical processes that may cause the detected phase travel-time shifts.
Interplay of Intra- and Intermolecular H-Bonding in a Progressively Solvated Macrocyclic Peptide
Authors: Nagornova Natalia S. , Rizzo Thomas R. , Boyarkin Oleg V.
Published: April 2012

Hydrated in a Hurry

Water has a major influence on the conformation of proteins and related biomolecules. However, so many water molecules participate in the hydrogen bonding networks that it can be difficult to pinpoint which specific interactions play the biggest role.

Nagornova
et al.

(p.
320
) sought to answer this question for the case of a 10–amino acid ring—the antibiotic compound Gramicidin S—by probing the conformational impact of successive additions of one to 50 water molecules to the naked gas-phase structure. The primary changes in the overall ring geometry came from the addition of just the first two waters.
Visualizing Amyloid Assembly
Authors: Eliezer David
Published: April 2012

Specific precursor states formed from soluble native proteins have been identified as leading to oligomerization and amyloid formation.
Toward an Alternative Biology
Authors: Joyce Gerald F.
Published: April 2012

The fundamental processes of genetics have been captured with synthetic molecules.
Inextricably Coupled
Environmental Literacy in Science and Society
From Knowledge to Decisions

by Roland W. Scholz
et al.

Cambridge University Press, Cambridge, 2011. 655 pp. $130, £80. ISBN 9780521192712. Paper, $75, £45. ISBN 9780521183338.
Authors: Mieg Harald A.
Published: April 2012

Presenting a detailed framework for working toward sustainability, Scholz stresses the coupling of humans and the environment at every systemic level.
Memory B Cell Responses to Vibrio cholerae O1 Lipopolysaccharide Are Associated with Protection against Infection from Household Contacts of Patients with Cholera in Bangladesh
Authors: Patel Sweta M. , Rahman Mohammad Arif , Mohasin M. , Riyadh M. Asrafuzzaman , Leung Daniel T. , Alam Mohammad Murshid , Chowdhury Fahima , Khan Ashraful I. , Weil Ana A. , Aktar Amena , Nazim Mohammad , LaRocque Regina C. , Ryan Edward T. , Calderwood Stephen B. , Qadri Firdausi , Harris Jason B.
Published: April 2012

Vibrio cholerae
O1 causes cholera, a dehydrating diarrheal disease. We have previously shown that
V. cholerae
-specific memory B cell responses develop after cholera infection, and we hypothesize that these mediate long-term protective immunity against cholera. We prospectively followed household contacts of cholera patients to determine whether the presence of circulating
V. cholerae
O1 antigen-specific memory B cells on enrollment was associated with protection against
V. cholerae
infection over a 30-day period. Two hundred thirty-six household contacts of 122 index patients with cholera were enrolled. The presence of lipopolysaccharide (LPS)-specific IgG memory B cells in peripheral blood on study entry was associated with a 68% decrease in the risk of infection in household contacts (
P
= 0.032). No protection was associated with cholera toxin B subunit (CtxB)-specific memory B cells or IgA memory B cells specific to LPS. These results suggest that LPS-specific IgG memory B cells may be important in protection against infection with
V. cholerae
O1.
Identification and Diagnostic Utility of Leishmania infantum Proteins Found in Urine Samples from Patients with Visceral Leishmaniasis
Authors: Abeijon Claudia , Kashino Suely S. , Silva Fernando O. , Costa Dorcas L. , Fujiwara Ricardo T. , Costa Carlos H. N. , Campos-Neto Antonio
Published: April 2012

Despite the clear need to control visceral leishmaniasis (VL), the existing diagnostic tests have serious shortcomings. Here, we introduce an innovative approach to directly identify
Leishmania infantum
antigens produced
in vivo
in humans with VL. We combined reverse-phase high-performance liquid chromatography (RP-HPLC) with mass spectrometry and categorized three distinct
L. infantum
proteins presumably produced in bone marrow/spleen/liver and excreted in the urine of patients with VL. The genes coding for these proteins (
L. infantum
iron superoxide dismutase, NCBI accession number
XP_001467866.1
;
L. infantum
tryparedoxin, NCBI accession number
XP_001466642.1
; and
L. infantum
nuclear transport factor 2, NCBI accession number
XP_001463738.1
) were cloned, and the recombinant molecules were produced in
Escherichia coli
. Antibodies to these proteins were produced in rabbits and chickens and were used to develop a capture enzyme-linked immunosorbent assay (ELISA) designed to detect these
L. infantum
antigens in the urine of VL patients. Specificity of the antibodies was confirmed by a Western blot analysis using both recombinant proteins and whole parasite extract. Importantly, a urinary antigen detection assay assembled with pairs of antibodies specific for each of these antigens identified 17 of 19 patients with VL. These results indicate that an improved antigen detection assay based on
L. infantum
proteins present in the urine of patients with VL may represent an important new strategy for the development of a specific and accurate diagnostic test that has the potential to both distinguish active VL from asymptomatic infection and serve as an important tool to monitor therapy efficacy.
TP-RT Domain Interactions of Duck Hepatitis B Virus Reverse Transcriptase in
cis
and in
trans
during Protein-Primed Initiation of DNA Synthesis
In Vitro
Authors: Boregowda Rajeev K. , Adams Christina , Hu Jianming
Published: April 2012

The hepadnavirus reverse transcriptase (RT) has the unique ability to initiate viral DNA synthesis using RT itself as a protein primer. Protein priming requires complex interactions between the N-terminal TP (terminal protein) domain, where the primer (a specific Y residue) resides, and the central RT domain, which harbors the polymerase active site. While it normally utilizes the
cis
-linked TP to prime DNA synthesis (
cis
-priming), we found that the duck hepatitis B virus (DHBV) RT domain, in the context of the full-length RT protein or a mini-RT construct containing only truncated TP and RT domains, could additionally use a separate TP or RT domain in
trans
as a primer (
trans
-priming).
trans
interaction could also be demonstrated by the inhibitory effect (
trans
-inhibition) on
cis
-priming by TP and RT domain sequences provided in
trans
. Protein priming was further shown to induce RT conformational changes that resulted in TP-RT domain dissociation, altered priming site selection, and a gain of sensitivity to a pyrophosphate analog inhibitor.
trans
-priming,
trans
-inhibition, and
trans
-complementation, which requires separate TP and RT domains to reconstitute a functional RT protein, were employed to define the sequences in the TP and RT domains that could mediate physical or functional inter- and intradomain interactions. These results provide new insights into TP-RT domain interactions and conformational dynamics during protein priming and suggest novel means to inhibit protein priming by targeting these interactions and the associated conformational transitions.
Profound Amplification of Pathogenic Murine Polytropic Retrovirus Release from Coinfected Cells
Authors: Rosenke Kyle , Lavignon Marc , Malik Frank , Kolokithas Angelo , Hendrick Duncan , Virtaneva Kimmo , Peterson Karin , Evans Leonard H.
Published: April 2012

Previous studies indicate that mice infected with mixtures of mouse retroviruses (murine leukemia viruses [MuLVs]) exhibit dramatically altered pathology compared to mice infected with individual viruses of the mixture. Coinoculation of the ecotropic virus Friend MuLV (F-MuLV) with Fr98, a polytropic MuLV, induced a rapidly fatal neurological disease that was not observed in infections with either virus alone. The polytropic virus load in coinoculated mice was markedly enhanced, while the ecotropic F-MuLV load was unchanged. Furthermore, pseudotyping of the polytropic MuLV genome within ecotropic virions was nearly complete in coinoculated mice. In an effort to better understand these phenomena, we examined mixed retrovirus infections by utilizing
in vitro
cell lines. Similar to
in vivo
mixed infections, the polytropic MuLV genome was extensively pseudotyped within ecotropic virions; polytropic virus release was profoundly elevated in coinfected cells, and the ecotropic virus release was unchanged. A reduced level of polytropic SU protein on the surfaces of coinfected cells was observed and correlated with a reduced level of nonpseudotyped polytropic virion release. Marked amplification and pseudotyping of the polytropic MuLV were also observed in mixed Fr98–F-MuLV infections of cell lines derived from the central nervous system (CNS), the target for Fr98 pathogenesis. Additional experiments indicated that pseudotyping contributed to the elevated polytropic virus titer by increasing the efficiency of packaging and release of the polytropic genomes within ecotropic virions. Mixed infections are the rule rather than the exception in retroviral infection, and the ability to examine them
in vitro
should facilitate a more thorough understanding of retroviral interactions in general.
Initial HIV-1 Antigen-Specific CD8
+
T Cells in Acute HIV-1 Infection Inhibit Transmitted/Founder Virus Replication
Authors: Freel Stephanie A. , Picking Ralph A. , Ferrari Guido , Ding Haitao , Ochsenbauer Christina , Kappes John C. , Kirchherr Jennifer L. , Soderberg Kelly A. , Weinhold Kent J. , Cunningham Coleen K. , Denny Thomas N. , Crump John A. , Cohen Myron S. , McMichael Andrew J. , Haynes Barton F. , Tomaras Georgia D.
Published: April 2012

CD8-mediated virus inhibition can be detected in HIV-1-positive subjects who naturally control virus replication. Characterizing the inhibitory function of CD8
+
T cells during acute HIV-1 infection (AHI) can elucidate the nature of the CD8
+
responses that can be rapidly elicited and that contribute to virus control. We examined the timing and HIV-1 antigen specificity of antiviral CD8
+
T cells during AHI. Autologous and heterologous CD8
+
T cell antiviral functions were assessed longitudinally during AHI in five donors from the CHAVI 001 cohort using a CD8
+
T cell-mediated virus inhibition assay (CD8 VIA) and transmitted/founder (T/F) viruses. Potent CD8
+
antiviral responses against heterologous T/F viruses appeared during AHI at the first time point sampled in each of the 5 donors (Fiebig stages 1/2 to 5). Inhibition of an autologous T/F virus was durable to 48 weeks; however, inhibition of heterologous responses declined concurrent with the resolution of viremia. HIV-1 viruses from 6 months postinfection were more resistant to CD8
+
-mediated virus inhibition than cognate T/F viruses, demonstrating that the virus escapes early from CD8
+
T cell-mediated inhibition of virus replication. CD8
+
T cell antigen-specific subsets mediated inhibition of T/F virus replication via soluble components, and these soluble responses were stimulated by peptide pools that include epitopes that were shown to drive HIV-1 escape during AHI. These data provide insights into the mechanisms of CD8-mediated virus inhibition and suggest that functional analyses will be important for determining whether similar antigen-specific virus inhibition can be induced by T cell-directed vaccine strategies.
Identification of the Galactose Binding Domain of the Adeno-Associated Virus Serotype 9 Capsid
Authors: Bell Christie L. , Gurda Brittney L. , Van Vliet Kim , Agbandje-McKenna Mavis , Wilson James M.
Published: April 2012

Adeno-associated virus serotype 9 (AAV9) vectors show promise for gene therapy of a variety of diseases due to their ability to transduce multiple tissues, including heart, skeletal muscle, and the alveolar epithelium of the lung. In addition, AAV9 is unique compared to other AAV serotypes in that it is capable of surpassing the blood-brain barrier and transducing neurons in the brain and spinal cord. It has recently been shown that AAV9 uses galactose as a receptor to transduce many different cell types
in vitro
, as well as cells of the mouse airway
in vivo
. In this study, we sought to identify the specific amino acids of the AAV9 capsid necessary for binding to galactose. By site-directed mutagenesis and cell binding assays, plus computational ligand docking studies, we discovered five amino acids, including N470, D271, N272, Y446, and W503, which are required for galactose binding that form a pocket at the base of the protrusions around the icosahedral 3-fold axes of symmetry. The importance of these amino acids for tissue tropism was also confirmed by
in vivo
studies in the mouse lung. Identifying the interactions necessary for AAV9 binding to galactose may lead to advances in vector engineering.
ENHANCEMENT OF LIGHT EXTRACTING FROM GaN-BASED BLUE LIGHT EMITTING DIODES USING PHOTONIC CRYSTAL
Authors: WANG YAN , WU FUGEN , ZHANG XIN , YAO YUANWEI , ZHONG HUILIN , YAN SHUYA , HE YUN
Published: April 2012

Photonic crystal (PC) structures on LED have been known to enhance the light extraction significantly. In this paper, we report the light energy of GaN -based blue lighting emitting diode (LED) with perfect area photonic crystal (PPC) structure and defect area photonic crystal (DPC) structure. As a result, the light extracting energy of LEDs with PPC structure enhanced little compared to that of without PC structure. In addition, the light extracting energy of blue LED with DPC structure was remarkably improved.
A neuronal population in hypothalamus that dramatically resists acute ischemic injury compared to neocortex
Authors: Brisson C. Devin , Andrew R. David
Published: April 2012

Pyramidal neurons (PyNs) of the cortex are highly susceptible to acute stroke damage, yet “lower” brain regions like hypothalamus and brain stem better survive global ischemia. Here we show for the first time that a “lower” neuron population intrinsically resists acute strokelike injury. In rat brain slices deprived of oxygen and glucose (OGD), we imaged anoxic depolarization (AD) as it propagated through neocortex or hypothalamus. AD, the initial electrophysiological event of stroke, is a front of depolarization that drains residual energy in compromised gray matter. The extent of AD reliably determines ensuing cortical damage, but do all CNS neurons generate a robust AD? During 10 min of OGD, PyNs depolarize without functional recovery. In contrast, magnocellular neuroendocrine cells (MNCs) in hypothalamus under identical stress generate a weak and delayed AD, resist complete depolarization, and rapidly repolarize when oxygen and glucose are restored. They recover their membrane potential, input resistance, and spike amplitude and can survive multiple OGD exposures. Two-photon microscopy in slices derived from a fluorescent mouse line confirms this protection, revealing PyN swelling and dendritic beading after OGD, whereas MNCs are not injured. Exposure to the Na+-K+-ATPase inhibitor ouabain (100 μM) induces AD similar to OGD in both cell types. Moreover, elevated extracellular K+ concentration ([K+]o) evokes spreading depression (SD), a milder version of AD, in PyNs but not MNCs. Therefore overriding the pump by OGD, ouabain, or elevated [K+]o evokes a propagating depolarization in higher gray matter but not in MNCs. We suggest that variation in Na+-K+-ATPase pump efficiency during ischemia injury determines whether a neuronal type succumbs to or resists stroke.
PPARαas a Transcriptional Regulator for Detoxification of Plant Diet-Derived Unfavorable Compounds
Authors: Ashibe Bunichiro , Nakajima Yu , Fukui Yuka , Motojima Kiyoto
Published: April 2012

Plants contain potentially toxic compounds for animals and animals have developed physiological strategies to detoxify the ingested toxins during evolution. Feeding mice with various plant seeds and grains showed unexpected result that only sesame killed PPARα-null mice but not wild-type mice at all. A detailed analysis of this observation revealed that PPARαis involved in the metabolism of toxic compounds from plants as well as endobiotic substrates by inducing phase I and phase II detoxification enzymes. PPARαplays a vital role in direct or indirect activation of the relevant genes via the complex network among other xenobiotic nuclear receptors. Thus, PPARαplays its wider and more extensive role in energy metabolism from natural food intake to fat storage than previously thought.
Astragalus Injection for Hypertensive Renal Damage: A Systematic Review
Authors: Sun Tian , Xu Hao , Xu Fengqin
Published: April 2012

Objective. To evaluate the effectiveness of astragalus injection (a traditional Chinese patent medicine) for patients with renal damage induced by hypertension according to the available evidence.Methods. We searched MEDLINE, China National Knowledge Infrastructure (CNKI), Chinese VIP Information, China Biology Medicine (CBM), and Chinese Medical Citation Index (CMCI), and the date of search starts from the first of database to August 2011. No language restriction was applied. We included randomized controlled trials testing astragalus injection against placebo or astragalus injection plus antihypertensive drugs against antihypertensive drugs. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane review standards.Results. 5 randomized trials (involving 429 patients) were included and the methodological quality was evaluated as generally low. The pooled results showed that astragalus injection was more effective in lowering β2-microglobulin (β2-MG), microalbuminuria (mAlb) compared with placebo, and it was also superior to prostaglandin in lowering blood urea nitrogen (BUN), creatinine clearance rate (Ccr). There were no adverse effects reported in the trials from astragalus injection.Conclusions. Astragalus injection showed protective effects in hypertensive renal damage patients, although available studies are not adequate to draw a definite conclusion due to low quality of included trials. More rigorous clinical trials with high quality are warranted to give high level of evidence.
Zinc-Inhibited MMP-Mediated Collagen Degradation after Different Dentine Demineralization Procedures
Authors: Toledano M. , Yamauti M. , Osorio E. , Osorio R.
Published: April 2012

Background: Dentine matrix metalloproteinases (MMPs) play an important role in the dentine caries process. Aims: To determine if MMP-mediated collagen degradation of acid-demineralized dentine may be inhibited by zinc or zinc chelators. Methods: Human dentine specimens were demineralized by phosphoric acid (PA), ethylenediaminetetraacetic acid (EDTA), Clearfil SE Bond primer (SE), or Xeno V (XE) and stored in artificial saliva. Chlorhexidine digluconate (CHX), doxycycline, EDTA, or ZnCl2 was added. C-terminal telopeptide determinations (ICTP) were performed by radioimmunoassay after 24 h and 4 weeks. Results: Collagen degradation was prominent in PA-demineralized (ICTP values from 74.01 µg/l at 24 h to 202.46 µg/l after 4 weeks) and EDTA-demineralized dentine (ICTP values from 83.93 µg/l at 24 h to 158.82 µg/l after 4 weeks) stored in artificial saliva. Doxycycline fully blocked proteolysis. CHX and EDTA reduced collagen degradation only at 24 h. Zinc in excess strongly inhibited hydrolysis of collagen in all tested groups (ICTP values were: PA, 13.56 µg/l; EDTA, 11.21 µg/l; SE, 1.52 µg/l, and XE, 2.37 µg/l) and its effect was maintained for up to 4 weeks, except for EDTA-treated dentine (ICTP values were: PA, 40.76 µg/l; EDTA, 79.15 µg/l; SE, 5.29 µg/l, and XE, 6.38 µg/l). Conclusion: EDTA and CHX exerted time-limited MMP inhibition, and excess zinc served as an effective inhibitor of MMP-mediated collagen degradation in strong or mildly demineralized dentine. MMP degradation of collagen was reduced in resin-infiltrated dentine; the presence of excess zinc chloride exerted an additional protective effect.
The Opioid System and Food Intake: Homeostatic and Hedonic Mechanisms
Authors: Nogueiras Ruben , Romero-Picó Amparo , Vazquez Maria J. , Novelle Marta G. , López Miguel , Diéguez Carlos
Published: April 2012

Opioids are important in reward processes leading to addictive behavior such as self-administration of opioids and other drugs of abuse including nicotine and alcohol. Opioids are also involved in a broadly distributed neural network that regulates eating behavior, affecting both homeostatic and hedonic mechanisms. In this sense, opioids are particularly implicated in the modulation of highly palatable foods, and opioid antagonists attenuate both addictive drug taking and appetite for palatable food. Thus, craving for palatable food could be considered as a form of opioid-related addiction. There are three main families of opioid receptors (µ, ĸ, and δ) of which µ-receptors are most strongly implicated in reward. Administration of selective µ-agonists into the NAcc of rodents induces feeding even in satiated animals, while administration of µ-antagonists reduces food intake. Pharmacological studies also suggest a role for ĸ- and δ-opioid receptors. Preliminary data from transgenic knockout models suggest that mice lacking some of these receptors are resistant to high-fat diet-induced obesity.
Net Clinical Benefit of Warfarin in Patients With Atrial Fibrillation
Authors: Friberg Leif , Rosenqvist Mårten , Lip Gregory Y.H.
Published: April 2012

Background—

Known risk factors for bleeding during anticoagulant treatment are largely the same as those predicting thromboembolic events in patients with atrial fibrillation (AF). Our objective was to investigate how to maximize the likelihood of avoiding both stroke and bleeding.

Methods and Results—

All 182 678 subjects with atrial fibrillation in the Swedish Hospital Discharge Register were studied for an average of 1.5 years (260 000 patient-years at risk). Patients were stratified according to risk scores with the use of historic
International Classification of Disease
diagnostic codes in the register. Information about medication was obtained from the Swedish Drug Registry. Our primary end point was net benefit defined as number of avoided ischemic strokes with anticoagulation minus the number of excess intracranial bleedings with a weight of 1.5 to compensate for the generally more severe outcome with intracranial bleedings. The adjusted net clinical benefit favored anticoagulation for almost all atrial fibrillation patients. The exceptions were patients at very low risk of ischemic stroke with a CHA
2
DS
2
-VASc score of 0 and moderately elevated bleeding risk (−1.7%/y). The results were broadly similar with CHADS
2
, except for patients with very low embolic risk; the CHA
2
DS
2
-VASc was able to identify those patients (n=6205, 3.9% of all patients) who had no net clinical benefit or even some disadvantage from anticoagulant treatment.

Conclusions—

In almost all patients with atrial fibrillation, the risk of ischemic stroke without anticoagulant treatment is higher than the risk of intracranial bleeding with anticoagulant treatment. Analysis of the net benefit indicates that more patients may benefit from anticoagulant treatment.
The Real and/as Representation: TV, Video, and Contemporary Art in Armenia
Authors: Harutyunyan Angela
Published: April 2012

The article situates video art produced in Armenia in the late 1990s and early 2000s in the framework of larger social transformations from modern to post-modern society. It explores the ways in which the paradigm shift in media representations in Armenia affected art production and reception. By critically examining theories of video art as developed in the context of the Euro-American academia and their applicability to historically specific contexts, the article argues that the late 1990s brought about a rapid shift in the relationship between the real and representation in which media images were perceived as more real than “reality” of everyday non-mediatized experiences.
Covariability of Surface Wind and Stress Responses to Sea Surface Temperature Fronts
Authors: O’Neill Larry W. , Chelton Dudley B. , Esbensen Steven K.
Published: April 2012

The responses of surface wind and wind stress to spatial variations of sea surface temperature (SST) are investigated using satellite observations of the surface wind from the Quick Scatterometer (QuikSCAT) and SST from the Advanced Microwave Scanning Radiometer on the Advanced Microwave Scanning Radiometer for Earth Observing System (EOS) (AMSR-E) Aqua satellite. This analysis considers the 7-yr period June 2002–May 2009 during which both instruments were operating. Attention is focused in the Kuroshio, North and South Atlantic, and Agulhas Return Current regions. Since scatterometer wind stresses are computed solely as a nonlinear function of the scatterometer-derived 10-m equivalent neutral wind speed (ENW), qualitatively similar responses of the stress and ENW to SST are expected. However, the responses are found to be more complicated on the oceanic mesoscale. First, the stress and ENW are both approximately linearly related to SST, despite a nonlinear relationship between them. Second, the stress response to SST is 2 to 5 times stronger during winter compared to summer, while the ENW response to SST exhibits relatively little seasonal variability. Finally, the stress response to SST can be strong in regions where the ENW response is weak and vice versa.

A straightforward algebraic manipulation shows that the stress perturbations are directly proportional to the ENW perturbations multiplied by a nonlinear function of the ambient large-scale ENW. This proportionality explains why both the stress and ENW depend linearly on the mesoscale SST perturbations, while the dependence of the stress perturbations on the ambient large-scale ENW explains both the seasonal pulsing and the geographic variability of the stress response to SST compared with the less variable ENW response.