bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Complementation of Hepatitis C Virus Nonstructural Protein Functions Associated with Replication Exhibits Requirements That Differ from Those for Virion Assembly
Authors: Herod Morgan R. , Schregel Vera , Hinds Chris , Liu Mengya , McLauchlan John , McCormick Christopher J. 
Published: December 2013

ABSTRACT

Within the polyprotein encoded by hepatitis C virus (HCV), the minimum components required for viral RNA replication lie in the NS3-5B region, while virion assembly requires expression of all virus components. Here, we have employed complementation systems to examine the role that HCV polyprotein precursors play in RNA replication and virion assembly. In a
trans
-complementation assay, an HCV NS3-5A polyprotein precursor was required to facilitate efficient complementation of a replication-defective mutation in NS5A. However, this requirement for precursor expression was partially alleviated when a second functional copy of NS5A was expressed from an additional upstream cistron within the RNA to be rescued. In contrast, rescue of a virion assembly mutation in NS5A was more limited but exhibited little or no requirement for expression of functional NS5A as a precursor, even when produced in the context of a second replicating helper RNA. Furthermore, expression of NS5A alone from an additional cistron within a replicon construct gave greater rescue of virion assembly in
cis
than in
trans
. Combined with the findings of confocal microscope analysis examining the extent to which the two copies of NS5A from the various expression systems colocalize, the results point to NS3-5A playing a role in facilitating the integration of nonstructural (NS) proteins into viral membrane-associated foci, with this representing an early stage in the steps leading to replication complex formation. The data further imply that HCV employs a minor virion assembly pathway that is independent of replication.

IMPORTANCE
In hepatitis C virus-infected cells, replication is generally considered an absolute prerequisite for virus particle formation. Here we investigated the role that the viral protein NS5A has in both replication and particle assembly using complementation assays and microscopy. We found that efficient rescue of replication required NS5A to be expressed as part of a larger polyprotein, and this correlated with detection of NS5A at sites where replication occurred. In contrast, rescue of particle assembly did not require expression of NS5A within the context of a polyprotein. Interestingly, although only partial restoration of particle assembly was possible by complementation, that proportion that could be rescued benefitted from expressing NS5A from the same RNA being packaged. Collectively, these findings provide new insight into aspects of polyprotein function. They also support the existence of a minor virion assembly pathway that bypasses replication.
Maternal mortality in Malawi, 1977–2012
Authors: Colbourn Tim , Lewycka Sonia , Nambiar Bejoy , Anwar Iqbal , Phoya Ann , Mhango Chisale 
Published: December 2013

BackgroundMillennium Development Goal 5 (MDG 5) targets a 75% reduction in maternal mortality from 1990 to 2015, yet accurate information on trends in maternal mortality and what drives them is sparse. We aimed to fill this gap for Malawi, a country in sub-Saharan Africa with high maternal mortality.MethodsWe reviewed the literature for population-based studies that provide estimates of the maternal mortality ratio (MMR) in Malawi, and for studies that list and justify variables potentially associated with trends in MMR. We used all population-based estimates of MMR representative of the whole of Malawi to construct a best-fit trend-line for the range of years with available data, calculated the proportion attributable to HIV and qualitatively analysed trends and evidence related to other covariates to logically assess likely candidate drivers of the observed trend in MMR.Results14 suitable estimates of MMR were found, covering the years 1977–2010. The resulting best-fit line predicted MMR in Malawi to have increased from 317 maternal deaths/100 000 live-births in 1980 to 748 in 1990, before peaking at 971 in 1999, and falling to 846 in 2005 and 484 in 2010. Concurrent deteriorations and improvements in HIV and health system investment and provisions are the most plausible explanations for the trend. Female literacy and education, family planning and poverty reduction could play more of a role if thresholds are passed in the coming years.ConclusionsThe decrease in MMR in Malawi is encouraging as it appears that recent efforts to control HIV and improve the health system are bearing fruit. Sustained efforts to prevent and treat maternal complications are required if Malawi is to attain the MDG 5 target and save the lives of more of its mothers in years to come.
Rear Operations Group medicine: a pilot study of psychological decompression in a Rear Operations Group during Operation HERRICK 14
Authors: Nimenko Wasyl , Simpson R G 
Published: December 2013

ObjectivesTo investigate group activity psychological decompression (GAPD) in a Rear Operations Group.MethodsProvision of military archaeological exercises for a Rear Operations Group's medical centre patients during Op HERRICK 14 with analysis of before and after Patient Health Questionnaires (PHQ), Work and Social Adjustment Scales, generalised anxiety disorder (GAD) 7 Anxiety, Audit Questionnaire and Impact of Events Scale Revised and analysis of interviews with supervisors and soldiers.ResultsSoldiers reported a mean of 13%–38% improvement across the self-reported domains. The civilian archaeologists reported improvements in self-esteem, morale and team-working. 10 out of 24 soldiers have expressed an interest to pursue archaeology further; eight soldiers disclosed mental health issues for the first time, four of whom required mental health referral.ConclusionsGAPD can help early-returned soldiers in reducing symptoms of anxiety, depression, isolation and psychological traumatic symptoms. It also helps to increase perception of their ability to work and socialise as a team and help them to an early return to work. It can provide soldiers with the opportunity to approach their supervisors in an informal manner and help in early detection of mental health problems.
TOWARD THE REDEFINITION OF THE KILOGRAM FROM THE 28Si INTERNATIONAL RESEARCH PROJECT
Authors: FUJII KENICHI 
Published: December 2013

In the international system of units, the kilogram in the only SI base unit still defined by a material artefact. In order to redefine this unit with a fundamental physical constant, an international research project was launched in 2004 for determining the Avogadro constant, NA, by counting the atoms in an isotopically enriched 28Si crystal. The counting procedure relies on the measurements of the molar and atomic volumes of 1 kg spheres made of the 28Si crystal. In 2011, the project succeeded in measuring the Avogadro constant with a smallest standard uncertainty, 3.0 × 10−8 NA. Because of an unexpected metallic contamination at the surface of the spheres, the measurement uncertainty was larger than the target of the project by a factor of 1.5. In order to further reduce the uncertainty, a new international research project was launched in 2012. Outline of the new project and the improvements of the measurements will be introduced at the forum. Note from Publisher: This article contains the abstract only.
MEASUREMENT OF CANTILEVER'S SPRING CONSTANT WITH CMS ELECTROSTATIC FORCE STANDARD
Authors: CHEN SHENG-JUI , PAN SHEAU-SHI , YEH YU-SHAN , LIN YI-CHING 
Published: December 2013

The mechanical property is one of the important parameters for evaluating micro/nano-scale materials. The measurement of micro/nano-mechanical property usually involves measurements of small displacement and force. To provide a traceable force standard in micro/nano-newton level, we have developed a force measurement system based on electrostatic sensing and actuation techniques. The system mainly consists of a monolithic flexure stage, a three-electrode capacitor and a digital controller. The three-electrode capacitor is utilized as a position sensor, and at the same time an electrostatic force actuator. The force under measurement is balanced by a compensation electrostatic force which is traceable to electrical and length standards. A commercial cantilever-type micro-force probe was used in this calibration experiment. The force probe was brought to contact with and press into the load button (a ruby sphere) of the force measurement system by a closed-loop controlled z-scanner. The spring constant was obtained from the average slope determined from measured force-displacement curves and was found to be (2.26 ± 0.01) N/m where the given uncertainty is one standard deviation. We have successfully demonstrated the calibration of the microforce probe using our self-developed electrostatic sensing and actuating force measurement system. The measured spring constant is consistent with the manufacturer's specification, and the relative standard deviation is less than 0.5%. Note from Publisher: This article contains the abstract only.
FANCJ Localization by Mismatch Repair Is Vital to Maintain Genomic Integrity after UV Irradiation
Authors: Guillemette Shawna , Branagan Amy , Peng Min , Dhruva Aashana , Schärer Orlando D. , Cantor Sharon B. 
Published: December 2013

Abstract
Nucleotide excision repair (NER) is critical for the repair of DNA lesions induced by UV radiation, but its contribution in replicating cells is less clear. Here, we show that dual incision by NER endonucleases, including XPF and XPG, promotes the S-phase accumulation of the BRCA1 and Fanconi anemia–associated DNA helicase FANCJ to sites of UV-induced damage. FANCJ promotes replication protein A phosphorylation and the arrest of DNA synthesis following UV irradiation. Interaction defective mutants of FANCJ reveal that BRCA1 binding is not required for FANCJ localization, whereas interaction with the mismatch repair (MMR) protein MLH1 is essential. Correspondingly, we find that FANCJ, its direct interaction with MLH1, and the MMR protein MSH2 function in a common pathway in response to UV irradiation. FANCJ-deficient cells are not sensitive to killing by UV irradiation, yet we find that DNA mutations are significantly enhanced. Thus, we considered that FANCJ deficiency could be associated with skin cancer. Along these lines, in melanoma we found several somatic mutations in FANCJ, some of which were previously identified in hereditary breast cancer and Fanconi anemia. Given that, mutations in XPF can also lead to Fanconi anemia, we propose collaborations between Fanconi anemia, NER, and MMR are necessary to initiate checkpoint activation in replicating human cells to limit genomic instability. Cancer Res; 74(3); 932–44. ©2013 AACR.
Managing Breast Cancers with Low Estrogen Receptor and HER2 by Drugging Both
Authors: Miller Todd W. 
Published: December 2013

Abstract
Low estrogen receptor (ER) levels in breast tumors are associated with poorer response to antiestrogen therapy. Finn and colleagues identify low ER levels as a biomarker predicting benefit from the addition of the EGFR/HER2 dual inhibitor lapatinib to an antiestrogen treatment regimen in patients with metastatic ER+/HER2− breast cancer. Clin Cancer Res; 20(3); 528–30. ©2013 AACR.
PDK1 selectively phosphorylates Thr(308) on Akt and contributes to human platelet functional responses
Authors: Dangelmaier Carol , Manne Bhanu Kanth , Liverani Elizabetta , Jin Jianguo , Bray Paul , Kunapuli Satya P. 
Published: December 2013

Summary3-phosphoinositide-dependent protein kinase 1 (PDK1), a member of the protein A,G and C (AGC) family of proteins, is a Ser/Thr protein kinase that can phosphorylate and activate other protein kinases from the AGC family, including Akt at Thr308, all of which play important roles in mediating cellular responses. The functional role of PDK1 or the importance of phosphorylation of Akt on Thr308 for its activity has not been investigated in human platelets. In this study, we tested two pharmacological inhibitors of PDK1, BX795 and BX912, to assess the role of Thr308 phosphorylation on Akt. PAR4-induced phosphorylation of Akt on Thr308 was inhibited by BX795 without affecting phosphorylation of Akt on Ser473. The lack of Thr308 phosphorylation on Akt also led to the inhibition of PAR4-induced phosphorylation of two downstream substrates of Akt, viz. GSK3β and PRAS40. In vitro kinase activity of Akt was completely abolished if Thr308 on Akt was not phosphorylated. BX795 caused inhibition of 2-MeSADP-induced or collagen-induced aggregation, ATP secretion and thromboxane generation. Primary aggregation induced by 2-MeSADP was also inhibited in the presence of BX795. PDK1 inhibition also resulted in reduced clot retraction indicating its role in outside-in signalling. These results demonstrate that PDK1 selectively phosphorylates Thr308 on Akt thereby regulating its activity and plays a positive regulatory role in platelet physiological responses.
Predictors of Improvement in Cardiometabolic Risk Factors With Weight Loss in Women
Authors: Dow Caitlin A. , Thomson Cynthia A. , Flatt Shirley W. , Sherwood Nancy E. , Pakiz Bilge , Rock Cheryl L. 
Published: December 2013

Background
Weight loss is associated with improvements in cardiometabolic risk factors, including serum glucose, insulin, C‐reactive protein, and blood lipids. Few studies have evaluated the long‐term (>18 months) effect of weight loss on these risk factors or sought to identify factors associated with sustained improvements in these measures.

Methods and Results

In 417 overweight/obese women (mean [
SD
] age, 44 [10] years) participating in a weight loss trial, we sought to identify predictors of weight loss–associated cardiometabolic risk factors after 12 and 24 months of intervention. Total cholesterol (
TC
), low‐density lipoprotein (LDL)–cholesterol (LDL‐C), high‐density lipoprotein (
HDL
)–cholesterol, non‐
HDL
‐cholesterol, triglycerides (TG), insulin, glucose, C‐reactive protein (CRP), and cardiopulmonary fitness were measured at baseline and at 12 and 24 months. After 24 months, significant reductions in body weight, waist circumference, CRP, TC,
HDL
‐cholesterol, and non‐
HDL
‐cholesterol were observed (
P
<0.01). After 24 months, mean TC and non‐
HDL
‐cholesterol were reduced regardless of the amount of weight lost, whereas reductions in LDL–cholesterol, CRP, insulin, and TG were observed only in those who lost ≥10% body weight. Step‐test performance improved only in those who lost ≥10% body weight after 24 months. Change in weight demonstrated a positive predictive value for change in cholesterol, insulin, glucose, and triglycerides. Baseline level of the biomarker showed the greatest predictive value for follow‐up measures for insulin, cholesterol, glucose, and triglycerides.

Conclusions
Our data extend the results from short‐term weight loss trials and suggest that the magnitude of weight loss and baseline values for risk factors are associated with improvements in cardiometabolic risk factors even after 24 months.

Clinical Trials Registration Information

URL:
http://www.clinicaltrials.gov/
. Unique identifier: NCT00640900.
A Minimum Variance Method for Lidar Signal Inversion
Authors: Sušnik Andreja , Holder Heidi , Eichinger William 
Published: December 2013

Abstract
A method for the inversion of elastic lidar data is proposed that determines the value of the extinction coefficient to be used as a boundary condition, by minimizing the variance of the extinction coefficients in a delimited region. The method works well for single-component atmospheres, where the delimited region contains aerosols from a single distribution of concentrations. For situations where there may be two or more distributions (e.g., a smoke plume in the ambient atmosphere), the spatial regions containing each distribution must be identified and treated separately. Examples of inversions are given, including an example of a range–time scan showing the amount of shot-to-shot consistency that may be obtained from the method.
Do Organizational Culture and Climate Matter for Successful Client Outcomes?
Authors: Wolf David A. Patterson Silver , Dulmus Catherine N. , Maguin Eugene , Cristalli Maria 
Published: December 2013

Objectives: The existing literature on the impact of workplace conditions on client care suggests that good cultures and climates provide the best outcomes for clients. The primary purpose of this study was to investigate the relationship between organizational culture and climate and the proportion of children and youth successfully discharged from a large organization in New York state. Method: Thirty-three child and youth programs with existing culture and climate data evaluated outcome information from 1,336 clients exiting its services. Results: Programs reported as having bad culture and climate yielded superior client outcomes, measured as discharge to a lower level of care and successfully completing. Conclusion: This study and its conclusion point to a gap in knowledge concerning the relation between workplace culture and climate and the impact on client care and workers’ perceptions; this warrants further investigation in similar studies of agencies and their outcomes.
Self-Reported Quality of Life in Patients With Diabetes
Authors: Raspovic Katherine M. , Wukich Dane K. 
Published: December 2013

Background: Previous reports using the Short Form-36 as a generic measure of quality of life have demonstrated reduced quality of life in patients with Charcot neuroarthropathy (CN). The aim of this study was to assess self-reported quality of life using the SF-36 and a region-specific assessment (the Foot and Ankle Ability Measure [FAAM]), hypothesizing that patients with diabetes and CN would have lower self-reported scores than patients with diabetes and no foot disease. Methods: Fifty patients with diabetes and CN were included in the study group. Fifty-six patients with diabetes and no pedal complaints comprised the control group. Quality of life was assessed with the SF-36 and the FAAM. Results: Patients with CN were more likely to have type 1 diabetes mellitus, were more likely to use insulin, had greater duration of diabetes, and were more likely to be neuropathic than patients in the control group. Patients with CN reported mean FAAM activities of daily living (ADL) scores that were 2 standard deviations below the control group and sports scores that were 1 standard deviation lower. There was no notable difference between the SF-36 mental component summary scores between the CN and control groups. SF-36 physical component summary scores in patients with CN were notably lower than scores in the control group. Conclusion: CN is associated with reduced quality of life as measured with the SF-36 and FAAM. To the best of our knowledge, this is the first study directly comparing self-reported outcome assessments in patients with both diabetes and CN and patients with diabetes without foot complaints. Level of Evidence: Level III, comparative series.
Aneurysmal Degeneration of Deep Lower Extremity Vein Conduits Used for Vascular Reconstruction
Authors: Chavez LeAnn A. , Leon Luis R. , Hughes John , Mills Joseph L. 
Published: December 2013

Background: Successful outcomes have been reported with the use of femoropopliteal vein (FPV) grafts as arterial conduits. We identified 2 patients with a rare complication, true, nonanastomotic aneurysmal degeneration. Methods: Patients from 1997 through 2009 that utilized FPV grafts for revascularization were analyzed. We contacted survivors by phone and conducted a literature search of FPV aneurysms. Results: Of the total of 14 patients in our practice whose FPV was used as a conduit during the study period, 2 developed nonanastomotic FPV graft aneurysms. The mean follow-up time was 33.44 months. Literature review uncovered only 1 previously published case of FPV aneurysmal degeneration. Conclusions: Our experience suggests that nonanastomotic aneurysms of FPV grafts may occur more often than those suspected previously. Our study represents the first reports of aneurysmal degeneration affecting FPV grafts when used for vascular reconstructions.
Increased use of the affected hand one and a half years after surgical correction for cerebral palsy and subsequent intensive hand therapy
Authors: Hansen Alice Ø , Tromborg Hans 
Published: December 2013

Introduction Good hand function is essential for carrying out daily activities. People with unilateral cerebral palsy often have spasticity in their affected hand and arm, which makes it difficult to perform bimanual tasks. The aim of this study was to measure changes in grip span, strength and functional use of the affected hand when assisting in two-handed activities after surgical correction for cerebral palsy and subsequent intensive hand therapy. Methods Since 1999, we have been evaluating all patients with unilateral cerebral palsy who had the potential for surgical correction of their forearm and hand, followed by intensive hand therapy at our university hospital. We tested their grip span, strength and use in two-handed activities preoperatively and six and 18 months postoperatively. Results Between 1999 and 2011, 39 patients have had a corrective operation with tendon transfer to correct a deformity of the wrist and most have had a correction of the thumb as well. All received subsequent hand therapy until six months after the operation. Grip span, strength and changes in the functional use of the affected hand when assisting in two-handed activities all increased significantly ( p<0.01), six and 18 months postoperatively. Discussion Patients demonstrated a more useful affected hand in everyday activities and results persisted after the rehabilitation ceased at six months. Our findings support surgical correction for cerebral palsy followed by intensive hand therapy improves hand position and hand function.
Randomized Trial of Harp Therapy During In Vitro Fertilization–Embryo Transfer
Authors: Murphy Erin M. , Nichols Jennifer , Somkuti Steve G. , Sobel Michael , Braverman Andrea , Barmat Larry I. 
Published: December 2013

Objective: This study evaluated whether harp therapy reduces levels of stress and improves clinical outcomes in patients undergoing embryo transfer. Design: This prospective randomized trial enrolled 181 women undergoing embryo transfer, who were randomized to harp therapy during embryo transfer or standard treatment. Patients underwent standardized psychological testing and physiologic assessment of stress. Setting: The study was conducted in a reproductive medicine practice. Results: No statistically significant differences were found in the heart and respiratory rates, nor was there a significant difference in event-based anxiety at baseline. Harp therapy had a significantly larger decrease in state anxiety from pre– to post–embryo transfer. Clinical pregnancy was 53% versus 48% for the harp therapy and standard treatment groups, respectively. Conclusion: Harp therapy decreases state, or event-based, anxiety, significantly lowering state scores posttransfer and having a positive effect on acute levels of stress. There was an increased pregnancy rate, but larger sample sizes are needed to evaluate whether harp therapy has an effect on clinical outcomes.
Reversal of in situ T-cell exhaustion during effective human antileukemia responses to donor lymphocyte infusion
Authors: Bachireddy Pavan , Hainz Ursula , Rooney Michael , Pozdnyakova Olga , Aldridge Julie , Zhang Wandi , Liao Xiaoyun , Hodi F. Stephen , O’Connell Karyn , Haining W. Nicholas , Goldstein Natalie R. , Canning Christine M. , Soiffer Robert J. , Ritz Jerome , Hacohen Nir , Alyea Edwin P. , Kim Haesook T. , Wu Catherine J. 
Published: December 2013

Key Points
Marrow CD8+ T-cell infiltrates may be a novel predictor of response to donor lymphocyte infusions in patients with relapsed CML. Reversal of T-cell exhaustion is tightly linked to effective antileukemia responses to donor lymphocyte infusions.