bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Alterations in Gray Matter Volume With Reduced Evoked‐Pain Connectivity Following Short‐Term Administration of Pregabalin in Patients With Fibromyalgia
Authors: Puiu Tudor , Kairys Anson E. , Pauer Lynne , Schmidt‐Wilcke Tobias , Ichesco Eric , Hampson Johnson P. , Napadow Vitaly , Clauw Daniel J. , Harris Richard E.
Published: January 2016

Objective

Pregabalin (PGB) is an α2δ calcium‐channel subunit ligand that has previously been shown to reduce chronic pain in multiple conditions. Preclinical studies indicate that PGB may down‐regulate brain glutamate release while also inhibiting astrocyte induction of glutamatergic synapse formation, and recent clinical findings support the notion that PGB modulates glutamatergic activity and functional brain connectivity in order to produce analgesia. The present study was undertaken to examine concurrent changes in brain gray matter volume (GMV) or evoked‐pain connectivity in humans receiving PGB.

Methods

Sixteen female fibromyalgia patients participated in a randomized double‐blind 2‐period crossover study of PGB versus placebo. Before and after each period, patients underwent high‐resolution structural and evoked pressure–pain functional brain imaging. GMV was analyzed using voxel‐based morphometry, and functional connectivity during evoked pressure–pain was assessed.

Results

PGB administration significantly reduced GMV within the posterior insula bilaterally, whereas there were no significant changes in insular GMV following placebo treatment. GMV reductions in the medial frontal gyrus were also observed when comparing PGB versus placebo treatment, and were associated with reduced clinical pain. These reductions in insular GMV were associated with concomitant reductions in connectivity to the default mode network, which was also associated with reduced clinical pain.

Conclusion

Short‐term PGB treatment altered brain structure and evoked‐pain connectivity, and these decreases were associated with reduced clinical pain. We speculate that these fairly rapid changes in GMV may be related to brain neuroplasticity. It is unknown whether these effects are generalizable to other chronic pain states.
Next‐Generation Sequencing Reveals Restriction and Clonotypic Expansion of Treg Cells in Juvenile Idiopathic Arthritis
Authors: Henderson Lauren A. , Volpi Stefano , Frugoni Francesco , Janssen Erin , Kim Susan , Sundel Robert P. , Dedeoglu Fatma , Lo Mindy S. , Hazen Melissa M. , Beth Son Mary , Mathieu Ronald , Zurakowski David , Yu Neng , Lebedeva Tatiana , Fuhlbrigge Robert C. , Walter Jolan E. , Nee Lee Yu , Nigrovic Peter A. , Notarangelo Luigi D.
Published: January 2016

Objective

Treg cell–mediated suppression of Teff cells is impaired in juvenile idiopathic arthritis (JIA); however, the basis for this dysfunction is incompletely understood. Animal models of autoimmunity and immunodeficiency demonstrate that a diverse Treg cell repertoire is essential to maintain Treg cell function. The present study was undertaken to investigate the Treg and Teff cell repertoires in JIA.

Methods

Treg cells (CD4+CD25+CD127low) and Teff cells (CD4+CD25−) were isolated from peripheral blood and synovial fluid obtained from JIA patients, healthy controls, and children with Lyme arthritis. Treg cell function was measured in suppressive assays. The T cell receptor β chain (TRB) was amplified by multiplex polymerase chain reaction and next‐generation sequencing was performed, with amplicons sequenced using an Illumina HiSeq platform. Data were analyzed using ImmunoSEQ, International ImMunoGeneTics system, and the Immunoglobulin Analysis Tools.

Results

Compared to findings in controls, the JIA peripheral blood Treg cell repertoire was restricted, and clonotypic expansions were found in both blood and synovial fluid Treg cells. Skewed usage and pairing of TRB variable and joining genes, including overuse of gene segments that have been associated with other autoimmune conditions, was observed. JIA patients shared a substantial portion of synovial fluid Treg cell clonotypes that were private to JIA and not identified in Lyme arthritis.

Conclusion

We identified restriction and clonotypic expansions in the JIA Treg cell repertoire with sharing of Treg cell clonotypes across patients. These findings suggest that abnormalities in the Treg cell repertoire, possibly engendered by shared antigenic triggers, may contribute to disease pathogenesis in JIA.
Distinct Functions of Autoantibodies Against Interferon in Systemic Lupus Erythematosus: A Comprehensive Analysis of Anticytokine Autoantibodies in Common Rheumatic Diseases
Authors: Gupta Sarthak , Tatouli Ioanna P. , Rosen Lindsey B. , Hasni Sarfaraz , Alevizos Ilias , Manna Zerai G. , Rivera Juan , Jiang Chao , Siegel Richard M. , Holland Steven M. , Moutsopoulos Haralampos M. , Browne Sarah K.
Published: January 2016

Objective

Anticytokine autoantibodies occur across a range of hematologic, pulmonary, and infectious diseases. However, systematic investigation of their presence and significance in autoimmune diseases is lacking. This study was undertaken to examine the distinct functions of anticytokine autoantibodies in patients with systemic lupus erythematosus (SLE) compared to patients with other rheumatic diseases and healthy controls.

Methods

Serum samples from patients with SLE (n = 199), patients with primary Sjögren's syndrome (SS) (n = 150), patients with rheumatoid arthritis (RA) (n = 149), and healthy controls (n = 200) were screened for 24 anticytokine autoantibodies using a multiplex bead‐based assay. To evaluate the biologic activity of anticytokine autoantibodies, their ability to block cytokine‐induced signal transduction or protein expression was measured. RNA sequencing was performed on whole blood in a subset of healthy controls and patients with SLE.

Results

Patients with SLE and those with SS had a striking excess of autoantibodies against interferons and the interferon‐responsive chemokine interferon‐inducible protein 10 (IP‐10). Only autoantibodies against type I interferon, interleukin‐12 (IL‐12), and IL‐22 exhibited neutralizing activity. In SLE, the presence of anti–interferon‐γ autoantibodies was correlated with more severe disease activity, higher levels of anti–double‐stranded DNA antibodies, and elevated expression of interferon‐α/β–inducible genes. Conversely, in SLE patients with blocking anti–interferon‐α autoantibodies, the type I interferon gene expression signature was normalized. Anti–type III interferon autoantibodies (λ2, λ3) and anti–IP‐10 autoantibodies were newly recognized in SLE patient serum, and autoantibodies against macrophage‐colony stimulating factor, IL‐4, IL‐7, IL‐17, and IL‐22, none of which have been previously identified in rheumatic conditions, were discovered.

Conclusion

Anticytokine autoantibodies are associated with distinct patterns of disease in SLE, SS, and RA. Anti‐interferon autoantibodies are overrepresented in patients with SLE and those with SS, and fall into distinct functional classes, with only a subset of anti–type I interferon antibodies exhibiting neutralizing activity. Anti–interferon‐γ autoantibodies are correlated with increased disease activity and interferon‐related gene expression, suggesting that such autoantibodies may contribute to the pathogenesis of SLE.
Brief Report: Spatial Heterogeneity of Systemic Sclerosis in France: High Prevalence in the Northeast Region
Authors: Meyer Alain , Chifflot Hélène , Chatelus Emmanuel , Kleinmann Jean‐François , Ronde‐Ousteau Cécile , Klein Delphine , Jégu Jérémy , Geny Bernard , Hirshi Sandrine , Canuet Matthieu , Blaison Gilles , Kieffer Pierre , Lipsker Dan , Martin Thierry , Sauleau Erik , Velten Michel , Sibilia Jean
Published: January 2016

Objective

Alsace is a region in eastern France with a population of ∼2 million. All residents have high access to health care and an accredited referral center for SSc. Seeking care outside of this region is difficult because of the peculiar geography. The aim of this study was to assess the prevalence and spatial variation of systemic sclerosis (SSc) in eastern France.

Methods

Data for SSc patients were obtained from 3 sources (all general practitioners and community specialists, capillaroscopy centers, and all public and private hospital records) and were used to estimate the prevalence of SSc. Surviving patients who resided in Alsace on January 1, 2008 and fulfilled the American College of Rheumatology and/or the LeRoy and Medsger criteria were included in this study. The clinical characteristics of the patients were also assessed. Potentially incomplete case ascertainment was corrected by capture–recapture analyses. Geographic disparities were assessed by spatial cluster analysis and by comparing our results with those for other geographic areas in the world for which data derived using similar methodology were available.

Results

The review of 499 potential cases identified a total of 244 SSc patients. A trend toward a west‐to‐east gradient was observed but did not reach statistical significance. According to log‐linear modeling, an estimated 83.87 additional cases were missed. Thus, the SSc prevalence was 228.42 cases per million adult inhabitants of Alsace (95% confidence interval 203.70–253.14); this prevalence was significantly higher than that in 2 other regions of France and comparable with the reported prevalence in Detroit, Michigan.

Conclusion

The stringent methodology used in the current study is very likely to provide an accurate estimation of the prevalence of SSc. Design similarity with 3 other surveys extends the scope of the results by identifying geographic disparities that were previously indistinguishable due to methodologic differences.
Trends in Long‐Term Outcomes Among Patients With Antineutrophil Cytoplasmic Antibody–Associated Vasculitis With Renal Disease
Authors: Rhee Rennie L. , Hogan Susan L. , Poulton Caroline J. , McGregor Julie Anne G. , Richard Landis J. , Falk Ronald J. , Merkel Peter A.
Published: January 2016

Objective

It is still not clear how advances in the management of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) have impacted long‐term outcomes. We undertook this study to examine changes over 25 years in long‐term clinical outcomes, including the impact of renal function at diagnosis (a potential marker of time to disease detection) and the duration of cyclophosphamide use in AAV patients with renal involvement.

Methods

We included ANCA‐positive patients with biopsy‐proven AAV diagnosed between 1985 and 2009 who were followed up in the Glomerular Disease Collaborative Network inception cohort. Outcomes included the composite outcome of end‐stage renal disease (ESRD) or death as well as relapse. Cox proportional hazards or competing risks regression models were adjusted for potential baseline confounders.

Results

Data from 554 patients were included in the analysis. There was a decreasing 5‐year risk of ESRD or death over time (P < 0.001 by log rank test for trend). After adjustment for baseline characteristics, the risk of relapse was similar across the time periods (P = 0.45 by test for trend). Serum creatinine level at baseline was the only significant predictor of an increased risk of ESRD or death (hazard ratio 1.11 per 1 mg/dl of serum creatinine [95% confidence interval 1.04–1.18], P = 0.002).

Conclusion

In patients with renal disease secondary to AAV, over 25 years the risk of ESRD or death has decreased but the risk of relapse has not changed. A higher serum creatinine level at diagnosis is associated with a higher risk of ESRD or death, suggesting that earlier disease detection is potentially an important measure to improve outcomes in AAV.
Detection of lysozyme with aptasensor based on fluorescence resonance energy transfer from carbon dots to graphene oxide
Authors: Wu Jing , Hou Yu , Wang Peiyao , Wang Zhenni , Li Yanjie , Wang Shan , Yang Mei
Published: January 2016

A photoluminescent aptasensor has been developed for the detection of lysozyme based on fluorescence resonance energy transfer (FRET) between the carbon dots (CDs) and graphene oxide (GO). In the sensing system, the CDs‐labeled aptamer is adsorbed onto the GO surface and the photoluminescence (PL) signal of the CDs is effectively quenched by GO. Addition of lysozyme can cause a significant FRET inhibition and recover the PL signal of the CDs due to the specific combination of lysozyme and its aptamer and the removal of the CDs‐labeled aptamer from GO surface. Under optimal conditions, the ratio of PL intensity change at 440 nm of the sensing system before and after the addition of lysozyme shows a good linear relationship against the concentration of lysozyme in the range of 0.01–2 μg/mL, with a low detection limit of 1 × 10−3 μg/mL. In addition, the aptasensor has good selectivity so it can distinguish lysozyme with no or little interference by many other biomolecules. It was applied to the detection of lysozyme in human sera with satisfactory recoveries. The results demonstrate the applicability of the aptasensor for monitoring lysozyme in real samples. Copyright © 2016 John Wiley & Sons, Ltd.
Rapid ester biosynthesis screening reveals a high activity alcohol‐O‐acyltransferase (AATase) from tomato fruit
Authors: Lin Jyun‐Liang , Zhu Jie , Wheeldon Ian
Published: January 2016

Ethyl and acetate esters are naturally produced in various yeasts, plants, and bacteria. The biosynthetic pathways that produce these esters share a common reaction step, the condensation of acetyl/acyl‐CoA with an alcohol by alcohol‐O‐acetyl/acyltransferase (AATase). Recent metabolic engineering efforts exploit AATase activity to produce fatty acid ethyl esters as potential diesel fuel replacements as well as short‐ and medium‐chain volatile esters as fragrance and flavor compounds. These efforts have been limited by the lack of a rapid screen to quantify ester biosynthesis. Enzyme engineering efforts have also been limited by the lack of a high throughput screen for AATase activity. Here, we developed a high throughput assay for AATase activity and used this assay to discover a high activity AATase from tomato fruit, Solanum lycopersicum (Atf‐S.l). Atf1‐S.l exhibited broad specificity towards acyl‐CoAs with chain length from C4 to C10 and was specific towards 1‐pentanol. The AATase screen also revealed new acyl‐CoA substrate specificities for Atf1, Atf2, Eht1, and Eeb1 from Saccharomyces cerevisiae, and Atf‐C.m from melon fruit, Cucumis melo, thus increasing the pool of characterized AATases that can be used in ester biosynthesis of ester‐based fragrance and flavor compounds as well as fatty acid ethyl ester biofuels.
Functionalized silk assembled from a recombinant spider silk fusion protein (Z‐4RepCT) produced in the methylotrophic yeast Pichia pastoris
Authors: Jansson Ronnie , Lau Cheuk H , Ishida Takuya , Ramström Margareta , Sandgren Mats , Hedhammar My
Published: January 2016

Functional biological materials are a growing research area with potential applicability in medicine and biotechnology. Using genetic engineering, the possibility to introduce additional functions into spider silk‐based materials has been realized. Recently, a recombinant spider silk fusion protein, Z‐4RepCT, was produced intracellularly in Escherichia coli and could after purification self‐assemble into silk‐like fibers with ability to bind antibodies via the IgG‐binding Z domain. In this study, the use of the methylotrophic yeast Pichia pastoris for production of Z‐4RepCT has been investigated. Temperature, pH and production time were influencing the amount of soluble Z‐4RepCT retrieved from the extracellular fraction. Purification of secreted Z‐4RepCT resulted in a mixture of full‐length and degraded silk proteins that failed to self‐assemble into fibers. A position in the C‐terminal domain of 4RepCT was identified as being subjected to proteolytic cleavage by proteases in the Pichia culture supernatant. Moreover, the C‐terminal domain was subjected to glycosylation during production in P. pastoris. These observed alterations of the CT domain are suggested to contribute to the failure in fiber assembly. As alternative approach, Z‐4RepCT retrieved from the intracellular fraction, which was less degraded, was used and shown to retain ability to assemble into silk‐like fibers after enzymatic deglycosylation.
High‐throughput cell quantification assays for use in cell purification development – enabling technologies for cell production
Authors: Zimmermann Sarah , Gretzinger Sarah , Scheeder Christian , Schwab Marie‐Luise , Oelmeier Stefan A. , Osberghaus Anna , Gottwald Eric , Hubbuch Jürgen
Published: January 2016

High‐throughput screening (HTS) technology is gaining increasing importance in downstream process development of cell‐based products. The development of such HTS‐technologies, however, is highly dependent on the availability of robust, accurate, and sensitive high‐throughput cell quantification methods. In this article, we compare state‐of‐the‐art cell quantification methods with focus on their applicability in HTS‐platforms for downstream processing of cell‐based products. Sensitivity, dynamic range, and precision were evaluated for four methods that differ in their respective mechanism. In addition, we evaluated the performance of these methods over a range of buffer compositions, medium densities, and viscosities, representing conditions found in many downstream processing methods. We found that CellTiter‐Glo™ and flow cytometry are excellent tools for high‐throughput cell quantification. Both methods have broad working ranges (3–4 log) and performed well over a wide range of buffer compositions. In comparison, CyQuant® Direct and CellTracker™ had smaller working ranges and were more sensitive to changes in buffer composition. For fast and sensitive quantification of a single cell type, CellTiter‐Glo™ performed best, while for more complex cell mixtures flow cytometry is the method of choice. Our analysis will facilitate the selection of the most suitable method for a specific application and provides a benchmark for future HTS development in downstream processing of cell‐based products.
Lean body mass as an independent determinant of dose‐limiting toxicity and neuropathy in patients with colon cancer treated with FOLFOX regimens
Authors: Ali Raafi , Baracos Vickie E. , Sawyer Michael B. , Bianchi Laurent , Roberts Sarah , Assenat Eric , Mollevi Caroline , Senesse Pierre
Published: January 2016

Evidence suggests that lean body mass (LBM) may be useful to normalize chemotherapy doses. Data from one prospective and one retrospective study were used to determine if the highest doses of oxaliplatin/kg LBM within FOLFOX regimens would be associated with dose‐limiting toxicity (DLT) in colon cancer patients. Toxicity over four cycles was graded according to NCI Common Toxicity Criteria V2 or V3 (Common Terminology Criteria for Adverse Events, National Cancer Institute, Bethesda, MD). Muscle tissue was measured by computerized tomography (CT) and used to evaluate the LBM compartment of the whole body. In prospective randomized clinical trials conducted in France (n = 58), for patients given FOLFOX‐based regimens according to body surface area, values of oxaliplatin/kg LBM were highly variable, ranging from 2.55 to 6.6 mg/kg LBM. A cut point of 3.09 mg oxaliplatin/kg LBM for developing toxicity was determined by Receiver Operating Characteristic (ROC) analysis, below this value 0/17 (0.0%) of patients experienced DLT; in contrast above this value 18/41 (44.0%) of patients were dose reduced or had treatment terminated owing to toxicity (≥Grade 3 or neuropathy ≥Grade 2); for 9/41 the DLT was sensory neuropathy. These findings were validated in an independent cohort of colon cancer patients (n = 80) receiving FOLFOX regimens as part of standard care, in Canada. Low LBM is a significant predictor of toxicity and neuropathy in patients administered FOLFOX‐based regimens using conventional body surface area (BSA) dosing.
Boron Arylations of Subporphyrins with Aryl Zinc Reagents
Authors: Kotani Ryota , Yoshida Kota , Tsurumaki Eiji , Osuka Atsuhiro
Published: January 2016

Boron arylations of B‐(methoxo)triphenylsubporphyrin have been developed with a combined use of ArZnI⋅LiCl and trimethylsilyl chloride. Aryl zinc reagents bearing bromo, cyano, amide, and ester groups can be employed for the B‐arylation reaction to provide the corresponding B‐arylated subporphyrins in moderate yields. Postmodifications of B‐arylated subporphyrins have been demonstrated without loss of the B−C bond. These modifications include conversion of the cyano group into a benzoyl group with PhMgBr, hydrolysis of the ester group to give B‐(4‐carboxyphenyl)subporphyrin, and Pd‐catalyzed Suzuki–Miyaura coupling of the 4‐bromophenyl group to give a 1,4‐phenylene‐bridged subporphyrin–ZnII porphyrin hybrid that displays intramolecular excitation energy transfer from the subporphyrin to the porphyrin. The newly synthesized B‐arylated subporphyrins have been fully characterized by NMR, UV/Vis absorption and fluorescence spectroscopies, mass spectrometry, electrochemical measurements, and X‐ray diffraction analysis.
Über die besonderen Herausforderungen einer Promotion am Fachgebiet Verfahrenstechnik der Technischen Universität Berlin
Authors: Rosenberger Sandra , Drews Anja
Published: January 2016

Eine Promotion ist mental herausfordernd, aber am Fachgebiet Verfahrenstechnik der TU Berlin ist sie es überdies auch physisch. Der Doktorvater besitzt nicht nur eine hohe Körperlänge, sondern neigt auch zu außerordentlich schnellem Gehen. Auf Basis theoretischer Überlegungen zur Pendelbewegung und experimenteller Befunde aus der Literatur diskutiert diese Arbeit, ob und wie seine DoktorandInnen mit ihm Schritt halten können.
Risk factors for depression and fatigue among survivors of hematopoietic cell transplantation
Authors: Jim Heather S.L. , Sutton Steven K. , Jacobsen Paul B. , Martin Paul J. , Flowers Mary E. , Lee Stephanie J.
Published: January 2016

BACKGROUND

Patients treated with hematopoietic cell transplantation (HCT) often experience depression and fatigue but analyses to determine risk factors have typically lacked statistical power. The current study examined sociodemographic and clinical risk factors for depression and fatigue in a large cohort of survivors of HCT.

METHODS

Measures of depression and fatigue were included in an annual survey of HCT recipients that also included self‐reported sociodemographic and health information. Patient clinical characteristics were obtained from the clinical database.

RESULTS

The sample consisted of 1869 recipients (with a mean age of 56 years; 53% male) who were a mean of 13 years (allogeneic recipients) and 6 years (autologous recipients) from HCT. Moderate to severe depression was reported by 13% of participants; moderate to severe fatigue was reported by 42%. Among allogeneic recipients, female sex, younger age, current presence of chronic pain, and current patient‐reported severity of chronic graft‐versus‐host disease were found to be independently associated with greater depression whereas female sex, current presence of chronic pain, and current severity of chronic graft‐versus‐host disease were independently associated with greater fatigue (P values <.01). Among autologous recipients, younger age and current presence of chronic pain were found to be independently associated with both greater depression and greater fatigue (P values <.01).

CONCLUSIONS

Rates of depression and fatigue in this group of survivors suggest a high symptom burden. Better screening, referral, and interventions are needed. Cancer 2016;122:1290–7. © 2016 American Cancer Society.
Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of ASP2408, a Potent Selective T‐Cell Costimulation Modulator After Single and Multiple Ascending Doses in Healthy Volunteers and RA Patients
Authors: Zhu Tong , Keirns James , Howieson Corrie , Kaibara Atsunori , Goldwater Ronald , Kivitz Alan J. , Chindalore Vishala , Cohen Stanley , Santos Vicki , Akinlade Bolanle , Kernstock Robert , Delgado‐Herrera Leticia , Blahunka Paul C , Karrer Erik E. , Garg Jay P. , Samberg Nancy , Zeiher Bernhardt G.
Published: January 2016

ASP2408 is a next‐generation anti–cytotoxic T lymphocyte antigen‐4 fusion protein engineered for improved CD86 binding affinity as a treatment for rheumatoid arthritis (RA). In 72 healthy subjects (n = 6/treatment), ASP2408 was administered as single ascending doses intravenously at 0.003 to 10.0 mg/kg or subcutaneously at 0.3 to 3.0 mg/kg. It showed decreased clearance and prolonged half‐life with increasing doses, consistent with target‐mediated disposition. The apparent bioavailability was 36.3%–56.7% across single subcutaneous doses. Sixteen RA patients (n = 8/treatment) on stable methotrexate received 3 × 3.0 mg/kg subcutaneously every 4 weeks or every 2 weeks. Similar to single‐dose treatment, ASP2408 concentrations peaked 2 to 3 days postdose, with a median t1/2 of approximately 8 days. Using CD86 receptor occupancy (RO) as a mechanistic biomarker, ASP2408 demonstrated dose‐dependent binding to its target. ASP2408 3.0 mg/kg subcutaneously every 4 weeks and every 2 weeks led to a mean %CD86 RO ≥ 74.7% and ≥ 81.5%, respectively, within each dosing interval. ASP2408 was well tolerated across studies with no evidence of dose‐limiting toxicity or clinically significant changes in clinical laboratory test results, vital signs, or 12‐lead electrocardiograms. ASP2408 elicited antidrug antibodies in the majority of patients, but with no clinical sequelae.
Nonequilibrium Green Functions Approach to Strongly Correlated Fermions in Lattice Systems
Authors: Schlünzen N. , Bonitz M.
Published: January 2016

Quantum dynamics in strongly correlated systems are of high current interest in many fields including dense plasmas, nuclear matter and condensed matter and ultracold atoms. An important model case are fermions in lattice systems that is well suited to analyze, in detail, a variety of electronic and magnetic properties of strongly correlated solids. Such systems have recently been reproduced with fermionic atoms in optical lattices which allow for a very accurate experimental analysis of the dynamics and of transport processes such as diffusion. The theoretical analysis of such systems far from equilibrium is very challenging since quantum and spin effects as well as correlations have to be treated non‐perturbatively. The only accurate method that has been successful so far are density matrix renormalization group (DMRG) simulations. However, these simulations are presently limited to one‐dimensional (1D) systems and short times. Extension of quantum dynamics simulations to two and three dimensions is commonly viewed as one of the major challenges in this field. Recently we have reported a breakthrough in this area [N. Schlünzen et al., Phys. Rev. B (2016)] where we were able to simulate the expansion dynamics of strongly correlated fermions in a Hubbard lattice following a quench of the confinement potential in 1D, 2D and 3D. The results not only exhibited excellent agreement with the experimental data but, in addition, revealed new features of the short‐time dynamics where correlations and entanglement are being build up. The method used in this work are nonequilibrium Green functions (NEGF) which are found to be very powerful in the treatment of fermionic lattice systems filling the gap presently left open by DMRG in 2D and 3D.

In this paper we present a detailed introduction in the NEGF approach and its application to inhomogeneous Hubbard clusters. In detail we discuss the proper strong coupling approximation which is given by T ‐matrix selfenergies that sum up two‐particle scattering processes to infinite order. The efficient numerical implemen‐tation of the method is discussed in detail as it has allowed us to achieve dramatic performance gains. This has been the basis for the treatment of more than 100 particles over large time intervals. The numerical results presented in this paper concentrate on the diffusion in 1D to 3D lattices. We find that the expansion dynamics consist of three different phases that are linked with the build‐up of correlations. In the long time limit, a universal scaling with the particle number is revealed. By extrapolating the expansion velocities to the macroscopic limit, the obtained results show excellent agreement with recent experiments on ultracold fermions in optical lattices. Moreover we present results for the site‐resolved behavior of correlations and entanglement that can be directly compared with experiments using the recently developed atomic microscope technique. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Atypical early histories predict lower extraversion in captive chimpanzees
Authors: Freeman Hani D. , Weiss Alexander , Ross Stephen R.
Published: January 2016

Although much research has been conducted to understand personality development in humans, there remain substantial gaps in our understanding of these processes, particularly in relation to social influences. As such, investigations into personality development in our closest living relative, the chimpanzee, may provide useful insight. We evaluated the impact of early social exposure (to both humans and conspecifics) on personality development by studying 88 chimpanzees, including former pets and entertainers, living in accredited zoos and sanctuaries. During infancy, subjects varied in the amount of time spent with conspecifics compared with humans. Caregivers familiar with the chimpanzees rated them using a modified version of the Hominoid Personality Questionnaire (HPQ) and the ratings were found to have strong inter‐rater reliability. We used the published structure of the HPQ to evaluate our results in relation to differences in early life experience. Chimpanzees who as infants spent less time with conspecifics were rated as lower in Extraversion later in life in comparison with chimpanzees who as infants spent more time with conspecifics. These results suggest that a broad range of social influences should be considered when evaluating the impact of early social environment on later personality expression. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 519–527, 2016.
Surgical treatment of the Charcot foot
Authors: Pinzur Michael S.
Published: January 2016

With the increased number of diabetics worldwide and the increased incidence of morbid obesity in more prosperous cultures, there has become an increased awareness of Charcot arthropathy of the foot and ankle. Outcome studies would suggest that patients with deformity associated with Charcot Foot arthropathy have impaired health related quality of life. This awareness has led reconstructive‐minded foot and ankle surgeons to develop surgical strategies to treat these acquired deformities. This article outlines the current clinical approach to this disabling medical condition. Copyright © 2016 John Wiley & Sons, Ltd.
Innovations in diabetic foot reconstruction using supermicrosurgery
Authors: Suh Hyun Suk , Oh Tae Suk , Hong Joon Pio
Published: January 2016

The treatment of diabetic foot ulceration is complex with multiple factors involved, and it may often lead to limb amputation. Hence, a multidisciplinary approach is warranted to cover the spectrum of treatment for diabetic foot, but in complex wounds, surgical treatment is inevitable. Surgery may involve the decision to preserve the limb by reconstruction or to amputate it. Reconstruction involves preserving the limb with secure coverage. Local flaps usually are able to provide sufficient coverage for small or moderate sized wound, but for larger wounds, soft tissue coverage involves flaps that are distantly located from the wound. Reconstruction of distant flap usually involves microsurgery, and now, further innovative methods such as supermicrosurgery have further given complex wounds a better chance to be reconstructed and limbs salvaged. This article reviews the microsurgery involved in reconstruction and introduces the new method of supermicrosurgery. Copyright © 2016 John Wiley & Sons, Ltd.
Integrating palliative care with usual care of diabetic foot wounds
Authors: Dunning Trisha
Published: January 2016

Palliative care is a philosophy and a system for deciding care and can be used alone or integrated with usual chronic disease care. Palliative care encompasses end‐of‐life care. Palliative care aims to enhance quality of life, optimize function and manage symptoms including early in the course of chronic diseases. The purposes of this article are to outline palliative care and discuss how it can be integrated with usual care of diabetic foot wounds. Many people with diabetes who have foot wounds also have other comorbidities and diabetes complications such as cardiovascular and renal disease and depression, which affect medicine and other treatment choices, functional status, surgical risk and quality of life. Two broad of diabetic foot disease exist: those likely to heal but who could still benefit from integrated palliative care such as managing pain and those where healing is unlikely where palliation can be the primary focus. People with diabetes can die suddenly, although the life course is usually long with periods of stable and unstable disease. Many health professionals are reluctant to discuss palliative care or suggest people to document their end‐of‐life care preferences. If such preferences are not documented, the person might not achieve their desired death or place of death and health professionals and families can be confronted with difficult decisions. Palliative care can be integrated with usual foot care and is associated with improved function, better quality of life and greater patient and family satisfaction. Copyright © 2016 John Wiley & Sons, Ltd.
The effects of proliferation and DNA damage on hematopoietic stem cell function determine aging
Authors: Khurana Satish
Published: January 2016

In most of the mammalian tissues, homeostasis as well as injury repair depend upon a small number of resident adult stem cells. The decline in tissue/organ function in aged organisms has been directly linked with poorly functioning stem cells. Altered function of hematopoietic stem cells (HSCs) is at the center of an aging hematopoietic system, a tissue with high cellular turnover. Poorly engrafting, myeloid‐biased HSCs with higher levels of DNA damage accumulation are the hallmark features of an aged hematopoietic system. These cells show a higher proliferation rate than their younger counterparts. It was proposed that quiescence of these cells over long period of time leads to accumulation of DNA damage, eventually resulting in poor function/pathological conditions in hematopoietic system. However, various mouse models with premature aging phenotype also show highly proliferative HSCs. This review examines the evidence that links proliferation of HSCs with aging, which leads to functional changes in the hematopoietic system. Developmental Dynamics 245:739–750, 2016. © 2016 Wiley Periodicals, Inc.
Syndactyly in a novel Fras1rdf mutant results from interruption of signals for interdigital apoptosis
Authors: Hines Elizabeth A. , Verheyden Jamie M. , Lashua Amber J. , Larson Sarah C. , Branchfield Kelsey , Domyan Eric T. , Gao Juan , Harvey Julie F. , Herriges John C. , Hu Linghan , Mcculley David J. , Throckmorton Kurt , Yokoyama Shigetoshi , Ikeda Akihiro , Xu Guoliang , Sun Xin
Published: January 2016

Background: Fras1 encodes an extracellular matrix protein that is critical for the establishment of the epidermal basement membrane during gestation. In humans, mutations in FRAS1 cause Fraser Syndrome (FS), a pleiotropic condition with many clinical presentations such as limb, eye, kidney, and craniofacial deformations. Many of these defects are mimicked by loss of Fras1 in mice, and are preceded by the formation of epidermal blisters in utero. Results: In this study, we identified a novel ENU‐derived rounded foot (rdf) mouse mutant with highly penetrant hindlimb soft‐tissue syndactyly, among other structural defects. Mapping and sequencing revealed that rdf is a novel loss‐of‐function nonsense allele of Fras1 (Fras1rdf). Focusing on the limb, we found that the Fras1rdf syndactyly phenotype originates from loss of interdigital cell death (ICD). Despite normal expression of bone morphogenetic protein (BMP) ligands and their receptors, the BMP downstream target gene Msx2, which is also necessary and sufficient to promote ICD, was down‐regulated in the interdigital regions of Fras1rdf hindlimb buds. Conclusions: The close correlation between limb bud epidermal blistering, decreased Msx2 expression, and reduced ICD in the Fras1rdf hindlimb buds suggests that epithelium detachment from the mesenchyme may create a physical gap that interrupts the transmission of BMP, among other signals, resulting in soft tissue syndactyly. Developmental Dynamics 245:497–507, 2016. © 2015 Wiley Periodicals, Inc.
Old males reduce melanin‐pigmented traits and increase reproductive outcome under worse environmental conditions in common kestrels
Authors: Lopez‐Idiaquez David , Vergara Pablo , Fargallo Juan Antonio , Martinez‐Padilla Jesús
Published: January 2016

Secondary sexual traits displayed by males and females may have evolved as a signal of individual quality. However, both individual quality and investment on producing or maintaining enhanced sexual traits change as individuals age. At the same time, the costs associated to produce sexual traits might be attenuated or increased if environmental conditions are benign or worse respectively. Accordingly, environmental conditions are expected to shape the association between the expression of sexual traits and their reproductive outcome as individuals age. Nonetheless, little is known about the environmental influence on the co‐variation between sexual traits and reproductive outcome throughout the life of individuals. We studied the age‐dependency of the number and size of back spots, a melanin‐based and sexual trait in adults of common kestrels (Falco tinnunculus). We analysed the age‐dependence of reproductive traits and the environmental influence, defined as vole abundance, using a 10‐year individual‐based dataset. We broke down age‐related changes of reproductive traits into within‐ and between‐individual variation to assess their contribution to population‐level patterns. Our results showed a within‐individual decrease in the number, but not the size, of back spots in males. The size of back spots was positively correlated with food availability in males. Reproductive performance of males increased as they aged, in agreement with the life‐history theory but depending of vole abundance. Remarkably, we found that having fewer back spots was positively associated with clutch size only for old individuals under low‐food conditions. We suggest that environmental variation may shape the association between the expression of a sexual signal and reproductive outcome. We speculate that the reliability of sexual traits is higher when environmental conditions are poor only for old individuals. Within an evolutionary context, we suggest that the expression of sexual traits might be constrained by environmental conditions at later stages of life.
Ferrocenyl Dithiocarbamate Based d10 Transition‐Metal Complexes as Potential Co‐Sensitizers in Dye‐Sensitized Solar Cells
Authors: Yadav Reena , Trivedi Manoj , Kociok‐Köhn Gabriele , Chauhan Ratna , Kumar Abhinav , Gosavi Suresh W.
Published: January 2016

Three new d10 transition‐metal dithiocarbamates containing ferrocene, namely [M(FcCH2EtOHdtc)2] (M = Zn, Cd and Hg; dtc = dithiocarbamate) have been synthesized and characterized by elemental analyses, IR, 1H, and 13C NMR spectroscopy, and X‐ray crystallography. The coordination geometries around the zinc and mercury ions in the complexes are distorted tetrahedral and distorted linear, respectively. The distorted linear geometry around the mercury complex can be attributed to the presence of the bulky methylferrocenyl groups. These complexes have been used in dye‐sensitized solar cells (DSSCs) as co‐sensitizers and co‐adsorbents. The assembly fabricated by using the zinc complex and N719 (Zn/N719) showed the best performance with an overall photon‐to‐current conversion efficiency (PCE) of 7.10 ± 0.02 %, which is an improvement of 23 % in the cell performance compared with the DSSC fabricated by using N719 (PCE 5.76 ± 0.04 %) alone under identical conditions.
A Ruthenium Complex/Carbon Nanotube Based Electrode as the First Electrochemical Sensor for Simultaneous Sensing of D‐Penicillamine, 6‐Thioguanine and Catecholamines
Authors: Mazloum‐Ardakani Mohammad , Sheikh‐Mohseni Mohammad Ali , Salavati‐Niasari Masoud
Published: January 2016

The electrochemical behavior of a synthesized Ru complex (RuL) was investigated at multiwalled carbon nanotubes modified carbon paste electrode. Some special properties of the electrochemical response of this modified electrode are suitable charge transfer rate, repeatability and independance of the pH of the solution. The modified electrode can catalyze the electrochemical oxidation of penicillamine (PA) by a heterogeneous chemical reaction between PA and RuL through catalytic EC’ mechanism. The rate constant of this catalytic reaction was obtained as 1.4×106 M−1 s−1 by chronoamperometry. Because of increasing the anodic current and decreasing the oxidation potential of PA at the prepared modified electrode, this electrode was used as an electrochemical sensor for determination of PA. This sensor can determine the concentration of PA in the wide concentration range of 0.20–750.0 µM with the low detection limit of 80 nM. Simultaneous determination of PA and 6‐thioguanine in the presence of catecholamines is the other important advantage of this sensor.
The Effect of Different Carbon Materials on Manganese Oxide‐Based Lithium–Air Batteries in Ambient Environment
Authors: Zhu Yongming , Shi Haihao , Hu Huili
Published: January 2016

Rodlike manganese oxide (α‐MnO2) was prepared through a homogeneous hydrothermal reaction. Air electrodes, made with a mixture of graphite/acetylene black (G/AB) with and without the as‐made α‐MnO2, were prepared for lithium–air cells. Linear sweep voltammetry (LSV) results show that the as‐made α‐MnO2 can greatly increase the rate of the oxygen reduction reaction (ORR), and that the graphite has a very low catalytic activity towards ORR, while acetylene black has a better catalytic activity towards ORR. The batteries were tested in ambient atmosphere. The results show that graphite can improve the charge and discharge performance, and acetylene black can improve the specific capacity. When using 28 % α‐MnO2+56 % graphite as catalyst, the initial discharge capacity was 200 mAh g−1, and the number of cycles reached up to 5. When using 28 % α‐MnO2+56 % acetylene black as catalyst, the initial discharge capacity was 1150 mAh g−1, but did not realize the charge and discharge cycles.
Is received dose from ingested soil independent of soil PAH concentrations?—Animal model results
Authors: Peters Rachel E. , James Kyle , Cave Mark , Wickstrom Mark , Siciliano Steven D.
Published: January 2016

Polycyclic aromatic hydrocarbon (PAH) bioavailability from ingested soils will vary between soils; however, the nature of this variation is not well characterized. A juvenile swine model was used to link external exposure to internal benzo[a]pyrene (BaP) and anthracene exposure following oral PAH ingestion of 27 different impacted site soils, soots, or spiked artificial soils. Internal exposure of BaP and anthracene, represented by area under the plasma-time curve, did not relate to soil concentration in impacted site soils, but did relate in spiked artificial soil. Point of departure modeling identified soil PAH concentrations greater than 1900 mg kg−1 as the point where area under the curve becomes proportional to external dose. A BaP internal exposure below 1900 mg kg−1 had an upper 95% confidence interval estimate of 33% of external exposure. Weak relationships between soil:simulated gastrointestinal fluid PAH partitioning and area under the curve values suggest that differences in internal PAH exposure between soils may not be dominated by differences in PAH partitioning. The data seem to best support exposure assessment assuming constant internal PAH exposure below soil concentrations of 1900 mg kg−1. However, because constant internal exposure would challenge several existing paradigms, a bioavailability estimate of 33% of the external exposure is suggested as a likely workable solution. Environ Toxicol Chem 2016;35:2261–2269. © 2016 SETAC
MarsAtlas: A cortical parcellation atlas for functional mapping
Authors: Auzias Guillaume , Coulon Olivier , Brovelli Andrea
Published: January 2016

An open question in neuroimaging is how to develop anatomical brain atlases for the analysis of functional data. Here, we present a cortical parcellation model based on macroanatomical information and test its validity on visuomotor‐related cortical functional networks. The parcellation model is based on a recently developed cortical parameterization method (Auzias et al., [2013]: IEEE Trans Med Imaging 32:873–887), called HIP‐HOP. This method exploits a set of primary and secondary sulci to create an orthogonal coordinate system on the cortical surface. A natural parcellation scheme arises from the axes of the HIP‐HOP model running along the fundus of selected sulci. The resulting parcellation scheme, called MarsAtlas, complies with dorsoventral/rostrocaudal direction fields and allows inter‐subject matching. To test it for functional mapping, we analyzed a MEG dataset collected from human participants performing an arbitrary visuomotor mapping task. Single‐trial high‐gamma activity, HGA (60–120 Hz), was estimated using spectral analysis and beamforming techniques at cortical areas arising from a Talairach atlas (i.e., Brodmann areas) and MarsAtlas. Using both atlases, we confirmed that visuomotor associations involve an increase in HGA over the sensorimotor and fronto‐parietal network, in addition to medial prefrontal areas. However, MarsAtlas provided: (1) crucial functional information along both the dorsolateral and rostrocaudal direction; (2) an increase in statistical significance. To conclude, our results suggest that the MarsAtlas is a valid anatomical atlas for functional mapping, and represents a potential anatomical framework for integration of functional data arising from multiple techniques such as MEG, intracranial EEG and fMRI. Hum Brain Mapp 37:1573‐1592, 2016. © 2016 Wiley Periodicals, Inc.