bluuebunny/crossref_metadata_2025 huggingface dataset:
Managerial response to constitutional constraints on shareholder power
Authors: Connelly Brian L. , Shi Wei , Zyung Jinyong
Published: August 2016

Research summary: We examine whether top managers engage in misconduct, such as illegal insider trading, illegal stock option backdating, bribery, and financial manipulation, in response to the presence, or absence, of governance provisions that impose constitutional constraints on shareholder power. Within the agency framework, shareholders typically oppose governance provisions that limit their power because those provisions could undermine shareholder influence and increase agency costs. However, when shareholders support provisions that constrain their power, managers could respond positively by refraining from self‐interested behavior in the form of managerial misconduct. We find this to be especially true in industries where these governance provisions are particularly relevant to managers and in scenarios where CEOs do not also serve as board chair.

Managerial summary: In recent years, shareholders have become central to organizations and the managers who run them. Shareholders and managers establish a rapport with one another, such that the behavior of one affects the behavior of the other. One of the most consequential decisions shareholders can make pertains to the reach of their influence: They can choose to impose strict governance over firms they own or they can allow for constitutional constraints that limit shareholder power. When they act in the mutual interest of managers by allowing such constraints, we find that managers respond in kind by refraining from bad behavior, such as illegal stock options backdating, insider trading, and financial manipulation. This is especially true in industries and scenarios in which shareholder pressure is most relevant to managers. Copyright © 2016 John Wiley & Sons, Ltd.
Nuclear Dynamics and Electronic Eﬀects of Hydrogen on Solid Surfaces
Authors: Fukutani K. , Wilde M. , Ogura S.
Published: August 2016

Hydrogen is involved in a variety of chemical processes on surfaces. While hydrogen exhibits vibrational and rotational dynamics in its adsorption state, it in some cases undergoes diffusion into the substrate as well as on the surface, and participates in chemical reactions. Furthermore, hydrogen exchanges an electron with surfaces having a significant effect on the surface electronic structure. In this personal account, we review our recent studies on surface nuclear dynamics of hydrogen, hydrogen transport across surfaces, catalytic hydrogenation/isotope exchange reactions, and charge transfer between the surface and hydrogen by using a depth‐resolved technique of nuclear reaction analysis and a quantum‐state‐selective detection of resonance enhanced multiphoton ionization in combination with surface science techniques. As a future prospect, we refer to ultraslow μ spin rotation spectroscopy for a direct probe of the hydrogen charge state at surfaces.
An efficient search algorithm for ISF vector quantization in AMR‐WB speech codec
Authors: Yeh Cheng‐Yu
Published: August 2016

The adaptive multi‐rate wideband (AMR‐WB) speech codec with a sampling rate of 16 kHz is one of the speech codecs applied to 4G mobile communication systems as a way to remarkably improve the speech quality of a smartphone. However, a major drawback is that the vector quantization of the immittance spectral frequency (ISF) coefficients takes up the second largest of the total computational load of the AMR‐WB encoder. In other words, the speech quality is improved at the cost of high battery power consumption. Accordingly, this letter presents a triangular inequality elimination algorithm equipped with a dynamic and an intersection mechanism, named DI‐TIE, as a means to considerably improve the performance of ISF coefficient quantization in AMR‐WB speech codec. Both mechanisms are designed in a way that recursively enhances the performance of TIE algorithm. This proposal is demonstrated by experimental results as a superior search algorithm relative to a conventional TIE and a multiple TIE (MTIE) approaches. With a full search algorithm as a benchmark for search load comparison, this work provides a search load reduction of more than 77%, a figure far beyond the 36% in the TIE and 49% in the MTIE approach. © 2016 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Application of fuzzy C‐means for understanding water quality in Lake Hachiroko, Japan
Authors: Kageyama Yoichi , Izumi Asako , Nishida Makoto , Yokoyama Hiroshi
Published: August 2016

This letter reports on the water quality conditions of Lake Hachiroko estimated by fuzzy c‐means clustering (FCM). Growth of blue‐green algae in the summer significantly degrades the water quality of the lake. On the basis of experimental results using ALOS AVNIR data from the months of August and September, and a comparison with results obtained from fuzzy regression analysis, it is found that the fuzzy c‐means technique is effective in determining the water surface conditions of the lake, especially in relation to blue‐green algae growth. © 2016 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Quick and easy preparation method for Kampo formula decoctions (part 4): IPCD method for rhubarb and aconite root
Authors: Fueki Tsukasa , Chiba Koki , Makino Toshiaki , Matsuoka Takanori , Satou Tadaaki , Koike Kazuo , Tanaka Koichiro , Sumino Megumi , Namiki Takao
Published: August 2016

Aim

The immersing powdered crude drugs (IPCD) method has been developed as a quick, easy and high‐yielding method for preparing decoctions. Given that the extraction process is different from the conventional decoction method, the safety of this method should be carefully examined. In the present study, the amounts of the diester alkaloids of aconite root, the tuberous root of
Aconitum carmichaeli, and sennoside A of rhubarb, the rhizome of
Rheum palmatum, were determined in the IPCD immersion. Both of these compounds have strong physiological activities and have been suggested to be decomposed during the decoction process.

Methods

The amounts of marker compounds in the IPCD immersion prepared from processed or unprocessed aconite root or rhubarb were measured and compared with those prepared using the conventional decoction method.

Results

The amount of sennoside A extracted with the IPCD method was 1.1‐fold increased compared with that from the conventional method. No diester alkaloids were detected in the IPCD immersion prepared from processed aconite root, whereas for unprocessed aconite root, the amount of diester alkaloids extracted from the IPCD immersion was 8.8‐fold higher than that from the conventional decoctions.

Conclusion

The IPCD method can be safely used on rhubarb or well‐processed aconite root under the same conditions as other less‐powerful crude drugs, whereas precautions are required for unprocessed aconite root.
Prediction of stillbirth from biochemical and biophysical markers at 11–13 weeks
Authors: Mastrodima S. , Akolekar R. , Yerlikaya G. , Tzelepis T. , Nicolaides K. H.
Published: August 2016

Objectives

To develop a model for the prediction of stillbirth that is based on a combination of maternal characteristics and medical history with first‐trimester biochemical and biophysical markers and to evaluate the performance of screening with this model for all stillbirths and those due to impaired placentation and unexplained causes.

Methods

This was a prospective screening study of 76 897 singleton pregnancies, including 76 629 live births and 268 (0.35%) antepartum stillbirths; 157 (59%) were secondary to impaired placentation and 111 (41%) were due to other or unexplained causes. Multivariable logistic regression analysis was used to determine if there was a significant contribution to prediction of stillbirth from the maternal factor‐derived a‐priori risk, fetal nuchal translucency thickness, ductus venosus pulsatility index for veins (DV‐PIV), uterine artery pulsatility index (UtA‐PI) and maternal serum free β‐human chorionic gonadotropin and pregnancy‐associated plasma protein‐A (PAPP‐A). The significant contributors were used to derive a model for first‐trimester prediction of stillbirth.

Results

Significant contribution to prediction of stillbirth was provided by maternal factors, PAPP‐A, UtA‐PI and DV‐PIV. A model combining these variables predicted 40% of all stillbirths and 55% of those due to impaired placentation, at a false‐positive rate of 10%. Within the impaired‐placentation group, the detection rate of stillbirth < 32 weeks' gestation was higher than that of stillbirth ≥ 37 weeks (64% vs 42%).

Conclusions

A model based on maternal factors and first‐trimester biomarkers can potentially predict more than half of subsequent stillbirths that occur due to impaired placentation. The extent to which such stillbirths could be prevented remains to be determined. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Intramolecular Cyclization of Butadiyne Functionalized Ligands coordinated to Triosmium‐Carbonyl Cluster
Authors: Arnanz Avelina , Medina Rosa‐María , Macazaga María‐José , Moreno Consuelo
Published: August 2016

Reactions between diynes and [Os3(CO)11(CH3CN)] in the presence of water give rise to the formation of intriguing hydride triosmium clusters [Os3(μ‐H)(CO)9{μ3,η1:η3:η1‐RC2COHC≡CR}] (1a–1c) under mild conditions in high yields. When these allylic alcohol compounds 1a–1c are dissolved in dry polar and donor solvents, an intramolecular cyclization process takes place to give [Os3(μ‐H)(CO)9{μ3,η1:η3:η1‐RC2CH=COCR}] (2a–2c) in quantitative yield. The utilization of [Os3(CO)11(CH3CN)] as starting material together with the addition of water can replace the inconvenient use of [Os3(μ‐H)2(CO)10]. This method of synthesis provides a facile pathway for diyne cyclizations and has a clear advantage over those described to date in the literature. Additionally, the analogous cyclized mixed‐metal complex [Os3(μ‐H)(CO)9{μ3,η1:η3:η1‐FcC2CH=COCFc}] (2d) (Fc = ferrocenyl), was synthesized in order to carry out a comparative electrochemical study with the related compounds [Os3(CO)11(μ3‐FcC4Fc)] (I) and [Os3(CO)10(μ3‐FcC4Fc)] (II), which were previously reported by R. D. Adams.
Recent trends in bioethanol production from food processing byproducts
Authors: Akbas Meltem Yesilcimen , Stark Benjamin C
Published: August 2016

The widespread use of corn starch and sugarcane as sources of sugar for the production of ethanol via fermentation may negatively impact the use of farmland for production of food. Thus, alternative sources of fermentable sugars, particularly from lignocellulosic sources, have been extensively investigated. Another source of fermentable sugars with substantial potential for ethanol production is the waste from the food growing and processing industry. Reviewed here is the use of waste from potato processing, molasses from processing of sugar beets into sugar, whey from cheese production, byproducts of rice and coffee bean processing, and other food processing wastes as sugar sources for fermentation to ethanol. Specific topics discussed include the organisms used for fermentation, strategies, such as co-culturing and cell immobilization, used to improve the fermentation process, and the use of genetic engineering to improve the performance of ethanol producing fermenters.
On the Influence of Material Parameters in a Complex Material Model for Powder Compaction
Authors: Staf Hjalmar , Lindskog Per , Andersson Daniel C. , Larsson Per-Lennart
Published: August 2016

Parameters in a complex material model for powder compaction, based on a continuum mechanics approach, are evaluated using real insert geometries. The parameter sensitivity with respect to density and stress after compaction, pertinent to a wide range of geometries, is studied in order to investigate completeness and limitations of the material model. Finite element simulations with varied material parameters are used to build surrogate models for the sensitivity study. The conclusion from this analysis is that a simplification of the material model is relevant, especially for simple insert geometries. Parameters linked to anisotropy and the plastic strain evolution angle have a small impact on the final result.
Vein Diameter for Peripherally Inserted Catheter Insertion: A Scoping Review
Authors: Sharp Rebecca , Grech Carol , Fielder Andrea , Mikocka-Walus Antonina , Esterman Adrian
Published: August 2016

Background: The risk of venous thromboembolism (VTE) may be reduced if a vein of appropriate diameter is used for peripherally inserted central catheter (PICC) insertion. However, clinicians may have predilections to cannulate certain vein types and use particular insertion sites (eg, right or left arm) and therefore do not necessarily assess all veins available to determine the most optimal vessel to introduce a catheter. It is important that clinicians have an understanding of the diameter of veins used for PICC insertion and the effect of patient factors such as hand dominance on vein size to determine whether their clinical practice is appropriate.

Methods: A scoping review of published literature was performed to determine existing knowledge regarding the diameters of veins used for PICC insertion and the influence of patient factors such as hand dominance and laterality (left or right arm) on vein size.

Results: There was limited published research about the diameters of the basilic, brachial, and cephalic veins at the midupper arm, with only 6 studies identified. Three of the 6 selected articles focused on vein diameter measurement to inform arteriovenous fistula development. Only 1 study included participants undergoing PICC insertion. Scant research examined the effect of laterality on vein diameter and 1 study was identified that reported the influence of hand dominance or vein type on the diameter of veins used for PICC insertion.

Conclusions: This review found that there is a paucity of studies that have examined the veins used for PICC insertion. Nevertheless, it appears that the basilic vein has the largest diameter (with smaller brachial and cephalic veins), although this is not always the case. Laterality and hand dominance does not seem to influence vein diameter. Further research about the vasculature used for PICC insertion is needed to inform clinical practice.
Transparent Film Intravenous Line Dressing Incorporating a Chlorhexidine Gluconate Gel Pad: A Clinical Staff Evaluation
Authors: Karpanen Tarja J. , Casey Anna L. , Das Ira , Whitehouse Tony , Nightingale Peter , Elliott Thomas S. J.
Published: August 2016

Background: Chlorhexidine gluconate (CHG) has been shown to reduce the microbial load at intravascular (IV) catheter insertion sites and the risk of catheter-related infections. The Centers for Disease Control and Prevention and the UK National Institute for Health and Care Excellence subsequently recommended CHG-containing IV dressings for specific clinical indications.

Aim: To evaluate clinical staff perceptions of a standard transparent IV dressing in comparison to a transparent IV dressing incorporating a 2% (w/w) CHG gel pad when used at the insertion site of short-term central venous catheters and vascular access catheters for dialysis in adult critical care patients.

Methods: Following a 9-month trial period during which a CHG dressing was introduced to critical care patients at a university hospital, the staff perception of this dressing in comparison to a standard transparent IV dressing was evaluated by a questionnaire. The number of dressing changes required and skin condition under the dressing was also determined in a proportion of patients.

Results: The majority of the clinical staff (70 out of 81 respondents) considered the performance of the IV dressing containing a CHG gel pad better or much better than the standard dressing, and 77 out of 78 of the respondents recommended continuing its use. Both types of dressing performed well when applied to the insertion site of IV catheters in the internal jugular, subclavian, or femoral vein.

Conclusions: Staff satisfaction with the IV dressing incorporating a CHG gel pad was rated good, and the dressing performed well in a diverse group of critical care patients.
Defining the Specialty of Vascular Access through Consensus: Shaping the Future of Vascular Access
Authors: Davis Lois , Owens Andrea K. , Thompson Judy
Published: August 2016

The Association for Vascular Access (AVA) is an organization of health care professionals founded in 1985 to support and promote the specialty of vascular access. The mission of AVA is to distinguish the vascular access specialty and define standards of vascular access through an evidence-based approach designed to enhance health care. There is little guidance for multidisciplinary procedures/practice, and this is the case for vascular access. There are also inconsistencies and conflicts in terminology. Additionally, there is no consensus of vascular access as a specialty. It is the focus of AVA to promote consistency in vascular access practice. This document embraces a common title for a clinician with knowledge and skills in the area of vascular access. This establishes a new paradigm that will strengthen the advancement of the vascular access specialty.
The Treatment of Chronic Coccydynia and Postcoccygectomy Pain With Pelvic Floor Physical Therapy
Authors: Scott Kelly M. , Fisher Lauren W. , Bernstein Ira H. , Bradley Michelle H.
Published: August 2016

Background

Coccydynia is a challenging disorder that often is refractory to treatments such as medications and injections. Physical therapy for coccydynia rarely has been studied.

Objective

To evaluate the efficacy of pelvic floor physical therapy for reducing pain levels in patients with coccydynia.

Design

Retrospective chart review.

Setting

The pelvic floor rehabilitation clinic of a major university hospital.

Patients

A total of 124 consecutive patients over age 18 with a chief complaint of coccydynia between 2009 and 2012. A subgroup of 17 of the 124 patients had previously undergone coccygectomy with continued pain postoperatively.

Methods or Interventions

The primary treatment intervention was pelvic floor physical therapy aimed at pelvic floor muscle relaxation. Secondary treatment interventions included the prescription of baclofen for muscle relaxation (19% of patients), ganglion impar blocks (8%), or coccygeus trigger point injections (17%).

Main Outcome Measures

Primary outcome measures included final minimum, average, and maximum pain numeric rating scales. A secondary outcome measure was the patient's subjective percent global improvement assessment. Baseline demographics were used to determine which pretreatment characteristics were correlated with treatment outcomes.

Results

Of the 124 patients, 93 participated in pelvic floor physical therapy and were included in statistical analysis. For the 79 patients who completed treatment (with a mean of 9 physical therapy sessions), the mean average pain ratings decreased from 5.08 to 1.91 (P < .001) and mean highest pain ratings decreased from 8.81 to 4.75 (P < .001). The mean percent global improvement was 71.9%. Mean average pain ratings in postcoccygectomy patients improved from 6.64 to 3.27 (P < .001). Greater initial pain scores and a history of previous injections were correlated with P < .001 pain scores on completion of physical therapy. Pain duration and history of trauma did not affect treatment outcomes.

Conclusions

Pelvic floor physical therapy is a safe and effective method of treating coccydynia.

Level of Evidence

III
Herausforderungen in der Diagnostik der periprothetischen Infektion
Authors: Zingg Patrick O. , Achermann Yvonne
Published: August 2016

Zusammenfassung. Zusammenfassung: Akute und chronische Infektionen sind eine gefürchtete Komplikation nach Implantation einer Gelenkprothese und sind schwierig zu diagnostizieren. Grund dafür ist der Biofilm-Modus des Bakteriums. Mikrobiologische Kulturen zur Bestimmung der Mikroorganismen können negativ bleiben, sodass Zusatzuntersuchungen wie eine Gelenkpunktion mit Bestimmung der Leukozyten oder die histologische Aufarbeitung des Gewebes wichtig sind. Zur besseren Sensitivität sollten mehrere Gewebeproben intraoperativ aus Arealen mit vermutlich hoher Keimdichte (Interphasenmembranen, Kapsel) abgenommen werden. Neuere Biomarker wie alpha-Defensin zur Diagnose eines periprothetischen Infektes oder der molekulargenetische Diagnostik (Multiplex-PCR) zur Bestimmung des auslösenden Pathogens gehören noch nicht zur Standarddiagnostik. Die folgende Arbeit fasst die Wertigkeit und Limiten der verschiedenen Diagnostikmöglichkeiten zusammen.
Kognitive Leistungen bei rechenschwachen Grundschulkindern
Authors: Werpup Lina , Petermann Franz
Published: August 2016

Zusammenfassung. Es werden die visuellen Wahrnehmungsleistungen und weitere kognitive Leistungen von Grundschulkindern mit Rechenstörungen betrachtet. Hierzu werden die Indexwerte der Wechsler Intelligence Scale for Childen – IV (WISC-IV) und die in Frostigs Entwicklungstest der visuellen Wahrnehmung für Jugendliche und Erwachsene (FEW-JE) erzielten Werte von 39 Kindern mit Rechenstörung und 40 Kontrollgruppenkindern analysiert. Die visuellen Wahrnehmungsleistungen unterscheiden sich signifikant. 39 % der rechenschwachen Kinder weisen klinisch auffällige Ergebnisse im FEW-JE auf. In Abhängigkeit von den diagnostischen Kriterien lässt sich für 3 bis 13 % eine „visuelle Wahrnehmungsstörung“ diagnostizieren. In der Regressionsanalyse erklären die Prädiktoren „visuellen Wahrnehmung“ und „Arbeitsgedächtnis“ 35 bis 53 % der Rechenleistung. Im Rahmen der klinischen Diagnostik von Rechenstörungen ist eine Überprüfung der visuellen Wahrnehmungs- und Arbeitsgedächtnisleistungen anzuraten.
„Das sieht man doch, dass das ein Talent ist!“
Authors: Jokuschies Nina , Conzelmann Achim
Published: August 2016

Zusammenfassung. Obwohl die Talentselektion im Profifußball auf dem subjektiven Urteil von Trainern und Trainerinnen basiert, liegen bislang nur wenige Untersuchungen zu deren subjektiven Talentkriterien vor. Einem konstruktivistischen Ansatz folgend ( Kelly, 1991 ), werden in der vorliegenden Studie sechs hauptberufliche Junioren-Trainer des Schweizer Spitzenfußballs mittels halb-strukturierten Interviews und Repertory Grid Technik ( Fromm, 2004 ) befragt. Die Ergebnisse zeigen, dass sich die subjektiven Talentkriterien der Trainer mithilfe der verwendeten Methodik erfassen lassen. Die Multidimensionalität und Differenziertheit der von den Trainern verwendeten Talentmodelle zeigt sich durch die Nennung verschiedener Aspekte aus den Bereichen Persönlichkeit, kognitiv-perzeptuelle Fertigkeiten, konditionelle Fähigkeiten, physische Konstitution und soziales Umfeld. Die Befunde deuten darauf hin, dass sich die Repertory Grid Technik für systematische Beurteilungen anhand der von Trainern verbalisierten subjektiven Talentkriterien nutzen lässt.
Stakeholder Perspectives on the Stigma of Suicide Attempt Survivors
Authors: Sheehan Lindsay L. , Corrigan Patrick W. , Al-Khouja Maya A. ,   the Stigma of Suicide Research Team
Published: August 2016

Abstract. Background: Past scholarly efforts to describe and measure the stigma surrounding suicide have largely viewed suicide stigma from the perspective of the general public. Aims: In the spirit of community-based participatory research (CBPR), the current study brought together a diverse stakeholder team to qualitatively investigate the suicide stigma as experienced by those most intimately affected by suicide. Method: Seven focus groups (n = 62) were conducted with suicide attempt survivors, family members of those who died by suicide, and suicide loss therapists. Results: Themes were derived for stereotypes (n = 30), prejudice (n = 3), and discrimination (n = 4). People who attempted suicide were seen as attention-seeking, selfish, incompetent, emotionally weak, and immoral. Participants described personal experiences of prejudice and discrimination, including those with health professionals. Conclusion: Participants experienced public stigma, self-stigma, and label avoidance. Analyses reveal that the stigma of suicide shares similarities with stereotypes of mental illness, but also includes some important differences. Attempt survivors may be subject to double stigma, which impedes recovery and access to care.
Idealized Female Beauty, Social Comparisons, and Awareness	Intervention Material
Authors: Arendt Florian , Peter Christina , Beck Julia
Published: August 2016

Abstract. Previous research indicates that exposure to the idealized thin media standard of female beauty can contribute to body dissatisfaction, negative self-perception, depressed mood, and disordered eating. Importantly, studies have revealed that social comparison processes underlie this negative media effect: Women routinely compare themselves with the encountered mass-mediated thin ideals, which, in turn, elicits negative consequences. While there are a multitude of studies on this topic, little is known about how this negative effect can be counteracted. We tested whether watching an awareness intervention video highlighting the artificial nature of mass-mediated idealized female beauty reduces social comparison processes in a subsequent situation. As a replication of previous research, we found that exposure to the awareness intervention material reduced social comparison processes. Supplementary analysis revealed that this effect was mediated through a change in the ideal self: Watching the awareness material elicited a more realistic perception of the specific body that individuals ideally wanted to possess. This more realistic ideal-self standard, in turn, reduced social comparison processes.
Stamps Celebrate National Parks on Agency's Centennial
Authors: Showstack Randy
Published: August 2016

Striking images showcase iconic and lesser known U.S. national parks, seashores, and historic sites.
Immunometabolism and autoimmunity
Authors: Freitag Jenny , Berod Luciana , Kamradt Thomas , Sparwasser Tim
Published: August 2016

A continuous increase in the prevalence of autoimmune diseases is to be expected in the aging societies worldwide. Autoimmune disorders not only cause severe disability and chronic pain, but also lead to considerable socio‐economic costs. Given that the current treatment options are not curative, have substantial side effects and a high percentage of non‐responders, innovative options to the existing therapeutic armament against autoimmune diseases are urgently required. Accumulating evidence suggests that changes in the metabolism of immune cells are associated with, and contribute to the pathogenesis of autoimmunity. Additionally, some autoimmune diseases share alterations in metabolic pathways, key metabolites or metabolic byproducts such as reactive oxygen species. Other examples for metabolic changes in autoimmune settings include modifications in amino acid and cholesterol levels or glucose catabolism. Thus, the emerging field of immunometabolism may hold the potential to discover new therapeutic targets. Here, we discuss recent findings describing metabolic changes in autoimmune arthritis, multiple sclerosis as well as type 1 diabetes, focusing on pathophysiological aspects.
Germinal centers and autoimmune disease in humans and mice
Authors: DeFranco Anthony L
Published: August 2016

Antibodies are involved in the pathogenesis of many autoimmune diseases. Although the mechanisms underlying the antibody response to infection or vaccination are reasonably well understood, we still have a poor understanding of the nature of autoimmune antibody responses. The most well studied are the anti‐nuclear antibody responses characteristic of systemic lupus erythematosus and studies over the past decade or so have demonstrated a critical role for signaling by TLR7 and/or TLR9 in B cells to promote these responses. These Toll‐like receptors (TLRs) can promote T‐cell‐independent extrafollicular antibody responses with a heavy‐chain class switch and a low degree of somatic mutation, but they can also strongly boost the germinal center response that gives rise to high‐affinity antibodies and long‐lived plasma cells. TLRs have been shown to enhance affinity maturation in germinal center responses to produce high‐affinity neutralizing antibodies in several virus infection models of mice. Although more data are needed, it appears that anti‐nuclear antibodies in mouse models of lupus and in lupus patients can be generated by either pathway, provided there are genetic susceptibility alleles that compromise B‐cell tolerance at one or another stage. Limited data in other autoimmune diseases suggest that the germinal center response may be the predominant pathway leading to autoantibodies in those diseases. A better understanding of the mechanisms of autoantibody production may ultimately be helpful in the development of targeted therapeutics for lupus or other autoimmune diseases.
The plastid metalloprotease FtsH6 and small heat shock protein HSP21 jointly regulate thermomemory in Arabidopsis
Authors: Sedaghatmehr Mastoureh , Mueller-Roeber Bernd , Balazadeh Salma
Published: August 2016

Acquired tolerance to heat stress is an increased resistance to elevated temperature following a prior exposure to heat. The maintenance of acquired thermotolerance in the absence of intervening stress is called ‘thermomemory’ but the mechanistic basis for this memory is not well defined. Here we show that Arabidopsis HSP21, a plastidial small heat shock protein that rapidly accumulates after heat stress and remains abundant during the thermomemory phase, is a crucial component of thermomemory. Sustained memory requires that HSP21 levels remain high. Through pharmacological interrogation and transcriptome profiling, we show that the plastid-localized metalloprotease FtsH6 regulates HSP21 abundance. Lack of a functional FtsH6 protein promotes HSP21 accumulation during the later stages of thermomemory and increases thermomemory capacity. Our results thus reveal the presence of a plastidial FtsH6–HSP21 control module for thermomemory in plants.
Prediction of allosteric sites and mediating interactions through bond-to-bond propensities
Authors: Amor B. R. C. , Schaub M. T. , Yaliraki S. N. , Barahona M.
Published: August 2016

Allostery is a fundamental mechanism of biological regulation, in which binding of a molecule at a distant location affects the active site of a protein. Allosteric sites provide targets to fine-tune protein activity, yet we lack computational methodologies to predict them. Here we present an efficient graph-theoretical framework to reveal allosteric interactions (atoms and communication pathways strongly coupled to the active site) without a priori information of their location. Using an atomistic graph with energy-weighted covalent and weak bonds, we define a bond-to-bond propensity quantifying the non-local effect of instantaneous bond fluctuations propagating through the protein. Significant interactions are then identified using quantile regression. We exemplify our method with three biologically important proteins: caspase-1, CheY, and h-Ras, correctly predicting key allosteric interactions, whose significance is additionally confirmed against a reference set of 100 proteins. The almost-linear scaling of our method renders it suitable for high-throughput searches for candidate allosteric sites.
The tumour suppressor CYLD regulates the p53 DNA damage response
Authors: Fernández-Majada Vanesa , Welz Patrick-Simon , Ermolaeva Maria A. , Schell Michael , Adam Alexander , Dietlein Felix , Komander David , Büttner Reinhard , Thomas Roman K. , Schumacher Björn , Pasparakis Manolis
Published: August 2016

The tumour suppressor CYLD is a deubiquitinase previously shown to inhibit NF-κB, MAP kinase and Wnt signalling. However, the tumour suppressing mechanisms of CYLD remain poorly understood. Here we show that loss of CYLD catalytic activity causes impaired DNA damage-induced p53 stabilization and activation in epithelial cells and sensitizes mice to chemical carcinogen-induced intestinal and skin tumorigenesis. Mechanistically, CYLD interacts with and deubiquitinates p53 facilitating its stabilization in response to genotoxic stress. Ubiquitin chain-restriction analysis provides evidence that CYLD removes K48 ubiquitin chains from p53 indirectly by cleaving K63 linkages, suggesting that p53 is decorated with complex K48/K63 chains. Moreover, CYLD deficiency also diminishes CEP-1/p53-dependent DNA damage-induced germ cell apoptosis in the nematode Caenorhabditis elegans. Collectively, our results identify CYLD as a deubiquitinase facilitating DNA damage-induced p53 activation and suggest that regulation of p53 responses to genotoxic stress contributes to the tumour suppressor function of CYLD.
Colloidal cholesteric liquid crystal in spherical confinement
Authors: Li Yunfeng , Jun-Yan Suen Jeffrey , Prince Elisabeth , Larin Egor M. , Klinkova Anna , Thérien-Aubin Héloïse , Zhu Shoujun , Yang Bai , Helmy Amr S. , Lavrentovich Oleg D. , Kumacheva Eugenia
Published: August 2016

The organization of nanoparticles in constrained geometries is an area of fundamental and practical importance. Spherical confinement of nanocolloids leads to new modes of packing, self-assembly, phase separation and relaxation of colloidal liquids; however, it remains an unexplored area of research for colloidal liquid crystals. Here we report the organization of cholesteric liquid crystal formed by nanorods in spherical droplets. For cholesteric suspensions of cellulose nanocrystals, with progressive confinement, we observe phase separation into a micrometer-size isotropic droplet core and a cholesteric shell formed by concentric nanocrystal layers. Further confinement results in a transition to a bipolar planar cholesteric morphology. The distribution of polymer, metal, carbon or metal oxide nanoparticles in the droplets is governed by the nanoparticle size and yields cholesteric droplets exhibiting fluorescence, plasmonic properties and magnetic actuation. This work advances our understanding of how the interplay of order, confinement and topological defects affects the morphology of soft matter.
Asymmetric cryo-EM reconstruction of phage MS2 reveals genome structure in situ
Authors: Koning Roman I , Gomez-Blanco Josue , Akopjana Inara , Vargas Javier , Kazaks Andris , Tars Kaspars , Carazo José María , Koster Abraham J.
Published: August 2016

In single-stranded ribonucleic acid (RNA) viruses, virus capsid assembly and genome packaging are intertwined processes. Using cryo-electron microscopy and single particle analysis we determined the asymmetric virion structure of bacteriophage MS2, which includes 178 copies of the coat protein, a single copy of the A-protein and the RNA genome. This reveals that in situ, the viral RNA genome can adopt a defined conformation. The RNA forms a branched network of stem-loops that almost all allocate near the capsid inner surface, while predominantly binding to coat protein dimers that are located in one-half of the capsid. This suggests that genomic RNA is highly involved in genome packaging and virion assembly.
Immune modulation enables a specialist insect to benefit from antibacterial withanolides in its host plant
Authors: Barthel Andrea , Vogel Heiko , Pauchet Yannick , Pauls Gerhard , Kunert Grit , Groot Astrid T. , Boland Wilhelm , Heckel David G. , Heidel-Fischer Hanna M.
Published: August 2016

The development of novel plant chemical defenses and counter adaptations by herbivorous insect could continually drive speciation, producing more insect specialists than generalists. One approach to test this hypothesis is to compare closely related generalist and specialist species to reveal the associated costs and benefits of these different adaptive strategies. We use the specialized mothHeliothis subflexa, which feeds exclusively on plants in the genusPhysalis, and its close generalist relativeH. virescens.Specialization onPhysalisplants necessitates the ability to tolerate withanolides, the secondary metabolites ofPhysalisspecies that are known to have feeding deterrent and immune inhibiting properties for other insects. Here we find that onlyH. subflexabenefits from the antibacterial properties of withanolides, and thereby gains a higher tolerance of the pathogenBacillus thuringiensis. We argue that the specialization inH. subflexahas been guided to a large extent by a unique role of plant chemistry on ecological immunology.
Single-molecule imaging of UvrA and UvrB recruitment to DNA lesions in living Escherichia coli
Authors: Stracy Mathew , Jaciuk Marcin , Uphoff Stephan , Kapanidis Achillefs N. , Nowotny Marcin , Sherratt David J. , Zawadzki Pawel
Published: August 2016

Nucleotide excision repair (NER) removes chemically diverse DNA lesions in all domains of life. In Escherichia coli, UvrA and UvrB initiate NER, although the mechanistic details of how this occurs in vivo remain to be established. Here, we use single-molecule fluorescence imaging to provide a comprehensive characterization of the lesion search, recognition and verification process in living cells. We show that NER initiation involves a two-step mechanism in which UvrA scans the genome and locates DNA damage independently of UvrB. Then UvrA recruits UvrB from solution to the lesion. These steps are coordinated by ATP binding and hydrolysis in the ‘proximal’ and ‘distal’ UvrA ATP-binding sites. We show that initial UvrB-independent damage recognition by UvrA requires ATPase activity in the distal site only. Subsequent UvrB recruitment requires ATP hydrolysis in the proximal site. Finally, UvrA dissociates from the lesion complex, allowing UvrB to orchestrate the downstream NER reactions.
A possible four-phase coexistence in a single-component system
Authors: Akahane Kenji , Russo John , Tanaka Hajime
Published: August 2016

For different phases to coexist in equilibrium at constant temperature T and pressure P, the condition of equal chemical potential μ must be satisfied. This condition dictates that, for a single-component system, the maximum number of phases that can coexist is three. Historically this is known as the Gibbs phase rule, and is one of the oldest and venerable rules of thermodynamics. Here we make use of the fact that, by varying model parameters, the Gibbs phase rule can be generalized so that four phases can coexist even in single-component systems. To systematically search for the quadruple point, we use a monoatomic system interacting with a Stillinger–Weber potential with variable tetrahedrality. Our study indicates that the quadruple point provides flexibility in controlling multiple equilibrium phases and may be realized in systems with tunable interactions, which are nowadays feasible in several soft matter systems such as patchy colloids.
Molecular logic of the Zur-regulated zinc deprivation response in Bacillus subtilis
Authors: Shin Jung-Ho , Helmann John D.
Published: August 2016

Bacteria respond dynamically to the changes in zinc availability. Repression by the Bacillus subtilis transcription factor Zur requires Zn(II), which binds with negative cooperativity to two regulatory sites per dimer to form, sequentially, Zur2:Zn3 and Zur2:Zn4 forms of the repressor. Here we show that, as cells transition from zinc sufficiency to deficiency, operons regulated by Zur are derepressed in three distinct waves. The first includes the alternative RpmEB(L31*) and RpmGC(L33*) ribosomal proteins, which mobilize zinc from the ribosome, whereas the second includes the ZnuACB uptake system and the YciC metallochaperone. Finally, as zinc levels decrease further, the Zur2:Zn3 form loses Zn(II) leading to derepression of RpsNB(S14*) and FolE2, which allow continued ribosome assembly and folate synthesis, respectively. We infer that zinc mobilization from intracellular zinc stores takes priority over energy-dependent import, and our results link the biochemistry of zinc sensing by Zur to the molecular logic of the zinc deprivation response.
Hypersensitivity to DNA damage in antephase as a safeguard for genome stability
Authors: Feringa Femke M. , Krenning Lenno , Koch André , van den Berg Jeroen , van den Broek Bram , Jalink Kees , Medema René H.
Published: August 2016

Activation of the DNA-damage response can lead to the induction of an arrest at various stages in the cell cycle. These arrests are reversible in nature, unless the damage is too excessive. Here we find that checkpoint reversibility is lost in cells that are in very late G2, but not yet fully committed to enter mitosis (antephase). We show that antephase cells exit the cell cycle and enter senescence at levels of DNA damage that induce a reversible arrest in early G2. We show that checkpoint reversibility critically depends on the presence of the APC/C inhibitor Emi1, which is degraded just before mitosis. Importantly, ablation of the cell cycle withdrawal mechanism in antephase promotes cell division in the presence of broken chromosomes. Thus, our data uncover a novel, but irreversible, DNA-damage response in antephase that is required to prevent the propagation of DNA damage during cell division.
Integrative proteomic profiling of ovarian cancer cell lines reveals precursor cell associated proteins and functional status
Authors: Coscia F. , Watters K. M. , Curtis M. , Eckert M. A. , Chiang C. Y. , Tyanova S. , Montag A. , Lastra R. R. , Lengyel E. , Mann M.
Published: August 2016

A cell line representative of human high-grade serous ovarian cancer (HGSOC) should not only resemble its tumour of origin at the molecular level, but also demonstrate functional utility in pre-clinical investigations. Here, we report the integrated proteomic analysis of 26 ovarian cancer cell lines, HGSOC tumours, immortalized ovarian surface epithelial cells and fallopian tube epithelial cells via a single-run mass spectrometric workflow. The in-depth quantification of >10,000 proteins results in three distinct cell line categories: epithelial (group I), clear cell (group II) and mesenchymal (group III). We identify a 67-protein cell line signature, which separates our entire proteomic data set, as well as a confirmatory publicly available CPTAC/TCGA tumour proteome data set, into a predominantly epithelial and mesenchymal HGSOC tumour cluster. This proteomics-based epithelial/mesenchymal stratification of cell lines and human tumours indicates a possible origin of HGSOC either from the fallopian tube or from the ovarian surface epithelium.
Room-temperature tetragonal non-collinear Heusler antiferromagnet Pt2MnGa
Authors: Singh Sanjay , D’Souza S. W. , Nayak J. , Suard E. , Chapon L. , Senyshyn A. , Petricek V. , Skourski Y. , Nicklas M. , Felser C. , Chadov S.
Published: August 2016

Antiferromagnetic spintronics is a rapidly growing field, which actively introduces new principles of magnetic storage. Despite that, most applications have been suggested for collinear antiferromagnets. In this study, we consider an alternative mechanism based on long-range helical order, which allows for direct manipulation of the helicity vector. As the helicity of long-range homogeneous spirals is typically fixed by the Dzyaloshinskii–Moriya interactions, bi-stable spirals (left- and right-handed) are rare. Here, we report a non-collinear room-temperature antiferromagnet in the tetragonal Heusler group. Neutron diffraction reveals a long-period helix propagating along its tetragonal axis. Ab-initio analysis suggests its pure exchange origin and explains its helical character resulting from a large basal plane magnetocrystalline anisotropy. The actual energy barrier between the left- and right-handed spirals is relatively small and might be easily overcome by magnetic pulse, suggesting Pt2MnGa as a potential candidate for non-volatile magnetic memory.
Individual-based approach to epidemic processes on arbitrary dynamic contact networks
Authors: Rocha Luis E. C. , Masuda Naoki
Published: August 2016

The dynamics of contact networks and epidemics of infectious diseases often occur on comparable time scales. Ignoring one of these time scales may provide an incomplete understanding of the population dynamics of the infection process. We develop an individual-based approximation for the susceptible-infected-recovered epidemic model applicable to arbitrary dynamic networks. Our framework provides, at the individual-level, the probability flow over time associated with the infection dynamics. This computationally efficient framework discards the correlation between the states of different nodes, yet provides accurate results in approximating direct numerical simulations. It naturally captures the temporal heterogeneities and correlations of contact sequences, fundamental ingredients regulating the timing and size of an epidemic outbreak and the number of secondary infections. The high accuracy of our approximation further allows us to detect the index individual of an epidemic outbreak in real-life network data.
Variations in Multiple Syndromic Deafness Genes Mimic Non-syndromic Hearing Loss
Authors: Bademci G. , Cengiz F. B. , Foster II J. , Duman D. , Sennaroglu L. , Diaz-Horta O. , Atik T. , Kirazli T. , Olgun L. , Alper H. , Menendez I. , Loclar I. , Sennaroglu G. , Tokgoz-Yilmaz S. , Guo S. , Olgun Y. , Mahdieh N. , Bonyadi M. , Bozan N. , Ayral A. , Ozkinay F. , Yildirim-Baylan M. , Blanton S. H. , Tekin M.
Published: August 2016

The genetics of both syndromic (SHL) and non-syndromic hearing loss (NSHL) is characterized by a high degree of genetic heterogeneity. We analyzed whole exome sequencing data of 102 unrelated probands with apparently NSHL without a causative variant in known NSHL genes. We detected five causative variants in different SHL genes (SOX10, MITF, PTPN11, CHD7, and KMT2D) in five (4.9%) probands. Clinical re-evaluation of these probands shows that some of them have subtle syndromic findings, while none of them meets clinical criteria for the diagnosis of the associated syndrome (Waardenburg (SOX10 and MITF), Kallmann (CHD7 and SOX10), Noonan/LEOPARD (PTPN11), CHARGE (CHD7), or Kabuki (KMT2D). This study demonstrates that individuals who are evaluated for NSHL can have pathogenic variants in SHL genes that are not usually considered for etiologic studies.
Mechanistic target of rapamycin (mTOR) regulates trophoblast folate uptake by modulating the cell surface expression of FR-α and the RFC
Authors: Rosario Fredrick J. , Powell Theresa L. , Jansson Thomas
Published: August 2016

Folate deficiency in fetal life is strongly associated with structural malformations and linked to intrauterine growth restriction. In addition, limited availability of methyl donors, such as folate, during pregnancy may result in abnormal gene methylation patterns and contribute to developmental programming. The fetus is dependent on placental transfer of folate, however the molecular mechanisms regulating placental folate transport are unknown. We used cultured primary human trophoblast cells to test the hypothesis that mechanistic target of rapamycin complex 1 (mTORC1) and 2 (mTORC2) regulate folate transport by post-translational mechanisms. Silencing raptor (inhibits mTORC1) or rictor (inhibits mTORC2) markedly decreased basal folate uptake. Folate uptake stimulated by insulin + IGF-1 was mediated by mTORC2 but did not involve mTORC1. mTORC1 or mTORC2 silencing markedly decreased the plasma membrane expression of FR-α and RFC transporter isoforms without affecting global protein expression. Inhibition of the ubiquitin ligase Nedd4-2 had no effect on folate transport. In conclusion, we report for the first time that mTORC1/C2 are positive regulators of cellular folate uptake by modulating the cell surface abundance of specific transporter isoforms. We propose that regulation of placental folate transport by mTOR signaling provide a direct link between placental function, gene methylation and fetal programming.