bluuebunny/crossref_metadata_2025 huggingface dataset:
An impediment to random walk: trehalose microenvironment drives preferential endocytic uptake of plasmonic nanoparticles
Authors: Siddhanta Soumik , Zheng Chao , Narayana Chandrabhas , Barman Ishan
Published: February 2016

Trehalose changes the mode of internalization of plasmonic nanoparticles predominantly from cytosolic diffusion to vesicular transport maintaining cell viability and reducing membrane-focused aggregation.
Self-regeneration of ferrites incorporated into matched matrices for thermochemical CO2 splitting
Authors: Fu Yu , Zhang Jun , Li Shenggang , Huang Jincheng , Sun Yuhan
Published: February 2016

Ferrite particles incorporated into matched matrices are capable of regeneration in each cycle, avoiding deactivation induced by sintering.
Pyrite FeS2as an efficient adsorbent of lithium polysulphide for improved lithium–sulphur batteries
Authors: Zhang Sheng S. , Tran Dat T.
Published: February 2016

Pyrite FeS2effectively adsorbs polysulphide anions by forming active Li2Sn–FeS2complexes, which significantly stabilise the capacity retention of Li–S batteries.
A new approach for additive-free room temperature sintering of conductive patterns using polymer-stabilized Sn nanoparticles
Authors: Shirai Hiroaki , Nguyen Mai Thanh , Ishida Yohei , Yonezawa Tetsu
Published: February 2016

Conductive patterns with a resistivity of 1.1 × 10−3 Ω cm were obtained by sintering of tin nanoparticle at room temperature.
Finite‐time attitude synchronisation for multiple spacecraft
Authors: Lyu Jianting , Qin Jiahu , Ma Qichao , Xing Zheng Wei , Kang Yu
Published: February 2016

This study investigates the finite‐time attitude synchronisation problem for multiple spacecraft under a directed communication topology. Attitude synchronisation problem for a leaderless formation system without specified reference attitude is studied, and finite‐time control laws are proposed and analysed without using neighbours' angular velocity measurements. By applying the graph theory, homogeneous method and Lyapunov stability theory, it is proved that the system is globally finite‐time stable and attitude synchronisation can be achieved. Then the obtained control results are extended in the scenario with a stationary leader. Numerical simulations are finally given to demonstrate the effectiveness and feasibility of the obtained results.
Information Sharing and User Behavior in Internet-enabled Peer-to-peer Lending Systems: An Empirical Study
Authors: Feller Joseph , Gleasure Rob , Treacy Stephen
Published: February 2016

Internet-based information systems (IS) have enabled various forms of collective intelligence, action, and resources (e.g. open source software, innovation marketplaces, crowdsourcing, and crowdfunding). Within the domain of crowdfunding, Internet-enabled Peer-to-Peer Lending Systems (IP2PLS) have emerged as a disruptive technology, with implications for the financial services sector, business capitalization strategies, and personal and community development. IS research investigating user behavior in IP2PLS has revealed the saliency of social identity and personal transparency (as expressed through information sharing) in such systems. Prior research has largely focused on a small number of IP2PLS providers, thus this study examines a very large but under-researched platform. The study tests a theoretical model based on Social Identity Theory and prior IP2PLS studies, through an analysis of 116,667 loan records, and a subsequent analysis of 1000 manually coded records, to investigate the impact of information sharing on user (lenders and borrowers) behavior. The study reveals the importance of social ( vs financial) data, and further reveals relationships that frequently contradict prior findings from other IP2PLS. The study thus implies the need for a more heterogeneous view of the IP2PLS domain, and the need to more fully understand as systems that support user behavior by enabling social information exchanges.
A laboratory-based quantification of the effect of live fuel moisture content on fire spread rate
Authors: Rossa Carlos G. , Veloso Ricardo , Fernandes Paulo M.
Published: February 2016

Observational evidence of an effect of live vegetation moisture content on fire spread rate remains extremely scarce despite the significance of fire activity in fuel complexes dominated by live components. This study assessed the moisture content effect of quasi-live fuels on fire spread rates measured in laboratory experiments. Fuel beds were built by vertically placing vegetation clippings to reproduce the natural upright fuel structure. The fuel drying process during storage resulted in a wide moisture content range (13–180%). An exponential damping function was fitted to rate of spread observations in four fuel types, indicating that rate of spread is halved by an increase in live moisture content from 50 to 180%. This effect, especially at higher moisture contents, was weaker than that predicted by theoretical formulations and from studies in mixtures of dead and live fuel.
Future sea level rise constrained by observations and long-term commitment
Authors: Mengel Matthias , Levermann Anders , Frieler Katja , Robinson Alexander , Marzeion Ben , Winkelmann Ricarda
Published: February 2016

Significance

Anthropogenic sea level rise poses challenges to coastal areas worldwide, and robust projections are needed to assess mitigation options and guide adaptation measures. Here we present an approach that combines information about the equilibrium sea level response to global warming and last century's observed contribution from the individual components to constrain projections for this century. This “constrained extrapolation” overcomes limitations of earlier global semiempirical estimates because long-term changes in the partitioning of total sea level rise are accounted for. While applying semiempirical methodology, our method yields sea level projections that overlap with the process-based estimates of the Intergovernmental Panel on Climate Change. The method can thus lead to a better understanding of the gap between process-based and global semiempirical approaches.
ER stress stimulates production of the key antimicrobial peptide, cathelicidin, by forming a previously unidentified intracellular S1P signaling complex
Authors: Park Kyungho , Ikushiro Hiroko , Seo Ho Seong , Shin Kyong-Oh , Kim Young il , Kim Jong Youl , Lee Yong-Moon , Yano Takato , Holleran Walter M. , Elias Peter , Uchida Yoshikazu
Published: February 2016

Significance

The cathelicidin antimicrobial peptide (CAMP) is an innate immune element that promotes antimicrobial defense, but excessive CAMP can stimulate inflammation and tumorigenesis. We recently discovered that external perturbations that induce subtoxic levels of endoplasmic reticulum (ER) stress increase sphingosine-1-phosphate (S1P) production, in turn activating NF-κB–mediated CAMP synthesis. We report here that S1P interacts with the heat shock proteins (HSP90α and GRP94) through a previously unidentified S1P receptor-independent intracellular mechanism, followed by the activation of NF-κB leading to stimulation of CAMP production. These studies illuminate the critical role of both ER stress and S1P in orchestrating stress-specific signals that enhance innate immunity.
Parallel computation with molecular-motor-propelled agents in nanofabricated networks
Authors: Nicolau Dan V. , Lard Mercy , Korten Till , van Delft Falco C. M. J. M. , Persson Malin , Bengtsson Elina , Månsson Alf , Diez Stefan , Linke Heiner , Nicolau Dan V.
Published: February 2016

Significance

Electronic computers are extremely powerful at performing a high number of operations at very high speeds, sequentially. However, they struggle with combinatorial tasks that can be solved faster if many operations are performed in parallel. Here, we present proof-of-concept of a parallel computer by solving the specific instance {2, 5, 9} of a classical nondeterministic-polynomial-time complete (“NP-complete”) problem, the subset sum problem. The computer consists of a specifically designed, nanostructured network explored by a large number of molecular-motor-driven, protein filaments. This system is highly energy efficient, thus avoiding the heating issues limiting electronic computers. We discuss the technical advances necessary to solve larger combinatorial problems than existing computation devices, potentially leading to a new way to tackle difficult mathematical problems.
Shame closely tracks the threat of devaluation by others, even across cultures
Authors: Sznycer Daniel , Tooby John , Cosmides Leda , Porat Roni , Shalvi Shaul , Halperin Eran
Published: February 2016

Significance

Prominent theories of shame hold that shame is inherently maladaptive. However, direct tests of the fit between shame and its probable target domain have not previously been conducted. Here we test the alternative hypothesis that shame, although unpleasant (like pain), serves the adaptive function of defending against the social devaluation that results when negative information reaches others—by deterring actions that would lead to more devaluation than benefits, for example. If so, the intensity of shame people feel regarding a given item of negative information should track the devaluation that would happen if that item became known. Indeed, the data indicate a close match between shame intensities and audience devaluation, which suggests that shame is an adaptation.
Clocking the social mind by identifying mental processes in the IAT with electrical neuroimaging
Authors: Schiller Bastian , Gianotti Lorena R. R. , Baumgartner Thomas , Nash Kyle , Koenig Thomas , Knoch Daria
Published: February 2016

Significance

What a person says is not necessarily an accurate representation of what she thinks. Implicit attitudes permeate every aspect of our life. The implicit association test (IAT)—the most well-known test of implicit attitudes—is a reaction time measure. So far, the fundamental question about the source of its reaction time differences, i.e., the IAT effect, has remained unanswered. For the first time to our knowledge in IAT research, we applied a sophisticated electrical neuroimaging approach—the microstate approach. Superior to other approaches, the microstate approach allowed us to identify and time the entire chain of mental processes as they unfolded during the IAT. We found that reaction time differences are due to quantitative and not qualitative differences in the underlying mental processes.
Rhythmic expression of cryptochrome induces the circadian clock of arrhythmic suprachiasmatic nuclei through arginine vasopressin signaling
Authors: Edwards Mathew D. , Brancaccio Marco , Chesham Johanna E. , Maywood Elizabeth S. , Hastings Michael H.
Published: February 2016

Significance

Daily cycles of behavior adapt us to the 24-h rhythm of day and night. These rhythms are coordinated by a central clock, the suprachiasmatic nucleus (SCN), in which self-sustaining transcriptional/posttranslational feedback loops define approximately 24-h (circadian) time. Cryptochrome1 (CRY1) and CRY2 are essential clock components, but how they sustain cell-autonomous and circuit-level circadian timing in the SCN is not clear. To explore this, we developed a genetic complementation assay, using virally expressed, fluorescently tagged CRY proteins to test whether molecular pacemaking can be induced in arrhythmic
Cry1/2
-deficient SCN. We demonstrate protein-specific and robust induction of molecular pacemaking, the efficacy of which depends on the circadian pattern and phase of
Cry
expression and functional signaling via neuropeptide (AVP) receptors.
Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing
Authors: Morozov Giora I. , Zhao Huaying , Mage Michael G. , Boyd Lisa F. , Jiang Jiansheng , Dolan Michael A. , Venna Ramesh , Norcross Michael A. , McMurtrey Curtis P. , Hildebrand William , Schuck Peter , Natarajan Kannan , Margulies David H.
Published: February 2016

Significance

This report explores the biochemical and structural basis of the interactions of TAP binding protein, related (TAPBPR), a tapasin homolog, with MHC-I molecules. TAPBPR associates with MHC-I molecules early in their biosynthesis and folding but is not part of the peptide-loading complex (PLC). Here, by examining the interactions of recombinant TAPBPR with peptide-free and peptide-complexed MHC-I molecules, we show that TAPBPR serves as a peptide editor. Structural comparison of TAPBPR with tapasin indicates the similarities of the two molecules and provides a basis for evaluating the steps of peptide loading. Understanding the molecular underpinnings of peptide loading of MHC-I by TAPBPR and tapasin has wide-ranging influence on our ability to modulate peptide loading for vaccine design and T-cell recognition.
CXCL13 is a plasma biomarker of germinal center activity
Authors: Havenar-Daughton Colin , Lindqvist Madelene , Heit Antje , Wu Jennifer E. , Reiss Samantha M. , Kendric Kayla , Bélanger Simon , Kasturi Sudhir Pai , Landais Elise , Akondy Rama S. , McGuire Helen M. , Bothwell Marcella , Vagefi Parsia A. , Scully Eileen ,   IAVI Protocol C Principal Investigators, Tomaras Georgia D. , Davis Mark M. , Poignard Pascal , Ahmed Rafi , Walker Bruce D. , Pulendran Bali , McElrath M. Juliana , Kaufmann Daniel E. , Crotty Shane , Price Matt A. , Gilmour Jill , Fast Pat , Kamali Anatoli , Sanders Eduard J. , Onzala Omu , Allen Susan , Hunter Eric , Karita Etienne , Kilembe William , Lakhi Shabir , Inambao Mubiana
Published: February 2016

Significance

A major challenge for vaccine science is that there is no way to measure germinal center activity in humans. This challenge is particularly acute for human clinical trials of candidate vaccines (and most nonhuman primate studies of candidate vaccines), because germinal centers are the engines of Ab affinity maturation, and generation of highly affinity-matured Ab responses is the goal of all Ab-eliciting vaccines. Here, we report that we have identified the chemokine CXCL13 [chemokine (C-X-C motif) ligand 13] as a biomarker of germinal center activity. We show explicit relationships between plasma CXCL13 concentrations and germinal center frequencies in lymph nodes in a series of different conditions, including licensed and experimental vaccines, and in humans, nonhuman primates, and mice.
Rare recombination events generate sequence diversity among balancer chromosomes in
Drosophila melanogaster
Authors: Miller Danny E. , Cook Kevin R. , Yeganeh Kazemi Nazanin , Smith Clarissa B. , Cockrell Alexandria J. , Hawley R. Scott , Bergman Casey M.
Published: February 2016

Significance

Balancer chromosomes are highly rearranged chromosomes that suppress recombination and are an important tool in
Drosophila
genetics, yet their precise molecular structure is unknown. Here we characterize the inversion breakpoints of the
X
chromosome balancer
FM7
, and provide evidence that rare double-crossover events with balanced homologs can occur. These rare exchange events do not undermine the use of balancers, but lead to diversity among balancers. We also provide genomic evidence that unequal exchange between duplicated regions underlies reversion at the
Bar
locus. Our work demonstrates the power of genome sequencing to understand the molecular nature of classical genetic resources, and cautions that mutations maintained over balancers in regions susceptible to exchange should be checked regularly to prevent their loss.
Drp1-dependent mitochondrial fission via MiD49/51 is essential for apoptotic cristae remodeling
Authors: Otera Hidenori , Miyata Non , Kuge Osamu , Mihara Katsuyoshi
Published: February 2016

Mitochondrial fission facilitates cytochrome c release from the intracristae space into the cytoplasm during intrinsic apoptosis, although how the mitochondrial fission factor Drp1 and its mitochondrial receptors Mff, MiD49, and MiD51 are involved in this reaction remains elusive. Here, we analyzed the functional division of these receptors with their knockout (KO) cell lines. In marked contrast to Mff-KO cells, MiD49/MiD51-KO and Drp1-KO cells completely resisted cristae remodeling and cytochrome c release during apoptosis. This phenotype in MiD49/51-KO cells, but not Drp1-KO cells, was completely abolished by treatments disrupting cristae structure such as OPA1 depletion. Unexpectedly, OPA1 oligomers generally thought to resist cytochrome c release by stabilizing the cristae structure were similarly disassembled in Drp1-KO and MiD49/51-KO cells, indicating that disassembly of OPA1 oligomers is not directly linked to cristae remodeling for cytochrome c release. Together, these results indicate that Drp1-dependent mitochondrial fission through MiD49/MiD51 regulates cristae remodeling during intrinsic apoptosis.
Leukemia-associated activating mutation of Flt3 expands dendritic cells and alters T cell responses
Authors: Lau Colleen M. , Nish Simone A. , Yogev Nir , Waisman Ari , Reiner Steven L. , Reizis Boris
Published: February 2016

A common genetic alteration in acute myeloid leukemia is the internal tandem duplication (ITD) in FLT3, the receptor for cytokine FLT3 ligand (FLT3L). Constitutively active FLT3-ITD promotes the expansion of transformed progenitors, but also has pleiotropic effects on hematopoiesis. We analyzed the effect of FLT3-ITD on dendritic cells (DCs), which express FLT3 and can be expanded by FLT3L administration. Pre-leukemic mice with the Flt3ITD knock-in allele manifested an expansion of classical DCs (cDCs) and plasmacytoid DCs. The expansion originated in DC progenitors, was cell intrinsic, and was further enhanced in Flt3ITD/ITD mice. The mutation caused the down-regulation of Flt3 on the surface of DCs and reduced their responsiveness to Flt3L. Both canonical Batf3-dependent CD8+ cDCs and noncanonical CD8+ cDCs were expanded and showed specific alterations in their expression profiles. Flt3ITD mice showed enhanced capacity to support T cell proliferation, including a cell-extrinsic expansion of regulatory T (T reg) cells. Accordingly, these mice restricted alloreactive T cell responses during graft-versus-host reaction, but failed to control autoimmunity without T reg cells. Thus, the FLT3-ITD mutation directly affects DC development, indirectly modulating T cell homeostasis and supporting T reg cell expansion. We hypothesize that this effect of FLT3-ITD might subvert immunosurveillance and promote leukemogenesis in a cell-extrinsic manner.
Control of Foxp3 stability through modulation of TET activity
Authors: Yue Xiaojing , Trifari Sara , Äijö Tarmo , Tsagaratou Ageliki , Pastor William A. , Zepeda-Martínez Jorge A. , Lio Chan-Wang J. , Li Xiang , Huang Yun , Vijayanand Pandurangan , Lähdesmäki Harri , Rao Anjana
Published: February 2016

Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine and other oxidized methylcytosines, intermediates in DNA demethylation. In this study, we examine the role of TET proteins in regulating Foxp3, a transcription factor essential for the development and function of regulatory T cells (T reg cells), a distinct lineage of CD4+ T cells that prevent autoimmunity and maintain immune homeostasis. We show that during T reg cell development in the thymus, TET proteins mediate the loss of 5mC in T reg cell–specific hypomethylated regions, including CNS1 and CNS2, intronic cis-regulatory elements in the Foxp3 locus. Similar to CNS2-deficient T reg cells, the stability of Foxp3 expression is markedly compromised in T reg cells from Tet2/Tet3 double-deficient mice. Vitamin C potentiates TET activity and acts through Tet2/Tet3 to increase the stability of Foxp3 expression in TGF-β–induced T reg cells. Our data suggest that targeting TET enzymes with small molecule activators such as vitamin C might increase induced T reg cell efficacy.
Dynamics of Communicator and Audience Power: The Persuasiveness of Competence versus Warmth
Authors: Dubois David , Rucker Derek D. , Galinsky Adam D.
Published: February 2016

The current research offers a new theoretical perspective on the relationship between power and persuasion. An agentic-communal model of power is presented that proposes power affects both the messages generated by communicators and the messages that persuade audiences. Compared to low-power states, high-power states produce a greater emphasis on information that conveys competence. As a consequence, high-power communicators generate messages with greater competence information, and high-power audiences are persuaded more by competence information. In contrast to high-power states, low-power states produce a greater emphasis on information that conveys warmth. As a result, low-power communicators generate messages with greater warmth information, and low-power audiences are persuaded more by warmth information. Because of these two outcomes, a power-matching effect occurs between communicator and audience power: high-power communicators are more effective in persuading high-power audience members, whereas low-power communicators are more effective in persuading low-power audience members. Four experiments find support for these effects in oral and written contexts with three distinct manipulations of power. Overall, these experiments demonstrate that the persuasiveness of messages can be affected by the alignment between the psychological sense of power of the communicator and the audience.
Detection of Vaccine-Induced Antibodies to Ebola Virus in Oral Fluid
Authors: Lambe Teresa , Rampling Tommy , Samuel Dhan , Bowyer Georgina , Ewer Katie J. , Venkatraman Navin , Edmans Matthew , Dicks Steve , Hill Adrian V. S. , Tedder Richard S. , Gilbert Sarah C.
Published: February 2016

Blood sampling to assess production of antigen-specific antibodies after immunization is commonly performed, but it presents logistical difficulties for trials carried out during an infectious disease outbreak. In this study, we show that antibodies may be reliably detected in oral fluid collected in a minimally invasive manner without use of sharps.

Clinical Trials Registration. NCT02240875.
Pain is Associated With Poorer Grades, Reduced Emotional Well-Being, and Attention Problems in Adolescents
Authors: Voerman Jessica S. , de Klerk Cora , Vander Heyden Karin M. , Passchier Jan , Idema Wietske , Timman Reinier , Jolles Jelle
Published: February 2016

Objectives:

The purpose of the present study was to determine whether pain is associated with specific aspects of academic performance, that is, poorer grades, and with factors critical to an adolescent’s academic performance, that is, decreased emotional well-being and attention problems. We hypothesized that the association between pain and school grades is mediated by emotional well-being and attention problems.

Methods:

In a cross-sectional study, we collected data from 2215 pupils, ages 12 to 13 years. Pain (no, occasional, and frequent), emotional well-being, and attention problems were measured with self-rating scales. Dutch, English, and math grades were taken as an index of academic performance.

Results:

Frequent pain in adolescents was associated with poorer grades (Dutch P=0.02 and math P=0.01). Both occasional and frequent pain were associated with reduced emotional well-being (P<0.001) and reduced self-reported attention (P<0.001). However, the association between pain and lower grades disappeared when controlling for emotional well-being and attention.

Discussion:

The present study shows that the association between pain and Dutch adolescents grades is mediated by reduced emotional well-being and attention problems. The association between pain and math grades is mediated by emotional problems. The results suggest that an intervention targeted at pain in adolescents could have a positive effect on their emotional well-being, attention, and school performance.
A Meta-Analysis
Authors: Chemali Mark E. , Eslick Guy D.
Published: February 2016

Introduction:

Enhanced Recovery After Surgery (ERAS) aims to minimize the length of a negative physiological response to surgical intervention. There are a number of aspects involved in ERAS protocols, one of which is postoperative pain relief. This meta-analysis investigates the current evidence for postoperative pain relief and its effect on patient pain and the length of stay after colorectal surgery.

Method/Results:

Medline, PubMed, and EMBASE databases were searched for relevant studies between January 1966 and February 2016. All randomized controlled trials comparing postoperative pain management strategies in an ERAS setting with the length of stay as an outcome measure were selected. In addition to the length of stay, other outcomes analyzed were pain scores at 24 hours postoperatively, nausea, vomiting, and the time to the first bowel motion.

Results:

There was a decrease in vomiting in the ERAS group compared with the control groups (relative risk=0.82; 95% confidence interval, 0.52-1.27). Mean differences in the length of stay (P=0.879), pain visual analogue scales (P=0.120), the time to the first bowel motion in hours (P=0.371), and nausea (P=0.083) were not statistically significant.

Conclusions:

In an ERAS setting with regard to a colorectal patient population, the choice of modality for postoperative pain relief does not impact the length of hospital stay, pain, the time to the first bowel motion, or nausea.
Robert W. Williams: Forgotten Pioneer of Spinal Мicrosurgery
Authors: Stone James L. , Arnold Paul M. , Chowdhry Shakeel A. , Charbel Fady
Published: February 2016

In the 1970's many neurosurgeons gradually adapted microsurgical techniques to spine surgery as the benefits of magnification, illumination, and use of fine instruments in cranial surgery became apparent. In the early 1970 s, Robert W. Williams, а neurosurgeon in private practice in Las Vegas, Nevada, independently began to devise spinal microneurosurgical techniques with the goal of improving surgical outcome in lumbar and cervical surgery. Much of his initial work with microlumbar discectomies and microcervical foraminotomies was presented at annual meetings of the American Association of Neurological Surgeons and Congress of Neurological Surgeons in the 1970s and 1980s. An outsider to organized academic neurosurgery, Dг. Williams found his work was received cautiously and with significant skepticism. He found the orthopedic spine surgery community and journals more receptive, thus much of his earlier work was published in the orthopedic literature. This resulted in an orthopedic and neurosurgical following which was unique at that time. Dr. William's interesting career and contribution to spinal microsurgery is outlined, demonstrating the contributions to surgery, both neurological and orthopedic, that can be achieved by a neurosurgeon in private practice.

Level of Evidence: N/A
Performance indicators in a newly established organized cervical screening programme: registry-based analysis in the Czech Republic
Authors: Májek Ondřej , Dušková Jaroslava , Dvořák Vladimír , Beková Alena , Klimeš Daniel , Blaha Milan , Anttila Ahti , Dušek Ladislav
Published: February 2016

In 2008, the organized Czech National Cervical Cancer Screening Programme (CNCCSP) was initiated by transformation of the existing opportunistic efforts. The aim of our study was to examine recent cervical cancer burden trends and to assess the quality of the Czech National Cervical Cancer Screening Programme using a set of standard performance indicators. Our study utilized data from the national Cervical Cancer Screening Registry and the Czech National Cancer Registry. We computed internationally accepted indicators and assessed time trends and variability among screening centres. Between 1995 and 2011, the incidence of age-standardized cervical cancer decreased by 21% (1023 cases in 2011), and the mortality decreased by 35% (399 deaths in 2011). The annual coverage of the target population by cervical screening increased to 56% in 2013 (as compared with 35% in 2001). If we consider a 2-year interval (2012–2013), the estimated coverage was 77%. Over two million women underwent screening in 2013; 96% of them had a negative result. About 0.2% of smears showed cytological signs of a high-grade intraepithelial lesion or a malignancy, and the estimated positive predictive value for advanced intraepithelial neoplasia (cervical intraepithelial neoplasia grade 2+) was 79.6%. However, performance indicators show considerable heterogeneity between screening centres. The reported values of performance indicators are in line with the results of programmes that have previously been shown to be successful in terms of decreasing the cervical cancer burden, and are promising with respect to an even more pronounced decrease in cervical cancer mortality in the near future, provided that continuous quality improvement can be maintained. Linkage studies between screening, cancer and cause-of-death registers can provide further information on screening effectiveness and validity issues.
How Long Is Too Long? Trials and Tribulations of an Indolent Tumor
Authors: Meena Nikhil K. , Jeffus Susanne K. , Lindberg Matthew R. , Bartter Thaddeus
Published: February 2016

A 31-year-old African American man presented for workup of a right hilar and tracheal mass. Stability of the mass when compared with a computed tomographic scan performed 3 years prior suggested an indolent process. On bronchoscopy, there were 2 separate although morphologically similar endobronchial lesions, one in the distal trachea and the second at the level of the right upper lobe bronchus. Biopsies of both lesions demonstrated granular cell tumors. Subsequent rigid bronchoscopy with ablation led to resolution of wheeze, decrease in dyspnea, and documented improvements in both ventilation and perfusion to the right lung. This case illustrates both a rare disease (multifocal endobronchial granular cell tumor) and the physiological impact of reducing large airway obstruction.
Inadequate seroprotection against hepatitis B virus and one detected case of hepatitis C virus infection among patients with inflammatory bowel disease
Authors: Waszczuk Ewa , Waszczuk Karolina M. , Mulak Agata , Paradowski Leszek
Published: February 2016

Objectives

The prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among patients with inflammatory bowel disease (IBD) from central and eastern European countries is unknown. Postvaccination HBV immunity in an immunocompromised host may wane. The aims of the study were as follows: to assess the immune status for HBV and HCV among IBD patients, the level of HBV seroprotection, and to compare the immune status of patients who received mandatory versus recommended HBV vaccination.

Materials and methods

Serological markers of HBV and HCV (anti-HBs, anti-HBc, HBsAg, and anti-HCV) were determined in 147 consecutive IBD patients. An anti-HBs of 10 IU/l or more was considered as immunity to HBV infection.

Results

HBV infection was detected in 21 patients, whereas 11 of them recalled previous HBV vaccination. Sixty-eight noninfected patients had a level of anti-HBs 10 IU/l or more and only 29% reached the cut-off level of 100 IU/l. Among patients vaccinated obligatorily, two patients had previous HBV infection and 15% did not have an adequate seroprotection against HBV. Patients who received a mandatory HBV vaccine more frequently had a protective anti-HBs level than those vaccinated voluntarily (P<0.001). One positive anti-HCV result was found.

Conclusion

A mandatory HBV vaccination significantly increased the number of patients effectively protected against HBV; however, a remarkable number of vaccinated IBD patients had inadequate HBV seroprotection. All IBD patients should be screened for HBV and HCV infections and monitored for anti-HBs titers.
Does Churning in Medicaid Affect Health Care Use?
Authors: Roberts Eric T. , Pollack Craig Evan
Published: February 2016

Background:

Transitions into and out of Medicaid, termed churning, may disrupt access to and continuity of care. Low-income, working adults who became eligible for Medicaid under the Affordable Care Act are particularly susceptible to income and employment changes that lead to churning.

Objective:

To compare health care use among adults who do and do not churn into and out of Medicaid.

Data:

Longitudinal data from 6 panels of the Medical Expenditure Panel Survey.

Methods:

We used differences-in-differences regression to compare health care use when adults reenrolled in Medicaid following a loss of coverage, to utilization in a control group of continuously enrolled adults.

Outcome Measures:

Emergency department (ED) visits, ED visits resulting in an inpatient admission, and visits to office-based providers.

Results:

During the study period, 264 adults churned into and out of Medicaid and 627 had continuous coverage. Churning adults had an average of approximately 0.05 Medicaid-covered office-based visits per month 4 months before reenrolling in Medicaid, significantly below the rate of approximately 0.20 visits in the control group. Visits to office-based providers did not reach the control group rate until several months after churning adults had resumed Medicaid coverage. Our comparisons found no evidence of significantly elevated ED and inpatient admission rates in the churning group following reenrollment.

Conclusions:

Adults who lose Medicaid tend to defer their use of office-based care to periods when they are insured. Although this suggests that enrollment disruptions lead to suboptimal timing of care, we do not find evidence that adults reenroll in Medicaid with elevated acute care needs.
Pharmacokinetics of Chemotherapeutic Drugs in Pediatric Patients With Down Syndrome and Leukemia
Authors: Hefti Erik , Blanco Javier G.
Published: February 2016

Children with Down syndrome (DS) have a 10- to 30-fold increased risk of developing acute myeloid leukemia or acute lymphoblastic leukemia. Patients with DS and leukemia are treated with the same chemotherapeutic agents as patients without DS. Treatment regimens for pediatric leukemia comprise multiple cytotoxic drugs including methotrexate, doxorubicin, vincristine, cytarabine, and etoposide. There have been reports of increased toxicity, as well as altered therapeutic outcomes in pediatric patients with DS and leukemia. This review is focused on the pharmacokinetics of cytotoxic drugs in pediatric patients with leukemia and DS. The available literature suggests that methotrexate and thioguanine display altered pharmacokinetic parameters in pediatric patients with DS. It has been hypothesized that the variable pharmacokinetics of these drugs may contribute to the increased incidence of treatment-related toxicities seen in DS. Data from a small number of studies suggest that the pharmacokinetics of vincristine, etoposide, doxorubicin, and busulfan are similar between patients with and without DS. Definitive conclusions regarding the pharmacokinetics of cytotoxic drugs in pediatric patients with leukemia and DS are difficult to reach due to limitations in the available studies.
Do Not Forget the Glycophorin A: An Unusual Case of Myeloid Sarcoma
Authors: Mohanlal Reena D. , Vaughan Jenifer , Ramparsad Narisha , Naidu Gita
Published: February 2016

Acute erythroid leukemia is rare, with isolated reports on presentation as an extramedullary tumor mass (myeloid sarcoma). We describe a case of pure erythroid leukemia presenting as an orbital mass in a 1-year, 9-month-old girl. This is only the second case described in a child. Tissue biopsy of the tumor mass showed medium-sized cells that were glycophorin A positive and negative with conventional myeloid markers. Flow cytometry, bone marrow aspirate, and trephine confirmed the diagnosis of pure erythroid leukemia.
Survival After Relapse of Medulloblastoma
Authors: Koschmann Carl , Bloom Karina , Upadhyaya Santhosh , Geyer J. Russell , Leary Sarah E.S.
Published: February 2016

Survival after recurrence of medulloblastoma has not been reported in an unselected cohort of patients in the contemporary era. We reviewed 55 patients diagnosed with medulloblastoma between 2000 and 2010, and treated at Seattle Children’s Hospital to evaluate patterns of relapse treatment and survival. Fourteen of 47 patients (30%) over the age of 3 experienced recurrent or progressive medulloblastoma after standard therapy. The median time from diagnosis to recurrence was 18.0 months (range, 3.6 to 62.6 mo), and site of recurrence was metastatic in 86%. The median survival after relapse was 10.3 months (range, 1.3 to 80.5 mo); 3-year survival after relapse was 18%. There were trend associations between longer survival and having received additional chemotherapy (median survival 12.8 vs. 1.3 mo, P=0.16) and radiation therapy (15.4 vs. 5.9 mo, P=0.20). Isolated local relapse was significantly associated with shorter survival (1.3 vs. 12.8 mo, P=0.009). Recurrence of medulloblastoma is more likely to be metastatic than reported in previous eras. Within the limits of our small sample, our data suggest a potential survival benefit from retreatment with cytotoxic chemotherapy and radiation even in heavily pretreated patients. This report serves as a baseline against which to evaluate novel therapy combinations.
Brief Report: Relationship Among Viral Load Outcomes in HIV Treatment Interruption Trials
Authors: Treasure Graham C. , Aga Evgenia , Bosch Ronald J. , Mellors John W. , Kuritzkes Daniel R. , Para Michael , Gandhi Rajesh T. , Li Jonathan Z.
Published: February 2016

Viral load (VL) rebound timing and set point were analyzed in 235 participants undergoing analytic treatment interruption (ATI) in 6 AIDS Clinical Trials Group studies. There was no significant association between rebound timing and ATI VL set point for those who rebounded ≤12 weeks. VL set points were lower in participants with rebound >12 weeks (P < 0.001) and participants treated during early infection (P < 0.001). Pre-antiretroviral therapy VL correlated with set point, though 68% of participants had a set point lower than pre-antiretroviral therapy VL. These results illustrate complex relationships between post-ATI virologic outcomes and the potential presence of biological factors mediating rebound timing and set point.
The kelvin redefinition and its
mise en pratique
Authors: Fellmuth B. , Fischer J. , Machin G. , Picard S. , Steur P. P. M. , Tamura O. , White D. R. , Yoon H.
Published: February 2016

In 2018, it is expected that there will be a major revision of the International System of Units (SI) which will result in all of the seven base units being defined by fixing the values of certain atomic or fundamental constants. As part of this revision, the kelvin, unit of thermodynamic temperature, will be redefined by assigning a value to the Boltzmann constant
k
. This explicit-constant definition will define the kelvin in terms of the SI derived unit of energy, the joule. It is sufficiently wide to encompass any form of thermometry. The planned redefinition has motivated the creation of an extended
mise en pratique
(‘practical realization’) of the definition of the kelvin (
MeP
-K), which describes how the new definition can be put into practice. The
MeP
-K incorporates both of the defined International Temperature Scales (ITS-90 and PLTS-2000) in current use and approved primary-thermometry methods for determining thermodynamic temperature values. The
MeP
-K is a guide that provides or makes reference to the information needed to perform measurements of temperature in accord with the SI at the highest level. In this article, the background and the content of the extended second version of the
MeP
-K are presented.
Progress towards the determination of thermodynamic temperature with ultra-low uncertainty
Authors: Gavioso Roberto M. , Ripa Daniele Madonna , Steur Peter P. M. , Gaiser Christof , Zandt Thorsten , Fellmuth Bernd , de Podesta Michael , Underwood Robin , Sutton Gavin , Pitre Laurent , Sparasci Fernando , Risegari Lara , Gianfrani Livio , Castrillo Antonio , Machin Graham
Published: February 2016

Previous research effort towards the determination of the Boltzmann constant has significantly improved the supporting theory and the experimental practice of several primary thermometry methods based on the measurement of a thermodynamic property of a macroscopic system at the temperature of the triple point of water. Presently, experiments are under way to demonstrate their accuracy in the determination of the thermodynamic temperature
T
over an extended range spanning the interval between a few kelvin and the copper freezing point (1358 K). We discuss how these activities will improve the link between thermodynamic temperature and the temperature as measured using the International Temperature Scale of 1990 (ITS-90) and report some preliminary results obtained by dielectric constant gas thermometry and acoustic gas thermometry. We also provide information on the status of other primary methods, such as Doppler broadening thermometry, Johnson noise thermometry and refractive index gas thermometry. Finally, we briefly consider the implications of these advancements for the dissemination of calibrated temperature standards.
Noise thermometry at ultra-low temperatures
Authors: Rothfuss D. , Reiser A. , Fleischmann A. , Enss C.
Published: February 2016

The options for primary thermometry at ultra-low temperatures are rather limited. In practice, most laboratories are using
195
Pt NMR thermometers in the microkelvin range. In recent years, current sensing direct current superconducting quantum interference devices (DC-SQUIDs) have enabled the use of noise thermometry in this temperature range. Such devices have also demonstrated the potential for primary thermometry. One major advantage of noise thermometry is the fact that no driving current is needed to operate the device and thus the heat dissipation within the thermometer can be reduced to a minimum. Ultimately, the intrinsic power dissipation is given by the negligible back action of the readout SQUID. For thermometry in low-temperature experiments, current noise thermometers and magnetic flux fluctuation thermometers have proved to be most suitable. To make use of such thermometers at ultra-low temperatures, we have developed a cross-correlation technique that reduces the amplifier noise contribution to a negligible value. For this, the magnetic flux fluctuations caused by the Brownian motion of the electrons in our noise source are measured inductively by two DC-SQUID magnetometers simultaneously and the signals from these two channels are cross-correlated. Experimentally, we have characterized a thermometer made of a cold-worked high-purity copper cylinder with a diameter of 5 mm and a length of 20 mm for temperatures between 42 
μ
K and 0.8 K. For a given temperature, a measuring time below 1 min is sufficient to reach a precision of better than 1%. The extremely low power dissipation in the thermometer allows continuous operation without heating effects.
Genome-culture coevolution promotes rapid divergence in the killer whale
Authors: Foote Andrew D. , Vijay Nagarjun , Ávila-Arcos María C. , Baird Robin W. , Durban John W. , Fumagalli Matteo , Gibbs Richard A. , Hanson M. Bradley , Korneliussen Thorfinn S. , Martin Michael D. , Robertson Kelly. M. , Sousa Vitor C. , Vieira Filipe. G. , Vinař Tomáš , Wade Paul , Worley Kim C. , Excoffier Laurent , Morin Phillip. A. , P. Gilbert M. Thomas. , Wolf Jochen. B.W.
Published: February 2016

The interaction between ecology, culture and genome evolution remains poorly understood. Analysing population genomic data from killer whale ecotypes, which we estimate have globally radiated within less than 250,000 years, we show that genetic structuring including the segregation of potentially functional alleles is associated with socially inherited ecological niche. Reconstruction of ancestral demographic history revealed bottlenecks during founder events, likely promoting ecological divergence and genetic drift resulting in a wide range of genome-wide differentiation between pairs of allopatric and sympatric ecotypes. Functional enrichment analyses provided evidence for regional genomic divergence associated with habitat, dietary preferences and postzygotic reproductive isolation. Our findings are consistent with expansion of small founder groups into novel niches by an initial plastic behavioural response, perpetuated by social learning imposing an altered natural selection regime. The study constitutes an important step toward an understanding of the complex interaction between demographic history, culture, ecological adaptation and evolution at the genomic level.
AC-PCA: simultaneous dimension reduction and adjustment for confounding variation
Authors: Lin Zhixiang , Yang Can , Zhu Ying , Duchi John C. , Fu Yao , Wang Yong , Jiang Bai , Zamanighomi Mahdi , Xu Xuming , Li Mingfeng , Sestan Nenad , Zhao Hongyu , Wong Wing Hung
Published: February 2016

Dimension reduction methods are commonly applied to high-throughput biological datasets. However, the results can be hindered by confounding factors, either biologically or technically originated. In this study, we extend Principal Component Analysis to propose AC-PCA for simultaneous dimension reduction and adjustment for confounding variation. We show that AC-PCA can adjust for a) variations across individual donors present in a human brain exon array dataset, and b) variations of different species in a model organism ENCODE RNA-Seq dataset. Our approach is able to recover the anatomical structure of neocortical regions, and to capture the shared variation among species during embryonic development. For gene selection purposes, we extend AC-PCA with sparsity constraints, and propose and implement an efficient algorithm. The methods developed in this paper can also be applied to more general settings.
PARAQUAT TOLERANCE3 is an E3 ligase and acts as a negative regulator of oxidative stress response
Authors: Luo Chao , Cai Xiao-Teng , Du Jin , Zhao Tao-Lan , Wang Peng-Fei , Zhao Ping-Xia , Liu Rui , Xie Qi , Cao Xiao-Feng , Xiang Cheng-Bin
Published: February 2016

Oxidative damage could be caused in plant cells when biotic and abiotic stresses are imposed. While the response to oxidative stress is well studied, little is known about how the activated response is switched off when oxidative stress is diminished. By studying Arabidopsis mutantparaquat tolerance3, we identified the genetic locusPARAQUAT TOLERANCE3(PQT3) as a major negative regulator of oxidative stress tolerance.PQT3, encoding an E3 ligase, is rapidly down-regulated by oxidative stress. PQT3 has E3 ubiquitin ligase activity in ubiquitination assay. Subsequently, we identified PRMT4b as a PQT3-interacting protein. By histone methylation, PRMT4b may regulate the expression ofAPX1andGPX1, encoding two key enzymes against oxidative stress. Moreover, PQT3 is able to recognize PRMT4b for targeted degradation via 26S proteasome. Therefore, we have identified PQT3 as an E3 ligase that acts as a negative regulator of activated response to oxidative stress.