bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensorless enhancement of an atomic force microscope micro-cantilever quality factor using piezoelectric shunt control
Authors: Fairbairn M. , Moheimani S. O. R.
Published: May 2013

The image quality and resolution of the Atomic Force Microscope (AFM) operating in tapping mode is dependent on the quality (Q) factor of the sensing micro-cantilever. Increasing the cantilever Q factor improves image resolution and reduces the risk of sample and cantilever damage. Active piezoelectric shunt control is introduced in this work as a new technique for modifying the Q factor of a piezoelectric self-actuating AFM micro-cantilever. An active impedance is placed in series with the tip oscillation voltage source to modify the mechanical dynamics of the cantilever. The benefit of using this control technique is that it removes the optical displacement sensor from the Q control feedback loop to reduce measurement noise in the loop and allows for a reduction in instrument size.
Optical properties of cubic and rhombohedral GeTe
Authors: Singh David J.
Published: May 2013

Calculations of the optical properties of GeTe in the cubic NaCl and rhombohedral ferroelectric structures are reported. The rhombohedral ferroelectric distortion increases the band gap from 0.11 eV to 0.38 eV. Remarkably, substantial changes in optical properties are found even at high energies up to 5 eV. The results are discussed in relation to the bonding of GeTe and to phase change materials based on it.
Comparing Effects of Transmitters within and among Populations: Application to Swimming Performance of Juvenile Chinook Salmon
Authors: Perry Russell W. , Plumb John M. , Fielding Scott D. , Adams Noah S. , Rondorf Dennis W.
Published: May 2013

The sensitivity of fish to a transmitter depends on factors such as environmental conditions, fish morphology, life stage, rearing history, and tag design. However, synthesizing general trends across studies is difficult because each study focuses on a particular performance measure, species, life stage, and transmitter model. These differences motivated us to develop simple metrics that allow effects of transmitters to be compared among different species, populations, or studies. First, we describe how multiple regression analysis can be used to quantify the effect of tag burden (transmitter mass relative to fish mass) on measures of physiological performance. Next, we illustrate how the slope and intercept parameters can be used to calculate two summary statistics: θ, which estimates the tag burden threshold above which the performance of tagged fish begins to decline relative to untagged fish; and k, which measures the percentage change in performance per percentage point increase in tag burden. When θ = 0, k provides a single measure of the tag's effect that can be compared among species, populations, or studies. We apply this analysis to two different experiments that measure the critical swimming speed (Ucrit) of tagged juvenile Chinook Salmon Oncorhynchus tshawytscha. In both experiments, Ucrit declined as tag burden increased, but we found no significant threshold in swimming performance. Estimates of θ ranged from −0.6% to 2.1% among six unique treatment groups, indicating that swimming performance began to decline at a relatively low tag burden. Estimates of k revealed that Ucrit of tagged fish declined by −2.68% to −4.86% for each 1% increase in tag burden. Both θ and k varied with the tag's antenna configuration, tag implantation method, and posttagging recovery time. Our analytical approach can be used to gain insights across populations to better understand factors affecting the ability of fish to carry a transmitter.
Cells surviving fractional killing by TRAIL exhibit transient but sustainable resistance and inflammatory phenotypes
Authors: Flusberg Deborah A. , Roux Jérémie , Spencer Sabrina L. , Sorger Peter K.
Published: May 2013

When clonal populations of human cells are exposed to apoptosis-inducing agents, some cells die and others survive. This fractional killing arises not from mutation but from preexisting, stochastic differences in the levels and activities of proteins regulating apoptosis. Here we examine the properties of cells that survive treatment with agonists of two distinct death receptors, tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and anti-FasR antibodies. We find that “survivor” cells are highly resistant to a second ligand dose applied 1 d later. Resistance is reversible, resetting after several days of culture in the absence of death ligand. “Reset” cells appear identical to drug-naive cells with respect to death ligand sensitivity and gene expression profiles. TRAIL survivors are cross-resistant to activators of FasR and vice versa and exhibit an NF-κB–dependent inflammatory phenotype. Remarkably, reversible resistance is induced in the absence of cell death when caspase inhibitors are present and can be sustained for 1 wk or more, also without cell death, by periodic ligand exposure. Thus stochastic differences in cell state can have sustained consequences for sen­sitivity to prodeath ligands and acquisition of proinflammatory phenotypes. The important role played by periodicity in TRAIL exposure for induction of opposing apoptosis and survival mechanisms has implications for the design of optimal therapeutic agents and protocols.
Toward the evolutionary roots of affective prosody in human acoustic communication: A comparative approach to mammalian voices
Authors: Zimmermann Elke , Leliveld Lisette , Schehka Simone
Published: May 2013

Recent findings from speech, music and nonverbal acoustic communication suggest that some basic acoustically conveyed emotions are universally expressed and recognized across cultures. In this review, we explore a “prehuman origin hypothesis of affective prosody” using a comparative approach with nonhuman mammals. Based on our own work and an extensive literature review, we extracted comparable behavioural contexts in which empirical data on the expression and perception of acoustically conveyed affect intensity could be compared across different mammalian orders. Despite different set-ups, study designs and methods of acoustic analysis, comparative data revealed that affect intensity was similarly encoded across contexts and species, and that acoustically conveyed affect intensity was of significant relevance for listeners. This work supports the hypothesis that affective prosody in human acoustic communication has deep-reaching phylogenetic roots, deriving from precursors already present and relevant in the vocal communication systems of nonhuman mammals.
All aboutAllin (Some) Salish Languages
Authors: Davis Henry
Published: May 2013

In the history of work on cross‐linguistic variation in quantification, Salish languages have played a special role. This is largely due to the programmatic work of Eloise Jelinek (see in particular Jelinek 1995), who identified Northern Straits Salish as a language that entirely lacked D‐type quantifiers. Instead, Jelinek claimed that Northern Straits had only A‐type quantification, in which an adverbial quantifier unselectively binds any appropriate variable in its scope. The purpose of the current chapter is twofold: to provide an update on research into D‐type quantification, and to explore A‐type quantification in more detail. Data will be drawn mainly from the Northern Interior Salish language Lillooet (a.k.a. St’at’imcets), supplemented where available with data from Central Salish languages, including Northern Straits Salish and its neighbour and close relative Halkomelem.
International Minimum Standard and International Law-Making
Authors: Paparinskis Martins
Published: May 2013

This chapter addresses the broader normative and historical context within which the legal development of the international minimum standard has taken place. International minimum standard is the body of international rules that address the treatment of aliens, and as such has to be addressed by the application of the traditional legal methodology of sources and interpretation. The historical legal background against which the elaboration of the international standard took place was initially defined by the disagreement between the traditional claimant States (that supported the international standard) and the traditional respondent States (that were sceptical about anything more demanding than non-discrimination and settlement of disputes in domestic courts). Since the time of these debates in the 19th century, many factors have influenced the development of the standard, including a rethinking of the law of State responsibility, international recognition of individual rights, and emergence of the corporate investor, all challenging the more limited traditional rationale.
Arguments for Change: Partisan Interests and Expectations about Process
Authors: Bowler Shaun , Donovan Todd
Published: May 2013

This chapter examines the public arguments found in dozens of referendum campaigns where voters were asked to make decisions on electoral reform matters. These arguments of reform advocates –at times echoing themes found in the academic literature on effects of institutions—have two main properties. First, they contend that institutions have important effects on the behaviour of elected officials and on the behaviour of voters. Second, regardless of the reform proposals examined, the predicted effects are generally quite similar: arguments for changing a wide range of rules seem to share goals and expectations about what the reform is supposed to accomplish. Reform advocates stress the transformative effects of reforming the political process, arguing that new rules will reduce partisanship, target ‘special interests,’ and promote fairness. Arguments against reform, in contrast, stress outcomes in terms of the partisan consequences of change.
Term Limits: Effects, but Not as Advertised
Authors: Bowler Shaun , Donovan Todd
Published: May 2013

Term limits in the US were a reform aimed at forcing greater turnover of legislators from office. As with many electoral reforms, it was promoted for the broader, indirect effects it would have on the political system. By changing the composition of legislatures, term limits would improve public regard for legislators, increase electoral competition, and, by extension, increase voter turnout. Although turnover of representatives may have increased, the transformative effects that reformers promoted did not materialize. In particular, there is no evidence of higher levels of turnout after adoption of term limits, and public regard for legislators continued to erode after term limits took effect.
Second Lumbrical and Mixed Nerve Segmental Conduction Studies in Carpal Tunnel Syndrome
Authors: Kikas Demetrios L. , Kikas Lazarus D. , Lewis Richard A.
Published: May 2013

Objectives:

We report the findings of 20 patients with carpal tunnel syndrome (CTS) who had segmental motor studies to the second lumbrical (2L) and mixed nerve action potential (MNAP) across the carpal tunnel.

Methods:

This was a prospective study of 20 patients randomly selected who had clinical and electrophysiologic evidence of CTS using standard techniques. Six CTS patients had studies pre- and post-surgical release.

Results:

Mean 2L motor amplitude reduction across the carpal tunnel was 55.19% ± 6.6% in patients (controls = 15.9% ± 9.4%). Mean motor velocity across the carpal tunnel was 23.4 ± 7.05 m/s versus 46.45 ± 6 m/s in controls. Mean reduction of the MNAP amplitudes was 79.0% ± 23% versus 20% ± 15% in controls. The mean MNAP velocity was 12.3 ± 13.1 m/s versus 48.35 ± 5.18 m/s in controls. The 6 surgical cases showed improvement in amplitude reduction and velocity at 2–6 months consistent with preoperative severity.

Conclusions:

These studies show that segmental conduction studies to the 2L and MNAP can demonstrate conduction block that improves with decompression.
Minimally invasive treatment of laparoscopic and endoscopic cooperative surgery for patients with gastric gastrointestinal stromal tumors
Authors: Qiu Wei Qing , Zhuang Jie , Wang Ming , Liu Hua , Shen Zhi Yong , Xue Han Bing , Shen Lei , Ge Zhi Zheng , Cao Hui
Published: May 2013

Objective

To evaluate the feasibility and safety of laparoscopic and endoscopic cooperative surgery (LECS) for the treatment of gastric gastrointestinal stromal tumors (GISTs).

Methods

We retrospectively reviewed the data of 69 consecutive patients who underwent LECS, including laparoscopy‐assisted endoscopic resection (LAER) and endoscopy‐assisted laparoscopic wedge resection (EAWR), for pathologically confirmed gastric GISTs of less than 5 cm in diameter from January 2006 to October 2012.

Results

The tumor was located at the upper third of the stomach in 22 patients, the middle third in 38 and the lower third in nine, with a mean tumor size of 2.8 ± 1.6 cm. The operating time was 81.6 ± 31.8 min in the LAER group and 86.3 ± 28.5 min in the EAWR group (P = 0.776). Intraoperative blood loss was 29.8 ± 15.4 mL in the LAER group and 31.4 ± 11.6 mL in the EAWR group (P = 0.561). Most patients had a very low or low risk of tumor recurrence, while six had an intermediate risk of tumor recurrence. The mean length of postoperative hospital stay was 4.6 days. Only two patients had postoperative complications after LECS, both of whom were treated successfully without open surgery. During a median follow‐up of 35 months, all patients were disease‐free, with no tumor recurrence or metastases.

Conclusion

LECS is a minimally invasive and safe alternative approach which can achieve fast recovery and satisfactory short‐term outcomes for appropriately selected patients with gastric GISTs.
Effect of human papillomavirus and Chlamydia trachomatis co‐infection on sperm quality in young heterosexual men with chronic prostatitis‐related symptoms
Authors: Cai Tommaso , Wagenlehner Florian M.E. , Mondaini Nicola , D'Elia Carolina , Meacci Francesca , Migno Serena , Malossini Gianni , Mazzoli Sandra , Bartoletti Riccardo
Published: May 2013

Objective

To investigate the effect of human papillomavirus (HPV) and Chlamydia trachomatis (Ct) co‐infection on sperm concentration, motility and morphology, in a large cohort of young heterosexual male patients with chronic prostatitis‐related symptoms.

Patients and Methods

Patients with chronic prostatitis‐related symptoms, attending the same centre for sexually transmitted diseases from January 2005 and December 2010, were consecutively enrolled in this cross‐sectional study.

All patients underwent clinical and instrumental examination, microbiological cultures for common bacteria, DNA extraction, mucosal and serum antibodies evaluation for Ct, specific tests for HPV and semen analysis. The semen variables analysed were: volume; pH; sperm concentration; motility; and morphology.

Subjects were subdivided in two groups: group A, patients with Ct infection alone and group B, patients with Ct and HPV co‐infection.

The main outcome measurement was the effect of Ct and HPV co‐infection on the semen variables examined.

Results

Of 3050 screened patients, 1003 were enrolled (32.9%) in the study. A total of 716 (71.3%) patients were allocated to group A, and 287 (28.7%) to group B.

Significant differences between the two groups were reported in terms of percentage of motile sperm (degrees of freedom [df] = 1001; t‐test = 11.85; P < 0.001) and percentage of normal morphological forms (df = 1001; t‐test = 7.18; P < 0.001), while no differences were reported in terms of semen volume or pH.

According to World Health Organization thresholds for normal semen, 364 (50.8%) men in group A and 192 (66.8%) men in group B were subfertile (odds ratio = 1.95; 95% confidence interval 1.46–2.60; P < 0.001).

No correlation between HPV genotype, mucosal IgA type and semen variables was found.

Conclusion

In a population of prostatitis‐related symptoms attributable to Ct infection, co‐infection with HPV has a significant role in decreasing male fertility, in particular with regard to sperm motility and morphology.
A randomized, double‐blind, crossover, placebo‐controlled trial of 6 weeks benfotiamine treatment on postprandial vascular function and variables of autonomic nerve function in Type 2 diabetes
Authors: Stirban A. , Pop A. , Tschoepe D.
Published: May 2013

Aims

In a pilot study we suggested that benfotiamine, a thiamine prodrug, prevents postprandial endothelial dysfunction in people with Type 2 diabetes mellitus. The aim of this study was to test these effects in a larger population.

Methods

In a double‐blind, placebo‐controlled, randomized, crossover study, 31 people with Type 2 diabetes received 900 mg/day benfotiamine or a placebo for 6 weeks (with a washout period of 6 weeks between). At the end of each treatment period, macrovascular and microvascular function were assessed, together with variables of autonomic nervous function in a fasting state, as well as 2, 4 and 6 h following a heated, mixed test meal.

Results

Participants had an impaired baseline flow‐mediated dilatation (2.63 ± 2.49%). Compared with the fasting state, neither variable changed postprandially following the placebo treatment. The 6 weeks' treatment with high doses of benfotiamine did not alter this pattern, either in the fasting state or postprandially. Among a subgroup of patients with the highest flow‐mediated dilatation, following placebo treatment there was a significant postprandial flow‐mediated dilatation decrease, while this effect was attenuated by benfotiamine pretreatment.

Conclusions

In people with Type 2 diabetes and markedly impaired fasting flow‐mediated dilatation, a mixed test meal does not further deteriorate flow‐mediated dilatation or variables of microvascular or autonomic nervous function. Because no significant deterioration of postprandial flow‐mediated dilatation, microvascular or autonomic nervous function tests occurred after placebo treatment, a prevention of the postprandial deterioration of these variables with benfotiamine was not feasible.
Differential androgen receptor expression andDNAmethylation state in striatum song nucleus Area X between wild and domesticated songbird strains
Authors: Wada Kazuhiro , Hayase Shin , Imai Raimu , Mori Chihiro , Kobayashi Masahiko , Liu Wan‐chun , Takahasi Miki , Okanoya Kazuo
Published: May 2013

In songbirds, a specialized neural system, the song system, is responsible for acquisition and expression of species‐specific vocal patterns. We report evidence for differential gene expression between wild and domesticated strains having different learned vocal phenotypes. A domesticated strain of the wild white‐rumped munia, the Bengalese finch, has a distinct song pattern with a more complicated syntax than the wild strain. We identified differentialandrogen receptor(AR) expression in basal ganglia nucleus Area XGABAergic neurons between the two strains, and within different domesticated populations. Differences inARexpression were correlated with the mean coefficient of variation of the inter‐syllable duration in the two strains. DifferentialARexpression in Area X was observed before the initiation of singing, suggesting that inherited and/or early developmental mechanisms may affect expression within and between strains. However, there were no distinct differences in regions upstream of theARstart codon among all the birds in the study. In contrast, an epigenetic modification,DNAmethylation state in regions upstream ofARin Area X, was observed to differ between strains and within domesticated populations. These results provide insight into the molecular basis of behavioral evolution through the regulation of hormone‐related genes and demonstrate the potential association between epigenetic modifications and behavioral phenotype regulation.
Role of CPI‐17 in restoring skin homoeostasis in cutaneous field of cancerization: effects of topical application of a film‐forming medical device containing photolyase and UV filters
Authors: Puig‐Butillé Joan Anton , Malvehy Josep , Potrony Miriam , Trullas Carles , Garcia‐García Francisco , Dopazo Joaquin , Puig Susana
Published: May 2013

Cutaneous field of cancerization (CFC) is caused in part by the carcinogenic effect of the cyclobutane pyrimidine dimers CPD and 6‐4 photoproducts (6‐4PPs). Photoreactivation is carried out by photolyases which specifically recognize and repair both photoproducts. The study evaluates the molecular effects of topical application of a film‐forming medical device containing photolyase and UV filters on the precancerous field in AK from seven patients. Skin improvement after treatment was confirmed in all patients by histopathological and molecular assessment. A gene set analysis showed that skin recovery was associated with biological processes involved in tissue homoeostasis and cell maintenance. The CFC response was associated with over‐expression of the CPI‐17 gene, and a dependence on the initial expression level was observed (P = 0.001). Low CPI‐17 levels were directly associated with pro‐inflammatory genes such as TNF (P = 0.012) and IL‐1B (P = 0.07). Our results suggest a role for CPI‐17 in restoring skin homoeostasis in CFC lesions.
Inhibition of frozen storage‐induced oxidation and structural changes in myofibril of common carp (Cyprinus carpio) surimi by cryoprotectant and hydrolysed whey protein addition
Authors: Li Yanqing , Kong Baohua , Xia Xiufang , Liu Qian , Li Peijun
Published: May 2013

The objective of the present study was to evaluate the efficacy of combined cryoprotectants (sucrose + sorbitol) and whey protein isolate (WPI) hydrolysates to inhibit protein oxidation and quality loss in common carp (Cyprinus carpio) surimi during frozen storage at −25 °C. With increasing storage time, the carbonyl content of myofibrillar proteins increased from 4.02 nmolmg‐1 protein (0 day) to 7.25, 6.31, 5.26 and 4.83 nmol mg−1 protein (180 days; P < 0.05) for the control and samples with cryoprotectants, with cryoprotectants + WPI hydrolysates and with cryoprotectants + propyl gallate, respectively; protein surface hydrophobicity and turbidity increased in a similar trend, while sulfhydryl content, Ca‐ATPase activity, protein solubility and protein thermal stability decreased (P < 0.05). These results suggest that treatments with combined cryoprotectants and antioxidative WPI hydrolysates offer an effective approach to reducing the extent of protein oxidation in common carp surimi, thereby limiting protein structural changes known to impair texture of surimi products.
In vitro and in vivo studies with tetra‐hydro‐jasmonic acid (LR2412) reveal its potential to correct signs of skin ageing
Authors: Tran C. , Michelet J.F. , Simonetti L. , Fiat F. , Garrigues A. , Potter A. , Segot E. , Watson R.E.B. , Griffiths C.E.M. , de Lacharrière O.
Published: May 2013

Background

LR2412, a synthetic derivative of jasmonic acid, improved the reconstruction and homeostasis of our organotypic skin models.

Objectives

The need for efficient ‘anti‐ageing’ treatments, in particular for the management of photoaged skin, prompted us to investigate this new ingredient for its potential to correct signs of skin ageing in vitro and in vivo and to identify its mode of action.

Results

In vitro, penetration of LR2412 was evaluated using a Franz diffusion cell on excised human skin. Its exfoliating properties and interactions with the stratum corneum were studied using electron microscopy and X‐ray diffraction. Experiments were performed on a human reconstructed skin model. In vivo, the effects of LR2412 on steroid‐induced skin atrophy, a clinical skin ageing model, were assessed vs. vehicle. A patch test study evaluated its effect on deposition of fibrillin‐rich microfibrils in the papillary dermis in clinically photoaged volunteers. A clinical study on the appearance of crow's feet wrinkles was conducted over 3 months of daily application. Penetration studies revealed that LR2412 reaches viable epidermis and superficial dermis, which are skin targets of anti‐ageing actives. Within the upper layers of the stratum corneum LR2412 accelerates desquamation and improves the mechanical properties. At the dermal–epidermal junction of reconstructed skin, collagen IV, laminin‐5 and fibrillin were stimulated. In vivo, LR2412 reversed steroid‐induced atrophy. The patch test model confirms the deposition of fibrillin‐rich microfibrils, then an in use clinical study revealed that it reduced facial wrinkles.

Conclusions

The in vitro and in vivo data demonstrate that based on its multiple interactions within human skin, LR2412 has potential to partially correct the signs of ageing in intrinsically and photoaged skin.
“Living With a Ball and Chain”: The Experience of Stroke for Individuals and Their Caregivers in Rural Appalachian Kentucky
Authors: Danzl Megan M. , Hunter Elizabeth G. , Campbell Sarah , Sylvia Violet , Kuperstein Janice , Maddy Katherine , Harrison Anne
Published: May 2013

Purpose

Individuals in rural Appalachian Kentucky face health disparities and are at increased risk for negative health outcomes and poor quality of life secondary to stroke. The purpose of this study is to describe the experience of stroke for survivors and their caregivers in this region. A description of their experiences is paramount to developing tailored interventions and ultimately improving health care and support.

Methods

An interprofessional research team used a qualitative descriptive study design and interviewed 13 individuals with stroke and 12 caregivers, representing 10 rural Appalachian Kentucky counties. The transcripts were analyzed using qualitative content analysis.

Findings

A descriptive summary of the participants’ experience of stroke is presented within the following structure: (1) Stroke onset, (2) Transition through the health care continuum (including acute care, inpatient rehabilitation, and community‐based rehabilitation), and (3) Reintegration into life and rural communities.

Conclusions

The findings provide insight for rural health care providers and community leaders to begin to understand the experience of stroke in terms of stroke onset, transition through the health care continuum, return to home, and community reintegration. An understanding of these experiences may lead to discussions of how to improve service provision, facilitate reintegration, support positive health outcomes, and improve quality of life for stroke survivors and their caregivers. The findings also indicate areas in need of future research including investigation of the effects of support groups, local health navigators to improve access to information and services, involvement of faith communities, proactive screening for management of mental health needs, and caregiver respite services.
The glutathione transferase of Nicotiana benthamiana NbGSTU4 plays a role in regulating the early replication of Bamboo mosaic virus
Authors: Chen I‐Hsuan , Chiu Meng‐Hsuen , Cheng Shun‐Fang , Hsu Yau‐Heiu , Tsai Ching‐Hsiu
Published: May 2013

Bamboo mosaic virus (BaMV) is a single‐stranded positive‐sense RNA virus. One of the plant glutathione S‐transferase (GST) genes, NbGSTU4, responds as an upregulated gene in Nicotiana benthamiana post BaMV infection.

In order to identify the role of NbGSTU4 in BaMV infection, the expression of NbGSTU4 was knocked down using a virus‐induced gene silencing technique or was transiently expressed in N. benthamiana in BaMV inoculation.

The results show a significant decrease in BaMV RNA accumulation when the expression level of NbGSTU4 is reduced; whereas the viral RNA accumulation increases when NbGSTU4 is transiently expressed. Furthermore, this study identified that the involvement of NbGSTU4 in viral RNA accumulation occurs by its participation in the viral early replication step. The findings show that the NbGSTU4 protein expressed from Escherichia coli can interact with the 3′ untranslated region (UTR) of the BaMV RNA in vitro in the presence of glutathione (GSH). The addition of GSH in the in vitro replication assay shows an enhancement of minus‐strand but not plus‐strand RNA synthesis.

The results suggest that the plant GST protein plays a role in binding viral RNA and delivering GSH to the replication complex to create a reduced condition for BaMV minus‐strand RNA synthesis.
Rivaroxaban: a novel oral anticoagulant for the prevention and treatment of several thrombosis‐mediated conditions
Authors: Sarich Troy C. , Peters Gary , Berkowitz Scott D. , Misselwitz Frank , Nessel Christopher C. , Burton Paul , Cook‐Bruns Nancy , Lensing Anthonie W.A. , Haskell Lloyd , Perzborn Elisabeth , Kubitza Dagmar , Moore Kenneth T. , Jalota Sanjay , Weber Juergen , Pan Guohua , Sun Xiang , Westermeier Torsten , Nadel Andrea , Oppenheimer Leonard , DiBattiste Peter M.
Published: May 2013

The development of rivaroxaban (XARELTO®) is an important new medical advance in the field of oral anticoagulation. Thrombosis‐mediated conditions constitute a major burden for patients, healthcare systems, and society. For more than 60 years, the prevention and treatment of these conditions have been dominated by oral vitamin K antagonists (such as warfarin) and the injectable heparins. Thrombosis can lead to several conditions, including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, and/or death. Prevention and treatment of thrombosis with an effective, convenient‐to‐use oral anticoagulant with a favorable safety profile is critical, especially in an aging society in which the risk of thrombosis, and the potential for bleeding complications, is increasing. Rivaroxaban acts to prevent and treat thrombosis by potently inhibiting coagulation Factor Xa in the blood. Factor Xa converts prothrombin to thrombin, which initiates the formation of blood clots by converting fibrinogen to clot‐forming fibrin and leads to platelet activation. After a large and novel clinical development program in over 75,000 patients to date, rivaroxaban has received approval for multiple indications in the United States, European Union, and other countries worldwide to prevent and treat several thrombosis‐mediated conditions. This review will highlight some of the unique aspects of the rivaroxaban development program.
Can Animals Envision the Future? Scientists Spar Over New Data
Authors: Balter Michael
Published: May 2013

Two researchers who coined the phrase mental time travel, using past memories to construct visions of the future that may never come true, insisted that animals couldn't do it. But now, one of them is changing his tune.
SPIN SQUEEZING DYNAMICS IN TWO-COMPONENT BOSE–EINSTEIN CONDENSATES
Authors: LI SONG-SONG , LAI XIAO-BING
Published: May 2013

We investigate spin squeezing dynamics in a two-component Bose–Einstein condensate (BEC) in the presence of the nonlinear interatomic interaction, interspecies interaction and Josephson-like tunneling interaction. In particular, we are interesting in the dependence of spin squeezing parameter on the interspecies interaction and the numbers of atom. By adopting the two-mode approximation and the rotating wave approximation, we succeed in obtaining analytical solutions for the optimally squeezed angle and spin squeezing parameter. It is shown that the stronger interspecies interaction induces faster spin squeezing and the more atoms or the larger population imbalance induces stronger squeezing; while the Josephson-like tunneling gives vanishing contribution to spin squeezing.
An annales school-based serious game creation framework for taiwanese indigenous cultural heritage
Authors: Huang Chih-Hong , Huang Yi-Ting
Published: May 2013

This study utilizes the characteristics of the Annales School, including their emphasis on total history and space and time integration, their focus on the economic world, and their use of structural analysis to develop a creation framework for a serious video game related to the cultural and life history of Taiwan's indigenous people. Game development comprised the tiers of data, logic, and presentation. During the data tier, we used taxonomy to extract the cultural components of Taiwan's Atayal tribe. During the logic tier, we employed an analysis of cultural characteristics and comparisons of historical education goals to confirm the game's framework and storytelling engine, selecting a construction management simulation game genre to present tribal life and economic operations. Finally, in the presentation tier, we converted cultural components into elements in the game's user interface.

The game evaluation results showed that “Papakwaqa” (our serious game) had positive benefits for enhancing schoolchildren's learning motivation and performance regarding indigenous life and history. Our research verified that integrating the cross-disciplinary methods of anthropologists, history teachers, tribal elders, and game designers to establish instructional goals and design foci for game development and to create a cultural heritage serious game-creation framework warrants further study and effort.
Computer security needs refocus, and be nice about it
Authors: Hong Jason , Robertson Judy
Published: May 2013

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Jason Hong wonders whether computer security is missing the mark, while Judy Robertson supports refusing to tolerate discourtesy.
Nanocomposite Coatings Codeposited with Nanoparticles Using Aerosol‐Assisted Chemical Vapour Deposition
Authors: Hou Xianghui , Choy Kwang-Leong , Brun Nathalie , Serín Virginie
Published: May 2013

Incorporating nanoscale materials into suitable matrices is an effective route to produce nanocomposites with unique properties for practical applications. Due to the flexibility in precursor atomization and delivery, aerosol‐assisted chemical vapour deposition (AACVD) process is a promising way to synthesize desired nanocomposite coatings incorporating with preformed nanoscale materials. The presence of nanoscale materials in AACVD process would significantly influence deposition mechanism and thus affect microstructure and properties of the nanocomposites. In the present work, inorganic fullerene‐like tungsten disulfide (IF‐WS2) has been codeposited with Cr2O3 coatings using AACVD. In order to understand the codeposition process for the nanocomposite coatings, chemical reactions of the precursor and the deposition mechanism have been studied. The correlation between microstructure of the nanocomposite coatings and the codeposition mechanism in the AACVD process has been investigated. The heterogeneous reaction on the surface of IF‐WS2 nanoparticles, before reaching the substrate surface, is the key feature of the codeposition in the AACVD process. The agglomeration of nanoparticles in the nanocomposite coatings is also discussed.
Inhibitory Effects of Hwangryunhaedok-Tang in 3T3-L1 Adipogenesis by Regulation of Raf/MEK1/ERK1/2 Pathway and PDK1/Akt Phosphorylation
Authors: Kwak Dong Hoon , Lee Ji-Hye , Kim Dong-Gun , Kim Taesoo , Lee Kwang Jin , Ma Jin Yeul
Published: May 2013

Hwangryunhaedok-tang (HRT) has been long used as traditional medicine in Asia. However, inhibitory role of HRT is unclear in early stage of 3T3-L1 adipocyte differentiation related to signaling. In the present study, we investigated the inhibitory effects of HRT on upstream signaling of peroxisome proliferation-activity receptor-γ(PPAR-γ) and CCAAT/enhancer binding protein-β(C/EBP-β) expression in differentiation of 3T3-L1 preadipocytes. We found that HRT significantly inhibited the adipocyte differentiation by downregulating several adipocyte-specific transcription factors including PPAR-γ, C/EBP-α, and C/EBP-βin 3T3-L1 preadipocytes. Furthermore, we observed that HRT markedly inhibited the differentiation media-mediated phosphorylation of Raf/extracellular mitogen-activated protein kinase 1 (MEK1)/signal-regulated protein kinase 1/2 (ERK1/2) and phosphorylation of phosphoinositide-dependent kinase 1 (PDK1)/Akt. These results indicate that anti-adipogenesis mechanism involves the downregulation of the major transcription factors of adipogenesis including PPAR-γand C/EBP-αthrough inhibition of Raf/MEK1/ERK1/2 phosphorylation and PDK1/Akt phosphorylation by HRT. Furthermore, high performance liquid chromatography (HPLC) analysis showed HRT contains active antiobesity constituents such as palmatine, berberine, geniposide, baicalin, baicalein, and wogonin. Taken together, this study suggested that anti-adipogenesis effects of HRT were accounted by downregulation of Raf/MEK1/ERK1/2 pathway and PDK1/Akt pathway during 3T3-L1 adipocyte differentiation.
Guidance of Autonomous Amphibious Vehicles for Flood Rescue Support
Authors: Ragi Shankarachary , Tan ChingSeong , Chong Edwin K. P.
Published: May 2013

We develop a path-planning algorithm to guide autonomous amphibious vehicles (AAVs) for flood rescue support missions. Specifically, we develop an algorithm to control multiple AAVs to reach/rescue multiple victims (also called targets) in a flood scenario in 2D, where the flood water flows across the scene and the targets move (drifted by the flood water) along the flood stream. A target is said to be rescued if an AAV lies within a circular region of a certain radius around the target. The goal is to control the AAVs such that each target gets rescued while optimizing a certain performance objective. The algorithm design is based on the theory ofpartially observable Markov decision process(POMDP). In practice, POMDP problems are hard to solve exactly, so we use an approximation method callednominal belief-state optimization(NBO). We compare the performance of the NBO approach with a greedy approach.
Preparation and Physicochemical Properties of Functionalized Silica/Octamethacryl‐Silsesquioxane Hybrid Systems
Authors: Szwarc-Rzepka Karolina , Ciesielczyk Filip , Jesionowski Teofil
Published: May 2013

Alkoxysilane‐grafted silica/polyhedral oligomeric silsesquioxane with methacryl substituents (SiO2/silane/POSS) hybrid material was synthesized according to hydrolyzation and condensation reactions in the so‐called “bifunctionalization process.” It is a new attractive system because of its physicochemical, especially thermal and structural, properties. This innovative method of preparation as well as specific physicochemical and useful properties determine the potential applications of such products in many industries. The structure and physicochemical parameters of obtained hybrid systems were characterized using infrared spectroscopy (FTIR), 13C and 29Si solid‐state nuclear magnetic resonance (CP MAS NMR), and thermal analysis. The mechanism of bifunctionalization reaction was proposed. The chemical immobilization of silane coupling agent and Methacryl POSS onto silica support surface was noted during the study. Those changes caused a significant increase in the hydrophobic character of fillers obtained. Moreover, changes in thermal stability of SiO2/silane/POSS hybrid systems in comparison to pure POSS modifier were also observed.
Evolution Procedure of Multiple Rock Cracks under Seepage Pressure
Authors: Liu Taoying , Cao Ping , Lin Hang
Published: May 2013

In practical geotechnical engineering, most of rock masses with multiple cracks exist in water environment. Under such circumstance, these adjacent cracks could interact with each other. Moreover, the seepage pressure, produced by the high water pressure, can change cracks’ status and have an impact on the stress state of fragile rocks. According to the theory of fracture mechanics, this paper discusses the law of crack initiation and the evolution law of stress intensity factor at the tip of a wing crack caused by compression-shear stress and seepage pressure. Subsequently, considering the interaction of the wing cracks and the additional stress caused by rock bridge damage, this paper proposes the intensity factor evolution equation under the combined action of compression-shear stress and seepage pressure. In addition, this paper analyzes the propagation of cracks under different seepage pressure which reveals that the existence of seepage pressure facilitates the wing crack’s growth. The result indicates that the high seepage pressure converts wing crack growth from stable form to unstable form. Meanwhile, based on the criterion and mechanism for crack initiation and propagation, this paper puts forward the mechanical model for different fracture transfixion failure modes of the crag bridge under the combined action of seepage pressure and compression-shear stress. At the last part, this paper, through investigating the flexibility tensor of the rock mass’s initial damage and its damage evolution in terms of jointed rock mass's damage mechanics, deduces the damage evolution equation for the rock mass with multiple cracks under the combined action of compression-shear stress and seepage pressure. The achievement of this investigation provides a reliable theoretical principle for quantitative research of the fractured rock mass failure under seepage pressure.
ATR-Dependent Phosphorylation of FANCM at Serine 1045 Is Essential for FANCM Functions
Authors: Singh Thiyam Ramsing , Ali Abdullah Mahmood , Paramasivam Manikandan , Pradhan Arun , Wahengbam Kebola , Seidman Michael M. , Meetei Amom Ruhikanta
Published: May 2013

Fanconi anemia (FA) is a genome instability syndrome that has been associated with both cancer predisposition and bone marrow failure. FA proteins are involved in cellular response to replication stress in which they coordinate DNA repair with DNA replication and cell-cycle progression. One regulator of the replication stress response is the ATP-dependent DNA translocase FANCM, which we have shown to be hyperphosphorylated in response to various genotoxic agents. However, the significance of this phosphorylation remained unclear. Here, we show that genotoxic stress–induced FANCM phosphorylation is ATR-dependent and that this modification is highly significant for the cellular response to replication stress. We identified serine (S1045) residue of FANCM that is phosphorylated in response to genotoxic stress and this effect is ATR-dependent. We show that S1045 is required for FANCM functions including its role in FA pathway integrity, recruiting FANCM to the site of interstrand cross links, preventing the cells from entering mitosis prematurely, and efficient activation of the CHK1 and G2–M checkpoints. Overall, our data suggest that an ATR-FANCM feedback loop is present in the FA and replication stress response pathways and that it is required for both efficient ATR/CHK1 checkpoint activation and FANCM function. Cancer Res; 73(14); 4300–10. ©2013 AACR.
Microtubule-Associated Histone Deacetylase 6 Supports the Calcium Store Sensor STIM1 in Mediating Malignant Cell Behaviors
Authors: Chen Ying-Ting , Chen Yih-Fung , Chiu Wen-Tai , Liu Kuan-Yu , Liu Yu-Lin , Chang Jang-Yang , Chang Hsien-Chang , Shen Meng-Ru
Published: May 2013

Stromal-interaction molecule 1 (STIM1) is an endoplasmic reticulum Ca2+ storage sensor that promotes cell growth, migration, and angiogenesis in breast and cervical cancers. Here, we report that the microtubule-associated histone deacetylase 6 (HDAC6) differentially regulates activation of STIM1-mediated store-operated Ca2+ entry (SOCE) between cervical cancer cells and normal cervical epithelial cells. Confocal microscopy of living cells indicated that microtubule integrity was necessary for STIM1 trafficking to the plasma membrane and interaction with Orai1, an essential pore subunit of SOCE. Cancer cells overexpressed both STIM1 and Orai1 compared with normal cervical epithelial cells. HDAC6 upregulation in cancer cells was accompanied by hypoacetylated α-tubulin. Tubastatin-A, a specific HDAC6 inhibitor, inhibited STIM1 translocation to plasma membrane and blocked SOCE activation in cancer cells but not normal epithelial cells. Genetic or pharmacologic inhibition of HDAC6 blocked STIM1 membrane trafficking and downstream Ca2+ influx, as evidenced by total internal reflection fluorescent images and intracellular Ca2+ determination. In contrast, HDAC6 inhibition did not affect interactions between STIM1 and the microtubule plus end-binding protein EB1. Analysis of surgical specimens confirmed that most cervical cancer tissues overexpressed STIM1 and Orai1, accompanied by hypoacetylated α-tubulin. Together, our results identify HDAC6 as a candidate target to disrupt STIM1-mediated SOCE as a general strategy to block malignant cell behavior. Cancer Res; 73(14); 4500–9. ©2013 AACR.
Lactate Dehydrogenase B: A Metabolic Marker of Response to Neoadjuvant Chemotherapy in Breast Cancer
Authors: Dennison Jennifer B. , Molina Jennifer R. , Mitra Shreya , González-Angulo Ana M. , Balko Justin M. , Kuba María G. , Sanders Melinda E. , Pinto Joseph A. , Gómez Henry L. , Arteaga Carlos L. , Brown Robert E. , Mills Gordon B.
Published: May 2013

Purpose: Although breast cancers are known to be molecularly heterogeneous, their metabolic phenotype is less well-understood and may predict response to chemotherapy. This study aimed to evaluate metabolic genes as individual predictive biomarkers in breast cancer.

Experimental Design: mRNA microarray data from breast cancer cell lines were used to identify bimodal genes—those with highest potential for robust high/low classification in clinical assays. Metabolic function was evaluated in vitro for the highest scoring metabolic gene, lactate dehydrogenase B (LDHB). Its expression was associated with neoadjuvant chemotherapy response and relapse within clinical and PAM50-derived subtypes.

Results: LDHB was highly expressed in cell lines with glycolytic, basal-like phenotypes. Stable knockdown of LDHB in cell lines reduced glycolytic dependence, linking LDHB expression directly to metabolic function. Using patient datasets, LDHB was highly expressed in basal-like cancers and could predict basal-like subtype within clinical groups [OR = 21 for hormone receptor (HR)-positive/HER2-negative; OR = 10 for triple-negative]. Furthermore, high LDHB predicted pathologic complete response (pCR) to neoadjuvant chemotherapy for both HR-positive/HER2-negative (OR = 4.1, P < 0.001) and triple-negative (OR = 3.0, P = 0.003) cancers. For triple-negative tumors without pCR, high LDHB posttreatment also identified proliferative tumors with increased risk of recurrence (HR = 2.2, P = 0.006).

Conclusions: Expression of LDHB predicted response to neoadjuvant chemotherapy within clinical subtypes independently of standard prognostic markers and PAM50 subtyping. These observations support prospective clinical evaluation of LDHB as a predictive marker of response for patients with breast cancer receiving neoadjuvant chemotherapy. Clin Cancer Res; 19(13); 3703–13. ©2013 AACR.
NF-κB2/p52 Induces Resistance to Enzalutamide in Prostate Cancer: Role of Androgen Receptor and Its Variants
Authors: Nadiminty Nagalakshmi , Tummala Ramakumar , Liu Chengfei , Yang Joy , Lou Wei , Evans Christopher P. , Gao Allen C.
Published: May 2013

Resistance of prostate cancer cells to the next-generation antiandrogen enzalutamide may be mediated by a multitude of survival signaling pathways. In this study, we tested whether increased expression of NF-κB2/p52 induces prostate cancer cell resistance to enzalutamide and whether this response is mediated by aberrant androgen receptor (AR) activation and AR splice variant production. LNCaP cells stably expressing NF-κB2/p52 exhibited higher survival rates than controls when treated with enzalutamide. C4-2B and CWR22Rv1 cells chronically treated with enzalutamide were found to express higher levels of NF-κB2/p52. Downregulation of NF-κB2/p52 in CWR22Rv1 cells chronically treated with enzalutamide rendered them more sensitive to cell growth inhibition by enzalutamide. Analysis of the expression levels of AR splice variants by quantitative reverse transcription PCR and Western blotting revealed that LNCaP cells expressing p52 exhibit higher expression of AR splice variants. Downregulation of expression of NF-κB2/p52 in VCaP and CWR22Rv1 cells by short hairpin RNA abolished expression of splice variants. Downregulation of expression of either full-length AR or the splice variant AR-V7 led to an increase in sensitivity of prostate cancer cells to enzalutamide. These results collectively demonstrate that resistance to enzalutamide may be mediated by NF-κB2/p52 via activation of AR and its splice variants. Mol Cancer Ther; 12(8); 1629–37. ©2013 AACR.