bluuebunny/crossref_metadata_2025 huggingface dataset:
An Overview of the IBM Power 775 Supercomputer Water Cooling System
Authors: Ellsworth Michael J. , Goth Gary F. , Zoodsma Randy J. , Arvelo Amilcar , Campbell Levi A. , Anderl William J.
Published: March 2013

In 2008 IBM reintroduced water cooling technology into its high performance computing platform, the Power 575 Supercomputing node/system. Water cooled cold plates were used to cool the processor modules which represented about half of the total system (rack) heat load. An air-to-liquid heat exchanger was also mounted in the rear door of the rack to remove a significant fraction of the other half of the rack heat load: the heat load to air. The next generation of this platform, the Power 775 Supercomputing node/system, is a monumental leap forward in computing performance and energy efficiency. The computer node and system were designed from the start with water cooling in mind. The result, a system with greater than 96% of its heat load conducted directly to water, is a system that, together with a rear door heat exchanger, removes 100% of its heat load to water with no requirement for room air conditioning. In addition to the processor, the memory, power conversion, and I/O electronics conduct their heat to water. Included within the framework of the system is a disk storage unit (disc enclosure) containing an interboard air-to-water heat exchanger. This paper will give an overview of the water cooling system featuring the water conditioning unit and rack manifolds. Advances in technology over this system’s predecessor will be highlighted. An overview of the cooling assemblies within the server drawer (i.e., central electronics complex,) the disc enclosure, and the centralized (bulk) power conversion system will also be given. Furthermore, techniques to enhance performance and energy efficiency will also be described.
Influences of Solder Wetting on Self-Alignment Accuracy and Modeling for Optoelectronic Devices Assembly
Authors: Kong Ming , Jeon Sungeun , Hwang Chiwon , Lee Y. C.
Published: March 2013

Solder self-alignment is an important phenomenon enabling cost-effective optoelectronics assembly. In this study, the wetting of Sn-rich solder to under bump metallization (UBM) pads is identified as a critical factor affecting self-alignment accuracy. Incomplete wetting of solder to the metallization pads is responsible for chip-to-substrate misalignment larger than 1 μm, while fabrication tolerances, such as solder volume variation and pad diameter deviation, only account for misalignments in the submicron range. To quantitatively investigate the effect of incomplete wetting on self-alignment accuracy, a three-dimensional (3D) model based on a force optimization method was developed. With the input parameters of incomplete solder metallurgical wetting area, position and diameter of metallization pad, volume of individual solder bumps, coefficient of solder surface tension, mass of the chip, external forces acting on the chip, and initial pick-and-place position of the chip before assembly, the model predicts the assembled position of the chip in terms of the misalignments in the X-Y plane and the rotation angle along the Z axis. The model further confirmed that incomplete wetting of solder is the most critical modulator among the undesirable factors affecting solder self-alignment accuracy.
Accelerated Temperature and Voltage Stress Tests of Embedded Planar Capacitors With Epoxy–BaTiO3 Composite Dielectric
Authors: Alam Mohammed A. , Azarian Michael H. , Osterman Michael , Pecht Michael
Published: March 2013

Accelerated temperature and voltage stress tests were conducted on embedded planar capacitors with epoxy–BaTiO3 composite dielectric. The failure modes were found to be a sudden increase in the leakage current across the capacitor dielectric and a gradual decrease in the capacitance. The failure mechanisms associated with these failure modes were investigated by performing data analysis and failure analysis. The time-to-failure as a result of a sudden increase in the leakage current was modeled using the Prokopowicz equation. The values of constants of the Prokopowicz equation, n and Ea, were determined for the epoxy–BaTiO3 composite. The degradation in capacitance was modeled by performing regression analysis. The time-to-failure and degradation models can be used for the qualification tests of embedded planar capacitors, for the development of new composite dielectric materials, and to improve the manufacturing processes of these capacitors.
Evidence for Two Distinct Populations of Type Ia Supernovae
Authors: Wang Xiaofeng , Wang Lifan , Filippenko Alexei V. , Zhang Tianmeng , Zhao Xulin
Published: March 2013

Fast and Young

Type Ia supernovae are thought to result from the thermonuclear explosion of a white dwarf star accreting material from a companion star in a binary system. Their adoption as cosmic yardsticks has led to the discovery of the accelerated expansion of the universe.

Wang
et al.

(p.
170
, published online 7 March) show that supernovae with higher expansion velocities are located in the central, brighter regions of their host galaxies and are found in larger, more luminous galaxies, suggesting that they are associated with younger stellar populations.
Draft Genome Sequence of the 2-Chloro-4-Nitrophenol-Degrading Bacterium
Arthrobacter
sp. Strain SJCon
Authors: Vikram Surendra , Kumar Shailesh , Vaidya Bhumika , Pinnaka Anil Kumar , Raghava Gajendra Pal Singh
Published: March 2013

We report the 4.39-Mb draft genome sequence of the 2-chloro-4-nitrophenol-degrading bacterium
Arthrobacter
sp. strain SJCon, isolated from a pesticide-contaminated site. The draft genome sequence of strain SJCon will be helpful in studying the genetic pathways involved in the degradation of several aromatic compounds.
Whole-Genome Sequencing of Micrococcus luteus Strain Modasa, of Indian Origin
Authors: Ghosh A. , Chaudhary S. A. , Apurva S. R. , Tiwari T. , Gupta S. , Singh A. K. , Katudia K. H. , Patel M. P. , Chikara S. K.
Published: March 2013

The hydrocarbon-degrading bacterium
Micrococcus luteus
strain Modasa was isolated from contaminated soil from Modasa, North Gujarat, India. Whole-genome sequencing and analysis provide an insight into the potentially important genes responsible for bioremediation.
Complete Genome Sequence of Dengue Virus Serotype 3 from Guangzhou, China
Authors: Bai Zhijun , Liu Li-Cheng , Jiang Li-Yun , Liu Qi , Cao Yi-Min , Xu Yang , Jing Qin-long , Luo Lei , Yang Zhi-Cong , Jiang Yong-Qiang , Chen Weijun , Di Biao
Published: March 2013

In 2009, dengue virus serotype 3 (DENV-3) was first detected in Guangzhou, China. In this study, we identified another isolated strain belonging to genotype II. Phylogenetic analysis shows that the GZ/10476/2012 strain has a close relationship with the DENV-3 genotype II from Southeast Asian strains.
A rare case of concurrent multichamber thrombosis complicated by cardioembolic stroke in a reversible postpartum thyrotoxic cardiomyopathy
Authors: Parisi Cristian , Canali Emanuele , Proietti Fabrizio
Published: March 2013

We describe a rare case of cardiac multichamber thrombosis in a young woman admitted with heart failure and atrial fibrillation, who was later found to have reversible postpartum thyrotoxic cardiomyopathy. A transoesophageal echocardiogram demonstrated a patent foramen ovalis with an over-riding thrombus. The clinical scenario was complicated by a cardioembolic stroke upon spontaneous restoration of sinus rhythm.
Central giant cell granuloma of the maxilla
Authors: Gupta Manish , Gupta Monica , Singh Sunder , Kaur Rupinder
Published: March 2013

Central giant cell granuloma (CGCG), formerly called giant cell reparative granuloma, is a non-neoplastic proliferative lesion of an unknown aetiology. It occurs most commonly in the mandible. The case reported here resembled a wide variety of conditions that led to a misdiagnosis both on clinical and radiographic examinations but was histopathologically diagnosed as CGCG. We managed this case by endoscopic excision and curettage via nasal route without producing external scar and avoiding damage to the un-erupted tooth.
Self-rated health and type 2 diabetes risk in the European Prospective Investigation into Cancer and Nutrition-InterAct study: a case-cohort study
Authors: Wennberg Patrik , Rolandsson Olov , van der A Daphne L , Spijkerman Annemieke M W , Kaaks Rudolf , Boeing Heiner , Feller Silke , Bergmann Manuela M , Langenberg Claudia , Sharp Stephen J , Forouhi Nita , Riboli Elio , Wareham Nicholas
Published: March 2013

Objectives

To investigate the association between self-rated health and risk of type 2 diabetes and whether the strength of this association is consistent across five European centres.

Design

Population-based prospective case-cohort study.

Setting

Enrolment took place between 1992 and 2000 in five European centres (Bilthoven, Cambridge, Heidelberg, Potsdam and Umeå).

Participants

Self-rated health was assessed by a baseline questionnaire in 3399 incident type 2 diabetic case participants and a centre-stratified subcohort of 4619 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study which was drawn from a total cohort of 340 234 participants in the EPIC.

Primary outcome measure

Prentice-weighted Cox regression was used to estimate centre-specific HRs and 95% CIs for incident type 2 diabetes controlling for age, sex, centre, education, body mass index (BMI), smoking, alcohol consumption, energy intake, physical activity and hypertension. The centre-specific HRs were pooled across centres by random effects meta-analysis.

Results

Low self-rated health was associated with a higher hazard of type 2 diabetes after adjusting for age and sex (pooled HR 1.67, 95% CI 1.48 to 1.88). After additional adjustment for health-related variables including BMI, the association was attenuated but remained statistically significant (pooled HR 1.29, 95% CI 1.09 to 1.53). I2index for heterogeneity across centres was 13.3% (p=0.33).

Conclusions

Low self-rated health was associated with a higher risk of type 2 diabetes. The association could be only partly explained by other health-related variables, of which obesity was the strongest. We found no indication of heterogeneity in the association between self-rated health and type 2 diabetes mellitus across the European centres.
Quality indicators for palliative and end of life care: a review of Swedish policy documents
Authors: Lind Susanne , Adolfsson Jan , Axelsson Bertil , Fürst Carl Johan
Published: March 2013

Background

All patients with palliative and end of life care needs should be guaranteed equal and safe treatment and care, regardless of their disease or site of care. The inclusion of quality indicators in national guidelines and other guiding documents supports quality assurance and improvement in provision of care. The aim of this paper was to review existing quality indicators in national Swedish policy documents relevant to palliative and end of life care.

Methods

We reviewed existing guidelines for diseases expected to require palliative care issued by the National Board of Health and Welfare, existing regional clinical practice guidelines and the annual report of the Swedish Register of Palliative Care (SRPC) up until 2010.

Results

We found 11 quality indicators pertinent to palliative and end of life care in the guidelines for cancer diseases and ‘The care and nursing of the elderly’. The indicators included assessment and treatment of pain, communication with the patient and the family, documentation in the patient record and registration in the SRPC. In the national guidelines for cardiology, pulmonary diseases, stroke, diabetes and dementia, there were no indicators relevant for palliative or end of life care.

Conclusions

In the existing Swedish national guidelines for many different diseases, there is still a great need to define clinically relevant and feasible outcome measures of quality of palliative and end of life care.
Point-of-care testing improves accuracy of STI care in an emergency department
Authors: Huppert Jill S , Taylor Regina G , St Cyr Sarah , Hesse Elizabeth A , Reed Jennifer L
Published: March 2013

Objectives

We aimed to examine the impact of a point-of-care (POC) test on overtreatment and undertreatment of sexually transmitted infections (STIs) by comparing treatment patterns for gonorrhoea (detected with nucleic acid amplification testing (NAAT)) with trichomoniasis (detected by POC test) for young women seen in an emergency department (ED).

Methods

We reviewed the database of a quality improvement (QI) project that aims to improve follow-up care for STIs in the ED. Data included the test result and antibiotic given (if any) during visits by women age 14–21 for whom an STI test was ordered. We generated Shewhart control charts and compared overtreatment and undertreatment rates for gonorrhoea and trichomoniasis using χ2testing.

Results

Of 1877 visits over 18 months, 8.8% of women had gonorrhoea and 16.5% had trichomoniasis. Overtreatment was higher for women with gonorrhoea than trichomoniasis (54% vs 23%, p<0.001). Overtreatment for gonorrhoea decreased from 58% to 47% (p<0.01) and overtreatment for trichomoniasis decreased from 24% to 18% (p<0.01), which corresponded to improvements in patient follow-up for the QI project. Undertreatment was higher for women with gonorrhoea than trichomoniasis (29% vs 21%, p=0.03), and did not change over time.

Conclusions

A POC test improves the accuracy of STI care in an ED compared with NAAT testing. An unanticipated benefit of QI efforts to improve patient follow-up is the observed decrease in antibiotic use in the ED. Given the ability of gonorrhoea to develop antibiotic resistance, future efforts should focus on development of an accurate POC test for gonorrhoea.
A survey on pure sampling in quantum Monte Carlo methods
Authors: Rothstein Stuart M.
Published: March 2013

The most commonly employed diffusion Monte Carlo algorithm and some of its variants afford a way to sample configuration space from a so-called “mixed distribution”, the product of an input trial solution to the Schrödinger equation for the ground state and its unknown exact solution. This mixed distribution is sufficient to compute the ground state energy and other properties represented by operators that commute with the Hamiltonian. These energy-related properties are exact, save for a small bias introduced by the input trial function’s incorrect exchange nodes, the so-called “fixed-node error”. However, properties represented by operators that commute with the position operator are also of interest. When calculated by sampling from the mixed distribution, these properties are much more strongly biased by the input trial function. Our objective is to review methods that allow sampling from the desired “pure” distribution, one that is unbiased except for the exchange node error. Thereby, one accurately calculates physical properties such as the dipole and other electrical moments, electrical response properties of molecules, and particle distribution functions for clusters. We survey the results of calculations that employ pure-sampling methods through what has been published in year 2012. Our review also touches on truly exact sampling methods.
BUSINESS MODEL INNOVATION: TOWARDS AN INTEGRATED FUTURE RESEARCH AGENDA
Authors: SCHNEIDER SABRINA , SPIETH PATRICK
Published: March 2013

Motivated by the high ubiquity of the term "business models" and its increasing proliferation in terms of the transition from a measure to commercialise innovations to the subject of innovations, this paper provides a systematic review of extant academic literature on business model innovation. The particular characteristics of business model innovation are discussed and three distinct research streams addressing prerequisites, process and elements, and effects of business model innovation are identified. A tentative theoretical framework emphasising the need to distinguish between developing and innovating business models as well as to apply an entrepreneurial perspective for further research on business model innovation is proposed. An integrated research agenda emphasising the need to further enhance our understanding of the process and elements of business model innovation as well as its enablers and effects in anticipation and response to increasing environmental volatility is suggested.
Designing for health activism
Authors: Parker Andrea Grimes
Published: March 2013

Community + Culture features practitioner perspectives on designing technologies for and with communities. We highlight compelling projects and provocative points of view that speak to both community technology practice and the interaction design field as a whole.

Christopher A. Le Dantec
Neurodiversity HCI
Authors: Dalton Nick S.
Published: March 2013

In this forum we celebrate research that helps to successfully bring the benefits of computing technologies to children, older adults, people with disabilities, and other populations that are often ignored in the design of mass-marketed products.

Juan Pablo Hourcade, Editor
Polygon mesh repairing
Authors: Attene Marco , Campen Marcel , Kobbelt Leif
Published: March 2013

Nowadays, digital 3D models are in widespread and ubiquitous use, and each specific application dealing with 3D geometry has its own quality requirements that restrict the class of acceptable and supported models. This article analyzes typical defects that make a 3D model unsuitable for key application contexts, and surveys existing algorithms that process, repair, and improve its structure, geometry, and topology to make it appropriate to case-by-case requirements.

The analysis is focused on polygon meshes, which constitute by far the most common 3D object representation. In particular, this article provides a structured overview of mesh repairing techniques from the point of view of the application context. Different types of mesh defects are classified according to the upstream application that produced the mesh, whereas mesh quality requirements are grouped by representative sets of downstream applications where the mesh is to be used. The numerous mesh repair methods that have been proposed during the last two decades are analyzed and classified in terms of their capabilities, properties, and guarantees. Based on these classifications, guidelines can be derived to support the identification of repairing algorithms best-suited to bridge the compatibility gap between the quality provided by the upstream process and the quality required by the downstream applications in a given geometry processing scenario.
Virtualization
Authors: Pearce Michael , Zeadally Sherali , Hunt Ray
Published: March 2013

Although system virtualization is not a new paradigm, the way in which it is used in modern system architectures provides a powerful platform for system building, the advantages of which have only been realized in recent years, as a result of the rapid deployment of commodity hardware and software systems. In principle, virtualization involves the use of an encapsulating software layer (Hypervisor or Virtual Machine Monitor) which surrounds or underlies an operating system and provides the same inputs, outputs, and behavior that would be expected from an actual physical device. This abstraction means that an ideal Virtual Machine Monitor provides an environment to the software equivalent to the host system, but which is decoupled from the hardware state. Because a virtual machine is not dependent on the state of the physical hardware, multiple virtual machines may be installed on a single set of hardware. The decoupling of physical and logical states gives virtualization inherent security benefits. However, the design, implementation, and deployment of virtualization technology have also opened up novel threats and security issues which, while not particular to system virtualization, take on new forms in relation to it. Reverse engineering becomes easier due to introspection capabilities, as encryption keys, security algorithms, low-level protection, intrusion detection, or antidebugging measures can become more easily compromised. Furthermore, associated technologies such as virtual routing and networking can create challenging issues for security, intrusion control, and associated forensic processes. We explain the security considerations and some associated methodologies by which security breaches can occur, and offer recommendations for how virtualized environments can best be protected. Finally, we offer a set of generalized recommendations that can be applied to achieve secure virtualized implementations.
What can coding theory do for storage systems?
Authors: Cassuto Yuval
Published: March 2013

Storage systems and coding theory are two very different but highly interdependent engineering disciplines. The development of storage systems has impacted research in coding theory, and coding-theoretic contributions changed the way storage systems work. The presentation aims to give a short summary of the different problems solved by coding theory at the service of storage systems.
Statistical Mechanics of Modularity and Horizontal Gene Transfer
Authors: Deem Michael W.
Published: March 2013

Biological structure organizes over evolutionary timescales. This review discusses the spontaneous emergence of hierarchical structure in biology as a result of environmental change. A body of theoretical and experimental work on evolutionary dynamics is reviewed, and a theory for these results based on a principle of least action is discussed. The structure that has emerged in biology is complementary to a type of evolutionary dynamics known as horizontal gene transfer. How horizontal gene transfer ameliorates the difficulty that finite populations would otherwise have to evolve on rugged fitness landscapes is also discussed.
Search for Majorana Fermions in Superconductors
Authors: Beenakker C.W.J.
Published: March 2013

Majorana fermions (particles that are their own antiparticle) may or may not exist in nature as elementary building blocks, but in condensed matter they can be constructed out of electron and hole excitations. What is needed is a superconductor to hide the charge difference and a topological (Berry) phase to eliminate the energy difference from zero-point motion. A pair of widely separated Majorana fermions, bound to magnetic or electrostatic defects, has non-Abelian exchange statistics. A qubit encoded in this Majorana pair is expected to have an unusually long coherence time. I discuss strategies to detect Majorana fermions in a topological superconductor, as well as possible applications in a quantum computer. The status of the experimental search is reviewed.
Shock Events in the Solar System: The Message from Minerals in Terrestrial Planets and Asteroids
Authors: Gillet Philippe , Goresy Ahmed El
Published: March 2013

Impacts are central to the origin and evolution of planets of the Solar System. The shapes of craters, which can reach up to 1,000 km in diameter on the Moon, provide critical information on the large-scale dynamics of the impact and related shock. Minerals formed at high pressure and temperature found in shocked terrestrial rocks and meteorites give additional and complementary insights on the shock process at a smaller scale, typically from a few micrometers to a few millimeters. Local flaws in rocks, such as voids and mineral interfaces, are the preferential sites for the formation of high-pressure melts and minerals. Calculations based on the physics of shocks and the thermodynamics and kinetics of mineral transformations provide orders of magnitude for the duration, transient pressure, and prevailing temperature conditions of shock events. Case studies on shocked terrestrial and extraterrestrial materials illustrate the links between these parameters and impact duration. Many of the high-pressure mineral phases of olivine, pyroxenes, feldspars, silica, phosphates, titanium oxide, and carbon have been discovered in these heavily shocked rocks and provide unique opportunities to study the high-pressure minerals that exist in the deep Earth.
The Fossil Record of Plant-Insect Dynamics
Authors: Labandeira Conrad C. , Currano Ellen D.
Published: March 2013

Progress toward understanding the dynamics of ancient plant-insect associations has addressed major patterns in the ecology and evolution of herbivory and pollination. This advancement involves development of more analytical ways of describing plant-insect associational patterns in time and space and an assessment of the role that the environment and internal biological processes have in their control. Current issues include the deep origins of terrestrial herbivory, the spread of herbivory across late Paleozoic landscapes, recoveries from sudden major crises, reaction to and accommodation of protracted environmental perturbations, and the nature of herbivory and pollination before the appearance of angiosperms during the mid-Mesozoic. These and other exploratory research themes provide a more complete account of a great nexus of ecological activity that has been wedged between the two most diverse organismic groups on land for the past 410 million years.
Molecular Recognition and Ligand Association
Authors: Baron Riccardo , McCammon J. Andrew
Published: March 2013

We review recent developments in our understanding of molecular recognition and ligand association, focusing on two major viewpoints: (a) studies that highlight new physical insight into the molecular recognition process and the driving forces determining thermodynamic signatures of binding and (b) recent methodological advances in applications to protein-ligand binding. In particular, we highlight the challenges posed by compensating enthalpic and entropic terms, competing solute and solvent contributions, and the relevance of complex configurational ensembles comprising multiple protein, ligand, and solvent intermediate states. As more complete physics is taken into account, computational approaches increase their ability to complement experimental measurements, by providing a microscopic, dynamic view of ensemble-averaged experimental observables. Physics-based approaches are increasingly expanding their power in pharmacology applications.
The Changing Landscape of US Unions in Historical and Theoretical Perspective
Authors: Goldfield Michael , Bromsen Amy
Published: March 2013

In certain states, most notably Wisconsin and Ohio, attempts have been made to eliminate public sector collective bargaining. Although the all-out attack on public sector unions is relatively new, it is best seen in the context of long-term trends. These include the long-standing assault on private sector unions; the ongoing conservative political critique of the public sector; and neoliberal policies that contract government services, deregulate virtually all economic activities, and privatize many government programs, as well as decreasing workers' wages and benefits (allegedly to make them more globally competitive). The racial and gender dimensions of these trends are worthy of note and at times central to the narrative. We discuss these issues in detail, within the broader context of the role of unions in modern society and the history of labor organization in both the private and public sectors in the United States.
Heat Flow, Heat Generation, and the Thermal State of the Lithosphere
Authors: Furlong Kevin P. , Chapman David S.
Published: March 2013

The thermal structure of the lithosphere controls many properties and processes of Earth's crust. The total ∼47-TW heat loss of Earth is key to understanding and modeling this thermal structure, as is partitioning the various sources of that heat into heat entering the base of the lithosphere, heat generated within the lithosphere by radioactive decay (primarily within the continental crust), and secular cooling of the mantle lithosphere (primarily in oceanic lithosphere). A set of framework geotherms for the continental lithosphere explains deep crustal melting in high heat flow regions, metamorphic pressure-temperature (P-T) space in the crust, partial melting at the base of the lithosphere to produce an S-wave low-velocity zone in Phanerozoic and younger terranes, and the P-T fields inferred from mantle xenoliths. Important perturbations to a standard thermal state are produced by orogenic overprints, transient thermal regimes, and exhumation.
Role of prostaglandin D2 in mast cell activation-induced sensitization of esophageal vagal afferents
Authors: Zhang Shizhong , Grabauskas Gintautas , Wu Xiaoyin , Joo Moon Kyung , Heldsinger Andrea , Song Il , Owyang Chung , Yu Shaoyong
Published: March 2013

Sensitization of esophageal afferents plays an important role in esophageal nociception, but the mechanism is less clear. Our previous studies demonstrated that mast cell (MC) activation releases the preformed mediators histamine and tryptase, which play important roles in sensitization of esophageal vagal nociceptive C fibers. PGD2 is a lipid mediator released by activated MCs. Whether PGD2 plays a role in this sensitization process has yet to be determined. Expression of the PGD2 DP1 and DP2 receptors in nodose ganglion neurons was determined by immunofluorescence staining, Western blotting, and RT-PCR. Extracellular recordings were performed in ex vivo esophageal-vagal preparations. Action potentials evoked by esophageal distension were compared before and after perfusion of PGD2, DP1 and DP2 receptor agonists, and MC activation, with or without pretreatment with antagonists. The effect of PGD2 on 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal nodose neurons was determined by patch-clamp recording. Our results demonstrate that DP1 and DP2 receptor mRNA and protein were expressed mainly in small- and medium-diameter neurons in nodose ganglia. PGD2 significantly increased esophageal distension-evoked action potential discharges in esophageal nodose C fibers. The DP1 receptor agonist BW 245C mimicked this effect. PGD2 directly sensitized DiI-labeled esophageal nodose neurons by decreasing the action potential threshold. Pretreatment with the DP1 receptor antagonist BW A868C significantly inhibited PGD2 perfusion- or MC activation-induced increases in esophageal distension-evoked action potential discharges in esophageal nodose C fibers. In conclusion, PGD2 plays an important role in MC activation-induced sensitization of esophageal nodose C fibers. This adds a novel mechanism of visceral afferent sensitization.
Racial differences in the response of cardiorespiratory fitness to aerobic exercise training in Caucasian and African American postmenopausal women
Authors: Swift Damon L. , Johannsen Neil M. , Lavie Carl J. , Earnest Conrad P. , Johnson William D. , Blair Steven N. , Church Timothy S. , Newton Robert L.
Published: March 2013

African American (AA) women have an elevated risk of cardiovascular disease and have been reported to have lower cardiorespiratory fitness (CRF) compared with Caucasian American (CA) women. However, little data exist that evaluate racial differences in the change in CRF following aerobic exercise training. CA ( n = 264) and AA ( n = 122) postmenopausal women from the Dose-Response to Exercise in Women study were randomized to 4, 8, and 12 kcal·kg body wt−1·wk−13 (KKW) of aerobic training or the control group for 6 mo. CRF was evaluated using a cycle ergometer. A greater increase in relative CRF was observed in CA compared with AA women in the 4 (CA: 1.00 vs. AA: 0.35 ml O2·kg−1·min −1, P = 0.034), 8 (CA: 1.59 vs. AA: 0.82 ml O2·kg−1·min −1, P = 0.041), and 12 (CA: 1.98 vs. AA: 0.50 ml O2·kg−1·min −1, P = 0.001) KKW groups. Similar effects were found in absolute CRF, with the exception of the 4-KKW (CA: 0.04 vs. AA: 0.02 l O2/min, P = 0.147) group. However, in categorical analyses, the percentages of women who improved in both relative (>0 ml O2·kg−1·min −1) and absolute (>0 l O2/min) CRF were not significantly different for CA and AA women in all exercise groups (all P > 0.05). AA postmenopausal women, in general, had an attenuated increase in CRF (both relative and absolute) following exercise training, but had similar response rates compared with CA women. Future studies should investigate the physiologic mechanisms responsible for this attenuated response.
Altitude, pasture type, and sheep breed affect bone metabolism and serum 25-hydroxyvitamin D in grazing lambs
Authors: Willems Helen , Leiber Florian , Kohler Martina , Kreuzer Michael , Liesegang Annette
Published: March 2013

This study aimed to investigate the bone development of two mountain sheep breeds during natural summer grazing either in the lowlands or on different characteristic alpine pastures. Pasture types differed in topographic slope, plant species composition, general nutritional feeding value, Ca and P content, and Ca:P ratio of herbage. Twenty-seven Engadine sheep (ES) lambs and 27 Valaisian Black Nose sheep (VS) lambs were divided into four groups of 6 to 7 animals per breed and allocated to three contrasting alpine pasture types and one lowland pasture type. The lambs were slaughtered after 9 wk of experimental grazing. The steep alpine pastures in combination with a high (4.8) to very high (13.6) Ca:P ratio in the forage decreased total bone mineral content as measured in the middle of the left metatarsus of the lambs from both breeds, and cortical bone mineral content and cortical bone mineral density of ES lambs. Breed × pasture type interactions occurred in the development of total and cortical bone mineral content, and in cortical thickness, indicating that bone metabolism of different genotypes obviously profited differently from the varying conditions. An altitude effect occurred for 25-hydroxyvitamin D with notably higher serum concentrations on the three alpine sites, and a breed effect led to higher concentrations for ES than VS. Despite a high variance, there were pasture-type effects on serum markers of bone formation and resorption.
Molecular Pathways: Inhibiting Steroid Biosynthesis in Prostate Cancer
Authors: Ferraldeschi Roberta , Sharifi Nima , Auchus Richard J. , Attard Gerhardt
Published: March 2013

A significant proportion of castration-resistant prostate cancers (CRPC) remains driven by ligand activation of the androgen receptor. Although the testes are the primary source of testosterone, testosterone can also be produced from peripheral conversion of adrenal sex hormone precursors DHEA and androstenedione in the prostate and other tissues. CYP17A1 catalyzes two essential reactions in the production of DHEA and androstenedione: the hydroxylation (hydroxylase activity) and the subsequent cleavage of the C17-20 side chain (lyase activity). Potent and selective inhibition of CYP17A1 by abiraterone depletes residual nongonadal androgens and is an effective treatment for CRPC. Elucidation of the mechanisms that underlie resistance to abiraterone will inform the development of novel therapeutic strategies post-abiraterone. Preclinical evidence that androgen biosynthesis in prostate cancer cells does not necessarily follow a single dominant pathway, and residual androgens or alternative ligands (including administered glucocorticoids) can reactivate androgen receptor signaling, supports cotargeting of more than one enzyme involved in steroidogenesis and combining a CYP17A1 inhibitor with an antiandrogen. Furthermore, given the drawbacks of 17α-hydroxylase inhibition, there is considerable interest in developing new CYP17A1 inhibitors that more specifically inhibit lyase activity and are therefore less likely to require glucocorticoid coadministration. Clin Cancer Res; 19(13); 3353–9. ©2013 AACR.
Analysis of Tumor Specimens at the Time of Acquired Resistance to EGFR-TKI Therapy in 155 Patients with EGFR-Mutant Lung Cancers
Authors: Yu Helena A. , Arcila Maria E. , Rekhtman Natasha , Sima Camelia S. , Zakowski Maureen F. , Pao William , Kris Mark G. , Miller Vincent A. , Ladanyi Marc , Riely Gregory J.
Published: March 2013

Purpose: All patients with EGF receptor (EGFR)–mutant lung cancers eventually develop acquired resistance to EGFR tyrosine kinase inhibitors (TKI). Smaller series have identified various mechanisms of resistance, but systematic evaluation of a large number of patients to definitively establish the frequency of various mechanisms has not been conducted.

Experimental Design: Patients with lung adenocarcinomas and acquired resistance to erlotinib or gefitinib enrolled onto a prospective biopsy protocol and underwent a rebiopsy after the development of acquired resistance. Histology was reviewed. Samples underwent genotyping for mutations in EGFR, AKT1, BRAF, ERBB2, KRAS, MEK1, NRAS and PIK3CA, and FISH for MET and HER2.

Results: Adequate tumor samples for molecular analysis were obtained in 155 patients. Ninety-eight had second-site EGFR T790M mutations [63%; 95% confidence interval (CI), 55%–70%] and four had small cell transformation (3%, 95% CI, 0%–6%). MET amplification was seen in 4 of 75 (5%; 95% CI, 1%–13%). HER2 amplification was seen in 3 of 24 (13%; 95% CI, 3%–32%). We did not detect any acquired mutations in PIK3CA, AKT1, BRAF, ERBB2, KRAS, MEK1, or NRAS (0 of 88, 0%; 95% CI, 0%–4%). Overlap among mechanisms of acquired resistance was seen in 4%.

Conclusions: This is the largest series reporting mechanisms of acquired resistance to EGFR-TKI therapy. We identified EGFR T790M as the most common mechanism of acquired resistance, whereas MET amplification, HER2 amplification, and small cell histologic transformation occur less frequently. More comprehensive methods to characterize molecular alterations in this setting are needed to improve our understanding of acquired resistance to EGFR-TKIs. Clin Cancer Res; 19(8); 2240–7. ©2013 AACR.
An Unholy Alliance: Cooperation between BRAF and NF1 in Melanoma Development and BRAF Inhibitor Resistance
Authors: Gibney Geoffrey T. , Smalley Keiran S.M.
Published: March 2013

Summary: In this issue of Cancer Discovery, 2 studies provide new evidence implicating loss of the tumor suppressor neurofibromin (NF1) in the biologic behavior of cutaneous melanoma. The first study from Maertens and colleagues describes a new transgenic mouse model in which mutant BRAF cooperates with NF1 loss to drive melanoma development through the abrogation of oncogene-induced senescence. The second, from Whittaker and colleagues, used a high-throughput short hairpin RNA screening approach to identify NF1 loss as a key mediator of acquired and intrinsic BRAF inhibitor resistance. Together these studies provide new insights into the signaling that underlies melanoma initiation and progression and suggests novel therapeutic strategies for patients whose melanomas are BRAF-mutant/NF1-deficient. Cancer Discov; 3(3); 260–3. ©2013 AACR.

See related article by Maertens et al., p. 338

See related article by Whittaker et al., p. 350
Bcl-2 Inhibition or FBXW7 Mutation Sensitizes Solid Tumor Cells to HDAC Inhibition In Vitro but Could Prove Difficult to Validate in Patients
Authors: Pickering Curtis R. , Myers Jeffrey N.
Published: March 2013

Summary: In this issue of Cancer Discovery, He and colleagues determined that Mcl-1 levels are a key factor in the response to histone deacetylase (HDAC) inhibitors, and FBXW7 mutation is a biomarker for sensitivity to HDAC inhibition. They also present evidence for synergy between treatment with HDAC inhibitors and Bcl-2–targeted therapeutics. These data provide an exciting new biomarker and combination therapy that should be evaluated clinically. Cancer Discov; 3(3); 258–9. ©2013 AACR.

See related article by He et al., p. 324
Impact of Associated Significant Aortic Regurgitation on Left Ventricular Remodeling and Hemodynamic Impairment in Severe Aortic Valve Stenosis
Authors: Popescu Andreea Catarina , Antonini-Canterin Francesco , Enache Roxana , Nicolosi Gian Luigi , Piazza Rita , Faggiano Pompilio , Cassin Matteo , Dimulescu Doina , Ginghină Carmen , Popescu Bogdan Alexandru
Published: March 2013

Objectives: The left ventricular (LV) response to combined pressure and volume overload [aortic stenosis (AS) and aortic regurgitation (AR)] versus pressure overload (isolated AS) has not been systematically studied. We aimed to assess LV remodeling, functional and hemodynamic consequences in patients with mixed aortic valve disease versus patients with isolated AS. Methods: We enrolled 181 patients (67 ± 9 years, 109 men) with severe AS (aortic valve area indexed to body surface area <0.6 cm2/m2) who underwent preoperative cardiac catheterization and a complete echocardiogram. Pulmonary capillary wedge pressure (PCWP), LV end-diastolic pressure (LVEDP) and pulmonary artery pressure (PAP) were measured. Results: One hundred and ten patients (group A) had isolated severe AS (AR 0-1) and 71 patients (group B) had mixed aortic valve disease (severe AS plus AR 2-3). Patients in group B were younger and in a higher New York Heart Association class (p < 0.01). Severity of AS was similar in both groups. Patients in group B had a higher indexed LV mass, a lower LV ejection fraction, and higher PCWP, LVEDP and PAP (all p ≤ 0.01). Conclusions: Patients with severe AS and significant AR are more symptomatic than patients with isolated severe AS. The increased burden due to the combined lesion induces pronounced LV remodeling and more severe hemodynamic consequences.
Komplementärmedizin und Wissenschaftspluralismus - von der staatlichen Forschungsförderung zum Dialogforum Pluralismus in der Medizin
Authors: Matthiessen Peter F.
Published: March 2013

Der Medizin liegt ein Pluralismus unterschiedlicher Denk- und Praxisansätze zugrunde. Vor dem Hintergrund dieser Annahme werden Entstehungsgeschichte sowie Erfahrungen der beiden staatlichen Forschungsförderprogramme «Unkonventionelle Methoden der Krebsbekämpfung» (UMK) und «Unkonventionelle Medizinische Richtungen» (UMR) aus Sicht der Projektbegleitung zweier Arbeitsgruppen beschrieben, die im Auftrag der Bundesregierung an der Universität Witten/Herdecke angesiedelt waren. Die Ergebnisse einer unter meiner Leitung in den Jahren 1989-1992 durchgeführten bundesweiten Bestandsanalyse ergaben für die Komplementärmedizin zur damaligen Zeit einen deutlichen Mangel an personellen und infrastrukturellen Ressourcen für wettbewerbsfähige Forschungsaktivitäten. Das Feld der Komplementärmedizin erwies sich als sehr heterogen und gliederte sich in Verfahren, bei denen ein Forschungsinteresse nicht zu erkennen war, aber auch in Ansätze, die die Mainstream-Medizin infolge ihres anders gearteten Paradigmas ergänzten, und deren Vertreter erkennbar an evaluativer, empirischer Forschung interessiert waren und sind. Aufgeführt finden sich unsere den zuständigen Bundesministerien gemachten Förderempfehlungen, die ausgeschriebenen Förderthemen sowie die durchgeführten Forschungsaktivitäten. Obwohl diese staatliche Forschungsförderung zeitlich und von den Fördermitteln begrenzt war, kann ihr rückblickend eine Signalfunktion zugesprochen werden. Denn im nachfolgenden Zeitraum ist es zu einer deutlichen Verbesserung der infrastrukturellen und personellen Forschungsbedingungen gekommen und damit zu einer deutlichen Anhebung des Qualitätsniveaus und der Akzeptanz der Forschungsergebnisse. Als Ausdruck einer zunehmend besseren Kooperationsbereitschaft werden Gründung, Anliegen und Aktivitäten des im Jahr 2000 gegründeten «Dialogforum Pluralismus in der Medizin» dargestellt und diese Situation mit derjenigen zum Zeitpunkt der staatlichen Forschungsförderung verglichen. Die gegenwärtigen Favorisierungen einer «Integrativen Medizin» werden als Ausdruck einer besseren wechselseitigen Akzeptanz begrüßt. Dennoch wird in der Komplementärmedizin nach wie vor ein kreatives, die Medizin und das Gesundheitswesen bereicherndes, die Patientenbezogenheit verbesserndes und insofern entwicklungsförderndes (Unruhe-)Element gesehen.
Evaluation of Dermatological Consultations of Patients treated in Intensive Care Unit
Authors: Emre Selma , Emre Cengizhan , Akoglu Gulsen , Demirseren D.Deniz , Metin Ahmet
Published: March 2013

Background: Skin disorders which require treatment are a common development in patients treated in intensive care units (ICUs). There are very few prospective studies about skin complications in adult ICUs. Objective: The aim of this study is to evaluate skin disorders in ICU-treated adult patients who were consulted for dermatological problems. Methods: Eighty-two of 591 patients admitted to ICUs who were consulted for dermatological problems were included in the study. The correlation between skin complications and associated comorbidities, age, gender and ICU length of stay were analyzed. Results: Ninety dermatological complications were observed. Cutaneous drug reactions were significantly more frequent in female patients than males (p = 0.020). Candidal intertrigo was more frequent in diabetic patients than in nondiabetic patients (p = 0.042). Conclusion: Patients in ICUs may develop various skin disorders that need to be evaluated by dermatological consultations. Clinical features of the patients, especially gender and comorbidities, may predispose skin complications.
Chewing Deficiencies in Adults with Multiple Untreated Carious Lesions
Authors: Decerle N. , Nicolas E. , Hennequin M.
Published: March 2013

Persons who have multiple untreated carious lesions are at high risk of chewing difficulties and consequently an unhealthy diet, but few data are available on the impact of untreated caries on mastication in adults. This study in adults with multiple untreated caries lesions aimed to evaluate chewing deficiencies using physiological and psychosocial indicators. Forty-five patients, mean (±SD) decayed teeth 11.5 (±5.2), and 20 fully dentate caries-free subjects were observed during mastication of raw carrot and two jelly model foods differing in hardness. Criteria for chewing evaluation were carrot bolus granulometry, food refusals, chewing activity (chewing time, number of chewing cycles, chewing frequency) and oral health-related quality of life (GOHAI). Dental status was characterized by caries experience (DMFT) and posterior functional pairs of teeth. Adults with multiple untreated caries lesions suffered from chewing deficiencies, demonstrated by a decrease in food comminution related to the number of posterior functional teeth, food selection and functional alterations in oral health-related quality of life. The ability to adapt chewing activity to food hardness was preserved in this group. Further studies should be conducted to determine whether chewing function could be improved after dental treatment.
Polymorphism in Endothelial Connexin40 Enhances Sensitivity to Intraluminal Pressure and Increases Arterial Stiffness
Authors: Chaston Daniel J. , Baillie Brett K. , Grayson T. Hilton , Courjaret Raphael J. , Heisler Jillian M. , Lau Katherine A. , Machaca Khaled , Nicholson Bruce J. , Ashton Anthony , Matthaei Klaus I. , Hill Caryl E.
Published: March 2013

Objective—

To determine whether impairment of endothelial connexin40 (Cx40), an effect that can occur in hypertension and aging, contributes to the arterial dysfunction and stiffening in these conditions.

Approach and Results—

A new transgenic mouse strain, expressing a mutant Cx40, (Cx40T202S), specifically in the vascular endothelium, has been developed and characterized. This mutation produces nonfunctional hemichannels, whereas gap junctions containing the mutant are electrically, but not chemically, patent. Mesenteric resistance arteries from Cx40T202S mice showed increased sensitivity of the myogenic response to intraluminal pressure in vitro, compared with wild-type mice, whereas transgenic mice overexpressing native Cx40 (Cx40Tg) showed reduced sensitivity. In control and Cx40Tg mice, the sensitivity to pressure of myogenic constriction was modulated by both NO and endothelium-derived hyperpolarization; however, the endothelium-derived hyperpolarization component was absent in Cx40T202S arteries. Analysis of passive mechanical properties revealed that arterial stiffness was enhanced in vessels from Cx40T202S mice, but not in wild-type or Cx40Tg mice.

Conclusions—

Introduction of a mutant form of Cx40 in the endogenous endothelial Cx40 population prevents endothelium-derived hyperpolarization activation during myogenic constriction, enhancing sensitivity to intraluminal pressure and increasing arterial stiffness. We conclude that genetic polymorphisms in endothelial Cx40 can contribute to the pathogenesis of arterial disease.