bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete Genome Sequence of Genotype Ib Newcastle Disease Virus Isolated from a Mallard (Anas platyrhynchos) in Russia
Authors: Yurchenko Kseniya S. , Sobolev Ivan A. , Glushchenko Alexandra V. , Shestopalov Alexander M.
Published: December 2015

We report here the complete genome sequence of a Newcastle disease virus isolate, NDV/Yakutiya/mallard/852/2011, isolated from a mallard in Russia. On the basis of phylogenetic analysis, this strain was clustered into class II genotype Ib.
How Many Samples and How Many Culture Media To Diagnose a Prosthetic Joint Infection: a Clinical and Microbiological Prospective Multicenter Study
Authors: Bémer Pascale , Léger Julie , Tandé Didier , Plouzeau Chloé , Valentin Anne Sophie , Jolivet-Gougeon Anne , Lemarié Carole , Kempf Marie , Héry-Arnaud Geneviève , Bret Laurent , Juvin Marie Emmanuelle , Giraudeau Bruno , Corvec Stéphane , Burucoa Christophe ,   the Centre de Référence des Infections Ostéo-articulaires du Grand Ouest (CRIOGO) Study Team
Published: December 2015

Although numerous perioperative samples and culture media are required to diagnose prosthetic joint infection (PJI), their exact number and types have not yet been definitely determined with a high level of proof. We conducted a prospective multicenter study to determine the minimal number of samples and culture media required for accurate diagnosis of PJI. Over a 2-year period, consecutive patients with clinical signs suggesting PJI were included, with five perioperative samples per patient. The bacteriological and PJI diagnosis criteria were assessed using a random selection of two, three, or four samples and compared with those obtained using the recommended five samples (references guidelines). The results obtained with two or three culture media were then compared with those obtained with five culture media for both criteria. The times-to-positivity of the different culture media were calculated. PJI was confirmed in 215/264 suspected cases, with a bacteriological criterion in 192 (89%). The PJI was monomicrobial (85%) or polymicrobial (15%). Percentages of agreement of 98.1% and 99.7%, respectively, for the bacteriological criterion and confirmed PJI diagnosis were obtained when four perioperative samples were considered. The highest percentages of agreement were obtained with the association of three culture media, a blood culture bottle, a chocolate agar plate, and Schaedler broth, incubated for 5, 7, and 14 days, respectively. This new procedure leads to significant cost saving. Our prospective multicenter study showed that four samples seeded on three culture media are sufficient for diagnosing PJI.
Depression and risk of hospitalisations and rehospitalisations for ambulatory care-sensitive conditions in Denmark: a population-based cohort study
Authors: Davydow Dimitry S , Fenger-Grøn Morten , Ribe Anette Riisgaard , Pedersen Henrik Søndergaard , Prior Anders , Vedsted Peter , Unützer Jürgen , Vestergaard Mogens
Published: December 2015

Objective

Hospitalisations for ambulatory care-sensitive conditions (ACSCs), a group of chronic and acute illnesses considered not to require inpatient treatment if timely and appropriate ambulatory care is received, and early rehospitalisations are common and costly. We sought to determine whether individuals with depression are at increased risk of hospitalisations for ACSCs, and rehospitalisation for the same or another ACSC, within 30 days.

Design

National, population-based cohort study.

Setting

Denmark.

Participants

5 049 353 individuals ≥18 years of age between 1 January 2005 and 31 December 2013.

Measurements

Depression was ascertained via psychiatrist diagnoses in the Danish Psychiatric Central Register or antidepressant prescription redemption from the Danish National Prescription Registry. Hospitalisations for ACSCs and rehospitalisations within 30 days were identified using the Danish National Patient Register.

Results

Overall, individuals with depression were 2.35 times more likely to be hospitalised for an ACSC (95% CI 2.32 to 2.37) versus those without depression after adjusting for age, sex and calendar period, and 1.45 times more likely after adjusting for socioeconomic factors, comorbidities and primary care utilisation (95% CI 1.43 to 1.46). After adjusting for ACSC-predisposing comorbidity, depression was associated with significantly greater risk of hospitalisations for all chronic (eg, angina, diabetes complications, congestive heart failure exacerbation) and acute ACSCs (eg, pneumonia) compared to those without depression. Compared to those without depression, persons with depression were 1.21 times more likely to be rehospitalised within 30 days for the same ACSC (95% CI 1.18 to 1.24) and 1.19 times more likely to be rehospitalised within 30 days for a different ACSC (95% CI 1.15 to 1.23).

Conclusions

Individuals with depression are at increased risk of hospitalisations for ACSCs, and once discharged are at elevated risk of rehospitalisations within 30 days for ACSCs.
Centrifuge modelling of an instrumented free-fall sphere for measurement of undrained strength in fine-grained soils
Authors: Morton J.P. , O’Loughlin C.D. , White D.J.
Published: December 2015

This paper describes centrifuge tests in which a model free-fall sphere was allowed to free fall in water before dynamically embedding within reconstituted samples of kaolin clay and two offshore natural clays. Instrumentation within the sphere measured accelerations along three orthogonal axes. The resultant acceleration was used to calculate sphere velocities and displacements. This allowed the penetration resistance acting on the sphere to be expressed in terms of a single capacity factor that captures soil resistance from both shearing and drag, and varies uniquely with the non-Newtonian Reynolds number. Undrained shear strength profiles obtained from a simple inverse analysis of the acceleration data show good agreement with those obtained using conventional push-in penetrometer tests.
Effects of winter warming on cold hardiness and spring budbreak of four boreal conifers
Authors: Man Rongzhou , Colombo Steve , Lu Pengxin , Dang Qing-Lai
Published: December 2015

Compared with the effects of spring frosts on opening buds or newly flushed tissues, winter freezing damage to conifers, owing to temperature fluctuations prior to budbreak, is rare and less known. In this study, changes in cold hardiness (measured based on electrolyte leakage and needle damage) and spring budbreak were assessed to examine the responses of four boreal conifer species — black spruce (Picea mariana (Mill.) B.S.P.), white spruce (Picea glauca) (Moench) Voss), jack pine (Pinus banksiana Lamb.), and lodgepole pine (Pinus contorta Dougl. ex. Loud.) — to different durations of experimental warming (16 °C day to –2 °C night with a 10 h photoperiod, except for night temperatures during November warming (+2 °C)). Seedlings showed increased responses to warming from November to March, while the capacity to regain the cold hardiness lost to warming decreased during the same period. This suggests an increasing vulnerability of conifers to temperature fluctuations and freezing damage with the progress of chilling and dormancy release from fall to spring. Both lodgepole pine and jack pine initiated spring growth earlier and had greater responses to experimental warming in bud phenology than black spruce and white spruce, suggesting a greater potential risk of frost/freezing damage to pine trees in the spring.
Global monopoles in f(R) gravity
Authors: Ulu Dog̃ru Melis , Taṣer Dog̃ukan
Published: December 2015

In this study, we investigate whether global monopoles cause black holes or wormholes to form. Field equations for static spherically symmetric spacetimes with global monopoles are obtained in [Formula: see text] gravity. We found exact solutions for the field equations without using any perturbation or approximation methods. It is shown that the obtained [Formula: see text] function is in accordance with the [Formula: see text]-cold dark matter ([Formula: see text]-CDM) model. Also, it is shown that the static spherically symmetric spacetimes associated with global monopoles form black holes or wormhole structures under some restrictions. Finally, geometrical and physical results of the solutions are discussed.
Software Engineering Project Courses with Industrial Clients
Authors: Bruegge Bernd , Krusche Stephan , Alperowitz Lukas
Published: December 2015

There is an acknowledged need for teaching realistic software development in project courses. The design space for such courses is wide, ranging from single-semester to two-semester courses, from single-client to multicustomer courses, from local to globally distributed courses, and from toy projects to projects with real clients. The challenge for a nontrivial project course is how to make the project complex enough to enrich students’ software engineering experience, yet realistic enough to have a teaching environment that does not unduly burden students or the instructor. We describe a methodology for project courses that is realizable for instructors, improves students’ skills, and leads to viable results for industry partners.

In particular, recent advances in release management and collaboration workflows reduce the effort of students and instructors during delivery and increase the quality of the deliverables. To enable release and feedback management, we introduce Rugby, an agile process model based on Scrum that allows reacting to changing requirements. To improve early communication, we use Tornado, a scenario-based design approach that emphasizes the use of informal models for the interaction between clients and students. The combination of Rugby and Tornado allows students to deal with changing requirements, produce multiple releases, and obtain client feedback through the duration of the course.

We describe our experience with more than 300 students working on 40 projects with external clients over a 4-year period. In the latest instance of our course, the students have produced more than 7000 builds with 600 releases for eleven clients. In an evaluation of the courses, we found that the introduction of Rugby and Tornado significantly increased students’ technical skills, especially with respect to software engineering, usability engineering, and configuration management, as well as their nontechnical skills such as communication with the client, teamwork, presentation, and demo management. Finally, we discuss how other instructors can adapt the course concept.
Assessing Large-Project Courses
Authors: Vasilevskaya Maria , Broman David , Sandahl Kristian
Published: December 2015

In a modern computing curriculum, large-project courses are essential to give students hands-on experience of working in a realistic software engineering project. Assessing such projects is, however, extremely challenging. There are various aspects and trade-offs of assessments that can affect course quality. Individual assessments may fairly grade individuals, but may lose focus of the project as a group activity. Extensive teacher involvement is necessary for objective assessment, but may affect the way that students work. Continuous feedback to students can enhance learning, but may be hard to combine with fair assessment. Most previous work focuses on some specific assessment aspect; in this article, we present an assessment model that consists of a collection of assessment activities, each covering different aspects. We have applied, developed, and improved these activities during a 7yr period. To evaluate the usefulness of the model, we perform questionnaire-based surveys over a 2yr period. Furthermore, we design and execute an experiment that studies to what extent students can perform fair peer assessment and to what degree the assessments of students and teachers agree. We analyze the results, discuss findings, and summarize lessons learned.
Memory Management Scheme to Improve Utilization Efficiency and Provide Fast Contiguous Allocation without a Statically Reserved Area
Authors: Kim Myungsun , Koo Jinkyu , Lee Hyojung , Geraci James R.
Published: December 2015

Fast allocation of large blocks of physically contiguous memory plays a crucial role to boost the performance of multimedia applications in modern memory-constrained portable devices, such as smartphones, tablets, etc. Existing systems have addressed this issue by provisioning a large
statically reserved memory area
(SRA) in which only dedicated applications can allocate pages. However, this in turn degrades the performance of applications that are prohibited to utilize the SRA due to the reduced available memory pool. To overcome this drawback while maintaining the benefits of the SRA, we propose a new memory management scheme that uses a special memory region, called
page-cache-preferred area
(PCPA), in concert with a quick memory reclaiming algorithm. The key of the proposed scheme is to enhance the memory utilization efficiency by enabling to allocate page-cached pages of all applications in the PCPA until predetermined applications require to allocate big chunks of contiguous memory. At this point, clean page-cached pages in the PCPA are rapidly evicted without write-back to a secondary storage. Compared to the SRA scheme, experimental results show that the average launch time of real-world applications and the execution time of I/O-intensive benchmarks are reduced by 9.2% and 24.7%, respectively.
Performance-Driven Unit-Capacitor Placement of Successive-Approximation-Register ADCs
Authors: Huang Chien-Chih , Wey Chin-Long , Chen Jwu-E , Luo Pei-Wen
Published: December 2015

The performance of many switched-capacitor analog integrated circuits, such as analog-to-digital converters (ADCs) and sample and hold circuits, is directly related to their accurate capacitance ratios. In general, capacitor mismatch can result from two sources of errors: random mismatch and systematic mismatch. Paralleling unit capacitance (UC) with a common-centroid structure can alleviate the random mismatch errors. The complexity of generating an optimal solution to the UC placement problem is extremely high, let alone if both placement and routing problems are to be optimized simultaneously. This article evaluates the performance of the UC placement generated in an existing work and proposes an alternative UC placement to achieve optimal ratio mismatch
M
and better linearity performance of SAR ADC design. Results show that the proposed UC placement achieves a ratio mismatch of
M
= 0.695, the effective number of bits ENOB = 8.314 bits, and the integral nonlinearity INL = 0.816 LSB (least significant bits) for a 9-bit SAR ADC design.
Enhanced Test Compaction for Multicycle Broadside Tests by Using State Complementation
Authors: Pomeranz Irith
Published: December 2015

Multicycle tests support test compaction by allowing each test to detect more target faults. The ability of multicycle broadside tests to provide test compaction depends on the ability of primary input sequences to take the circuit between pairs of states that are useful for detecting target faults. This ability can be enhanced by adding design-for-testability (DFT) logic that allows states to be complemented. This article describes a test compaction procedure that uses such DFT logic to form a compact multicycle broadside test set for transition faults where the tests use constant primary input vectors. The use of complemented states also allows the procedure to increase the transition fault coverage beyond the transition fault coverage of a broadside test set. The procedure has the option of increasing the switching activity of the tests gradually in order to explore the tradeoff between the number of tests, the fault coverage, and the switching activity.
Auctions for Heterogeneous Items and Budget Limits
Authors: Dütting Paul , Henzinger Monika , Starnberger Martin
Published: December 2015

We study individual rational, Pareto-optimal, and incentive compatible mechanisms for auctions with heterogeneous items and budget limits. We consider settings with multiunit demand and additive valuations. For single-dimensional valuations we prove a positive result for randomized mechanisms, and a negative result for deterministic mechanisms. While the positive result allows for private budgets, the negative result is for public budgets. For multidimensional valuations and public budgets we prove an impossibility result that applies to deterministic and randomized mechanisms. Taken together this shows the power of randomization in certain settings with heterogeneous items, but it also shows its limitations.
Complexity Theory Column 88
Authors: Forbes Michael A. , Shpilka Amir
Published: December 2015

Algebraic complexity theory studies the complexity of computing (multivariate) polynomials efficiently using algebraic circuits. This succinct representation leads to fundamental algorithmic challenges such as the
polynomial identity testing (PIT)
problem (decide nonzeroness of the computed polynomial) and the
polynomial factorization problem
(compute succinct representations of the factors of the circuit). While the Schwartz-Zippel-DeMillo-Lipton Lemma [Sch80,Zip79,DL78] gives an easy randomized algorithm for PIT, randomized algorithms for factorization require more ideas as given by Kaltofen [Kal89]. However, even derandomizing PIT remains a fundamental problem in understanding the power of randomness.

In this column, we survey the factorization problem, discussing the algorithmic ideas as well as the applications to other problems. We then discuss the challenges ahead, in particular focusing on the goal of obtaining deterministic factoring algorithms. While deterministic PIT algorithms have been developed for various restricted circuit classes, there are very few corresponding factoring algorithms. We discuss some recent progress on the
divisibility testing
problem (test if a given polynomial divides another given polynomial) which captures some of the difficulty of factoring. Along the way we attempt to highlight key challenges whose solutions we hope will drive progress in the area.
Computational Geometry Column 62
Authors: Cardinal Jean
Published: December 2015

In this column, we consider natural problems in computational geometry that are polynomialtime equivalent to finding a real solution to a system of polynomial inequalities. Such problems are called ⇿R-complete, and typically involve geometric graphs. We describe the foundations of those completeness proofs, in particular Mnëv's Universality Theorem, as well as some known ⇿R-completeness results, and recent additions to the list. The results shed light on the complex structure of those problems, beyond mere NP-hardness.
Haustral boundary contractions in the proximal 3-taeniated rabbit colon
Authors: Chen Ji-Hong , Yang Zixian , Yu Yuanjie , Huizinga Jan D.
Published: December 2015

The rabbit proximal colon is similar in structure to the human colon. Our objective was to study interactions of different rhythmic motor patterns focusing on haustral boundary contractions, which create the haustra, using spatiotemporal mapping of video recordings. Haustral boundary contractions were seen as highly rhythmic circumferential ring contractions that propagated slowly across the proximal colon, preferentially but not exclusively in the anal direction, at ∼0.5 cycles per minute; they were abolished by nerve conduction blockers. When multiple haustral boundary contractions propagated in the opposite direction, they annihilated each other upon encounter. Ripples, myogenic propagating ring contractions at ∼9 cycles per min, induced folding and unfolding of haustral muscle folds, creating an anarchic appearance of contractile activity, with different patterns in the three intertaenial regions. Two features of ripple activity were prominent: frequent changes in propagation direction and the occurrence of dislocations showing a frequency gradient with the highest intrinsic frequency in the distal colon. The haustral boundary contractions showed an on/off/on/off pattern at the ripple frequency, and the contraction amplitude at any point of the colon showed waxing and waning. The haustral boundary contractions are therefore shaped by interaction of two pacemaker activities hypothesized to occur through phase-amplitude coupling of pacemaker activities from interstitial cells of Cajal of the myenteric plexus and of the submuscular plexus. Video evidence shows the unique role haustral folds play in shaping contractile activity within the haustra. Muscarinic agents not only enhance the force of contraction, they can eliminate one and at the same time induce another neurally dependent motor pattern.
The NRF2 knockout rat: a new animal model to study endothelial dysfunction, oxidant stress, and microvascular rarefaction
Authors: Priestley Jessica R. C. , Kautenburg Katie E. , Casati Marc C. , Endres Bradley T. , Geurts Aron M. , Lombard Julian H.
Published: December 2015

Nuclear factor (erythroid-derived 2)-like-2 (NRF2) is a master antioxidant and cell protective transcription factor that upregulates antioxidant defenses. In this study we developed a strain of Nrf2 null mutant rats to evaluate the role of reduced NRF2-regulated antioxidant defenses in contributing to endothelial dysfunction and impaired angiogenic responses during salt-induced ANG II suppression. Nrf2−/− mutant rats were developed using transcription activator-like effector nuclease technology in the Sprague-Dawley genetic background, and exhibited a 41-bp deletion that included the start codon for Nrf2 and an absence of immunohistochemically detectable NRF2 protein. Expression of mRNA for the NRF2-regulated indicator enzymes heme oxygenase-1, catalase, superoxide dismutase 1, superoxide dismutase 2, and glutathione reductase was significantly lower in livers of Nrf2−/− mutant rats fed high salt (HS; 4% NaCl) for 2 wk compared with wild-type controls. Endothelium-dependent dilation to acetylcholine was similar in isolated middle cerebral arteries (MCA) of Nrf2−/− mutant rats and wild-type littermates fed low-salt (0.4% NaCl) diet, and was eliminated by short-term (3 days) HS diet in both strains. Low-dose ANG II infusion (100 ng/kg sc) reversed salt-induced endothelial dysfunction in MCA and prevented microvessel rarefaction in wild-type rats fed HS diet, but not in Nrf2−/− mutant rats. The results of this study indicate that suppression of NRF2 antioxidant defenses plays an essential role in the development of salt-induced oxidant stress, endothelial dysfunction, and microvessel rarefaction in normotensive rats and emphasize the potential therapeutic benefits of directly upregulating NRF2-mediated antioxidant defenses to ameliorate vascular oxidant stress in humans.
Hopping locomotion at different gravity: metabolism and mechanics in humans
Authors: Pavei Gaspare , Minetti Alberto E.
Published: December 2015

Previous literature on the effects of low gravity on the mechanics and energetics of human locomotion already dealt with walking, running, and skipping. The aim of the present study is to obtain a comprehensive view on that subject by including measurements of human hopping in simulated low gravity, a gait often adopted in many Apollo Missions and documented in NASA footage. Six subjects hopped at different speeds at terrestrial, Martian, and Lunar gravity on a treadmill while oxygen consumption and 3D body kinematic were sampled. Results clearly indicate that hopping is too metabolically expensive to be a sustainable locomotion on Earth but, similarly to skipping (and running), its economy greatly (more than ×10) increases at lower gravity. On the Moon, the metabolic cost of hopping becomes even lower than that of walking, skipping, and running, but the general finding is that gaits with very different economy on Earth share almost the same economy on the Moon. The mechanical reasons for such a decrease in cost are discussed in the paper. The present data, together with previous findings, will allow also to predict the aerobic traverse range/duration of astronauts when getting far from their base station on low gravity planets.
Bereavement Is Associated with an Increased Risk of HPV Infection and Cervical Cancer: An Epidemiological Study in Sweden
Authors: Lu Donghao , Sundström Karin , Sparén Pär , Fall Katja , Sjölander Arvid , Dillner Joakim , Helm Nathalie Ylitalo , Adami Hans-Olov , Valdimarsdóttir Unnur , Fang Fang
Published: December 2015

Grief over the loss of a family member may cause physical and mental illness, but an association between bereavement and cancer risk has not been established. Based on the Swedish National Cervical Screening Register (1969–2011) including 14,011,269 smears from 2,466,107 women, we conducted two nested case–control studies to examine the associations of bereavement (i.e., loss of a family member due to death) with abnormal cytology (390,310 first abnormal and 1,951,319 normal smears) and in situ/invasive cervical cancer (75,128 case and 375,640 control women), both individually matched on year of birth and screening adherence. Among 1,696 of the control women, we further investigated bereavement in association with human papillomavirus (HPV) infection, both HPV16 and other HPV types. Bereavement was consistently associated with a 4% to 9% increased risk for first abnormal cytology, in situ and invasive cervical cancer (all P < 0.02). The associations became stronger when multiple losses, loss of child, sibling or spouse, and loss due to unnatural cause were analyzed separately (P for trend or difference < 0.0001), and for women with high screening adherence (P for difference < 0.05). Among 1,696 women who had not developed cervical cancer, we further investigated the link between bereavement and HPV infection. Bereavement was associated with a 62% increased risk of HPV16 infection, high viral load, and recurrent infection, and was also more strongly associated with HPV infections designated as high-risk compared with low-risk determinants of cervical carcinogenesis. Collectively, our findings demonstrate that bereavement is associated with an increased risk of developing cervical cancer. Further, they suggest that this association may be attributed to stress-induced oncogenic HPV infections. Cancer Res; 76(3); 643–51. ©2015 AACR.
Selective Toxicity of Investigational Ixazomib for Human Leukemia Cells Expressing Mutant Cytoplasmic NPM1: Role of Reactive Oxygen Species
Authors: Garcia Jacqueline S. , Huang Min , Medeiros Bruno C. , Mitchell Beverly S.
Published: December 2015

Purpose: This study was performed to determine whether the investigational proteasome inhibitor ixazomib demonstrated selective antineoplastic activity against acute myelogenous leukemia cells expressing a mutated nucleophosmin-1 gene and to gain a better understanding of its mechanisms of action.

Experimental Design: The cytotoxic effects of ixazomib treatment were analyzed in human acute myelogenous leukemia (AML) cell lines and primary AML samples expressing wild-type or mutated NPM1 (NPMc+). The potential roles of oxidative stress in mediating cytotoxic activity were determined using flow cytometry, enzyme-based assays, and Western blots.

Results: Apoptosis induced by ixazomib was abrogated by knockdown of NPM1/NPMc+ expression using an inducible shRNA construct and enhanced by NPMc+ overexpression. Cytotoxicity was associated with superoxide generation and was reduced by the addition of the antioxidant N-acetylcysteine. AML cells expressing NPMc+ had significantly reduced levels of intracellular glutathione and NADPH associated with reduced antioxidant responses to drug treatment. Treatment of 3 patients with relapsed NPMc+ AML resulted in an antileukemic effect in 1 patient as demonstrated by a marked reduction of leukemic blasts in the peripheral blood. Efficacy was associated with superoxide generation, reduced glutathione levels, and reduced mRNA and protein expression of antioxidant effectors in responding cells.

Conclusions: In this study, a direct association was observed between NPMc+ expression in AML, reduced antioxidant responses, and enhanced sensitivity to an oral proteasome inhibitor that induces oxidative stress. These data suggest that intracellular determinants of antioxidant responses may be good predictors of therapeutic response to ixazomib. Clin Cancer Res; 22(8); 1978–88. ©2015 AACR.
Overcoming Antigen Escape with CAR T-cell Therapy
Authors: Jackson Hollie J. , Brentjens Renier J.
Published: December 2015

Summary: Sotillo and colleagues describe the molecular events associated with apparent loss of target antigen expression following CAR T-cell therapy. We propose that broader immune activation is required to prevent outgrowth of tumor antigen escape variants following targeted therapies. Cancer Discov; 5(12); 1238–40. ©2015 AACR.

See related article by Sotillo et al., p. 1282.
Individual and Complementary Effects of Human Papillomavirus Oncogenes on Epithelial Cell Proliferation and Differentiation
Authors: Bergner Sven , Halec Gordana , Schmitt Markus , Aubin François , Alonso Angel , Auvinen Eeva
Published: December 2015

Previous studies on human papillomavirus (HPV) type 16 protein functions have established the oncogenic nature of three viral proteins: E5, E6 and E7. Here we have studied the functions of these proteins by functional deletion of the individual E5, E6 or E7, or both E6 and E7 oncogenes in the context of the whole viral genome. These mutants, or the intact wild-type genome, were expressed from the natural viral promoters along with differentiation of epithelial HaCaT cells in three-dimensional collagen raft cultures. High episomal viral copy numbers were obtained using a transfection-based loxp-HPV16-eGFP-N1 vector system. All epithelial equivalents carrying the different HPV type 16 genomes showed pronounced hyperplastic and dysplastic morphology. Particularly the E7 oncogene, with contribution of E6, was shown to enhance cell proliferation. Specifically, the crucial role of E7 in HPV-associated hyperproliferation was clearly manifested. Based on morphological characteristics, immunohistochemical staining for differentiation and proliferation markers, and low expression of E1^E4, we propose that our raft culture models produce cervical intraepithelial neoplasia (CIN)1 and CIN2-like tissue. Our experimental setting provides an alternative tool to study concerted functions of HPV proteins in the development of epithelial dysplasia.
Recent Progress in Stem Cell Therapy for Diabetic Nephropathy
Authors: Liu Yang , Tang Sydney C.W.
Published: December 2015

Background: Diabetic nephropathy (DN) represents the leading cause of end-stage renal disease. Current therapeutic strategies for DN are very limited, and none of them can stop end-stage renal disease progression. Stem cell-based therapy showed encouraging outcomes in kidney disease, including experimental DN. Summary: Both podocytes and proximal tubular epithelial cells play key roles in the pathogenesis of DN and, accordingly, could be regarded as treatment targets. Multiple kinds of stem cells contribute to the regeneration of the injured kidney, including embryonic stem cells (ESCs), mesenchymal stem cells, and induced pluripotent stem cells (iPSCs). Stem cells exert reparatory effects mainly by homing to injured sites, directing differentiation, paracrine action, and immunoregulation. However, poor survival after transplantation under diabetic conditions and unsatisfactory animal models of advanced DN are major obstacles for achieving an efficacious therapeutic effect from stem cell transplantation. Recently, remarkable progress has been made both in the direct differentiation of human ESCs and iPSCs into renal cells and in the generation of tissue- and patient-specific iPSCs, offering a powerful tool to investigate DN mechanisms and to identify the ideal candidate cell for future clinical application. Key Message: This review provides updated information on recent progress and limitations of stem cell-based therapy for DN.
Comprehensive Molecular Analyses in a Case of Masked Philadelphia Chronic Myeloid Leukemia
Authors: Cattaneo Daniele , Morotti Denise , Bucelli Cristina , Cannone Marta , Zappa Manuela , Guerneri Silvana , Iurlo Alessandra
Published: December 2015

Here, we report the case of an 80-year-old woman with masked Philadelphia chronic myeloid leukemia (Ph CML). At diagnosis, qualitative PCR demonstrated the presence of a typical e14a2 configuration, and chromosome analysis showed an apparently normal female karyotype. However, FISH with BCR-ABL1 dual fusion probes gave a positive signal in 152/200 analyzed nuclei, with the fusion signal detected on the long arm of a cytogenetically normal chromosome 9. Using locus-specific probes for chromosome 9 and 22 telomeres, a third chromosome involvement was excluded. Furthermore, microarray analysis from the same specimens showed a normal result. Due to a high Charlson Comorbidity Index, the patient was treated with a reduced dose of imatinib, achieving a rapid hematological response after 1 month. However, after 6 months of imatinib therapy, she had to be considered as warning (Ph+ 26.5%, BCR-ABL1 >1%) according to the European LeukemiaNet 2013 recommendations. In conclusion, we confirmed the importance of a combination of cytogenetic and molecular techniques for the diagnosis and therapy monitoring of masked Ph CML, but, different from what has been reported in the literature so far, we cannot completely exclude the fact that the unusual cytogenetic pattern of this patient may have negatively influenced her response to tyrosine kinase inhibitor therapy.
Choroidal Thickness Changes in the Acute Attack Period in Patients with Familial Mediterranean Fever
Authors: Gundogan Fatih C. , Akay Fahrettin , Uzun Salih , Ozge Gokhan , Toyran Sami , Genç Halil
Published: December 2015

Purpose: The aim of this study was to evaluate choroidal thickness changes during acute attacks of familial Mediterranean fever (FMF). Methods: Fifty patients with FMF and 50 healthy controls were included. Choroidal thickness of each participant was measured at the foveola and horizontal nasal and temporal quadrants at 500-µm intervals to 1,500 µm from the foveola using spectral-domain optical coherence tomography. White blood cell count, erythrocyte sedimentation rate (ESR) and serum levels of fibrinogen and C-reactive protein (CRP) were evaluated. The clinical findings (peritonitis, arthritis and pleuritis) were noted. Results: Choroidal thickness was significantly thicker at all measurement points in FMF patients compared to healthy controls during an acute attack (p < 0.05). There were positive correlations between the choroidal thickness and ESR, fibrinogen and, particularly, CRP levels. Clinical findings did not change the choroidal thickness significantly (p > 0.05). Conclusions: Increased choroidal thickness in the acute phase of FMF is possibly related to the inflammatory edematous changes in the choroid.
Decreased Risk of Colorectal Cancer after Colonoscopy in Patients 76-85 Years Old in the United States
Authors: Wang Yize R. , Cangemi John R. , Loftus, Jr. Edward V. , Picco Michael F.
Published: December 2015

Background/Aims: The benefits of colonoscopy in reducing colorectal cancer (CRC) risk for patients over 75 years are controversial. We aimed to determine whether colonoscopy use is associated with a decreased risk of CRC in patients 76-85 years old in the United States (US). Patients and Methods: All patients in the Medicare 5% random sample of the Surveillance, Epidemiology and End Results-Medicare linked database 76-85 years old at outpatient colonoscopy between January 1, 1998 and December 31, 2002 were identified. Using the Kaplan-Meier method, we estimated the cumulative incidence of CRC in the above-mentioned colonoscopy group and compared with the control group of patients without colonoscopy. All patients were followed until diagnosis of CRC or carcinoma in situ, death or December 31, 2005. The multivariate Cox proportional hazards model was used in statistical analysis. CRC was separated by location into distal vs. proximal CRC in subgroup analysis. Results: Of 5,701 patients in the colonoscopy group, 37 (0.65%) patients were diagnosed with CRC, compared to 379 (1.55%) out of 24,437 patients in the control group (p < 0.001). The cumulative incidences of distal and proximal CRC were lower in the colonoscopy group compared to those in the control group (5-year distal CRC: 0.26 vs. 0.77%; 5-year proximal CRC: 0.43 vs. 0.79%, both p < 0.05). In multivariate Cox regression, colonoscopy was associated with decreased risk of all CRC (hazard ratio ((HR) 0.42, 95% CI 0.28-0.65), distal CRC (HR 0.36, 95% CI 0.18-0.70), and proximal CRC (HR 0.53, 95% CI 0.30-0.92)). Conclusion: Among patients 76-85 years old in the United States, colonoscopy use was associated with decreased risks of both distal and proximal CRC, with a smaller risk reduction in distal colon. Due to inherent limitations associated with our retrospective design, future prospective studies are needed to validate these findings.
LRP1 Regulates Retinal Angiogenesis by Inhibiting PARP-1 Activity and Endothelial Cell Proliferation
Authors: Mao Hua , Lockyer Pamela , Townley-Tilson W.H. Davin , Xie Liang , Pi Xinchun
Published: December 2015

Objective—

We recently demonstrated that low-density lipoprotein receptor–related protein 1 (LRP1) is required for cardiovascular development in zebrafish. However, what role LRP1 plays in angiogenesis remains to be determined. To better understand the role of LRP1 in endothelial cell function, we investigated how LRP1 regulates mouse retinal angiogenesis.

Approach and Results—

Depletion of LRP1 in endothelial cells results in increased retinal neovascularization in a mouse model of oxygen-induced retinopathy. Specifically, retinas in mice lacking endothelial LRP1 have more branching points and angiogenic sprouts at the leading edge of the newly formed vasculature. Increased endothelial proliferation as detected by Ki67 staining was observed in LRP1-deleted retinal endothelium in response to hypoxia. Using an array of biochemical and cell biology approaches, we demonstrate that poly(ADP-ribose) polymerase-1 (PARP-1) directly interacts with LRP1 in human retinal microvascular endothelial cells. This interaction between LRP1 and PARP-1 decreases under hypoxic condition. Moreover, LRP1 knockdown results in increased PARP-1 activity and subsequent phosphorylation of both retinoblastoma protein and cyclin-dependent kinase 2, which function to promote cell cycle progression and angiogenesis.

Conclusions—

Together, these data reveal a pivotal role for LRP1 in endothelial cell proliferation and retinal neovascularization induced by hypoxia. In addition, we demonstrate for the first time the interaction between LRP1 and PARP-1 and the LRP1-dependent regulation of PARP-1–signaling pathways. These data bring forth the possibility of novel therapeutic approaches for pathological angiogenesis.
National Trends in the Use of Cardiac Resynchronization Therapy With or Without Implantable Cardioverter-Defibrillator
Authors: Lindvall Charlotta , Chatterjee Neal A. , Chang Yuchiao , Chernack Betty , Jackson Vicki A. , Singh Jagmeet P. , Metlay Joshua P.
Published: December 2015

Background—

Candidates for cardiac resynchronization therapy (CRT) receive either a biventricular pacemaker or a biventricular pacemaker with an implantable cardioverter-defibrillator (CRT-D). Optimal device selection remains challenging because the benefit of implantable cardioverter-defibrillator therapy may not be uniform, particularly in patients at competing risk of nonsudden death.

Methods and Results—

In this serial cross-sectional study using the National Inpatient Sample database, we identified 311 086 admissions associated with CRT implant between 2006 to 2012. CRT-D was the most common device type (86.1%), including in patients ≥75 years of age with ≥5 Elixhauser comorbidities (75.5%). Multivariate predictors of CRT-D implant included demographic, clinical, and geographic factors: prior ventricular arrhythmia (rate ratio [RR], 1.14; 95% CI, 1.13–1.14), ischemic heart disease (RR, 1.11; 95% CI, 1.10–1.11), male sex (RR, 1.10; 95% CI, 1.09–1.10), black race (RR, 1.06; 95% CI: 1.04–1.07), and Northeast geographic region (RR, 1.06; 95% CI, 1.04–1.09). There was significant interhospital variation in the use of CRT-D (10–90 percentile range, 72.9%–98.0% CRT-D).

Conclusions—

The majority of patients in this contemporary US cohort underwent implantation of CRT-D. Predictors of CRT-D implant included demographic, clinical, and geographic factors. In patient subgroups predicted to have an attenuated benefit from implantable cardioverter-defibrillator therapy (older adults with multiple comorbidities), CRT-D remained the dominant device type. An improved understanding of the determinants of device selection may aid in decision making and ultimately better align patient risk with device benefit at the time of CRT implantation.
The effect of steroid hormone feeds on the reproductive biology of the spiny lobster, Panulirus interruptus (J. W. Randall, 1840) (Decapoda, Palinura)
Authors: Nan Fan-Hua , Wu Yu-Sheng , Chang Nung-Chieh
Published: December 2015

In this study, the effects of adding steroid hormones to the feeds administered to cultures of the spiny lobster, Panulirus interruptus (J. W. Randall, 1840), were investigated. The results indicate that the addition of steroid hormones in the feeds evoke (1) an increase in the ratio of ovigerous versus non-ovigerous females of up to 13.68% as compared to the controls; (2) fertilized females were present several months longer in the treatment group than in the control group; and (3) the ovigerous period, i.e., the time from fertilization until release of the young, was substantially shorter under a regime of feeding with steroid hormone additions. As a conclusion, enrichment of the feeds with steroid hormones thus distinctly increases the yield of young spiny lobsters in the course of a year cycle.
The interannual variability of size at maturity of the brown crab Callinectes bellicosus Stimpson, 1859 (Brachyura, Portunidae) in the Gulf of California
Authors: Rodríguez-Domínguez Guillermo , Castillo-Vargasmachuca Sergio G. , Pérez-González Raúl , Aragón-Noriega E. Alberto
Published: December 2015

This study examines how the size at maturity (CW50%) of Callinectes bellicosus Stimpson, 1859 is affected by environmental variability and by the source of the data. The samples were obtained from a coastal lagoon in the eastern Gulf of California between 2000 and 2003, and in 2011. To explore for interannual variation in environmental conditions, an extended negative power-law model was used, with SSTa as the annual sum of monthly sea surface temperature anomalies and Chl-a as the monthly chlorophyll a mean in a year. The interannual variability in the CW50% of C. bellicosus was also calculated. We found that the percent of mature female drives inter-annual variability in CW50% and that the addition of Chl-a to the model does not contribute further to the explanation of this phenomenon. The hypothesis that environmental variations affect the reproductive dynamics of the stocks needs to be tested in this species in another area.
Paromola alcocki faughni Serène & Lohavanijaya, 1973, a junior synonym of Paromola macrochira Sakai, 1961 (Decapoda, Brachyura, Homolidae)
Authors: Ng Peter K. L.
Published: December 2015

The identity of the homolidMoloha alcocki faughni(Serène & Lohavanijaya, 1973), from the South China Sea, is clarified, and is here regarded as a junior subjective synonym ofParomola macrochiraSakai, 1916. The taxonomy and reliability of various generic and specific characters ofP. macrochiraare also discussed.
Using DNA barcodes to detect non-indigenous species: the case of the Asian copepod Mesocyclops pehpeiensis Hu, 1943 (Cyclopidae) in two regions of the world
Authors: Montoliu Lucía , Miracle María R. , Elías-Gutiérrez Manuel
Published: December 2015

To date, little attention has been paid to analyses of copepods as exotic species. The genusMesocyclops, a freshwater cyclopoid, has a worldwide distribution, but individual species within the genus have a quite restricted geographical range.Mesocyclops pehpeiensisHu, 1943 is a Central-East Asian species, rarely found outside of this area, and when it appears should be considered as non-native. Based on morphology and DNA barcode analyses, using the COI gene, we confirmed records ofM. pehpeiensisin two ponds in Mexico and in a rice paddy near Valencia, Spain. The morphology of this species, based on morphometric analyses, was found to be variable, but DNA barcoding confirmed the same identity for specimens from two continents. The extremely low COI genetic divergence among these disjunct populations ofM. pehpeiensisstrongly evidences anthropogenic translocations. DNA barcoding can be a fast and useful analytical tool to accurately identify exotic species across the world.
Prayer and Identity in Varying Contexts: The Case of the Words of the Luminaries
Authors: Chazon Esther G.
Published: December 2015

This article examines the ways in which a single liturgical text, the Words of the Luminaries, would be read by two diachronically and ideologically different audiences: the implied audience of the pre-Qumranic author and the actual audience of the Yaḥad community at Qumran, which preserved this text. The text’s first person plural rhetorical stance invites the implied audience to identify with its “we, Israel” voice and with the fundamental beliefs, ideas, and values encoded in the “we” discourse. These major ideological themes conjoined with the pan-Israelite rhetorical stance convey messages about identity and ideology that are dissonant with the Yaḥad’s deterministic, dualistic ideology and sectarian identity as the elect “Congregation of God.” Nonetheless, the common past, foundational narratives, and shared values, especially regarding the Torah, would facilitate the Yaḥad’s reception of this originally non-Qumranic text and enable it to be read through the lens of the Yaḥad’s sectarian identity.
On the Accentuation of Vedic -ti-Abstracts
Authors: Lundquist Jesse
Published: December 2015

This paper offers a new explanation for the barytone and oxytone accents attested for the Vedic -ti-stems. The two accents are commonly taken to derive from separate reflexes of a once unified proterokinetic paradigm, and it is against this account I will propose the divergence is instead chronological: oxytones belong to the oldest layer of the Vedas, barytones to the younger. The diachronic change we observe occurs within the Vedic period, and is localized to the accentual properties associated with the suffix -ti-. Our philological analysis of the -ti-stems across Vedic texts will support the “compositional approach” championed recently by Kiparsky (2010) and Kümmel (2014) against previous approaches. Finally, I will suggest answers to the question of how the accentual properties of -ti- changed based on recent research into the lexical phonology of accent systems.
Can playing Minecraft improve teenagers’ information literacy?
Authors: Bebbington Sandra , Vellino Andre
Published: December 2015

Some research suggests that a significant number of Generation Z teenagers (those born in the late 1990s or early 2000s) display an insufficient level of information literacy (IL) to function effectively in an information-based society. Yet many of them are gamers who succeed at accomplishing game-related tasks that require a number of IL skills such as information seeking, the critical assessment of sources and relevance ranking of information. This paper describes the results of an interpretive case study of the information behaviours of teenage gamers that supports the hypothesis that the online game Minecraft supports the development of such IL skills. The online interactions of 510 participants of a public discussion forum on Minecraft and interviews from eight teenage Minecraft gamers, as well as the game itself, were analysed. This study suggest that some aspects of Minecraft’s design effectively induce players to seek out game-related information in affinity spaces (online informal learning spaces), select appropriate sources, evaluate the information shared by fellow gamers and decide which information best satisfies their needs.