bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Sequence Coverage through Combined Targeting of Variant and Conserved Epitopes Correlates with Control of HIV Replication
Authors: Sunshine Justine , Kim Moon , Carlson Jonathan M. , Heckerman David , Czartoski Julie , Migueles Stephen A. , Maenza Janine , McElrath M. Juliana , Mullins James I. , Frahm Nicole
Published: November 2013

A major challenge in the development of an HIV vaccine is that of contending with the extensive sequence variability found in circulating viruses. Induction of HIV-specific T-cell responses targeting conserved regions and induction of HIV-specific T-cell responses recognizing a high number of epitope variants have both been proposed as strategies to overcome this challenge. We addressed the ability of cytotoxic T lymphocytes from 30 untreated HIV-infected subjects with and without control of virus replication to recognize all clade B Gag sequence variants encoded by at least 5% of the sequences in the Los Alamos National Laboratory HIV database (1,300 peptides) using gamma interferon and interleukin-2 (IFN-γ/IL-2) FluoroSpot analysis. While targeting of conserved regions was similar in the two groups (
P
= 0.47), we found that subjects with control of virus replication demonstrated marginally lower recognition of Gag epitope variants than subjects with normal progression (
P
= 0.05). In viremic controllers and progressors, we found variant recognition to be associated with viral load (
r
= 0.62,
P
= 0.001). Interestingly, we show that increased overall sequence coverage, defined as the overall proportion of HIV database sequences targeted through the Gag-specific repertoire, is inversely associated with viral load (
r
= −0.38,
P
= 0.03). Furthermore, we found that sequence coverage, but not variant recognition, correlated with increased recognition of a panel of clade B HIV founder viruses (
r
= 0.50,
P
= 0.004). We propose sequence coverage by HIV Gag-specific immune responses as a possible correlate of protection that may contribute to control of virus replication. Additionally, sequence coverage serves as a valuable measure by which to evaluate the protective potential of future vaccination strategies.
Evolution of Bovine Ephemeral Fever Virus in the Australian Episystem
Authors: Trinidad Lee , Blasdell Kim R. , Joubert D. Albert , Davis Steven S. , Melville Lorna , Kirkland Peter D. , Coulibaly Fasséli , Holmes Edward C. , Walker Peter J.
Published: November 2013

Bovine ephemeral fever virus (BEFV) is an arthropod-borne rhabdovirus that causes a debilitating disease of cattle in Africa, Asia, and Australia; however, its global geodynamics are poorly understood. An evolutionary analysis of G gene (envelope glycoprotein) ectodomain sequences of 97 BEFV isolates collected from Australia during 1956 to 2012 revealed that all have a single common ancestor and are phylogenetically distinct from BEFV sampled in other geographical regions. The age of the Australian clade is estimated to be between 56 and 65 years, suggesting that BEFV has entered the continent on few occasions since it was first reported in 1936 and that the 1955-1956 epizootic was the source of all currently circulating viruses. Notably, the Australian clade has evolved as a single genetic lineage across the continent and at a high evolutionary rate of ∼10
−3
nucleotide substitutions/site/year. Screening of 66 isolates using monoclonal antibodies indicated that neutralizing antigenic sites G1, G2, and G4 have been relatively stable, although variations in site G3a/b defined four antigenic subtypes. A shift in an epitope at site G3a, which occurred in the mid-1970s, was strongly associated with a K218R substitution. Similarly, a shift at site G3b was associated primarily with substitutions at residues 215, 220, and 223, which map to the tip of the spike on the prefusion form of the G protein. Finally, we propose that positive selection on residue 215 was due to cross-reacting neutralizing antibody to Kimberley virus (KIMV).

IMPORTANCE
This is the first study of the evolution of BEFV in Australia, showing that the virus has entered the continent only once during the past 50 to 60 years, it is evolving at a relatively constant rate as a single genetic lineage, and although the virus is relatively stable antigenically, mutations have resulted in four antigenic subtypes. Furthermore, the study shows that the evolution of BEFV in Australia appears to be driven, at least in part, by cross-reactive antibodies to KIMV which has a similar distribution and ecology but has not been associated with disease. As BEFV and KIMV are each known to be present in Africa and Asia, this interaction may occur on a broader geographic scale.
The Connection Domain Mutation N348I in HIV-1 Reverse Transcriptase Enhances Resistance to Etravirine and Rilpivirine but Restricts the Emergence of the E138K Resistance Mutation by Diminishing Viral Replication Capacity
Authors: Xu Hong-Tao , Colby-Germinario Susan P. , Oliveira Maureen , Han Yingshan , Quan Yudong , Zanichelli Veronica , Wainberg Mark A.
Published: November 2013

Clinical resistance to rilpivirine (RPV), a novel nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI), is associated an E-to-K mutation at position 138 (E138K) in RT together with an M184I/V mutation that confers resistance against emtricitabine (FTC), a nucleoside RT inhibitor (NRTI) that is given together with RPV in therapy. These two mutations can compensate for each other in regard to fitness deficits conferred by each mutation alone, raising the question of why E138K did not arise spontaneously in the clinic following lamivudine (3TC) use, which also selects for the M184I/V mutations. In this context, we have investigated the role of a N348I connection domain mutation that is prevalent in treatment-experienced patients. N348I confers resistance to both the NRTI zidovudine (ZDV) and the NNRTI nevirapine (NVP) and was also found to be associated with M184V and to compensate for deficits associated with the latter mutation. Now, we show that both N348I alone and N348I/M184V can prevent or delay the emergence of E138K under pressure with RPV or a related NNRTI, termed etravirine (ETR). N348I also enhanced levels of resistance conferred by E138K against RPV and ETR by 2.2- and 2.3-fold, respectively. The presence of the N348I or M184V/N348I mutation decreased the replication capacity of E138K virus, and biochemical assays confirmed that N348I, in a background of E138K, impaired RT catalytic efficiency and RNase H activity. These findings help to explain the low viral replication capacity of viruses containing the E138K/N348I mutations and how N348I delayed or prevented the emergence of E138K in patients with M184V-containing viruses.
A Cell-Biased Effect of Estrogen in Prion Infection
Authors: Molloy Brendan , McMahon Hilary E. M.
Published: November 2013

Prion disorders are associated with the accumulation of a misfolded form (PrP
Sc
) of the normal prion protein, PrP
C
. Here, we show that estrogen acts as a regulator of the processes of both prion infection and prion maintenance. Estrogen was found to be cell biased in its effect; it protected cells against prion infection in a prevention mode and enabled prion maintenance in a treatment mode. These processes were regulated by the estrogen receptor subtypes Erα and Erβ. By using specific receptor agonists, Erα was found to be the main receptor active in slowing prion infection, whereas in chronically infected cells, although Erα allowed partial maintenance of PrP
Sc
levels, Erβ was the main receptor involved in maintaining PrP
Sc
in a treatment paradigm. A cell-biased effect of estrogen has been reported for other neurodegenerative disorders, including Alzheimer's disease. Estrogen's effect is dependent on the cell's health status, which impacts the use of estrogen. This work also identified that by targeting the estrogen receptors with the selective estrogen receptor modulators tamoxifen (Tam) and 4-hydroxy-tamoxifen (OHT), PrP
Sc
could be cleared from prion-infected cell culture. Tam and OHT had half-maximal inhibitory concentrations for clearance of PrP
Sc
of 0.47 μM and 0.14 nM, respectively. This work identifies further factors involved in the prion disease process, and through antagonism of the estrogen system, we demonstrate that the estrogen system is a target for controlling PrP
Sc
levels.
APOBEC3 Deaminases Induce Hypermutation in Human Papillomavirus 16 DNA upon Beta Interferon Stimulation
Authors: Wang Zhe , Wakae Kousho , Kitamura Kouichi , Aoyama Satoru , Liu Guangyan , Koura Miki , Monjurul Ahasan M. , Kukimoto Iwao , Muramatsu Masamichi
Published: November 2013

Apolipoprotein B mRNA-editing catalytic polypeptide 3 (APOBEC3) proteins are interferon (IFN)-inducible antiviral factors that counteract various viruses such as hepatitis B virus (HBV) and human immunodeficiency virus type 1 (HIV-1) by inducing cytidine (C)-to-uracil (U) mutations in viral DNA and inhibiting reverse transcription. However, whether APOBEC3 proteins (A3s) can hypermutate human papillomavirus (HPV) viral DNA and exhibit antiviral activity in human keratinocyte remains unknown. Here we examined the involvement of A3s in the HPV life cycle using cervical keratinocyte W12 cells, which are derived from low-grade lesions and retain episomal HPV16 genomes in their nuclei. We focused on the viral E2 gene as a potential target for A3-mediated hypermutation because this gene is frequently found as a boundary sequence in integrated viral DNA. Treatment of W12 cells with beta interferon (IFN-β) increased expression levels of A3s such as A3A, A3F, and A3G and induced C-to-U conversions in the E2 gene in a manner depending on inhibition of uracil DNA glycosylase. Exogenous expression of A3A and A3G also induced E2 hypermutation in W12 cells. IFN-β-induced hypermutation was blocked by transfection of small interfering RNAs against A3G (and modestly by those against A3A). However, the HPV16 episome level was not affected by overexpression of A3A and A3G in W12 cells. This study demonstrates that endogenous A3s upregulated by IFN-β induce E2 hypermutation of HPV16 in cervical keratinocytes, and a pathogenic consequence of E2 hypermutation is discussed.
Headache after lumbar puncture: randomised crossover trial of 22-gauge versus 25-gauge needles
Authors: Crock Catherine , Orsini Francesca , Lee Katherine J , Phillips Roderic J
Published: November 2013

Objectives

To compare the frequency of headache and the procedure time following lumbar puncture (LP) using a 25-gauge needle compared to a 22-gauge needle.

Design

4-period crossover blinded randomised controlled trial.

Setting

Oncology unit, Royal Children's Hospital, Melbourne.

Patients

Children aged 4–15 years at enrolment having LPs as part of their treatment for leukaemia.

Interventions

Each child was allocated a random sequence of four LPs, two with a 22-gauge and two with a 25-gauge needle.

Outcome measures

The presence of post-LP headache. Secondary outcomes included the presence of any headache, procedure time and impact of headache on the family.

Results

Data on 341 procedures in 93 randomised children were analysed. There was little difference in the incidence of post-LP headache between the two needle sizes (22-gauge 7.2%, 95% CI 3.8 to 12.2; 25-gauge 4.6%, 95% CI 2.0 to 8.9, p=0.3) or in the incidence of any headache (22-gauge 18% 95% CI 12.5 to 24.6; 25-gauge 15%, 95% CI 10.0 to 21.1, p=0.4). Use of the 25-gauge needle was associated with longer procedure times. The incidence of post-LP headache showed little evidence of an age effect (OR =1.1, 95% CI 0.98 to 1.3) and was higher in girls than in boys (11% vs 3%, respectively, OR=3.3, 95% CI 1.3 to 8.4, p=0.014). Fifty-five per cent of families with a child with a post-LP headache assessed the overall functional impact as moderate or severe.

Conclusions

There was little difference in the occurrence of post-LP headache or any headache between procedures carried out using the 22-gauge or 25-gauge needles. Depending on the circumstances of the procedure and the experience of the operator, either gauge may be appropriate for an LP in a child.
Seizure as an initial presentation of human immunodeficiency virus: acute toxoplasmosis mimicking glioblastoma multiforme
Authors: Parekh Parth , Boggs Jody P , Silverberg Marc , Marik Paul
Published: November 2013

We present a case of a 46-year-old man with a history significant only for hypertension and depression that presented with a new onset seizure resulting from a right parietal lobe mass. Further evaluation determined the parietal mass to be central nervous system toxoplasmosis, which was the initial presentation of his underlying HIV/AIDS. This case provided a diagnostic challenge and demonstrates the importance of a thorough evaluation as it pertains to a newly diagnosed brain lesion.
Predictive role of C reactive protein in stroke recurrence after cardioembolic stroke: the Fukuoka Stroke Registry
Authors: Kuwashiro Takahiro , Sugimori Hiroshi , Ago Tetsuro , Kuroda Junya , Kamouchi Masahiro , Kitazono Takanari ,   for the FSR Investigators (see appendix)
Published: November 2013

Objectives

We investigated the clinical characteristics of patients with stroke recurrence in the first year after cardioembolic stroke, and determined the predictors associated with recurrence.

Design

A prospective cohort study.

Setting

Multicentre study at the Fukuoka prefecture in Japan.

Participants

We enroled 2084 consecutive patients who were hospitalised in stroke centres within 7 days of onset from June 2007 to October 2009. The clinical characteristics of patients were assessed on admission, and the clinical course of all patients was followed for 1 year.

Results

Of all patients, 425 (234 men, 76±11 years of age) had cardioembolic stroke and were included in this study. Fifty-one patients (12%) suffered a recurrence during the follow-up period. Age (HR 1.04, 95% CI 1.01 to 1.06, p=0.014), and level of C reactive protein (HR 1.01, 95% CI 1.00 to 1.02, p=0.018) on admission were significantly associated with recurrence in the univariate analyses. Male gender (HR 0.61, 95% CI 0.35 to 1.05, p=0.076), body mass index (HR 0.94, 95% CI 0.87 to 1.01, p=0.093), hypertension (HR 0.59, 95% CI 0.33 to 1.06, p=0.079), diastolic blood pressure (HR 0.99, 95% CI 0.97 to 1.00, p=0.087) and haematocrit (HR 0.95, 95% CI 0.91 to 1.00, p=0.052) were marginally significant in the univariate Cox analyses. Multivariate Cox proportional hazards analysis showed that age (HR 1.03, 95% CI 1.00 to 1.06, p=0.031, per 1-year increase), and C reactive protein (HR 1.01, 95% CI 1.00 to 1.02, p=0.022, per 1 mg/L increase) were independent predictors of a recurrence in the first year after cardioembolic stroke.

Conclusions

In patients with cardioembolic ischaemic stroke, age and C reactive protein are independent risk factors for recurrence in the first year after onset.
Type 1 plasminogen activator inhibitor as a common risk factor for cancer and ischaemic vascular disease: the EPICOR study
Authors: Iacoviello Licia , Agnoli Claudia , De Curtis Amalia , di Castelnuovo Augusto , Giurdanella Maria Concetta , Krogh Vittorio , Mattiello Amalia , Matullo Giuseppe , Sacerdote Carlotta , Tumino Rosario , Vineis Paolo , de Gaetano Giovanni , Panico Salvatore , Donati Maria Benedetta
Published: November 2013

Objectives

We examined the association of plasminogen activator inhibitor-1 (PAI-1) levels with colorectal cancer, breast cancer, acute coronary syndrome (ACS) and ischaemic stroke.

Design

Nested case-cohort study.

Setting

The European Prospective Investigation into Cancer and Nutrition-Italy cohort.

Participants

A centre-stratified random sample of 850 participants (286 men, 564 women) was selected as subcohort and compared with 303 colorectal cancers, 617 breast cancers, 688 ACS and 158 ischaemic strokes, in a mean follow-up of 9.11 years.

Main outcomes and measures

Primary incident cases of colon cancer, breast cancer, ACS and ischaemic stroke. PAI-1 levels were measured in citrated plasma by ELISA. HR and 95% CI, adjusted by relevant confounders and stratified by centre, were estimated by a Cox regression model using Prentice method.

Results

Individuals in the highest compared with the lowest quartile of PAI-1 had significantly increased risk of colorectal cancer (RR=2.28; 95% CI 1.46 to 3.55; P for trend<0.0012), breast cancer (HR=1.70; 95% CI 1.21 to 2.39; p<0.0055), ACS (HR=2.57; 95% CI 1.75 to 3.77; p<0.001) and ischaemic stroke (HR=2.27; 95% CI 1.28 to 4.03; p<0.0017), after adjustment for sex and age. Additional adjustment for disease-specific confounders, insulin or other metabolic variables did not modify the associations. Risk of colon cancer was stronger for men and for whole and distal colon localisation. Risk for breast cancer was stronger in postmenopausal women.

Conclusions

Our data provide the first evidence that elevated levels of PAI-1 are potential risk factors for colorectal and breast cancer and a common pathway for cancer and cardiovascular disease.
Socioeconomic and disability consequences of injuries in the Sudan: a community-based survey in Khartoum State
Authors: El Tayeb Sally , Abdalla Safa , Heuch Ivar , Van den Bergh Graziella
Published: November 2013

Background

Fatal and non-fatal injuries are of increasing public health concern globally, particularly in low and middle-income countries. Injuries sustained by individuals also impact society, creating a loss of productivity with serious economic consequences. In Sudan, there is no documentation of the burden of injuries on individuals and society.

Methods

A community-based survey was performed in Khartoum State, using a stratified two-stage cluster sampling technique. Households were selected in each cluster by systematic random sampling. Face-to-face interviews during October and November 2010 were conducted. Fatal injuries occurring during 5 years preceding the survey and non-fatal injuries occurring during 12 months preceding interviews were included.

Results

The total number of individuals included was 5661, residing in 973 households. There were 28 deaths due to injuries out of a total of 129 reported deaths over 5 years. A total of 441 cases of non-fatal injuries occurred during the 12 months preceding the survey. The number of disability days differed significantly between mechanisms of injury. Road traffic crashes and falls caused the longest duration of disability. Men had a higher probability than women of losing a job due to an injury.

Conclusions

This study demonstrates the importance of prioritising prevention of road traffic crashes and falls. The loss of productivity in lower socioeconomic strata highlights the need for social security policies. Further research is needed for estimating the economic cost of injuries in Sudan.
Location-based HIV behavioural surveillance among MSM in Auckland, New Zealand 2002–2011: condom use stable and more HIV testing
Authors: Saxton Peter J W , Dickson Nigel P , Hughes Anthony J
Published: November 2013

Objectives

Over the last decade, annual HIV diagnoses among men who have sex with men (MSM) in New Zealand increased, then stabilised in 2006 and have not increased further. The aim was to examine trends in behaviours in order to better understand this pattern and inform community-based prevention.

Methods

From 2002 to 2011, we conducted five repeat cross-sectional behavioural surveillance surveys among MSM at community locations in Auckland (fair day, gay bars, sex-on-site venues; n=6091). Participation was anonymous and self-completed. Recruitment methods were consistent at each round.

Results

Overall, the samples became more ethnically diverse and less gay community attached over time. Condom use during anal intercourse was stable across three partnering contexts (casual, current regular fuckbuddy, current regular boyfriend), with a drop among casual contacts in 2011 only. In the 6 months prior to surveys, there was a gradual decline over time in the proportion reporting >20 male partners, an increase in acquiring partners from the internet and increases in engagement in anal intercourse in some partnering contexts. HIV testing in the 12 months prior to surveys rose from 35.1% in 2002 to 50.4% in 2011, mostly from 2008.

Conclusions

This first indepth examination of trends in HIV-related behaviours among five consecutive large and diverse samples of MSM in New Zealand does not suggest condom use is declining. However, subtle changes in sexual networks and partnering may be altering the epidemic determinants in this population and increasing exposure.
Protective Effect of Calculus Bovis Sativus on Intrahepatic Cholestasis in Rats Induced by α-Naphthylisothiocyanate
Authors: Wu Tao , Chang Mu-Jun , Xu Yan-Jiao , Li Xi-Ping , Du Guang , Liu Dong
Published: November 2013

Calculus Bovis Sativus (also referred to as in vitro Cultured Calculus Bovis), an artificial substitute of natural Calculus Bovis (Niuhuang in Chinese, a traditional Chinese medicine), has been widely used to relieve fever, diminish inflammation and normalize gallbladder function in the last decade. This study aims to investigate the effects and possible mechanisms of Calculus Bovis Sativus on α-naphthylisothiocyanate (ANIT)-induced intrahepatic cholestasis in rats. Calculus Bovis Sativus (50, 100 and 200 mg/kg per day) was intragastrically (i.g.) given to experimental rats for seven consecutive days. A single dose of ANIT (100 mg/kg i.g.) was given to rats on the fifth day to induce intrahepatic cholestasis. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkalinephosphatase (ALP) and total bilirubin (TBIL) were determined through biochemical methods. The bile duct was cannulated with a PE 10 polyethylene tube to collect bile for two hours and bile flow was calculated by the weight of each specimen. Moreover, the mechanism of Calculus Bovis Sativus was elucidated by determining liver malondialdehyde (MDA) content and superoxide dismutase (SOD) activity. The biochemical observations were supplemented by histopathological examinations. Our results showed that Calculus Bovis Sativus (50, 100 and 200 mg/kg) significantly prevented ANIT-induced changes in bile flow and serum levels of ALT, AST, ALP and TBIL. Furthermore, Calculus Bovis Sativus (50, 100 and 200 mg/kg) significantly reduced the elevated hepatic MDA content induced by ANIT and increased the hepatic SOD activity suppressed by ANIT. Accordingly, histopathology of the liver tissue showed that pathological injuries were relieved after Calculus Bovis Sativus (50, 100 and 200 mg/kg) pretreatment. In conclusion, Calculus Bovis Sativus exerted a protective effect on ANIT-induced intrahepatic cholestasis in rats, which may result from the attenuated oxidative damage in liver tissues.
FTIR SPECTROSCOPIC STUDIES ON CROSS LINKING OF SU-8 PHOTORESIST
Authors: KALAISELVI S. M. P. , TAN T. L. , RAWAT R. S. , LEE P. , HEUSSLER S. P. , BREESE M. B. H.
Published: November 2013

The usage of chemically-amplified, negative tone SU-8 photoresist is numerous, spanning industrial, scientific and medical fields. Hence, in this study, some preliminary studies were conducted to understand the dosage and heat treatment requirements of the SU-8 photoresist essential for pattern generation using X-ray lithography. In this work, using Synchrotron as the X-ray source, SU-8 photoresist was characterized for X-ray lithography in terms of its process parameters such as X-ray exposure dose, post exposure bake (PEB) time and temperature for various photoresist thicknesses which is considered worthwhile in view of applications of SU-8 for the fabrication of very high aspect ratio micro structures. The process parameters were varied and the resultant cross linking of the molecular chains of the photoresist was accurately monitored using a Fourier Transform Infra-Red (FTIR) spectrometer and the results are discussed. The infrared absorption peak at 914 cm-1 in the spectrum of the SU-8 photoresist was found to be a useful indicator for the completion of cross linking in the SU-8 photoresist. Results show that the cross linking of the SU-8 photoresist is at a higher rate from 0 J/cm3 to 30 J/cm3 after which the peak almost saturates regardless of the PEB time. It is a good evidence for the validation of dosage requirement of SU-8 photoresist for effective completion of cross linking, which in turn is a requirement for efficient fabrication of micro and nano structures. An analogous behavior was also observed between the extent of cross linking and the PEB time and temperature. The rate of cross linking declines after a certain period of PEB time regardless of PEB temperature. The obtained results also show a definite relation between variation of the absorbance area of the peak at 914 cm-1 and the X-ray exposure dose.
SHEAR ANISOTROPIC INHOMOGENEOUS BESOV SPACES IN ℝd
Authors: VERA DANIEL
Published: November 2013

We define distribution spaces in ℝd via ℓq(Lp) norms of a sequence of convolutions of [Formula: see text] with smooth functions, the shearlet system. Then, we define associated sequence spaces and prove characterization with the shearlet coefficients. We also prove continuous embeddings between some shear anisotropic inhomogeneous spaces and between classical (dyadic isotropic) inhomogeneous spaces and shear anisotropic inhomogeneous spaces.
A Review of Generic Program Visualization Systems for Introductory Programming Education
Authors: Sorva Juha , Karavirta Ville , Malmi Lauri
Published: November 2013

This article is a survey of program visualization systems intended for teaching beginners about the runtime behavior of computer programs. Our focus is on generic systems that are capable of illustrating many kinds of programs and behaviors. We inclusively describe such systems from the last three decades and review findings from their empirical evaluations. A comparable review on the topic does not previously exist; ours is intended to serve as a reference for the creators, evaluators, and users of educational program visualization systems. Moreover, we revisit the issue of learner engagement which has been identified as a potentially key factor in the success of educational software visualization and summarize what little is known about engagement in the context of the generic program visualization systems for beginners that we have reviewed; a proposed refinement of the frameworks previously used by computing education researchers to rank types of learner engagement is a side product of this effort. Overall, our review illustrates that program visualization systems for beginners are often short-lived research prototypes that support the user-controlled viewing of program animations; a recent trend is to support more engaging modes of user interaction. The results of evaluations largely support the use of program visualization in introductory programming education, but research to date is insufficient for drawing more nuanced conclusions with respect to learner engagement. On the basis of our review, we identify interesting questions to answer for future research in relation to themes such as engagement, the authenticity of learning tasks, cognitive load, and the integration of program visualization into introductory programming pedagogy.
An Empirical Investigation into Programming Language Syntax
Authors: Stefik Andreas , Siebert Susanna
Published: November 2013

Recent studies in the literature have shown that syntax remains a significant barrier to novice computer science students in the field. While this syntax barrier is known to exist, whether and how it varies across programming languages has not been carefully investigated. For this article, we conducted four empirical studies on programming language syntax as part of a larger analysis into the, so called, programming language wars. We first present two surveys conducted with students on the intuitiveness of syntax, which we used to garner formative clues on what words and symbols might be easy for novices to understand. We followed up with two studies on the accuracy rates of novices using a total of six programming languages: Ruby, Java, Perl, Python, Randomo, and Quorum. Randomo was designed by randomly choosing some keywords from the ASCII table (a metaphorical placebo). To our surprise, we found that languages using a more traditional C-style syntax (both Perl and Java) did not afford accuracy rates significantly higher than a language with randomly generated keywords, but that languages which deviate (Quorum, Python, and Ruby) did. These results, including the specifics of syntax that are particularly problematic for novices, may help teachers of introductory programming courses in choosing appropriate first languages and in helping students to overcome the challenges they face with syntax.
RBP-J in FOXD1+ renal stromal progenitors is crucial for the proper development and assembly of the kidney vasculature and glomerular mesangial cells
Authors: Lin E. E. , Sequeira-Lopez M. L. S. , Gomez R. A.
Published: November 2013

The mechanisms underlying the establishment, development, and maintenance of the renal vasculature are poorly understood. Here, we propose that the transcription factor “recombination signal binding protein for immunoglobulin kappa J region” (RBP-J) plays a key role in the differentiation of the mural cells of the kidney arteries and arterioles, as well as the mesangial cells of the glomerulus. Deletion of RBP-J in renal stromal cells of the forkhead box D1 (FOXD1) lineage, which differentiate into all the mural cells of the kidney arterioles along with mesangial cells and pericytes, resulted in significant kidney abnormalities and mortality by day 30 postpartum ( P30). In newborn mutant animals, we observed a decrease in the total number of arteries and arterioles, along with thinner vessel walls, and depletion of renin cells. Glomeruli displayed striking abnormalities, including a failure of FOXD1-descendent cells to populate the glomerulus, an absence of mesangial cells, and in some cases complete loss of glomerular interior structure and the development of aneurysms. By P30, the kidney malformations were accentuated by extensive secondary fibrosis and glomerulosclerosis. We conclude that RBP-J is essential for proper formation and maintenance of the kidney vasculature and glomeruli.
Normalization of input patterns in an associative network
Authors: Liu Andreas , Regehr Wade G.
Published: November 2013

Numerous brain structures have a cerebellum-like architecture in which inputs diverge onto a large number of granule cells that converge onto principal cells. Plasticity at granule cell-to-principal cell synapses is thought to allow these structures to associate spatially distributed patterns of granule cell activity with appropriate principal cell responses. Storing large sets of associations requires the patterns involved to be normalized, i.e., to have similar total amounts of granule cell activity. Using a general model of associative learning, we describe two ways in which granule cells can be configured to promote normalization. First, we show how heterogeneity in firing thresholds across granule cells can restrict pattern-to-pattern variation in total activity while also limiting spatial overlap between patterns. These effects combine to allow fast and flexible learning. Second, we show that the perceptron learning rule selectively silences those synapses that contribute most to pattern-to-pattern variation in the total input to a principal cell. This provides a simple functional interpretation for the experimental observation that many granule cell-to-Purkinje cell synapses in the cerebellum are silent. Since our model is quite general, these principles may apply to a wide range of associative circuits.
Fault Prognostic Based on Hybrid Method of State Judgment and Regression
Authors: Li Xiaobin , Qian Jiansheng , Wang Gai-ge
Published: November 2013

Fault prognostic is one of the most important problems in equipment health management system. This paper presents a hybrid method of mixture of Gaussian hidden Markov model (MG-HMM) and fixed size least squares support vector regression (FS-LSSVR) for fault prognostic. The system is established based on three parts. The first part trains the MG-HMM and FS-LSSVR model. According to the known samples, several MG-HMM models can be learned based on expectation maximization (EM) algorithm. Then, the forward variables can be calculated based on these MG-HMM models. Based on these forward variables, the corresponding FS-LSSVR models are built. All the MG-HMM models and corresponding FS-LSSVR models are combined into a model library. The second part recognizes the unknown sample based on the model library. This part obtains the MG-HMM model and FS-LSSVR model by maximization likelihood calculation between the unknown sample and MG-HMM models. The third part of the system calculates the forward variables based on the MG-HMM obtained from the second part. These forward variables are inputted into the corresponding FS-LSSVR model to compute the remaining useful life (RUL) of the unknown sample. Finally, we carry out experiments on benchmark data set to verify the proposed method. The results illustrate the effectiveness of the hybrid method.
Positive Solutions Using Bifurcation Techniques for Boundary Value Problems of Fractional Differential Equations
Authors: Liu Yansheng
Published: November 2013

This paper is concerned with the existence of positive solutions for a class of boundary value problems of fractional differential equations with parameter. The main tools used here are bifurcation techniques and topological degree theory. Finally, an example is worked out to demonstrate the main result.
Association of FAS and FAS Ligand Genes Polymorphism and Risk of Systemic Lupus Erythematosus
Authors: Moudi Bita , Salimi Saeedeh , Farajian Mashhadi Farzaneh , Sandoughi Mahnaz , Zakeri Zahra
Published: November 2013

FAS/FASL pathway plays a critical role in maintaining peripheral immune tolerance; therefore, the apoptosis genes, Fas and Fas ligand (FasL), could be suitable candidate genes in human SLE susceptibility. Materials and Methods. In this case‐control study, 106 SLE patients and 149 sex, age, and ethnicity matched healthy controls were genotyped for the Fas A‐670G and FasLC‐844T polymorphisms by polymerase chain reaction‐restriction fragment length polymorphism method (PCR‐RFLP). Results. The frequency of ‐670AA genotype was significantly higher in SLE patients than control group and the risk of SLE was 2.1‐fold greater in subjects with AA genotype (P = 0.03). The frequency of ‐670A allele was significantly higher in SLE patients than in controls too (58% versus 49%, P = 0.03). The ‐844CC genotype frequency was significantly higher in SLE patients than in healthy controls and the risk of SLE was 2.8‐fold greater in these subjects (P = 0.01). The C allele frequency was significantly higher in patients than in controls (69% versus 49%, P = 0.001). Increased SLE risk was observed in individuals with combined effect of Fas‐670AA and FasL‐844CC genotypes (P = 0.001). Conclusion. Fas‐670AA and FasL‐844CC genotypes were associated with SLE risk, and combined effect of ‐670AA and ‐844CC genotypes might increase SLE susceptibility.
Carbon Monoxide Attenuates Dextran Sulfate Sodium-Induced Colitis via Inhibition of GSK-3βSignaling
Authors: Uddin Md. Jamal , Jeong Sun-oh , Zheng Min , Chen Yingqing , Cho Gyeong Jae , Chung Hun Taeg , Joe Yeonsoo
Published: November 2013

Endogenous carbon monoxide (CO) is produced by heme oxygenase-1 (HO)-1 which mediates the degradation of heme into CO, iron, and biliverdin. Also, CO ameliorates the human inflammatory bowel diseases and ulcerative colitis. However, the mechanism for the effect of CO on the inflammatory bowel disease has not yet been known. In this study, we showed that CO significantly increases survival percentage, body weight, colon length as well as histologic parameters in DSS-treated mice. In addition, CO inhalation significantly decreased DSS induced pro-inflammatory cytokines by inhibition of GSK-3βin mice model. To support the in vivo observation, TNF-α, iNOS and IL-10 after CO and LiCl treatment were measured in mesenteric lymph node cells (MLNs) and bone marrow-derived macrophages (BMMs) from DSS treated mice. In addition, we determined that CO potentially inhibited GSK-3βactivation and decreased TNF-αand iNOS expression by inhibition of NF-κB activation in LPS-stimulated U937 and MLN cells pretreated with CO. Together, our findings indicate that CO attenuates DSS-induced colitis via inhibition of GSK-3βsignaling in vitro and in vivo. Importantly, this is the first report that investigated the molecular mechanisms mediated the novel effects of CO via inhibition GSK-3βin DSS-induced colitis model.
MOORA-Based Tribological Studies on Red Mud Reinforced Aluminum Metal Matrix Composites
Authors: Rajesh S. , Rajakarunakaran S. , Suthakarapandian R. , Pitchipoo P.
Published: November 2013

This paper presents the findings of an experimental investigation on the effects of applied load, sliding velocity, wt.% of reinforcement and hardness of the counterface material in dry sliding wear studies performed on red mud-based aluminum metal matrix composites (MMC). The specific wear rate and the coefficient of friction are considered as the output quality characteristics. Taguchi-based L9orthogonal array has been used to accomplish the objective of the experimental study. Analysis of variance (ANOVA) is employed to find the optimal setting and the effect of each parameter on the output performance characteristics. It has been observed that optimal factor setting for each output performance is different. In order to minimize the two responses simultaneously, multiobjective optimization based on ratio analysis (MOORA) is adopted. MOORA revealed that the optimal combination of the dry sliding wear parameters for the multiperformance characteristics of the red mud based aluminium is the set normal load at 20 N, sliding velocity 3 m/s, % of reinforcement 20%, and counterface hardness of the material 58 HRC.
Accelerated Aging in Major Depression: The Role of Nitro-Oxidative Stress
Authors: Luca Maria , Luca Antonina , Calandra Carmela
Published: November 2013

Nitro-oxidative stress (NOS) plays a fundamental role in aging, as well as in the pathogenesis of neurodegenerative disorders, and major depression (MD). The latter is a very frequent psychiatric illness characterized by accelerated aging, neurodegeneration, high comorbidity with age-related disorders, and premature mortality; all of these conditions find an explanation in an altered redox homeostasis. If aging, neurodegeneration, and major depression share a common biological base in their pathophysiology, common therapeutic tools could be investigated for the prevention and treatment of these disorders. As an example, antidepressants have been demonstrated to present neuroprotective and anti-inflammatory properties and to stimulate neurogenesis. In parallel, antioxidants that stimulate the antioxidant defense systems and interact with the monoaminergic system show an antidepressant-like activity. Further research on this topic could lead, in the near future, to the expansion of the therapeutic possibilities for the treatment of NOS-related disorders.
Numerical Optimization Design of Dynamic Quantizer via Matrix Uncertainty Approach
Authors: Sawada Kenji , Shin Seiichi
Published: November 2013

In networked control systems, continuous-valued signals are compressed to discrete-valued signals via quantizers and then transmitted/received through communication channels. Such quantization often degrades the control performance; a quantizer must be designed that minimizes the output difference between before and after the quantizer is inserted. In terms of the broadbandization and the robustness of the networked control systems, we consider the continuous-time quantizer design problem. In particular, this paper describes a numerical optimization method for a continuous-time dynamic quantizer considering the switching speed. Using a matrix uncertainty approach of sampled-data control, we clarify that both the temporal and spatial resolution constraints can be considered in analysis and synthesis, simultaneously. Finally, for the slow switching, we compare the proposed and the existing methods through numerical examples. From the examples, a new insight is presented for the two-step design of the existing continuous-time optimal quantizer.
Explicit Dynamic Finite Element Method for Failure with Smooth Fracture Energy Dissipations
Authors: Song Jeong-Hoon , Menouillard Thomas , Tabarraei Alireza
Published: November 2013

A numerical method for dynamic failure analysis through the phantom node method is further developed. A distinct feature of this method is the use of the phantom nodes with a newly developed correction force scheme. Through this improved approach, fracture energy can be smoothly dissipated during dynamic failure processes without emanating noisy artifact stress waves. This method is implemented to the standard 4-node quadrilateral finite element; a single quadrature rule is employed with an hourglass control scheme in order to decrease computational cost and circumvent difficulties associated with the subdomain integration schemes for cracked elements. The effectiveness and robustness of this method are demonstrated with several numerical examples. In these examples, we showed the effectiveness of the described correction force scheme along with the applicability of this method to an interesting class of structural dynamic failure problems.
Cross-Layer Power-Control-Based Real-Time Routing Protocol for Wireless Sensor Networks
Authors: Feng Lin , Lu Yang , Wei Zhenchun , Zhu Zengxi , Ding Xu
Published: November 2013

In order to solve contradictions between real-time applications of wireless sensor networks and limited energy of nodes, Cross-Layer Power Control Algorithm (CLPCA) is proposed in this paper. Moreover, Power-Control-Based Real-Time Routing Protocol (PCBRRP) is designed capable with CLPCA. In this protocol, the transmission power of the node is adjusted dynamically to increase the energy efficiency. The next hop node is selected via the link quality of the communication and the residual energy of every node. Simulation results show that the energy consumption of the network is reduced while real-time end-to-end data transmission is guaranteed.
A Novel Dual-Electrode Plug to Achieve Intensive Electric Field for High Performance Ignition
Authors: Shen Chih-Lung , Su Jye-Chau , Liang Tsair-Chun
Published: November 2013

A thorough analysis of electric field is carried out so as to verify that a novel dual-electrode plug can build intensive electric field and can improve the main drawbacks of feeble electric field and low ignition efficiency of the traditional plug. With intensive electric field, the proposed novel plug can achieve high performance ignition, resulting in fuel saving and exhaust reduction. Gauss law is applied for electric field analysis to show that intensive electric field can be built by the novel plug. Then, according to Faraday law a lower-voltage ignition feature accomplished by the plug is discussed. Compared with traditional plug, the novel dual-electrode plug has the following advantages. (1) Much higher energy density is built between the plug electrodes, lowering ignition voltage requirement. (2) Electromagnetic interference (EMI) problem caused by high ignition voltage is readily resolved. (3) Ignition time delay can be improved. (4) The feature to save fuel consuming is achieved. (5) The exhaust of CO and HC is reduced significantly. Practical measurements are fulfilled to validate the electric field analysis and to demonstrate the features of the proposed dual-electrode plug.
Interaction of Green Polymer Blend of Modified Sodium Alginate and Carboxylmethyl Cellulose Encapsulation of Turmeric Extract
Authors: Riyajan Sa-Ad , Nuim Janthanipa
Published: November 2013

Turmeric extract (tmr) loaded nanoparticles were prepared by crosslinking modified carboxylmethyl cellulose (CMC) and modified sodium alginate (SA) with calcium ions, in a high pressure homogenizer. The FTIR spectra of CMC and SA were affected by blending due to hydrogen bonding. The negative zeta potential increased in magnitude with CMC content. The smallest nanoparticles were produced with a 10 : 5 SA/CMC blend. Also the release rates of the extract loading were measured, with model fits indicating that the loading level affected the release rate through nanoparticle structure. The 10 : 5 SA/CMC blend loading with tmr and pure tmr showed a good % growth inhibition of colon cancer cells which indicate that tmr in the presence of curcumin in tmr retains its anticancer activity even after being loaded into SA/CMC blend matrix.
Dermoid Cyst of the Pancreas: A Report of an Unusual Case and a Review of the Literature
Authors: Albayrak Aynur , Yildirim Umran , Aydin Metin
Published: November 2013

Pancreatic dermoid cysts are a rare entity. Preoperative diagnosis is difficult. The diagnosis is generally taking intraoperative. A 20-year-old female presented with epigastric pain without nausea, vomiting, diarrhea, fever, jaundice, and weight loss of one-month duration. Ultrasonography and computed tomography showed a smooth borders, solid, hyperechoic tumor within midline abdomen, without any connection to the stomach or spleen. At surgery, the entire mass was excised off of the head and inferior part of pancreas. Histopathologic evaluation revealed the rare diagnosis of a dermoid cyst. The diagnosis is difficult preoperatively in evaluating cystic pancreatic lesions by imaging. Therefore, we want to summarize the literature on this rare entity knowledge.
Variability in HOMA‐IR, Lipoprotein Profile and Selected Hormones in Young Active Men
Authors: Keska Anna , Lutoslawska Grazyna , Czajkowska Anna , Tkaczyk Joanna , Mazurek Krzysztof
Published: November 2013

Resistance to insulin actions is contributing to many metabolic disturbances. Such factors as age, sex, nutrition, body fat, and physical activity determine body insulin resistance. Present study attempted to asses insulin resistance and its metabolic effects with respect to energy intake in young, lean, and active men. A total of 87 men aged 18–23 participated in the study. Plasma levels of glucose, insulin, lipoproteins, cortisol, and TSH were determined. Insulin resistance was expressed as Homeostasis Model Assessment for Insulin Resistance (HOMA‐IR) and calculated using homeostatic model. The median value of HOMA‐IR (1.344) was used to divide subjects into two groups. Men did not differ in anthropometric parameters, daily physical activity, and plasma TSH and cortisol levels. However, in men with higher HOMA‐IR significantly lower daily energy intake was observed concomitantly with higher TG, TC, and HDL‐C concentrations in plasma versus their counterparts with lower HOMA‐IR. Exclusively in subjects with higher HOMA‐IR significant and positive correlation was noted between HOMA‐IR and TC and LDL‐C. We concluded that despite a normal body weight and physical activity, a subset of young men displayed unfavorable changes in insulin sensitivity and lipid profile, probably due to insufficient energy intake.