bluuebunny/crossref_metadata_2025 huggingface dataset:
The Demand for Younger and Older Workers
Authors: Allen W. David
Published: October 2012

This study examines how worker productivity and risk factors affect the demand for younger and older workers modeled using concepts from labor economics. The two primary National Football League player labor markets—the draft process and veteran free agent market—provide rich empirical environments for testing hypotheses from the model. Clubs demonstrate greater demand for rookies by drafting them earlier and for veterans by signing them faster. Greater physical productivity enhances labor demand for all players, but risk factors exert a more severe labor market penalty for veterans, patterns consistent with theory and with previous research on the demand for risky workers and older workers.
United We Stand? African Americans, Self-Interest, and Immigration Reform
Authors: Nteta Tatishe
Published: October 2012

Alongside the growth of the immigrant population has been a corresponding backlash by citizens who increasingly support restrictive immigration policies aimed at undocumented immigrants. Much of what we know about this backlash is based on data from White Americans. Are African Americans among the growing segment of anti-immigrant supporters? Employing data from the 2006 Pew Center “America’s Immigration Quandary Survey,” I uncover that African Americans support restrictive immigration policies, and that class membership alongside subjective and objective measures of self-interest influence these policy stances. These findings challenge prior assertions that self-interest does little to account for American public opinion, demonstrating that on the issue of immigration reform that self-interest matters for African Americans.
Contingent Party Pressure and Legislative Gridlock
Authors: Lee Jongkon
Published: October 2012

Although several legislative gridlock models have produced different results in terms of legislative gridlock under divided government, these studies have neglected contingent party pressures. This paper suggests an alternative contingent party pressure model. The main result of this model is that legislative gridlock is affected by the interactions of issue salience and government types. High issue salience increases legislative gridlock under unified government and, in contrast, decreases under divided government.
The Effects of Legislative Term Limits on State Fiscal Conditions
Authors: Cummins Jeff
Published: October 2012

Advocates of term limits argued that term limits would help reduce out-of-control government spending by removing veteran legislators who became acclimated to the prospending environment in our nation’s capitals. However, previous research shows that term limits may increase spending, which could jeopardize state fiscal health. The primary purpose of this article is to examine whether states with term limits encounter more fiscal problems than non-term-limited states. I suggest that the short-term fiscal outlooks and loss of experienced legislators produced by term-limit turnover lead to poor fiscal conditions. Myopic legislators may avoid tough fiscal decisions, while inexperienced legislators may be ill-equipped to develop sound fiscal policy. Analysis of budget data on U.S. states from 1983 to 2008 reveals that legislative turnover decreases budget balances. Results further show that these effects do not appear in the upper chamber, perhaps because state senates have more experienced legislators than the lower chamber.
Politicizing Priority Departments
Authors: Parsneau Kevin
Published: October 2012

Presidents have the power to nominate the top ranks of the executive branch and they use it toward their own goals. Presidents need a mixture of experienced and loyal officers to promote bureaucratic competence and responsiveness, and advance their policies within the executive branch, but scholars’ focus has often been senatorial obstructionism rather than when presidents prefer loyal nominees and experienced nominees. This study uses a sample of 573 subcabinet nominations between 1961 and 2006, and relates presidents’ nominee choices to their policy priorities and departmental jurisdictions. It finds that presidents nominate significantly more loyalists and fewer experienced officers to higher priority departments, indicating the importance of responsiveness, as well as their suspicion of experienced officers. Presidents select more experienced nominees for lower priority departments to assure competence where they are least concerned with responsiveness. Furthermore, it finds that increased Senate ideological opposition has no significant effect on presidents’ selections.
The Politics of Presidential Press Conferences
Authors: Eshbaugh-Soha Matthew
Published: October 2012

What explains the president’s tendency to deliver press conferences? Unlike other forms of going public, the press conference presents a unique venue that allows presidents to grapple with their policy and political decisions in a highly public and interactive format with journalists. This should influence how the political environment affects not only the number of press conferences presidents deliver in a month but also the time between press conferences. Indeed, lower approval ratings and unified government lead to more solo press conferences and less time between them. Whereas reelection years and political scandal decrease the number of solo press conferences, only reelection years increase the time between them. This article also reminds us of the relevance of individual presidents to explaining press conference activity and has implications for a broader understanding of the president’s public appeals.
A Time-Series Study of Depression Using Cognitive-Behavioral Techniques Subsequent to Short-Term Psychodynamic Psychotherapy
Authors: Ritter Kathrin , Moore Todd M.
Published: October 2012

This study examined the sequential use of two distinct treatment modalities in the care of a client with depression and comorbid anxiety. The client was initially treated with 16 sessions of short-term psychodynamic psychotherapy (STPP) followed by seven sessions of cognitive-behavioral therapy (CBT). Simulation modeling analysis was used to assess the symptom changes across both treatment phases. Symptoms tracked included level of self-esteem, degree of sadness, and overall distress. Results indicated that the client did not experience any significant changes in response to STPP, but did experience a reduction in distress and sadness, and an increase in self-esteem subsequent to CBT. This study highlights the importance of clinical flexibility in cases in which a particular treatment modality may not be effective. Complicating factors and implications are also discussed.
Functional Brain Changes Following Cognitive and Motor Skills Training
Authors: Patel Ronak , Spreng R. Nathan , Turner Gary R.
Published: October 2012

Background. Functional neuroimaging is increasingly used in rehabilitation research to map the neural mechanisms subserving training targets. These data can inform intervention design and improve evaluation of treatment outcomes. Reliable neural markers may provide standard metrics of treatment impact and allow consideration of behavioral outcomes in the context of functional brain changes. Objective. To identify common patterns of functional brain changes associated with training across a diverse range of intervention protocols. Reliable brain changes could inform development of candidate neural markers to guide intervention research. Methods. Taking a quantitative meta-analytic approach, we review the functional neuroimaging studies of cognitive and motor skills training interventions in healthy young adults (N = 38). Results. Reliable decreases in functional brain activity from pretraining to posttraining were observed in brain regions commonly associated with cognitive control processes, including lateral prefrontal, left anterior inferior parietal lobule, and dorsal anterior cingulate cortex. Training-related increases were observed in the medial prefrontal cortex and posterior cingulate and angular gyrus, core regions of the default network. Activity within the subcortical striatum also showed reliable increases pretraining to posttraining. Conclusions. These data suggest that altered engagement of large-scale, spatially distributed cortical brain networks and subcortical striatal brain regions may serve as candidate neural markers of training interventions. The development of reliable metrics based on activity and functional connectivity among large-scale brain networks may prove fruitful in identifying interactions between domain-general and -specific changes in brain activity that affect behavioral outcomes.
Condom Use, Disclosure, and Risk for Unprotected Sex in HIV-Negative Midlife and Older Men Who Have Sex With Men
Authors: Jacobs Robin J. , Kane Michael N. , Ownby Raymond L.
Published: October 2012

Sexual risk behaviors account for most HIV infections in men who have sex with men (MSM), and the risk of exposure from each sexual encounter increases with age. The focus of this study was to investigate which behaviors in midlife and older MSM influence their sexual risk/protection. Cross-sectional data were collected from a community-based sample of 802 MSM aged 40 years and older from community venues (e.g., bars) who completed an anonymous questionnaire. Data from a subset of 420 MSM who were HIV-negative (aged 40-81 years) were used to investigate which behaviors were associated with greater risk for unprotected anal sex. Regression analyses indicated that erection difficulties (odds ratio [OR] = 4.7; 95% confidence interval [CI] = 1.8-12.2), practicing safe sex with outside partners but not with one’s primary partner (OR = 0.54; 95% CI = 0.3-0.94), and recreational drug use (OR = 2.6; 95% CI = 1.3-5.1) were associated with higher risk for unprotected receptive anal intercourse. Younger age (OR = 0.96; 95% CI = 0.9- 0.9), not telling partners about HIV status (OR = 3.2; 95% CI = 1.5-6.5), finding partners in backrooms/sex clubs (OR = 2.8; 95% CI = 1.1- 6.8), and erection difficulties (OR = 10.3; 95% CI = 2.8-37.8) were associated with higher risk for unprotected insertive anal intercourse. These data indicate there may be certain factors specific to older MSM that influence their sexual risk taking behaviors. Programs may be more effective if they are tailored for older cohorts of MSM and address interpersonal communication, erection problems, and substance use to reduce health risks and promote healthier lifestyles.
The Limitations of Language
Authors: Affleck William , Glass KC , Macdonald Mary Ellen
Published: October 2012

The semistructured, open-ended interview has become the gold standard for qualitative health research. Despite its strengths, the long interview is not well suited for studying topics that participants find difficult to discuss, or for working with those who have limited verbal communication skills. A lack of emotional expression among male research participants has repeatedly been described as a significant and pervasive challenge by health researchers in a variety of different fields. This article explores several prominent theories for men’s emotional inexpression and relates them to qualitative health research. The authors argue that investigators studying emotionally sensitive topics with men should look beyond the long interview to methods that incorporate other modes of emotional expression. This article concludes with a discussion of several such photo-based methods, namely, Photovoice, Photo Elicitation, and Visual Storytelling.
Abdominal Aortic Aneurysm
Authors: Tillman Ken , Lee O. Danny , Whitty Kristin
Published: October 2012

Men are more likely than women to develop an abdominal aortic aneurysm (AAA), a disease that is often asymptomatic and has up to a 90% risk of mortality if the aneurysm ruptures. What many men do not know is that an AAA can easily be identified through an ultrasound screening, and if the aneurysm is >5.5 cm, it can be surgically repaired to prevent a life-threatening rupture. Although current AAA screening recommendations focus on men between the ages of 65 and 75 years, who have ever smoked, recent evidence suggest many men of ages 50 to 80 years, regardless of smoking status, may also be at risk for developing an AAA. This article presents a comprehensive overview of AAA disease and summarizes current evidence-based diagnostic and treatment guidelines, the importance of educating men about this health issue, and the need for more widespread AAA ultrasound screening opportunities.
Sisters in crime: Representations of gender and class in the media coverage and court proceedings of the triple homicide at Orderud Farm
Authors: Skilbrei May-Len
Published: October 2012

In 1999, three people were found dead on a farm in the Norwegian countryside. Two pensioners and their middle-aged daughter were victims of a brutal murder that in the coming three years filled the Norwegian news media. Four people, two women and two men, were charged and convicted of the crime. The perpetrators were the son of the murdered pensioners, his wife, her sister and her sister’s boyfriend. As is the case in many countries, women are rarely involved in planned and brutal homicide for gain in Norway, and this makes it interesting to investigate how such cases and female defendants are represented. This article investigates how cultural assumptions about gender and class influenced how the case and the four defendants were represented in media and court, and concludes that the two women were constructed as opposites in a variety of ways, a finding in line with studies elsewhere on female offenders. Differently from much of the research literature, the male perpetrators were not represented as the brains and muscle of the crime, but rather as dominated by two women who in ways related to class were described as dangerous femme fatales.
Evaluation of the solar reflectance of highly reflective roofing sheets installed on building roofs
Authors: Yuan Jihui , Emura Kazuo , Sakai Hideki
Published: October 2012

There is a strong need to prevent the heat island effect. One of the important countermeasures to the heat island effect is to reduce thermal storage in buildings. The highly reflective material on outer walls and roofs is a significant way to prevent heat from penetrating indoors; such materials have been installed on the surface of buildings in Osaka, Japan. To evaluate the solar reflectance of such highly reflective material, we measured the solar reflectance of reflective roofing sheets installed on the building roofs in Osaka, Japan, over a span of time from February 2010 until September 2011, and examined the change in solar reflectance during this time.
Effective foam insulation for single-wythe concrete masonry walls
Authors: Lohonyai Adam J , Korany Yasser , Ross Michael D
Published: October 2012

The objective of this study was to evaluate the effectiveness of three different methods to apply closed-cell polyurethane foam to single-wythe concrete masonry wall panels, namely, surface spray-on, filled formwork, and grouting the cores of the concrete blocks. Foams with two densities were applied at three different thicknesses. Two-dimensional heat flow simulations were conducted using THERM to determine the overall thermal resistance of the insulated masonry wall panels. Filled formwork application using normal-density foam yielded the highest thermal resistance. Hygrothermal analysis using WUFI Plus revealed that exterior application of the foam is preferred to avoid durability issues and take advantage of the thermal mass and fire resistance of masonry walls.
Technical note: Airtightness of older-generation energy-efficient houses in Saskatoon
Authors: Orr Harold , Wang Jieying , Fetsch Dave , Dumont Rob
Published: October 2012

The aim of this study was to collect long-term in-service energy efficiency data from older-generation energy-efficient houses built in Canada in the past decades. Six houses with highly insulated building envelope assemblies built (or retrofitted) from 1979 to 1992 in the Saskatoon area were inspected during March 2012. As typical energy-efficient houses for this area, all were built with double 2 × 4 stud walls with the gap between walls ranging from 4 to about 12 in and with nominal wall insulation varying from RSI * 6.34 (R* 36) to RSI 10.57 (R 60). The roof insulation ranged from RSI 10.57 (R 60) to RSI 14.09 (R 80). The below-grade walls were also well insulated, and these were mainly permanent wood foundations. Polyethylene was used as a combined air barrier and vapour barrier for the building envelopes. The major results included the following: the airtightness values based on blower-door tests ranged from 0.78 to 2.55 air changes per hour at 50 Pa measured under normal operation conditions, with four houses below 1.50 air changes per hour at 50 Pa after 20–30 years. The No. 2 house had an original airtightness of 0.29 air changes per hour at 50 Pa and 0.22 air changes per hour when the windows were sealed with masking tape after the energy retrofit in 1982. The airtightness was measured to be 1.23 air changes per hour at 50 Pa in this survey after the owner installed new windows without properly sealing the interior air barrier. The No. 4 house had an airtightness of 0.78 air changes per hour, while the original airtightness test was 0.47 air changes per hour when the house was built over 20 years ago. All the six houses had EnerGuide Rating System of over 80, and one had a remarkable EnerGuide Rating System of 87. Windows and ventilation air were identified to be the largest heat loss components, followed by basement and exterior walls.
The point of probation: On effectiveness, human rights and the virtues of obliquity
Authors: Canton Rob
Published: October 2012

Policy debate assumes the point of probation is to administer community punishment, reduce reoffending and protect the public. Dominant punitive and instrumental understandings of probation’s work have regarded the human rights of offenders as of secondary importance or even as obstacles to attaining these objectives. This article argues that, on the contrary, policy and practice should be grounded on human rights rather than on direct endeavours for effectiveness. It advances a personal and ethical understanding of probation and, considering probation’s principal tasks of enforcement, rehabilitation and public protection, argues that a respectful professional relationship is indispensable, though threatened by punitive and instrumental approaches. The concept of obliquity – the idea that some of our most important goals are best achieved indirectly – can explain how a personal approach can turn out not only to respect ethical entitlements, but indeed to be more effective in the terms that probation sets for itself.
Burden of comorbidities among patients with atrial fibrillation
Authors: LaMori Joyce C. , Mody Samir H. , Gross Hillary J. , daCosta DiBonaventura Marco , Patel Aarti A. , Schein Jeffrey R. , Nelson Winnie W.
Published: October 2012

Objective:

This study examined comorbidity prevalence and general medication use among individuals with atrial fibrillation in the United States to convey a more comprehensive picture of their total disease burden.

Methods:

This was a retrospective, observational evaluation of responses to the 2009 wave of the annual Internet-based National Health and Wellness survey, which collects health data including epidemiologic data and information on medical treatment from a representative nationwide sample of adults in the United States. Responses were assessed to determine three measures of comorbidity: mean number of comorbidities, CHADS2 score reflecting stroke risk (0–6 points; low risk: 0; moderate risk: 1; high risk: ≥2), and scores on the Charlson Comorbidity Index, which is a measure of general comorbidity reflecting presence of a wide range of comorbidities.

Results:

Of the overall sample, 1297 participants reported having been diagnosed with atrial fibrillation. Almost all (98%) of the predominantly male (65.1%) and older (≥65 years of age, 65.7%) population with atrial fibrillation had at least one additional comorbidity, and 90% had cardiovascular comorbidities. On the Charlson Comorbidity Index, 44.9% of the respondents had scores of 1–2 and 20.5% had scores of 3 or higher. High risk for stroke, demonstrated by a CHADS2 score of at least 2, was present in 45% and moderate risk (CHADS2 score 1) in 36%. Of the respondents with atrial fibrillation, 71% reported current use of medication to manage the condition, but only 48% of individuals at high risk for stroke reported use of anticoagulation therapy. Of those who reported having common risk factors for stroke, the majority reported receiving prescription therapy for these conditions.

Conclusions:

The health burden carried by patients often extends far beyond atrial fibrillation. Physicians should carefully consider comorbidities and concomitant medications when managing patients with atrial fibrillation.
Biosimilars: what clinicians should know
Authors: Weise Martina , Bielsky Marie-Christine , De Smet Karen , Ehmann Falk , Ekman Niklas , Giezen Thijs J. , Gravanis Iordanis , Heim Hans-Karl , Heinonen Esa , Ho Kowid , Moreau Alexandre , Narayanan Gopalan , Kruse Nanna A. , Reichmann Gabriele , Thorpe Robin , van Aerts Leon , Vleminckx Camille , Wadhwa Meenu , Schneider Christian K.
Published: October 2012

Biosimilar medicinal products (biosimilars) have become a reality in the European Union and will soon be available in the United States. Despite an established legal pathway for biosimilars in the European Union since 2005 and increasing and detailed regulatory guidance on data requirements for their development and licensing, many clinicians, particularly oncologists, are reluctant to consider biosimilars as a treatment option for their patients. Major concerns voiced about biosimilars relate to their pharmaceutical quality, safety (especially immunogenicity), efficacy (particularly in extrapolated indications), and interchangeability with the originator product. In this article, the members and experts of the Working Party on Similar Biologic Medicinal Products of the European Medicines Agency (EMA) address these issues. A clear understanding of the scientific principles of the biosimilar concept and access to unbiased information on licensed biosimilars are important for physicians to make informed and appropriate treatment choices for their patients. This will become even more important with the advent of biosimilar monoclonal antibodies. The issues also highlight the need for improved communication between physicians, learned societies, and regulators.
Fcγ receptor antigen targeting potentiates cross-presentation by human blood and lymphoid tissue BDCA-3+ dendritic cells
Authors: Flinsenberg Thijs W. H. , Compeer Ewoud B. , Koning Dan , Klein Mark , Amelung Femke J. , van Baarle Debbie , Boelens Jaap Jan , Boes Marianne
Published: October 2012

The reactivation of human cytomegalovirus (HCMV) poses a serious health threat to immune compromised individuals. As a treatment strategy, dendritic cell (DC) vaccination trials are ongoing. Recent work suggests that BDCA-3+ (CD141+) subset DCs may be particularly effective in DC vaccination trials. BDCA-3+ DCs had however been mostly characterized for their ability to cross-present antigen from necrotic cells. We here describe our study of human BDCA-3+ DCs in elicitation of HCMV-specific CD8+ T-cell clones. We show that Fcgamma-receptor (FcγR) antigen targeting facilitates antigen cross-presentation in several DC subsets, including BDCA-3+ DCs. FcγR antigen targeting stimulates antigen uptake by BDCA-1+ rather than BDCA-3+ DCs. Conversely, BDCA-3+ DCs and not BDCA-1+ DCs show improved cross-presentation by FcγR targeting, as measured by induced release of IFNγ and TNF by antigen-specific CD8+ T cells. FcγR-facilitated cross-presentation requires antigen processing in both an acidic endosomal compartment and by the proteasome, and did not induce substantial DC maturation. FcγRII is the most abundantly expressed FcγR on both BDCA-1+ and BDCA-3+ DCs. Furthermore we show that BDCA-3+ DCs express relatively more stimulatory FcγRIIa than inhibitory FcγRIIb in comparison with BDCA-1+ DCs. These studies support the exploration of FcγR antigen targeting to BDCA-3+ DCs for human vaccination purposes.
Unwinding the von Willebrand factor strings puzzle
Authors: De Ceunynck Karen , De Meyer Simon F. , Vanhoorelbeke Karen
Published: October 2012

von Willebrand factor (VWF) is amongst others synthesized by endothelial cells and stored as ultra-large (UL) VWF multimers in Weibel-Palade bodies. Although UL-VWF is proteolysed by ADAMTS13 (a disintegrin-like and metalloprotease domain with thrombospondin type-1 motif, number 13) on secretion from endothelial cells, in vitro experiments in the absence of ADAMTS13 have demonstrated that a proportion of these UL-VWF multimers remain anchored to the activated endothelium. These multimers unravel, bind platelets, and wave in the direction of the flow. These so-called VWF “strings” have also been visualized in vivo, lining the lumen of activated mesenteric veins of Adamts13−/− mice. Various studies have demonstrated the extraordinary length of these VWF strings, the availability of their platelet binding and ADAMTS13 cleavage sites, and the possible nature of their endothelial attachment. VWF strings are also capable of tethering leukocytes and parasite-infected red blood cells. However, the majority of studies have been performed in the absence of ADAMTS13, a condition only experienced in thrombotic thrombocytopenic purpura. A normal functional role of VWF strings in healthy persons or in other disease pathologies remains unclear. In this review, we discuss some of the puzzling characteristics of VWF strings, and we debate whether the properties of VWF strings in the absence of ADAMTS13 might be relevant for understanding (patho)physiologic mechanisms.
Historically low mitochondrial DNA diversity in koalas (Phascolarctos cinereus)
Authors: Tsangaras Kyriakos , Ávila-Arcos María C , Ishida Yasuko , Helgen Kristofer M , Roca Alfred L , Greenwood Alex D
Published: October 2012

Background

The koala (Phascolarctos cinereus) is an arboreal marsupial that was historically widespread across eastern Australia until the end of the 19th century when it suffered a steep population decline. Hunting for the fur trade, habitat conversion, and disease contributed to a precipitous reduction in koala population size during the late 1800s and early 1900s. To examine the effects of these reductions in population size on koala genetic diversity, we sequenced part of the hypervariable region of mitochondrial DNA (mtDNA) in koala museum specimens collected in the 19th and 20th centuries, hypothesizing that the historical samples would exhibit greater genetic diversity.

Results

The mtDNA haplotypes present in historical museum samples were identical to haplotypes found in modern koala populations, and no novel haplotypes were detected. Rarefaction analyses suggested that the mtDNA genetic diversity present in the museum samples was similar to that of modern koalas.

Conclusions

Low mtDNA diversity may have been present in koala populations prior to recent population declines. When considering management strategies, low genetic diversity of the mtDNA hypervariable region may not indicate recent inbreeding or founder events but may reflect an older historical pattern for koalas.
Constructing a question bank based on script concordance approach as a novel assessment methodology in surgical education
Authors: Aldekhayel Salah A , ALselaim Nahar A , Magzoub Mohi Eldin , AL-Qattan Mohammad M , Al-Namlah Abdullah M , Tamim Hani , Al-Khayal Abdullah , Al-Habdan Sultan I , Zamakhshary Mohammed F
Published: October 2012

Background

Script Concordance Test (SCT) is a new assessment tool that reliably assesses clinical reasoning skills. Previous descriptions of developing SCT-question banks were merely subjective. This study addresses two gaps in the literature: 1) conducting the first phase of a multistep validation process of SCT in Plastic Surgery, and 2) providing an objective methodology to construct a question bank based on SCT.

Methods

After developing a test blueprint, 52 test items were written. Five validation questions were developed and a validation survey was established online. Seven reviewers were asked to answer this survey. They were recruited from two countries, Saudi Arabia and Canada, to improve the test’s external validity. Their ratings were transformed into percentages. Analysis was performed to compare reviewers’ ratings by looking at correlations, ranges, means, medians, and overall scores.

Results

Scores of reviewers’ ratings were between 76% and 95% (mean 86% ± 5). We found poor correlations between reviewers (Pearson’s: +0.38 to −0.22). Ratings of individual validation questions ranged between 0 and 4 (on a scale 1–5). Means and medians of these ranges were computed for each test item (mean: 0.8 to 2.4; median: 1 to 3). A subset of test items comprising 27 items was generated based on a set of inclusion and exclusion criteria.

Conclusion

This study proposes an objective methodology for validation of SCT-question bank. Analysis of validation survey is done from all angles, i.e., reviewers, validation questions, and test items. Finally, a subset of test items is generated based on a set of criteria.
Metabolic engineering of the purine biosynthetic pathway in Corynebacterium glutamicum results in increased intracellular pool sizes of IMP and hypoxanthine
Authors: Peifer Susanne , Barduhn Tobias , Zimmet Sarah , Volmer Dietrich A , Heinzle Elmar , Schneider Konstantin
Published: October 2012

Background

Purine nucleotides exhibit various functions in cellular metabolism. Besides serving as building blocks for nucleic acid synthesis, they participate in signaling pathways and energy metabolism. Further, IMP and GMP represent industrially relevant biotechnological products used as flavor enhancing additives in food industry. Therefore, this work aimed towards the accumulation of IMP applying targeted genetic engineering of Corynebacterium glutamicum.

Results

Blocking of the degrading reactions towards AMP and GMP lead to a 45-fold increased intracellular IMP pool of 22 μmol gCDW
-1. Deletion of the pgi gene encoding glucose 6-phosphate isomerase in combination with the deactivated AMP and GMP generating reactions, however, resulted in significantly decreased IMP pools (13 μmol gCDW
-1). Targeted metabolite profiling of the purine biosynthetic pathway further revealed a metabolite shift towards the formation of the corresponding nucleobase hypoxanthine (102 μmol gCDW
-1) derived from IMP degradation.

Conclusions

The purine biosynthetic pathway is strongly interconnected with various parts of the central metabolism and therefore tightly controlled. However, deleting degrading reactions from IMP to AMP and GMP significantly increased intracellular IMP levels. Due to the complexity of this pathway further degradation from IMP to the corresponding nucleobase drastically increased suggesting additional targets for future strain optimization.
Imbalance in superoxide dismutase/thioredoxin reductase activities in hypercholesterolemic subjects: relationship with low density lipoprotein oxidation
Authors: Augusti Paula Rossini , Ruviaro Amanda Roggia , Quatrin Andréia , Somacal Sabrina , Conterato Greicy Michelle Marafiga , Vicentini Juliana Tanara , Duarte Marta Medeiros Frescura , Emanuelli Tatiana
Published: October 2012

Background

There is a relationship among hypercholesterolemia, oxidative stress and inflammation in the atherogenesis. Thus, the objective of the present study was to assess paraoxonase (PON1), superoxide dismutase (SOD) and thioredoxin reductase (TrxR-1) activities and their relationship with lipids, oxidative stress and inflammation in subjects with different low density lipoprotein-cholesterol (LDL) levels.

Methods

Serum lipids, highly sensitive C-reactive protein (hs-CRP), lipid and protein oxidation, oxidized LDL (LDLox) and LDLox autoantibodies (LDLoxAB) levels and enzymes activities were measured in a total of 116 subjects that were divided into the following groups according to their LDL levels: low-LDL group (LDL < 100 mg/dL, n = 23), intermediate-LDL group (LDL 100–160 mg/dL, n = 50) and high-LDL group (LDL > 160 mg/dL, n = 43).

Results

The LDLox and hs-CRP levels increased in the high-LDL group (2.7- and 3.7- fold, respectively), whereas the intermediate and high-LDL groups had higher LDLoxAB (2.2- and 3.1-fold) when compared to low-LDL group (p < 0.05). Similarly, SOD activity, the atherogenic index (AI) and protein oxidation were also higher in the intermediate (1.3-, 1.3- and 1.2-fold) and high-LDL (1.6-, 2.3- and 1.6-fold) groups when compared to the low-LDL group (p < 0.05). Lipid oxidation and SOD/TrxR-1 ratio increased only in the high-LDL group (1.3- and 1.6-fold) when compared to the low-LDL group (p < 0.05). The SOD/TrxR-1 ratio was positively correlated to TBARS (r = 0.23, p < 0.05), LDLox (r = 0.18, p < 0.05), LDLoxAB (r = 0.21, p < 0.05), LDL (r = 0.19, p < 0.05) and AI (r = 0.22, p < 0.05). PON1 and TrxR-1 activities were similar among groups.

Conclusions

Some oxidative events initiate when LDL levels are clinically acceptable. Moreover, hypercholesterolemic patients have an imbalance in SOD and TrxR-1 activities that is positively associated to LDL oxidation.
The role of the 5-hydroxytryptamine pathway in reflux-induced esophageal mucosal injury in rats
Authors: Yang Lingrong , Cai Haifang , Tou Jinfa , Gu Weizhong , Shu Xiaoli , Zhang Ting , Yang Xi , Shen Zheng , Jiang Mizu
Published: October 2012

Background

Dysfunction of the 5-hydroxytryptamine (5-HT) signaling pathway can lead to gastrointestinal motility and secretion abnormalities and to visceral hypersensitivity. The aim of this study is to investigate the role of 5-HT in reflux-induced esophageal mucosal injury.

Methods

Fifty 8-week-old male Sprague-Dawley (SD) rats were randomly divided into a gastroesophageal reflux (GER) model group (30 rats) and a sham surgery control group (20 rats). Four weeks after surgery, the esophageal mucosa was collected for histological evaluation, 5-HT concentrations, and 5-HT selective reuptake transporter (SERT) mRNA and 5-HT4 receptor (5-HT4R) protein expressions.

Results

Twenty-seven rats in the GER model group survived, and three rats died. Histologically, in the GER model group, 20 rats had reflux esophagitis (RE group), and 7 rats had non-erosive reflux disease (NERD group). The 5-HT levels in the esophageal tissue from the RE group were significantly higher than those from the control and NERD groups. Both the RE and NERD groups showed significant increases in SERT mRNA expression of the esophageal mucosa than that of the controls, and the SERT mRNA level in the RE group was significantly higher than that in the NERD group. The 5-HT4R protein level of the esophageal mucosa in the RE group was significantly lower than that in the controls and the NERD group.

Conclusions

We conclude that a 5-HT signaling pathway disorder could be a major factor in the pathogenesis of GER and RE.
Tripled fixed point and tripled coincidence point theorems in intuitionistic fuzzy normed spaces
Authors: Abbas Mujahid , Ali Basit , Sintunavarat Wutiphol , Kumam Poom
Published: October 2012

The aim of this paper is to prove the existence of tripled fixed point and tripled coincidence point theorems in intuitionistic fuzzy normed spaces (IFNS). Our results generalize and extend recent coupled fixed point theorems in IFNS.

MSC:47H09, 47H10, 54H25.
Identification and characterization of naturally occurring splice variants of SAMHD1
Authors: Welbourn Sarah , Miyagi Eri , White Tommy E , Diaz-Griffero Felipe , Strebel Klaus
Published: October 2012

Background

Sterile Alpha Motif and HD domain-containing protein 1 (SAMHD1) is a recently identified host factor that restricts HIV-1 replication in dendritic and myeloid cells. SAMHD1 is a dNTPase that presumably reduces the cellular dNTP levels to levels too low for retroviral reverse transcription to occur. However, HIV-2 and SIV encoded Vpx counteracts the antiviral effects of SAMHD1 by targeting the protein for proteasomal degradation. SAMHD1 is encoded by a multiply spliced mRNA and consists of 16 coding exons.

Results

Here, we identified two naturally occurring splice variants lacking exons 8–9 and 14, respectively. Like wildtype SAMHD1, both splice variants localize primarily to the nucleus, interact with Vpx, and retain some sensitivity to Vpx-dependent degradation. However, the splice variants differ from full-length SAMHD1 in their metabolic stability and catalytic activity. While full-length SAMHD1 is metabolically stable in uninfected cells, both splice variants were inherently metabolically unstable and were rapidly degraded even in the absence of Vpx. Vpx strongly increased the rate of degradation of full-length SAMHD1 and further accelerated the degradation of the splice variants. However, the effect of Vpx on the splice variants was more modest due to the inherent instability of these proteins. Analysis of dNTPase activity indicates that neither splice variant is catalytically active.

Conclusions

The identification of SAMHD1 splice variants exposes a potential regulatory mechanism that could enable the cell to control its dNTPase activity on a post-transcriptional level.
Sensory Discrimination between Innocuous and Noxious Cold by TRPM8-Expressing DRG Neurons of Rats
Authors: Sarria Ignacio , Ling Jennifer , Xu Guang-Yin , Gu Jianguo G
Published: October 2012

The TRPM8 channel is a principal cold transducer that is expressed on some primary afferents of the somatic and cranial sensory systems. However, it is uncertain whether TRPM8-expressing afferent neurons have the ability to convey innocuous and noxious cold stimuli with sensory discrimination between the two sub-modalities. Using rat dorsal root ganglion (DRG) neurons and the patch-clamp recording technique, we characterized membrane and action potential properties of TRPM8-expressing DRG neurons at 24°C and 10°C. TRPM8-expressing neurons could be classified into TTX-sensitive (TTXs/TRPM8) and TTX-resistant (TTXr/TRPM8) subtypes based on the sensitivity to tetrodotoxin (TTX) block of their action potentials. These two subtypes of cold-sensing cells displayed different membrane and action potential properties. Voltage-activated inward Na+ currents were highly susceptible to cooling temperature and abolished by ∼95% at 10°C in TTXs/TRPM8 DRG neurons, but remained substantially large at 10°C in TTXr/TRPM8 cells. In both TTXs/TRPM8 and TTXr/TRPM8 cells, voltage-activated outward K+ currents were substantially inhibited at 10°C, and the cooling-sensitive outward currents resembled A-type K+ currents. TTXs/TRPM8 neurons and TTXr/TRPM8 neurons were shown to fire action potentials at innocuous and noxious cold temperatures respectively, demonstrating sensory discrimination between innocuous and noxious cold by the two subpopulations of cold-sensing DRG neurons. The effects of cooling temperatures on voltage-gated Na+ channels and A-type K+ currents are likely to be contributing factors to sensory discrimination of cold by TTXs/TRPM8 and TTXr/TRPM8 afferent neurons.
DRD2 and PPP1R1B (DARPP-32) polymorphisms independently confer increased risk for autism spectrum disorders and additively predict affected status in male-only affected sib-pair families
Authors: Hettinger Joe A , Liu Xudong , Hudson Melissa L , Lee Alana , Cohen Ira L , Michaelis Ron C , Schwartz Charles E , Lewis Suzanne ME , Holden Jeanette JA
Published: October 2012

Background

The neurotransmitter dopamine (DA) modulates executive functions, learning, and emotional processing, all of which are impaired in individuals with autism spectrum disorders (ASDs). Our previous findings suggest a role for dopamine-related genes in families with only affected males.

Methods

We examined two additional genes which affect DA function, the DRD2 and PPP1R1B (DARPP-32) genes, in a cohort of 112 male-only affected sib-pair families. Selected polymorphisms spanning these genes were genotyped and both family-based and population-based tests were carried out for association analysis. General discriminant analysis was used to examine the gene-gene interactions in predicting autism susceptibility.

Results

There was a significantly increased frequency of the DRD2 rs1800498TT genotype (P = 0.007) in affected males compared to the comparison group, apparently due to over-transmission of the T allele (P = 0.0003). The frequency of the PPP1R1B rs1495099CC genotype in affected males was also higher than that in the comparison group (P = 0.002) due to preferential transmission of the C allele from parents to affected children (P = 0.0009). Alleles rs1800498T and rs1495099C were associated with more severe problems in social interaction (P = 0.0002 and P = 0.0016, respectively) and communication (P = 0.0004 and P = 0.0046), and increased stereotypic behaviours (P = 0.0021 and P = 0.00072). General discriminant analysis found that the DRD2 and PPP1R1B genes additively predicted ASDs (P = 0.00011; Canonical R = 0.26) and explain ~7% of the variance in our families. All findings remained significant following corrections for multiple testing.

Conclusion

Our findings support a role for the DRD2 and PPP1R1B genes in conferring risk for autism in families with only affected males and show an additive effect of these genes towards prediction of affected status in our families.
Terpenes From the Root of Salvia hypoleuca Benth
Authors: Saeidnia Soodabeh , Ghamarinia Mitra , Gohari Ahmad R , Shakeri Alireza
Published: October 2012

Background

The genus Salvia, with nearly 900 species, is one of the largest members of Lamiaceae family. In the Flora of Iran, the genus Salvia is represented by 58 species of which 17 species are endemic. Salvia hypoleuca Benth., is one of these species growing wildly in northern and central parts of Iran. Salvia species are well known in folk medicine and widely used for therapeutic purposes. Literature review shows that there is no report on phytochemical investigation of the roots of S. hypoleuca.

Results

The separation and purification process were carried out using various chromatographic methods. Structural elucidation was on the basis of NMR and MS data, in comparison with those reported in the literature. The isolated compounds were identified as sitosteryl oleate (1), β-sitosterol (2), stigmasterol (3), manool (4), 7α-acetoxy royleanone (5), ursolic acid (6), oleanolic acid (7), 3-epicorosolic acid (8), 3-epimaslinic acid (9) and coleonolic acid (10).

Conclusions

In the present study, three sterols, two diterpenes and five triterpenes were isolated from the ethyl acetate extract of the roots of S. hypoleuca. As the chemotaxonomic significance, some of the isolated compounds (1–7, 9) have not been previously reported from the species S. hypoleuca, while the triterpenes 8 and 10 are now documented from Salvia genus for the first time.
Strategy for eliciting antigen-specific CD8+ T cell-mediated immune response against a cryptic CTL epitope of merkel cell polyomavirus large T antigen
Authors: Gomez Bianca P , Wang Connie , Viscidi Raphael P , Peng Shiwen , He Liangmei , Wu T-C , Hung Chien-Fu
Published: October 2012

Background

Merkel cell carcinoma (MCC) is a relatively new addition to the expanding category of oncovirus-induced cancers. Although still comparably rare, the number of cases has risen dramatically in recent years. Further complicating this trend is that MCC is an extremely aggressive neoplasm with poor patient prognosis and limited treatment options for advanced disease. The causative agent of MCC has been identified as the merkel cell polyomavirus (MCPyV). The MCPyV-encoded large T (LT) antigen is an oncoprotein that is theorized to be essential for virus-mediated tumorigenesis and is therefore, an excellent MCC antigen for the generation of antitumor immune responses. As a foreign antigen, the LT oncoprotein avoids the obstacle of immune tolerance, which normally impedes the development of antitumor immunity. Ergo, it is an excellent target for anti-MCC immunotherapy. Since tumor-specific CD8+ T cells lead to better prognosis for MCC and numerous other cancers, we have generated a DNA vaccine that is capable of eliciting LT-specific CD8+ T cells. The DNA vaccine (pcDNA3-CRT/LT) encodes the LT antigen linked to a damage-associated molecular pattern, calreticulin (CRT), as it has been demonstrated that the linkage of CRT to antigens promotes the induction of antigen-specific CD8+ T cells.

Results

The present study shows that DNA vaccine-induced generation of LT-specific CD8+ T cells is augmented by linking CRT to the LT antigen. This is relevant since the therapeutic effects of the pcDNA3-CRT/LT DNA vaccine is mediated by LT-specific CD8+ T cells. Mice vaccinated with the DNA vaccine produced demonstrably more LT-specific CD8+ T cells. The DNA vaccine was also able to confer LT-specific CD8+ T cell-mediated protective and therapeutic effects to prolong the survival of mice with LT-expressing tumors. In the interest of determining the LT epitope which most MCC-specific CD8+ T cells recognize, we identified the amino acid sequence of the immunodominant LT epitope as aa19-27 (IAPNCYGNI) and found that it is H-2kb-restricted.

Conclusion

The results of this study can facilitate the development of other modes of MCC treatment such as peptide-based vaccines and adoptive transfer of LT-specific CD8+ T cells. Likewise, the MCC DNA vaccine has great potential for clinical translation as the immunologic specificity is high and the treatment strategy can be exported to address other virus-induced tumors.
Counteracting ring formation in rotary kilns
Authors: Pisaroni M , Sadi R , Lahaye D
Published: October 2012

Avoiding the formation of rings in rotary kilns is an issue of primary concern to the cement production industry. We developed a numerical combustion model that revealed that in our case study rings are typically formed in zones of maximal radiative heat transfer. This local overheating causes an overproduction of the liquid phase of the granular material, which tends to stick to the oven’s wall and to form rings. To counteract for this phenomenon, we propose to increase the amount of secondary air injected to cool the oven. Experimental validation at the plant has confirmed that our solution is indeed effective. For the first time in years, the kiln has been operating without unscheduled shut-downs, resulting in hugely important cost savings.
An approach to predict the risk of glaucoma development by integrating different attribute data
Authors: Tokuda Yuichi , Yagi Tomohito , Yoshii Kengo , Ikeda Yoko , Fuwa Masahiro , Ueno Morio , Nakano Masakazu , Omi Natsue , Tanaka Masami , Mori Kazuhiko , Kageyama Masaaki , Nagasaki Ikumitsu , Yagi Katsumi , Kinoshita Shigeru , Tashiro Kei
Published: October 2012

Primary open-angle glaucoma (POAG) is one of the major causes of blindness worldwide and considered to be influenced by inherited and environmental factors. Recently, we demonstrated a genome-wide association study for the susceptibility to POAG by comparing patients and controls. In addition, the serum cytokine levels, which are affected by environmental and postnatal factors, could be also obtained in patients as well as in controls, simultaneously. Here, in order to predict the effective diagnosis of POAG, we developed an “integration approach” using different attribute data which were integrated simply with several machine learning methods and random sampling. Two data sets were prepared for this study. The one is the “training data set”, which consisted of 42 POAG and 42 controls. The other is the “test data set” consisted of 73 POAG and 52 controls. We first examined for genotype and cytokine data using the training data set with general machine learning methods. After the integration approach was applied, we obtained the stable accuracy, using the support vector machine method with the radial basis function. Although our approach was based on well-known machine learning methods and a simple process, we demonstrated that the integration with two kinds of attributes, genotype and cytokines, was effective and helpful in diagnostic prediction of POAG.