bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the pathophysiology of hypogonadism in men with type 2 diabetes: Kisspeptin‐10 stimulates serum testosterone and LH secretion in men with type 2 diabetes and mild biochemical hypogonadism
Authors: George Jyothis T. , Veldhuis Johannes D. , Tena‐Sempere Manuel , Millar Robert P. , Anderson Richard A.
Published: November 2012

Rationale

Low serum testosterone is commonly observed in men with type 2 diabetes (T2DM), but the neuroendocrine pathophysiology remains to be elucidated.

Objectives

The hypothalamic neuropeptide kisspeptin integrates metabolic signals with the reproductive axis in animal models. We hypothesized that administration of exogenous kisspeptin‐10 will restore luteinizing hormone (LH) and testosterone secretion in hypotestosteronaemic men with T2DM.

Participants

Five hypotestosteronaemic men with T2DM (age 33·6 ± 3 years, BMI 40·6 ± 6·3, total testosterone 8·5 ± 1·0 nmol/l, LH 4·7 ± 0·7 IU/l, HbA1c 7·4±2%, duration of diabetes <5 years) and seven age‐matched healthy men.

Experiment 1

Mean LH increased in response to intravenous administration of kisspeptin‐10 (0·3 mcg/kg bolus) both in healthy men (5·5 ± 0·8 to 13·9 ± 1·7 IU/l P < 0·001) and in men with T2DM (4·7 ± 0·7 to 10·7 ± 1·2 IU/l P = 0·02) with comparable ΔLH (P = 0·18).

Experiment 2

Baseline 10‐min serum sampling for LH and hourly testosterone measurements were performed in four T2DM men over 12 h. An intravenous infusion of kisspeptin‐10 (4 mcg/kg/h) was administered for 11 h, 5 days later. There were increases in LH (3·9 ± 0·1 IU/l to 20·7 ± 1·1 IU/l P = 0·03) and testosterone (8·5 ± 1·0 to 11·4 ± 0·9 nmol/l, P = 0·002). LH pulse frequency increased from 0·6 ± 0·1 to 0·9 ± 0 pulses/h (P = 0·05) and pulsatile component of LH secretion from 32·1 ± 8·0 IU/l to 140·2 ± 23·0 IU/l (P = 0·007).

Conclusions

Kisspeptin‐10 administration increased LH pulse frequency and LH secretion in hypotestosteronaemic men with T2DM in this proof‐of‐concept study, with associated increases in serum testosterone. These data suggest a potential novel therapeutic role for kisspeptin agonists in enhancing endogenous testosterone secretion in men with T2DM and central hypogonadism.
Establishing release dynamics for plant nutrients from biochar
Authors: Angst Teri E. , Sohi Saran P.
Published: November 2012

To assess the value of biochar to direct supply of crop nutrients we considered the release of phosphorus, magnesium and potassium from a hardwood biochar in a sequential leaching experiment with deionized water. Cumulative P release was proportionally large despite being quantitatively small, and the sixth extraction yielded 44–73% of the first, indicating that provision of soil P might be sustained for several seasons. Conversely, K release was quantitatively large but declined rapidly from first extraction to the last (6–18% of the first extraction). Only 6–27% of total Mg was recovered. These results indicate that these elements have contrasting associations with biochar that govern the trajectory and ultimate extent of their release. Fitting cumulative loss curves enabled these patterns to be quantitatively captured and compared and could provide a means to develop predictive capacity for the supply of nutrients from biochar to soil and plant.
Was He Murdered Or Was He Not?—Part I: Analyses of Mercury in the Remains of Tycho Brahe
Authors: Rasmussen K. L. , Kučera J. , Skytte L. , Kameník J. , Havránek V. , Smolík J. , Velemínský P. , Lynnerup N. , Bruzek J. , Vellev J.
Published: November 2012

World‐renowned Renaissance astronomer Tycho Brahe died on 24 October 1601, after 11 days of illness. Several conspiracy theories regarding his death have been aired, the first shortly after his death by William Shakespeare in the play Hamlet, published in 1603. A key factor in the still lively debate is whether he was administered mercury—as medicine by his own hand, or as poison by an unfriendly hand. In 2010, Brahe's grave was reopened and samples of his bones, hair, teeth and the textiles were procured and analysed. Here, we present evidence that Brahe was not administered lethal doses of mercury.
Acid‐Base Physiology in Uremia
Authors: DuBose Thomas D.
Published: November 2012

Chronic renal failure represents the most common disorder responsible for chronic stable metabolic acidosis. This type of metabolic acidosis has been characterized as “hyperchloremic“ in pre‐end‐stage disease and the “anion‐gap“ form as the GFR falls below 20 ml/min. The early hyperchloremic, hyperkalemic variety may result from disease of the juxtaglomerular apparatus, a distal acidification defect, or volume depletion. The anion‐gap acidosis of advanced renal disease occurs as a result of the inability of the diminished nephron mass to keep pace with the metabolic acid load which depletes extracellular fluid bicarbonate. Total ammonium excretion diminishes despite an adaptive increase in ammonia production per nephron. The observation that the serum bicarbonate rarely falls below 15 mEq/L and the anion gap stays below 20 mEq/L despite positive hydrogen ion balance attests to the important role of extrarenal buffers. Bone buffers, primarily calcium carbonate, titrate a portion of the excess hydrogen ions at the expense of progressive loss of bone salts. Parathyroid hormone (PTH) appears to be involved in the control of bone buffering capacity. Both PTH‐dependent and PTH‐independent mechanisms must therefore be considered. PTH mediates bone buffering capacity by activating intracellular shifts of calcium, phosphorus, and carbonate or by stimulation of bone carbonic anhydrase. A direct effect of pH on bone mineral mobilization has been demonstrated. Adequate alkali therapy to maintain serum bicarbonate levels of 20–22 mEq/L may prevent bone dissolution and minimize risk of volume overload.
Advantages of Bicarbonate Hemodialysis
Authors: Hampl H. , Klopp H. , Wolfgruber M. , Pustelnik A. , Schiller R. , Hanefeld F. , Kessel M.
Published: November 2012

Six patients with frequent episodes of symptomatic hypotension during acetate dialysis were treated with bicarbonate dialysis. In all patients blood pressure, heart rate, and arterial acid‐base values were measured every 30 minutes during each of the five treatments with acetate dialysis and bicarbonate dialysis. Hemodynamic parameters were measured in‐vasively in all patients during bicarbonate dialysis and in three of them also during acetate dialysis. Additionally, continuous long‐time monitoring with electroencephalography was performed during acetate dialysis and bicarbonate dialysis. During acetate dialysis the patients showed a frequent onset of sudden hypotension and arrhythmia with concomitant symptoms of the so‐called disequilibrium syndrome, whereas these symptoms were nonexistent in the same patients during bicarbonate dialysis.
Dialysis Performance of Single Lumen Subclavian Hemodialysis: A Comparative Study with Single Lumen Fistula Hemodialysis
Authors: Vanholder R. , Hoenich N. , Ringoir S.
Published: November 2012

Study of hemodialysis performance and recirculation ratios of subclavian catheter hemodialysis is Reported. Data are compared to the results obtained when a conventional in‐trafistular single‐lumen hemodialysis needle is used under similar conditions.

Renal blood flow values were slightly but not significantly lower for subclavian hemodialysis. Small molecular extraction ratios were identical. Small molecular clearances were somewhat lower for the subclavian approach, especially at high dialyzer blood flow rates. However, the differences were not significant, and overall extraction ratios, calculated for the entire dialysis period with both access methods in 43 patients, were identical. Recirculation averaged 12.5% for the fistular approach and 20% for the subclavian approach.

It is concluded that, as a whole, dialysis performance is somewhat lower with the subclavian vascular access method. This is mainly due to a higher recirculation rate, and in turn to the consequence of the length of the intravascular device. However, this minor differences do not necessitate changes in dialysis schedules.
Clinical Experience of Postoperative Hepatic Failure Treatment with Pig or Baboon Liver Cross‐Hemodialysis with an Interposed Membrane
Authors: Ozawa Kazue , Kamiyama Yasuo , Kimura Kenichi , Ukikusa Minoru , Kono Yukihiro , Yamato Toshio , Shimahara Yasuyuki , Nakatani Toshio , Asano Motokazu , Irie Ryuichi , Kawashima Sadao , Uchida Kenichi , Ohtoshi Masahiro , Aoyama Hidehisa , Hirai Fumihiko , Yasuda Kazuhiro , Tobe Takayoshi
Published: November 2012

The present study emphasizes the principle of using liver support to restore the blood ketone body ratio (acetoacetate/β‐hydroxybutyrate), which reflects the redox potential of liver mitochondria and correlates with hepatic energy charge (ATP + 0.5ADP/ATP + ADP + AMP). Eleven surgical patients with grade IV hepatic coma were treated by an ex vivo pig or baboon liver cross‐hemodialysis with an interposed Cuprophan membrane when their blood ketone body ratios had decreased to below 0.4 compared with the normal of above 0.7. Three patients were treated by cross‐hemodialysis using a standard Cuprophan membrane dialyzer without increase of blood ketone body ratio and without marked beneficial effect. However, five of eight patients who had bood ketone body ratios of above 0.25 became fully alert after treatment by cross‐hemodialysis using the larger pore size and greater surface area Cuprophan membrane, concurrent with a rise in the decreased blood ketone body ratio, and three of them were later discharged. By contrast, in the three patients with blood ketone body ratios below 0.25, there was no restoration of consciousness and no improvement in their blood ketone body ratios by this liver support. It is suggested that, as long as the blood ketone body ratio remained over 0.25, this metabolic liver support is effective in restoring grade IV hepatic coma.
Infusion‐Free Hemodiafiltration: Simultaneous Hemofiltration and Dialysis with No Need for Infusion Fluid
Authors: Shinzato Toru , Sezaki Ryozo , Usuda Masatsune , Maeda Kenji , Ohbayashi Shogo , Toyota Tatsumi
Published: November 2012

A new simultaneous hemofiltration and dialysis system was developed which has no need of infusion fluid. The system employs two hemodiafilters in a direct series. An ultrafiltration rate and dialysate flow rate control system was employed to control the dialysate flow at the inlet and outlet, and the difference in volume was arranged to be the amount of water removed from the body. When the blood circuit was narrowed between the two hemodiafilters, the ultrafiltration was performed at the first hemodiafilter; at the second one, the dialysate moved to the blood side as a dilution fluid. To remove pyrogens and bacteria, tap water was subjected to activated charcoal, ion exchange and reverse osmosis treatment, followed by preparation of the dialysate. In clinical evaluation, this system showed marked improvement in clearance of middle and large molecules.
Regulatory Pathways to the Market: An Overview
Authors: Morton William A.
Published: November 2012

This paper presents an overview of the U.S. Food and Drug Administration's regulatory requirements for introducing medical device and diagnostic products into commercial distribution in the United States. For any specific product, the requirements vary depending upon the product's associated risks, classification, and when it or a similar product was first introduced into commercial distribution. Regulatory pathways available and/or required for a manufacturer to introduce a medical product into the U.S. marketplace are outlined.
Road Traffic Noise Prediction with Neural Networks - A Review
Authors: KUMAR Kranti , PARIDA Manoranjan , KATIYAR Vinod Kumar
Published: November 2012

This paper aims to summarize the findings of research concerning the application of neural networks in traffic noise prediction. Noise is an environmental agent, regarded as a stressful stimulus. Noise exposure causes changes at different levels in living beings, such as the cardiovascular, endocrine and nervous system. Study of traffic noise prediction models began in 1950s to predict a single vehicle sound pressure level at the road side. After that, several traffic noise prediction models such as FHWA, CORTN, STOP and GO, MITHRA, ASJ etc. were developed depending upon various parameters and conditions. Complexity of error identification by means of classical approaches has led to researchers and designers to explore the possibility of neural solution to the problem of traffic noise prediction. Present study is focused on review of various neural network models developed for road traffic noise prediction.
Optimal Testing Effort Control for Modular Software System Incorporating The Concept of Independent and Dependent Faults: A Control Theoretic Approach
Authors: CHAUDHARY Kuldeep , JHA P. C.
Published: November 2012

In this paper, we discuss modular software system for Software Reliability Growth Models using testing effort and study the optimal testing effort intensity for each module. The main goal is to minimize the cost of software development when budget constraint on testing expenditure is given. We discuss the evolution of faults removal dynamics in incorporating the idea of leading /independent and dependent faults in modular software system under the assumption that testing of each of the modulus is done independently. The problem is formulated as an optimal control problem and the solution to the proposed problem has been obtained by using Pontryagin Maximum Principle.
Linear Optimal Multi-periodic Repetitive Control - A Low Order Controller Scheme
Authors: HAN Youde , OWENS David H. , CHU Bing
Published: November 2012

This article proposes a new method for treating the computational problem in discrete time linear multi-periodic repetitive control systems, where the reference signal includes several periodic components with already known periods.  As periods get large, the computational problem becomes prominent. This work thus investigates the frequency contents of reference signals, where the order of original repetitive controller is lowered by considering only a reduced number of poles, namely, the most important contributors to the total energy of the multi-periodic reference signal. A lower order multi-periodic repetitive controller is designed which assures BIBO stability of the closed-loop system, and approximate tracking is achieved. Finally, experimental tests on a non-minimum phase spring mass damper system demonstrate the effectiveness of this new controller.
Synthetic Lipid Membrane Channels Formed by Designed DNA Nanostructures
Authors: Langecker Martin , Arnaut Vera , Martin Thomas G. , List Jonathan , Renner Stephan , Mayer Michael , Dietz Hendrik , Simmel Friedrich C.
Published: November 2012

Channels from DNA

Artificial transmembrane channels are of interest for applications, such as sensing and modifying cell signaling.

Langecker
et al.

(p.
932
; see the Perspective by

Strano

) used α-hemolysin as a model for creating a nanostructure with DNA origami that, when inserted into a lipid bilayer membrane, acted as a membrane channel. Ion channel responses were similar to those measured for natural ion channels, and channels that protruded further into the membrane exhibited greater gating responses. The channels were used to detect single-DNA molecules.
Multifunctional Nanoparticles: Cost Versus Benefit of Adding Targeting and Imaging Capabilities
Authors: Cheng Zhiliang , Al Zaki Ajlan , Hui James Z. , Muzykantov Vladimir R. , Tsourkas Andrew
Published: November 2012

Nanoparticle-based drug delivery systems have been developed to improve the efficacy and reduce the systemic toxicity of a wide range of drugs. Although clinically approved nanoparticles have consistently shown value in reducing drug toxicity, their use has not always translated into improved clinical outcomes. This has led to the development of “multifunctional” nanoparticles, where additional capabilities like targeting and image contrast enhancement are added to the nanoparticles. However, additional functionality means additional synthetic steps and costs, more convoluted behavior and effects in vivo, and also greater regulatory hurdles. The trade-off between additional functionality and complexity is the subject of ongoing debate and the focus of this Review.
Responsible Research Conduct
Authors: Nath Indira , Winnacker Ernst-Ludwig
Published: November 2012

Last Month, the Interacademy Council (IAC) and the Interacademy Panel (IAP), the Global network of science academies, released a report on responsible behavior in science.
*
The recommendations of the committee, which we chaired, were inspired by several trends in today's research environment that have made it an exciting time to do research, but have also made science a more complicated enterprise, raising concerns about ethical conduct and values.
Researchers Lobby to Spare Science From E.U. Budget Cuts
Authors: Vogel Gretchen
Published: November 2012

An increasingly loud chorus of scientists and research organizations is demanding that any cuts to the European Union's budget for the remainder of the decade be made in areas other than research.
Change Versus Experience?
Authors: Malakoff David
Published: November 2012

This month, Republicans in the U.S. House of Representatives will choose from among a trio of veteran politicians vying to become the next chair of the House Committee on Science, Space, and Technology.
Winds of Change
Authors: Qiu Jane
Published: November 2012

Antarctica's fate is not as simple as that of an ice cube melting in the sun, scaled up a trillionfold.
Diagnostic Accuracy of the GenoType MTBDR
sl
Assay for Rapid Diagnosis of Extensively Drug-Resistant Tuberculosis in HIV-Coinfected Patients
Authors: Kontsevaya Irina , Ignatyeva Olga , Nikolayevskyy Vladyslav , Balabanova Yanina , Kovalyov Alexander , Kritsky Andrey , Matskevich Olesya , Drobniewski Francis
Published: November 2012

The Russian Federation is a high-tuberculosis (TB)-burden country with high rates of
Mycobacterium tuberculosis
multidrug resistance (MDR) and extensive drug resistance (XDR), especially in HIV-coinfected patients. Rapid and reliable diagnosis for detection of resistance to second-line drugs is vital for adequate patient management. We evaluated the performance of the GenoType MTBDR
sl
(Hain Lifescience GmbH, Nehren, Germany) assay on smear-positive sputum specimens obtained from 90 HIV-infected MDR TB patients from Russia. Test interpretability was over 98%. Specificity was over 86% for all drugs, while sensitivity varied, being the highest (71.4%) for capreomycin and lowest (9.4%) for kanamycin, probably due to the presence of mutations in the
eis
gene. The sensitivity of detection of XDR TB was 13.6%, increasing to 42.9% if kanamycin (not commonly used in Western Europe) was excluded. The assay is a highly specific screening tool for XDR detection in direct specimens from HIV-coinfected TB patients but cannot be used to rule out XDR TB.
Diagnostic Accuracy and Reproducibility of WHO-Endorsed Phenotypic Drug Susceptibility Testing Methods for First-Line and Second-Line Antituberculosis Drugs
Authors: Horne David J. , Pinto Lancelot M. , Arentz Matthew , Lin S.-Y. Grace , Desmond Edward , Flores Laura L. , Steingart Karen R. , Minion Jessica
Published: November 2012

In an effort to update and clarify policies on tuberculosis drug susceptibility testing (DST), the World Health Organization (WHO) commissioned a systematic review evaluating WHO-endorsed diagnostic tests. We report the results of this systematic review and meta-analysis of the diagnostic accuracy and reproducibility of phenotypic DST for first-line and second-line antituberculosis drugs. This review provides support for recommended critical concentrations for isoniazid and rifampin in commercial broth-based systems. Further studies are needed to evaluate critical concentrations for ethambutol and streptomycin that accurately detect susceptibility to these drugs. Evidence is limited on the performance of DST for pyrazinamide and second-line drugs.
Straightforward Selection of Broadly Neutralizing Single-Domain Antibodies Targeting the Conserved CD4 and Coreceptor Binding Sites of HIV-1 gp120
Authors: Matz Julie , Kessler Pascal , Bouchet Jérôme , Combes Olivier , Ramos Oscar Henrique Pereira , Barin Francis , Baty Daniel , Martin Loïc , Benichou Serge , Chames Patrick
Published: November 2012

Few broadly neutralizing antibodies targeting determinants of the HIV-1 surface envelope glycoprotein (gp120) involved in sequential binding to host CD4 and chemokine receptors have been characterized. While these epitopes show low diversity among various isolates, HIV-1 employs many strategies to evade humoral immune response toward these sensitive sites, including a carbohydrate shield, low accessibility to these buried cavities, and conformational masking. Using trimeric gp140, free or bound to a CD4 mimic, as immunogens in llamas, we selected a panel of broadly neutralizing single-domain antibodies (sdAbs) that bind to either the CD4 or the coreceptor binding site (CD4BS and CoRBS, respectively). When analyzed as monomers or as homo- or heteromultimers, the best sdAb candidates could not only neutralize viruses carrying subtype B envelopes, corresponding to the Env molecule used for immunization and selection, but were also efficient in neutralizing a broad panel of envelopes from subtypes A, C, G, CRF01_AE, and CRF02_AG, including tier 3 viruses. Interestingly, sdAb multimers exhibited a broader neutralizing activity spectrum than the parental sdAb monomers. The extreme stability and high recombinant production yield combined with their broad neutralization capacity make these sdAbs new potential microbicide candidates for HIV-1 transmission prevention.
Systematic Identification of H274Y Compensatory Mutations in Influenza A Virus Neuraminidase by High-Throughput Screening
Authors: Wu Nicholas C. , Young Arthur P. , Dandekar Sugandha , Wijersuriya Hemani , Al-Mawsawi Laith Q. , Wu Ting-Ting , Sun Ren
Published: November 2012

Compensatory mutations contribute to the appearance of the oseltamivir resistance substitution H274Y in the neuraminidase (NA) gene of H1N1 influenza viruses. Here, we describe a high-throughput screening method utilizing error-prone PCR and next-generation sequencing to comprehensively screen NA genes for H274Y compensatory mutations. We found four mutations that can either fully (R194G, E214D) or partially (L250P, F239Y) compensate for the fitness deficiency of the H274Y mutant. The compensatory effect of E214D is applicable in both seasonal influenza virus strain A/New Caledonia/20/1999 and 2009 pandemic swine influenza virus strain A/California/04/2009. The technique described here has the potential to profile a gene at the single-nucleotide level to comprehend the dynamics of mutation space and fitness and thus offers prediction power for emerging mutant species.
Alternative Serotype Adenovirus Vaccine Vectors Elicit Memory T Cells with Enhanced Anamnestic Capacity Compared to Ad5 Vectors
Authors: Penaloza-MacMaster Pablo , Provine Nicholas M. , Ra Joshua , Borducchi Erica N. , McNally Anna , Simmons Nathaniel L. , Iampietro Mark J. , Barouch Dan H.
Published: November 2012

The failure of the adenovirus serotype 5 (Ad5) vector-based human immunodeficiency virus type 1 (HIV-1) vaccine in the STEP study has led to the development of adenovirus vectors derived from alternative serotypes, such as Ad26, Ad35, and Ad48. We have recently demonstrated that vaccines using alternative-serotype Ad vectors confer partial protection against stringent simian immunodeficiency virus (SIV) challenges in rhesus monkeys. However, phenotypic differences between the T cell responses elicited by Ad5 and those of alternative-serotype Ad vectors remain unexplored. Here, we report the magnitude, phenotype, functionality, and recall capacity of memory T cell responses elicited in mice by Ad5, Ad26, Ad35, and Ad48 vectors expressing lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP). Our data demonstrate that memory T cells elicited by Ad5 vectors were high in magnitude but exhibited functional exhaustion and decreased anamnestic potential following secondary antigen challenge compared to Ad26, Ad35, and Ad48 vectors. These data suggest that vaccination with alternative-serotype Ad vectors offers substantial immunological advantages over Ad5 vectors, in addition to circumventing high baseline Ad5-specific neutralizing antibody titers.
Cyclophilin Inhibitors Block Arterivirus Replication by Interfering with Viral RNA Synthesis
Authors: de Wilde Adriaan H. , Li Yanhua , van der Meer Yvonne , Vuagniaux Grégoire , Lysek Robert , Fang Ying , Snijder Eric J. , van Hemert Martijn J.
Published: November 2012

Virus replication strongly depends on cellular factors, in particular, on host proteins. Here we report that the replication of the arteriviruses equine arteritis virus (EAV) and porcine reproductive and respiratory syndrome virus (PRRSV) is strongly affected by low-micromolar concentrations of cyclosporine A (CsA), an inhibitor of members of the cyclophilin (Cyp) family. In infected cells, the expression of a green fluorescent protein (GFP) reporter gene inserted into the PRRSV genome was inhibited with a half-maximal inhibitory concentration (IC
50
) of 5.2 μM, whereas the GFP expression of an EAV-GFP reporter virus was inhibited with an IC
50
of 0.95 μM. Debio-064, a CsA analog that lacks its undesirable immunosuppressive properties, inhibited EAV replication with an IC
50
that was 3-fold lower than that of CsA, whereas PRRSV-GFP replication was inhibited with an IC
50
similar to that of CsA. The addition of 4 μM CsA after infection prevented viral RNA and protein synthesis in EAV-infected cells, and CsA treatment resulted in a 2.5- to 4-log-unit reduction of PRRSV or EAV infectious progeny. A complete block of EAV RNA synthesis was also observed in an
in vitro
assay using isolated viral replication structures. The small interfering RNA-mediated knockdown of Cyp family members revealed that EAV replication strongly depends on the expression of CypA but not CypB. Furthermore, upon fractionation of intracellular membranes in density gradients, CypA was found to cosediment with membranous EAV replication structures, which could be prevented by CsA treatment. This suggests that CypA is an essential component of the viral RNA-synthesizing machinery.
Significant Reductions in Gag-Protease-Mediated HIV-1 Replication Capacity during the Course of the Epidemic in Japan
Authors: Nomura Shigeru , Hosoya Noriaki , Brumme Zabrina L. , Brockman Mark A. , Kikuchi Tadashi , Koga Michiko , Nakamura Hitomi , Koibuchi Tomohiko , Fujii Takeshi , Carlson Jonathan M. , Heckerman David , Kawana-Tachikawa Ai , Iwamoto Aikichi , Miura Toshiyuki
Published: November 2012

Human immunodeficiency virus type 1 (HIV-1) evolves rapidly in response to host immune selection pressures. As a result, the functional properties of HIV-1 isolates from earlier in the epidemic may differ from those of isolates from later stages. However, few studies have investigated alterations in viral replication capacity (RC) over the epidemic. In the present study, we compare Gag-Protease-associated RC between early and late isolates in Japan (1994 to 2009). HIV-1 subtype B sequences from 156 antiretroviral-naïve Japanese with chronic asymptomatic infection were used to construct a chimeric NL4-3 strain encoding plasma-derived
gag-protease
. Viral replication capacity was examined by infecting a long terminal repeat-driven green fluorescent protein-reporter T cell line. We observed a reduction in the RC of chimeric NL4-3 over the epidemic, which remained significant after adjusting for the CD4
+
T cell count and plasma virus load. The same outcome was seen when limiting the analysis to a single large cluster of related sequences, indicating that our results are not due to shifts in the molecular epidemiology of the epidemic in Japan. Moreover, the change in RC was independent of genetic distance between patient-derived sequences and wild-type NL4-3, thus ruling out potential temporal bias due to genetic similarity between patient and historic viral backbone sequences. Collectively, these data indicate that Gag-Protease-associated HIV-1 replication capacity has decreased over the epidemic in Japan. Larger studies from multiple geographical regions will be required to confirm this phenomenon.
p38 and OGT Sequestration into Viral Inclusion Bodies in Cells Infected with Human Respiratory Syncytial Virus Suppresses MK2 Activities and Stress Granule Assembly
Authors: Fricke Jens , Koo Lily Y. , Brown Charles R. , Collins Peter L.
Published: November 2012

Respiratory syncytial virus (RSV) forms cytoplasmic inclusion bodies (IBs) that are thought to be sites of nucleocapsid accumulation and viral RNA synthesis. The present study found that IBs also were the sites of major sequestration of two proteins involved in cellular signaling pathways. These are phosphorylated p38 mitogen-activated protein kinase (MAPK) (p38-P), a key regulator of cellular inflammatory and stress responses, and O-linked
N
-acetylglucosamine (OGN) transferase (OGT), an enzyme that catalyzes the posttranslational addition of OGN to protein targets to regulate cellular processes, including signal transduction, transcription, translation, and the stress response. The virus-induced sequestration of p38-P in IBs resulted in a substantial reduction in the accumulation of a downstream signaling substrate, MAPK-activated protein kinase 2 (MK2). Sequestration of OGT in IBs was associated with suppression of stress granule (SG) formation. Thus, while the RSV IBs are thought to play an essential role in viral replication, the present results show that they also play a role in suppressing the cellular response to viral infection. The sequestration of p38-P and OGT in IBs appeared to be reversible: oxidative stress resulting from arsenite treatment transformed large IBs into a scattering of smaller bodies, suggestive of partial disassembly, and this was associated with MK2 phosphorylation and OGN addition. Unexpectedly, the RSV M2-1 protein was found to localize in SGs that formed during oxidative stress. This protein was previously shown to be a viral transcription elongation factor, and the present findings provide the first evidence of possible involvement in SG activities during RSV infection.
Support systems for and barriers to diabetes management in South Asians and Whites in the UK: qualitative study of patients’ perspectives
Authors: Singh Harsimran , Cinnirella Marco , Bradley Clare
Published: November 2012

Objectives

To explore experiences of UK-based South Asian and White patients with diabetes in relation to their support systems for and barriers to diabetes management.

Design

Qualitative study (semistructured interviews analysed using a form of Interpretative Phenomenological Analysis).

Participants

20 outpatients with diabetes (12 British South Asians and 8 British Whites) with either good or poor glycaemic control.

Setting

Hillingdon Hospital, Uxbridge, UK.

Results

Qualitative analysis revealed distinct themes for the two ethnic groups. For the South Asian participants, challenges surrounding diet management and social stigma attached to having diabetes were the two predominant barriers to effective diabetes management. Support from immediate family members was commonly reported as a strong support system for optimising diabetes management by the South Asian sample in addition to the perceived positive impact of religion (healing power of prayer), the valuable informational support from their diabetes-care team, patient leaflets and diabetes magazines. Similar to the South Asians, adhering to dietary recommendations was the most difficult aspect of diabetes management for the White participants followed by the inconveniences surrounding injecting insulin. The hospital diabetes-care team was considered as the most effective support system for diabetes management by the White sample and interestingly, this was the only dominant theme in their reported sources of support.

Conclusions

Both South Asian and White participants emphasised adherence to dietary recommendations as the most difficult aspect of living with diabetes. In addition, social stigma attached to diabetes was a prominent concern among South Asian participants that seemed to have a significant negative impact on their diabetes control and overall management. Given South Asian patients’ reliance on their family for the management of their condition, interventions targeting improved diabetes outcomes in this population may prove more successful if they are designed to involve significant family members.
Breaking the speed limit — comparative sprinting performance of brook trout (Salvelinus fontinalis) and brown trout (Salmo trutta)
Authors: Castro-Santos Theodore , Sanz-Ronda Francisco Javier , Ruiz-Legazpi Jorge
Published: November 2012

Sprinting behavior of free-ranging fish has long been thought to exceed that of captive fish. Here we present data from wild-caught brook trout (Salvelinus fontinalis) and brown trout (Salmo trutta), volitionally entering and sprinting against high-velocity flows in an open-channel flume. Performance of the two species was nearly identical, with the species attaining absolute speeds > 25 body lengths·s−1. These speeds far exceed previously published observations for any salmonid species and contribute to the mounting evidence that commonly accepted estimates of swimming performance are low. Brook trout demonstrated two distinct modes in the relationship between swim speed and fatigue time, similar to the shift from prolonged to sprint mode described by other authors, but in this case occurring at speeds > 19 body lengths·s−1. This is the first demonstration of multiple modes of sprint swimming at such high swim speeds. Neither species optimized for distance maximization, however, indicating that physiological limits alone are poor predictors of swimming performance. By combining distributions of volitional swim speeds with endurance, we were able to account for >80% of the variation in distance traversed by both species.
Direct determination of age in shrimps, crabs, and lobsters
Authors: Kilada Raouf , Sainte-Marie Bernard , Rochette Rémy , Davis Neill , Vanier Caroline , Campana Steven
Published: November 2012

The detection and measurement of annual growth bands preserved in calcified structures underlies the assessment and management of exploited fish populations around the world. However, the estimation of growth, mortality, and other age-structured processes in crustaceans has been severely limited by the apparent absence of permanent growth structures. Here, we report the detection of growth bands in calcified regions of the eyestalk or gastric mill in shrimps, crabs, and lobsters. Comparison of growth band counts with reliable, independent estimates of age strongly suggests that the bands form annually, thus providing a direct and accurate method of age determination in all of the species examined. Chemical tags in the lobster cuticle were retained through one or two molts that occurred over the duration of an experiment, as apparently was the mesocardiac ossicle containing the growth bands in the gastric mill. Growth bands are not the previously documented lamellae of the endocuticle, and their formation was not associated with molting. Sex-specific growth curves were readily developed from growth band examination in multiple species, suggesting that routine measurement of growth and mortality in decapod crustaceans may now be possible.
Influence of treatment with quercetin on lipid parameters and oxidative stress of pregnant diabetic rats
Authors: Pereira Braga Camila , Momentti Ana Carolina , Barbosa Peixoto Fernando , de Fátima Ferreira Baptista Rafaela , dos Santos Felipe André , Fava Fábio Henrique , Fernandes Ana Angélica Henrique
Published: November 2012

Among the numerous coadjuvant therapies that could influence the incidence and progression of diabetic complications, antioxidants and flavonoids are currently being tested in clinical trials. We investigated the effect of quercetin on biochemical parameters in streptozotocin-induced (60 mg/kg body mass, by intraperitoneal injection) diabetic rats. A total of 32 female Wistar rats were distributed among 4 groups as follows: control (G1); control treated with quercetin (G2); diabetic (G3); and diabetic treated with quercetin (G4). Quercetin administered to pregnant diabetic rats controlled dyslipidemia and improved lipid profiles in diabetes mellitus, regulated oxidative stress by reducing the generation of lipid hydroperoxides, and increased the activity of the antioxidant enzyme glutathione peroxidase.
Estimating recruitment dynamics and movement of rainbow trout (Oncorhynchus mykiss) in the Colorado River in Grand Canyon using an integrated assessment model
Authors: Korman Josh , Martell Steven J.D. , Walters Carl J. , Makinster Andrew S. , Coggins Lewis G. , Yard Michael D. , Persons William R.
Published: November 2012

We used an integrated assessment model to examine effects of flow from Glen Canyon Dam, Arizona, USA, on recruitment of nonnative rainbow trout ( Oncorhynchus mykiss ) in the Colorado River and to estimate downstream migration from Glen Canyon to Marble Canyon, a reach used by endangered native fish. Over a 20-year period, recruitment of rainbow trout in Glen Canyon increased with the annual flow volume and when hourly flow variation was reduced and after two of three controlled floods. The model predicted that approximately 16 000 trout·year–1emigrated to Marble Canyon and that the majority of trout in this reach originate from Glen Canyon. For most models that were examined, over 70% of the variation in emigration rates was explained by variation in recruitment in Glen Canyon, suggesting that flow from the dam controls in large part the extent of potential negative interactions between rainbow trout and native fish. Controlled floods and steadier flows, which were originally aimed at partially restoring conditions before the dam (greater native fish abundance and larger sand bars), appear to have been more beneficial to nonnative rainbow trout than to native fish.
Reply to comment by Jackson and Martin on “Does timber harvest influence the dynamics of marine-derived nutrients in Southeast Alaska streams?” 1Original article by Levi et al. appears in Can. J. Fish. Aquat. Sci. 68(8): 1316–1329 and is available at http://www.nrcresearchpress.com/doi/full/10.1139/f2011-067. Comment by Jackson and Martin appears in Can. J. Fish. Aquat. Sci. 69: this issue, and is available at http://www.nrcresearchpress.com/doi/full/10.1139/f2012-104.
Authors: Levi Peter S. , Tank Jennifer L. , Tiegs Scott D. , Rüegg Janine , Chaloner Dominic T. , Lamberti Gary A.
Published: November 2012

The stated goal of Levi et al. (2011, Can. J. Fish. Aquat. Sci. 68: 1316–1329) was to determine the influence of geomorphic complexity on the dynamics of salmon-derived nutrients. We studied seven streams in Southeast Alaska with varying degrees of historical (mid-1900s) timber harvest and, as a result, differences in stream geomorphology. In a comment on our study, Jackson and Martin (2012, Can. J. Fish. Aquat. Sci. 69: this issue) suggest that the geomorphic complexity we ascribe to timber harvest may be due to natural variation in watershed characteristics and offer alternative hypotheses. We sought to reduce the natural variation among our study streams by using a stratified sampling design (i.e., selecting reaches classified as floodplain 4 or 5 by the USDA Forest Service), but acknowledge that, as with any ecological field study, alternative hypotheses may exist to explain observed patterns in ecological responses. We maintain that our study design was sufficiently robust (i.e., 300 m reaches studied in seven streams for 3 years, totaling 21 stream-years) to draw inferences about the influence of salmon on streamwater nutrients and, secondarily, the role of geomorphic variation in mediating nutrient dynamics. Our data also support our finding that the legacy of timber harvest altered nutrient dynamics in salmon-bearing streams via alterations to stream geomorphology that were quantifiable.
A simplified nonlinear approach for single pile settlement analysis
Authors: Zhang Qian-qing , Zhang Zhong-miao
Published: November 2012

A simple analytical approach for nonlinear analysis of the load–displacement response of a single pile is presented. Two models are adopted in the proposed approach. One model uses a softening nonlinear relationship to simulate the degradation behavior between the unit skin friction and the pile–soil relative displacement developed in the pile–soil interface, and the other model adopts a bilinear load–displacement relationship to capture the pile-end response. Based on the two proposed models, a highly effective computer program has been developed for nonlinear analysis of the load–settlement behavior of a single pile. Comparisons are made between the present method, other analytical methods, and a well-documented field experimental pile loading case. The results of the comparisons indicate that the proposed method is generally in good agreement with field-observed behavior and the calculated results derived from other approaches. A parametric study is conducted to assess the influence of the parameters related to the proposed model on the load–displacement response of a single pile.
THE BEAUTY OF LATTICE PERTURBATION THEORY: THE ROLE OF LATTICE PERTURBATION THEORY IN B PHYSICS
Authors: MONAHAN C. J.
Published: November 2012

As new experimental data arrive from the LHC the prospect of indirectly detecting new physics through precision tests of the Standard Model grows more exciting. Precise experimental and theoretical inputs are required to test the unitarity of the CKM matrix and to search for new physics effects in rare decays. Lattice QCD calculations of non-perturbative inputs have reached a precision at the level of a few percent; in many cases aided by the use of lattice perturbation theory. This review examines the role of lattice perturbation theory in B physics calculations on the lattice in the context of two questions: how is lattice perturbation theory used in the different heavy quark formalisms implemented by the major lattice collaborations? And what role does lattice perturbation theory play in determinations of non-perturbative contributions to the physical processes at the heart of the search for new physics? Framing and addressing these questions reveals that lattice perturbation theory is a tool with a spectrum of applications in lattice B physics.
EVALUATION OF TAG MOVING DIRECTION DETECTION IN A UHF RFID GATE SYSTEM
Authors: OIKAWA YOSHINORI
Published: November 2012

A UHF-band RFID system handling many RF tags has some advantages over a bar code system such as simultaneous multi-reading and long read range. Especially, it has been strongly desired by the logistics and the retail industries for efficiency of operation. Recently, user-friendly RFID systems are being studied. We focused on a gate system using RFID technologies. If the tag moving direction can be recognized at the RFID gate system, it will be very useful for the efficiency of inventory management and the checking of pilferage or shoplifting. In this paper, new methods of tag moving direction detection using the difference of passing time of two antennas without expensive external sensors is proposed and evaluated. Two methods are proposed for the specific procedure. The first one is to detect the time when the received power goes over the preset threshold. The second one is to estimate the aimed time using the maximum likelihood approach. Some experimental results of these methods are also shown and their feasibility is proved.
DUAL PLS ANALYSIS
Authors: LIPOVETSKY STAN
Published: November 2012

A new multivariate statistical technique is obtained for comparing and combining two or more data sets each of which has a different number of respondents but the same variables. This approach can be considered as dual to such techniques as partial least squares, also known as inter-battery factor analysis and robust canonical correlation analysis for two data sets. It is shown that the problem can be reduced to the eigenproblem of the product of correlation matrices of each data set. The technique is generalized to three or more data sets in an eigenproblem of block-matrices of the correlations within each data set. This type of multivariate analysis can serve various practical problems of integration of data obtained from heterogeneous sources, particularly, for data merging in constructing data warehouses.
Effect of chronic perinatal hypoxia on the role of rho-kinase in pulmonary artery contraction in newborn lambs
Authors: Blood Arlin B. , Terry Michael H. , Merritt Travis A. , Papamatheakis Demosthenes G. , Blood Quintin , Ross Jonathon M. , Power Gordon G. , Longo Lawrence D. , Wilson Sean M.
Published: November 2012

Exposure to chronic hypoxia during gestation predisposes infants to neonatal pulmonary hypertension, but the underlying mechanisms remain unclear. Here, we test the hypothesis that moderate continuous hypoxia during gestation causes changes in the rho-kinase pathway that persist in the newborn period, altering vessel tone and responsiveness. Lambs kept at 3,801 m above sea level during gestation and the first 2 wk of life were compared with those with gestation at low altitude. In vitro studies of isolated pulmonary arterial rings found a more forceful contraction in response to KCl and 5-HT in high-altitude compared with low-altitude lambs. There was no difference between the effects of blockers of various pathways of extracellular Ca2+ entry in low- and high-altitude arteries. In contrast, inhibition of rho-kinase resulted in significantly greater attenuation of 5-HT constriction in high-altitude compared with low-altitude arteries. High-altitude lambs had higher baseline pulmonary artery pressures and greater elevations in pulmonary artery pressure during 15 min of acute hypoxia compared with low-altitude lambs. Despite evidence for an increased role for rho-kinase in high-altitude arteries, in vivo studies found no significant difference between the effects of rho-kinase inhibition on hypoxic pulmonary vasoconstriction in intact high-altitude and low-altitude lambs. We conclude that chronic hypoxia in utero results in increased vasopressor response to both acute hypoxia and serotonin, but that rho-kinase is involved only in the increased response to serotonin.
Increasing temperature speeds intracellular Po2kinetics during contractions in singleXenopusskeletal muscle fibers
Authors: Koga S. , Wüst R. C. I. , Walsh B. , Kindig C. A. , Rossiter H. B. , Hogan M. C.
Published: November 2012

Precise determination of the effect of muscle temperature (Tm) on mitochondrial oxygen consumption kinetics has proven difficult in humans, in part due to the complexities in controlling for Tm-related variations in blood flow, fiber recruitment, muscle metabolism, and contractile properties. To address this issue, intracellular Po2(PiO2) was measured continuously by phosphorescence quenching following the onset of contractions in single Xenopus myofibers ( n = 24) while controlling extracellular temperature. Fibers were subjected to two identical contraction bouts, in random order, at 15°C (cold, C) and 20°C (normal, N; n = 12), or at N and 25°C (hot, H; n = 12). Contractile properties were determined for every contraction. The time delay of the PiO2response was significantly greater in C (59 ± 35 s) compared with N (35 ± 26 s, P = 0.01) and H (27 ± 14 s, P = 0.01). The time constant for the decline in PiO2was significantly greater in C (89 ± 34 s) compared with N (52 ± 15 s; P < 0.01) and H (37 ± 10 s; P < 0.01). There was a linear relationship between the rate constant for PiO2kinetics and Tm( r = 0.322, P = 0.03). Estimated ATP turnover was significantly greater in H than in C ( P < 0.01), but this increased energy requirement alone with increased Tmcould not account for the differences observed in PiO2kinetics among conditions. These results demonstrate that PiO2kinetics in single contracting myofibers are dependent on Tm, likely caused by temperature-induced differences in metabolic demand and by temperature-dependent processes underlying mitochondrial activation at the start of muscle contractions.