bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors That Might Impact Intrathecal Drug Delivery (IDD) Dose Escalation: A Longitudinal Study
Authors: Mekhail Nagy , Mahboobi Ramatia , Farajzadeh Deroee Armin , Costandi Shrif , Dalton Jarrod , Guirguis Maged , Mehta Pankaj
Published: June 2013

Background

Intrathecal drug delivery (IDD) system with implantable pumps has been used to treat cancer‐related pain as well as noncancer‐related chronic pain. Opioids, including morphine and hydromorphone, are the most commonly used intrathecal (IT) agents. Although technology, techniques, and knowledge of IDD have improved, dose escalation occurs relatively rapidly in noncancer pain.

Methods

Retrospective chart review of IDD pump patients, implanted for a minimum of 2 years, was designed to investigate possible existing predictors that might impact IDD dose escalation, such as patient's demographic risk factors, duration of the treatment, and diagnosis of the patient's pain correlates with increase in medication requirement. Primary outcome was defined as the annual percent escalation in daily opioid dosage, and secondary outcome was the average annual percent reduction in VRS pain scores.

Results

Median dosage escalation was 17% per year for patients with neuropathic pain compared with 12% per year for patients with other pain modalities. Mean opioid dosage increased 30.4% more rapidly for patients with neuropathic pain than for other pain modalities. The adjusted difference in means was 28.8% (P = 0.001). None of the secondary exposures were statistically significant after the Bonferroni adjustment. No association was found between pain modality and annual percent change in VRS pain score.

Conclusion

Annual increases in daily opioid dosage were higher among patients with neuropathic pain than among patients with other modalities; we also found no evidence of difference in annual pain reduction.
The use of transient elastography and non‐invasive serum markers of fibrosis in pediatric liver transplant recipients
Authors: Goldschmidt Imeke , Stieghorst Henrik , Munteanu Mona , Poynard Thierry , Schlue Jerome , Streckenbach Carolin , Baumann Ulrich
Published: June 2013

The use of non‐invasive markers to diagnose liver allograft fibrosis is not well established in children after LTx. TE, FT, and ELF score were performed in 117 liver‐transplanted children (60M, 8.9 [0.5–18.5] yr) and 336 healthy controls. Liver biopsy was available in 36 children. Results of histology and non‐invasive markers were compared using correlation coefficient or Mann–Whitney U‐test as appropriate. TE correlated best with histological degree of fibrosis (r = 0.85 vs. r = 0.04 [FT] or r = −0.38 [ELF]). Liver stiffness values for transplanted children without fibrosis were significantly higher than those of healthy controls (7.55 [5.4–20.4] kPa vs. 4.5 [2.5–8.9] kPa). Presence of rejection was a potent confounder for the performance of TE. Both TE and FT reflected clinical changes (acute rejection, cholestasis, increasing fibrosis) in a total of 16 patients who underwent serial measurements. TE correlates better with histological degree of fibrosis in liver‐transplanted children than FT or ELF, but an individual baseline value needs to be determined for each patient. Normal or cutoff values for pathological degrees of fibrosis cannot be transferred from non‐transplanted children. Follow‐up studies, preferably with protocol biopsies, might help to improve the diagnostic quality of TE.
Knowledge Diversity, Turnover, and Organizational‐Unit Productivity: An Empirical Analysis in a Knowledge‐Intensive Context
Authors: Narayanan Sriram , Swaminathan Jayashankar M. , Talluri Srinivas
Published: June 2013

We examine the role of knowledge diversity among unit members on an organizational unit's productivity. Utilizing a proprietary data set of corrective maintenance tasks from a large software‐services firm, we investigate the impact of two key within‐unit diversity metrics: interpersonal diversity and intrapersonal diversity. We analyze the independent influence of interpersonal diversity and the interactive influence of interpersonal diversity and intrapersonal diversity on organizational unit's productivity. Finally, we examine how diversity moderates productivity of an organizational unit when employee turnover occurs. Our analysis reveals the following key insights: (a) interpersonal diversity has an inverted U‐shaped effect on organizational unit's productivity; (b) intrapersonal diversity moderates the influence of interpersonal diversity on organizational‐unit productivity; (c) at higher levels of interpersonal diversity, rate of decrease in productivity of the organizational unit due to turnover is higher. We discuss the resulting theoretical and managerial insights associated with these findings.
Freak Observers and the Simulation Argument
Authors: Crawford Lyle
Published: June 2013

The simulation hypothesis claims that the whole observable universe, including us, is a computer simulation implemented by technologically advanced beings for an unknown purpose. The simulation argument (as I reconstruct it) is an argument for this hypothesis with moderately plausible premises. I develop two lines of objection to the simulation argument. The first takes the form of a structurally similar argument for a conflicting conclusion, the claim that I am a so‐called freak observer, formed spontaneously in a quantum or thermodynamic fluctuation rather than through ordinary processes of evolution and growth. The second rejects the basic line of reasoning of both arguments: the sort of evidence they cite is not capable of supporting either the claim that I am a simulant or the claim that I am a freak observer. The evidence that simulants or freak observers exist is not a reason to think that I am one of them.
A method for estimating the residual risk of transfusion‐transmitted HBV infection associated with occult hepatitis B virus infection in a donor population without universal anti‐HBc screening
Authors: Seed C. R. , Kiely P.
Published: June 2013

Background and Objectives

This report describes a method for estimating the risk of transfusion‐transmitted HBV infection attributable to blood components from donors with occult hepatitis B virus infection (OBI) applicable where universal anti‐HBc screening is not performed.

Materials and Methods

In the context of parallel HBsAg and individual donation HBV DNA testing, we developed a mathematical function p(OBI) to estimate the probability of failing to detect [p(NAT nondetection)] a potentially infectious [p(transmission)] donation from a donor with OBI.

Results

Among 1 312 451 donations tested for HBsAg and HBV DNA, 29 (from 17 anti‐HBc reactive donors classified as OBI) were individual donation NAT negative, giving a p(NAT nondetection) of 2·2096 (95 CI: 1·538–3·173) × 10−5. To date, lookback on OBI donors has identified 35 (8·2%) recipients with evidence of current or past HBV infection among 427 tested recipients. After correcting for the background anti‐HBc rate in recipients, this results in a p(transmission) of 0·0384 (0·0167–0·0601). The product, pOBI is 1 in 981 920 (95% CI: 437 181–3 223 701). When this is summed with the WP risk for the 2011–2012 period, the overall HBV residual risk estimate is 1 in 538 224 (95% CI: 209 732–1 552 443).

Conclusion

We estimate the OBI residual risk in Australia is approximately 1 in 982 000 per unit transfused, and this risk represents 55% of the total HBV residual risk and is declining as consequence of ID‐NAT identifying repeat donors with OBI.
Systematic Review and Meta‐Analysis of Nonpharmacological Interventions for Fatigue in Children and Adolescents With Cancer
Authors: Chang Chi‐Wen , Mu Pei‐Fan , Jou Shiann‐Tarng , Wong Tai‐Tong , Chen Yu‐Chih
Published: June 2013

Background

Fatigue is one of the most distressing and prevalent symptoms reported by pediatric oncology patients. With the increase in cancer survival rates, medical teams have focused on methods that control cancer‐related fatigue in children during the disease and its treatment in order to increase the quality of life for these patients.

Aim

The objective of this systematic review was to synthesize the best available evidence concerning the effectiveness of nonpharmacological interventions for fatigue in children and adolescents with cancer.

Methods

The search strategy was designed to retrieve studies published between 1960 and 2010 in either English or Chinese. This review included randomized controlled trials and quasi‐experimental studies. The studies that were selected for retrieval were assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical‐appraisal instruments.

Results

The review included six studies, and the meta‐analysis revealed a statistically significant effect of exercise interventions in reducing general fatigue (effect size = –0.76; 95% CI [–1.35, –0.17]) in children and adolescents with cancer.

Conclusions and Implications

The review provides an evidence‐based guide to future priorities for clinical practice. Exercise interventions could reduce the levels of general fatigue in children aged 6–18 years. In particular, exercise interventions for fatigue are feasible and safe.
Cyclic Control: Problem Formulation and Stability Analysis
Authors: Eun Yongsoon , Gross Eric M. , Kabamba Pierre T. , Meerkov Semyon M. , Menezes Amor A. , Ossareh Hamid R.
Published: June 2013

This paper considers the problem of controlling rotating machinery with actuators and sensors fixed in inertial space. Such a problem arises in control of charging and fusing stages in the xerographic process, drilling and milling machines, and turbo machinery. If a rotating device is represented as a set of discrete wedges, the resulting system can be conceptualized as a set of plants (wedges) with a single actuator and sensor. In such architecture, each plant can be controlled only intermittently, in a stroboscopic manner. This leads to the problem of cyclic control (CC) considered in this paper. Specifically, the problem of stabilizability in CC architecture is considered, and the resulting stabilizability conditions are compared with those in the usual, permanently acting control (PAC). In this regard, it is shown that the domain of asymptotic stability under CC is an open disc in the open left half plane (OLHP), rather than the OLHP itself, and the controller gains that place the closed loop poles at the desired locations under CC are N times larger than those under PAC, where N is the number of wedges. The results are applied to temperature stabilization of the fusing stage of a xerographic process.
Influence of Minimum Quantity Lubrication on Friction Coefficient and Work-Material Adhesion During Machining of Cast Aluminum With Various Cutting Tool Substrates Made of Polycrystalline Diamond, High Speed Steel, and Carbides
Authors: Faverjon Pierre , Rech Joël , Leroy René
Published: June 2013

Due to the increasing emphasis on environmental constraints, industry works on how to limit the massive use of lubricants by using the micro-pulverization of oil in machining processes and, especially, in the machining of aluminum alloys for the automotive industry. The success of a machining operation is dependent on a friction coefficient and weak adhesion with the tool-work material interface. This paper aims at identifying the influence of cutting tool substrates (high speed steel (HSS), carbide, polycrystalline diamond (PCD)) and of minimum quantity lubrication (MQL) on the friction coefficient and on adhesion in tribological conditions corresponding to the ones observed in the cutting of aluminum alloys (sliding velocity: 20-1500 m/min). An open ball-on-cylinder tribometer, especially designed to simulate these tribological conditions through Hertz contact, has been used. It has been shown that HSS and carbide substrates lead to large friction coefficients (0.8–1) and substantial adhesion in dry conditions, whereas PCD substrates would lead to lower average friction coefficient values (0.4–0.5) and very limited adhesion, which proves the necessity of using PCD tools in the dry machining of aluminum. It has also been shown that the application of MQL leads to a large decrease of the friction coefficient (0.1–0.2) and eliminates almost all traces of adhesions on pins for any substrates, which shows that MQL is an interesting compromise between dry machining and flood cooling.
Worlds Built on Avian Excrement
Guano and the Opening of the Pacific World
A Global Ecological History

by Gregory T. Cushman

Cambridge University Press, Cambridge, 2013. 414 pp. $99. ISBN 9781107004139.
Authors: Davis Frederick R.
Published: June 2013

In this environmental history of the Pacific world, Cushman demonstrates the fundamental role played by guano.
Eliminating Malaria
Authors: Fidock David A.
Published: June 2013

Global eradication requires concerted efforts to combat emerging resistance to the potent antimalarial artemisinin.
Between Brain and Imaging Hype
Brainwashed
The Seductive Appeal of Mindless Neuroscience

by Sally Satel and Scott O. Lilienfeld

Basic Books, New York, 2013. 250 pp. $26.99, C$30. ISBN 9780465018772.
Authors: Gross Charles
Published: June 2013

The authors offer a set of cautionary essays on unproven or incorrect claims about the applications of neuroimaging.
The Science of Sustainability
Authors: Dye Christopher , McNutt Marcia
Published: June 2013

The question of what can be achieved in 1000 days has preoccupied kings, queens, presidents, and, very recently, the Secretary-General of the United Nations (UN). Ban Ki-moon has not only appealed for a last big push to reach as many as possible of the UN's Millennium Development Goals (MDGs) by the deadline of 31 December 2015, he is advocating the establishment of objectives that should succeed the MDGs as well. Strong clues about the shape of the post-2015 agenda can be found in two recent reports, one published last month by a High-Level Panel
*
convened by Ban Ki-moon and chaired by the presidents of Indonesia and Liberia and the prime minister of the United Kingdom, and the other released this month by the Sustainable Development Solutions Network.
†
Both reports list the eradication of poverty as the number-one priority and set out complementary goals concerned with gender equality, education, health, food, water and sanitation, climate change, energy, employment, natural resources, governance, peace, and finance. These reports are unlikely to be the last contributions to the debate, but the proposed goals represent a call to action for the science community.
Intestinal Dysbiosis and Depletion of Butyrogenic Bacteria in Clostridium difficile Infection and Nosocomial Diarrhea
Authors: Antharam Vijay C. , Li Eric C. , Ishmael Arif , Sharma Anuj , Mai Volker , Rand Kenneth H. , Wang Gary P.
Published: June 2013

Clostridium difficile
infection (CDI) causes nearly half a million cases of diarrhea and colitis in the United States each year. Although the importance of the gut microbiota in
C. difficile
pathogenesis is well recognized, components of the human gut flora critical for colonization resistance are not known. Culture-independent high-density Roche 454 pyrosequencing was used to survey the distal gut microbiota for 39 individuals with CDI, 36 subjects with
C. difficile
-negative nosocomial diarrhea (CDN), and 40 healthy control subjects. A total of 526,071 partial 16S rRNA sequence reads of the V1 to V3 regions were aligned with 16S databases, identifying 3,531 bacterial phylotypes from 115 fecal samples. Genomic analysis revealed significant alterations of organism lineages in both the CDI and CDN groups, which were accompanied by marked decreases in microbial diversity and species richness driven primarily by a paucity of phylotypes within the
Firmicutes
phylum. Normally abundant gut commensal organisms, including the
Ruminococcaceae
and
Lachnospiraceae
families and butyrate-producing C2 to C4 anaerobic fermenters, were significantly depleted in the CDI and CDN groups. These data demonstrate associations between the depletion of
Ruminococcaceae
,
Lachnospiraceae
, and butyrogenic bacteria in the gut microbiota and nosocomial diarrhea, including
C. difficile
infection. Mechanistic studies focusing on the functional roles of these organisms in diarrheal diseases and resistance against
C. difficile
colonization are warranted.
PCR for Detection of Herpes Simplex Virus in Cerebrospinal Fluid: Alternative Acceptance Criteria for Diagnostic Workup
Authors: López Roa Paula , Alonso Roberto , de Egea Viviana , Usubillaga Rafael , Muñoz Patricia , Bouza Emilio
Published: June 2013

The determination of herpes simplex virus (HSV) infection using a PCR assay is one of the most commonly requested tests for analysis of cerebrospinal fluid (CSF), although only a very low proportion of results are positive. A previously reported study showed that selecting only those CSF samples with >5 leukocytes/mm
3
or a protein level of >50 mg/dl was adequate for the diagnostic workup. The aim of the present study was to assess the reliability of alternative acceptance criteria based on elevated CSF white blood cell counts (>10 cells/mm
3
). We analyzed all requests for HSV PCR received between January 2008 and December 2011. CSF samples were accepted for analysis if they had >10 cells/mm
3
or if the sample was from an immunocompromised patient or a child aged <2 years. In order to evaluate our selection criteria, we identified those CSF samples with a leukocyte count of 5 to 10 cells/mm
3
or protein levels of >50 mg/dl in order to test them for HSV type 1 and 2 (HSV-1 and HSV-2) DNA. During the study period, 466 CSF samples were submitted to the microbiology laboratory for HSV PCR. Of these, 268 (57.5%) were rejected, and 198 (42.5%) were tested according to our routine criteria. Of the tested samples, 11 (5.5%) were positive for HSV DNA (7 for HSV-1 and 4 for HSV-2). Of the 268 rejected specimens, 74 met the criteria of >5 cells/mm
3
and/or protein levels of >50 mg/dl. Of these, 70 (94.6%) were available for analysis. None of the samples yielded a positive HSV PCR result. Acceptance criteria based on CSF leukocyte counts, host immune status, and age can help to streamline the application of HSV PCR without reducing sensitivity.
Multiplex 5′ Nuclease Quantitative Real-Time PCR for Clinical Diagnosis of Malaria and Species-Level Identification and Epidemiologic Evaluation of Malaria-Causing Parasites, Including Plasmodium knowlesi
Authors: Reller Megan E. , Chen Wan Hsin , Dalton Justin , Lichay Marguerite A. , Dumler J. Stephen
Published: June 2013

Molecular diagnosis of malaria offers many potential advantages over microscopy, including identification of malaria to the species level in an era with few experienced microscopists. We developed high-throughput multiplex 5′ nuclease quantitative PCR (qPCR) assays, with the potential to support large studies, to specifically identify
Plasmodium falciparum
,
P. vivax
,
P. ovale
,
P. malariae
, and
P. knowlesi
. We compared qPCR to microscopy and confirmed discordant results with an alternative target PCR assay. The assays specifically detected 1 to 6 parasites/μl of blood. The clinical sensitivities (95% confidence intervals [CIs]) of the 4-plex assay to detect microscopically confirmed malaria were 95.8% (88.3 to 99.1%) for
P. falciparum
, 89.5% (75.2 to 97.1%) for
P. vivax
, 94.1% (71.3 to 99.9%) for
P. ovale
, and 100% (66.4 to 100%) for
P. malariae
. The specificities (95% CIs) were 98.6% (92.4 to 100%) for
P. falciparum
, 99% (84.8 to 100%) for
P. vivax
, 98.4% (94.4 to 99.8%) for
P. ovale
, and 99.3% (95.9 to 100%) for
P. malariae
. The clinical specificity for samples without malaria was 100%. The clinical sensitivity of the 5-plex assay for confirmed
P. knowlesi
malaria was 100% (95% CI, 69.2 to 100%), and the clinical specificity was 100% (95% CI, 87.2 to 100%). Coded retesting and testing with an alternative target PCR assay showed improved sensitivity and specificity of multiplex qPCR versus microscopy. Additionally, 91.7% (11/12) of the samples with uncertain species by microscopy were identified to the species level identically by both our multiplex qPCR assay and the alternative target PCR assay, including 9
P. falciparum
infections. Multiplex qPCR can rapidly and simultaneously identify all 5
Plasmodium
species known to cause malaria in humans, and it offers an alternative or adjunct to microscopy for clinical diagnosis as well as a needed high-throughput tool for research.
Blind Evaluation of the Microwave-Accelerated Metal-Enhanced Fluorescence Ultrarapid and Sensitive Chlamydia trachomatis Test by Use of Clinical Samples
Authors: Melendez Johan H. , Huppert Jill S. , Jett-Goheen Mary , Hesse Elizabeth A. , Quinn Nicole , Gaydos Charlotte A. , Geddes Chris D.
Published: June 2013

Accurate point-of-care (POC) diagnostic tests for
Chlamydia trachomatis
infection are urgently needed for the rapid treatment of patients. In a blind comparative study, we evaluated microwave-accelerated metal-enhanced fluorescence (MAMEF) assays for ultrafast and sensitive detection of
C. trachomatis
DNA from vaginal swabs. The results of two distinct MAMEF assays were compared to those of nucleic acid amplification tests (NAATs). The first assay targeted the
C. trachomatis
16S rRNA gene, and the second assay targeted the
C. trachomatis
cryptic plasmid. Using pure
C. trachomatis
, the MAMEF assays detected as few as 10 inclusion-forming units/ml of
C. trachomatis
in less than 9 min, including DNA extraction and detection. A total of 257 dry vaginal swabs from 245 female adolescents aged 14 to 22 years were analyzed. Swabs were eluted with water, the solutions were lysed to release and to fragment genomic DNA, and MAMEF-based DNA detection was performed. The prevalence of
C. trachomatis
by NAATs was 17.5%. Of the 45 samples that were
C. trachomatis
positive and the 212 samples that were
C. trachomatis
negative by NAATs, 33/45 and 197/212 were correctly identified by the MAMEF assays if both assays were required to be positive (sensitivity, 73.3%; specificity, 92.9%). Using the plasmid-based assay alone, 37/45
C. trachomatis
-positive and 197/212
C. trachomatis
-negative samples were detected (sensitivity, 82.2%; specificity, 92.9%). Using the 16S rRNA assay alone, 34/45
C. trachomatis
-positive and 197/212
C. trachomatis
-negative samples were detected (sensitivity, 75.5%; specificity, 92.9%). The overall rates of agreement with NAAT results for the individual 16S rRNA and cryptic plasmid assays were 89.5% and 91.0%, respectively. Given the sensitivity, specificity, and rapid detection of the plasmid-based assay, the plasmid-based MAMEF assay appears to be suited for clinical POC testing.
Glycoproteins gE and gI Are Required for Efficient KIF1A-Dependent Anterograde Axonal Transport of Alphaherpesvirus Particles in Neurons
Authors: Kratchmarov Radomir , Kramer Tal , Greco Todd M. , Taylor Matthew P. , Ch'ng Toh Hean , Cristea Ileana M. , Enquist Lynn W.
Published: June 2013

Alphaherpesviruses, including pseudorabies virus (PRV), spread directionally within the nervous systems of their mammalian hosts. Three viral membrane proteins are required for efficient anterograde-directed spread of infection in neurons, including Us9 and a heterodimer composed of the glycoproteins gE and gI. We previously demonstrated that the kinesin-3 motor KIF1A mediates anterograde-directed transport of viral particles in axons of cultured peripheral nervous system (PNS) neurons. The PRV Us9 protein copurifies with KIF1A, recruiting the motor to transport vesicles, but at least one unidentified additional viral protein is necessary for this interaction. Here we show that gE/gI are required for efficient anterograde transport of viral particles in axons by mediating the interaction between Us9 and KIF1A. In the absence of gE/gI, viral particles containing green fluorescent protein (GFP)-tagged Us9 are assembled in the cell body but are not sorted efficiently into axons. Importantly, we found that gE/gI are necessary for efficient copurification of KIF1A with Us9, especially at early times after infection. We also constructed a PRV recombinant that expresses a functional gE-GFP fusion protein and used affinity purification coupled with mass spectrometry to identify gE-interacting proteins. Several viral and host proteins were found to associate with gE-GFP. Importantly, both gI and Us9, but not KIF1A, copurified with gE-GFP. We propose that gE/gI are required for efficient KIF1A-mediated anterograde transport of viral particles because they indirectly facilitate or stabilize the interaction between Us9 and KIF1A.
AN ADAPTIVE GRADIENT ALGORITHM FOR LARGE-SCALE NONLINEAR BOUND CONSTRAINED OPTIMIZATION
Authors: CHENG WANYOU , CAO ERBAO
Published: June 2013

In this paper, an adaptive gradient algorithm (AGM) for box constrained optimization is developed. The algorithm is based on an active set identification technique and consists of a nonmonotone gradient projection step, a conjugate gradient step and a rule for branching between the two steps. We show that the method is globally convergent under appropriate conditions. Numerical experiments are presented using bound constrained problems in the CUTEr test problem library.
THREE OPTIMIZATION MODELS FOR MULTISPLITTING PRECONDITIONER
Authors: WEI LIANG , WANG CHUAN-LONG
Published: June 2013

In this paper, we use matrix multisplitting with weighting parameters as the preconditioner of A. The optimal weighting parameters are determined by the approaching theory, and the scale of approaching is defined by F-norm, 2-norm, and ∞-norm, respectively. Base on these three minimize models, three algorithms are presented and the convergence theories are established. Finally, numerical examples show that the preconditioner with the optimal weighting parameters, which are obtained from minimize F-norm and 2-norm models, can improve the condition number of A effectively. Besides, general weighting parameters are more effective than non-negative weighting parameters.
AN IMPROVED CONVEX 0-1 QUADRATIC PROGRAM REFORMULATION FOR CHANCE-CONSTRAINED QUADRATIC KNAPSACK PROBLEMS
Authors: JI SHUHUI , ZHENG XIAOJIN , SUN XIAOLING
Published: June 2013

We consider a chance-constrained quadratic knapsack problem (CQKP) where each item has a random size that is finitely distributed. We present a new convex 0-1 quadratic program reformulation for CQKP. This new reformulation improves the existing reformulation for general 0-1 quadratic program based on diagonal perturbation in the sense that the continuous relaxation of the new reformulation is tighter than or at least as tight as that of the existing reformulation. The improved reformulation is derived from a general matrix decomposition of the objective function and piecewise linearization of 0-1 variables. We show that the optimal parameters in the improved reformulation can be obtained by solving an SDP problem. Extension to k-item probabilistic quadratic knapsack problems is also discussed. Preliminary comparison results are reported to demonstrate the effectiveness of the improved reformulation.
STUDIES OF NUCLEON RESONANCE STRUCTURE IN EXCLUSIVE MESON ELECTROPRODUCTION
Authors: Aznauryan I. G. , Bashir A. , Braun V. M. , Brodsky S. J. , Burkert V. D. , Chang L. , Chen Ch. , El-Bennich B. , Cloët I. C. , Cole P. L. , Edwards R. G. , Fedotov G. V. , Giannini M. M. , Gothe R. W. , Gross F. , Lin Huey-Wen , Kroll P. , Lee T.-S. H. , Melnitchouk W. , Mokeev V. I. , Peña M. T. , Ramalho G. , Roberts C. D. , Santopinto E. , de Teramond G. F. , Tsushima K. , Wilson D. J.
Published: June 2013

Studies of the structure of excited baryons are key factors to the N* program at Jefferson Lab (JLab). Within the first year of data taking with the Hall B CLAS12 detector following the 12 GeV upgrade, a dedicated experiment will aim to extract the N* electrocouplings at high photon virtualities Q2. This experiment will allow exploration of the structure of N* resonances at the highest photon virtualities ever achieved, with a kinematic reach up to Q2 = 12 GeV 2. This high-Q2 reach will make it possible to probe the excited nucleon structures at distance scales ranging from where effective degrees of freedom, such as constituent quarks, are dominant through the transition to where nearly massless bare-quark degrees of freedom are relevant. In this document, we present a detailed description of the physics that can be addressed through N* structure studies in exclusive meson electroproduction. The discussion includes recent advances in reaction theory for extracting N* electrocouplings from meson electroproduction off protons, along with Quantum Chromodynamics (QCD)-based approaches to the theoretical interpretation of these fundamental quantities. This program will afford access to the dynamics of the nonperturbative strong interaction responsible for resonance formation, and will be crucial in understanding the nature of confinement and dynamical chiral symmetry breaking in baryons, and how excited nucleons emerge from QCD.
Quantifying fracture density and connectivity of fractured chalk reservoirs from core samples: implications for fluid flow
Authors: Sagi D. A. , Arnhild M. , Karlo J. F.
Published: June 2013

Fractured carbonate reservoirs, characterized by high structural porosity/permeability, are of great economic importance because in such systems a single well can access large volumes of easily migrating hydrocarbons. Therefore, the accurate quantification of fracture density and connectivity values within a reservoir can be an important input for reservoir models and field development plans. However, a large number of the fractures that are present in a field are smaller than the resolution of most industry standards methods. In this paper we use two independent methods to quantify small-scale fracture density and connectivity, such as two-dimensional image analysis of slabbed cores and rubble-size measurements.
Human-induced pluripotent stem cell-derived cardiomyocytes for studies of cardiac ion transporters
Authors: Fine Michael , Lu Fang-Min , Lin Mei-Jung , Moe Orson , Wang Hao-Ran , Hilgemann Donald W.
Published: June 2013

Human-induced pluripotent stem cells (hiPSCs) can differentiate into functional cardiomyocytes (iCell Cardiomyocytes) with ion channel activities that are remarkably similar to adult cardiomyocytes. Here, we extend this characterization to cardiac ion transporters. Additionally, we document facile molecular biological manipulation of iCell Cardiomyocytes to overexpress and knockdown transporters and regulatory proteins. Na/Ca exchange (NCX1) and Na/K pump currents were recorded via patch clamp, and Na/H and Cl/OH exchanges were recorded via oscillating proton-selective microelectrodes during patch clamp. Flux densities of all transport systems are similar to those of nonrodent adult cardiomyocytes. NCX1 protein and NCX1 currents decline after NCX1 small interfering (si)RNA transfection with similar time courses (τ ≈ 2 days), and an NCX1-Halo fusion protein is internalized after its extracellular labeling by AlexaFluor488 Ligand with a similar time course. Loss of the cardiac regulatory protein phospholemman (PLM) occurs over a longer time course (τ ≈ 60 h) after PLM small interfering RNA transfection. Similar to multiple previous reports for adult cardiomyocytes, Na/K pump currents in iCell Cardiomyocytes are not enhanced by activating cAMP production with either maximal or submaximal cytoplasmic Na and using either forskolin or isoproterenol to activate adenylate cyclases. Finally, we describe Ca influx-dependent changes of iCell Cardiomyocyte capacitance ( Cm). Large increases of Cm occur during Ca influx via NCX1, thereby documenting large internal membrane reserves that can fuse to the sarcolemma, and subsequent declines of Cm document active endocytic processes. Together, these results document a great potential of iCell Cardiomyocytes for both short- and long-term studies of cardiac ion transporters and their regulation.
Production of free glutamate in milk requires the leucine transporter LAT1
Authors: Matsumoto Takuya , Nakamura Eiji , Nakamura Hidehiro , Hirota Mariko , San Gabriel Ana , Nakamura Ken-ichiro , Chotechuang Nattida , Wu Guoyao , Uneyama Hisayuki , Torii Kunio
Published: June 2013

The concentration of free glutamate (Glu) in rat's milk is ∼10 times higher than that in plasma. Previous work has shown that mammary tissue actively transports circulatory leucine (Leu), which is transaminated to synthesize other amino acids such as Glu and aspartate (Asp). To investigate the molecular basis of Leu transport and its conversion into Glu in the mammary gland, we characterized the expression of Leu transporters and [3H]Leu uptake in rat mammary cells. Gene expression analysis indicated that mammary cells express two Leu transporters, LAT1 and LAT2, with LAT1 being more abundant than LAT2. This transport system is sodium independent and transports large neutral amino acids. The Leu transport system in isolated rat mammary cells could be specifically blocked by the LAT1 inhibitors 2-aminobicyclo-[2.2.1]-heptane-2-carboxylic acid (BCH) and triiodothyronine (T3). In organ cultures, Glu secretion was markedly inhibited by these LAT1 inhibitors. Furthermore, the profiles of Leu uptake inhibition by amino acids in mammary cells were similar to those reported for LAT1. In vivo, concentrations of free Glu and Asp increased in milk by oral gavage with Leu at 6, 12, and 18 days of lactation. These results indicate that the main Leu transporter in mammary tissue is LAT1 and the transport of Leu is a limiting factor for the synthesis and release of Glu and Asp into milk. Our studies provide the bases for the molecular mechanism of Leu transport in mammary tissue by LAT1 and its active role on free Glu secretion in milk, which confer umami taste in suckling pups.
Prediction and assessment of responses to renal artery revascularization with dynamic contrast-enhanced magnetic resonance imaging: a pilot study
Authors: Lim Su Wei , Chrysochou Constantina , Buckley David L. , Kalra Philip A. , Sourbron Steven P.
Published: June 2013

The aim of this study was to assess the potential of dynamic contrast-enhanced (DCE) MRI to predict and evaluate functional outcomes after renal artery revascularization for renal artery stenosis (RAS). The single-kidney glomerular filtration rate (SK-GFR) was measured in 15 patients with atherosclerotic RAS with DCE-MRI and radioisotopes at baseline and 4 mo after revascularization. DCE-MRI also produced measurements of blood flow, blood volume, extraction fraction, tubular transit time, and functional volume. Stented kidneys ( n = 22) were divided into three response groups on the basis of the changes in radioisotope SK-GFR: improved ( n = 5), stable ( n = 13), and deteriorated ( n = 4). A good agreement was found between SK-GFR values from DCE-MRI and radioisotopes (correlation coefficient: 0.91). Before intervention, kidneys that improved had lower extraction fraction, higher blood volume, longer tubular transit time, and lower SK-GFR. After intervention, improved kidneys had increased functional volume, and deteriorated kidneys had reduced functional volume and extraction fraction. Revascularization improved blood flow and blood volume in all groups. This pilot study led to the hypothesis that well-vascularized kidneys with reduced extraction fractions are most likely to benefit from revascularization. More generally, DCE-MRI has the potential to replace radioisotope measurement of SK-GFR and may improve patient management by providing additional information on tissue perfusion.
Sp1 trans-activates and is required for maximal aldosterone induction of the αENaC gene in collecting duct cells
Authors: Yu Zhiyuan , Kong Qun , Kone Bruce C.
Published: June 2013

The epithelial Na+ channel (ENaC) in the distal nephron constitutes the rate-limiting step for renal sodium reabsorption. Aldosterone increases tubular sodium absorption in large part by increasing αENaC transcription in collecting duct principal cells. We previously reported that Af9 binds to +78/+92 of αENaC and recruits Dot1a to repress basal and aldosterone-sensitive αENaC transcription in mouse inner medullary collecting duct (mIMCD)3 cells. Despite this epigenetic repression, basal αENaC transcription is still evident and physiologically necessary, indicating basal operation of positive regulators. In the present study, we identified Sp1 as one such regulator. Gel shift and antibody competition assays using a +208/+240 probe revealed DNA-Sp1-containing complexes in mIMCD3 cells. Mutation of the +222/+229 element abrogated Sp1 binding in vitro and in promoter-reporter constructs stably expressed in mIMCD3 cells. Compared with the wild-type promoter, an αENaC promoter-luciferase construct with +222/+229 mutations exhibited much lower activity and impaired trans-activation in Sp1 overexpression experiments. Conversely, Sp1 knockdown inhibited endogenous αENaC mRNA and the activity of the wild-type αENaC promoter but not the mutated construct. Aldosterone triggered Sp1 recruitment to the αENaC promoter, which was required for maximal induction of αENaC promoter activity and was blocked by spironolactone. Sequential chromatin immunoprecipitation assays and functional tests of +78/+92 and +222/+229 αENaC promoter mutants indicated that while Sp1, Dot1a, and Af9 co-occupy the αENaC promoter, the Sp1 effects are functionally independent from Dot1a and Af9. In summary, Sp1 binding to a cis-element at +222/+229 represents the first identified constitutive driver of αENaC transcription, and it contributes to maximal aldosterone trans-activation of αENaC.
On the Problem of Electromagnetic Waves Propagating along a Nonlinear Inhomogeneous Cylindrical Waveguide
Authors: Smirnov Yury G. , Valovik Dmitry V.
Published: June 2013

Electromagnetic TE wave propagation in an inhomogeneous nonlinear cylindrical waveguide is considered. The permittivity inside the waveguide is described by the Kerr law. Inhomogeneity of the waveguide is modeled by a nonconstant term in the Kerr law. Physical problem is reduced to a nonlinear eigenvalue problem for ordinary differential equations. Existence of propagating waves is proved with the help of fixed point theorem and contracting mapping method. For numerical solution, an iteration method is suggested and its convergence is proved. Existence of eigenvalues of the problem (propagation constants) is proved and their localization is found. Conditions of k waves existence are found.
Meta-Analysis of Microarray Data IdentifiesGAS6Expression as an Independent Predictor of Poor Survival in Ovarian Cancer
Authors: Buehler Michelle , Tse Brian , Leboucq Alix , Jacob Francis , Caduff Rosmarie , Fink Daniel , Goldstein Darlene R. , Heinzelmann-Schwarz Viola
Published: June 2013

Seeking new biomarkers for epithelial ovarian cancer, the fifth most common cause of death from all cancers in women and the leading cause of death from gynaecological malignancies, we performed a meta-analysis of three independent studies and compared the results in regard to clinicopathological parameters. This analysis revealed thatGAS6was highly expressed in ovarian cancer and therefore was selected as our candidate of choice.GAS6encodes a secreted protein involved in physiological processes including cell proliferation, chemotaxis, and cell survival. We performed immunohistochemistry on various ovarian cancer tissues and found that GAS6 expression was elevated in tumour tissue samples compared to healthy control samples (). In addition, GAS6 expression was also higher in tumours from patients with residual disease compared to those without. Our data propose GAS6 as an independent predictor of poor survival, suggesting GAS6, both on the mRNA and on the protein level, as a potential biomarker for ovarian cancer. In clinical practice, the staining of a tumour biopsy for GAS6 may be useful to assess cancer prognosis and/or to monitor disease progression.
MicroRNAs: New Insights into Chronic Childhood Diseases
Authors: Omran Ahmed , Elimam Dalia , Yin Fei
Published: June 2013

Chronic diseases are the major cause of morbidity and mortality worldwide and have shown increasing incidence rates among children in the last decades. Chronic illnesses in the pediatric population, even if well managed, affect social, psychological, and physical development and often limit education and active participation and increase the risk for health complications. The significant pediatric morbidity and mortality rates caused by chronic illnesses call for serious efforts toward better understanding of the pathogenesis of these disorders. Recent studies have shown the involvement of microRNAs (miRNAs) in various aspects of major pediatric chronic non-neoplastic diseases. This review focuses on the role of miRNAs in four major pediatric chronic diseases including bronchial asthma, diabetes mellitus, epilepsy and cystic fibrosis. We intend to emphasize the importance of miRNA-based research in combating these major disorders, as we believe this approach will result in novel therapies to aid securing normal development and to prevent disabilities in the pediatric population.
Regulation and Prognostic Relevance of Symmetric Dimethylarginine Serum Concentrations in Critical Illness and Sepsis
Authors: Koch Alexander , Weiskirchen Ralf , Bruensing Jan , Dückers Hanna , Buendgens Lukas , Kunze Julian , Matthes Michael , Luedde Tom , Trautwein Christian , Tacke Frank
Published: June 2013

In systemic inflammation and sepsis, endothelial activation and microvascular dysfunction are characteristic features that promote multiorgan failure. As symmetric dimethylarginine (SDMA) impacts vascular tension and integrity via modulating nitric oxide (NO) pathways, we investigated circulating SDMA in critical illness and sepsis. 247 critically ill patients (160 with sepsis, 87 without sepsis) were studied prospectively upon admission to the medical intensive care unit (ICU) and on day 7, in comparison to 84 healthy controls. SDMA serum levels were significantly elevated in critically ill patients at admission to ICU compared to controls and remained stably elevated during the first week of ICU treatment. The highest SDMA levels were found in patients with sepsis. SDMA levels closely correlated with disease severity scores, biomarkers of inflammation, and organ failure (renal, hepatic, and circulatory). We identified SDMA serum concentrations at admission as an independent prognostic biomarker in critically ill patients not only for short-term mortality at the ICU but also for unfavourable long-term survival. Thus, the significant increase of circulating SDMA in critically ill patients indicates a potential pathogenic involvement in endothelial dysfunction during sepsis and may be useful for mortality risk stratification at the ICU.
Affinity Labeling of Membrane Receptors Using Tissue-Penetrating Radiations
Authors: Wong Franklin C. , Boja John , Ho Beng , Kuhar Michael J. , Wong Dean F.
Published: June 2013

Photoaffinity labeling, a usefulin vivobiochemical tool, is limited when appliedin vivobecause of the poor tissue penetration by ultraviolet (UV) photons. This study investigates affinity labeling using tissue-penetrating radiation to overcome the tissue attenuation and irreversibly label membrane receptor proteins. Using X-ray (115 kVp) at low doses (<50 cGy or Rad), specific and irreversible binding was found on striatal dopamine transporters with 3 photoaffinity ligands for dopamine transporters, to different extents. Upon X-ray exposure (115 kVp), RTI-38 and RTI-78 ligands showed irreversible and specific binding to the dopamine transporter similar to those seen with UV exposure under other conditions. Similarly, gamma rays at higher energy (662 keV) also affect irreversible binding of photoreactive ligands to peripheral benzodiazepine receptors (by PK14105) and to the dopamine (D2) membrane receptors (by azidoclebopride), respectively. This study reports that X-ray and gamma rays induced affinity labeling of membrane receptors in a manner similar to UV with photoreactive ligands of the dopamine transporter, D2 dopamine receptor (D2R), and peripheral benzodiazepine receptor (PBDZR). It may provide specific noninvasive irreversible block or stimulation of a receptor using tissue-penetrating radiation targeting selected anatomic sites.
Role of Corneal Epithelium in Riboflavin/Ultraviolet-A Mediated Corneal Cross-Linking Treatment in Rabbit Eyes
Authors: Tao Xiangchen , Yu Haiqun , Zhang Yong , Li Zhiwei , Jhanji Vishal , Ni Shouxiang , Wang Ya , Mu Guoying
Published: June 2013

Purpose. To evaluate the role of corneal epithelium in riboflavin/ultraviolet-A (UVA) mediated corneal collagen cross-linking treatment.Methods. Fifty New Zealand rabbits were divided into 5 groups: UVA treatment with or without corneal epithelium, UVA+riboflavin treatment with or without corneal epithelium, and control without any treatment. All rabbits were sacrificed after irradiation and subsequently 4 mm × 10 mm corneal strips were harvested for biomechanical evaluation.Results. UVA irradiation alone did not enhance the maximal stress and Young’s modulus of corneal specimens with (3.15 ± 0.56 mpa, 1.00 ± 0.09 mpa) or without (3.53 ± 0.85 mpa, 0.94 ± 0.21 mpa) the corneal epithelium, compared to specimens in the control group (4.30 ± 0.68 mpa, 1.03 ± 0.24 mpa). However, UVA irradiation combined with riboflavin significantly increased the maximal stress and Young’s modulus of corneal specimens with (5.27 ± 1.09 mpa, 1.23 ± 0.23 mpa,P<0.05) or without (7.16 ± 1.88 mpa, 1.42 ± 0.16 mpa,P<0.05) corneal epithelium when compared to the control group. The maximal stress and Young’s modulus of cornea in UVA+riboflavin and “epithelium-off” group were 35.9% and 15.4% higher compared to the UVA+riboflavin and “epithelium-on” group, respectively (P<0.05).Conclusions. Our study shows that UVA+riboflavin treatment significantly affects the biomechanical properties of the cornea with and without epithelial removal. However, corneas without epithelium seem to benefit more compared to corneas with the epithelium.
Fekete-Szegö Coefficient Functional for Certain Subclasses of Close-to-Star Functions
Authors: Mehrok B. S. , Singh Gagandeep
Published: June 2013

We introduce some subclasses of close-to-star functions defined by subordination and obtain sharp upper bounds of the functional |a3-μa22|, μ real, for an analytic function f(z)=z+∑n=2∞‍anzn, |z|<1, belonging to these sub-classes.
Reliability Analysis of Semiactive Magnetorheological Dampers Subjected to Harmonic Excitations
Authors: Rahbari N. Mohajer , Talatahari S. , Aalami R.
Published: June 2013

It has been seen that semiactive magnetorheological (MR) dampers are not sometimes reliable when employed in the building to contract acceleration demand of the stories. In the current paper, a three-storey sample building with semiactive MR dampers subjected to harmonic base excitation is taken under examination to clarify the reliability of such semiactive control systems in mitigation of absolute acceleration response of the buildings. Comparison between semiactively controlled building and uncontrolled original building is chosen as an implicit reliability limit-state function. Firstly, first-order reliability method (FORM) is engaged to examine the reliability of the system by linearizing the chosen nonlinear limit-state function. Afterwards, Monte Carlo simulation (MCS) is used to verify the obtained results by FORM method.