bluuebunny/crossref_metadata_2025 huggingface dataset:
SCE1, the SUMO-Conjugating Enzyme in Plants That Interacts with NIb, the RNA-Dependent RNA Polymerase of Turnip Mosaic Virus, Is Required for Viral Infection
Authors: Xiong Ruyi , Wang Aiming
Published: January 2013

SUMOylation, which is catalyzed by small ubiquitin-like modifier (SUMO) enzymes, is a transient, reversible posttranslational protein modification that regulates diverse cellular processes. Potyviruses, the largest group of known plant viruses, comprise many agriculturally important viruses, such as
Turnip mosaic virus
(TuMV). The potyviral genome encodes 11 mature proteins. To investigate if SUMOylation plays a role in potyvirus infection, a yeast two-hybrid screen was performed to examine possible interactions of each of the 11 viral proteins of TuMV with AtSCE1, the only SUMO-conjugating enzyme in
Arabidopsis thaliana
homologous to the key SUMO-conjugating enzyme E2 in mammalian cells or Ubc9 in yeast. A positive reaction was found between AtSCE1 and NIb, the potyviral RNA-dependent RNA polymerase. Further bimolecular fluorescence complementation (BiFC) and fluorescence resonance energy transfer (FRET) assays revealed that the NIb and AtSCE1 interaction occurred in both the cytoplasm and nuclei of epidermal cells of
Nicotiana benthamiana
. The interaction motif was mapped to a region encompassing NIb amino acids 171 to 300 which contains a potential negatively charged amino acid-dependent SUMOylation motif (NDSM). An
Escherichia coli
SUMOylation assay showed that NIb can be SUMOylated and that the lysine residue (K172) in the motif is a potent SUMOylation site. A TuMV infectious clone with an arginine (R) substitution mutation at K172 compromised TuMV infectivity in plants. In comparison with wild-type
Arabidopsis
plants,
sce1
knockdown plants exhibited increased resistance to TuMV as well as a nonrelated RNA virus. To the best of our knowledge, this is the first report showing that the host SUMO modification system plays an essential role in infection by plant RNA viruses.
Matriptase Proteolytically Activates Influenza Virus and Promotes Multicycle Replication in the Human Airway Epithelium
Authors: Beaulieu Alexandre , Gravel Émilie , Cloutier Alexandre , Marois Isabelle , Colombo Éloïc , Désilets Antoine , Verreault Catherine , Leduc Richard , Marsault Éric , Richter Martin V.
Published: January 2013

Influenza viruses do not encode any proteases and must rely on host proteases for the proteolytic activation of their surface hemagglutinin proteins in order to fuse with the infected host cells. Recent progress in the understanding of human proteases responsible for influenza virus hemagglutinin activation has led to the identification of members of the type II transmembrane serine proteases TMPRSS2 and TMPRSS4 and human airway trypsin-like protease; however, none has proved to be the sole enzyme responsible for hemagglutinin cleavage. In this study, we identify and characterize matriptase as an influenza virus-activating protease capable of supporting multicycle viral replication in the human respiratory epithelium. Using confocal microscopy, we found matriptase to colocalize with hemagglutinin at the apical surface of human epithelial cells and within endosomes, and we showed that the soluble form of the protease was able to specifically cleave hemagglutinins from H1 virus, but not from H2 and H3 viruses, in a broad pH range. We showed that small interfering RNA (siRNA) knockdown of matriptase in human bronchial epithelial cells significantly blocked influenza virus replication in these cells. Lastly, we provide a selective, slow, tight-binding inhibitor of matriptase that significantly reduces viral replication (by 1.5 log) of H1N1 influenza virus, including the 2009 pandemic virus. Our study establishes a three-pronged model for the action of matriptase: activation of incoming viruses in the extracellular space in its shed form, upon viral attachment or exit in its membrane-bound and/or shed forms at the apical surface of epithelial cells, and within endosomes by its membrane-bound form where viral fusion takes place.
Recruitment of Brd4 to the Human Papillomavirus Type 16 DNA Replication Complex Is Essential for Replication of Viral DNA
Authors: Wang Xin , Helfer Christine M. , Pancholi Neha , Bradner James E. , You Jianxin
Published: January 2013

Replication of the human papillomavirus (HPV) DNA genome relies on viral factors E1 and E2 and the cellular replication machinery. Bromodomain-containing protein 4 (Brd4) interacts with viral E2 protein to mediate papillomavirus (PV) genome maintenance and viral transcription. However, the functional role of Brd4 in the HPV life cycle remains to be clearly defined. In this study, we provide the first look into the E2-Brd4 interaction in the presence of other important viral factors, such as the HPV16 E1 protein and the viral genome. We show that Brd4 is recruited to actively replicating HPV16 origin foci together with HPV16 E1, E2, and a number of the cellular replication factors: replication protein A70 (RPA70), replication factor C1 (RFC1), and DNA polymerase δ. Mutagenesis disrupting the E2-Brd4 interaction abolishes the formation of the HPV16 replication complex and impairs HPV16 DNA replication in cells. Brd4 was further demonstrated to be necessary for HPV16 viral DNA replication using a cell-free replication system in which depletion of Brd4 by small interfering RNA (siRNA) silencing leads to impaired HPV16 viral DNA replication and recombinant Brd4 protein is able to rescue viral DNA replication. In addition, releasing endogenous Brd4 from cellular chromatin by using the bromodomain inhibitor JQ1(+) enhances HPV16 DNA replication, demonstrating that the role of Brd4 in HPV DNA replication could be uncoupled from its function in chromatin-associated transcriptional regulation and cell cycle control. Our study reveals a new role for Brd4 in HPV genome replication, providing novel insights into understanding the life cycle of this oncogenic DNA virus.
Alphaherpesviral US3 Kinase Induces Cofilin Dephosphorylation To Reorganize the Actin Cytoskeleton
Authors: Jacob Thary , Van den Broeke Céline , van Troys Marleen , Waterschoot Davy , Ampe Christophe , Favoreel Herman W.
Published: January 2013

The conserved alphaherpesviral serine/threonine kinase US3 causes dramatic actin rearrangements, associated with increased viral spread. Here, we show that US3 of pseudorabies virus (PRV) leads to activation (dephosphorylation) of the central actin regulator cofilin. A mutation that impairs US3 kinase activity and the group I p21-activated kinase inhibitor IPA-3 inhibited US3-mediated cofilin activation. Additionally, expression of phosphomimetic S3D cofilin significantly suppressed the ability of US3 to cause cell projections and cell rounding. In conclusion, the US3 kinase of PRV leads to activation (dephosphorylation) of cofilin, and cofilin contributes to US3-mediated actin rearrangements.
Measles Virus Infection of Epithelial Cells in the Macaque Upper Respiratory Tract Is Mediated by Subepithelial Immune Cells
Authors: Ludlow Martin , Lemon Ken , de Vries Rory D. , McQuaid Stephen , Millar Emma L. , van Amerongen Geert , Yüksel Selma , Verburgh R. Joyce , Osterhaus Albert D. M. E. , de Swart Rik L. , Duprex W. Paul
Published: January 2013

Measles virus (MV), one of the most contagious viruses infecting humans, causes a systemic infection leading to fever, immune suppression, and a characteristic maculopapular rash. However, the specific mechanism or mechanisms responsible for the spread of MV into the respiratory epithelium in the late stages of the disease are unknown. Here we show the crucial role of PVRL4 in mediating the spread of MV from immune to epithelial cells by generating a PVRL4 “blind” recombinant wild-type MV and developing a novel
in vitro
coculture model of B cells with primary differentiated normal human bronchial epithelial cells. We utilized the macaque model of measles to analyze virus distribution in the respiratory tract prior to and at the peak of MV replication. Expression of PVRL4 was widespread in both the lower and upper respiratory tract (URT) of macaques, indicating MV transmission can be facilitated by more than only epithelial cells of the trachea. Analysis of tissues collected at early time points after experimental MV infection demonstrated the presence of MV-infected lymphoid and myeloid cells contacting respiratory tract epithelium in the absence of infected epithelial cells, suggesting that these immune cells seed the infection
in vivo
. Thereafter, lateral cell-to-cell spread of MV led to the formation of large foci of infected cells in the trachea and high levels of MV infection in the URT, particularly in the nasal cavity. These novel findings have important implications for our understanding of the high transmissibility of measles.
HLA-B*57 versus HLA-B*81 in HIV-1 Infection: Slow and Steady Wins the Race?
Authors: Prentice Heather A. , Porter Travis R. , Price Matthew A. , Cormier Emmanuel , He Dongning , Farmer Paul K. , Kamali Anatoli , Karita Etienne , Lakhi Shabir , Sanders Eduard J. , Anzala Omu , Amornkul Pauli N. , Allen Susan , Hunter Eric , Kaslow Richard A. , Gilmour Jill , Tang Jianming
Published: January 2013

Two human leukocyte antigen (HLA) variants, HLA-B*57 and -B*81, are consistently known as favorable host factors in human immunodeficiency virus type 1 (HIV-1)-infected Africans and African-Americans. In our analyses of prospective data from 538 recent HIV-1 seroconverters and cross-sectional data from 292 subjects with unknown duration of infection, HLA-B*57 (mostly B*57:03) and -B*81 (exclusively B*81:01) had mostly discordant associations with virologic and immunologic manifestations before antiretroviral therapy. Specifically, relatively low viral load (VL) in HLA-B*57-positive subjects (
P
≤ 0.03 in various models) did not translate to early advantage in CD4
+
T-cell (CD4) counts (
P
≥ 0.37). In contrast, individuals with HLA-B*81 showed little deviation from the normal set point VL (
P
> 0.18) while maintaining high CD4 count during early and chronic infection (
P
= 0.01). These observations suggest that discordance between VL and CD4 count can occur in the presence of certain HLA alleles and that effective control of HIV-1 viremia is not always a prerequisite for favorable prognosis (delayed immunodeficiency). Of note, steady CD4 count associated with HLA-B*81 in HIV-1-infected Africans may depend on the country of origin, as observations differed slightly between subgroups enrolled in southern Africa (Zambia) and eastern Africa (Kenya, Rwanda, and Uganda).
Structural Analysis of the Evolutionary Origins of Influenza Virus Hemagglutinin and Other Viral Lectins
Authors: Chen Lang , Li Fang
Published: January 2013

Influenza virus and other viruses use host cell surface sugars as receptors. Here we show that the sugar-binding domains in influenza virus hemagglutinin and other viral lectins share the same structural fold as human galectins (host lectins). Unlike the easily accessible sugar-binding sites in human galectins, the sugar-binding sites in viral lectins are hidden in cavities. We propose that these viral lectins originated from host lectins but have evolved to use hidden sugar-binding sites to evade host immune attacks.
Simultaneous bilateral torsion of the adnexae in an adult female without any history of ovarian stimulation
Authors: Abdusamad Kula , Hamoudi Raied , Maiti S
Published: January 2013

Simultaneous bilateral adnexal torsion is very rare especially in adults. There have been few cases reported in children with only one previous case reported in adults since 1984, which was complicated by entanglement of both adnexae. In adults, the use of ovarian stimulation for treatment of infertility can increase the risk of ovarian torsion. We report the second case of simultaneous bilateral adnexal torsion in an adult female without follicular stimulation.
Histological percutaneous diagnosis of stage IV microcystic serous cystadenocarcinoma of the pancreas
Authors: Bassam Abu-Wasel , Keough Valerie , Huang Weei-Yuan , Molinari Michele
Published: January 2013

Malignant serous cystic neoplasms (SCN) of the pancreas are exceptionally rare, and only a few cases have been reported. As a result, SCN have been unanimously classified as benign tumours. Contrary to this conviction, in 1989, Georgeet alpublished the very first case of a patient found to have a malignant pancreatic SCN. Up to the time of the submission of this paper, 27 cases of serous cystoadenocarcinomas have been published. In all the previously published cases of malignant SCN, the correct diagnosis was made postoperatively or at the time of autopsy. The authors present a case of a 68-year-old patient who was incidentally found to have a large liver mass on transthoracic echocardiogram ordered for suspected coronary artery insufficiency. Subsequent investigations revealed an additional large mass in the pancreas and percutaneous biopsies of both lesions revealed histological features consistent with malignant SCN metastasised to the left hepatic lobe.
Classic tongue lipoma: a common tumour at a rare site
Authors: Magadum Dilip , Sanadi Appasab , Agrawal Jiwanasha Manish , Agrawal Manish Suresh
Published: January 2013

Lipoma is the commonest benign tumour occurring at any anatomical site where fat is present, but occurrence in the oral cavity is rare. Tongue which is totally devoid of fat cells is a rare site for lipoma. This is one such rare case of the universal tumour, presenting at the lateral margin of the tongue, for which complete tumour excision was done. Macroscopically the mass had a hard consistency and measured 3.0×2.0 cm. From microscopic examination, diagnosis of lipoma was made. Recurrence of tongue lipoma is rare.
Adrenal ganglioneuroma: a rare incidental finding
Authors: Leão Ricardo R , Pereira Bruno Jorge , Borges Ricardo , Grenha Vãnia
Published: January 2013

The widespread use of imaging technology as a diagnostic tool has resulted in the identification of many previously unknown, clinically benign lesions. The current era of easy access to imaging studies places physicians in a difficult position, since many lesions are not precisely diagnosed by imaging. For example, the accurate diagnosis of non-functioning adrenal lesions remains a clinical challenge. This report describes a patient with the incidental CT finding of an uncommon adrenal ganglioneuroma. Clinical and radiological findings can guide suspicion towards this rare lesion; however, the actual diagnosis is based on histological findings. Specific characteristics of adrenal ganglioneuromas that would allow their diagnosis without invasive procedures have not been established. This case report is an attempt to add more data that will help to establish diagnostic criteria for this rare disease.
A multidisciplinary approach to management of autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED)
Authors: Gouda Mohammed Ramzy , Al-Amin Azzam , Grabsch Heike , Donnellan Clare
Published: January 2013

We present a case of an 18-year-old Caucasian man with a rare autosomal recessive disorder called autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED). This patient had manifestations of all clinical components of this multisystemic disease which included intestinal failure secondary to autoimmune enteropathy. We present a unique multidisciplinary management for this genetic condition. Although patients with APECED do not always have all the disease components (a total of eight exist), the majority have at least 3–5 components. This excludes the psychosexual implications which are often ignored. This case highlights the importance of (1) management of APECED in a multidisciplinary nature that includes a gastroenterologist, immunologist, endocrinologist, dietitians, etc and the (2) management of intestinal failure component of APECED is best suited in a specialist intestinal failure unit where expertise is available for complex malabsorption disorders.
Scrotal siliconoma: complications of an unapproved substance to an uninformed public
Authors: Sepehripour Sarvnaz , Filobbos George , Drake Marcus , Orlando Antonio
Published: January 2013

Liquid silicone is not approved for cosmetic injections in the USA and the UK because of possible adverse reactions. Despite this ban it is, unfortunately, still used by unlicensed practitioners and is offered to an uninformed public. This case report presents a case of scrotal siliconoma in a patient who received a liquid silicone injection for scrotal augmentation in an unlicensed practice in London and developed complications. The case should serve as a warning and encourage more patient education and public awareness about the dangers of liquid silicone injection.
Perioperative risk stratification for a patient with severe obstructive sleep apnoea undergoing laparoscopic banding surgery
Authors: Weinberg Laurence , Tay Stan , Lai Chung Fei , Barnes Maree
Published: January 2013

Despite the increasing prevalence of obstructive sleep apnoea (OSA), there is limited evidence to guide appropriate preoperative investigations, inpatient or outpatient surgery allocation, and the anticipated level of postoperative care. With reference to our institution's perioperative risk stratification, we describe the case of a 46-year-old Caucasian male with a body mass index of 51 kg/m2admitted for laparoscopic band insertion. Management based on our guidelines involved a preoperative polysomnography where the patient was confirmed to have severe OSA. His postoperative care was then managed in the high dependency care unit. He was discharged home on day 2 with no further sequelae. We provide evidence that adoption of this model of care can simplify clinical decision making and resource allocation with favourable patient outcomes.
Exercise during pregnancy and gestational diabetes-related adverse effects: a randomised controlled trial
Authors: Barakat Ruben , Pelaez Mireia , Lopez Carmina , Lucia Alejandro , Ruiz Jonatan R
Published: January 2013

Objective

To examine the effect of regular moderate-intensity exercise (three training sessions/week) on the incidence of gestational diabetes mellitus (GDM, primary outcome). We also examined if the exercise intervention modifies the association between GDM and birth weight and risk of macrosomia, gestational age, risk of caesarean delivery and maternal weight gain (secondary outcomes).

Methods

We randomly assigned 510 healthy gravida to either an exercise intervention or a usual care (control) group (n=255 each). The exercise programme focused on moderate-intensity resistance and aerobic exercises (three times/week, 50–55 min/session). GDM diabetes was diagnosed according to the WHO criteria and the International Association for Diabetes in Pregnancy Study Group (IADPSG).

Results

The intervention did not reduce the risk of developing GDM (OR 0.84, 95% CI 0.50 to 1.40) when using the WHO criteria. We observed that the intervention reduced by 58% the GDM-related risk (WHO criteria) of having a newborn with macrosomia (OR 1.76, 95% CI 0.04 to 78.90 vs 4.22, 95% CI 1.35 to 13.19) in exercise and control groups, respectively), and by 34% the GDM-related risk of having acute and elective caesarean delivery (OR 1.30, 95% CI 0.44 to 3.84 vs 1.99, 95% CI 0.98 to 4.06 in exercise and control groups, respectively). Gestational age was similar across the treatment groups (control, exercise) and GDM category (GDM or non-GDM), and maternal weight gain was ∼12% lower in the exercise group independent of whether women developed GDM. The results were similar when the IADPSG criteria were used instead.

Conclusions

Regular moderate-intensity exercise performed over the second-third trimesters of pregnancy can be used to attenuate important GDM-related adverse outcomes.
A specialist, second-tier response to out-of-hospital cardiac arrest: setting up TOPCAT2
Authors: Clarke Scott , Lyon Richard M , Short Steven , Crookston Colin , Clegg Gareth R
Published: January 2013

Background

Out-of-hospital cardiac arrest (OHCA) is the most common, immediately life-threatening, medical emergency faced by ambulance crews. Survival from OHCA is largely dependent on quality of prehospital resuscitation. Non-technical skills, including resuscitation team leadership, communication and clinical decision-making are important in providing high quality prehospital resuscitation. We describe a pilot study (TOPCAT2, TC2) to establish a second tier, expert paramedic response to OHCA in Edinburgh, Scotland.

Methods

Eight paramedics were selected to undergo advanced training in resuscitation and non-technical skills. Simulation and video feedback was used during training. The designated TC2 paramedic manned a regular ambulance service response car and attended emergency calls in the usual manner. Emergency medical dispatch centre dispatchers were instructed to call the TC2 paramedic directly on receipt of a possible OHCA call. Call and dispatch timings, quality of cardiopulmonary resuscitation and return-of-spontaneous circulation were all measured prospectively.

Results

Establishing a specialist, second-tier paramedic response was feasible. There was no overall impact on ambulance response times. From the first 40 activations, the TC2 paramedic was activated in a median of 3.2 min (IQR 1.6–5.8) and on-scene in a median of 10.8 min (8.0–17.9). Bimonthly team debrief, case review and training sessions were successfully established. OHCA attended by TC2 showed an additional trend towards improved outcome with a rate of return of spontaneous circulation of 22.5%, compared with a national average of 16%.

Conclusions

Establishing a specialist, second-tier response to OHCA is feasible, without impacting on overall ambulance response times. Improving non-technical skills, including prehospital resuscitation team leadership, has the potential to save lives and further research on the impact of the TOPCAT2 pilot programme is warranted.
Socioeconomic development and girl child survival in rural North India: solution or problem?
Authors: Krishnan Anand , Dwivedi Purva , Gupta Vivek , Byass Peter , Pandav Chandrakant S , Ng Nawi
Published: January 2013

Background

Socioeconomic development has been considered as a solution to the problem of sex differentials at birth and under-five mortality. This paper analyses longitudinal data from the Ballabgarh Health and Demographic Surveillance System (HDSS) site in north India to check its veracity.

Methods

A cohort of children born between 1 January 2006 and 31 December 2011 at Ballabgarh HDSS were followed till death, emigration, 3 years of age or end of the study. Socioeconomic status (SES) was measured by caste, parental combined years of schooling and wealth index and divided into low, mid and high strata for each of them. Sex ratio at birth (SRB) was reported as the number of girls per 1000 boys. The Kaplan-Meier survival curves were drawn and a Cox Proportional HR of girls over boys was estimated.

Results

A total of 12 517 native born children (25 797 child years) were enrolled of which 710 died (death rate of 56.7/1000-live births and 27.5/1000 child-years. Socioeconomically advantaged children had significantly lower death rates. The SRB (10–16% lower) and neonatal death rate were consistently adverse for girls in the advantaged groups by all the three indicators of SES. The first month survival rates were better for girls in the lower SES categories (significant only in caste (HR 0.58; 0.37 to 0.91). High SES categories consistently showed adverse survival rates for girls (HR of 1.22 to 1.59).

Conclusions

Better socioeconomic situation worsened the sex differentials, especially at birth. Therefore, specific interventions targeting gender issues are required, at least as a short-term measure.
Changes to DNA methylation and homologous recombination frequency in the progeny of stressed plants
Authors: Migicovsky Zoë , Kovalchuk Igor
Published: January 2013

Plants undergo changes in response to biotic and abiotic stresses that help them adjust and survive. Some of these changes may even be passed on to progeny and eventually lead to adaptive evolution. Transgenerational changes in response to stress include alterations in DNA methylation and changes in homologous recombination frequency (HRF). The progeny of plants that were stressed often show elevated HRF as well as genomic hypermethylation, although specific loci that are beneficial in times of stress may be hypomethylated. One of the possible mechanisms responsible for passing the memory to the progeny involves small interfering RNAs; Dicer-like proteins, DCL2 and DCL3, are in part required for this process. However, while epigenetic modifications are often present in the untreated progeny of stressed plants, they are not usually sustained for multiple unexposed generations. Still, transgenerational inheritance of such changes has already begun to provide evidence for an important role of epigenetics in enhancing stress resistance.
Physiological and endocrine changes in Atlantic salmon smolts during hatchery rearing, downstream migration, and ocean entry
Authors: McCormick Stephen D. , Sheehan Timothy F. , Björnsson Björn Thrandur , Lipsky Christine , Kocik John F. , Regish Amy M. , O'Dea Michael F.
Published: January 2013

Billions of hatchery salmon smolts are released annually in an attempt to mitigate anthropogenic impacts on freshwater habitats, often with limited success. Mortality of wild and hatchery fish is high during downstream and early ocean migration. To understand changes that occur during migration, we examined physiological and endocrine changes in Atlantic salmon (Salmo salar) smolts during hatchery rearing, downstream migration, and early ocean entry in two successive years. Gill Na+/K+-ATPase activity increased in the hatchery during spring, increased further after river release, and was slightly lower after recapture in the ocean. Plasma growth hormone levels increased in the hatchery, were higher in the river, and increased further in the ocean. Plasma IGF-I remained relatively constant in the hatchery, increased in the river, then decreased in the ocean. Plasma thyroid hormones were variable in the hatchery, but increased in both river- and ocean-captured smolts. Naturally reared fish had lower condition factor, gill NKA activity, and plasma thyroxine than hatchery fish in the river but were similar in the ocean. This novel data set provides a vital first step in understanding the role and norms of endocrine function in smolts and the metrics of successful marine entry.
A comparison of temporal patterns in the ocean spatial distribution of California's Central Valley Chinook salmon runs
Authors: Satterthwaite William H. , Mohr Michael S. , O'Farrell Michael R. , Wells Brian K.
Published: January 2013

We developed a broadly applicable method for estimating stock-specific spatial distributions based on patterns in contacts per unit effort determined from data collected in ocean fisheries. The method fully accounts for fishing effort and quantifies uncertainty in total contacts due to sampling error and the effects of annual variability in size-at-age on estimated contacts with sublegal-sized fish. As a case study, we used coded-wire tag recoveries to compare ocean spatial distributions among fish from four return run timings (fall, late-fall, winter, and spring) of Chinook salmon from the Central Valley, California, USA, and explored how distributions varied annually, seasonally, and with fish age in the data-rich fall run. All runs were rarely contacted in ocean fisheries north of Cape Falcon, Oregon (45°46′N). Late-fall and winter run fish appeared relatively restricted to the south compared with fall run fish, corresponding to life history differences and highlighting the ability of spatial management to control impacts on the endangered winter run. For the fall run, the location of highest relative contacts per unit effort of age-3 fish varied across years. This variation correlated with sea surface temperature the previous summer, suggesting ocean distributions may be more responsive to the environment than previously appreciated.
Prospects for the measurement of the Higgs Yukawa couplings to b and c quarks, and muons at CLIC
Authors: Grefe Christian , Laštovička Tomáš , Strube Jan
Published: January 2013

The investigation of the properties of the Higgs boson, especially a test of the predicted linear dependence of the branching ratios on the mass of the final state is going to be an integral part of the physics program at colliders at the energy frontier for the foreseeable future. The large Higgs boson production cross section at a 3 TeV CLIC machine allows for a precision measurement of the Higgs branching ratios. The cross section times branching ratio of the decays $\mathrm {H}\to \mathrm {b}\overline {\mathrm {b}}$, $\mathrm {H}\to \mathrm {c}\overline {\mathrm {c}}$ and H→μ+μ− of a Standard Model Higgs boson with a mass of 120 GeV can be measured with a statistical uncertainty of 0.23 %, 3.1 % and 15 %, respectively, assuming an integrated luminosity of 2 ab−1.
Debt Issuance Under Rule 144A and Equity Valuation Effects
Authors: Carayannopoulos Peter , Nayak Subhankar
Published: January 2013

We compare valuation effects associated with debt issuance under SEC Rule 144A versus issuance in the public market. We find that nonconvertible debt Rule 144A issuers experience an incremental positive announcement effect when compared to their counterparts issuing in the public market. We attribute this to the timing of issuance under favorable market conditions and a reduction in informational asymmetry due to lender specialization. When compared to their public counterparts, convertible Rule 144A bond issuers often experience negative announcement effects and inferior post-issuance stock performance. We argue that this negative market reaction arises from a stronger opportunistic market-timing signal.
DISRUPTION OF PROTEIN COMPLEXES
Authors: TAHERI GOLNAZ , HABIBI MAHNAZ , WONG LIMSOON , ESLAHCHI CHANGIZ
Published: January 2013

Protein complexes are a cornerstone of many biological processes and, together, they form various types of molecular machinery that perform a vast array of biological functions. Different complexes perform different functions and, the same complex can perform very different functions that depend on a variety of factors. Thus disruption of protein complexes can be lethal to an organism. It is interesting to identify a minimal set of proteins whose removal would lead to a massive disruption of protein complexes and, to understand the biological properties of these proteins. A method is presented for identifying a minimum number of proteins from a given set of complexes so that a maximum number of these complexes are disrupted when these proteins are removed. The method is based on spectral bipartitioning. This method is applied to yeast protein complexes. The identified proteins participate in a large number of biological processes and functional modules. A large proportion of them are essential proteins. Moreover, removing these identified proteins causes a large number of the yeast protein complexes to break into two fragments of nearly equal size, which minimizes the chance of either fragment being functional. The method is also superior in these aspects to alternative methods based on proteins with high connection degree, proteins whose neighbors have high average degree, and proteins that connect to lots of proteins of high connection degree. Our spectral bipartitioning method is able to efficiently identify a biologically meaningful minimal set of proteins whose removal causes a massive disruption of protein complexes in an organism.
PROLIFERATION OF OBSERVABLES AND MEASUREMENT IN QUANTUM-CLASSICAL HYBRIDS
Authors: ELZE HANS-THOMAS
Published: January 2013

Following a review of quantum-classical hybrid dynamics, we discuss the ensuing proliferation of observables and relate it to measurements of (would-be) quantum mechanical degrees of freedom performed by (would-be) classical ones (if they were separable). Hybrids consist in coupled classical (CL) and quantum mechanical (QM) objects. Numerous consistency requirements for their description have been discussed and are fulfilled here. We summarize a representation of quantum mechanics in terms of classical analytical mechanics which is naturally extended to QM–CL hybrids. This framework allows for superposition, separable, and entangled states originating in the QM sector, admits experimenter's "Free Will", and is local and nonsignaling. Presently, we study the set of hybrid observables, which is larger than the Cartesian product of QM and CL observables of its components; yet it is smaller than a corresponding product of all-classical observables. Thus, quantumness and classicality infect each other.
AN EFFICIENT SMOOTHED POINT INTERPOLATION METHOD FOR DYNAMIC ANALYSES
Authors: SOARES DELFIM , SCHÖNEWALD ANNE , ESTORFF OTTO VON
Published: January 2013

In this work, a new procedure to compute the mass matrix in the smoothed point interpolation method is discussed. Therefore, the smoothed subdomains are employed to evaluate the mass matrix, which have already been computed for the construction of the stiffness matrix, rendering a more efficient methodology. The procedure is discussed, taking into account the edge-based, cell-based, and node-based smoothed point interpolation methods, as well as different T-schemes for the construction of the support domain of the approximating shape function, which is here formulated based on the radial point interpolation method. Numerical results of different dynamic analyses are presented, illustrating the potentialities of the proposed methodology.
PREPARATION AND PHOTOCATALYTIC PROPERTY OF MULTI-WALLED CARBON NANOTUBES/TiO2 NANOHYBRIDS
Authors: CHEN C. S. , XIE X. D. , CAO S. Y. , LIU Q. C. , KUANG J. C. , MEI Y. P. , ZHAO G. J. , LIU T. G. , ZENG B. , NING X. T. , CHEN X. H.
Published: January 2013

A simple and versatile approach decorated TiO2 nanoparticles on the surface of multi-walled carbon nanotube (MWNTs) was reported. MWNTs can be continuously coated by the layer of anatase TiO2 nanoparticles with the thickness of about 20 nm by the assistance of salicylamide. Moreover, anatase TiO2 nanoparticles with the size of about 10 nm are uniformly deposited on MWNTs by using microwave radiation. The synthetic MWNTs/ TiO2 hybrids have been proven to be very high photocatalytic ability for methyl orange (MO) without any additional treatment.
The cardiomyocyte molecular clock, regulation of Scn5a, and arrhythmia susceptibility
Authors: Schroder Elizabeth A. , Lefta Mellani , Zhang Xiping , Bartos Daniel C. , Feng Han-Zhong , Zhao Yihua , Patwardhan Abhijit , Jin Jian-Ping , Esser Karyn A. , Delisle Brian P.
Published: January 2013

The molecular clock mechanism underlies circadian rhythms and is defined by a transcription-translation feedback loop. Bmal1 encodes a core molecular clock transcription factor. Germline Bmal1 knockout mice show a loss of circadian variation in heart rate and blood pressure, and they develop dilated cardiomyopathy. We tested the role of the molecular clock in adult cardiomyocytes by generating mice that allow for the inducible cardiomyocyte-specific deletion of Bmal1 (iCSΔ Bmal1). ECG telemetry showed that cardiomyocyte-specific deletion of Bmal1 (iCSΔ Bmal1−/−) in adult mice slowed heart rate, prolonged RR and QRS intervals, and increased episodes of arrhythmia. Moreover, isolated iCSΔ Bmal1−/− hearts were more susceptible to arrhythmia during electromechanical stimulation. Examination of candidate cardiac ion channel genes showed that Scn5a, which encodes the principle cardiac voltage-gated Na+ channel (NaV1.5), was circadianly expressed in control mouse and rat hearts but not in iCSΔ Bmal1−/− hearts. In vitro studies confirmed circadian expression of a human Scn5a promoter-luciferase reporter construct and determined that overexpression of clock factors transactivated the Scn5a promoter. Loss of Scn5a circadian expression in iCSΔ Bmal1−/− hearts was associated with decreased levels of NaV1.5 and Na+ current in ventricular myocytes. We conclude that disruption of the molecular clock in the adult heart slows heart rate, increases arrhythmias, and decreases the functional expression of Scn5a. These findings suggest a potential link between environmental factors that alter the cardiomyocyte molecular clock and factors that influence arrhythmia susceptibility in humans.
Reduced carbohydrate availability enhances exercise-induced p53 signaling in human skeletal muscle: implications for mitochondrial biogenesis
Authors: Bartlett Jonathan D. , Louhelainen Jari , Iqbal Zafar , Cochran Andrew J. , Gibala Martin J. , Gregson Warren , Close Graeme L. , Drust Barry , Morton James P.
Published: January 2013

The mechanisms that regulate the enhanced skeletal muscle oxidative capacity observed when training with reduced carbohydrate (CHO) availability are currently unknown. The aim of the present study was to test the hypothesis that reduced CHO availability enhances p53 signaling and expression of genes associated with regulation of mitochondrial biogenesis and substrate utilization in human skeletal muscle. In a repeated-measures design, muscle biopsies (vastus lateralis) were obtained from eight active males before and after performing an acute bout of high-intensity interval running with either high (HIGH) or low CHO availability (LOW). Resting muscle glycogen (HIGH, 467 ± 19; LOW, 103 ± 9 mmol/kg dry wt) was greater in HIGH compared with LOW ( P < 0.05). Phosphorylation (P-) of ACCSer79(HIGH, 1.4 ± 0.4; LOW, 2.9 ± 0.9) and p53Ser15(HIGH, 0.9 ± 0.4; LOW, 2.6 ± 0.8) was higher in LOW immediately postexercise and 3 h postexercise, respectively ( P < 0.05). Before and 3 h postexercise, mRNA content of pyruvate dehydrogenase kinase 4, mitochondrial transcription factor A, cytochrome- c oxidase IV, and PGC-1α were greater in LOW compared with HIGH ( P < 0.05), whereas carnitine palmitoyltransferase-1 showed a trend toward significance ( P = 0.09). However, only PGC-1α expression was increased by exercise ( P < 0.05), where three-fold increases occurred independently of CHO availability. We conclude that the exercise-induced increase in p53 phosphorylation is enhanced in conditions of reduced CHO availability, which may be related to upstream signaling through AMPK. Given the emergence of p53 as a molecular regulator of mitochondrial biogenesis, such nutritional modulation of contraction-induced p53 activation has implications for both athletic and clinical populations.
Inherited secondary nephrogenic diabetes insipidus: concentrating on humans
Authors: Bockenhauer D. , Bichet D. G.
Published: January 2013

The study of human physiology is paramount to understanding disease and developing rational and targeted treatments. Conversely, the study of human disease can teach us a lot about physiology. Investigations into primary inherited nephrogenic diabetes insipidus (NDI) have contributed enormously to our understanding of the mechanisms of urinary concentration and identified the vasopressin receptor AVPR2, as well as the water channel aquaporin-2 (AQP2), as key players in water reabsorption in the collecting duct. Yet, there are also secondary forms of NDI, for instance as a complication of lithium treatment. The focus of this review is secondary NDI associated with inherited human diseases, such as Bartter syndrome or apparent mineralocorticoid excess. Currently, the underlying pathophysiology of this inherited secondary NDI is unclear, but there appears to be true AQP2 deficiency. To better understand the underlying mechanism(s), collaboration between clinical and experimental physiologists is essential to further investigate these observations in appropriate experimental models.
Role of guanine-nucleotide exchange factor Epac in renal physiology and pathophysiology
Authors: Yang Shi-kun , Xiao Li , Li Jun , Liu Fuyou , Sun Lin , Kanwar Yashpal S.
Published: January 2013

Exchange proteins directly activated by cAMP [Epac(s)] were discovered more than a decade ago as new sensors for the second messenger cAMP. The Epac family members, including Epac1 and Epac2, are guanine nucleotide exchange factors for the Ras-like small GTPases Rap1 and Rap2, and they function independently of protein kinase A. Given the importance of cAMP in kidney homeostasis, several molecular and cellular studies using specific Epac agonists have analyzed the role and regulation of Epac proteins in renal physiology and pathophysiology. The specificity of the functions of Epac proteins may depend upon their expression and localization in the kidney as well as their abundance in the microcellular environment. This review discusses recent literature data concerning the involvement of Epac in renal tubular transport physiology and renal glomerular cells where various signaling pathways are known to be operative. In addition, the potential role of Epac in kidney disorders, such as diabetic kidney disease and ischemic kidney injury, is discussed.
On a Level-Set Method for Ill-Posed Problems with Piecewise Nonconstant Coefficients
Authors: De Cezaro A.
Published: January 2013

We investigate a level-set-type method for solving ill-posed problems, with the assumption that the solutions are piecewise, but not necessarily constant functions with unknown level sets and unknown level values. In order to get stable approximate solutions of the inverse problem, we propose a Tikhonov-type regularization approach coupled with a level-set framework. We prove the existence of generalized minimizers for the Tikhonov functional. Moreover, we prove convergence and stability for regularized solutions with respect to the noise level, characterizing the level-set approach as a regularization method for inverse problems. We also show the applicability of the proposed level-set method in some interesting inverse problems arising in elliptic PDE models.
Application of Flower‐Like ZnO Nanorods Gas Sensor Detecting SF6 Decomposition Products
Authors: Peng Shudi , Wu Gaolin , Song Wei , Wang Qian
Published: January 2013

Gas insulated switchgear (GIS) is an important electric power equipment in a substation, and its running state has a significant relationship with stability, security, and reliability of the whole electric power system. Detecting and analyzing the decomposition byproducts of sulfur hexafluoride gas (SF6) is an effective method for GIS state assessment and fault diagnosis. This paper proposes a novel gas sensor based on flower‐like ZnO nanorods to detect typical SF6 decompositions. Flower‐like ZnO nanoparticles were synthesized via a simple hydrothermal method and characterized by X‐ray powder diffraction and field‐emission scanning electron microscopy, respectively. The gas sensor was fabricated with a planar‐type structure and applied to detect SF6 decomposition products. It shows excellent sensing properties to SO2, SOF2, and SO2F2 with rapid response and recovery time and long‐term stability and repeatability. Moreover, the sensor shows a remarkable discrimination among SO2, SOF2, and SO2F2 with high linearity, which makes the prepared sensor a good candidate and a wide application prospect detecting SF6 decomposition products in the future.
Arrhythmias following Revascularization Procedures in the Course of Acute Myocardial Infarction: Are They Indicators of Reperfusion or Ongoing Ischemia?
Authors: Tatli Ersan , Alicik Güray , Buturak Ali , Yilmaztepe Mustafa , Aktoz Meryem
Published: January 2013

Objective. The most important step in the treatment of ST elevation myocardial infarction is to sustain myocardial blood supply as soon as possible. The two main treatment methods used today to provide myocardial reperfusion are thrombolytic therapy and percutaneous coronary intervention. In our study, reperfusion arrhythmias were investigated as if they are indicators of coronary artery patency or ongoing ischemia after revascularization. Methods. 151 patients with a diagnosis of acute ST elevation myocardial infarction were investigated. 54 patients underwent primary percutaneous coronary intervention and 97 patients were treated with thrombolytic therapy. The frequency of reperfusion arrythmias following revascularization procedures in the first 48 hours after admission was examined. The relation between reperfusion arrhythmias, ST segment regression, coronary artery patency, and infarct related artery documented by angiography were analyzed. Results. There was no statistically significant difference between the two groups in the frequency of reperfusion arrhythmias (P = 0.355). Although angiographic vessel patency was higher in patients undergoing percutaneous coronary intervention, there was no significant difference between the patency rates of each group with and without reperfusion arrythmias. Conclusion. Our study suggests that recorded arrhythmias following different revascularization procedures in acute ST elevation myocardial infarction may not always indicate vessel patency and reperfusion. Ongoing vascular occlusion and ischemia may lead to various arrhythmias which may not be distinguished from reperfusion arrhythmias.
Adjusted Empirical Likelihood for Varying Coefficient Partially Linear Models with Censored Data
Authors: Zhao Peixin
Published: January 2013

By constructing an adjusted auxiliary vector ingeniously, we propose an adjusted empirical likelihood ratio function for the parametric components of varying coefficient partially linear models with censored data. It is shown that its limiting distribution is standard central chi-squared. Then the confidence intervals for the parametric components are constructed. A simulation study and a real data analysis are undertaken to assess the finite sample performance of the proposed method.
Chloroquine Inhibits Dengue Virus Type 2 Replication in Vero Cells but Not in C6/36 Cells
Authors: Farias Kleber Juvenal Silva , Machado Paula Renata Lima , da Fonseca Benedito Antônio Lopes
Published: January 2013

Dengue viruses are the most important arthropod‐borne viruses in terms of morbidity and mortality in the world. Since there is no dengue vaccine available for human use, we have set out to investigate the use of chloroquine as an antiviral drug against dengue. Chloroquine, an amine acidotropic drug known to affect intracellular exocytic pathways by increasing endosomal pH, was used in the in vitro treatment of Vero and C6/36 cells infected with dengue virus type 2 (DENV‐2). Real‐time RT‐PCR and plaque assays were used to quantify the DENV‐2 load in infected Vero and C6/36 cells after chloroquine treatment. Our results showed that a dose of 50 μg/ml of chloroquine was not toxic to the cells and induced a statistically significant inhibition of virus production in infected Vero cells when compared to untreated cells. In C6/36 cells, chloroquine does not induce a statistically significant difference in viral replication when compared to untreated cells, showing that this virus uses an unlikely pathway of penetration in these cells, and results were also confirmed by the plaque assay (PFU). These data suggest that the inhibition of virus infection induced by chloroquine is due to interference with acidic vesicles in mammalian cells.
Retroperitoneal Paraganglioma Presenting as a Chest Pain: A Case Report
Authors: Brahmbhatt Parag , Patel Pranav , Saleem Atif , Narayan Rathi , Young Mark
Published: January 2013

Paragangliomas are very rare tumors derived from neuroendocrine cells of autonomic nervous system. Extra-adrenal paragangliomas account for only 10 to 15% of all paragangliomas and may present incidentally as a mass. Typical triad of fluctuating hypertension, headache, and sweating is not always present which makes the diagnosis difficult sometimes. Definitive diagnosis is usually made with histologic findings and surgery is the treatment of choice. We report a case of a 53-year-old male who presented with chest pain and vomiting.