bluuebunny/crossref_metadata_2025 huggingface dataset:
Trafficking of Bluetongue Virus Visualized by Recovery of Tetracysteine-Tagged Virion Particles
Authors: Du Junzheng , Bhattacharya Bishnupriya , Ward Theresa H. , Roy Polly
Published: August 2014

Bluetongue virus (BTV), a member of theOrbivirusgenus in theReoviridaefamily, is a double-capsid insect-borne virus enclosing a genome of 10 double-stranded RNA segments. Like those of other members of the family, BTV virions are nonenveloped particles containing two architecturally complex capsids. The two proteins of the outer capsid, VP2 and VP5, are involved in BTV entry and in the delivery of the transcriptionally active core to the cell cytoplasm. Although the importance of the endocytic pathway in BTV entry has been reported, detailed analyses of entry and the role of each protein in virus trafficking have not been possible due to the lack of availability of a tagged virus. Here, for the first time, we report on the successful manipulation of a segmented genome of a nonenveloped capsid virus by the introduction of tags that were subsequently fluorescently visualized in infected cells. The genetically engineered fluorescent BTV particles were observed to enter live cells immediately after virus adsorption. Further, we showed the separation of VP2 from VP5 during virus entry and confirmed that while VP2 is shed from virions in early endosomes, virus particles still consisting of VP5 were trafficked sequentially from early to late endosomes. Since BTV infects both mammalian and insect cells, the generation of tagged viruses will allow visualization of the trafficking of BTV farther downstream in different host cells. In addition, the tagging technology has potential for transferable application to other nonenveloped complex viruses.

IMPORTANCELive-virus trafficking in host cells has been highly informative on the interactions between virus and host cells. Although the insertion of fluorescent markers into viral genomes has made it possible to study the trafficking of enveloped viruses, the physical constraints of architecturally complex capsid viruses have imposed practical limitations. In this study, we have successfully genetically engineered the segmented RNA genome of bluetongue virus (BTV), a complex nonenveloped virus belonging to theReoviridaefamily. The resulting fluorescent virus particles could be visualized in virus entry studies of both live and fixed cells. This is the first time a structurally complex capsid virus has been successfully genetically manipulated to generate virus particles that could be visualized in infected cells.
Immunogenicity Studies of Proteins Forming the T4 Phage Head Surface
Authors: Dąbrowska Krystyna , Miernikiewicz Paulina , Piotrowicz Agnieszka , Hodyra Katarzyna , Owczarek Barbara , Lecion Dorota , Kaźmierczak Zuzanna , Letarov Andrey , Górski Andrzej
Published: August 2014

Advances in phage therapy and novel applications of phages in biotechnology encourage interest in phage impact on human and animal immunity. Here we present comparative studies of immunogenic properties of T4 phage head surface proteins gp23*, gp24*, Hoc, and Soc, both as elements of the phage capsid and as isolated agents. Studies comprise evaluation of specific antibodies in the human population, analysis of the proteins' impact on the primary and secondary responses in mice, and the effect of specific antibodies on phage antibacterial activityin vitroandin vivoin mice. In humans, natural antibodies specific to T4-like phages were abundant (81% of investigated sera). Among those, significantly elevated levels of IgG antibodies only against major head protein (gp23*) were found, which probably reflected cross-reactions of T4 with antibodies induced by other T4-like phages. Both IgM and IgG antibodies were induced mostly by gp23* and Hoc, while weak (gp24*) and very weak (Soc) reactivities of other head proteins were noticed. Thus, T4 head proteins that markedly contribute to immunological memory to the phage are highly antigenic outer capsid protein (Hoc) and major capsid protein (gp23*). Specific anti-gp23* and anti-Hoc antibodies substantially decreased T4 phage activityin vitroand to some extentin vivo. Cooperating with antibodies, the immune complement system also contributed to annihilating phages.

IMPORTANCECurrent descriptions of phage immunogenicity and its biological consequences are still vague and incomplete; thus, the central problem of this work is timely and may have strong practical implications. Here is presented the very first description of the contribution of bacteriophage proteins to immunological memory of the phage. Understanding of interactions between phages and mammalian immunology may help in biotechnological adaptations of phages for therapeutic requirements as well as for better appreciation of phage ecology and their role in the biosphere.
Comprehensive Analysis of Herpes Simplex Virus 1 (HSV-1) Entry Mediated by Zebrafish 3-
O
-Sulfotransferase Isoforms: Implications for the Development of a Zebrafish Model of HSV-1 Infection
Authors: Yakoub Abraam M. , Rawal Nistha , Maus Erika , Baldwin John , Shukla Deepak , Tiwari Vaibhav
Published: August 2014

Binding of herpes simplex virus 1 (HSV-1) envelope glycoprotein D (gD) to the receptor 3-
O
-sulfated heparan sulfate (3-
O
S HS) mediates viral entry. 3-
O
-Sulfation of HS is catalyzed by the 3-
O
-sulfotransferase (3-
O
ST) enzyme. Multiple isoforms of 3-
O
ST are differentially expressed in tissues of zebrafish (ZF) embryos. Here, we performed a comprehensive analysis of the role of ZF 3-
O
ST isoforms (3-
O
ST-1, 3-
O
ST-5, 3-
O
ST-6, and 3-
O
ST-7) in HSV-1 entry. We found that a group of 3-
O
ST gene family isoforms (3-
O
ST-2, -3, -4, and -6) with conserved catalytic and substrate-binding residues of the enzyme mediates HSV-1 entry and spread, while the other group (3-
O
ST-1, -5, and -7) lacks these properties. These results demonstrate that HSV-1 entry can be recapitulated by certain ZF 3-
O
ST enzymes, a significant step toward the establishment of a ZF model of HSV-1 infection and tissue-specific tropism.
APOBEC3F Determinants of HIV-1 Vif Sensitivity
Authors: Land Allison M. , Shaban Nadine M. , Evans Leah , Hultquist Judd F. , Albin John S. , Harris Reuben S.
Published: August 2014

HIV-1 Vif counteracts restrictive APOBEC3 proteins by targeting them for proteasomal degradation. To determine the regions mediating sensitivity to Vif, we compared human APOBEC3F, which is HIV-1 Vif sensitive, with rhesus APOBEC3F, which is HIV-1 Vif resistant. Rhesus-human APOBEC3F chimeras and amino acid substitution mutants were tested for sensitivity to HIV-1 Vif. This approach identified the α3 and α4 helices of human APOBEC3F as important determinants of the interaction with HIV-1 Vif.
Comparison of obturator prosthesis fabricated using different techniques and its effect on the management of a hemipalatomaxillectomy patient
Authors: Badadare Mokshada M , Patil Sanjayagouda B , Bhat Sudhakara , Tambe Abhijit
Published: August 2014

Odontogenic tumours involving the maxilla or mandible are usually treated with surgical resection. To prevent recurrence, extensive surgical intervention might be carried out leaving the patient with anatomical defects. However, rehabilitation of such patients with an obturator can improve function, facial form and social acceptance. In this case, we have evaluated the different designs and techniques of fabrication of an obturator prosthesis used for the rehabilitation of a hemipalatomaxillectomy patient. A 40-year-old man presented with a loose fitting obturator prosthesis. He had undergone hemipalatomaxillectomy for the treatment of an ameloblastoma 2 years earlier and had been using an obturator prosthesis since then. Hollow-bulb obturator prostheses were fabricated using two different methods, the lost salt and open lid techniques. The obturator prosthesis fabricated with the lost salt technique weighed less than the patient's old obturator. But the obturator fabricated using the open lid technique did not only considerably reduce the weight of the prosthesis but also improved health, function, aesthetics, phonetics and quality of life in this hemipalatomaxillectomy patient.
Robotic-assisted laparoscopic management of a caliceal diverticular calculus
Authors: Torricelli Fabio Cesar Miranda , Batista Lucas T , Colombo Jose Roberto , Coelho Rafael Ferreira
Published: August 2014

Purpose

To report the first case of robotic-assisted laparoscopic management of a symptomatic caliceal diverticular calculus and review the literature on laparoscopic treatment for this condition.

Case report

A 33-year-old obese woman with a 2×1 cm calculus within an anterior caliceal diverticulum located in the middle pole of the left kidney was referred to our service. She had already undergone two flexible ureterorenoscopies without success. We considered that a percutaneous approach would be very challenging due to stone location, thus we elected to perform a robotic-assisted laparoscopic procedure for stone removal and diverticulum fulguration. The procedure was uneventfully performed with no intraoperative or postoperative complications. The patient was discharged from the hospital on the second postoperative day and after 1.5 years of follow-up she is asymptomatic with no recurrence.

Conclusions

The robotic-assisted laparoscopic approach to caliceal diverticular calculi is feasible and safe, providing one more option for treatment of stones in challenging locations.
Customised component corneal transplantation: a blessing for three patients
Authors: Sati Alok , Shankar Sandeep , Jha Ashok , Gurunadh Velamakanni Satyanarayana
Published: August 2014

The existing acute shortage of good quality donor corneas in a developing country like India, prompted us to attempt customised component corneal transplantation. Using this surgical strategy, one corneoscleral button was used for three recipients. Anterior and posterior lamellar discs were used for anterior lamellar keratoplasty and Descemet's stripping endothelial keratoplasty in patients with superficial corneal scar and pseudophakic bullous keratopathy, respectively. From the remnant peripheral corneoscleral rim, a patch graft was taken and used for a case of perforated corneal ulcer. Postoperatively, the two earlier mentioned cases achieved visual acuities of 20/30 and 20/60, respectively, whereas the latter mentioned patient with the patch graft achieved good tectonic stability. This case report highlights the optimal utilisation of a corneoscleral button by customising it for three recipients. Moreover, a patch graft has been introduced in the armamentarium of customised component corneal transplantation for the first time.
Prospective analysis of the accuracy of diagnosis of carpal tunnel syndrome using a web-based questionnaire
Authors: Bland Jeremy D P , Rudolfer Stephan , Weller Peter
Published: August 2014

Objective

To confirm the accuracy of a diagnostic questionnaire for carpal tunnel syndrome (CTS) when presented via a public website rather than on paper.

Design

Prospective comparison of the probability of CTS as assessed by the web-based questionnaire athttp://www.carpal-tunnel.netwith the results of nerve conduction studies.

Setting

Subregional neurophysiology laboratory serving a population of 700 000 in East Kent, UK.

Participants

2821 individuals who were able to complete an online diagnostic questionnaire out of 4899 referred for initial diagnostic testing for new presentations with suspected CTS from April 2011 to March 2013. No exclusions were made on grounds of age, gender or coincident pathology.

Main outcome measure—nerve conduction results confirming CTS. The severity of median nerve impairment demonstrated was also assessed using a validated neurophysiological scale.

Results

The web-based questionnaire accurately estimates the probability of CTS being confirmed on nerve conduction studies. Using a website diagnostic score of ≥40% as an example cut-off value the questionnaire achieves 78% sensitivity and 68% specificity in predicting the finding of evidence of CTS on nerve conduction studies. The web-based version of the diagnostic questionnaire was as accurate as the original paper version with an area under the receiver operating characteristic curve of 0.79. There was also a significant correlation between the diagnostic score given by the website and the severity of CTS with higher scores being associated with greater nerve dysfunction (r=0.3, p<0.00001).

Conclusions

Completion of the symptom questionnaire on the website by patients at home provides a prediction of the likelihood of CTS which is sufficiently accurate to be used in initial planning of investigation and treatment.
The effects of financial incentives for case finding for depression in patients with diabetes and coronary heart disease: interrupted time series analysis
Authors: McLintock Kate , Russell Amy M , Alderson Sarah L , West Robert , House Allan , Westerman Karen , Foy Robbie
Published: August 2014

Objective

To evaluate the effects of Quality and Outcomes Framework (QOF) incentivised case finding for depression on diagnosis and treatment in targeted and non-targeted long-term conditions.

Design

Interrupted time series analysis.

Setting

General practices in Leeds, UK.

Participants

65 (58%) of 112 general practices shared data on 37 229 patients with diabetes and coronary heart disease targeted by case finding incentives, and 101 008 patients with four other long-term conditions not targeted (hypertension, epilepsy, chronic obstructive pulmonary disease and asthma).

Intervention

Incentivised case finding for depression using two standard screening questions.

Main outcome measures

Clinical codes indicating new depression-related diagnoses and new prescriptions of antidepressants. We extracted routinely recorded data from February 2002 through April 2012. The number of new diagnoses and prescriptions for those on registers was modelled with a binomial regression, which provided the strength of associations between time periods and their rates.

Results

New diagnoses of depression increased from 21 to 94/100 000 per month in targeted patients between the periods 2002–2004 and 2007–2011 (OR 2.09; 1.92 to 2.27). The rate increased from 27 to 77/100 000 per month in non-targeted patients (OR 1.53; 1.46 to 1.62). The slopes in prescribing for both groups flattened to zero immediately after QOF was introduced but before incentivised case finding (p<0.01 for both). Antidepressant prescribing in targeted patients returned to the pre-QOF secular upward trend (Wald test for equivalence of slope, z=0.73, p=0.47); the slope was less steep for non-targeted patients (z=−4.14, p<0.01).

Conclusions

Incentivised case finding increased new depression-related diagnoses. The establishment of QOF disrupted rising trends in new prescriptions of antidepressants, which resumed following the introduction of incentivised case finding. Prescribing trends are of concern given that they may include people with mild-to-moderate depression unlikely to respond to such treatment.
Lung ultrasonography: an effective way to diagnose community-acquired pneumonia
Authors: Liu Xiao-lei , Lian Rui , Tao Yong-kang , Gu Cheng-dong , Zhang Guo-qiang
Published: August 2014

Purpose

To analyse the ultrasonographic findings of community-acquired pneumonia (CAP) and its efficacy for diagnosis of CAP compared with chest X-ray (CXR).

Methods

Patients who presented to the Emergency Department with suspected CAP were included in the study. Bedside ultrasonography was performed at each intercostal space in the midclavicular, anterior axillary, midaxillary and paravertebral lines. Any pulmonary consolidation, focal interstitial pattern, pleural-line abnormalities and subpleural lesions were recorded, and the numbers of subpleural lesions and intercostal spaces with pleural-line abnormalities were counted. All patients received bedside CXR and CT. Using CT scan as the gold standard, ultrasonography findings were compared between CAP group and non-CAP group, and between CAP patients with CT showing consolidation or diffuse ground-glass opacification. The sensitivity of ultrasonography was compared with CXR for the diagnosis of CAP.

Results

Of 179 patients included in the study, 112 were diagnosed with CAP by CT. Patients in CAP group were more likely to have consolidation (p<0.001), focal interstitial pattern (p<0.001) and had higher number of subpleural lesions (p<0.001) and intercostal spaces with pleural-line abnormalities (p<0.001) on ultrasound than those without CAP. CAP patients whose CT showed consolidation were more likely to have consolidation (p<0.001) and had lower numbers of subpleural lesions (p<0.001) and intercostal spaces with pleural-line abnormalities (p<0.001) compared to CAP patients whose CT showed diffuse ground-glass opacification. The diagnostic sensitivity, specificity, and accuracy for ultrasonography and CXR were 94.6% versus 77.7% (p<0.001), 98.5% versus 94.0% (p=0.940) and 96.1% versus 83.8% (p<0.001), respectively.

Conclusions

Lung ultrasonography has a better diagnostic sensitivity and accuracy for diagnosing CAP compared with CXR.
Rising inequality in mortality among working-age men and women in Sweden: a national registry-based repeated cohort study, 1990–2007
Authors: Kondo Naoki , Rostila Mikael , Åberg Yngwe Monica
Published: August 2014

Background

In the past two decades, health inequality has persisted or increased in states with comprehensive welfare.

Methods

We conducted a national registry-based repeated cohort study with a 3-year follow-up between 1990 and 2007 in Sweden. Information on all-cause mortality in all working-age Swedish men and women aged between 30 and 64 years was collected. Data were subjected to temporal trend analysis using joinpoint regression to statistically confirm the trajectories observed.

Results

Among men, age-standardised mortality rate decreased by 38.3% from 234.9 to 145 (per 100 000 population) over the whole period in the highest income quintile, whereas the reduction was only 18.3% (from 774.5 to 632.5) in the lowest quintile. Among women, mortality decreased by 40% (from 187.4 to 112.5) in the highest income group, but increased by 12.1% (from 280.2 to 314.2) in the poorest income group. Joinpoint regression identified that the differences in age-standardised mortality between the highest and the lowest income quintiles decreased among men by 18.85 annually between 1990 and 1994 (p trend=0.02), whereas it increased later, with a 2.88 point increase per year (p trend <0.0001). Among women, it continuously increased by 9.26/year (p trend <0.0001). In relative terms, age-adjusted mortality rate ratios showed a continuous increase in both genders.

Conclusions

Income-based inequalities among working-age male and female Swedes have increased since the late 1990s, whereas in absolute terms the increase was less remarkable among men. Structural and behavioural factors explaining this trend, such as the economic recession in the early 1990s, should be studied further.
Percutaneous coronary intervention causes a rapid but transient mobilisation of CD34+CD45−cells
Authors: Padfield Gareth J , Tura-Ceide Olga , Freyer Elizabeth , Barclay G Robin , Turner Marc , Newby David E , Mills Nicholas L
Published: August 2014

Objective

Circulating CD34+CD45−cell concentrations are increased in patients with coronary artery disease, however their pathophysiological significance is unknown. We determined CD34+CD45−cell concentrations following percutaneous coronary intervention (PCI) in order to explore their role in acute vascular injury.

Methods

In a prospective time-course analysis, we quantified using flow cytometry circulating CD34+CD45−cells, traditional CD34+VEGFR-2+putative endothelial progenitor cells (EPCs), CD14+VEGFR−2+Tie-2+angiogenic monocytes and intercellular adhesion molecule expression (CXCR-4 and CD18) in patients, before and during the first week following diagnostic angiography (n=13) or PCI (n=23). Vascular endothelial growth factor-A (VEGF-A) and C reactive protein (CRP) were quantified by ELISA.

Results

Unlike diagnostic angiography, PCI increased circulating neutrophil and CRP concentrations at 24 and 48 h, respectively (p<0.002 for both). CD34+CD45−cell concentrations were unaffected by angiography (p>0.4), but were transiently increased 6 h following PCI (median (IQR) 0.93 (0.43–1.49) vs 1.51 (0.96–2.15)×106 cells/L; p=0.01), returning to normal by 24 h.

This occurred in the absence of any change in serum VEFG-A concentration, adhesion molecule expression on CD34+cells, or mobilisation of traditional EPCs or angiogenic monocytes (p>0.1 for all).

Conclusions

PCI transiently increases circulating CD34+CD45−cells, without increasing CD34+adhesion molecule expression or VEGF-A concentrations, suggesting that CD34+CD45−cells may be mobilised from the vessel wall directly as a result of mechanical injury. Traditional putative EPC and angiogenic monocytes are unaffected by PCI, and are unlikely to be important in the acute response to vascular injury.
Effects of fibroblast growth factor 21 on cell damage in vitro and atherosclerosis in vivo
Authors: Zhu Wenhe , Wang Changwen , Liu Lei , Li Yan , Li Xiaokun , Cai Jianhui , Wang Huiyan
Published: August 2014

Fibroblast growth factor 21 (FGF-21), which is a modulator of glucose and lipid homeostasis, acts as a novel therapeutic reagent for many metabolic perturbations. However, its potential as a treatment for cardiovascular disease, especially atherosclerosis (AS) has not been fully explored. Here, we report that recombinant FGF-21 improves resistance to cell damage from oxidative stress in vitro, and from atherosclerosis in vivo. Human umbilical vein endothelial cells (HUVECs) were induced with H2O2, followed by treatment with high purity recombinant FGF-21. The results indicated that FGF-21 significantly enhanced cell viability and decreased the degree of DNA fragmentation in HUVECs, as caused by H2O2 stress induction. Further studies revealed that FGF-21 inhibited H2O2-induced cell apoptosis by preventing the activation of mitogen-activated protein kinase (MAPK) signaling pathways. In an established rat model, FGF-21 dramatically improved the condition of atherosclerotic rats by decreasing serum levels of total triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and total cholesterol (TC), and by increasing the serum levels of high density lipoprotein cholesterol (HDL-C). FGF-21 also has antioxidant effects in the atherosclerotic rat, such that increased levels of superoxide dismutase, reduced glutathione, and reduced malondialdehyde were observed. These data provide novel insight into the potential use of FGF-21 in the prevention and treatment of human cardiovascular diseases.
Torsion-gravity for Dirac fields and their effective phenomenology
Authors: Fabbri Luca
Published: August 2014

We will consider the torsional completion of gravity for a background filled with Dirac matter fields, studying the weak-gravitational non-relativistic approximation, in view of an assessment about their effective phenomenology: we discuss how the torsionally-induced nonlinear interactions among fermion fields in this limit are compatible with all experiments and remarks on the role of torsion to suggest new physics are given.
Mass hierarchy and physics beyond the Standard Theory
Authors: Antoniadis I.
Published: August 2014

I discuss the status of the mass hierarchy problem and prospects for beyond the Standard Model physics in the light of the Higgs scalar discovery at the LHC and the experimental searches for new physics. In particular, I will discuss in this context low energy supersymmetry and large extra dimensions with low string scale.
One-loop nonbirefringent effects on the electromagnetic vertex in the Standard Model Extension
Authors: Moyotl A. , Novales-Sanchez H. , Toscano J. J. , Tututi E. S.
Published: August 2014

Lorentz violation emerged from a fundamental description of nature may impact, at low energies, the Maxwell sector, so that contributions from such new physics to the electromagnetic vertex would be induced. Particularly, nonbirefringent CPT-even effects from the electromagnetic sector modified by the Lorentz- and CPT-violating Standard Model Extension alter the structure of the free photon propagator. We calculate Lorentz-violating contributions to the electromagnetic vertex, at the one-loop level, by using a modified photon propagator carrying this sort of effects. We take the photon off shell, and find an expression that involves both isotropic and anisotropic effects of nonbirefringent violation of Lorentz invariance. Our analysis of the one-loop vertex function includes gauge invariance, transformation properties under C, P and T, and tree-level contributions from Lorentz-violating nonrenormalizable interactions. These elements add to previous studies of the one-loop contributions to the electromagnetic vertex in the context of Lorentz violation in the photon sector. Finally, we restrict our analysis to the isotropic case and derive a finite contribution from isotropic Lorentz violation to the anomalous magnetic moment of fermions that coincides with the result already reported in the literature.
High-order expanded XAFS Debye–Waller factors of HCP crystals based on classical anharmonic correlated Einstein model
Authors: Hung Nguyen Van , Tien Tong Sy , Duc Ngyen Ba , Vuong Dinh Quoc
Published: August 2014

In this paper, high-order expanded anharmonic effective potential and Debye–Waller factors in X-ray absorption fine structure (XAFS) of hcp crystals have been studied based on classical anharmonic correlated Einstein model. Here XAFS Debye–Waller factors are presented in terms of cumulant expansion up to the fourth order and their analytical expressions have been derived based on classical statistical theory. They contain the parameters of a derived high-order anharmonic effective potential that takes into account all nearest neighbors of absorber and backscattering atoms, where Morse potential is assumed to describe interatomic interaction included in this derived anharmonic effective potential. The dependence of the derived cumulants on atomic vibrations is described by their proportionality to the correlated Einstein frequency. This model avoids full lattice dynamical calculations yet provides good agreement of numerical results for Zn and Cd with experiment at several temperatures.
ANALYSIS AND EVALUATION OF RANDOM PLACEMENT STRATEGIES IN WIRELESS SENSOR NETWORKS
Authors: HAYAJNEH THAIER , KHASAWNEH SAMER
Published: August 2014

Wireless sensor networks (WSNs) are an attractive choice for many applications where sensors are densely and efficiently deployed in an area of interest. For example, in surveillance applications, where deterministic placement is not applicable, the sensors have to be randomly deployed entirely or partially in an area. Whether random or deterministic, the strategy of deploying the sensors has a large impact on the performance of WSNs. In this paper, we propose a systematic methodology for sensors placement based on several random distributions. The quality of deployment is evaluated using a set of proposed measures, the significance of which highly depends on the WSN application. The impact of these deployment strategies on the network performance is thoroughly studied. Moreover, we propose a new hybrid deployment strategy that aims to achieve the best performance based on the suggested deployment quality measures. Both the placement strategies with the deployment quality measures are evaluated using extensive simulations. The results show that the proposed hybrid strategy outperformed other strategies including uniform, random, Gaussian, and exponential distributions. In addition, the paper identifies the family of applications where each of the quality measures is highly critical.
The Usefulness of Enterprise Support Services to Kenyan Manufacturing Micro-Enterprises
Authors: Mulu-Mutuku Milcah , Namusonge Gregory Simiyu , Odhuno Margaret Adhiambo
Published: August 2014

This paper examines the usefulness of support services to manufacturing microenterprises as perceived by the microenterprise owners. In Kenya, there is an emphasis on financial support services at the expense of other services but evidence of their usefulness to the survival and maintenance of manufacturing microenterprises is scarce. Convenience sampling was used to select 172 manufacturing microenterprises that had received any kind of support. Data was collected through researcher-administered questionnaires and analysed using frequencies, percentages and chi-square tests. Results revealed that though financial support was utilised by almost two thirds of the enterprises, over three quarters of the owners did not perceive it as useful, mainly due to the little amount of money given as credit. Training was considered useful to microenterprises, especially in the areas of record keeping and marketing. Social networks, in terms of ROSCAs, friends and relatives, were the major sources of support for manufacturing microenterprises.
Existence of Equilibria in Incomplete Markets with Non-Ordered Preferences
Authors: Yalcin Erkan , Yengin Duygu
Published: August 2014

We consider a two-period exchange economy with a finite set of consumers, states of nature, independent assets and a single consumption good. We prove the existence of competitive equilibrium in incomplete markets, when consumption set is not assumed to be compact, set of assets is linearly independent, and individuals' preferences are not assumed to be complete or transitive. Our study therefore generalizes various results in the existing literature.
Maximum Quadratic Assignment Problem
Authors: Makarychev Konstantin , Manokaran Rajsekar , Sviridenko Maxim
Published: August 2014

We show that for every positive ε > 0, unless NP ⊂ BPQP, it is impossible to approximate the maximum quadratic assignment problem within a factor better than 2

log
1-ε
n

by a reduction from the maximum label cover problem. Our result also implies that Approximate Graph Isomorphism is not robust and is, in fact, 1 - ε versus ε hard assuming the Unique Games Conjecture.

Then, we present an
O
(√n)-approximation algorithm for the problem based on rounding of the linear programming relaxation often used in state-of-the-art exact algorithms.
Stochastically Constrained Ranking and Selection via SCORE
Authors: Pasupathy Raghu , Hunter Susan R. , Pujowidianto Nugroho A. , Lee Loo Hay , Chen Chun-Hung
Published: August 2014

Consider the context of
constrained
Simulation Optimization (SO); that is, optimization problems where the objective and constraint functions are known through dependent Monte Carlo estimators. For solving such problems on
large finite spaces
, we provide an easily implemented sampling framework called SCORE (Sampling Criteria for Optimization using Rate Estimators) that approximates the optimal simulation budget allocation. We develop a general theory, but, like much of the existing literature on ranking and selection, our focus is on SO problems where the distribution of the simulation observations is Gaussian. We first characterize the nature of the optimal simulation budget as a bi-level optimization problem. We then show that under a certain asymptotic limit, the solution to the bi-level optimization problem becomes surprisingly tractable and is expressed through a single intuitive measure, the
score
. We provide an iterative SO algorithm that repeatedly estimates the score and determines how the available simulation budget should be expended across contending systems. Numerical experience with the algorithm resulting from the proposed sampling approximation is very encouraging—in numerous examples of constrained SO problems having 1,000 to 10,000 systems, the optimal allocation is identified to negligible error within a few seconds to 1 minute on a typical laptop computer. Corresponding times to solve the full bi-level optimization problem range from tens of minutes to several hours.
A Design and Analysis Framework for Thermal-Resilient Hard Real-Time Systems
Authors: Hettiarachchi Pradeep M. , Fisher Nathan , Ahmed Masud , Wang Le Yi , Wang Shinan , Shi Weisong
Published: August 2014

We address the challenge of designing predictable real-time systems in an unpredictable thermal environment where environmental temperature may dynamically change (e.g., implantable medical devices). Towards this challenge, we propose a control-theoretic design methodology that permits a system designer to specify a set of hard real-time performance modes under which the system may operate. The system automatically adjusts the real-time performance mode based on the external thermal stress. We show (via analysis, simulations, and a hardware testbed implementation) that our control design framework is stable and control performance is equivalent to previous real-time thermal approaches, even under dynamic temperature changes. A crucial and novel advantage of our framework over previous real-time control is the ability to guarantee hard deadlines even under transitions between modes. Furthermore, our system design permits the calculation of a new metric called
thermal resiliency
that characterizes the maximum external thermal stress that any hard real-time performance mode can withstand. Thus, our design framework and analysis may be classified as a
thermal stress analysis
for real-time systems.
Cache-Related Preemption Delay Analysis for Multilevel Noninclusive Caches
Authors: Chattopadhyay Sudipta , Roychoudhury Abhik
Published: August 2014

With the rapid growth of complex hardware features, timing analysis has become an increasingly difficult problem. The key to solving this problem lies in the precise and scalable modeling of performance-enhancing processor features (e.g., cache). Moreover, real-time systems are often multitasking and use preemptive scheduling, with fixed or dynamic priority assignment. For such systems,
cache related preemption delay
(CRPD) may increase the execution time of a task. Therefore, CRPD may affect the overall schedulability analysis. Existing works propose to bound the value of CRPD in a single-level cache. In this article, we propose a CRPD analysis framework that can be used for a two-level, noninclusive cache hierarchy. In addition, our proposed framework is also applicable in the presence of shared caches. We first show that CRPD analysis faces several new challenges in the presence of a multilevel, noninclusive cache hierarchy. Our proposed framework overcomes all such challenges and we can formally prove the correctness of our framework. We have performed experiments with several subject programs, including an
unmanned aerial vehicle
(UAV) controller and an in-situ space debris monitoring instrument. Our experimental results suggest that we can provide sound and precise CRPD estimates using our framework.
Real-Time Power Management for Embedded M2M Using Intelligent Learning Methods
Authors: Paul Anand
Published: August 2014

In this work, an embedded system working model is designed with one server that receives requests by a requester by a service queue that is monitored by a Power Manager (PM). A novel approach is presented based on reinforcement learning to predict the best policy amidst existing DPM policies and deterministic markovian nonstationary policies (DMNSP). We apply reinforcement learning, namely a computational approach to understanding and automating goal-directed learning that supports different devices according to their DPM. Reinforcement learning uses a formal framework defining the interaction between agent and environment in terms of states, response action, and reward points. The capability of this approach is demonstrated by an event-driven simulator designed using Java with a power-manageable machine-to-machine device. Our experiment result shows that the proposed dynamic power management with timeout policy gives average power saving from 4% to 21% and the novel dynamic power management with DMNSP gives average power saving from 10% to 28% more than already proposed DPM policies.
Testing Properties of Sparse Images
Authors: Ron Dana , Tsur Gilad
Published: August 2014

We initiate the study of testing properties of images that correspond to
sparse
0/1-valued matrices of size
n
×
n
. Our study is related to but different from the study initiated by Raskhodnikova (
Proceedings of RANDOM, 2003
), where the images correspond to
dense
0/1-valued matrices. Specifically, in the model studied by Raskhodnikova, the distance that an image has to a specific property is the number of entries that should be modified in the corresponding matrix so that the property can be obtained, divided by the total number of entries:
n
2
. In the model we consider, the distance is the number of entries that should be modified divided by the actual number of 1’s in the matrix, which may be much smaller than
n
2
. We study several natural properties: connectivity, convexity, monotonicity, and being a line. In all cases, we give testing algorithms with sublinear complexity, and, in some of the cases, we also provide corresponding lower bounds.
FPT is characterized by useful obstruction sets
Authors: Fellows Michael R. , Jansen Bart M. P.
Published: August 2014

Many graph problems were first shown to be fixed-parameter tractable using the results of Robertson and Seymour on graph minors. We show that the combination of finite, computable obstruction sets and efficient order tests is not just one way of obtaining strongly uniform FPT algorithms, but that all of FPT may be captured in this way. Our new characterization of FPT has a strong connection to the theory of kernelization, as we prove that problems with polynomial kernels can be characterized by obstruction sets whose elements have polynomial size. Consequently we investigate the interplay between the sizes of problem kernels and the sizes of the elements of such obstruction sets, obtaining several examples of how results in one area yield new insights in the other. We show how exponential-size minor-minimal obstructions for pathwidth
k
form the crucial ingredient in a novel
or
-cross-composition for
k
-
Pathwidth
, complementing the trivial
and
-composition that is known for this problem. In the other direction, we show that
or
-cross-compositions into a parameterized problem can be used to rule out the existence of efficiently generated quasi-orders on its instances that characterize the
no
-instances by polynomial-size obstructions.
Proteasome inhibition in skeletal muscle cells unmasks metabolic derangements in type 2 diabetes
Authors: Al-Khalili Lubna , de Castro Barbosa Thais , Östling Jörgen , Massart Julie , Cuesta Pablo Garrido , Osler Megan E. , Katayama Mutsumi , Nyström Ann-Christin , Oscarsson Jan , Zierath Juleen R.
Published: August 2014

Two-dimensional difference gel electrophoresis (2-D DIGE)-based proteome analysis has revealed intrinsic insulin resistance in myotubes derived from type 2 diabetic patients. Using 2-D DIGE-based proteome analysis, we identified a subset of insulin-resistant proteins involved in protein turnover in skeletal muscle of type 2 diabetic patients, suggesting aberrant regulation of the protein homeostasis maintenance system underlying metabolic disease. We then validated the role of the ubiquitin-proteasome system (UPS) in myotubes to investigate whether impaired proteasome function may lead to metabolic arrest or insulin resistance. Myotubes derived from muscle biopsies obtained from people with normal glucose tolerance (NGT) or type 2 diabetes were exposed to the proteasome inhibitor bortezomib (BZ; Velcade) without or with insulin. BZ exposure increased protein carbonylation and lactate production yet impaired protein synthesis and UPS function in myotubes from type 2 diabetic patients, marking the existence of an insulin-resistant signature that was retained in cultured myotubes. In conclusion, BZ treatment further exacerbates insulin resistance and unmasks intrinsic features of metabolic disease in myotubes derived from type 2 diabetic patients. Our results highlight the existence of a confounding inherent abnormality in cellular protein dynamics in metabolic disease, which is uncovered through concurrent inhibition of the proteasome system.
Probiotic Bifidobacterium species stimulate human SLC26A3 gene function and expression in intestinal epithelial cells
Authors: Kumar Anoop , Hecht Cameron , Priyamvada Shubha , Anbazhagan Arivarasu N. , Alakkam Anas , Borthakur Alip , Alrefai Waddah A. , Gill Ravinder K. , Dudeja Pradeep K.
Published: August 2014

SLC26A3, or downregulated in adenoma (DRA), plays a major role in mediating Cl− absorption in the mammalian intestine. Disturbances in DRA function and expression have been implicated in intestinal disorders such as congenital Cl− diarrhea and gut inflammation. We previously showed that an increase in DRA function and expression by Lactobacillus acidophilus and its culture supernatant (CS) might underlie antidiarrheal effects of this probiotic strain. However, the effects of Bifidobacterium species, important inhabitants of the human colon, on intestinal Cl−/HCO3− exchange activity are not known. Our current results demonstrate that CS derived from Bifidobacterium breve, Bifidobacterium infantis, and Bifidobacterium bifidum increased anion exchange activity in Caco-2 cells (∼1.8- to 2.4-fold). Consistent with the increase in DRA function, CS also increased the protein, as well as the mRNA, level of DRA (but not putative anion transporter 1). CS of all three Bifidobacterium sp. increased DRA promoter activity (−1,183/+114 bp) in Caco-2 cells (1.5- to 1.8-fold). Furthermore, the increase in DRA mRNA expression by CS of B. breve and B. infantis was blocked in the presence of the transcription inhibitor actinomycin D (5 μM) and the ERK1/2 MAPK pathway inhibitor U0126 (10 μM). Administration of live B. breve, B. infantis, and B. bifidum by oral gavage to mice for 24 h increased DRA mRNA and protein levels in the colon. These data demonstrate an upregulation of DRA via activation of the ERK1/2 pathway that may underlie potential antidiarrheal effects of Bifidobacterium sp.
Differential regulation of placental amino acid transport by saturated and unsaturated fatty acids
Authors: Lager Susanne , Jansson Thomas , Powell Theresa L.
Published: August 2014

Fatty acids are critical for normal fetal development but may also influence placental function. We have previously reported that oleic acid (OA) stimulates amino acid transport in primary human trophoblasts (PHTs). In other tissues, saturated and unsaturated fatty acids have distinct effects on cellular signaling, for instance, palmitic acid (PA) but not OA reduces IκBα expression. We hypothesized that saturated and unsaturated fatty acids differentially affect trophoblast amino acid transport and cellular signaling. To test this hypothesis, PHTs were cultured in docosahexaenoic acid (DHA; 50 μM), OA (100 μM), or PA (100 μM). DHA and OA were also combined to test whether DHA could counteract the OA stimulatory effect on amino acid transport. The effects of fatty acids were compared against a vehicle control. Amino acid transport was measured by isotope-labeled tracers. Activation of inflammatory-related signaling pathways and the mechanistic target of rapamycin (mTOR) pathway were determined by Western blot analysis. Exposure of PHTs to DHA for 24 h reduced amino acid transport and phosphorylation of p38 MAPK, STAT3, mTOR, eukaryotic initiation factor 4E-binding protein 1, and ribosomal protein (rp)S6. In contrast, OA increased amino acid transport and phosphorylation of ERK, mTOR, S6 kinase 1, and rpS6. The combination of DHA with OA increased amino acid transport and rpS6 phosphorylation. PA did not affect amino acid transport but reduced IκBα expression. In conclusion, these fatty acids differentially regulated placental amino acid transport and cellular signaling. Taken together, these findings suggest that dietary fatty acids could alter the intrauterine environment by modifying placental function, thereby having long-lasting effects on the developing fetus.
Cellular Mechanisms of Endoplasmic Reticulum Stress Signaling in Health and Disease. 1. An overview
Authors: Dufey Estefanie , Sepúlveda Denisse , Rojas-Rivera Diego , Hetz Claudio
Published: August 2014

Increased demand on the protein folding capacity of the endoplasmic reticulum (ER) engages an adaptive reaction known as the unfolded protein response (UPR). The UPR regulates protein translation and the expression of numerous target genes that contribute to restore ER homeostasis or induce apoptosis of irreversibly damaged cells. UPR signaling is highly regulated and dynamic and integrates information about the type, intensity, and duration of the stress stimuli, thereby determining cell fate. Recent advances highlight novel physiological outcomes of the UPR beyond specialized secretory cells, particularly in innate immunity, metabolism, and cell differentiation. Here we discuss studies on the fine-tuning of the UPR and its physiological role in diverse organs and diseases.
Endothelial cells but not platelets are the major source of Toll-like receptor 4 in the arterial thrombosis and tissue factor expression in mice
Authors: Ren Meiping , Li Rong , Luo Mao , Chen Ni , Deng Xin , Yan Kai , Zeng Min , Wu Jianbo
Published: August 2014

It is known that Toll-like receptor (TLR)-4 plays an important role in myocardial infarction and atherothrombosis. The role of TLR-4 in arterial thrombosis is undefined. Both TLR-4-deficient ( TLR-4−/−) and wild-type (WT) mice were subjected to FeCl3carotid artery injury, and the time required to form an occlusive thrombus was measured. The mean time to occlusion in TLR-4−/−mice was significantly greater than that in WT mice after injury (303 ± 32 vs. 165 ± 34 s, P < 0.05). Furthermore, when we used a WT or TLR-4−/−-derived platelet reinfusion in a platelet depletion/reinfusion procedure, there was no significant change in the occlusion time and tissue factor (TF) activity in injured arteries between WT mice and platelet-depleted WT mice. Similarly, no significant difference was observed between TLR-4−/−mice and platelet-depleted TLR-4−/−mice for the WT or TLR-4−/−-derived platelet reinfusion. However, TF expression and activity were significantly reduced in the vascular wall of TLR-4−/−mice compared with WT mice. In vivo, lipopolysaccharide accelerated the occlusion time in WT mice but not TLR-4−/−mice. In vitro, LPS-induced TF activity was reduced in endothelial cells of TLR-4−/−mice relative to WT mice. The data demonstrate that TLR-4 contributes to arterial thrombosis formation in vivo and causes increased TF expression and activity in vitro. The results further suggest that the stimulation is mainly derived by endothelial cells but is not due to platelet-derived TLR-4.
Decreasing podocyte number during human kidney intrauterine development
Authors: Crobe A. , Desogus M. , Sanna A. , Fraschini M. , Gerosa C. , Fanni D. , Fanos V. , Van Eyken P. , Faa G.
Published: August 2014

Nephron number at birth has relevant clinical importance with implications for long-term renal health. In recent years, the podocyte depletion hypothesis has emerged as an important concept in kidney pathology. This study was aimed at verifying whether human podocyte number changes significantly during intrauterine life. To this end, 62 subjects with gestational ages ranging from 20 to 41 wk were examined. Kidney sections were stained with hematoxylin and eosin and digitally scanned at ×400 magnification. Subjects were subdivided into fetuses (gestational age ≤24 wk, n = 5), preterms (gestational age ≥25 and ≤36 wk, n = 39), and full-term newborns (gestational age ≥37 wk, n = 18). The average podocyte number of 1,908 ± 645, 1,394 ± 498, and 1,126 ± 256 was, respectively, observed in fetuses, preterms, and full-term newborns. A significant main effect ( P = 0.0051) of gestational age on podocyte number was observed with a significantly lower number in full-term newborns than in fetuses ( P < 0.01). Intragroup variability was also observed. We speculate that variations in podocyte number could be correlated with factors such as drugs and maternal diet occurring during intrauterine life. In conclusion, this study shows, for the first time, a decreasing trend in podocyte number during gestation.