bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design solutions to Address Garment Industry Issues in Egypt
Authors: Abd El Megid Z.M. , Hamdi A. 
Published: March 2016

This research aims to develop design solutions for all the obstacles that workers face during the sewing process, and these solutions are focused on the following: chair design, sewing table design and sewing machine pedal. The design of the workplace includes the order of the components of the work according to the ability of the human body to handle lighting, ventilation and noise. Both the university and research centre consider that the purpose of the research is to examine these obstacles and propose appropriate solutions that could eliminate these occupational diseases that result from the process of sewing, and increase the production rates and quality which will consequently stimulate the Egyptian economy.
The research originates from the work of an integrated regulatory framework of design tools and equipment used for the sewing process and the related work place in accordance with design ergonomic objectives that when achieved, will accelerate the performance and quality of production, and prevent occupational diseases resultant from poor design. The research has also developed a set of recommendations that deal with the deficiencies in the performance of the sewing process, in order to raise the competitiveness of the garment industry in Egypt.
BN‐9, a chimeric peptide with mixed opioid and neuropeptide FF receptor agonistic properties, produces nontolerance‐forming antinociception in mice
Authors: Li Ning , Han Zheng‐lan , Wang Zi‐long , Xing Yan‐hong , Sun Yu‐long , Li Xu‐hui , Song Jing‐jing , Zhang Ting , Zhang Run , Zhang Meng‐na , Xu Biao , Fang Quan , Wang Rui 
Published: March 2016

Background and PurposeNeuropeptide FF (NPFF) behaves as an endogenous opioid‐modulating peptide. In the present study, the opioid and NPFF pharmacophore‐containing chimeric peptide BN‐9 was synthesized and pharmacologically characterized.Experimental ApproachAgonist activities of BN‐9 at opioid and NPFF receptors were characterized in in vitro cAMP assays. Antinociceptive activities of BN‐9 were evaluated in the mouse tail‐flick and formalin tests. Furthermore, its side effects were investigated in rotarod, antinociceptive tolerance, reward and gastrointestinal transit tests.Key ResultsBN‐9 acted as a novel multifunctional agonist at μ, δ, κ, NPFF1 and NPFF2 receptors in cAMP assays. In the tail‐flick test, BN‐9 produced dose‐related antinociception and was approximately equipotent to morphine; this antinociception was blocked by μ and κ receptor antagonists, but not by the δ receptor antagonist. In the formalin test, supraspinal administration of BN‐9 produced significant analgesia. Notably, repeated administration of BN‐9 produced analgesia without loss of potency over 8 days. In contrast, repeated i.c.v. co‐administration of BN‐9 with the NPFF receptor antagonist RF9 produced significant antinociceptive tolerance. Furthermore, i.c.v. BN‐9 induced conditioned place preference. When given by the same routes, BN‐9 had a more than eightfold higher ED50 value for gastrointestinal transit inhibition compared with the ED50 values for antinociception.Conclusions and ImplicationsBN‐9 produced a robust, nontolerance‐forming analgesia with limited inhibition of gastrointestinal transit. As BN‐9 is able to activate both opioid and NPFF systems, this provides an interesting approach for the development of novel analgesics with minimal side effects.
Alleviation of renal mitochondrial dysfunction and apoptosis underlies the protective effect of sitagliptin in gentamicin-induced nephrotoxicity
Authors: Abuelezz Sally A , Hendawy Nevien , Abdel Gawad Sara 
Published: March 2016

Abstract

Objective
This study aimed to investigate the potential protective effect of sitagliptin on gentamicin-induced nephrotoxicity and to elucidate the underlying mechanism.

Methods
Wistar rats were allocated as follows: Gentamicin group: received gentamicin intraperitoneally (100 mg/kg/day); Gentamicin plus sitagliptin group: received simultaneous gentamicin and sitagliptin (30 mg/kg/day orally); Sitagliptin group: received only sitagliptin; and Control group: received saline. Blood urea nitrogen (BUN), serum creatinine, urine protein levels and histopathology of kidney tissues were evaluated. The activity of mitochondrial enzyme complexes reflects the mitochondrial function. Oxidative stress biomarkers and immunohistochemical studies for apoptotic markers caspase-3 and bax were evaluated.

Key findings
Gentamicin causes significant elevation of BUN, serum creatinine and urine proteins. Oxidative stress was revealed by decreased superoxide dismutase activity and catalase activity, glutathione depletion and increased malondialdehyde. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicates mitochondrial dysfunction, along with significant elevation in renal caspase-3 and bax. The aforementioned markers and the histological injury in renal tubules were significantly reversed upon sitagliptin treatment.

Conclusion
These findings suggest that sitagliptin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction and apoptosis in the kidney.
Bioavailability enhancement and pharmacokinetic profile of an anticancer drug ibrutinib by self-nanoemulsifying drug delivery system
Authors: Shakeel Faiyaz , Iqbal Muzaffar , Ezzeldin Essam 
Published: March 2016

Abstract

Objective
The current studies were undertaken to enhance dissolution and bioavailability/pharmacokinetic profile of a newly approved anticancer drug ibrutinib (IBR) via encapsulation of drug into self-nanoemulsifying drug delivery system (SNEDDS).

Methods
Various SNEDDS formulations of IBR were developed by aqueous phase titration method using Capryol-PGMC (oil phase), Tween-20 (surfactant), Carbitol (cosurfactant) and water (aqueous phase). Developed SNEDDS of IBR was evaluated in vitro for various physicochemical properties and drug release profile.

Key findings
Based on lowest droplet size (28.7 ± 3.2 nm), least polydispersity (0.123), optimal values of zeta potential (−32.8 mV) and refractive index (1.336), highest % transmittance (98.7 ± 0.2%), highest drug release profile via dialysis membrane (98.9 ± 8.2% after 48 h) and the presence of lowest concentration of Capryol-PGMC (12% w/w), SNEDDS I1 was selected for in-vivo pharmacokinetic/bioavailability studies in female Wistar rats. In-vivo pharmacokinetic studies in rats showed that optimized SNEDDS I1 controlled the absorption of IBR compared with IBR suspension. The bioavailability of IBR from optimized SNEDDS I1 was enhanced around 2.64 times in comparison with IBR suspension.

Conclusion
These results indicated the potential of developed SNEDDS as an alternative drug delivery system for IBR to enhance its bioavailability and anticancer efficacy.
Quantitative proteomics links metabolic pathways to specific developmental stages of the plant‐pathogenic oomycete Phytophthora capsici
Authors: Pang Zhili , Srivastava Vaibhav , Liu Xili , Bulone Vincent 
Published: March 2016

SummaryThe oomycete Phytophthora capsici is a plant pathogen responsible for important losses to vegetable production worldwide. Its asexual reproduction plays an important role in the rapid propagation and spread of the disease in the field. A global proteomics study was conducted to compare two key asexual life stages of P. capsici, i.e. the mycelium and cysts, to identify stage‐specific biochemical processes. A total of 1200 proteins was identified using qualitative and quantitative proteomics. The transcript abundance of some of the enriched proteins was also analysed by quantitative real‐time polymerase chain reaction. Seventy‐three proteins exhibited different levels of abundance between the mycelium and cysts. The proteins enriched in the mycelium are mainly associated with glycolysis, the tricarboxylic acid (or citric acid) cycle and the pentose phosphate pathway, providing the energy required for the biosynthesis of cellular building blocks and hyphal growth. In contrast, the proteins that are predominant in cysts are essentially involved in fatty acid degradation, suggesting that the early infection stage of the pathogen relies primarily on fatty acid degradation for energy production. The data provide a better understanding of P. capsici biology and suggest potential metabolic targets at the two different developmental stages for disease control.
Deep sequencing leads to the identification of eukaryotic translation initiation factor 5A as a key element in Rsv1‐mediated lethal systemic hypersensitive response to Soybean mosaic virus infection in soybean
Authors: Chen Hui , Adam Arsovski Andrej , Yu Kangfu , Wang Aiming 
Published: March 2016

SummaryRsv1, a single dominant resistance locus in soybean, confers extreme resistance to the majority of Soybean mosaic virus (SMV) strains, but is susceptible to the G7 strain. In Rsv1‐genotype soybean, G7 infection provokes a lethal systemic hypersensitive response (LSHR), a delayed host defence response. The Rsv1‐mediated LSHR signalling pathway remains largely unknown. In this study, we employed a genome‐wide investigation to gain an insight into the molecular interplay between SMV G7 and Rsv1‐genotype soybean. Small RNA (sRNA), degradome and transcriptome sequencing analyses were used to identify differentially expressed genes (DEGs) and microRNAs (DEMs) in response to G7 infection. A number of DEGs, DEMs and microRNA targets, and the interaction network of DEMs and their target mRNAs responsive to G7 infection, were identified. Knock‐down of one of the identified DEGs, the eukaryotic translation initiation factor 5A (eIF5A), diminished the LSHR and enhanced viral accumulation, suggesting the essential role of eIF5A in the G7‐induced, Rsv1‐mediated LSHR signalling pathway. This work provides an in‐depth genome‐wide analysis of high‐throughput sequencing data, and identifies multiple genes and microRNA signatures that are associated with the Rsv1‐mediated LSHR.
LATERAL MOVEMENT OF VEHICLES UNDER WEAK-LANE DISCIPLINE HETEROGENEOUS TRAFFIC
Authors: Mahapatra Geetimukta , Maurya Akhilesh Kumar , Minhans Anil 
Published: March 2016

Safe driving can be achieved by prevention of risky situations which requires the knowledge of the vehicle dynamics and road geometry. The Indian traffic condition is heterogeneous in nature and has weak lane discipline. Hence, vehicles interactions takes place laterally also along with their longitudinal interaction. Vehicles lateral movements (interactions) are quite high due to absence of lane discipline. Therefore, the lateral acceleration of vehicles are an important variable which characterizes the corresponding vehicle dynamics. Several studies have been done by various authors on lateral acceleration in curves, however, lateral movement study of vehicles on straight road section is also important to analyze vehicles’ maneuver in such traffic (i.e. traffic stream with weak lane discipline). Therefore, the present study is about the observation of lateral movements of vehicles over different types of roads in three metropolitan cities of India (Kolkata, Mumbai and Pune) under moderate traffic conditions. Lateral acceleration variation of five different types of vehicles (SUV cars, Sedan cars, Hutch Back cars, motorized three wheeler and two wheeler) have been recorded to investigate its relationship with vehicles longitudinal characteristics (i.e. longitudinal speed) in Indian heterogeneous and weak lane disciplined traffic. Lateral acceleration values quickly rises with initial increase in speed afterward lateral acceleration values reduces with further increase in vehicles longitudinal speed. Impact of vehicle type and locations on the lateral maneuvering of vehicles have also been studied
Pharmacokinetics of Posaconazole Suspension in Lung Transplant Patients with and without Cystic Fibrosis
Authors: Zhang Hongfei , Nguyen M. Hong , Clancy Cornelius J. , Joshi Rujuta , Zhao Wenchen , Ensor Chris , Venkataramanan Raman , Shields Ryan K. 
Published: March 2016

ABSTRACT

Invasive fungal infections (IFIs) are common among lung transplant recipients (LTRs). Posaconazole is an important antifungal agent for both prophylaxis and treatment of IFIs; however, detailed pharmacokinetic data are limited among LTRs, particularly those with cystic fibrosis (CF). Our objective was to conduct a pharmacokinetic study of posaconazole oral suspension among LTRs, with particular attention to patients with CF. We enrolled 20 LTRs, 7 with CF and 13 with other underlying lung diseases. Average daily doses in CF and non-CF patients were 829 and 862 mg, respectively. After ≥5 days of treatment, only 4 patients had average plasma concentrations of >0.7 μg/ml. Average steady-state plasma concentrations were 61% lower in CF patients (0.233 μg/ml) than in non-CF LTRs (0.594 μg/ml;
P
= 0.03). The average dose-normalized plasma area-under-the-curve (AUC) values were also lower in CF (0.007 h·μg/ml) than in non-CF LTRs (0.02 h·μg/ml;
P
= 0.02). The weight-normalized apparent oral clearance values were 2.51 and 0.74 liters/h/kg among CF and non-CF LTRs, respectively (
P
= 0.005). Despite significant interpatient variability, plasma trough concentrations were strongly correlated with posaconazole AUC across all LTRs (
r
2
= 0.95,
P
< 0.0001). Taken together, our study highlights a critical need to incorporate new formulations of posaconazole into prophylaxis and treatment strategies for LTRs, particularly those with CF. Future pharmacokinetic studies of both tablet and intravenous formulations must consider LTR-specific factors and incorporate a therapeutic drug monitoring plan in this patient population.
Pilot Study of the Pharmacokinetics of Cefotaxime in Critically Ill Patients with Acute Kidney Injury Treated with Continuous Renal Replacement Therapy
Authors: Koedijk Joost B. , Valk-Swinkels Corinne G. H. , Rijpstra Tom A. , Touw Daan J. , Mulder Paul G. H. , van der Voort Peter H. J. , van 't Veer Nils E. , van der Meer Nardo J. M. 
Published: March 2016

ABSTRACT
The objective of this study was to describe the pharmacokinetics of cefotaxime (CTX) in critically ill patients with acute kidney injury (AKI) when treated with continuous renal replacement therapy (CRRT) in the intensive care unit (ICU). This single-center prospective observational pilot study was performed among ICU-patients with AKI receiving ≥48 h concomitant CRRT and CTX. CTX was administered intravenously 1,000 mg (bolus) every 6 h for 4 days. CRRT was performed as continuous venovenous hemofiltration (CVVH). Plasma concentrations of CTX and its active metabolite desacetylcefotaxime (DAC) were measured during CVVH treatment. CTX plasma levels and patient data were used to construct concentration-time curves. By using this data, the duration of plasma levels above 4 mg/liter (four times the MIC) was calculated and analyzed. Twenty-seven patients were included. The median CTX peak level was 55 mg/liter (range, 19 to 98 mg/liter), the median CTX trough level was 12 mg/liter (range, 0.8 to 37 mg/liter), and the median DAC plasma level was 15 mg/liter (range, 1.5 to 48 mg/liter). Five patients (19%) had CTX plasma levels below 4 mg/liter at certain time points during treatment. In at least 83% of the time any patient was treated with CTX, the CTX plasma level stayed above 4 mg/liter. A dosing regimen of 1,000 mg of CTX given four times daily is likely to achieve adequate plasma levels in patients with AKI treated with CVVH. Dose reduction might be a risk for suboptimal treatment.
Hepatitis C Virus Genotype 1 to 6 Protease Inhibitor Escape Variants:
In Vitro
Selection, Fitness, and Resistance Patterns in the Context of the Infectious Viral Life Cycle
Authors: Serre Stéphanie B. N. , Jensen Sanne B. , Ghanem Lubna , Humes Daryl G. , Ramirez Santseharay , Li Yi-Ping , Krarup Henrik , Bukh Jens , Gottwein Judith M. 
Published: March 2016

ABSTRACT
Hepatitis C virus (HCV) NS3 protease inhibitors (PIs) are important components of novel HCV therapy regimens. Studies of PI resistance initially focused on genotype 1. Therefore, knowledge about the determinants of PI resistance for the highly prevalent genotypes 2 to 6 remains limited. Using Huh7.5 cell culture-infectious HCV recombinants with genotype 1 to 6 NS3 protease, we identified protease positions 54, 155, and 156 as hot spots for the selection of resistance substitutions under treatment with the first licensed PIs, telaprevir and boceprevir. Treatment of a genotype 2 isolate with the newer PIs vaniprevir, faldaprevir, simeprevir, grazoprevir, paritaprevir, and deldeprevir identified positions 156 and 168 as hot spots for resistance; the Y56H substitution emerged for three newer PIs. Substitution selection also depended on the specific recombinant. The substitutions identified conferred cross-resistance to several PIs; however, most substitutions selected under telaprevir or boceprevir treatment conferred less resistance to certain newer PIs. In a single-cycle production assay, across genotypes, PI treatment primarily decreased viral replication, which was rescued by PI resistance substitutions. The substitutions identified resulted in differential effects on viral fitness, depending on the original recombinant and the substitution. Across genotypes, fitness impairment induced by resistance substitutions was due primarily to decreased replication. Most combinations of substitutions that were identified increased resistance or fitness. Combinations of resistance substitutions with fitness-compensating substitutions either rescued replication or compensated for decreased replication by increasing assembly. This comprehensive study provides insight into the selection patterns and effects of PI resistance substitutions for HCV genotypes 1 to 6 in the context of the infectious viral life cycle, which is of interest for clinical and virological HCV research.
Hepatitis C Virus RNA-Dependent RNA Polymerase Interacts with the Akt/PKB Kinase and Induces Its Subcellular Relocalization
Authors: Valero María Llanos , Sabariegos Rosario , Cimas Francisco J. , Perales Celia , Domingo Esteban , Sánchez-Prieto Ricardo , Mas Antonio 
Published: March 2016

ABSTRACT
Hepatitis C virus (HCV) interacts with cellular components and modulates their activities for its own benefit. These interactions have been postulated as a target for antiviral treatment, and some candidate molecules are currently in clinical trials. The multifunctional cellular kinase Akt/protein kinase B (PKB) must be activated to increase the efficacy of HCV entry but is rapidly inactivated as the viral replication cycle progresses. Viral components have been postulated to be responsible for Akt/PKB inactivation, but the underlying mechanism remained elusive. In this study, we show that HCV polymerase NS5B interacts with Akt/PKB. In the presence of transiently expressed NS5B or in replicon- or virus-infected cells, NS5B changes the cellular localization of Akt/PKB from the cytoplasm to the perinuclear region. Sequestration of Akt/PKB by NS5B could explain its exclusion from its participation in early Akt/PKB inactivation. The NS5B-Akt/PKB interaction represents a new regulatory step in the HCV infection cycle, opening possibilities for new therapeutic options.
Coxiella burnetii Infects Primary Bovine Macrophages and Limits Their Host Cell Response
Authors: Sobotta Katharina , Hillarius Kirstin , Mager Marvin , Kerner Katharina , Heydel Carsten , Menge Christian 
Published: March 2016

ABSTRACTAlthough domestic ruminants have long been recognized as the main source of human Q fever, little is known about the lifestyle that the obligate intracellular Gram-negative bacteriumCoxiella burnetiiadopts in its animal host. Because macrophages are considered natural target cells of the pathogen, we established primary bovine monocyte-derived macrophages (MDM) as anin vitroinfection model to study reservoir host-pathogen interactions at the cellular level. In addition, bovine alveolar macrophages were included to take cell type peculiarities at a host entry site into account. Cell cultures were inoculated with the virulent strain Nine Mile I (NMI; phase I) or the avirulent strain Nine Mile II (NMII; phase II). Macrophages from both sources internalized NMI and NMII. MDM were particularly permissive for NMI internalization, but NMI and NMII replicated with similar kinetics in these cells. MDM responded to inoculation with a general upregulation of Th1-related cytokines such as interleukin-1β (IL-1β), IL-12, and tumor necrosis factor alpha (TNF-α) early on (3 h postinfection). However, inflammatory responses rapidly declined whenC. burnetiireplication started.C. burnetiiinfection inhibited translation and release of IL-1β and vastly failed to stimulate increased expression of activation markers, such as CD40, CD80, CD86, and major histocompatibility complex (MHC) molecules. Such capability of limiting proinflammatory responses may helpCoxiellato protect itself from clearance by the host immune system. The findings provide the first detailed insight intoC. burnetii-macrophage interactions in ruminants and may serve as a basis for assessing the virulence and the host adaptation ofC. burnetiistrains.
Borrelia burgdorferi CheD Promotes Various Functions in Chemotaxis and the Pathogenic Life Cycle of the Spirochete
Authors: Moon Ki Hwan , Hobbs Gerry , Motaleb M. A. 
Published: March 2016

ABSTRACT

Borrelia burgdorferi
possesses a sophisticated chemotaxis signaling system; however, the roles of the majority of the chemotaxis proteins in the infectious life cycle have not yet been demonstrated. Specifically, the role of CheD during host colonization has not been demonstrated in any bacterium. Here, we systematically characterized the
B. burgdorferi
CheD homolog using genetics and biochemical and mouse-tick-mouse infection cycle studies.
Bacillus subtilis
CheD plays an important role in chemotaxis by deamidation of methyl-accepting chemotaxis protein receptors (MCPs) and by increasing the receptor kinase activity or enhancing CheC phosphatase activity, thereby regulating the levels of the CheY response regulator. Our biochemical analysis indicates that
B. burgdorferi
CheD significantly enhances CheX phosphatase activity by specifically interacting with the phosphatase. Moreover, CheD specifically binds two of the six MCPs, indicating that CheD may also modulate the receptor proteins. Although the motility of the
cheD
mutant cells was indistinguishable from that of the wild-type cells, the mutant did exhibit reduced chemotaxis. Importantly, the mutant showed significantly reduced infectivity in C3H/HeN mice via needle inoculation. Mouse-tick-mouse infection assays indicated that CheD is dispensable for acquisition or transmission of spirochetes; however, the viability of
cheD
mutants in ticks is marginally reduced compared to that of the wild-type or complemented
cheD
spirochetes. These data suggest that CheD plays an important role in the chemotaxis and pathogenesis of
B. burgdorferi
. We propose potential connections between CheD, CheX, and MCPs and discuss how these interactions play critical roles during the infectious life cycle of the spirochete.