bluuebunny/crossref_metadata_2025 huggingface dataset:
Fidaxomicin Inhibits Clostridium difficile Toxin A-Mediated Enteritis in the Mouse Ileum
Authors: Koon Hon Wai , Ho Samantha , Hing Tressia C. , Cheng Michelle , Chen Xinhua , Ichikawa Yoshi , Kelly Ciarán P. , Pothoulakis Charalabos
Published: June 2014

Clostridium difficile
infection (CDI) is a common, debilitating infection with high morbidity and mortality.
C. difficile
causes diarrhea and intestinal inflammation by releasing two toxins, toxin A and toxin B. The macrolide antibiotic fidaxomicin was recently shown to be effective in treating CDI, and its beneficial effect was associated with fewer recurrent infections in CDI patients. Since other macrolides possess anti-inflammatory properties, we examined the possibility that fidaxomicin alters
C. difficile
toxin A-induced ileal inflammation in mice. The ileal loops of anesthetized mice were injected with fidaxomicin (5, 10, or 20 μM), and after 30 min, the loops were injected with purified
C. difficile
toxin A or phosphate-buffered saline alone. Four hours after toxin A administration, ileal tissues were processed for histological evaluation (epithelial cell damage, neutrophil infiltration, congestion, and edema) and cytokine measurements.
C. difficile
toxin A caused histologic damage, evidenced by increased mean histologic score and ileal interleukin-1β (IL-1β) protein and mRNA expression. Treatment with fidaxomicin (20 μM) or its primary metabolite, OP-1118 (120 μM), significantly inhibited toxin A-mediated histologic damage and reduced the mean histology score and ileal IL-1β protein and mRNA expression. Both fidaxomicin and OP-1118 reduced toxin A-induced cell rounding in human colonic CCD-18Co fibroblasts. Treatment of ileal loops with vancomycin (20 μM) and metronidazole (20 μM) did not alter toxin A-induced histologic damage and IL-1β protein expression. In addition to its well known antibacterial effects against
C. difficile
, fidaxomicin may possess anti-inflammatory activity directed against the intestinal effects of
C. difficile
toxins.
RecO and RecR Are Necessary for RecA Loading in Response to DNA Damage and Replication Fork Stress
Authors: Lenhart Justin S. , Brandes Eileen R. , Schroeder Jeremy W. , Sorenson Roderick J. , Showalter Hollis D. , Simmons Lyle A.
Published: June 2014

RecA is central to maintaining genome integrity in bacterial cells. Despite the near-ubiquitous conservation of RecA in eubacteria, the pathways that facilitate RecA loading and repair center assembly have remained poorly understood in
Bacillus subtilis
. Here, we show that RecA rapidly colocalizes with the DNA polymerase complex (replisome) immediately following DNA damage or damage-independent replication fork arrest. In
Escherichia coli
, the RecFOR and RecBCD pathways serve to load RecA and the choice between these two pathways depends on the type of damage under repair. We found in
B. subtilis
that the rapid localization of RecA to repair centers is strictly dependent on RecO and RecR in response to all types of damage examined, including a site-specific double-stranded break and damage-independent replication fork arrest. Furthermore, we provide evidence that, although RecF is not required for RecA repair center formation
in vivo
, RecF does increase the efficiency of repair center assembly, suggesting that RecF may influence the initial stages of RecA nucleation or filament extension. We further identify single-stranded DNA binding protein (SSB) as an additional component important for RecA repair center assembly. Truncation of the SSB C terminus impairs the ability of
B. subtilis
to form repair centers in response to damage and damage-independent fork arrest. With these results, we conclude that the SSB-dependent recruitment of RecOR to the replisome is necessary for loading and organizing RecA into repair centers in response to DNA damage and replication fork arrest.
‘A stroke of luck’: a case report of a right-sided cerebellar cerebrovascular accident in a young man
Authors: Waterfield John
Published: June 2014

A 27-year-old man with a history of migraines, epilepsy and pulmonary stenosis presented to the emergency department with symptoms of vomiting, headache, visual disturbance and problems with balance. The team considered the possibility of intracranial pathology and an urgent CT head with contrast showed what appeared to be a large posterior fossa mass with an appearance suggestive of a primary haemangioblastoma, which was causing considerable mass effect. The patient had neurosurgery to relieve the obstruction and a biopsy of the area showed the mass to be an ischaemic infarct rather than a tumour. Further investigations following the stroke confirmed that the cause was due to having antiphospholipid syndrome and a patent foramen ovale. The patient made a good recovery following the operation and remains well.
Awareness of occupational hazards and use of safety measures among welders: a cross-sectional study from eastern Nepal
Authors: Budhathoki Shyam Sundar , Singh Suman Bahadur , Sagtani Reshu Agrawal , Niraula Surya Raj , Pokharel Paras Kumar
Published: June 2014

Objective

The proper use of safety measures by welders is an important way of preventing and/or reducing a variety of health hazards that they are exposed to during welding. There is a lack of knowledge about hazards and personal protective equipments (PPEs) and the use of PPE among the welders in Nepal is limited. We designed a study to assess welders’ awareness of hazards and PPE, and the use of PPE among the welders of eastern Nepal and to find a possible correlation between awareness and use of PPE among them.

Materials and methods

A cross-sectional study of 300 welders selected by simple random sampling from three districts of eastern Nepal was conducted using a semistructured questionnaire. Data regarding age, education level, duration of employment, awareness of hazards, safety measures and the actual use of safety measures were recorded.

Results

Overall, 272 (90.7%) welders were aware of at least one hazard of welding and a similar proportion of welders were aware of at least one PPE. However, only 47.7% used one or more types of PPE. Education and duration of employment were significantly associated with the awareness of hazards and of PPE and its use. The welders who reported using PPE during welding were two times more likely to have been aware of hazards (OR=2.52, 95% CI 1.09 to 5.81) and five times more likely to have been aware of PPE compared with the welders who did not report the use of PPE (OR=5.13, 95% CI 2.34 to 11.26).

Conclusions

The welders using PPE were those who were aware of hazards and PPE. There is a gap between being aware of hazards and PPE (90%) and use of PPE (47%) at work. Further research is needed to identify the underlying factors leading to low utilisation of PPE despite the welders of eastern Nepal being knowledgeable of it.
On the cosmological singularity
Authors: Belinski Vladimir A.
Published: June 2014

The long story of the oscillatory approach to the initial cosmological singularity and its more recent incarnation in multidimensional universe models is told.
From B-modes to quantum gravity and unification of forces
Authors: Krauss Lawrence M. , Wilczek Frank
Published: June 2014

It is commonly anticipated that gravity is subjected to the standard principles of quantum mechanics. Yet some — including Einstein — have questioned that presumption, whose empirical basis is weak. Indeed, recently Dyson has emphasized that no conventional experiment is capable of detecting individual gravitons. However, as we describe, if inflation occurred, the universe, by acting as an ideal graviton amplifier, affords such access. It produces a classical signal, in the form of macroscopic gravitational waves, in response to spontaneous (not induced) emission of gravitons. Thus recent BICEP2 observations of polarization in the cosmic microwave background (CMB) will, if confirmed, provide firm empirical evidence for the quantization of gravity. Their details also support quantitative ideas concerning the unification of strong, electromagnetic and weak forces, and of all these with gravity.
What drives the time evolution of the spacetime geometry?
Authors: Padmanabhan T.
Published: June 2014

I show that in a general, dynamic spacetime, the rate of change of gravitational momentum is related to the difference between the number of bulk and boundary degrees of freedom. All static spacetimes maintain holographic equipartition; i.e. in these spacetimes, the number of degrees of freedom in the boundary is equal to the number of degrees of freedom in the bulk. It is the departure from holographic equipartition that drives the time evolution of the spacetime. This result, which is equivalent to Einstein's equations, provides an elegant, holographic, description of spacetime dynamics.
Study on structures and electronic properties of neutral and anionic TiSin(0,-1)(n = 1–8) clusters using G4 theory
Authors: Lu Jun , Yang Jucai , Xing Zhifei , Ning Hongmei
Published: June 2014

The geometries, electronic structures and energies of small TiSi n species (n = 1–8) and their anions were systematically investigated by G4 theory. The ground-state structures of these clusters are presented herein. For neutral TiSi n (n = 1–8), the spin multiplicities of the ground-state structures are singlet, with the exception of n = 2, which exists in a triplet state. For anionic TiSi n-, the spin multiplicities of the ground-state structures are doublet, with the exception of n = 2, which is quartet. The adiabatic electron affinities for TiSi n are estimated to be 1.31 eV ( TiSi ), 1.46 eV ( TiSi 2), 1.53 eV ( TiSi 3), 1.71 eV ( TiSi 4), 2.06 eV ( TiSi 5), 2.16 eV ( TiSi 6), 2.20 eV ( TiSi 7) and 2.39 eV ( TiSi 8). In comparison with the available experimental data, the calculated adiabatic electron affinities differ from experimental values by an average absolute deviation of only 0.03 eV. Additionally, the dissociation energies of Ti atoms from TiSi n, and Si atoms from TiSi n and Si n clusters are estimated to examine relative stabilities.
Mean Square Convergent Particle Swarm Optimization Based on Fuzzy Migratory Operator
Authors: Cai Guorong , Li Shaozi , Chen Shuili , Su Songzhi
Published: June 2014

This paper proposes a novel cooperative particle swarm PSO (particle swarm optimization)algorithm, which makes the use of the property of the fuzzy migratory operator to achieve the optimization performance. To avoid the drawback of the possibility of being trapped in local optimum, the proposed method uses a migrate-based strategy to control the diversity of the swarm. During the iteration aspect of the algorithm, the comprehensive fuzzy evaluation method is employed to evaluate the diversity. Furthermore, the fuzzy migratory operator is then used to remove bad particles once the diversity is far from ideal. Moreover, we have proven that the proposed migrate strategy is a mean square convergence. The experimental results conducted on three benchmark functions also proved that the proposed method is superior to that of classical PSO and conventional cooperative PSO, where the comparison has been based primarily upon the global optimality, solution accuracy and diversity value.
ARGININE- AND ACRYLONITRILE-MODIFIED CHITOSAN NANOPARTICLES FOR ANTICANCER DRUG DELIVERY
Authors: YIN LIANCHENG , SU TING , CHANG JING , LIU RONG , HE BIN , GU ZHONGWEI
Published: June 2014

Chitosan (CS) is an excellent natural biodegradable and biocompatible polymer for biomedical applications, however, its poor solubility in water or organic solvents limits its applications in drug delivery. In order to resolve this problem, chitosan was modified with acrylonitrile (AN) and arginine (Arg), the modified chitosan (AN–CS–Arg) was characterized by 1 H NMR and Fourier transform infrared (FTIR). The AN–CS–Arg was self-assembled into nanoparticles to encapsulate anticancer drug doxorubicin (DOX). The size and morphology of the blank and drug-loaded AN–CS–Arg (AN–CS–Arg/DOX) nanoparticles were measured by dynamic light scattering (DLS), scanning electron microscopy (SEM) and atomic force microscopy (AFM). The mean size of both blank and AN–CS–Arg/DOX nanoparticles were around 50 nm and 170 nm, respectively. The drug-loading content was about 12%. The release profile of AN–CS–Arg/DOX nanoparticles was investigated in vitro, 80% encapsulated DOX could be released within 80 h. The AN–CS–Arg nanoparticles were nontoxic to both NIH 3T3 fibroblasts and HepG2 cancer cells. The cellular uptake of the AN–CS–Arg nanoparticles was trafficked via Confocal Laser Scanning Microscopy and Flow Cytometry, both results showed that the AN–CS–Arg nanoparticles could be internalized in HepG2 cells efficiently. The IC50 of AN–CS–Arg/DOX nanoparticles to HepG2 cancer cells was 10.0 μg/mL. The AN–CS–Arg nanoparticles are potential carriers for anticancer drug delivery.
Large strain and pyroelectric properties of Pb(Mg1/3Nb2/3)O3–PbTiO3 ceramics prepared by partial oxalate route
Authors: Fang Bijun , Qian Kun , Chen Zhihui , Yuan Ningyi , Ding Jianning , Zhao Xiangyong , Xu Haiqing , Luo Haosu
Published: June 2014

Partial oxalate route is an efficient method to synthesize complex perovskite ferroelectric ceramics, in which the synthesized (1 - x) Pb ( Mg 1/3 Nb 2/3) O 3–x PbTiO 3 (PMN–PT) ceramics exhibit rather pure perovskite structure, densified microstructure morphology, and excellent dielectric and piezoelectric properties. The PMN–PT ceramics synthesized by the partial oxalate route exhibit rather symmetric strain–electric (S–E) field hysteresis loops, where the strain is large and far less than saturated at 2 kV/mm. The PMN–PT ceramics exhibit excellent pyroelectric properties, in which the values of the pyroelectric coefficient and the calculated pyroelectric figures of merit maintain almost stable over the frequency range of 100 Hz–2000 Hz, and vary differently depending on composition with the increase of temperature. Such investigations reveal that high-performance piezoelectric and pyroelectric devices can be prepared by the partial oxalate route in low production cost.
Oxidation front and oxygen transfer in the fractured zone surrounding the Meuse/Haute-Marne URL drifts in the Callovian–Oxfordian argillaceous rock
Authors: Vinsot Agnès , Leveau François , Bouchet Alain , Arnould Apolline
Published: June 2014

Deep argillaceous rocks are reducing environments. When exposed to air, reduced minerals of these rocks react with oxygen, modifying the surrounding chemical conditions. Thus, oxidation is an issue in studies about the confining properties of such rocks in the framework of geological disposal projects for radioactive waste. Previous studies in several underground research laboratories (URLs) in argillaceous rocks have shown that oxidation reactions mainly occurred in the excavation-induced fracture network surrounding the drifts. In the Callovian–Oxfordian argillaceous rock, at −490 m in drifts from the Meuse/Haute-Marne URL, oxidized features were systematically looked for in 115 borehole cores. The concerned drifts were of various ages, from a few days to 6.5 years. After 5 months, oxidized features were encountered in numerous excavation-induced extensional fractures. In excavation-induced shear fractures, oxidized features were observed in a few borehole cores after 2 years, and they became frequent after 6 years. In all cases, the oxidized features observed were found on the fracture walls or were connected to them, and were less than 1.8 m from the drift walls. These observations about the oxidation front and its evolution over time provide insights regarding the properties of excavation-induced fractures with respect to oxygen transfer.
Discovering General Prominent Streaks in Sequence Data
Authors: Zhang Gensheng , Jiang Xiao , Luo Ping , Wang Min , Li Chengkai
Published: June 2014

This article studies the problem of prominent streak discovery in sequence data. Given a sequence of values, a prominent streak is a long consecutive subsequence consisting of only large (small) values, such as consecutive games of outstanding performance in sports, consecutive hours of heavy network traffic, and consecutive days of frequent mentioning of a person in social media. Prominent streak discovery provides insightful data patterns for data analysis in many real-world applications and is an enabling technique for computational journalism. Given its real-world usefulness and complexity, the research on prominent streaks in sequence data opens a spectrum of challenging problems.

A baseline approach to finding prominent streaks is a quadratic algorithm that exhaustively enumerates all possible streaks and performs pairwise streak dominance comparison. For more efficient methods, we make the observation that prominent streaks are in fact skyline points in two dimensions—streak interval length and minimum value in the interval. Our solution thus hinges on the idea to separate the two steps in prominent streak discovery: candidate streak generation and skyline operation over candidate streaks. For candidate generation, we propose the concept of local prominent streak (LPS). We prove that prominent streaks are a subset of LPSs and the number of LPSs is less than the length of a data sequence, in comparison with the quadratic number of candidates produced by the brute-force baseline method. We develop efficient algorithms based on the concept of LPS. The nonlinear local prominent streak (NLPS)-based method considers a superset of LPSs as candidates, and the linear local prominent streak (LLPS)-based method further guarantees to consider only LPSs. The proposed properties and algorithms are also extended for discovering general top-
k
, multisequence, and multidimensional prominent streaks. The results of experiments using multiple real datasets verified the effectiveness of the proposed methods and showed orders of magnitude performance improvement against the baseline method.
Optimizing Data Misuse Detection
Authors: Shabtai Asaf , Bercovitch Maya , Rokach Lior , Elovici Yuval
Published: June 2014

Data misuse may be performed by entities such as an organization's employees and business partners who are granted access to sensitive information and misuse their privileges. We assume that users can be either trusted or untrusted. The access of untrusted parties to data objects (e.g., client and patient records) should be monitored in an attempt to detect misuse. However, monitoring data objects is resource intensive and time-consuming and may also cause disturbance or inconvenience to the involved employees. Therefore, the monitored data objects should be carefully selected. In this article, we present two optimization problems carefully designed for selecting specific data objects for monitoring, such that the detection rate is maximized and the monitoring effort is minimized. In the first optimization problem, the goal is to select data objects for monitoring that are accessed by at most
c
trusted agents while ensuring access to at least
k
monitored objects by each untrusted agent (both
c
and
k
are integer variable). As opposed to the first optimization problem, the goal of the second optimization problem is to select monitored data objects that maximize the number of monitored data objects accessed by untrusted agents while ensuring that each trusted agent does not access more than
d
monitored data objects (
d
is an integer variable as well). Two efficient heuristic algorithms for solving these optimization problems are proposed, and experiments were conducted simulating different scenarios to evaluate the algorithms’ performance. Moreover, we compared the heuristic algorithms’ performance to the optimal solution and conducted sensitivity analysis on the three parameters (
c
,
k
, and
d
) and on the ratio between the trusted and untrusted agents.
Microcomputations as Micropayments in Web-based Services
Authors: Karame Ghassan O. , Francillon Aurélien , Budilivschi Victor , Čapkun Srdjan , Čapkun Vedran
Published: June 2014

In this article, we propose a new micropayment model for nonspecialized commodity web-services based on microcomputations. In our model, a user that wishes to access online content (offered by a website) does not need to register or pay to access the website; instead, he will accept to run microcomputations on behalf of the service provider in exchange for access to the content. These microcomputations can, for example, support ongoing computing projects that have clear social benefits (e.g., projects relating to medical research) or can contribute towards commercial computing projects. We analyze the security and privacy of our proposal and we show that it preserves the privacy of users. We argue that this micropayment model is economically and technically viable and that it can be integrated in existing distributed computing frameworks (e.g., the BOINC platform). In this respect, we implement a prototype of a system based on our model and we deploy our prototype on Amazon Mechanical Turk to evaluate its performance and usability given a large number of users. Our results show that our proposed scheme does not affect the browsing experience of users and is likely to be used by a non-trivial proportion of users. Finally, we empirically show that our scheme incurs comparable bandwidth and CPU consumption to the resource usage incurred by online advertisements featured in popular websites.
Dissecting Darknets
Authors: Chu Xiaowen , Chen Xiaowei , Jia Adele Lu , Pouwelse Johan A. , Epema Dick H. J.
Published: June 2014

BitTorrent (BT) plays an important role in Internet content distribution. Because public BTs suffer from the free-rider problem, Darknets are becoming increasingly popular, which use Sharing Ratio Enforcement to increase their efficiency. We crawled and traced 17 Darknets from September 2009 to February 2011, and obtained datasets about over 5 million torrents. We conducted a broad range of measurements, including traffic, sites, torrents, and users activities. We found that some of the features of Darknets are noticeably different from public BTs. The results of our study reflect both macroscopic and microscopic aspects of the overall ecosystem of BitTorrent Darknets.
Efficient Power and Channel Allocation Strategies in Cooperative Potential Games for Cognitive Radio Sensor Networks
Authors: Minhas Qurratul-Ain , Tawhid Mohamed A. , Mahmood Hasan
Published: June 2014

In wireless cognitive sensor networks, natural antagonism arises among unlicensed users when nodes opportunistically compete for unused frequency bands and the operations are seriously hampered by acute scarcity of resources. The transmitted power, which is inherently pertinent to the signal-to-interference-plus-noise ratio (SINR), cognition methodology, and lack of central management, must be preserved for longer network lifetime. In the midst of this struggle to acquire desired frequency band, where the performance of the entire network is dependent upon the behavior and etiquette exhibited by individual nodes, it is pivotal to introduce an effective cooperation mechanism in order to improve the vital network parameters. In this paper, we employ the concepts of game theory to develop an efficient and sustainable cooperation mechanism for efficient cognition and improved spectrum utilization. The nodes exhibit autochthonous pattern in opting for spectrum choices, which results in acceptable level of cooperation and consequently improvement in spectrum utilization. In order to achieve this global benefit, the users are motivated to carefully analyze the impact of their own choice in selecting a channel for transmission and its peers.
Radiofrequency Ablation for Early-Stage Nonsmall Cell Lung Cancer
Authors: Hiraki Takao , Gobara Hideo , Iguchi Toshihiro , Fujiwara Hiroyasu , Matsui Yusuke , Kanazawa Susumu
Published: June 2014

This review examines studies of radiofrequency ablation (RFA) of nonsmall cell lung cancer (NSCLC) and discusses the role of RFA in treatment of early-stage NSCLC. RFA is usually performed under local anesthesia with computed tomography guidance. RFA-associated mortality, while being rare, can result from pulmonary events. RFA causes pneumothorax in up to 63% of cases, although pneumothorax requiring chest drainage occurs in less than 15% of procedures. Other severe complications are rare. After RFA of stage I NSCLC, 31–42% of patients show local progression. The 1-, 2-, 3-, and 5-year overall survival rates after RFA of stage I NSCLC were 78% to 100%, 53% to 86%, 36% to 88%, and 25% to 61%, respectively. The median survival time ranged from 29 to 67 months. The 1-, 2-, and 3-year cancer-specific survival rates after RFA of stage I NSCLC were 89% to 100%, 92% to 93%, and 59% to 88%, respectively. RFA has a higher local failure rate than sublobar resection and stereotactic body radiation therapy (SBRT). Therefore, RFA may currently be reserved for early-stage NSCLC patients who are unfit for sublobar resection or SBRT. Various technologies are being developed to improve clinical outcomes of RFA for early-stage NSCLC.
Thermal-Acoustic Fatigue of a Multilayer Thermal Protection System in Combined Extreme Environments
Authors: Liu Liu , Guo Qiong , He Tiren
Published: June 2014

In order to ensure integrity of thermal protection system (TPS) structure for hypersonic vehicles exposed to severe operating environments, a study is undertaken to investigate the response and thermal-acoustic fatigue damage of a representative multilayer TPS structure under combined thermal and acoustic loads. An unsteady-state flight of a hypersonic vehicle is composed of a series of steady-state snapshots, and for each snapshot an acoustic load is imposed to a static steady-state TPS structure. A multistep thermal-acoustic fatigue damage intensity analysis procedure is given and consists of a heat transfer analysis, a nonlinear thermoelastic analysis, and a random response analysis under a combined loading environment and the fatigue damage intensity has been evaluated with two fatigue analysis techniques. The effects of thermally induced deterministic stress and nondeterministic dynamic stress due to the acoustic loading have been considered in the damage intensity estimation with a maximum stress fatigue model. The results show that the given thermal-acoustic fatigue intensity estimation procedure is a viable approach for life prediction of TPS structures under a typical mission cycle with combined loadings characterized by largely different time-scales. A discussion of the effects of the thermal load, the acoustic load, and fatigue analysis methodology on the fatigue damage intensity has been provided.
An Optimized Forecasting Approach Based on Grey Theory and Cuckoo Search Algorithm: A Case Study for Electricity Consumption in New South Wales
Authors: Jiang Ping , Zhou Qingping , Jiang Haiyan , Dong Yao
Published: June 2014

With rapid economic growth, electricity demand is clearly increasing. It is difficult to store electricity for future use; thus, the electricity demand forecast, especially the electricity consumption forecast, is crucial for planning and operating a power system. Due to various unstable factors, it is challenging to forecast electricity consumption. Therefore, it is necessary to establish new models for accurate forecasts. This study proposes a hybrid model, which includes data selection, an abnormality analysis, a feasibility test, and an optimized grey model to forecast electricity consumption. First, the original electricity consumption data are selected to construct different schemes (Scheme 1: short-term selection and Scheme 2: long-term selection); next, the iterative algorithm (IA) and cuckoo search algorithm (CS) are employed to select the best parameter of GM(1,1). The forecasted day is then divided into several smooth parts because the grey model is highly accurate in the smooth rise and drop phases; thus, the best scheme for each part is determined using the grey correlation coefficient. Finally, the experimental results indicate that the GM(1,1) optimized using CS has the highest forecasting accuracy compared with the GM(1,1) and the GM(1,1) optimized using the IA and the autoregressive integrated moving average (ARIMA) model.
A Chinese Herbal Medicine, Jia-Wei-Xiao-Yao-San, Prevents Dimethylnitrosamine-Induced Hepatic Fibrosis in Rats
Authors: Chien Shu-Chen , Chang Wei-Chiao , Lin Pu-Hua , Chang Wei-Pin , Hsu Shih-Chung , Chang Jung-Chen , Wu Ya-Chieh , Pei Jin-Kuo , Lin Chia-Hsien
Published: June 2014

Jia-wei-xiao-yao-san (JWXYS) is a traditional Chinese herbal medicine that is widely used to treat neuropsychological disorders. Only a few of the hepatoprotective effects of JWXYS have been studied. The aim of this study was to investigate the hepatoprotective effects of JWXYS on dimethylnitrosamine- (DMN-) induced chronic hepatitis and hepatic fibrosis in rats and to clarify the mechanism through which JWXYS exerts these effects. After the rats were treated with DMN for 3 weeks, serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels were significantly elevated, whereas the albumin level decreased. Although DMN was continually administered, after the 3 doses of JWXYS were orally administered, the SGOT and SGPT levels significantly decreased and the albumin level was significantly elevated. In addition, JWXYS treatment prevented liver fibrosis induced by DMN. JWXYS exhibited superoxide-dismutase-like activity and dose-dependently inhibited DMN-induced lipid peroxidation and xanthine oxidase activity in the liver of rats. Our findings suggest that JWXYS exerts antifibrotic effects against DMN-induced chronic hepatic injury. The possible mechanism is at least partially attributable to the ability of JWXYS to inhibit reactive-oxygen-species-induced membrane lipid peroxidation.
Nonionic Surfactant Vesicles in Ocular Delivery: Innovative Approaches and Perspectives
Authors: Sahoo Ranjan Ku. , Biswas Nikhil , Guha Arijit , Sahoo Nityananda , Kuotsu Ketousetuo
Published: June 2014

With the recent advancement in the field of ocular therapy, drug delivery approaches have been elevated to a new concept in terms of nonionic surfactant vesicles (NSVs), that is, the ability to deliver the therapeutic agent to a patient in a staggered profile. However the major drawbacks of the conventional drug delivery system like lacking of permeability through ocular barrier and poor bioavailability of water soluble drugs have been overcome by the emergence of NSVs. The drug loaded NSVs (DNSVs) can be fabricated by simple and cost-effective techniques with improved physical stability and enhance bioavailability without blurring the vision. The increasing research interest surrounding this delivery system has widened the areas of pharmaceutics in particular with many more subdisciplines expected to coexist in the near future. This review gives a comprehensive emphasis on NSVs considerations, formulation approaches, physicochemical properties, fabrication techniques, and therapeutic significances of NSVs in the field of ocular delivery and also addresses the future development of modified NSVs.
Local Intracoronary Eptifibatide versus Mechanical Aspiration in Patients with Acute ST-Elevation Myocardial Infarction
Authors: Hamza Mohamed A. , Galal Ayman , Suweilam Salwa , Ismail Mohamed
Published: June 2014

Objectives. We compared local delivery of intracoronary eptifibatide via perfusion catheter to thrombus aspiration in primary PCI.Background. Perfusion catheter increases local concentration of the drugs at the culprit site and prolongs their residency time.Methods. 75 patients with acute STEMI were randomized to three groups: 25 received local intracoronary eptifibatide and verapamil via perfusion catheter; 25 patients were managed by Diver CE thrombectomy device and 25 patients by primary PCI without thrombus aspiration. Primary end point was assessment of postprocedural TIMI flow, MPG, and corrected TIMI frame count (cTFC) in the culprit vessel.Results. Perfusion catheter was superior to thrombus aspiration and conventional PCI as regards MBG (68% versus 36% in Diver CE and 20% in the control arm;Pvalue = 0.002), with shorter cTFC rates than thrombectomy and control groups (20.76±4.44versus26.68±8.40and28.16±5.96,resp.;P=0.001). TIMI flow was not different between the 3 groups. Eptifibatide led to less time to peak CK (13.12 hours versus 16.5 and 19.5 hours, respectively,Pvalue = 0.001).Conclusion. Local intracoronary eptifibatide by perfusion catheter reduces thrombus burden with better results in microvascular perfusion assessed by cTFC and MBG compared to aspiration device or conventional PCI.
Downregulation of Angiogenesis Factors, VEGF and PDGF, after Rapid IgE Desensitization and Oral Immunotherapy in Children with Food Allergy
Authors: Poza-Guedes Paloma , Barrios Yvelise , Fuentes Victoria , Franco Andres , Sánchez-Machín Inmaculada , Alonso Elena , González Pérez Ruperto , Infante Sonsoles , Zapatero Lydia , Matheu Víctor
Published: June 2014

Background. Angiogenesis has a key role in several conditions and is regulated by several factors such as the platelet-derived growth factor (PDGF) or the vascular endothelial growth factor (VEGF). The goal of this study was to investigate the possible role of PDGF and VEGF in a group of patients with severe food allergy.Methods. We design a prospective longitudinal study (n=30) with patients with persistent cow’s milk proteins (CMP) allergy. After achieving a CMP rush desensitization protocol, a clinical followup including SPT and blood samples to determine sIgE, protein levels, PDGF, and VEGF-A and a panel of the most representative Th1, Th2, Treg, and Th17cytokines were also monitored.Results. Baseline levels of PDGF and VEGF in the CMP allergic patients (1170 pg/mL and 253 pg/mL) were different compared to those nonallergic CMP control subjects (501 pg/mL and 108 pg/mL). Both PDGF and VEGF were significantly downregulated (P<0.05) 6 months after completion of the CMP desensitization process and remained significantly decreased 12 months later.Conclusion. The present study shows a significant increase of PDGF and VEGF in anaphylaxis suffering children compared to a control group. Interestingly, both VEGF and PDGF were significantly downregulated after completing a full CMP rush IgE desensitization.
Pretreatment of Cottage Cheese to Enhance Biogas Production
Authors: Prabhudessai Vidhya , Salgaonkar Bhakti , Braganca Judith , Mutnuri Srikanth
Published: June 2014

This study evaluated the possibility of pretreating selected solid fraction of an anaerobic digester treating food waste to lower the hydraulic retention time and increase the methane production. The study investigated the effect of different pretreatments (thermal, chemical, thermochemical and enzymatic) for enhanced methane production from cottage cheese. The most effective pretreatments were thermal and enzymatic. Highest solubilisation of COD was observed in thermal pretreatment, followed by thermochemical. In single enzyme systems, lipase at low concentration gave significantly higher methane yield than for the experiments without enzyme additions. The highest lipase dosages decreased methane yield from cottage cheese. However, in case of protease enzyme an increase in concentration of the enzyme showed higher methane yield. In the case of mixed enzyme systems, pretreatment at 1 : 2 ratio of lipase : protease showed higher methane production in comparison with 1 : 1 and 2 : 1 ratios. Methane production potentials for different pretreatments were as follows: thermal 357 mL/g VS, chemical 293 mL/g VS, and thermochemical 441 mL/g VS. The average methane yield from single enzyme systems was 335 mL/g VS for lipase and 328 mL/g VS for protease. Methane potentials for mixed enzyme ratios were 330, 360, and 339 mL/g VS for 1 : 1, 1 : 2, and 2 : 1 lipase : protease, respectively.
Relationship betweenLeishmaniaIFAT Titer and Clinicopathological Manifestations (Clinical Score) in Dogs
Authors: Proverbio Daniela , Spada Eva , Bagnagatti de Giorgi Giada , Perego Roberta , Valena Emanuela
Published: June 2014

During canine leishmaniasis (CanL) due toLeishmania infantum,high levels of antibodies production are associated with the presence of various clinical signs, because of the deposition of soluble immune complexes in organs and tissues. The immunofluorescence antibody test (IFAT) is one of the most commonly used techniques for detection of anti-Leishmaniaantibodies. The purpose of this study was to assess whether there is a correlation between clinical signs and IFAT titers in dogs naturally infected withLeishmania. A retrospective study was performed on medical records of 49 dogs diagnosed with CanL. Information extracted from the medical records of each dog with CanL was clinical score, IFAT titer, serum total protein (TP), gamma globulin (IgG) and creatinine concentration, and protein creatinine ratio in urine sample (UP/UC) at each follow-up examination. Results show that dogs with highest IFAT titers recorded had higher mean clinical scores indicating a positive relationship (P<0.0001) between anti-Leishmaniaantibodies (IgG) and clinical manifestations, which becomes more evident in severe clinical forms of canine leishmaniasis. Higher TP and IgG serum concentrations were recorded in dogs with higher clinical scores. Significant association was observed between UP/UC and the IFAT titer (P=0.004).
Development of Pathological Diagnostics of Human Kidney Cancer by Multiple Staining Using New Fluorescent Fluolid Dyes
Authors: Wuxiuer Dilibaier , Zhu Yun , Ogaeri Takunori , Mizuki Keiji , Kashiwa Yuki , Nishi Kentaro , Isobe Shin-ichiro , Aoyagi Tei-ichiro , Kiyama Ryoiti
Published: June 2014

New fluorescent Fluolid dyes have advantages over others such as stability against heat, dryness, and excess light. Here, we performed simultaneous immunostaining of renal tumors, clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, acquired cystic disease-associated RCC (ACD-RCC), and renal angiomyolipoma (AML), with primary antibodies against Kank1, cytokeratin 7 (CK7), and CD10, which were detected with secondary antibodies labeled with Fluolid-Orange, Fluolid-Green, and Alexa Fluor 647, respectively. Kank1 was stained in normal renal tubules, papillary RCC, and ACD-RCC, and weakly or negatively in all other tumors. CK7 was positive in normal renal tubules, papillary RCC, and ACD-RCC. In contrast, CD10 was expressed in renal tubules and clear cell RCC, papillary RCC, AML, and AC-RCC, and weakly in chromophobe RCC. These results may contribute to differentiating renal tumors and subtypes of RCCs. We also examined the stability of fluorescence and found that fluorescent images of Fluolid dyes were identical between a tissue section and the same section after it was stored for almost three years at room temperature. This indicates that tissue sections can be stored at room temperature for a relatively long time after they are stained with multiple fluorescent markers, which could open a door for pathological diagnostics.
Capitalizing on the Autophagic Response for Treatment of Liver Disease Caused by Alpha-1-Antitrypsin Deficiency and Other Genetic Diseases
Authors: Chu Andrew S. , Perlmutter David H. , Wang Yan
Published: June 2014

Alpha-1-antitrypsin deficiency (ATD) is one of the most common genetic causes of liver disease and is a prototype of liver diseases caused by the pathologic accumulation of aggregated mutant alpha-1-antitrypsin Z (ATZ) within liver cells. In the case of ATD-associated liver disease, the resulting “gain-of-function” toxicity can lead to serious clinical manifestations, including cirrhosis and hepatocellular carcinoma. Currently, the only definitive therapy for ATD-associated liver disease is liver transplantation, but recent efforts have demonstrated the exciting potential for novel therapies that target disposal of the mutant protein aggregates by harnessing a cellular homeostasis mechanism called autophagy. In this review, we will summarize research advances on autophagy and genetic liver diseases. We will discuss autophagy enhancer strategies for liver disease due to ATD and another genetic liver disease, inherited hypofibrinogenemia, caused by the proteotoxic effects of a misfolded protein. On the basis of recent evidence that autophagy plays a role in cellular lipid degradation, we also speculate about autophagy enhancer strategies for treatment of hepatic lipid storage diseases such as cholesterol ester storage disease.
Solubility and Bioavailability Enhancement of Poorly Aqueous Soluble Atorvastatin:In Vitro,Ex Vivo, andIn VivoStudies
Authors: Rodde Madhuri S. , Divase Ganesh T. , Devkar Tejas B. , Tekade Avinash R.
Published: June 2014

The objective of this investigation was to improve the solubility of the poorly water soluble drug atorvastatin (ATR), using solid dispersion (SD) techniques, with Neem Gum (NG) as a hydrophilic carrier. The effects of the polymer concentration and method of preparation on the solubility and dissolution rate were studied. The results showed that the solubility of ATR increases with increasing NG concentration. However, dissolution rate of ATR from its SD was dependent on the method used to prepare SD. Anin vitrodrug release study revealed that the solvent evaporation technique is a more convenient and effective method of preparing SD than kneading method. The SD was characterized using DSC, SEM, and XRD study. Anin vivostudy was performed in which the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase inhibition activity was measured. A significant reduction in HMG CoA reductase activity was observed with SD of ATR compared with the plain drug. Anex vivoabsorption study was carried out using modified apparatus developed in our laboratory. Thein vitrodrug release andin vivoandex vivostudies clearly demonstrated the potential of hydrophilic NG in enhancing the solubility, dissolution rate, and bioavailability of ATR.
Complications of Trauma Patients Admitted to the ICU in Level I Academic Trauma Centers in the United States
Authors: Mondello Stefania , Cantrell Amy , Italiano Domenico , Fodale Vincenzo , Mondello Patrizia , Ang Darwin
Published: June 2014

Background. The aims of this study were to evaluate the complications that occur after trauma and the characteristics of individuals who develop complications, to identify potential risk factors that increase their incidence, and finally to investigate the relationship between complications and mortality.Methods. We did a population-based retrospective study of trauma patients admitted to ICUs of a level I trauma center. Logistic regression analyses were performed to determine independent predictors for complications.Results. Of the 11,064 patients studied, 3,451 trauma patients developed complications (31.2%). Complications occurred significantly more in younger male patients. Length of stay was correlated with the number of complications(R=0.435,P<0.0001). The overall death rate did not differ between patients with or without complications. The adjusted odds ratio (OR) of developing complication for patients over age 75 versus young adults was 0.7(P<0.0001). Among males, traumatic central nervous system (CNS) injury was an important predictor for complications (adjusted OR 1.24).Conclusions. Complications after trauma were found to be associated with age, gender, and traumatic CNS injury. Although these are not modifiable factors, they may identify subjects at high risk for the development of complications, allowing for preemptive strategies for prevention.
Fractional Dynamics of Computer Virus Propagation
Authors: Pinto Carla M. A. , Tenreiro Machado J. A.
Published: June 2014

We propose a fractional model for computer virus propagation. The model includes the interaction between computers and removable devices. We simulate numerically the model for distinct values of the order of the fractional derivative and for two sets of initial conditions adopted in the literature. We conclude that fractional order systems reveal richer dynamics than the classical integer order counterpart. Therefore, fractional dynamics leads to time responses with super‐fast transients and super‐slow evolutions towards the steady‐state, effects not easily captured by the integer order models.
A Dynamic Microblog Network and Information Dissemination in “@” Mode
Authors: Tang Mingsheng , Mao Xinjun , Yang Shuqiang , Zhou Huiping
Published: June 2014

Social media, especially the microblogs, emerge as a part of our daily life and become a key way to information spread. Thus, information dissemination in the microblog became a research hotspot. Based on some principles that are summarized from the microblog users’ behaviors, this paper proposes a dynamic microblog network model. Through simulations this network has the features of periodicity of average degree, high clustering coefficient, high degree of modularity, and community. Besides, an information dissemination model through “@” in the microblog has been presented. With the microblog network model and the zombie‐city model, this paper has modelled an artificial microblog and has simulated the information dissemination in the artificial microblog with different scenes. Therefore, some interesting findings have been presented. (1) Due to a better connectivity, information could spread widely in a random network; (2) information spreads more quickly in a stable microblog network; (3) the decay rate of the relationships will have an effect on information dissemination; that is, with a lower decay rate, information spreads more quickly and widely; (4) the higher active level of users in microblog could promote information spread widely and quickly; (5) the “@” mode of information dissemination makes a high modularity of the information diffusion network.
MicroRNA: Important Player in the Pathobiology of Multiple Myeloma
Authors: Bi Chonglei , Chng Wee Joo
Published: June 2014

Recent studies have revealed a pivotal role played by a class of small, noncoding RNAs, microRNA (miRNA), in multiple myeloma (MM), a plasma cell (PC) malignancy causing significant morbidity and mortality. Deregulated miRNA expression in patient’s PCs and plasma has been associated with tumor progression, molecular subtypes, clinical staging, prognosis, and drug response in MM. A number of important oncogenic and tumor suppressor miRNAs have been discovered to regulate important genes and pathways such as p53 and IL6-JAK-STAT signaling. miRNAs may also form complex regulatory circuitry with genetic and epigenetic machineries, the deregulation of which could lead to malignant transformation and progression. The translational potential of miRNAs in the clinic is being increasingly recognized that they could represent novel biomarkers and therapeutic targets. This review comprehensively summarizes current progress in delineating the roles of miRNAs in MM pathobiology and management.
Microenvironment, Oncoantigens, and Antitumor Vaccination: Lessons Learned from BALB-neuT Mice
Authors: Conti Laura , Ruiu Roberto , Barutello Giuseppina , Macagno Marco , Bandini Silvio , Cavallo Federica , Lanzardo Stefania
Published: June 2014

The tyrosine kinase human epidermal growth factor receptor 2 (HER2) gene is amplified in approximately 20% of human breast cancers and is associated with an aggressive clinical course and the early development of metastasis. Its crucial role in tumor growth and progression makes HER2 a prototypic oncoantigen, the targeting of which may be critical for the development of effective anticancer therapies. The setup of anti-HER2 targeting strategies has revolutionized the clinical outcome of HER2+breast cancer. However, their initial success has been overshadowed by the onset of pharmacological resistance that renders them ineffective. Since the tumor microenvironment (TME) plays a crucial role in drug resistance, the design of more effective anticancer therapies should depend on the targeting of both cancer cells and their TME as a whole. In this review, starting from the successful know-how obtained with a HER2+mouse model of mammary carcinogenesis, the BALB-neuT mice, we discuss the role of TME in mammary tumor development. Indeed, a deeper knowledge of antigens critical for cancer outbreak and progression and of the mechanisms that regulate the interplay between cancer and stromal cell populations could advise promising ways for the development of the best anticancer strategy.