bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL‐12B Gene Polymorphisms and IL‐12 p70 Serum Levels Among Patients with Rheumatoid Arthritis
Authors: Paradowska‐Gorycka A. , Sowinska A. , Stypińska B. , Haladyj E. , Pawlik A. , Romanowska‐Próchnicka K. , Olesinska M. 
Published: November 2016

AbstractRheumatoid arthritis (RA) is one of the autoimmune diseases, where different polymorphisms in cytokine genes play a pathogenic role. IL‐12 is now recognized as a critical cytokine in terms of regulating the balance between Th1 and Th2 cells. We investigated the role of single nucleotide polymorphisms (SNPs) (rs3212227 (A/C) and rs17860508 (CTCTAA/GC)) of the IL‐12B gene in the genetic susceptibility to RA and in the severity of the disease. Six hundred and thirty‐four Caucasian RA patients and 341 healthy matched controls were studied using PCR‐RFLP method and high‐resolution melting analysis. Concentration of IL‐12 cytokine level in serum was evaluated using ELISA. The genotype frequency did not deviate from HWE in each examined group. Frequencies of the rs3212227 CC genotype were statistically higher in patients with RA compared with the healthy control group in both codominant and recessive models (P = 0.037; P = 0.04, respectively). The frequency of rs3212227 C allele also showed similar tendency (P = 0.07). IL‐12 level in serum was significantly higher in RA group compared with control (P < 0.0001). We observed that increased IL‐12 serum level was correlated with higher number of tender and swollen joints, ExRA presence and higher levels of haemoglobin, CRP and PLT. Also higher IL‐12 level in serum was observed within RA patients with hypertension. Present findings indicated that IL‐12p40 + 1188A/C polymorphism as well as IL‐12p70 protein levels may be associated with RA in the Polish population.
Quantitating the lateral skin stiffness by a new and versatile electro‐mechanical instrument. Preliminary studies
Authors: Nomura M. , Velleman D. , Pierre J. , Flament F. 
Published: November 2016

BackgroundA new electro‐mechanical device for measuring the lateral stiffness of the skin is now available. It basically allows to recording the forces that the skin opposes to a lateral displacement (1–2 mm) of a pinching type movement. Preliminary assays of this device to various skin sites and an artificial substrate aimed at defining its major characteristics (sensitivity, reproducibility, variations according to skin site).MethodsThe calibration of the device (Khelometer®) and assessment of its reproducibility were carried out through the use of elastometer substrates of various stiffness's. The device was then used,in vivo, at different skin sites (scalp, inner and outer forearms, cheeks) of 213 healthy Japanese women of various ages. The short‐time effect of a hydrating regimen (7% glycerol) was recorded on the outer forearm.ResultsThis new device offers an appreciable reproducibilityin vitroandin vivo(coefficient of variation of 2–4% and 5–14%, respectively). Unlike other biophysical methods, the Khelometer®can be easily applied onto the human scalp that shows a higher stiffness than the two other skin sites, increasing with age and presence of alopecia. In all the three studied skin sites, the impact of age leads to significantly higher lateral skin stiffness (LSS, expressed as N/mm) values. The latter were found significantly different between the two sides of the forearms where the outer (sun‐exposed) side showed statistically slightly higherLSS, than the unexposed inner side.LSSvalues found on cheeks (≈0.5 N/mm) were about four times lower than those of the scalp (≈2 N/mm) and about half those of forearms (≈1 N/mm). The effect of a 7% glycerol based formula was recorded 20 min post application onto the forearm, leading to a slight drop inLSS(approx. 15%) as compared to a vehicle‐applied skin site.ConclusionThese preliminary studies clearly indicate that this new device, applicable to any skin site, offers appreciable assets such as sensitivity and reproducibility. Accordingly, it appears as a new approach in the non‐invasive biophysical measurements of the skin surface, in both advanced and applied research investigations.
Researching Authoritarianism in the Discipline of Democracy*
Authors: Ahram Ariel I. , Goode J. Paul 
Published: November 2016

ObjectThis article examines the ways social science research approaches the study of authoritarian regimes and identifies ways to engage with regimes that are both deliberately opaque and oppressive.MethodThe article examines existing methodological prescriptions and practices as they pertain to the study of authoritarian regimes. These cover issues of data collection, research safety, subjective safety, and the positioning of knowledge about authoritarianism within the wider scope of social sciences.ResultsThe article identifies three distinct but interrelated challenges in the study of authoritarian regimes: (1) access and timing, (2) data validity and integrity, and (3) ethical issues.ConclusionMethods commonly deployed in the study of democratic and open regimes cannot be readily deployed to the study of authoritarian ones. Greater reflexivity is needed to understand the methodological challenges inherent to the study of authoritarianism.
Eyes Wide Shut: Democratic Reversals, Scientific Closure, and the Study of Politics in Eurasia*
Authors: Goode J. Paul 
Published: November 2016

ObjectivesThe article examines the relationship between democratic reversals and scientific closure. It focuses on the effects that authoritarian and hybrid regimes are likely to have on the ways scholars study them and conduct their fieldwork.MethodThematic content analysis of articles on Eurasian politics published over a 10‐year period, with particular attention paid to reported methods and fieldwork.ResultsScientific closure had as much to do with research cycles in the discipline as with democratic reversals. Notions of the region as democratizing persisted into the 2000s as scholars recycled data and conceptual frames from the 1990s. Fieldwork‐driven research was more likely to detect autocratization.ConclusionWhile disciplinary consensus reframed the region as autocratizing, the field remains vulnerable to scientific closure. Aside from the challenges posed by autocracies for fieldwork, the new disciplinary consensus may deter qualitative fieldwork and innovation in studying authoritarianism in Eurasia.
Differential response at the seafloor during Palaeocene and Eocene ocean warming events at Walvis Ridge, Atlantic Ocean (ODP Site 1262)
Authors: Deprez Arne , Jehle Sofie , Bornemann André , Speijer Robert P. 
Published: November 2016

AbstractThe Latest Danian Event (LDE, c. 62.1 Ma) is an early Palaeogene hyperthermal or transient (<200 ka) ocean warming event. We present the first deep‐sea benthic foraminiferal faunal record to study deep‐sea biotic changes together with new benthic (Nuttallides truempyi) stable isotope data from Walvis Ridge Site 1262 (Atlantic Ocean) to evaluate whether the LDE was controlled by similar processes as the minor early Eocene hyperthermals. The spacing of the double negative δ13C and δ18O excursion and the slope of the δ18O–δ13C regression are comparable, strongly suggesting a similar orbital control and pacing of eccentricity maxima as well as a rather homogeneous carbon pool. However, in contrast to early Eocene hyperthermals, the LDE exhibits a remarkable stability of the benthic foraminiferal fauna. This lack of benthic response could be related to the absence of threshold‐related circulation changes or better pre‐adaptation to elevated deep‐sea temperatures, as the LDE was superimposed on a cooling trend, in contrast to early Eocene warming.
How and why are calcium currents curtailed in the skeletal muscle voltage‐gated calcium channels?
Authors: Flucher Bernhard E. , Tuluc Petronel 
Published: November 2016

AbstractVoltage‐gated calcium channels represent the sole mechanism converting electrical signals of excitable cells into cellular functions such as contraction, secretion and gene regulation. Specific voltage‐sensing domains detect changes in membrane potential and control channel gating. Calcium ions entering through the channel function as second messengers regulating cell functions, with the exception of skeletal muscle, where CaV1.1 essentially does not function as a channel but activates calcium release from intracellular stores. It has long been known that calcium currents are dispensable for skeletal muscle contraction. However, the questions as to how and why the channel function of CaV1.1 is curtailed remained obscure until the recent discovery of a developmental CaV1.1 splice variant with normal channel functions. This discovery provided new means to study the molecular mechanisms regulating the channel gating and led to the understanding that in skeletal muscle, calcium currents need to be restricted to allow proper regulation of fibre type specification and to prevent mitochondrial damage.
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Suppression of High Frequency Oscillations on Suspension System of Snow Groomer With Evolutionary Algorithms Optimization
Authors: Marani Pietro , Ferrari Cristian 
Published: November 2016

In current engineering practice for the design and dimensioning of hydropneumatic suspension systems, the effect of main parameters is considered; this approach can be used to implement approximate models basically suitable to describe low frequency and high amplitude oscillations of the machine.
The target of this study is a Snow Groomer, a tracked vehicle driven by diesel engines and equipped in front with a shovel and behind with a cutter. When the machine drives over a snowfield, it pushes snow ahead of it and, at the same time, smooths out any surface unevenness.
The suspension system is the key element to ensure the driver’s safety and comfort, the effectiveness of snow grooming and finally enhance the reliability of the machine components. The on-field testing had shown high frequency pressure oscillations transmitted from the sprocket to hydraulic system, propagated through the flexible hoses. Those Pressure Oscillations cause noise and can affect negatively the durability and reliability of the Machine. A lumped parameter non-linear dynamic model of the hydraulic circuit and of the machine interactions is built in Amesim environment, including Lax Wendroff wave propagation models, to make it able to catch the high frequency oscillations experienced in the test field.
Most of the design parameters are fixed (such as vehicle weight and hydraulic lines length), other parameters can be varied to study the optimal solution, these parameters define the “factors” of the optimization problem.
As a next step it is important to define the objectives of the optimization, in this case corresponding to various figures of merit describing the behavior of the system in different work conditions. The large number of factors included in the lumped parameter model generates an exponentially larger number of possible configurations. Moreover the relationship between factors and objective is not always possible to express with explicit mathematical models. Finally the presence of multiple and sometimes conflicting objectives forces more refined analysis methods to be adopted.
For the above mentioned reasons a Multi-objective Optimization method is proposed taking advantage of Evolutionary Algorithms and Pareto Front optimization. Two different architectural solutions are analyzed and optimized using two different algorithms, Non Sorting Genetic Algorithm II (NSGAII) and Multiple Object Swarm Particle Optimization Algorithm (MOPSO).
The results of the optimization belonging to the Pareto Front will be analyzed to assess the expected improvement of the suspension performance and will be chosen as candidates for a new setting of the Snow Groomer. Furthermore a comparison in terms of effectiveness and speed in finding solutions will be given for the current simulation environment.
Aspects of Parameter Sensitivity for Series Hydraulic Hybrid Light-Weight Duty Vehicle Design
Authors: Baer Katharina , Ericson Liselott , Krus Petter 
Published: November 2016

Hybridization of a vehicle’s drivetrain can in principle help to improve its energy efficiency by allowing for recuperation of kinetic energy and modulating the engine’s load. How well this can be realized depends on appropriate sizing and control of the additional components. The system is typically designed sequentially, with the hardware setup preceding the development and tuning of advanced controller architectures. Taking an alternative approach, component sizing and controller tuning can be addressed simultaneously through simulation-based optimization.
The results of such optimizations, especially with standard algorithms with continuous design variable ranges, can however be difficult to realize, considering for example limitations in available components. Furthermore, drive-cycle based optimizations are prone to cycle-beating. This paper examines the results of such simulation-based optimization for a series hydraulic hybrid vehicle in terms of sensitivity to variations in design parameters, system parameters and drive cycle variations. Additional relevant aspects concerning the definition of the optimization problem are pointed out.
Dynamic Model of Tendon-Driven Robotic Chains Forming a Shape-Shifting Surface
Authors: Lasagni Matteo , Römer Kay 
Published: November 2016

This paper presents Kinematics and Dynamics of a Shape-Shifting Surface, a robotic system able to take on the shape of arbitrary connected 3D surfaces. Such a surface, which we introduced and described in previous work, consists of piecewise controllable chains in turn composed of serially connected foldable “robotic particles”. Aiming at a high resolution rendering, where tiny particles need to be combined in a large number, a tendon-driven design is a lightweight and scalable solution.
However, improper actuation strategies might expose the system to undesired forces, which can compromise its integrity and stability. To tackle this problem, optimal actuation and planning strategies are required to anticipate unacceptable situations. To this end, a dynamic model is derived to predict the reaction of the system subject to control actions. Being the system both tendon-driven and under-actuated, we have to overcome a number of challenges in deriving this model.
Using
In Vitro
Dynamic Models To Evaluate Fluoroquinolone Activity against Emergence of Resistant Salmonella enterica Serovar Typhimurium
Authors: Lee Seung-Jin , Awji Elias Gebru , Park Na-hye , Park Seung-Chun 
Published: November 2016

ABSTRACT

The objectives of this study were to determine pharmacokinetic/pharmacodynamic (PK/PD) indices of fluoroquinolones that minimize the emergence of resistant
Salmonella enterica
serovar Typhimurium (
S
. Typhimurium) using
in vitro
dynamic models and to establish mechanisms of resistance. Three fluoroquinolones, difloxacin (DIF), enrofloxacin (ENR), and marbofloxacin (MAR), at five dose levels and 3 days of treatment were simulated. Bacterial killing-regrowth kinetics and emergence of resistant bacteria after antibacterial drug exposure were quantified. PK/PD indices associated with different levels of antibacterial activity were computed. Mechanisms of fluoroquinolone resistance were determined by analyzing target mutations in the quinolone resistance-determining regions (QRDRs) and by analyzing overexpression of efflux pumps. Maximum losses in susceptibility of fluoroquinolone-exposed
S
. Typhimurium occurred at a simulated AUC/MIC ratio (area under the concentration-time curve over 24 h in the steady state divided by the MIC) of 47 to 71. Target mutations in
gyrA
(S83F) and overexpression of
acrAB-tolC
contributed to decreased susceptibility in fluoroquinolone-exposed
S
. Typhimurium. The current data suggest AUC/MIC (AUC/mutant prevention concentration [MPC])-dependent selection of resistant mutants of
S
. Typhimurium, with AUC/MPC ratios of 69 (DIF), 62 (ENR), and 39 (MAR) being protective against selection of resistant mutants. These values could not be achieved in veterinary clinical areas under the current recommended therapeutic doses of the fluoroquinolones, suggesting the need to reassess the current dosing regimen to include both clinical efficacy and minimization of emergence of resistant bacteria.
Inhibition of Plasmodium Liver Infection by Ivermectin
Authors: Mendes António M. , Albuquerque Inês S. , Machado Marta , Pissarra Joana , Meireles Patrícia , Prudêncio Miguel 
Published: November 2016

ABSTRACT

Avermectins are powerful endectocides with an established potential to reduce the incidence of vector-borne diseases. Here, we show that several avermectins inhibit the hepatic stage of
Plasmodium
infection
in vitro
. Notably, ivermectin potently inhibits liver infection
in vivo
by impairing parasite development inside hepatocytes. This impairment has a clear impact on the ensuing blood stage parasitemia, reducing disease severity and enhancing host survival. Ivermectin has been proposed as a tool to control malaria transmission because of its effects on the mosquito vector. Our study extends the effect of ivermectin to the early stages of mammalian host infection and supports the inclusion of this multipurpose drug in malaria control strategies.
Nephrotoxicity during Vancomycin Therapy in Combination with Piperacillin-Tazobactam or Cefepime
Authors: Rutter W. Cliff , Cox Jessica N. , Martin Craig A. , Burgess Donna R. , Burgess David S. 
Published: November 2016

ABSTRACT

Recent reports have demonstrated that vancomycin (VAN) may lead to an increase in the incidence of acute kidney injury (AKI) when it is combined with antipseudomonal beta-lactams. This study compared the incidence of AKI associated with VAN plus piperacillin-tazobactam (TZP) or cefepime (FEP). This was a retrospective, matched cohort study that was conducted at an academic medical center between September 2010 and September 2014 and that included adult patients without severe chronic or structural kidney disease, dialysis, pregnancy, cystic fibrosis, or a hospital transfer receiving TZP-VAN or FEP-VAN for at least 48 h. The primary outcome was the difference in the AKI incidence between the TZP-VAN and FEP-VAN groups, evaluated using the risk, injury, failure, loss of kidney function, and end-stage kidney disease (RIFLE) criteria. Patients in the two groups were matched on the basis of age, sex, severity of illness, baseline creatinine clearance, hypotension, number of nephrotoxicity risk factors, and intravenous contrast exposure. In total, 4,193 patients met all inclusion criteria (3,605 received TZP-VAN and 588 received FEP-VAN). The unadjusted AKI incidence was 21.4% in patients receiving TZP-VAN, whereas it was 12.6% in patients receiving FEP-VAN (
P
< 0.001). After the patients were matched, 1,633 patients receiving TZP-VAN and 578 patients receiving FEP-VAN were evaluated. The AKI incidence remained higher in patients receiving TZP-VAN than in those receiving FEP-VAN (21.4% versus 12.5%,
P
< 0.0001). This trend remained true for all classifications of the RIFLE criteria. After controlling for remaining confounders, TZP-VAN therapy was associated with 2.18 times the odds of AKI than FEP-VAN therapy (95% confidence interval, 1.64 to 2.94 times) in logistic regression. AKI was significantly more common in patients receiving vancomycin in combination with piperacillin-tazobactam than in those receiving vancomycin in combination with cefepime. This finding reinforces the need for the judicious use of combination empirical antimicrobial therapy.
IncP Plasmid Carrying Colistin Resistance Gene
mcr-1
in Klebsiella pneumoniae from Hospital Sewage
Authors: Zhao Feifei , Feng Yu , Lü Xiaoju , McNally Alan , Zong Zhiyong 
Published: November 2016

ABSTRACT

A
Klebsiella pneumoniae
strain of sequence type 313 (ST313) recovered from hospital sewage was found carrying the plasmid-borne colistin resistance gene
mcr-1
, which was bracketed by two copies of the insertion sequence IS
Apl1
on a 57-kb self-transmissible IncP-type plasmid of a new IncP-1 clade. The carriage of
mcr-1
on a self-transmissible broad-host-range plasmid highlights that
mcr-1
has the potential to spread beyond the
Enterobacteriaceae
family.
MetQ of Neisseria gonorrhoeae Is a Surface-Expressed Antigen That Elicits Bactericidal and Functional Blocking Antibodies
Authors: Semchenko Evgeny A. , Day Christopher J. , Seib Kate L. 
Published: November 2016

ABSTRACTNeisseria gonorrhoeae, the causative agent of the sexually transmitted infection (STI) gonorrhea, is a growing public health threat for which a vaccine is urgently needed. We characterized the functional role of the gonococcal MetQ protein, which is the methionine binding component of an ABC transporter system, and assessed its potential as a candidate antigen for inclusion in a gonococcal vaccine. MetQ has been found to be highly conserved in all strains investigated to date, it is localized on the bacterial surface, and it bindsl-methionine with a high affinity. MetQ is also involved in gonococcal adherence to cervical epithelial cells. Mutants lacking MetQ have impaired survival in human monocytes, macrophages, and serum. Furthermore, antibodies raised against MetQ are bactericidal and are able to block gonococcal adherence to epithelial cells. These data suggest that MetQ elicits both bactericidal and functional blocking antibodies and is a valid candidate antigen for additional investigation and possible inclusion in a vaccine for prevention of gonorrhea.
Associations of specific types of sports and exercise with all-cause and cardiovascular-disease mortality: a cohort study of 80 306 British adults
Authors: Oja Pekka , Kelly Paul , Pedisic Zeljko , Titze Sylvia , Bauman Adrian , Foster Charlie , Hamer Mark , Hillsdon Melvyn , Stamatakis Emmanuel 
Published: November 2016

Background/AimEvidence for the long-term health effects of specific sport disciplines is scarce. Therefore, we examined the associations of six different types of sport/exercise with all-cause and cardiovascular disease (CVD) mortality risk in a large pooled Scottish and English population-based cohort.MethodsCox proportional hazards regression was used to investigate the associations between each exposure and all-cause and CVD mortality with adjustment for potential confounders in 80 306 individuals (54% women; mean±SD age: 52±14 years).ResultsSignificant reductions in all-cause mortality were observed for participation in cycling (HR=0.85, 95% CI 0.76 to 0.95), swimming (HR=0.72, 95% CI 0.65 to 0.80), racquet sports (HR=0.53, 95% CI 0.40 to 0.69) and aerobics (HR=0.73, 95% CI 0.63 to 0.85). No significant associations were found for participation in football and running. A significant reduction in CVD mortality was observed for participation in swimming (HR=0.59, 95% CI 0.46 to 0.75), racquet sports (HR=0.44, 95% CI 0.24 to 0.83) and aerobics (HR=0.64, 95% CI 0.45 to 0.92), but there were no significant associations for cycling, running and football. Variable dose–response patterns between the exposure and the outcomes were found across the sport disciplines.ConclusionsThese findings demonstrate that participation in specific sports may have significant benefits for public health. Future research should aim to further strengthen the sport-specific epidemiological evidence base and understanding of how to promote greater sports participation.