Miracle-dz/UniFAR-FTUs huggingface dataset:
Coupling of protein and hydration-water dynamics in biological membranes

The dynamical coupling between proteins and their hydration water is important for the understanding of macromolecular function in a cellular context. In the case of membrane proteins, the environment is heterogeneous, composed of lipids and hydration water, and the dynamical coupling might be more complex than in the case of the extensively studied soluble proteins. Here, we examine the dynamical coupling between a biological membrane, the purple membrane (PM), and its hydration water by a combination of elastic incoherent neutron scattering, specific deuteration, and molecular dynamics simulations. Examining completely deuterated PM, hydrated in H2O, allowed the direct experimental exploration of water dynamics. The study of natural abundance PM in D2O focused on membrane dynamics. The temperature-dependence of atomic mean-square displacements shows inflections at 120 K and 260 K for the membrane and at 200 K and 260 K for the hydration water. Because transition temperatures are different for PM and hydration water, we conclude that ps–ns hydration water dynamics are not directly coupled to membrane motions on the same time scale at temperatures <260 K. Molecular-dynamics simulations of hydrated PM in the temperature range from 100 to 296 K revealed an onset of hydration-water translational diffusion at ≈200 K, but no transition in the PM at the same temperature. Our results suggest that, in contrast to soluble proteins, the dynamics of the membrane protein is not controlled by that of hydration water at temperatures <260 K. Lipid dynamics may have a stronger impact on membrane protein dynamics than hydration water.
The influence of genetic innate resistance and acquired immunity on drug treatment outcome of uncomplicated Plasmodium falciparum malaria in Tanzania.

In malaria endemic areas, the prevalence of parasites resistant to commonly used anti-malarial drugs, such as chloroquine (CQ), amodiaquine (AQ) and sulfadoxine/pyrimethamine (SP), is widespread and evolving quickly. This has led to an increasing numbers of treatment failures. However, children with clinical malaria, who receive drug treatment, often overcome their infection despite the reduced effect of these drugs. The reason for this contradiction remains unknown; however, host immunity and genetic factors most likely contribute to the treatment outcome. The aim of this study is to test the impact of host immunity and inherited human genetic polymorphisms on the clearance of drug resistant parasites upon SP and AQ treatment. This will be done through a combined assessment of SP and AQ efficacy and the level of innate and acquired immunity in children with malaria attending health clinics at sites of different intensities of malaria transmission in Tanzania. As part of ongoing in vivo SP and AQ efficacy trials, conducted by our collaborators in Tanzania, the objective is to monitor parasite mutation genes that may induce resistance to SP and AQ in vitro together with detailed immunological investigations. The results of this study could provide important information on malaria resistance genes in humans and for a more accurate assessment of drug resistance in vivo and possibly of targeting drug therapy with new combinations towards those most susceptible.
Synthetic Cathinones: A New Public Health Problem

New psychoactive substances (NPS) have completely modified the drug scene and the current landscape of addiction. Synthetic substances, such as substituted or synthetic cathinones, also known as « legal highs », are often produced and used to mimic the effects of controlled drugs such as cocaine, methylenedioxymethamphetamine (MDMA, ecstasy), and methamphetamine. The overwhelming majority of synthetic cathinones are produced in China and South East Asian countries. The Internet has emerged as the new marketplace for NPS, playing a major role in providing information on acquisition, synthesis, extraction, identification, and substance use. All these compounds are intentionally mislabeled and sold on-line under slang terms such as bath salts, plant food, plant feeders and research chemicals. They are sometimes labeled « not for human use » or « not tested for hazards or toxicity ». The rapid spread of NPS forces member countries of the European Union to adapt their response to the potential new dangers that may cause. To date, not only health actors but also the general public need to be clearly informed and aware of dangers resulting from NPS spread and use. Here, we review the major clinical effects of synthetic cathinones to highlight their impact on public health. A literature search was conducted from 2009 to 2014 based on PubMed, Google Scholar, Erowid, and governmental websites, using the following keywords alone or in combination: “new psychoactive substances”, “synthetic cathinones”, “substituted cathinones”, “mephedrone”, “methylone”, “MDPV”, “4-MEC”, “addiction”, and “substance use disorder”.
Lsh controls silencing of the imprinted Cdkn1c gene

Epigenetic regulation, such as DNA methylation plays an important role in the control of imprinting. Lsh, a member of the SNF2 family of chromatin remodeling proteins, controls DNA methylation in mice. To investigate whether Lsh affects imprinting, we examined CpG methylation and allelic expression of individual genes in Lsh-deficient embryos. We report here that loss of Lsh specifically alters expression of the Cdkn1c gene (also known as p57(Kip2)) but does not interfere with maintenance of imprints at the H19, Igf2, Igf2r, Zac1 and Meg9 genes. The reactivation of the silenced paternal Cdkn1c allele correlates closely with a loss of CpG methylation at the 5′ DMR at the Cdkn1c promoter, whereas KvDMR1 and DMRs of other imprinted genes were not significantly changed. Chromatin immunoprecipitations demonstrate a direct association of Lsh with the 5′ DMR at the Cdkn1c promoter, but not with Kv DMR1 or other imprinted loci. These data suggest that methylation of the 5′ DMR plays an important role in the imprinting of the Cdkn1c gene. Furthermore, it suggests that Lsh is not required for maintenance of imprinting marks in general, but is only crucial for imprinting at distinct genomic sites.
Intraductal Papillary Mucinous Neoplasms of the Pancreas: An Analysis of Clinicopathologic Features and Outcome

Objective:To define the natural history of resected intraductal papillary mucinous neoplasms (IPMN) of the pancreas and to identify clinical and pathologic prognostic features. Summary Background Data:IPMN of the pancreas is a recently described pancreatic tumor. Because of a limited number of cases, prognostic factors and the natural history of resected cases have not been well defined. Materials and Methods:A prospective pancreatic database was reviewed to identify patients with IPMN who were surgically managed. Pathologic re-review of each case was performed, and the clinicopathologic features were examined. Log rank and χ2 analysis were used to identify factors predictive of survival and recurrence. Results:Over a 17-year period, 63 patients were identified. One patient was unresectable, 6 (10%) underwent a total pancreatectomy, and 56 (89%) had a partial pancreatectomy. Invasive carcinoma was present in 30 patients (48%). Transection margins were involved with atypia or carcinoma in 32 patients (51%). The median follow-up for survivors was 38 months. Disease-specific 5- and 10-year survival were 75% and 60%, respectively. Significant predictors of poor outcome included presentation with elevated bilirubin, presence of invasive carcinoma, increasing size and percentage of invasive carcinoma, histologic type of invasive carcinoma, positive lymph nodes, and vascular invasion. The presence of atypia or carcinoma in situ at the ductal resection margin was not associated with a poor outcome. Conclusions:Overall, IPMN has a favorable prognosis. Poor outcome in a subset of patients is largely the result of the presence, extent, and type of an invasive component, lymph node metastases, and vascular invasion.
Elucidating Conformational Changes in the γ-Aminobutyric Acid Transporter-1*

The GABA transporter-1 (GAT-1) has three current-generating modes: GABA-coupled current, Li+-induced leak current, and Na+-dependent transient currents. We earlier hypothesized that Li+ is able to substitute for the first Na+ in the transport cycle and thereby induce a distinct conformation in GAT-1 and that the onset of the Li+-induced leak current at membrane potentials more negative than −50 mV was due to a voltage-dependent conformational change of the Li+-bound transporter. In this study, we set out to verify this hypothesis and seek insight into the structural dynamics underlying the leak current, as well as the sodium-dependent transient currents, by applying voltage clamp fluorometry to tetramethylrhodamine 6-maleimide-labeled GAT-1 expressed in Xenopus laevis oocytes. MTSET accessibility studies demonstrated the presence of two distinct conformations of GAT-1 in the presence of Na+ or Li+. The voltage-dependent fluorescence intensity changes obtained in Li+ buffer correlated with the Li+-induced leak currents, i.e. both were highly voltage-dependent and only present at hyperpolarized potentials (<−50 mV). The transient currents correlated directly with the voltage-dependent fluorescence data obtained in sodium buffer and the associated conformational changes were distinct from those associated with the Li+-induced leak current. The inhibitor potency of SKF89976A of the Li+- versus Na+-bound transporter confirmed the cationic dependence of the conformational occupancy. Our observations suggest that the microdomain situated at the external end of transmembrane I is involved in different conformational changes taking place either during the binding and release of sodium or during the initiation of the Li+-induced leak current.
Attitude control based on fuzzy logic for continuum aircraft fuel tank inspection robot

With a compliant structure and excellent bending properties, continuum robot has hyper-redundant degrees of freedom, and can be used in space-constrained environments as the aircraft fuel tank. Therefore, a continuum robot is designed to help crews inspect aircraft fuel tanks, which can improve maintenance efficiency and reduce the intensity of crews. According to the requirements of aircraft fuel tank inspection, the compliant and extensible drive mechanisms of the continuum robot are designed. The kinematic models of single joint segment and multi-joint segments of continuum robot are analyzed, and homogeneous transformation matrices are obtained. To improve control performance, a closed-loop fuzzy controller based on attitude feedback is proposed. The attitude sensor is installed on the top of each joint segment of a snake-like arm to form a closed-loop control system, and a fuzzy controller is designed to achieve fast and accurate control of the robot. The prototype platform of the continuum robot is built, and practical experiments are implemented on the platform. The effectiveness and stability of the fuzzy controller based on attitude feedback are verified.
Cutting Edge: TLR2-Mediated Proinflammatory Cytokine and Chemokine Production by Microglial Cells in Response to Herpes Simplex Virus1

Recent studies indicate that TLRs are critical in generating innate immune responses during infection with HSV-1. In this study, we investigated the role of TLR2 signaling in regulating the production of neuroimmune mediators by examining cytokine and chemokine expression using primary microglial cells obtained from TLR2−/− as well as wild-type mice. Data presented here demonstrate that TLR2 signaling is required for the production of proinflammatory cytokines and chemokines: TNF-α, IL-1β, IL-6, IL-12, CCL7, CCL8, CCL9, CXCL1, CXCL2, CXCL4, and CXCL5. CXCL9 and CXCL10 were also induced by HSV, but their production was not dependent upon TLR2 signaling. Because TLR2−/− mice display significantly reduced mortality and diminished neuroinflammation in response to brain infection with HSV, the TLR2-dependent cytokines identified here might function as key players influencing viral neuropathogenesis.
Requirements and design principles for multisimulation with multiresolution, multistage multimodels

The significance of simulation modeling at multiple levels, scales, and perspectives is well recognized. However, existing proposals for developing such models are often application specific. The position advocated in this paper is that generic design principles for specifying and realizing multiresolution, multistage models are still lacking. Requirements for simulation environments that facilitate multiresolution multistage model specification are introduced. A multimodel specification formalism based on graph of models is suggested along with design precepts to enable flexible dynamic model updating. The notion of multisimulation is introduced to enable exploratory simulation using various types of multimodels.
Coffee Consumption and Risk of Stroke in Women

Background— Data on the association between coffee consumption and risk of stroke are sparse. We assessed the association between coffee consumption and the risk of stroke over 24 years of follow-up in women. Methods and Results— We analyzed data from a prospective cohort of 83 076 women in the Nurses’ Health Study without history of stroke, coronary heart disease, diabetes, or cancer at baseline. Coffee consumption was assessed first in 1980 and then repeatedly every 2 to 4 years, with follow-up through 2004. We documented 2280 strokes, of which 426 were hemorrhagic, 1224 were ischemic, and 630 were undetermined. In multivariable Cox regression models with adjustment for age, smoking status, body mass index, physical activity, alcohol intake, menopausal status, hormone replacement therapy, aspirin use, and dietary factors, the relative risks (RRs) of stroke across categories of coffee consumption (<1 cup per month, 1 per month to 4 per week, 5 to 7 per week, 2 to 3 per day, and ≥4 per day) were 1, 0.98 (95% CI, 0.84 to 1.15), 0.88 (95% CI, 0.77 to 1.02), 0.81 (95% CI, 0.70 to 0.95), and 0.80 (95% CI, 0.64 to 0.98) (P for trend=0.003). After further adjustment for high blood pressure, hypercholesterolemia, and type 2 diabetes, the inverse association remained significant. The association was stronger among never and past smokers (RR for ≥4 cups a day versus <1 cup a month, 0.57; 95% CI, 0.39 to 0.84) than among current smokers (RR for ≥4 cups a day versus <1 cup a month, 0.97; 95% CI, 0.63 to 1.48). Other drinks containing caffeine such as tea and caffeinated soft drinks were not associated with stroke. Decaffeinated coffee was associated with a trend toward lower risk of stroke after adjustment for caffeinated coffee consumption (RR for ≥2 cups a day versus <1 cup a month, 0.89; 95% CI, 0.73 to 1.08; P for trend=0.05). Conclusions— Long-term coffee consumption was not associated with an increased risk of stroke in women. In contrast, our data suggest that coffee consumption may modestly reduce risk of stroke.
Profile-directed optimization of event-based programs

Events are used as a fundamental abstraction in programs ranging from graphical user interfaces (GUIs) to systems for building customized network protocols. While providing a flexible structuring and execution paradigm, events have the potentially serious drawback of extra execution overhead due to the indirection between modules that raise events and those that handle them. This paper describes an approach to addressing this issue using static optimization techniques. This approach, which exploits the underlying predictability often exhibited by event-based programs, is based on first profiling the program to identify commonly occurring event sequences. A variety of techniques that use the resulting profile information are then applied to the program to reduce the overheads associated with such mechanisms as indirect function calls and argument marshaling. In addition to describing the overall approach, experimental results are given that demonstrate the effectiveness of the techniques. These results are from event-based programs written for X Windows, a system for building GUIs, and Cactus, a system for constructing highly configurable distributed services and network protocols.
In Vitro Induction of Neospora caninum Bradyzoites in Vero Cells Reveals Differential Antigen Expression, Localization, and Host-Cell Recognition of Tachyzoites and Bradyzoites

ABSTRACT We report on an optimized method for the in vitro culture of tissue cyst-forming Neospora caninum bradyzoites in Vero cells and the separation of viable parasites from host cells. Treatment of tachyzoite-infected Vero cell cultures with 17 μM sodium nitroprusside for 8 days severely scaled down parasite proliferation, led to reduced expression of tachyzoite surface antigens, and induced the expression of the bradyzoite marker NcBAG1 and the cyst wall antigen recognized by the monoclonal antibody MAbCC2. Transmission electron microscopy demonstrated that intracellular parasites were located within parasitophorous vacuoles that were surrounded by a cyst wall-like structure, and the dense granule antigens NcGRA1, NcGRA2, and NcGRA7 were incorporated into the cyst wall. Adhesion-invasion assays employing purified tachyzoites and bradyzoites showed that tachyzoites adhered to, and invaded, Vero cells with higher efficiency than bradyzoites. However, removal of terminal sialic acid residues from either the host cell or the parasite surface increased the invasion of Vero cells by bradyzoites, but not tachyzoites.
The design of a pen-based musical input system

Computerising the task of music editing can avoid a considerable amount of tedious work for musicians, particularly for tasks such as key transposition, part extraction, and layout. However the task of getting the music onto the computer can still be time consuming and is usually done with the help of bulky equipment. This paper reports on the design of a pen-based input system that uses easily-learned gestures to facilitate fast input, particularly if the system must be portable. The design is based on observations of musicians writing music by hand, and an analysis of the symbols in samples of music. A preliminary evaluation of the system is presented, and the speed is compared with the alternatives of handwriting, synthesiser keyboard input, and optical music recognition. Evaluations suggest that the gesture-based system could be approximately three times as fast as other methods of music data entry reported in the literature.
A cooperative coevolutionary algorithm with Correlation based Adaptive Variable Partitioning

A cooperative coevolutionary algorithm (CCEA) is an extension to an evolutionary algorithm (EA); it employs a divide and conquer strategy to solve an optimization problem. In its basic form, a CCEA splits the variables of an optimization problem into multiple smaller subsets and evolves them independently in different subpopulations. The dynamics of a CCEA is far more complex than an EA and its performance can vary from good to bad depending on the separability of the optimization problem. This paper provides some insights into why CCEA in its basic form is not suitable for nonseparable problems and introduces a Cooperative Coevolutionary Algorithm with Correlation based Adaptive Variable Partitioning (CCEA-AVP) to deal with such problems. The performance of CCEA-AVP is compared with CCEA and EA to highlight its benefits. CCEA-AVP offers the possibility to deal with problems where separability among variables might vary in different regions of the search space.
Speed and Power Optimization of FPGASBased on Modified Viterbi Decoder

Advancement in the VlSI technology using low power, less area and high speed constraints is mostly used for encoding and decoding of data. In this paper power and cost reduction with increase in speed using viterbi decoder(VD) for trellis coded modulation(TCM) is proposed. Viterbi decoder uses viterbi algorithm for TCM decoding, but the efficient speed and power reduction is not achieved at the receiving ends. A pipelined architecture with a pre-computational approach which incorporated T-algorithm for VD is proposed in this paper. Priority encoder is used along with convolution encoders to send data bits of high priority first with a code rate of ½ in TCM system. The proposed architecture reduces power consumption of 80% without performance loss. The degradation of clock speed used in the architecture is negligible. Proposed architecture is simulated and synthesized using Xilinx ISE successfully and analyzed using FPGA Spartan-6 XC6SLX45 which is a low power target device. The results obtained are found to be consuming low power.
Turismo comunitario en Ecuador.Comprendiendo el community-based tourism desde la comunidad

The growing impetus of community-based tourism (CBT) as a means of achieving sustainable tourism and a strategy for social development forces us to seek a deeper understanding of this phenome- non. This paper proposes an analytical focus on the community as a theoretical/methodological tactic. The empirical reference point in this research paper is the concept of turismo comunitario (TC) in Ecua- dor, where five communities were chosen to conduct an in-depth ethnographic study. By means of a conclusion, a comprehensive framework is put forward for TC, founded on three main pillars: the analy- tical centrality of the communities; the consideration of TC as a 'translation' rather than an 'adaptation' to the market; and the fortifying - rather than debilitating - nature of TC for the communities involved. This provides a series of factors that can be used to gain a general understanding of CBT, from a theore- tical point of view, and which can also be used to evaluate the social viability of CBT projects and expe- riments.
Varieties of Attention

1 Attention and Magic 2 A Few Gross Characteristics of Attention 3 Three-Network Model of Attention 4 Methods of Investigating Attention 5 Atypical Attention 6 Magic, Psychology, and Attention 7 Summary Keywords: attention; control networks; magic; misdirection; deception; expectation; atypical attention; orienting; conflict; alerting
Active vibration control algorithm for impulsive noise

Impulsive noise is an important challenge for the engineering implementation of active vibration control systems. It can generates larger amplitude outputs of the adaptive filter which are prohibited in practical active vibration control system and destroys the updated stability of the algorithm. An improved filtered-x least mean square algorithm is proposed for impulsive noise in this paper. The proposed algorithm process the reference signal with a new approach which uses a finite impulse response filter. The outputs of the adaptive filter with large amplitudes will be limited through this approach. In order to improve the updated stability, the updating formula of the filter coefficients in the proposed algorithm is derived from a kind of minimization criterion that minimizes the summation of each squared Euclidean norm of difference between the currently updated coefficient vectors and past coefficient vectors. The effectiveness of the improved filter-x least mean square algorithm is proved through simulations comparing with some existing algorithms.