Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy, safety and patient-reported outcomes of combination etanercept and sulfasalazine versus etanercept alone in patients with rheumatoid arthritis: a double-blind randomised 2-year study

Objective: To determine the efficacy and safety of etanercept and etanercept plus sulfasalazine versus sulfasalazine in patients with rheumatoid arthritis (RA) despite sulfasalazine therapy. Methods: Patients were randomly assigned to etanercept (25 mg twice weekly; sulfasalazine was discontinued at baseline), etanercept plus sulfasalazine (unchanged regimen of 2–3 g/day) or sulfasalazine in a double-blind, randomised, 2-year study in adult patients with active RA despite sulfasalazine therapy. Efficacy was assessed using the American College of Rheumatology criteria, disease activity scores (DAS) and patient-reported outcomes (PRO). Results: Demographic variables and baseline disease characteristics were comparable among treatment groups; mean DAS 5.1, 5.2 and 5.1 for etanercept (n = 103), etanercept plus sulfasalazine (n = 101) and sulfasalazine (n = 50), respectively. Withdrawal due to lack of efficacy was highest with sulfasalazine (26 (52%) vs 6 (6%) for either etanercept group, p<0.001). Patients receiving etanercept or etanercept plus sulfasalazine had a more rapid initial response, which was sustained at 2 years, than those receiving sulfasalazine: mean DAS 2.8, 2.5 versus 4.5, respectively (p<0.05); ACR 20 response was achieved by 67%, 77% versus 34% of patients, respectively (p<0.01) Overall, PRO followed a similar pattern; a clinically significant improvement in health assessment questionnaire was achieved by 76%, 78% versus 40% of patients, respectively (p<0.01). Commonly reported adverse events occurring in the etanercept groups were injection site reactions and pharyngitis/laryngitis (p<0.01). Conclusion: Etanercept and etanercept plus sulfasalazine are efficacious for the long-term management of patients with RA. The addition of etanercept or substitution with etanercept should be considered as treatment options for patients not adequately responding to sulfasalazine.
A spatially balanced design with probability function proportional to the within sample distance

The units observed in a biological, agricultural, and environmental survey are often randomly selected from a finite population whose main feature is to be geo‐referenced thus its spatial distribution should be used as essential information in designing the sample. In particular our interest is focused on probability samples that are well spread over the population in every dimension which in recent literature are defined as spatially balanced samples. To approach the problem we used the within sample distance as the summary index of the spatial distribution of a random selection criterion. Moreover numerical comparisons are made between the relative efficiency, measured with respect to the simple random sampling, of the suggested design and some other classical solutions as the Generalized Random Tessellation Stratified (GRTS) design used by the US Environmental Protection Agency (EPA) and other balanced or spatially balanced selection procedures as the Spatially Correlated Poisson Sampling (SCPS), the balanced sampling (CUBE), and the Local Pivotal method (LPM). These experiments on real and simulated data show that the design based on the within sample distance selects samples with a better spatial balance thus gives estimates with a lower sampling error than those obtained by using the other methods. The suggested method is very flexible to the introduction of stratification and coordination of samples and, even if in its nature it is computationally intensive, it is shown to be a suitable solution even when dealing with high sampling rates and large population frames where the main problem arises from the size of the distance matrix.
Clinical guidelines on the management of hepatitis C

### 1.1 THE NEED FOR GUIDELINES Hepatitis C virus (HCV) is a major health care concern in the UK affecting some 200 000 to 400 000 individuals. The majority of these patients will have chronic HCV infection and many will develop chronic liver disease with the risk of developing cirrhosis and hepatocellular carcinoma (HCC). Successful treatment will arrest the progression of liver disease and so prevent the serious complications of chronic HCV infection. In addition, treatment will reduce the numbers of HCV infected individuals. The relatively high cost of treatment enforces the need for a systematic approach for this condition so that resources are used most effectively. The development of clinical guidelines is important, as these will assist purchasing authorities, providers, clinicians, primary care groups, and patients in making decisions about appropriate treatment. ### 1.2 THE DEVELOPMENT OF GUIDELINES: RIGOUR OF DEVELOPMENT/SYSTEMATIC CRITICAL REVIEW OF THE LITERATURE #### 1.2. 1 Guideline development group The development of these clinical guidelines follows a workshop held at the Royal College of Physicians on 3 December 1997. This meeting was jointly coordinated by the NHS Executive, the Royal College of Physicians, the British Society of Gastroenterology, British Liver Trust, and the British Association for the Study of the Liver (BASL). The workshop was attended by hepatologists, gastroenterologists, histopathologists, virologists, general practitioners, clinical nurse specialists, patient representatives, health care economists, and NHS managers. Attendants were chosen to represent key professional disciplines and interest groups likely to be affected by the guidelines. The literature was reviewed by a clinician attending the workshop and the guidelines written under the guidance of a steering committee, which met regularly during the development process. The document was circulated to both clinicians (including gastroenterologists and hepatologists) and non-clinicians for comments before the final guidelines were drawn up (see appendix). The guidelines were presented at the 1999 BASL meeting in London where consensus was achieved on some of the more controversial issues. #### 1.2. 2 Strategy The literature was searched comprehensively so …
Phonetic realization of contrastive focus in Korean

It has been observed that a focused item in Korean is by and large realized with higher pitch, longer duration and greater intensity. But it is not fully clear how much focus affects the pre-focus and post-focus regions. The present study examines the full scale of focus effect in Korean in pre-focus, on-focus and post-focus words. Results show that focused words have significantly increased F0, duration and intensity, post-focus words have significantly reduced F0
Survivable and bandwidth-guaranteed embedding of virtual clusters in cloud data centers

Cloud computing has emerged as a powerful and elastic platform for internet service hosting, yet it also draws concerns of the unpredictable performance of cloud-based services due to network congestion. To offer predictable performance, the virtual cluster abstraction of cloud services has been proposed, which enables allocation and performance isolation regarding both computing resources and network bandwidth in a simplified virtual network model. One issue arisen in virtual cluster allocation is the survivability of tenant services against physical failures. Existing works have studied virtual cluster backup provisioning with fixed primary embeddings, but have not considered the impact of primary embeddings on backup resource consumption. To address this issue, in this paper we study how to embed virtual clusters survivably in the cloud data center, by jointly optimizing primary and backup embeddings of the virtual clusters. We formally define the survivable virtual cluster embedding problem. We then propose a novel algorithm, which computes the most resource-efficient embedding given a tenant request. Since the optimal algorithm has high time complexity, we further propose a faster heuristic algorithm, which is several orders faster than the optimal solution, yet able to achieve similar performance. Besides theoretical analysis, we evaluate our algorithms via extensive simulations.
Raf-1 regulates Rho signaling and cell migration

Raf kinases relay signals inducing proliferation, differentiation, and survival. The Raf-1 isoform has been extensively studied as the upstream kinase linking Ras activation to the MEK/ERK module. Recently, however, genetic experiments have shown that Raf-1 plays an essential role in counteracting apoptosis, and that it does so independently of its ability to activate MEK. By conditional gene ablation, we now show that Raf-1 is required for normal wound healing in vivo and for the migration of keratinocytes and fibroblasts in vitro. Raf-1–deficient cells show a symmetric, contracted appearance, characterized by cortical actin bundles and by a disordered vimentin cytoskeleton. These defects are due to the hyperactivity and incorrect localization of the Rho-effector Rok-α to the plasma membrane. Raf-1 physically associates with Rok-α in wild-type (WT) cells, and reintroduction of either WT or kinase-dead Raf-1 in knockout fibroblasts rescues their defects in shape and migration. Thus, Raf-1 plays an essential, kinase-independent function as a spatial regulator of Rho downstream signaling during migration.
The language system in schizophrenia: effects of capacity and linguistic structure.

Dysfunction in receptive language processes has been reliably observed in individuals diagnosed with schizophrenia and their first degree family members. The present study addressed the unresolved issue of whether receptive syntax is intact in schizophrenia. The principal question concerned whether comprehension dysfunction in schizophrenia involves a disturbance in the processing of syntactic structure, a susceptibility to demands placed on temporal auditory processing, or some combination of these two general factors. Comprehension accuracy was compared between 32 males diagnosed with schizophrenia and 22 males with no lifetime diagnosis of psychiatric disorder. Accuracy was examined for responses to Who questions ("Who did X? " and "Who was done X? ") about information in the sentential clauses (main vs. relative) of two types of relative sentences (subject-relatives vs. object-relatives) that were presented aurally at conversational and accelerated rates. The relationship between cognitive functions and comprehension accuracy was also tested. Results showed highly significant effects of diagnosis, syntactic structure, and temporal demand. Patients were characterized by reduced overall comprehension accuracy compared to controls. More important, patients and controls differed in their patterns of accuracy across the different types of syntactic structure. Finally, cognitive functions predicted but did not completely account for comprehension accuracy. Findings suggest the hypothesis that receptive syntax is disrupted in schizophrenia, and this dysfunction may not be entirely explained by compromised general cognitive ability.
Evaluation of using crushed brick as coarse aggregate in concrete layer within rigid highway pavement

Most of the present studies related to the field of highway pavement construction technique tend to make use of the local available materials as substitutes for the imported and necessary materials for some of the practical application. For this reason this research aims at looking for the prospect of used locally available aggregate such as crushed clay bricks for the aim of producing proper concrete with suitable thermal and mechanical properties. Experimental investigations have been carried out to asses the effect of partial replacement of coarse aggregate by free manually crushed Brick with percentages (10, 20, 30 and 40)% of virgin coarse aggregate in concrete mix for highway rigid pavement. While the percentage (0)% replacement represent reference mix. Mix proportion based on the target of compressive strength for all replacement percentage of (33) MPa at (28) days to achieve AASHTO requirement for highway concrete rigid pavement . The results of flexural strength, modulus of elasticity, density and thermal conductivity refers to better performance (less thickness of concrete layer with large spacing between contraction or expansion joints and less stresses due to warping induced concrete layer) for concrete mix with 20% crushed brick as replacement of coarse aggregate.
Domain-based multiple description coding of images and video

In this paper we present a method of creating domain-based multiple descriptions of images and video. Descriptions are created by partitioning the domain of the signal into sets whose points are maximally separated from each other. This property enables simple error concealment methods to produce good estimates of lost signal samples. We present the approach in the context of Internet transmission of subband-coded images and scalable motion compensated 3-D subband-coded video, but applications are not limited to these scenarios.
Construction of Slepian-Wolf Source Code and Broadcast Channel Code Based on Hash Property

The aim of this paper is to prove theorems for the Slepian-Wolf source coding and the broadcast channel coding (independent messages and no common message) based on the the notion of a stronger version of the hash property for an ensemble of functions. Since an ensemble of sparse matrices has a strong hash property, codes using sparse matrices can realize the achievable rate region. Furthermore, extensions to the multiple source coding and multiple output broadcast channel coding are introduced.
vesicular glutamate transporters Docking and homology modeling explain inhibition of the human

As membrane transporter proteins, VGLUT1–3 mediate the uptake of glutamate into synaptic vesicles at presynaptic nerve terminals of excitatory neural cells. This function is crucial for exocytosis and the role of glutamate as the major excitatory neurotransmitter in the central nervous system. The three transporters, sharing 76% amino acid sequence identity in humans, are highly homologous but differ in regional expression in the brain. Although little is known regarding their three-dimensional structures, hydropathy analysis on these proteins predicts 12 transmembrane segments connected by loops, a topology similar to other members in the major facilitator superfamily, where VGLUT1–3 have been phylogenetically classified. In this work, we present a three-dimensional model for the human VGLUT1 protein based on its distant bacterial homolog in the same superfamily, the glycerol-3phosphate transporter from Escherichia coli. This structural model, stable during molecular dynamics simulations in phospholipid bilayers solvated by water, reveals amino acid residues that face its pore and are likely to affect substrate translocation. Docking of VGLUT1 substrates to this pore localizes two different binding sites, to which inhibitors also bind with an overall trend in binding affinity that is in agreement with previously published experimental data.
Purification of mammalian cone photoreceptors by lectin panning and the enhancement of their survival in glia-conditioned medium.

PURPOSE In retinal diseases characterized by photoreceptor degeneration, the main cause of clinically significant vision loss is cone, rather than rod, loss. In the present study, a technique was designed to purify cones to make it possible to screen for neuroprotective molecules. METHODS A suspension of porcine retinal cells was incubated on coverslips coated with the peanut agglutinin (PNA) lectin, which selectively binds to cones. Cones were identified and quantified by using an antibody specific for cone arrestin. Their identity and viability were also assessed by single-cell RT-PCR and patch-clamp recording. RESULTS This panning method provided a population of cones that was 80% to 92% pure, depending on the counting strategy used. The panned cells contained both short (S)- and medium/long (M/L)-wavelength opsin cones. The panned retinal cells exhibited the physiological signature of cone photoreceptors and single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) showed that they expressed the cone arrestin mRNA. Most (69%) cone photoreceptors produced neurites and survived for up to 7 days when cultured in a glia-conditioned medium, whereas very few (4%) survived after 7 days in the control medium. CONCLUSIONS This PNA-lectin-panning method can provide highly pure and viable mammalian cones, the survival of which can be prolonged by glia-conditioned medium. Because PNA lectin binds to cone photoreceptors from various species in both normal and pathologic conditions, this technique should enable the screening of neuroprotective molecules like those released by glial cells and enable the physiological, genomic, and proteomic characterization of cones.
Contrasting effects of reindeer grazing on CO2, CH4, and N2O fluxes originating from the northern boreal forest floor

Reindeer (Rangifer tarandus L.) is considered to be an important mammalian herbivore, strongly influencing Arctic lichen‐dominated ecosystems. There is no wide knowledge about the effect of reindeer on greenhouse gas (GHG) fluxes in northern boreal forests. Ground vegetation plays an important role in absorbing nitrogen (N) and carbon dioxide (CO2) from the atmosphere. Lately, it has also been found to be a significant source of nitrous oxide (N2O) and a small source of methane (CH4). We investigated the influence of reindeer grazing on field layer GHG (CO2, CH4, and N2O) fluxes, ground vegetation coverage and biomass, and soil physical properties (temperature and moisture) in a northern boreal forest. At our study site, the reindeer‐induced replacement of lichen by mosses had contrasting effects on the GHG fluxes originating from the field layer. Field layer CO2 efflux was significantly higher in grazed areas. The field layer was a CH4 sink in all areas, but grazed areas absorbed more CH4 compared to non‐grazed areas. Although total N2O fluxes remained around 0 in grazed areas, a small N2O sink occurred in non‐grazed areas with lower moss biomass. Our results indicated that grazing by reindeer in northern boreal forests affects GHG fluxes from the forest field layer both positively and negatively, and these emissions largely depend on grazing‐induced changes in vegetation composition.
Hebbian and Anti-Hebbian Spike-Timing-Dependent Plasticity of Human Cortico-Cortical Connections

Learning of new skills may occur through Hebbian associative changes in the synaptic strength of cortical connections [spike-timing-dependent plasticity (STDP)], but how the precise temporal relationship of the presynaptic and postsynaptic inputs determines the STDP effects in humans is poorly understood. We used a novel paired associative stimulation protocol to repeatedly activate the short-latency connection between the posterior parietal cortex and the primary motor cortex (M1) of the left-dominant hemisphere. In different experiments, we systematically varied the temporal relationships between the stimuli and the preferential activation of different M1 neuronal populations by applying transcranial magnetic stimulation over M1 with different coil orientations and in different states of cortical excitability (rest vs muscular contraction). We found evidence for the existence of both Hebbian and anti-Hebbian STDP in human long-range connections. The induction of bidirectional long-term potentiation or depression in M1 depended not only on the relative timing between the stimuli but, crucially, on the stimulation of specific neuronal populations and the activity state of the cortex. Our findings demonstrate that these mechanisms are not fixed but susceptible to rapid adaptations. This sudden transition from anti-Hebbian to Hebbian plasticity likely involves local dynamics of interaction with different populations of postsynaptic neurons.
Inhibition of Metalloprotease Botulinum Serotype A from a Pseudo-peptide Binding Mode to a Small Molecule That Is Active in Primary Neurons*

An efficient research strategy integrating empirically guided, structure-based modeling and chemoinformatics was used to discover potent small molecule inhibitors of the botulinum neurotoxin serotype A light chain. First, a modeled binding mode for inhibitor 2-mercapto-3-phenylpropionyl-RATKML (Ki = 330 nm) was generated, and required the use of a molecular dynamic conformer of the enzyme displaying the reorientation of surface loops bordering the substrate binding cleft. These flexible loops are conformationally variable in x-ray crystal structures, and the model predicted that they were pivotal for providing complementary binding surfaces and solvent shielding for the pseudo-peptide. The docked conformation of 2-mercapto-3-phenylpropionyl-RATKML was then used to refine our pharmacophore for botulinum serotype A light chain inhibition. Data base search queries derived from the pharmacophore were employed to mine small molecule (non-peptidic) inhibitors from the National Cancer Institute's Open Repository. Four of the inhibitors possess Ki values ranging from 3.0 to 10.0 μm. Of these, NSC 240898 is a promising lead for therapeutic development, as it readily enters neurons, exhibits no neuronal toxicity, and elicits dose-dependent protection of synaptosomal-associated protein (of 25 kDa) in a primary culture of embryonic chicken neurons. Isothermal titration calorimetry showed that the interaction between NSC 240898 and the botulinum A light chain is largely entropy-driven, and occurs with a 1:1 stoichiometry and a dissociation constant of 4.6 μm.
Impact of Different Shades of Plastic Mulch and Plant Geometry on Yield and Economics on Tender Stem Broccoli in Punjab, India

Tender Stem or tender stem broccoli is a green vegetable similar to tender stem broccoli but with smaller floret and longer, thin stalks. Often misidentified as young tender stem broccoli, it is a hybrid of tender stem broccoli and Chinese Kale which was first developed in 1993 by Sakata Seed Company in Yokohama, Japan, Sakata. Presently due to its small florets and subtle sweet flavor it is very popular in European market.
A floor sensor system for gait recognition

This paper describes the development of a prototype floor sensor as a gait recognition system. This could eventually find deployment as a standalone system (e.g. a burglar alarm system) or as part of a multimodal biometric system. The new sensor consists of 1536 individual sensors arranged in a 3 m by 0.5 m rectangular strip with an individual sensor area of 3 cm/sup 2/. The sensor floor operates at a sample rate of 22 Hz. The sensor itself uses a simple design inspired by computer keyboards and is made from low cost, off the shelf materials. Application of the sensor floor to a small database of 15 individuals was performed. Three features were extracted : stride length, stride cadence, and time on toe to time on heel ratio. Two of these measures have been used in video based gait recognition while the third is new to this analysis. These features proved sufficient to achieve an 80% recognition rate.