Miracle-dz/UniFAR-FTUs huggingface dataset:
A randomized study of two interferon- beta treatments in relapsing–remitting multiple sclerosis

Objective: To investigate whether the efficacy of interferon-beta (IFNβ) treatment of relapsing–remitting MS (RR-MS) was influenced by type, dose, and frequency of administration. Methods: From June 1996 through October 1997, the authors offered participation to all Danish RR-MS patients who met the following criteria: definite MS, at least two relapses within 2 years, age 18 to 55, and an Expanded Disability Status Scale (EDSS) score of ≤5.5. The study was multicenter, controlled, open-label, randomized, head-to-head comparing IFNβ-1a 22 μg once a week (n = 143) with IFNβ-1b 250 μg every other day (n = 158), both subcutaneously, for 24 months. Patients who declined randomization were offered treatment with IFNβ-1b 250 μg every other day (n = 120). The primary end-points were the annualized relapse rate, the time to first relapse, and neutralizing antibody formation. The secondary endpoint was time to sustained progression Results: The annual relapse rates were virtually equal in the two arms of the randomized study (IFNβ-1a: 0.70; IFNβ-1b: 0.71); so were the time to first relapse and the time to sustained progression. In the nonrandomized patients (IFNβ-1b), the annual relapse rate was not significantly different, but the time to progression was shorter. Conclusion: In this study, 250 μg interferon-beta-1b administered every other day did not prove clinically superior to once-a-week administration of 22 μg interferon-beta-1a.
The degradation (by distinct pathways) of human d‐amino acid oxidase and its interacting partner pLG72 – two key proteins in d‐serine catabolism in the brain

Human d‐amino acid oxidase (EC 1.4.3.3; hDAAO) is a peroxisomal flavoenzyme significantly enriched in the mammalian brain. hDAAO has been proposed to play (with serine racemase; EC 5.1.1.18) an essential role in the catabolism of d‐serine, an ‘atypical’ key signalling molecule that acts as allosteric activator of the N‐methyl‐d‐aspartate‐type glutamate receptor (NMDAr). hDAAO and its interacting partner pLG72 have been related to schizophrenia, a highly disabling psychiatric disorder in which a dysfunction of NMDA‐mediated neurotransmission is widely assumed to occur. We previously demonstrated that the d‐serine cellular concentration depends on hDAAO and pLG72 expression levels and that newly‐synthesized hDAAO interacts with its modulator in the cytosol, being progressively destabilized and inactivated. To obtain insight into the mechanisms regulating cellular d‐serine levels, we investigated the degradation pathways of hDAAO and pLG72 in U87 glioblastoma cells stably expressing enhanced yellow fluorescent protein‐hDAAO (peroxisomal), hDAAO‐enhanced yellow fluorescent protein (cytosolic) or pLG72‐enhanced cyan fluorescent protein (mitochondrial) proteins. hDAAO is a long‐lived protein: the peroxisomal fraction of this flavoprotein is degraded via the lysosomal/endosomal pathway (and blocking this pathway increases the cellular hDAAO activity and decreases d‐serine levels), whereas the cytosolic portion is ubiquitinated and targeted to the proteasome. By contrast, pLG72 shows a rapid turnover (t1/2 ≈ 25–40 min) and is degraded via the proteasome system, albeit not ubiquitinated. Overexpression of pLG72 increases the turnover of hDAAO, in turn playing a protective role against excessive d‐serine depletion.
Cytochrome c release and caspase‐3 activation during colchicine‐induced apoptosis of cerebellar granule cells

The microtubule‐disrupting agent colchicine is known to be neurotoxic toward certain neuronal populations including cerebellar granule cells (CGCs). In this study we investigated the involvement of cytochrome c release and caspase‐3 activation during colchicine‐induced CGC apoptosis. Treatment of rat CGCs with 1 μm colchicine (for up to 24 h) caused high molecular weight DNA fragmentation and nuclear condensation. An involvement of group II caspases (which includes caspase‐3) was demonstrated by the proteolytic degradation of poly(ADP‐ribose) polymerase (PARP) after 18 h exposure to colchicine. Colchicine induced a time‐dependent increase in Ac‐Asp‐Glu‐Val‐Asp‐α‐(4‐methyl‐coumaryl‐7‐amide) (DEVD‐MCA) cleavage activity in CGCs, which was blocked with a specific, peptide‐based, aldehyde inhibitor of group II caspases, i.e. DEVD‐CHO. We also observed a time‐dependent proteolysis of caspase‐3 as judged by the appearance of p17 which is one of the subunits of active caspase‐3. Activation of caspase‐3 during colchicine‐induced apoptosis may be mediated by cytochrome c since there was a close correlation between the time courses of cytochrome c release from the mitochondria and of caspase‐3 activation. Furthermore, colchicine‐induced apoptosis, as assessed by propidium iodide visualization of the nuclei, could be blocked by the caspase inhibitor benzyloxycarbonyl‐Val‐Ala‐Asp (O‐methyl) fluoromethyl ketone.
Chinese Herbal Medicines Attenuate Acute Pancreatitis: Pharmacological Activities and Mechanisms

Acute pancreatitis (AP) is a commonly occurring gastrointestinal disorder. An increase in the annual incidence of AP has been observed, and it causes acute hospitalization and high mortality. The diagnosis and treatment guidelines for AP recommend conservative medical treatments focused on reducing pancreatic secretion and secondary injury, as a primary therapeutic approach. Unfortunately, the existing treatment options have limited impact on the incidence and severity of AP due to the complex and multifaceted pathological process of this disease. In recent decades, Chinese herbal medicines (CHMs) have been used as efficient therapeutic agents to attenuate AP in Asian countries. Despite early cell culture, animal models, and clinical trials, CHMs are capable of interacting with numerous molecular targets participating in the pathogenesis of AP; however, comprehensive, up-to-date communication in this field is not yet available. This review focuses on the pharmacological activities of CHMs against AP in vitro and in vivo and the underlying mechanisms. A computational prediction of few selected and promising plant-derived molecules (emodin, baicalin, resveratrol, curcumin, ligustrazine, and honokiol) to target numerous proteins or networks involved in AP was initially established based on a network pharmacology simulation. Moreover, we also summarized some potential toxic natural products for pancreas in order to more safe and reasonable medication. These breakthrough findings may have important implications for innovative drug research and the future development of treatments for AP.
Trafficking mechanism of water channel aquaporin‐2

Targeted positioning of the water channel AQP2 (aquaporin‐2) strictly regulates body water homoeostasis. Trafficking of AQP2 to the apical membrane is critical for the reabsorption of water in renal collecting ducts. In addition to the cAMP‐mediated effect of vasopressin on AQP2 trafficking to the apical membrane, other signalling cascades can also induce this sorting. Recently, AQP2‐binding proteins which could regulate this trafficking have been discovered; SPA‐1 (signal‐induced proliferation‐associated gene‐1), a GAP (GTPase‐activating protein) for Rap1, and the cytoskeletal protein actin. This review summarizes recent advances related to the trafficking mechanisms of AQP2.
An evaluation of oral health-related quality of life in orthodontic patients treated with fixed and twin blocks appliances

Objective: To study the impact of orthodontic treatment on the quality of life in two patient groups, one treated with the twin block appliance and the other with fixed appliances. Materials and Methods: Ninety-eight patients, aged between 10 and 16 years, were recruited in the fixed (20 males and 29 females) or functional (29 males and 20 females) treatment groups. The oral health-related quality of life (OHRQoL) was measured before treatment and followed up at the end of the treatment. The instrument used to measure OHRQoL was a modified self-administered short version of the English Oral Health Impact profile (OHIP-16[E]) questionnaire. Results: OHRQoL worsened at the initial stages of the treatment. The overall score of OHRQoL reduced significantly at the end of the treatment in both groups. Both groups showed comparable improvements in OHRQoL as the treatment progressed (analysis of variance test P = 0.05). Conclusions: The OHRQoL patterns, during the treatment with fixed and twin block appliances, were very similar. This suggests that the functional appliance's impact on the QoL may be overestimates by clinicians. OHRQoL improved significantly with both fixed and functional appliances by the end of the treatment. The OHRQoL trends observed during the study can be communicated to patients and used to increase patients' compliance since they are made aware of the whole treatment process.
The Derived Equivalent Circuit Model for Magnetized Anisotropic Graphene

Due to the static magnetic field, the conductivity for graphene becomes a dispersive and anisotropic tensor, which complicates most modeling methodologies. In this communication, a novel equivalent circuit model is proposed for graphene with the magnetostatic bias based on the electric field integral equation. To characterize the anisotropic property of the biased graphene, the resistive part of the unit circuit is replaced by a resistor in series with current-controlled voltage sources (CCVSs). The CCVSs account for the off-diagonal parts of the surface conductivity tensor for the magnetized graphene. This proposed method is benchmarked with numerical examples. This communication also provides a new equivalent circuit model to deal with anisotropic materials.
Genetic Allee effects on performance, plasticity and developmental stability in a clonal plant

Negative effects of small population size on fitness, so-called Allee effects, may threaten population persistence even in intact habitat remnants. We studied genotypes of 14 isolated populations of the clonal plant Ranunculus reptans, for which molecular genetic (RAPD-) variability is higher for large than for small populations. In a competition-free greenhouse environment vegetative offspring of genotypes from large populations produced more rosettes and flowers, indicating higher fitness. Within-genotype coefficients of variation in performance traits, indicating developmental instability, were lower for genotypes from populations with higher RAPD-variability. In competition with a taller grass, we found relative reduction in leaf length less pronounced for plants from large populations, suggesting higher adaptive plasticity. Our experimental study of a plant with predominantly vegetative reproduction suggests, that negative genetic effects of recent habitat fragmentation, which so far rather were expected in plants with frequent sexual reproduction, are more severe and more common than previously acknowledged.
Anatomy of T cell autoimmunity to myelin oligodendrocyte glycoprotein (MOG): Prime role of MOG44F in selection and control of MOG‐reactive T cells in H‐2b mice

Myelin oligodendrocyte glycoprotein (MOG) is an important myelin target antigen, and MOG‐induced EAE is now a widely used model for multiple sclerosis. Clonal dissection revealed that MOG‐induced EAE in H‐2b mice is associated with activation of an unexpectedly large number of T cell clones reactive against the encephalitogenic epitope MOG35–55. These clones expressed extremely diverse TCR with no obvious CDR3α/CDR3β motif(s). Despite extensive TCR diversity, the cells required MOG40–48 as their common core epitope and shared MOG44F as their major TCR contact. Fine epitope‐specificity analysis with progressively truncated peptides suggested that the extensive TCR heterogeneity is mostly related to differential recognition of multiple overlapping epitopes nested within MOG37–52, each comprised of a MOG40–48 core flanked at the N‐ and/or the C‐terminus by a variable number of residues important for interaction with different TCR. Abrogation of both the encephalitogenic potential of MOG and T cell reactivity against MOG by a single mutation (MOG44F/MOG44A), together with effective down‐regulation of MOG‐induced EAE by MOG37–44A–52, confirmed in vivo the primary role for MOG44F in the selection/activation of MOG‐reactive T cells. We suggest that such a highly focused T cell autoreactivity could be a selective force that offsets the extensive TCR diversity to facilitate a more “centralized control” of pathogenic MOG‐related T cell autoimmunity.
Multiphase induction motor drives - : a technology status review

The area of multiphase variable-speed motor drives in general and multiphase induction motor drives in particular has experienced a substantial growth since the beginning of this century. Research has been conducted worldwide and numerous interesting developments have been reported in the literature. An attempt is made to provide a detailed overview of the current state-of-the-art in this area. The elaborated aspects include advantages of multiphase induction machines, modelling of multiphase induction machines, basic vector control and direct torque control schemes and PWM control of multiphase voltage source inverters. The authors also provide a detailed survey of the control strategies for five-phase and asymmetrical six-phase induction motor drives, as well as an overview of the approaches to the design of fault tolerant strategies for post-fault drive operation, and a discussion of multiphase multi-motor drives with single inverter supply. Experimental results, collected from various multiphase induction motor drive laboratory rigs, are also included to facilitate the understanding of the drive operation.
Convulsiones en los niños

Las convulsiones son el trastorno neurologico pediatrico mas frecuente, y del 4 al 10% de los ninos padece al menos una convulsion en los primeros 16 anos de vida [1]. La incidencia es maxima en los ninos menores de 3 anos de edad, y disminuye gradualmente en los ninos mayores [2]. Los estudios epidemiologicos revelan que unos 150.000 ninos padeceran un primer episodio convulsivo no provocado cada ano y, de ellos, 30.000 desarrollaran epilepsia [1]. La convulsion se define como una alteracion transitoria e involuntaria de la conciencia, el comportamiento, la actividad motora, la sensacion o la funcion autonomica causada por una tasa excesiva y la hipersincronia de las descargas de un grupo de neuronas cerebrales. La mayoria de las convulsiones van seguidas de un periodo postictal de menor capacidad de respuesta, cuya duracion es proporcional a la duracion de la actividad convulsiva. La epilepsia describe una situacion de susceptibilidad a las convulsiones recurrentes. La definicion clasica de estado epileptico es la actividad convulsiva continua o recurrente de mas de 30 minutos de duracion sin recuperacion de la conciencia. Durante la convulsion aumenta el flujo sanguineo cerebral, el consumo de oxigeno y de glucosa y la produccion de dioxido de carbono y de acido lactico. Las alteraciones sistemicas tempranas consisten en taquicardia, hipertension, hiperglucemia e hipoxemia. Las convulsiones breves raras veces producen efectos duraderos en el cerebro. Sin embargo, las convulsiones prolongadas pueden desembocar en acidosis lactica, rabdomiolisis, hiperpotasemia, hipertermia e hipoglucemia, situaciones que pueden asociarse con un dano neurologico permanente. El manejo de la via respiratoria y la finalizacion de la convulsion son las prioridades iniciales en los pacientes con convulsiones activas.
Super-Pipelined Implementation of IP Packet Classification

Abstract With developing all-optical communication networks, highly-functional and highspeed boundary routers and home gateways are becoming to be required. In this paper, high-speed pipelined algorithm for packet classification which is one of heavy load functions within boundary routers is proposed. Its software implementation scheme on a data-driven processor equipped with flexible capability of pipelined parallel processing is also discussed. Finally, it is shown at maximum performance exchanged for simulation and experimental hardware evaluation that the scheme achieves 12M IPv4 packets per second by only 6% additional hardware cost.
A mathematical model for synergistic eukaryotic gene activation.

The precise biochemical mechanism underlying the synergistic action of gene activators on eukaryotic transcription has eluded a solution, largely because of the technical difficulties inherent in analyzing the mechanics of a 2.5 MDa complex comprising greater than 50 polypeptide components. To complement the biochemical approach we have employed mathematical modeling as a means to understand the mechanism of synergy. Parameters relevant to activated transcription were varied in a simple biochemical system and the data were compared to the transcriptional response predicted by a multi-component statistical model. We found that the model achieved a consistent, semi-quantitative description of the measured transcriptional response, and enabled the characterization and measurement of thermodynamic parameters in the in vitro system. The results provide evidence for the existence of cooperativity in the activation process beyond what would be predicted from one current model suggesting that activators function solely by simple recruitment of the general transcription machinery to the promoter.
Exact eigenstates of a nanoscopic paraboloidal emitter: Field emission quantities and spot size of the near field electron microscope

The eigenstates of a paraboloidal nano-tip are obtained by solving exactly Schroedinger's equation. Then the incident current density (ICD) and parallel velocity of such an emitter are obtained and shown to exhibit a non-Fowler-Nordheim behavior. These explain partly the resolution of Near-Field SEM. Competing effects between the ICD and an applied field at constant voltage are found.
Predictors of upper limb recovery after stroke: a systematic review and meta-analysis

Objective: To systematically review and summarize the current available literature on prognostic variables relating to upper limb recovery following stroke. To identify which, if any variables predict upper limb recovery following stroke. Data sources: We completed searches in MEDLINE, EMBASE, AMED, CINAHL and Cochrane CENTRAL databases. Searches were completed in November 2010. Review methods: Studies were included if predictor variables were measured at baseline and linked to an outcome of upper limb recovery at a future time point. Exclusion criteria included predictor variables relating to response to treatment and outcome measurements of very specific upper limb impairments such as spasticity or pain. Two independent reviewers completed data extraction and assessed study quality. Results: Fifty-eight studies met the inclusion criteria. Predictor variables which have been considered within these studies include; age, sex, lesion site, initial motor impairment, motor-evoked potentials andsomatosensory-evoked potentials. Initial measures of upper limb impairment and function were found to be the most significant predictors of upper limb recovery; odds ratio 14.84 (95% confidence intervals (CI) 9.08–24.25) and 38.62 (95% CI 8.40–177.53), respectively. Conclusions: Interpretation of these results is complicated by methodological factors including variations in study populations, upper limb motor outcome scales, timing of baseline and outcome assessments and predictors selected. The most important predictive factors for upper limb recovery following stroke appears to the initial severity of motor impairment or function.
Safe and Effective Procedural Sedation for Gastrointestinal Endoscopy in Children

Objective: The aim of the study was to assess, by a review of published evidence, the safest and most effective way to provide procedural sedation (PS) in children undergoing gastrointestinal endoscopy (GIE). Methods: The databases MEDLINE, Cochrane Library, and Embase were used. Search terms “endoscopy, gastrointestinal” or “endoscopy, digestive system” were combined with “sedation,” “conscious sedation,” “moderate sedation,” “deep sedation,” and “hypnotics and sedatives. ” The final review was restricted to studies reporting specifically on safety (incidences of adverse events) and/or effectiveness (time characteristics, need for supplemental sedation, need for restraint, procedural success, provider satisfaction, and patient comfort) of PS for GIE in children younger than 18 years. Results: The search yielded 182 references and the final selection included 11 randomized controlled trials (RCTs) and 15 non-RCTs. Six sedation categories were identified: propofol, opioid/benzodiazepine, premedication, ketamine-, sevoflurane-, and midazolam-based. Only a few RCTs have compared different categories. Opioid/benzodiazepine- and propofol-based PS have a similar safety profile and a low incidence of major adverse events. Propofol-based sedation turned out to be the most effective regimen, with effectiveness comparable to general anesthesia. The addition of midazolam, fentanyl, remifentanil, and/or ketamine to propofol may increase the effectiveness without creating more adverse events. Data on midazolam-, ketamine- and sevoflurane-based sedation were generally too limited to draw conclusions. Conclusions: Despite a lack of RCTs containing all aspects of effectiveness and safety, the present evidence indicates propofol-based PS to be the best practice for PS in children undergoing GIE. Propofol can be safely administered by specifically trained nonanesthesiologists.
A high-performance blue filter for a white-led-based visible light communication system

A high-performance blue filter was demonstrated and employed to increase the modulation bandwidth and dramatically reduce the bit error rate of a white-LED-based VLC system. It has a very wide stopband (500-1050 nm), high transmittance passband (average 97.5 percent in the blue signal range of 430-485 nm), and a sharp and precise cutoff edge. Not only can the blue filter completely remove the slow phosphorescent component from modulated signals, but it can also effectively reject ambient solar radiation. Meanwhile, the blue light signals of the LED can almost be retained. This results in a high SNR and improves the performance of a VLC system, including increased modulation bandwidth and reduced BER. The BER can be dramatically reduced from 3.6 × 10-2 to 1.7 × 10-4 at 50 MHz bandwidth, and from 2.6 × 10-2 to 1.9 × 10-5 at a distance of 30 cm compared to a VLC system without our blue filter. More importantly, the stop band covers the whole response range of the receiver except for the blue signal band, which strongly increases the ability of a VLC system used in the sun or outdoors.