Miracle-dz/UniFAR-FTUs huggingface dataset:
The Actin Cytoskeleton Controls the Efficiency of Killer Ig-Like Receptor Accumulation at Inhibitory NK Cell Immune Synapses1

Killer cell Ig-like receptors (KIRs) are MHC class I-specific receptors expressed in NK and T lymphocytes. KIR antagonism of activation signals occurs at the immune synapse between the effector and target cells. The processes that regulate clustering of KIR are not well defined. We have expressed KIR-GFP receptor chimeras in two human NK-like lines, YTS and NK92. In this study, we show that the frequency of KIR enrichment at the synapse was decreased for a KIR that lacks a portion of the cytoplasmic tail. Strikingly, blocking actin polymerization with a high dose of cytochalasin D also substantially decreased clustering of KIR as well as KIR-induced clustering of HLA-C-GFP in target cells. However, the effect of inhibiting actin polymerization was only clearly evident at the earlier time points after cell mixing, and eventually clustering of KIR and HLA-C occurred independently of actin remodeling. Although treatment with anti-LFA-1 also decreased conjugate formation, the frequency of KIR clustering remained normal within the population of conjugates that did form, suggesting that the effect of cytochalasin D is not solely through LFA-1. Collectively, these data suggest that the actin cytoskeleton and the cytoplasmic tail of KIR regulate the efficiency by which KIR accumulates at inhibitory NK cell synapses.
Longitudinal evaluation reveals a complex spectrum of virological profiles in hepatitis B virus/hepatitis C virus–coinfected patients

Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection is often associated with severe forms of liver disease. However, comprehensive studies are lacking, and scant information is available regarding the virological behavior over time in coinfected patients. This study enrolled 133 untreated HBV/HCV‐positive patients (male/female = 102/31; median age 51 years [range: 22‐83 years]) who were longitudinally followed up for 1 year with bimonthly evaluation of HBV/HCV viremia levels and liver biochemistry. Thirty of these patients had triple infection with hepatitis Delta virus (HDV), while 103 patients were HDV‐negative. In the HDV‐negative group, active infection with both HBV and HCV was revealed in 24 cases, inactive infection by both viruses was seen in 15 cases, active HBV/inactive HCV was seen in 15 cases, and inactive HBV/active HCV was seen in 49 cases. However, 32 subjects (31%) presented dynamic virological profiles characterized by fluctuation of HBV and/or HCV viremia levels that at different time points were over or under the cutoff limits. Consequently, a correct diagnosis could be performed in these subjects only by serially repeating the virological tests 1 year apart. Similarly, 15 of the 30 HDV‐positive subjects showed active HBV and/or HCV infection, with fluctuating virological patterns in 8 cases. In conclusion, this study showed that the virological patterns in HBV/HCV coinfection are widely divergent and have dynamic profiles. A careful longitudinal evaluation of the viremia levels of both viruses is essential for making a correct diagnosis and tailoring the appropriate therapeutic schedule in coinfected patients. (HEPATOLOGY 2005.)
Transmit diversity combining for wideband DS/CDMA in wireless communication systems

Wideband code-division multiple-access (CDMA) will be utilized in the third generation or 3G wireless communication systems because of its high frequency utilization efficiency and suitability for handling multimedia and multi-rate services. In this paper, we present a system with a simplified receiver structure for DS/CDMA wireless communication handsets, in which improved performance is demonstrated when compared to a conventional DS/CDMA system with a RAKE receiver at the mobile station. The proposed system is obtained by finding the optimal solution to a general multiple-input single-output (MISO) DS/CDMA smart antenna system. It is shown that this solution reduces to a pre-RAKE with space transmit diversity system under the assumption that a simplified receiver structure is invoked. Numerical results show that significant system performance and capacity improvements are possible. They also reveal that the proposed system is not too sensitive to channel estimation errors.
Graphes linguistiques multiniveau pour l'extraction de connaissances : l'exemple des collocations. (Multilevel linguistic graphs for knowledge extraction : the example of collocations)

Pour modeliser au mieux les phenomenes linguistiques dans les systemes de traitement automatique des langues (traduction, analyse, etc.), il faut disposer de ressources de qualite. Or, les ressources existantes sont souvent incompletes et ne permettent pas de traiter correctement les donnees. Cette these s'interesse a l'acquisition de connaissances linguistiques, plus precisement a leur extraction a partir de corpus. Nous etudions en particulier le probleme des collocations, ces couples de termes dont l'un est choisi en fonction de l'autre pour exprimer un sens particulier (comme " pluie battante " ou " pluie " exprime l'intensification). Pour permettre l'acquisition de donnees a grande echelle, il faut la rendre facile a realiser de maniere automatique, et simple a parametrer par des linguistes aux connaissances limitees en programmation ; cela necessite une modelisation adaptee et precise des donnees et des processus. Nous avons realise et decrivons MuLLinG, modele de graphes linguistiques multiniveau, ou chaque niveau represente l'information d'une maniere differente,et les operations de manipulation de ces graphes. Ce modele permet de representer et traiter divers types de ressources. En effet, les operations associees ont ete ecrites pour etre les plus generiques possibles : elles sont independantes de ce que peuvent representer les nœuds et les arcs du graphe, et de la tâche a realiser. Cela permet a notre modele, mis en œuvre et utilise pour plusieurs experimentations (entre autres l'extraction de collocations), de voir un processus parfois complexe d'extraction de connaissances linguistiques comme une succession d'operations simples de manipulation de graphes.
Duloxetine for the Treatment of Generalized Social Anxiety Disorder: A Preliminary Randomized Trial of Increased Dose to Optimize Response

ABSTRACT Objective: This is the first trial examining duloxetine for generalized social anxiety disorder (GSAD) and the effect of increased dose for those without early remission. Methods: Individuals (n=39) with GSAD received 6 weeks of open-label duloxetine 60 mg/day; those with a Liebowitz Social Anxiety Disorder Scale (LSAS) score >30 at week 6 were randomized in double-blind fashion to an additional 18 weeks of continued duloxetine 60 mg/day or to duloxetine 120 mg/day. Results: Duloxetine was associated with a significant LSAS reduction at week 6 (91.3 [17.7] to 69.8 [28.5], paired t [df]=5.2 [38], P<.0001), and randomized participants overall continued to improve at week 24 (74.6 [23.9] to 60.3 [29.7]; paired t [df]=3.3 [27], P=.0026). Though the increased dose strategy was associated with a moderate effect size (Cohen's d=.57), there was no significant difference at week 24 endpoint in LSAS reduction (20.5 [26.0] versus 7.3 [17.2], t [df]=1.6 [26], P=.13) nor remission (33% versus 8%) for duloxetine with dose increased to 120 mg/day compared to duloxetine continued at 60 mg/day. Overall, 44% (17/39) discontinued prior to week 24. Conclusions: Though with limited power, these data provide preliminary support for the efficacy of duloxetine for GSAD, and suggest continued improvement but limited remission overall at 24 weeks for individuals remaining symptomatic at week 6. These observations warrant further controlled study.
Effects of carbonic anhydrase inhibitors on contraction, intracellular pH and energy‐rich phosphates of rat skeletal muscle.

1. The effects of carbonic anhydrase inhibitors on contractile parameters, intracellular pH (pHi) and energy‐rich phosphates were studied in isolated rat soleus and extensor digitorum longus (EDL) muscles. 2. The muscles were incubated either in Ringer solutions (95% O2/5% CO2 = control) or in solutions to which one of the inhibitors, 5 X 10(‐4) M‐chlorzolamide or 10(‐2) M‐NaCNO, had been added. Muscles were stimulated directly and contracted under isometric conditions. 3. Compared with control muscles, both inhibitor‐treated muscles showed a significantly decreased tetanic force and an increased half‐relaxation time of twitches and tetani. Chlorzolamide increased time‐to‐peak in both muscles. Cyanate decreased isometric twitch force in both muscles. 4. Both inhibitors decreased pHi in both muscles; chlorzolamide by 0.1 unit, cyanate by 0.4 unit in soleus and by 0.8 unit in EDL. 5. Chlorzolamide increased the concentrations of creatine and inorganic phosphate (Pi) in soleus (the effect of chlorzolamide was not studied in EDL). Cyanate caused these same changes in soleus as well as EDL and in addition decreased the concentrations of ATP and phosphocreatine in soleus and EDL. 6. In muscles acidified by either low external HCO3‐ (2 mM) or by elevated PCO2 (30% CO2 in the gas phase) in the bath, decreases in isometric force and increases in half‐relaxation time of tetani were observed. In addition there were increases in muscle Pi. These effects were more pronounced with 30% CO2 than with 2 mM‐HCO3‐. 7. Neither acidifying solutions prolonged either half‐relaxation time or time‐to‐peak of twitches. 8. We conclude that carbonic anhydrase inhibition exerts its effect (a) on isometric tension at least partly via an elevated Pi (perhaps in combination with lowered pHi); (b) on the half‐relaxation time of tetani by means of lowered pHi and elevated concentration of Pi; (c) on relaxation and time‐to‐peak of twitches by some unknown mechanism, neither directly by a change in pHi nor in Pi.
POBREZA ANTROPOMÉTRICA: UN ANÁLISIS BIDIMENSIONAL PARA EL NEA

Desde una perspectiva multidimensional al analisis de la pobreza, se adiciono una dimension antropometrica como referencia integral de bienestar humano, reinterpretando el signiﬁcado ﬁsiologico de la existencia de diferentes tipos de desnutricion presente en ninos entre 0,5 y 6 anos de edad como el de aquellos que sufriran carencias globales sobre sus capacidades y funcionalidades esenciales en el futuro. Por medio del analisis de datos recientes correspondientes al periodo 2004-2005 compuesto de 2157 observaciones del Nordeste Argentino, tasas de incidencias, brechas de la pobreza e indigencia asi como indices de Foster-Greer-Thorbecke convencionales y bidimensionales, fueron calculados para cada provincia de la region del NEA, ya sea utilizando solamente la variable ingreso o utilizando variables antropometricas como medidas de bienestar general para aquellas persona en desarrollo en la primera infancia. Dentro de un NEA comprometido, las provincias de Corrientes y Formosa seran las mas perjudicadas en terminos de capacidades cognitivas y culturales en la siguiente generacion de pobres.
Perceived causes of prescribing errors by junior doctors in hospital inpatients: a study from the PROTECT programme

Introduction Prescribing errors are a major cause of patient safety incidents. Understanding the underlying factors is essential in developing interventions to address this problem. This study aimed to investigate the perceived causes of prescribing errors among foundation (junior) doctors in Scotland. Methods In eight Scottish hospitals, data on prescribing errors were collected by ward pharmacists over a 14-month period. Foundation doctors responsible for making a prescribing error were interviewed about the perceived causes. Interview transcripts were analysed using content analysis and categorised into themes previously identified under Reason's Model of Accident Causation and Human Error. Results 40 prescribers were interviewed about 100 specific errors. Multiple perceived causes for all types of error were identified and were categorised into five categories of error-producing conditions, (environment, team, individual, task and patient factors). Work environment was identified as an important aspect by all doctors, especially workload and time pressures. Team factors included multiple individuals and teams involved with a patient, poor communication, poor medicines reconciliation and documentation and following incorrect instructions from other members of the team. A further team factor was the assumption that another member of the team would identify any errors made. The most frequently noted individual factors were lack of personal knowledge and experience. The main task factor identified was poor availability of drug information at admission and the most frequently stated patient factor was complexity. Conclusions This study has emphasised the complex nature of prescribing errors, and the wide range of error-producing conditions within hospitals including the work environment, team, task, individual and patient. Further work is now needed to develop and assess interventions that address these possible causes in order to reduce prescribing error rates.
Use of Top-down Fourier Transform Ion Cyclotron Resonance Mass Spectrometry for Mapping Calmodulin Sites modified by Platinum Anticancer Drugs

Calmodulin (CaM) is a highly conserved, ubiquitous, calcium-binding protein; it binds to and regulates many different protein targets, thereby functioning as a calcium sensor and signal transducer. CaM contains 9 methionine (Met), 1 histidine (His), 17 aspartic acid (Asp), and 23 glutamine acid (Glu) residues, all of which can potentially react with platinum compounds; thus, one third of the CaM sequence is a possible binding target of platinum anticancer drugs, which represents a major challenge for identification of specific platinum modification sites. Here, topdown electron capture dissociation (ECD) was used to elucidate the transition metal-platinum(II) modification sites. By using a combination of top-down and bottom-up mass spectrometric (MS) approaches, ten specific binding sites for mononuclear complexes, cisplatin and [Pt(dien)Cl]Cl, dinuclear complex [{cis-PtCl2(NH3)}2(μ-NH2(CH2)4NH2)] on CaM were identified. High resolution MS of cisplatin-modified CaM revealed that cisplatin mainly targets Met residues in solution at low
Impaired Interferon Gamma-Mediated Immunity and Susceptibility to Mycobacterial Infection in Childhood

Mendelian susceptibility to poorly virulent mycobacteria such as bacillus Calmette-Guerin (BCG) and environmental nontuberculous mycobacteria is a clinically heterogeneous syndrome. The clinical features of affected children cover a continuous spectrum from disseminated lethal bacillus Calmette-Guerin infection to local recurrent nontuberculous mycobacterial infection. Different types of mutations in four genes (IFNGR1, IFNGR2, IL12B, IL12RB1) have revealed both allelic and nonallelic heterogeneity and result in eight different disorders whose common pathogenic pathway is impaired interferon gamma (IFNγ) mediated immunity. The severity of the clinical phenotype depends on the genotype. Complete IL-12 p40 and IL-12 receptor β1 deficiencies and partial IFNγ receptor 1 (IFNγR1) and IFNγR2 deficiencies generally lead to curable infections at various ages, and antibiotics supplemented with IFNγ if required are likely to be effective. Complete IFNγR1 and IFNγR2 deficiencies predispose to overwhelming infection in early childhood, which may respond to antibiotics but relapse when antibiotics are discontinued. Rapid discrimination between complete IFNγR1 and IFNγR2 deficiency and other defects, therefore, is an important diagnostic step for planning clinical management.
Spatial and temporal memories are affected by sleep fragmentation in obstructive sleep apnea syndrome

This study evaluated episodic memory, with an emphasis on the recollection of spatial and temporal contexts, in 28 patients suffering from obstructive sleep apnea syndrome and 29 healthy controls. Recollection was assessed by means of the R/K paradigm and the process-dissociation procedure. Attentional abilities were also evaluated. A polysomnographic assessment, including nocturnal oxygen saturation and daytime sleepiness, was conducted. Recollection was strongly disturbed in patients, the number of microarousals being the best predictor of the memory deficit. Attention was only slightly disturbed. Results suggest a link between episodic memory deficit and those areas of the brain that are particularly sensitive to sleep fragmentation, in particular the hippocampus.
Two-Year Assessment of Entecavir Resistance in Lamivudine-Refractory Hepatitis B Virus Patients Reveals Different Clinical Outcomes Depending on the Resistance Substitutions Present

ABSTRACT Entecavir (ETV) is a deoxyguanosine analog approved for use for the treatment of chronic infection with wild-type and lamivudine-resistant (LVDr) hepatitis B virus (HBV). In LVD-refractory patients, 1.0 mg ETV suppressed HBV DNA levels to below the level of detection by PCR (<300 copies/ml) in 21% and 34% of patients by Weeks 48 and 96, respectively. Prior studies showed that virologic rebound due to ETV resistance (ETVr) required preexisting LVDr HBV reverse transcriptase substitutions M204V and L180M plus additional changes at T184, S202, or M250. To monitor for resistance, available isolates from 192 ETV-treated patients were sequenced, with phenotyping performed for all isolates with all emerging substitutions, in addition to isolates from all patients experiencing virologic rebounds. The T184, S202, or M250 substitution was found in LVDr HBV at baseline in 6% of patients and emerged in isolates from another 11/187 (6%) and 12/151 (8%) ETV-treated patients by Weeks 48 and 96, respectively. However, use of a more sensitive PCR assay detected many of the emerging changes at baseline, suggesting that they originated during LVD therapy. Only a subset of the changes in ETVr isolates altered their susceptibilities, and virtually all isolates were significantly replication impaired in vitro. Consequently, only 2/187 (1%) patients experienced ETVr rebounds in year 1, with an additional 14/151 (9%) patients experiencing ETVr rebounds in year 2. Isolates from all 16 patients with rebounds were LVDr and harbored the T184 and/or S202 change. Seventeen other novel substitutions emerged during ETV therapy, but none reduced the susceptibility to ETV or resulted in a rebound. In summary, ETV was effective in LVD-refractory patients, with resistant sequences arising from a subset of patients harboring preexisting LVDr/ETVr variants and with approximately half of the patients experiencing a virologic rebound.
An FIR-Embedded Noise Filtering Method for $\Delta \Sigma$ Fractional-N PLL Clock Generators

This paper describes a noise filtering method for ¿¿ fractional- N PLL clock generators to reduce out-of-band phase noise and improve short-term jitter performance. Use of a low-cost ring VCO mandates a wideband PLL design and complicates filtering out high-frequency quantization noise from the ¿¿ modulator. A hybrid finite impulse response (FIR) filtering technique based on a semidigital approach enables low-OSR ¿¿ modulation with robust quantization noise reduction despite circuit mismatch and nonlinearity. A prototype 1-GHz ¿¿ fractional-N PLL is implemented in 0.18 ¿m CMOS. Experimental results show that the proposed semidigital method effectively suppresses the out-of-band quantization noise, resulting in nearly 30% reduction in short-term jitter.
Molecular basis of slow activation of the human ether‐á‐go‐go related gene potassium channel

The human ether‐á‐go‐go related gene (HERG) encodes the pore forming α‐subunit of the rapid delayed rectifier K+ channel which is central to the repolarization phase of the cardiac action potential. HERG K+ channels have unusual kinetics characterized by slow activation and deactivation, yet rapid inactivation. The fourth transmembrane domain (S4) of HERG, like other voltage‐gated K+ channels, contains multiple positive charges and is the voltage sensor for activation. In this study, we mutated each of the positively charged residues in this region to glutamine (Q), expressed the mutant and wild‐type (WT) channels in Xenopus laevis oocytes and studied them using two‐electrode voltage clamp methods. K525Q channels activated at more hyperpolarized potentials than WT, whereas all the other mutant channels activated at more depolarized potentials. All mutants except for R531Q also had a reduction in apparent gating charge associated with activation. Mutation of K525 to cysteine (C) resulted in a less dramatic phenotype than K525Q. The addition of the positively charged MTSET to K525C altered the phenotype to one more similar to K525Q than to WT. Therefore it is not charge per se, but the specific lysine side chain at position 525, that is crucial for stabilizing the closed state. When rates of activation and deactivation for WT and mutant channels were compared at equivalent total (chemical + electrostatic) driving forces, K525Q and R528Q accelerated activation but had no effect on deactivation, R531Q slowed activation and deactivation, R534Q accelerated activation but slowed deactivation and R537Q accelerated deactivation but had no effect on activation. The main conclusions we can draw from these data are that in WT channels K525 stabilizes the closed state, R531 stabilizes the open state and R534 participates in interactions that stabilize pre‐open closed states.
Starting Dose Calculation for Medicinal Plants in Animal Studies; Recommendation of a Simple and Reliable Method

Background and purpose: Research studies indicate that almost 80% of the present day drugs are derived directly or indirectly from medicinal plants. The estimation of a safe starting dose is a concern when a new substance is to be investigated including medicinal plants, in clinical and laboratory studies. This study was intended to explore a simple and reliable method of calculating the starting dose for animal studies. Actually, the method helps to calculate the accurate animal dose based on Persian medicine. Methods: After the botanical names were identified, the dosages of the plants recommended in Persian medicine (PM) were converted to gram unit. Then the body surface area normalization method (BSA) was used for an allometric dose translation. Results: Ninety eight plants were identified and their effective parts and dosages were determined based Persian medicine. Conclusions: Dosing calculations for drugs could be performed based both on BSA method and experiences of ancient Persian scholars.