Miracle-dz/UniFAR-FTUs huggingface dataset:
Production and characterization of pharmacologically active recombinant human phosphodiesterase 4B in Dictyostelium discoideum

Phosphodiesterase 4B (PDE4B) is an important therapeutic target for asthma and chronic obstructive pulmonary disease. To identify PDE4 subtype‐specific compounds using high‐throughput assays, full‐length recombinant PDE4 proteins are needed in bulk quantity. In the present study, full‐length human PDE4B2 was expressed in the cellular slime mould Dictyostelium discoideum (Dd). A cell density of 2 x 107 cells/mL was obtained and up to 1 mg/L recombinant PDE4B2 was purified through Ni‐NTA affinity chromatography. The expressed protein was soluble and its activity was comparable to PDE4B2 protein expressed in mammalian cells (Km=1.7 μM). The functional significance of the Dd expression system is supported by the demonstration that, in concert with proteins expressed in mammalian systems, there are no major changes in the affinity for PDE4B2 inhibitors and substrates. These findings thus provide the first evidence that Dd can be utilized for the expression and purification of functionally active full‐length human PDE4B2 in large amounts required for high‐throughput screening of pharmacologically active compounds against this therapeutic target.
Idiopathic Generalized Epilepsies Recognized by the International League Against Epilepsy

Summary: There are eight syndromes currently recognized by the International League Against Epilepsy (ILAE) that would fit the original operational definition of idiopathic generalized epilepsy (IGE) syndromes, including benign myoclonic epilepsy in infancy; generalized epilepsy with febrile seizures plus, an entity in evolution; epilepsy with myoclonic absences; epilepsy with myoclonic‐astatic seizures; childhood absence epilepsy; juvenile absence epilepsy; juvenile myoclonic epilepsy; and epilepsy with generalized tonic–clonic seizures only. All of these syndromes can be easily diagnosed when distinctive features are present. In some cases, such features are not present or only appear later in the course of the disease, making it challenging to distinguish the various syndromes. Electroencephalogram (EEG) is the most helpful laboratory test and often will strongly support the diagnosis of IGE, but may not be very helpful in discriminating between several of the syndromes with overlapping features. The same applies for genetic testing, although it is expected that further research exploring the genotype‐phenotype relationships will enhance our abilities to make definitive diagnoses. At the current time, clinical features are still the cornerstone of accurate classification, and accurate classification, in turn, is the best predictor of outcome.
Current concepts in schizophrenia research: advancing progress towards understanding etiology and new treatments in year 2004.

Kraepelin [1] described a heritable illness, ‘Dementia Praecox’, later known as ‘schizophrenia’, that varied among individuals, but eventually progressed into profound cognitive impairment accompanied by neuronal degeneration. The times changed, however, following his classic published descriptions and several subsequent large-scale family studies confirming his views. These data were misinterpreted and abused to formulate the eugenic policies of the mid-20th-century Nazi regime in order to justify exterminating persons with these disabilities, particularly those with schizophrenia. For several years following this destructive era, schizophrenia was often only diagnosed after the so-called ‘organic’ causes could be ruled out. Thus, schizophrenia became a disorder, by definition, with no biologically known cause, but likely induced by a psychologically deficient earlychildhood environment.
Promoting behavior change from alcohol use through mobile technology: the future of ecological momentary assessment.

BACKGROUND Interactive and mobile technologies (i.e., smartphones such as Blackberries, iPhones, and palm-top computers) show promise as an efficacious and cost-effective means of communicating health-behavior risks, improving public health outcomes, and accelerating behavior change. The present study was conducted as a "needs assessment" to examine the current available mobile smartphone applications (e.g., apps) that utilize principles of ecological momentary assessment (EMA)-daily self-monitoring or near real-time self-assessment of alcohol-use behavior-to promote positive behavior change, alcohol harm reduction, psycho-education about alcohol use, or abstinence from alcohol. METHODS Data were collected and analyzed from iTunes for Apple iPhone(©) . An inventory assessed the number of available apps that directly addressed alcohol use and consumption, alcohol treatment, or recovery, and whether these apps incorporated empirically based components of alcohol treatment. RESULTS Findings showed that few apps addressed alcohol-use behavior change or recovery. Aside from tracking drinking consumption, a minority utilized empirically based components of alcohol treatment. Some apps claimed they could serve as an intervention; however, no empirical evidence was provided. CONCLUSIONS More studies are needed to examine the efficacy of mobile technology in alcohol intervention studies. The large gap between availability of mobile apps and their use in alcohol treatment programs indicates several important future directions for research.
Structural and Histologic Eyelid Changes Associated with 6 Months of Topical Bimatoprost in the Rabbit

Purpose: To determine the periorbital effects of daily 0.03% bimatoprost in New Zealand white (NZW) rabbits. Materials and Methods: NZW rabbits were treated with daily 0.03% bimatoprost, artificial tears, or left untreated. Following 3 and 6 months of treatment, eyelid measurements were obtained for both upper and lower eyelid distraction, as well as canthus-to-canthus measurements. Once complete, subjects were humanely euthanized and eyelid tissue was utilized for histology. Hematoxylin and eosin staining, along with Verhoeff Van Giesen staining was performed on paraffin-embedded sections. Tissue was also stained with mActin antibodies as a marker for fibroblast activity. Results: Daily, topical 0.03% bimatoprost induced eyelid tightening and shortening the NZW rabbit. These findings were most striking at the 6-month timepoint, suggesting a temporal component to these induced changes. Histologically, eyelid tissue demonstrated thinning in bimatoprost-treated eyelids compared with those receiving artificial tears. Slightly increased mActin and Verhoeff Van Giesen staining was observed, suggesting increased fibroblast activity and elastin production in prostaglandin analogs–treated eyelids. Conclusions: These findings suggest that eyelid tissue thins and tightens over time, following daily administration of 0.03% bimatoprost in the NZW rabbit. These findings are similar to what has been observed in human patients.
Expression of the Activating Transcription Factor 3 Prevents c-Jun N-Terminal Kinase-Induced Neuronal Death by Promoting Heat Shock Protein 27 Expression and Akt Activation

Activating transcription factor 3 (ATF3) is induced and functions both as a cellular response to stress and to stimulate proliferation in multiple tissues. However, in the nervous system ATF3 is expressed only in injured neurons. Here we reveal a function of ATF3 in neurons under death stress. Overexpression of ATF3 by adenovirus inhibits the mitogen-activated kinase kinase kinase 1 (MEKK1)–c-Jun N-Terminal Kinase (JNK)-induced apoptosis and induces neurite elongation via Akt activation in PC12 cells and superior nerve ganglion neurons. A DNA microarray study reveals that ATF3 expression and JNK activation induce expression of the heat shock protein 27 (Hsp27). Immunoprecipitation analysis and promoter assay for Hsp27 expression suggest that both ATF3 and c-Jun are necessary for transcriptional activation of Hsp27. Hsp27 expression significantly inhibits JNK-induced apoptosis as well as Akt activation in PC12 cells and superior cervical ganglion neurons. We conclude that the combination of ATF3 and c-Jun induces the anti-apoptotic factor Hsp27, which directly or indirectly activates Akt, and thereby possibly inhibits apoptosis and induces nerve elongation. Our results suggest that ATF3- and c-Jun-induced Hsp27 expression is a novel survival response in neurons under death stress such as nerve injury.
Neonatal screening for critical cardiovascular anomalies using pulse oximetry

Introduction Babies with cardiac anomalies are often asymptomatic at birth, and many remain undetected despite routine newborn examination. We retrospectively assessed the effect of routine pulse oximetry in detection of such anomalies from a hospital birth population of 31 946 babies born between 1 April 1999 and 31 March 2009. Method 29 925 babies who were not admitted to the neonatal unit at birth underwent postductal oxygen saturation measurement before discharge. If saturation was below 95% an examination was performed. If this was abnormal or saturation remained low, an echocardiogram was performed. All babies with cardiac anomaly diagnosed before 1-year were identified from the region's fetal abnormality database. Results Critical anomalies affected 27 infants (1 in 1180); 10 identified prenatally, 2 after echocardiogram was performed because of other anomalies, 2 in preterm infants, 2 when symptomatic before screening, 5 by oximetry screening, 1 when symptomatic in hospital after a normal screen and 5 after discharge home. Serious anomalies affected 50 infants (1 in 640); 8 identified antenatally, 7 because of other anomalies, 3 in the neonatal unit, 5 by pulse oximetry screening, 11 by routine newborn examination, and 16 after discharge home. Conclusions Routine pulse oximetry aided detection of 5/27 of critical and 5/50 of serious anomalies in this sample, but did not prevent five babies with critical and 15 with serious anomalies being discharged undiagnosed. Results from screening over 250 000 babies have now been published, but this total includes only 49 babies with transposition, and even smaller numbers of rarer anomalies.
Comunidades virtuales en el ciberespacio

Las nuevas tecnologias de la comunicacion estan desarrollando nuevas formas de socializacion. Alrededor de Internet han ido apareciendo comunidades virtuales que desarrollan sus propias formas de funcionamiento. En el articulo, partiendo de la definicion de los terminos comunidad y virtual, se senalan las caracteristicas de este nuevo tipo de socializacion y el papel que muchas de estas comunidades pueden jugar en la formacion de lo que Pierre Levy denomina la inteligencia colectiva. Despues de presentar una clasificacion de las comunidades virtuales, se analizan algunos aspectos que suelen concitar mas criticas sobre las relaciones que en estas comunidades se crean como el aislamiento de los individuos, el problema de la identidad y el caracter efimero o la precariedad de las relaciones que en ellas se establecen
Comparison of the tolerance and efficacy of LV5FU2-CPT11 and FOLFIRI regimens in front-line treatment of advanced colorectal cancer -A pooled analysis of 254 patients included in 2 randomised trials.

3576 Background: With only one 5FU bolus injection and an increased dose of 5FU by continuous infusion, the simplified LV5FU2 regimen is considered as effective as but less toxic and more convenient than the original LV5FU2 de Gramont regimen [Tournigand ASCO 1998 #1052]. LV5FU2-CPT11 and FOLFIRI are safe and active in the front-line treatment of metastatic colorectal cancer [Douillard Lancet 2000 -V303 trial, Tournigand JCO 2004 -V308 trial]. In both regimens, CPT11 is given at a dose of 180 mg/m2 combined with the LV5FU2 regimen for LV5FU2-CPT11 or with the simplified LV5FU2 regimen for FOLFIRI. METHODS We performed a comparison based on the individual data from the V303 and V308 trials to assess the safety profile and efficacy of LV5FU2-CPT11 and FOLFIRI. Main severe adverse events (NCI grade 3-4) possibly and probably related to treatment as well as the objective response rate (ORR) and progression-free survival (PFS) were compared by treatment group. RESULTS 145 pts received the LV5FU2-CPT11 combination in the V303 trial and 109 pts received the FOLFIRI regimen in the V308 trial. Pre-treatment characteristics appeared to be similar in the two groups except for the sex-ratio (F: LV5FU2-CPT11: 29.0%, FOLFIRI: 43.1%) and number of metastatic sites (≥3 sites: LV5FU2-CPT11: 14.5%, FOLFIRI: 4.6%). Severe neutropenia (24% vs. 45%, p=0.001) and asthenia (4% vs. 9%, ns) were less frequent whereas mucositis (10% vs. 4%, ns), nausea and vomiting (10% vs. 3%; ns) were more frequent with the FOLFIRI regimen. The frequency of severe diarrhea was 14% in both groups. ORR: LV5FU2-CPT11: 33.1% [95CI: 25.5-41.4], FOLFIRI: 56.0% [95CI: 46.1-65.5] (p<0.01, HR= 1.2 [1.1-1.3]. PFS: LV5FU2-CPT11: 5.7 months [95CI: 4.1-6.7], FOLFIRI: 8.5 months [95CI: 7.0-9.5] (ns). CONCLUSIONS This non-randomized retrospective comparison suggests that the FOLFIRI regimen has a different toxicity profile and may have higher efficacy than the LV5FU2-CPT11 regimen. [Table: see text].
Detection and quantitation by fluorescence in situ hybridization (FISH) and image analysis of HER‐2/neu gene amplification in breast cancer fine‐needle samples

Fine‐needle sampling, although a practical and noninvasive method of tissue acquisition, has rarely been used for HER‐2/neu fluorescent in situ hybridization (FISH). To assess HER‐2/neu gene amplification in mammary carcinoma, FISH signals on cytology and corresponding tissue biopsies were detected visually and measured by image analysis. The results were correlated with patient and tumor characteristics.
A morphometric study of the vagus nerve in amyotropic lateral sclerosis with circulatory collapse

Abstract Amyotrophic lateral sclerosis (ALS) shows peculiar abnormalities of the autonomic nervous system, including sympathetic hyperactivity, which might result in sudden death. In general, the sympathetic hyperactivity could be caused by disruption of vagal inhibition. Our objective was to evaluate the vagus nerve morphometrically in autopsy cases of ALS with sympathetic hyperactivity and circulatory collapse (CC). We investigated 10 autopsied ALS patients, six of whom had exhibited autonomic storms or CC. We also examined 10 patients without ALS as controls, and one patient with Guillain-Barré syndrome (GBS) who died from CC, for comparison. After obtaining the visceral branch of the left vagus nerve at necropsy, we analyzed the density of the myelinated and unmyelinated fibers, and the fiber diameter distribution for each fiber. Results showed that the densities of both myelinated and unmyelinated fibers in ALS patients with or without CC were not significantly different from those in control patients. In contrast, the GBS patient showed marked reduction in the whole myelinated and large unmyelinated fiber density. In conclusion, the autonomic storms or CC due to sympathetic hyperactivity in ALS could not be ascribed to the deafferentation of the baroreflex, and more central neural pathophysiology should be investigated.
Modeling of gauge predictive control system in hot rolling mill based on BP network

This article draws from the four-high mill production line upgrading project. Through the careful research and analysis on threading process in a hot rolling mill, we proposed a new gauge predictive control system in hot rolling mill based on BP network forecasting model. The experimental result indicated that the BP neural network control model rolls over the end product, the crosswise thick difference for ≤0.002mm, is higher than the common precise request.
Study of Nitric Oxide in Patients with Chronic Hepatitis C Genotype 4: Relationship to Viremia and Response to Antiviral Therapy

Hepatitis C virus (HCV) infection is a global medical problem. The role of Nitric oxide (NO) in chronic viral hepatitis is still unknown. It may play a prominent role as an antiviral agent that reduces its replication or as a mediator that causes accumulation of oxidative DNA damage and oncogenesis. The present study was carried out to study effect of combined peginterferon and ribavirin therapy for hepatitis C on NO in both responders and in non responder patients. The study included seventy three patients with positive serological markers for HCV. They were classified according to presence or absence of HCV viremia and the response to therapy. In addition sixteen control subjects were included. NO levels were determined as the stable end product nitrate and nitrite. Serum nitrite and nitrate concentrations in the patients with viral hepatitis were significantly higher than normal subjects and patients with serological evidence of hepatitis C infection in absence of viral load. The levels of nitrite ≥ 31 μM, nitrate ≥ 15 μM and NO2/NO3 ratio < 1.5 μM were associated with increased risk of resistance to therapy. The multivariate logistic regression analysis showed that NO2/NO3 ratio at levels < 1.5 μM was associated with HCV eradication independently. This study provides new insight into the pathogenesis of hepatitis C and highlights the effect of combined peginterferon and ribavirin on nitrite and nitrate as markers of endogenous NO system. There is a limitation level of NO that if it is increased above it may lead to non response to antiviral therapy. Therefore, it may be an important factor for chronic hepatitis C, which suggests an additional therapeutic pathway of anti-oxidants in combination with the standard regimen for further study.
Effects of increased nerve growth factor plasma levels on the expression of TrkA and p75NTR in rat testicles

In addition to their well‐known roles within the nervous system, the neurotrophins and their receptors regulate some functions in the reproductive system. In this study we used combined morphological and immunohistochemical techniques to investigate the presence and cellular localization in the rat testicle of the two receptors of nerve growth factor (NGF), i.e. TrkA and p75NTR. Furthermore, to evaluate whether increased plasma levels of NGF affect the ageing process, 4‐methylcathechol (4‐MC), an inductor of NGF synthesis, was administered. Both TrkA and p75NTR were expressed in rat testicles, but the pattern and intensity of immunoreaction were marginally different between them. In adult rats TrkA was expressed in spermatozoa and spermatids, and p75 was expressed in spermatogonia. In newborn rats TrkA immunoreactivity was found in the Leydig cells, whereas p75 was detected in a cellular layer that surrounds the seminiferous tubules. In adult treated animals the immunoreaction for TrkA and p75NTR was also localized in the spermatocytes, whereas in newborn treated rats no changes in the pattern of immunoreaction was observed. The present findings suggest a role of the NGF/TrkA/p75 system in the physiology of reproduction, but the practical relevance of this remains to be established.
Control performance of an air motor-can air motors replace electric motors?

Pneumatic actuators are among a variety of actuators under active study by the robotics community, for the advantages they offer over conventional electric actuators widely used in present-day robots. So far, however, only pneumatic cylinders which provide linear actuation have been mainly studied in literature. Air motors are the pneumatic counterparts of electric motors, providing rotary actuation. They have several advantages over electric motors, especially high power-to-weight and power-to-size ratios, good compliance, and resistance to environmental hazards. We consider the model-based control of vane-type air motors which are the most commonly used class of air motors. Various control problems are considered namely, position control, trajectory control, adaptive control, and force control. Results of experimental implementation on an industrial vane-type air motor illustrate the effectiveness of the air motor as a high-performance rotary actuator.
Clinical and neuropsychological characteristics of child and adolescent bipolar disorder

Background. The diagnosis of bipolar disorder in pre-pubertal populations remains difficult and often controversial. Consequently, the clinical and neuropsychological characteristics of mania in the child and adolescent years remain poorly defined. This review provides a clinical account of childhood and adolescent bipolar disorder and compares the neuropsychology and neuroanatomy of young BPD patients compared with adult BPD and childhood syndromes of attention deficit hyperactivity disorder (ADHD) and conduct disorder (CD). Method. Literature review based on Pubmed searches. Results. Early- and adult-onset mania and BPD may share a common pattern of neurobiological characteristics despite developmental variations in the clinical presentation. In contrast, important distinctions are apparent between the child-onset syndromes of BPD, ADHD and CD, specifically at the neural level. Conclusions. Disorders of affect dysregulation in childhood deserve closer neuroscientific and phenotypic scrutiny than given hitherto.
Moclobemide compared with second‐generation antidepressants in elderly people

Two multicentre studies are described here; the first compared moclobemide with mianserin and the second with maprotiline, both in elderly patients with a DSM‐III diagnosis of major depressive episode. In the first study, 80 eligible patients were randomized to either moclobemide 300–500 mg or mianserin 75–125 mg per day for 4 weeks. Mean reduction in Hamilton Rating Scale for Depression (HRSD) score was 52% in both groups. The overall assessment of efficacy was good or very good for 60% of the patients, and tolerance was considered good or very good for 85% of the patients in both groups; no significant differences between the 2 treatments were seen. The second study comprised 39 hospitalized patients randomized to either moclobemide 150–300 mg daily or maprotiline 75–150 mg daily for 6 weeks. At the end of treatment, HRSD scores declined 85% in both groups compared with baseline. The overall assessment of efficacy was over 90% good or very good in both groups. Tolerance was rated good or very good for 80% of moclobemide and 75% of maprotiline patients; none of these results differed significantly between the groups, indicating that moclobemide is as effective in elderly patients as the 2 second‐generation antidepressants. In view of the safety of moclobemide, it should be considered first‐line therapy for depression in elderly people.
Inhibition of gallbladder emptying decreases cholesterol saturation in bile in the richardson ground squirrel

Impaired gallbladder emptying is frequent in cholesterol gallstone disease as well as in predisposing conditions like pregnancy and obesity. Gallbladder hypomotility is considered a pathogenic factor for gallstone formation, providing the residence time for cholesterol crystal nucleation, but any effect on the enterohepatic circulation of bile acids and subsequently on biliary lipid composition is unknown. Therefore, we studied the effect of prolonged suppression of gallbladder emptying with a cholecystokinin (CCK‐A) receptor antagonist on bile formation in Richardson ground squirrels fed a trace versus a 1% cholesterol diet. Biliary lipid secretion was measured directly and bile acid pool size assessed by isotope dilution ([14C]‐cholic acid). Gallbladder contraction was determined in vitro in response to CCK. The CCK‐antagonist (MK‐329) greatly inhibited gallbladder contraction in vitro and increased gallbladder fasting volume and bile acid pool size in vivo. It significantly lowered the cholesterol saturation index by 35% and 46% in hepatic bile and by 18% and 28% in gallbladder bile in the trace and cholesterol diet groups, respectively. Bile acid secretion and bile flow doubled with the CCK‐receptor antagonist. Chronic CCK receptor antagonist–induced inhibition of gallbladder emptying increases bile acid secretion and thereby decreases cholesterol saturation in bile. Extensive biliary hypomotility thus leads to a more rapid cycling of bile acids by depriving the gallbladder of its function in the enterohepatic circulation. (HEPATOLOGY 1995; 22:325–331.)