Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapamycin and Interleukin-1β Impair Brain-derived Neurotrophic Factor-dependent Neuron Survival by Modulating Autophagy*

Background: Autophagy is essential for normal neuron maintenance but can also promote death. Results: Brain-derived neurotrophic factor (BDNF) increases autophagosome formation but prevents excessive autophagic degradation by activating the mammalian target of rapamycin (mTOR). Conclusion: BDNF-dependent neuron survival requires suppression of autophagic flux, which was impaired by both rapamycin and interleukin-1β (IL-1β). Significance: mTOR inhibition subverts BDNF survival signals. The mammalian target of rapamycin (mTOR) pathway has multiple important physiological functions, including regulation of protein synthesis, cell growth, autophagy, and synaptic plasticity. Activation of mTOR is necessary for the many beneficial effects of brain-derived neurotrophic factor (BDNF), including dendritic translation and memory formation in the hippocampus. At present, however, the role of mTOR in BDNF's support of survival is not clear. We report that mTOR activation is necessary for BDNF-dependent survival of primary rat hippocampal neurons, as either mTOR inhibition by rapamycin or genetic manipulation of the downstream molecule p70S6K specifically blocked BDNF rescue. Surprisingly, however, BDNF did not promote neuron survival by up-regulating mTOR-dependent protein synthesis or through mTOR-dependent suppression of caspase-3 activation. Instead, activated mTOR was responsible for BDNF's suppression of autophagic flux. shRNA against the autophagic machinery Atg7 or Atg5 prolonged the survival of neurons co-treated with BDNF and rapamycin, suggesting that suppression of mTOR in BDNF-treated cells resulted in excessive autophagy. Finally, acting as a physiological analog of rapamycin, IL-1β impaired BDNF signaling by way of inhibiting mTOR activation as follows: the cytokine induced caspase-independent neuronal death and accelerated autophagic flux in BDNF-treated cells. These findings reveal a novel mechanism of BDNF neuroprotection; BDNF not only prevents apoptosis through inhibiting caspase activation but also promotes neuron survival through modulation of autophagy. This protection mechanism is vulnerable under chronic inflammation, which deregulates autophagy through impairing mTOR signaling. These results may be relevant to age-related changes observed in neurodegenerative diseases.
Pulmonary nodules and the CT halo sign.

PURPOSE To determine whether the "halo sign" at computed tomography (CT) could be used to differentiate hemorrhagic from nonhemorrhagic pulmonary nodules. MATERIALS AND METHODS CT scans of 12 patients with hemorrhagic pulmonary nodules and of a control group of 10 patients with nonhemorrhagic pulmonary nodules were randomized and reviewed by two chest radiologists. Nodules were considered hemorrhagic if a surrounding halo of ground-glass attenuation was present. RESULTS Nodules were correctly identified as either hemorrhagic or nonhemorrhagic by both observers in 19 of the 22 cases (86%). Eight of the 12 patients with hemorrhagic nodules had an infectious process including invasive aspergillosis, candidiasis, cytomegalovirus, herpes simplex virus, or coccidioidomycosis. Four of 12 patients with hemorrhagic nodules had a noninfectious cause including Wegener granulomatosis, metastatic angiosarcoma, and Kaposi sarcoma. CONCLUSION Most hemorrhagic pulmonary nodules have a characteristic CT appearance consisting of a central area of soft-tissue attenuation with a surrounding halo of ground-glass attenuation that allows distinction from nonhemorrhagic nodules.
Role of free Cys121 in stabilization of bovine beta-lactoglobulin B.

Mixed disulfide derivatives of bovine beta-lactoglobulin (BLG) were studied by circular dichroism (CD), gel-permeation HPLC and high-sensitivity differential scanning calorimetry (HS-DSC). It was shown that modification of Cys121 with mercaptopropionic acid and mercaptoethanol does not affect the secondary structure of BLG, but results instead in tertiary and quaternary structure changes. At neutral pH, the equilibrium dimer<==>monomer of modified beta-lactoglobulin is shifted towards monomeric form. In contrast to native BLG, thermal denaturation of modified beta-lactoglobulin is fully reversible in neutral and acidic pH as demonstrated by CD and HS-DSC measurements. Modification of Cys121 results in a significant decrease of transition temperature (-6 degrees C) and enthalpy (-106 kJ/mol) at pH 2.05 while unfolding heat capacity increment remains unchanged. Thermal unfolding transitions of native and modified beta-lactoglobulin at pH 2.05 are well approximated by a two-state model suggesting that no intermediate states appear after modification. The difference in Gibbs energy of denaturation between native and modified beta-lactoglobulin, 8.5 kJ/mol at 37 degrees C and pH 2.05, does not depend on the nature of the introduced group (charged or neutral). Computer analysis of possible interactions involving Cys121 in a three-dimensional structure of beta-lactoglobulin revealed that the thiol group is too far away from neighboring residues to form side-chain hydrogen bonds. This suggests that the sulfhydryl group of Cys121 may contribute to the maintenance of BLG tertiary structure via water mediated H-bonding.
Herpes Simplex Virus-Specific CD8+ T Cells Can Clear Established Lytic Infections from Skin and Nerves and Can Partially Limit the Early Spread of Virus after Cutaneous Inoculation1

HSV infects skin or mucosal epithelium as well as entering the sensory nerves and ganglia. We have used TCR-transgenic T cells specific for the immunodominant class I-restricted determinant from HSV glycoprotein B (gB) combined with a flank zosteriform model of infection to examine the ability of CD8+ T cells to deal with infection. During the course of zosteriform disease, virus rapidly spreads from the primary inoculation site in the skin to sensory dorsal root ganglia and subsequently reappears in the distal flank. Virus begins to be cleared from all sites about 5 days after infection when gB-specific CD8+ T cells first appear within infected tissues. Although activated gB-specific effectors can partially limit virus egress from the skin, they do so only at the earliest times after infection and are ineffective at halting the progression of zosteriform disease once virus has left the inoculation site. In contrast, these same T cells can completely clear ongoing lytic replication if transferred into infected immunocompromised RAG-1−/− mice. Therefore, we propose that the role of CD8+ T cells during the normal course of disease is to clear replicating virus after infection is well established rather than limit the initial spread of HSV from the primary site of inoculation.
: A Graph-based Fuzzy NoSQL Querying Model

NoSQL (Not only SQL) is an efficient database model for storing and manipulating huge quantities of precise data. However, most NoSQL databases scale well as data grows and often are flexible enough to accommodate imprecise and ambiguous data. This comprehensive hands-on guide presents fundamental concepts and practical solutions for using fuzziness with NoSQL to deals with fuzzy databases (FDB). In this paper, the authors present a graph-based fuzzy NoSQL model to deal with large fuzzy databases while extending the NoSQL one. The authors consider the cypher declarative query language proposed for Neo4j which is the current leader on this market to querying fuzzy databases.
Efficacy of Topical Cyclosporine 0.05% in the Treatment of Dry Eye Associated With Graft Versus Host Disease

Purpose: To assess the efficacy of topical cyclosporine 0.05% (Restasis) in patients with dry eye associated with graft versus host disease after stem cell transplantation. Methods: After completing a 3-month run-in period of using only artificial tears to control dry eye symptoms in both eyes, patients who failed to achieve adequate relief (n = 8) were instructed to instill topical cyclosporine twice a day. Visual acuity, slit-lamp appearance, and intraocular pressure were evaluated every 2 weeks for a minimum of 3 months. In addition, Schirmer basal secretion tests, noninvasive fluorescein breakup time, and tear lysozyme were also performed. Patients were also given a dry eye questionnaire regarding symptoms of burning, tearing, and blurred vision. Results: Dry eye signs improved significantly with cyclosporine treatment in 7 of 8 patients. Cyclosporine provided statistically significant improvements in Schirmer basal secretion scores (P = 0.003), tear breakup time (P = 0.002), and tear lysozyme levels (P = 0.033) after 3 months of treatment. Conclusion: The findings in this prospective study suggest that dry eye associated with graft versus host disease can be effectively treated with topical cyclosporine, especially in patients unresponsive to other treatment modalities. These findings should be further evaluated in large-scale, controlled clinical trials.
The metabolic cost of passive walking during robotics-assisted treadmill exercise.

BACKGROUND We are investigating the potential of robotics-assisted treadmill technology as a mode of exercise in people with spinal cord injury (SCI). People with incomplete SCI can actively contribute to this form of exercise, but in the clinical setting they often walk passively in the system. It is not known whether in doing so they are meeting the recommended guidelines for increasing cardiopulmonary fitness. OBJECTIVE The aims of this study were twofold: to characterise the intensity of passive walking during robotics-assisted treadmill exercise (RATE) in incomplete SCI; and to determine if this intensity meets the recommended guidelines for cardiopulmonary training in this population. METHODS 10 subjects with incomplete SCI twice performed an exercise test on a robotics-assisted treadmill. The test comprised a period of passive walking and a ramp phase to the limit of tolerance. Oxygen uptake VO(2) heart rate (HR) were continuously measured. RESULTS VO(2) during passive exercise was on average 1.4 times higher than resting VO(2R), but this was only 29% of peak VO(2) (VO(2 peak))(range 16-43%). Relative to rest, passive VO(2) (VO(2P) was only 12% of VO(2 peak). HR did not increase from rest to passive walking (81 ± 10 bpm to 81 ± 13 bpm respectively). The HR associated with passive walking was on average 50% of peak HR (HR(peak)) (161 ± 13 bpm). Test-retest reliability was moderate for VO(2R) (R=0.62) and resting HR (HR(R)) (R=0.68), high for VO(2P) (R=0.81), passive HR (HR(P)) (R=0.87) and HR(peak) (R=0.88), and very high (R=0.95) for VO(2 peak). Only HR(p) differed significantly between tests (p=0.029). CONCLUSIONS The intensity of passive walking during RATE is low and is insufficient to increase cardiopulmonary fitness in people with SCI. Subjects must actively contribute to the exercise in order to achieve the recommended training intensity.
Rates of primary percutaneous coronary intervention worldwide.

BACKGROUND Primary percutaneous coronary intervention (PCI) is at present the most effective procedure for reducing the mortality rate of patients with acute myocardial infarction (AMI). However, there is a great difference between Japan and other countries in the rate of primary PCI. METHODS AND RESULTS Registration period, number of patients with AMI, rates of primary PCI or thrombolysis and in-hospital or 30-day mortality rates were analyzed in 3 Japanese, 4 European, 4 American and 2 world-wide databases of AMI. The primary PCI rate is higher (75-94%) in Japan than in the other countries (5.5-49.6%), particularly in low-volume hospitals, and the mortality rates at these centers were similar to those in high-volume hospitals (approximately 4-10%). The primary PCI rate has recently been rising (25-50%) worldwide and most PCI procedures are performed in large-volume centers, except in Japan. CONCLUSIONS Comparison of the AMI databases suggest there is a relationship between the primary PCI rate and annual PCI caseload in each country. It is interesting that in Japan even low-volume PCI hospitals have comparable numbers of primary PCI cases.
'They are marvellous with you whilst you are in but the aftercare is rubbish': a grounded theory study of patients' and their carers' experiences after discharge following day surgery.

AIMS AND OBJECTIVES To explore patients' experiences following discharge from the day surgery unit. BACKGROUND The shape of twenty-first surgical care is changing. Due to political drivers, the self-care ethos and cost containment as well as technological advances, surgery, which previously required a lengthy hospital stay can now be performed in a day. Care that was previously performed by nurses is now transferred to the patient and their carer. DESIGN A Glaserian grounded theory methodology was used. METHODOLOGY A semi-structured interview took place by telephone on two occasions following discharge from 2004-2006. One hundred and forty-five patients and their carers were recruited from two day surgery units in the UK. Analysis took place by constant comparisons of interview data, line by line analysis and referral to field notes and memos until core categories emerged. RESULTS Three major themes emerged from this study: the difficulties patients encountered in caring for themselves or their loved ones; the desire for obtaining professional support once they were discharged home; and nostalgia for past times. CONCLUSION This study adds new insights to the discharge experiences of day surgery patients. Discharge planning should be started at the pre-assessment stage of the day surgery process and should be a joint venture between community staff, patients and day surgery nurses. More information should be given concerning community services available to the patients and educational programmes need to be developed to address the changing nature of surgical care. RELEVANCE TO CLINICAL PRACTICE Raising awareness of the problems patients may experience following discharge from day surgery may encourage a more pro-active attitude towards planning discharge services by a combined approach from day surgery nurses and community (district) nurses.
Kinetics and prognostic value of inflammatory-sensitive protein, IL-6, and white blood cell levels in patients undergoing coronary stent implantation.

BACKGROUND The levels of interleukin-6 (IL-6), white blood cells (WBCs), and some inflammatory-sensitive proteins (ISPs), such as fibrinogen (FIB) and C-reactive protein (CRP), have been related to coronary stent restenosis. The aim was to investigate the time course of the levels of IL-6, WBC, and several ISPs, i.e. FIB, CRP, cerruloplasmin (CER), haptoglobin (HPT), alpha-1 antitrypsin (A1AT), and alpha-1 acid glycoprotein (A1GP), after successful coronary stenting in patients with stable angina and to relate them to prognosis. MATERIAL/METHODS FIB, CRP, IL-6, CER, HPT, A1AT, A1GP, and WBC levels were measured in 40 patients with stable angina before, and 6, 12, 24, 48, and 72 hours and 6 months after successful coronary stenting. The patients were followed up for 12 months. RESULTS FIB levels increased significantly (p<0.05) 48 hours, CRP and WBC count 24 hours, CER, HPT, A1AT, and A1GP 72 hours, and IL-6 6 hours after stenting. All the levels remained unchanged in 20 control patients undergoing coronary angiography. During follow-up, stent restenosis occurred in 7 patients. Time-course and mean values of all the studied substances did not significantly differ in patients with or without restenosis (p>0.05). CONCLUSIONS FIB, CRP, IL-6, CER, HPT, A1AT, A1GP, and WBC levels increase significantly after stenting, but they are not related to prognosis.
Oxidant/antioxidant Parameters and their Relationship with Chemotherapy in Hodgkin's Lymphoma

This study investigated changing levels of serum oxidant/antioxidant with chemotherapy and their relation to treatment in 34 Hodgkin's lymphoma patients. The patient population consisted of 19 males and 15 females. Mean age was 30.41 ± 12.08 years. All patients received the adriamycin, bleomycin, vincristine and dexamethasone (ABVD) treatment protocol. Blood samples were taken before treatment, and on days 1 and 7 during treatment for measurement of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA), nitric oxide (NO) and enzyme activities. After ABVD treatment, mean free radical levels were increased and antioxidant levels were significantly decreased in the serum. ABVD treatment results in an increase of free radical levels and a decrease of antioxidant levels in the serum of patients with Hodgkin's lymphoma.
Synergism between a siRNA targeted to survivin and 5-FU in inhibiting MCF-7 cell proliferation in vitro.

OBJECTIVE To investigate the role of small interfering RNA (siRNA) targeted to survivin in combination with 5-fluorouracil (5-FU) in inhibiting the proliferation of MCF-7 cells. METHODS A siRNA targeted to survivin was synthesized and transfected into MCF-7 cells via lipofectin. Changes of the cell growth activity in response to combined treatment with survivin siRNA and 5-FU or 5-FU treatment alone was evaluated by MTT assay. The Q method of Jin Zhenjun was used to evaluated synergism between the synthesized siRNA and 5-FU. RESULTS Treatment with 5 nmol/L siRNA reduced the IC50 of 5-FU from 4.42 to 1.18 microg/ml, and the inhibitory effect of combined treatment on MCF-7 cells was higher than that of 5-FU alone (F=26.74, P<0.01). Synergism effect was observed between 5-FU at lower concentrations and survivin siRNA. CONCLUSION siRNA may enhance the effectiveness of 5-FU in inhibiting the proliferation of MCF-7 cells.
Effects of Exercise on Systemic Inflammatory, Coagulatory, and Cardiac Autonomic Parameters in an Inhalational Exposure Study

Background: Intermittent moderate-intensity exercise is used in human inhalational exposure studies to increase the effective dose of air pollutants. Objective: To investigate the inflammatory, coagulatory, and autonomic effects of intermittent moderate-intensity exercise. Methods: We measured hemodynamic, electrocardiographic, inflammatory, and coagulatory parameters in peripheral blood of 25 healthy subjects across an exercise protocol that included running on a treadmill or pedaling a cycle ergometer for 30 minutes every hour over 4 hours in a climate-controlled chamber with a target ventilation of 20 L/min/m2 body surface area. Results: Intermittent moderate-intensity exercise induced a systemic proinflammatory response characterized by increases in leukocyte counts, C-reactive protein, monocyte chemoattractant protein–1, and interleukin-6, but did not change coagulation tendency or heart rate variability. Conclusion: Interpretation of pollutant-induced inflammatory responses in inhalational exposure studies should account for signals and noises caused by exercise, especially when the effect size is small.
Effect of agar percentage, agar thickness, and medium constituents on antibiotics assay by disc diffusion method.

The factors affecting the sensitivity of nafcillin, vancomycin, oleandomycin, chloramphenicol, methacycline and novobiocin assay, using the paper disc diffusion method, were studied. Agar concentration and pour volume were found to influence the assay sensitivity of antibiotics. The type of assay medium was effective e.g. brain heart infusion agar was the best medium for nafcillin and methacycline; synthetic amino acid medium for oleandomycin; Muller Hinton agar for vancomycin and chloramphenicol; and G & R medium for novobiovicin. All additives, including inorganic ions, sugar, organic acids, complexing agents, surface active agents and blood, decreased the activities of the studied antibiotics. Higher activities of vancomycin, methacycline were observed at pH = 5, of nafcillin, chloramphenicol, and novobiocin at pH = 6, and of oleandomycin at pH = 7.
A Survey on Machine Learning: Concept,Algorithms and Applications

Over the past few decades, Machine Learning (ML) has evolved from the endeavour of few computer enthusiasts exploiting the possibility of computers learning to play games, and a part of Mathematics (Statistics) that seldom considered computational approaches, to an independent research discipline that has not only provided the necessary base for statistical-computational principles of learning procedures, but also has developedvarious algorithms that are regularly used for text interpretation, pattern recognition, and a many other commercial purposes and has led to a separate research interest in data mining to identify hidden regularities or irregularities in social data that growing by second. This paper focuses on explaining the concept and evolution of Machine Learning, some of the popular Machine Learning algorithms and try to compare three most popular algorithms based on some basic notions. Sentiment140 dataset was used and performance of each algorithm in terms of training time, prediction time and accuracy of prediction have been documented and compared.
Breed predisposition to congenital alacrima in dogs.

OBJECTIVE To evaluate the clinical characteristics and breed predisposition of congenital alacrima in dogs. Animals studied Dogs with congenital keratoconjunctivitis sicca. PROCEDURES A search of the medical records of the University of Tennessee Veterinary Teaching Hospital from 1974-2005 and the University of California-Davis Veterinary Teaching Hospital from 1986-2006 for dogs under 1 year of age with a diagnosis of keratoconjunctivitis sicca (KCS) was performed. These cases were further reviewed for dogs with a Schirmer's tear test I of <or= 5 mm/min before 6 months of age, with no known causes for KCS, which did not respond to appropriate KCS therapy; these cases were considered to have congenital alacrima. These breeds were compared to all other breeds using the Fisher's exact test with correction for multiple comparisons. RESULTS Congenital alacrima was identified in 19 dogs representing 11 breeds and mixed breeds. Yorkshire Terriers and Bedlington Terriers were statistically overrepresented compared to reference populations (P < 0.01 and P = 0.04, respectively). CONCLUSIONS Yorkshire terriers are significantly at risk for congenital alacrima compared to other breeds. The significance of the increase in congenital alacrima in Bedlington Terriers in this study may not be clinically relevant and may be due to the small total number of dogs of this breed that presented to the both hospitals. Based on the poor response to therapy in humans with congenital alacrima, it may be prudent to offer guarded prognoses for KCS in juvenile Yorkshire terriers.