Miracle-dz/UniFAR-FTUs huggingface dataset:
Concentration-jump experiments with NMDA antagonists in mouse cultured hippocampal neurons.

1. Voltage-clamp experiments were used to study N-methyl-D-aspartic acid (NMDA) receptor antagonists applied by fast perfusion to mouse hippocampal neurons in dissociated culture. 2. Preincubation with the NMDA antagonists zinc (3-30 microM) and magnesium (30-300 microM) reduced subsequent responses to 100 microM NMDA applied together with these antagonists. No time dependence of antagonism was observed when responses were measured at the start and at the end of NMDA pulses 1.25-1.5 s in duration. 3. Two competitive antagonists of similar affinity in equilibrium experiments, D-2-amino-5-phosphonopentanoic acid (D-AP5) and 3-((+-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), had different profiles of action when applied as described above. With D-AP5, pulses of NMDA produced fast-on, fast-off responses, of reduced amplitude, similar to the effect of Zn and Mg. Responses to NMDA in the presence of CPP were also of reduced amplitude but, in addition, showed slow activation, such that the antagonist action of CPP decreased with time after the application of NMDA. 4. In the presence of 3 microM glycine and NMDA receptor antagonists with activity at the glycine modulatory site, either kynurenic acid (Kyn), 7-chlorokynurenic acid (7Cl-Kyn), or 5-chloro-indole-2-carboxylic acid (5Cl-I2CA), NMDA-evoked responses showed apparent use-dependent antagonism, such that the peak response to NMDA was much greater than the equilibrium response. A similar effect was produced by preincubation with low concentrations of glycine (less than 300 nM), which enhances desensitization of responses to NMDA. The apparent use-dependent action of glycine antagonists could be reversed on raising the glycine concentration and did not vary appreciably with changes in membrane potential over the range -60 to +50 mV. 5. Concentration-jump application of NMDA antagonists, in the presence of 100 microM NMDA and 3 microM glycine, were used to study antagonist association and dissociation kinetics directly. For D-AP5 and CPP, the dissociation rate was independent of antagonist concentration, and approximately 15 times faster for D-AP5 (19.6 s-1) than for CPP (1.36 s-1). The association rate for D-AP5 and CPP increased with antagonist concentration in a linear manner over the range 3-30 microM and was slower for CPP than for D-AP5, consistent with their similar potency at equilibrium. 6. In contrast to results obtained with CPP and D-AP5, the association rate for 7Cl-Kyn was approximately 3 times slower than the dissociation rate and did not change with concentration of antagonist. (ABSTRACT TRUNCATED AT 400 WORDS)
Piezoelectric energy harvesting from transverse galloping of bluff bodies

The concept of harvesting energy from transverse galloping oscillations of a bluff body with different cross-section geometries is investigated. The energy is harvested by attaching a piezoelectric transducer to the transverse degree of freedom of the body. The power levels that can be generated from these vibrations and the variations of these levels with the load resistance, cross-section geometry, and freestream velocity are determined. A representative model that accounts for the transverse displacement of the bluff body and harvested voltage is presented. The quasi-steady approximation is used to model the aerodynamic loads. A linear analysis is performed to determine the effects of the electrical load resistance and the cross-section geometry on the onset of galloping, which is due to a Hopf bifurcation. The normal form of this bifurcation is derived to determine the type (supercritical or subcritical) of the instability and to characterize the effects of the linear and nonlinear parameters on the level of harvested power near the bifurcation. The results show that the electrical load resistance and the cross-section geometry affect the onset speed of galloping. The results also show that the maximum levels of harvested power are accompanied with minimum transverse displacement amplitudes for all considered (square, D, and triangular) cross-section geometries, which points to the need for performing a coupled analysis of the system.
Subarachnoid hemorrhage and cerebral vasospasm – Literature review

Subarachnoid hemorrhage represents a serious disease with high mortality and morbidity. Two important areas are becoming the central research interest of subarachnoid hemorrhage: cerebral vasospasm and early brain injury. The authors have reviewed the major contributions in experimental subarachnoid hemorrhage documented in the medical literature in the past 5 years. Treatments interfering with nitric oxide - or endothelin-pathways continue to show antispasmotic effects in experimental models of subarachnoid hemorrhage. Inflammation and oxidative stress play a vital role in the pathophysiology of cerebral vasospasm. Apoptosis, a relevant cause of early brain injury after subarachnoid hemorrhage, also underline the etiology of cerebral vasospasm. Future research studies will continue to elucidate the pathophysiological pathways and treatment modalities targeting cerebral vasospasm and early brain injury, enabling an improvement in outcome for patients with subarachnoid hemorrhage.
Sterilizing Activity of Second-Line Regimens Containing TMC207 in a Murine Model of Tuberculosis

Rationale The sterilizing activity of the regimen used to treat multidrug resistant tuberculosis (MDR TB) has not been studied in a mouse model. Objective and Methods Swiss mice were intravenously inoculated with 6 log10 of Mycobacterium tuberculosis (TB) strain H37Rv, treated with second-line drug combinations with or without the diarylquinoline TMC207, and then followed without treatment for 3 more months to determine relapse rates (modified Cornell model). Measurements Bactericidal efficacy was assessed by quantitative lung colony-forming unit (CFU) counts. Sterilizing efficacy was assessed by measuring bacteriological relapse rates 3 months after the end of treatment. Main Results The relapse rate observed after 12 months treatment with the WHO recommended MDR TB regimen (amikacin, ethionamide, pyrazinamide and moxifloxacin) was equivalent to the relapse rate observed after 6 months treatment with the recommended drug susceptible TB regimen (rifampin, isoniazid and pyrazinamide). When TMC207 was added to this MDR TB regimen, the treatment duration needed to reach the same relapse rate dropped to 6 months. A similar relapse rate was also obtained with a 6-month completely oral regimen including TMC207, moxifloxacin and pyrazinamide but excluding both amikacin and ethionamide. Conclusions In this murine model the duration of the WHO MDR TB treatment could be reduced to 12 months instead of the recommended 18–24 months. The inclusion of TMC207 in the WHO MDR TB treatment regimen has the potential to further shorten the treatment duration and at the same time to simplify treatment by eliminating the need to include an injectable aminoglycoside.
Comparative Action of Sedative Hypnotics on Neurophysiology of Sleep

In spite of tremendous advances in medical science, sleep has not been understood completely. The causes for many of parasomnias are still not evident. Even then these parasomnias are treated with different drugs, one of the major groups among them being sedative hypnotics. The use of sedative hypnotics are always associated with adverse effect, and there is many a times loss of the normal sleep architecture. This causes problems both during drug intake and with the withdrawal of drugs. Hence the need for today is the use of sedative hypnotics with minimum alteration in sleep architecture. The changes in the sleep architecture with the administration of sedative hypnotics can be recorded with the changes in the normal sleep EEG pattern. In this review effort has been made in elaborating the various sleep EEG pattern changes, resulting with the use of different groups of sedative hypnotic drugs with a brief note on their respective mechanism of action and pharmacological properties.
Diabetic Vascular Disease : Pathophysiological Mechanisms in the Diabetic Milieu and Therapeutic Implications

In diabetes and insulin resistance, activation of protein kinase C (PKC) in vascular cells may be a key link between elevated plasma and tissue concentrations of glucose and nonesterified fatty acids and abnormal vascular cell signaling. Initial studies of PKC activation in diabetes focused on microvascular complications, but increasing evidence supports that PKC plays a role in several mechanisms promoting atherosclerosis. This review explains how PKC is thought to be activated in diabetes and insulin resistance through de novo synthesis of diacylglycerol. Furthermore, the review summarizes studies that implicate PKC in promoting proatherogenic mechanisms or inhibiting antiatherogenic mechanisms, including studies of endothelial dysfunction; gene induction and activation of vascular NAD(P)H oxidase; endothelial nitric oxide synthase expression and function; endothelin-1 expression; growth, migration, and apoptosis of vascular smooth muscle cells; induction of adhesion molecules; and oxidized low-density lipoprotein uptake by monocyte-derived macrophages. (Arterioscler Thromb Vasc Biol. 2005;25:487-496.)
Non-Union Rate With Stand-Alone Lateral Lumbar Interbody Fusion

AbstractRetrospective radiographic analysis.To determine the fusion rate of stand-alone lateral lumbar interbody fusion (LLIF). Biomechanical studies have indicated that LLIF may be more stable than anterior or transforaminal lumbar interbody fusion. Early clinical reports of stand-alone LLIF have shown success in obtaining fusion and indirectly decompressing nerve roots.A consecutive case series of stand-alone LLIF was analyzed with chart and radiographic review. Non-union was determined by symptomatology consistent with non-union and absence of bridging bone on the CT scan.Thirty-nine levels of stand alone LLIF were performed in 23 patients. Eleven patients received 1-level surgery, 7 patients received 2-level surgery, 3 patients received 3-level surgery, and 1 patient received 4-level surgery. Excluding 1 infected case, we analyzed 37 levels of stand alone LLIF in 22 patients. Non-union incidence was 7 levels in 6 patients. Non-union rate was 7/37 (19%) per level and 6/22 (27%) per patient.While our study population was relatively low, a non-union rate of 19% to 27% is concerning for modern spine surgery. Currently in our practice, we occasionally still perform stand-alone LLIF utilizing 22 mm wide grafts in low-demand levels in non-smoking and non-osteoporotic patients. However, in a majority of patients, we provide supplemental fixation: bilateral pedicle screws in most patients and unilateral pedicle screws or spinous process plates in some patients.
Evaluating Machine Translation Utility via Semantic Role Labels

We present the methodology that underlies mew metrics for semantic machine translation evaluation we are developing. Unlike widely-used lexical and n-gram based MT evaluation metrics, the aim of semantic MT evaluation is to measure the utility of translations. We discuss the design of empirical studies to evaluate the utility of machine translation output by assessing the accuracy for key semantic roles. These roles are from the English 5W templates (who, what, when, where, why) used in recent GALE distillation evaluations. Recent work by Wu and Fung (2009) introduced semantic role labeling into statistical machine translation to enhance the quality of MT output. However, this approach has so far only been evaluated using lexical and n-gram based SMT evaluation metrics like BLEU which are not aimed at evaluating the utility of MT output. Direct data analysis are still needed to understand how semantic models can be leveraged to evaluate the utility of MT output. In this paper, we discuss a new methodology for evaluating the utility of the machine translation output, by assessing the accuracy with which human readers are able to complete the English 5W templates.
Ticagrelor Does Not Inhibit Adenosine Transport at Relevant Concentrations: A Randomized Cross-Over Study in Healthy Subjects In Vivo

Background and Purpose In patients with myocardial infarction, ticagrelor reduces cardiovascular and sepsis-related mortality, and can cause dyspnea. It is suggested that this is caused by adenosine receptor stimulation, because in preclinical studies, ticagrelor blocks the nucleoside transporter and increases cellular ATP release. We now investigated the effects of ticagrelor on the adenosine system in humans in vivo. Experimental Approach In a double-blinded, placebo-controlled cross-over trial in 14 healthy subjects, we have tested whether ticagrelor (180 mg) affects adenosine- and dipyridamole-induced forearm vasodilation, as surrogates of nucleoside uptake inhibition and adenosine formation, respectively. Also, ex vivo uptake of adenosine and uridine in isolated red blood cells was measured. Primary endpoint was adenosine-induced vasodilation. Key Results Ticagrelor did not affect adenosine- or dipyridamole-induced forearm vasodilation. Also, ex vivo uptake of adenosine and uridine in isolated red blood cells was not affected by ticagrelor. In vitro, ticagrelor dose-dependently inhibited nucleoside uptake, but only at supra-physiological concentrations. Conclusion and Implications In conclusion, at relevant plasma concentration, ticagrelor does not affect adenosine transport, nor adenosine formation in healthy subjects. Therefore, it is unlikely that this mechanism is a relevant pleiotropic effect of ticagrelor. Trial Registration ClinicalTrials.gov NCT01996735
Mobile device-based mindfulness intervention promotes emotional regulation during anticipatory stress

Mindfulness training applications for mobile devices are increasing in number and use, but little is known on their effectiveness. Our study (N = 107) is the first to examine the effect of a brief mobile-based mindfulness intervention on the emotional reactions to anticipatory social stress. Results show that the intervention is effective in weakening the increase of negative affect related to anticipatory stress, mostly in men. Implications and future research directions are discussed.
Partial Purification and Characterization of Rhodanese from Rainbow Trout (Oncorhynchus mykiss) Liver

Cyanide is one of the most toxic substances present in a wide variety of food materials that are consumed by animals. Rhodanese, a ubiquitous enzyme, can catalyse the detoxification of cyanide by sulphuration reaction. In this study, rhodanese was partially purified and characterized from the liver tissue homogenate of the rainbow trout. The enzyme was active in a broad range of pH, from 5 to 12. The optimal activity was found at a high pH (pH 10.5), and the temperature optimum was 25°C. The enzyme was heat labile, losing > 50% of relative activity after only 5 min of incubation at 40°C. The K m values for KCN and Na2S2O3 as substrates were 36.81 mM and 19.84 mM, respectively. Studies on the enzyme with a number of cations showed that the activity of the enzyme was not affected by Sn2+, but Hg2+, Ba2+, Pb2+, and Ca2+ inhibited and Cu2+ activated the enzyme with a concentration-dependent manner.
Predicting Ligand Binding Modes from Neural Networks Trained on Protein-Ligand Interaction Fingerprints

We herewith present a novel approach to predict protein-ligand binding modes from the single two-dimensional structure of the ligand. Known protein-ligand X-ray structures were converted into binary bit strings encoding protein-ligand interactions. An artificial neural network was then set up to first learn and then predict protein-ligand interaction fingerprints from simple ligand descriptors. Specific models were constructed for three targets (CDK2, p38-α, HSP90-α) and 146 ligands for which protein-ligand X-ray structures are available. These models were able to predict protein-ligand interaction fingerprints and to discriminate important features from minor interactions. Predicted interaction fingerprints were successfully used as descriptors to discriminate true ligands from decoys by virtual screening. In some but not all cases, the predicted interaction fingerprints furthermore enable to efficiently rerank cross-docking poses and prioritize the best possible docking solutions.
Independence Detection for Multi-Agent Pathfinding Problems

Problems that require multiple agents to follow noninterfering paths from their current states to their respective goal states are called multi-agent pathfinding problems (MAPFs). In previous work, we presented Independence Detection (ID), an algorithm for breaking a large MAPF problem into smaller problems that can be solved independently. Independence Detection is complete and can be used in combination with both optimal and approximation algorithms. This paper serves as an introduction to Independence Detection and aims to clarify its details.
Sebaceous carcinoma of the vulva: critical approach to grading and review of the literature.

BACKGROUND Sebaceous glands are abundant on the vulva, but vulvar sebaceous carcinoma (SC) is an uncommon neoplasm. METHODS We report a case of SC of the vulva in a 51 year-old woman. RESULTS The patient presented a 6-month history of an asymptomatic 2.5 x 1.5 cm exophytic tumour localized on the left labium majora. Tumorectomy was performed. Histologically, the lesion had an irregular lobular growth pattern composed of lobules or sheets of malignant cells separated by fibrovascular stroma. There was a mixture of sebaceous-type differentiation, small ducts and areas showing basaloid or squamous features. Centrally-located tumour cells showed moderate EMA immunoreactivity, especially enhancing cytoplasmic "bubbliness". Tumour cells were immunoreactive for CAM 5.2. The immunoreactivity for intranuclear p53 staining was > 10%. Southern blot hybridization and PCR studies did not detect HPV DNA. Hemivulvectomy was performed. After 18 months of follow-up, the patient has no evidence of recurrence, metastases or other malignant tumours. CONCLUSIONS The grading of cutaneous SC proposed by Rutten et al. (World Health Organization Classification of Skin Tumours) and Patterson & Wick (Nonmelanocytic Tumours of the Skin. Armed Forces Institute of Pathology) is based on patterns of tumour growth rather than cytological features. Such grading of skin SC, including vulvar SC, should not be used since its prognostic value has not been sufficiently documented. As the number of reported vulvar SCs is very limited, their natural history is unknown and the optimal treatment has not been established. The follow-up of 7 reported cases supports the general opinion that the tumour may be aggressive. SC groin node metastases carry a devastating prognosis, and unrecognized disease in the inguinofemoral lymph nodes is nearly always fatal. The use of sentinel lymph nodes (SLN) has evolved as an effective surgical technique for identifying early subclinical regional nodal involvement for many solid tumours throughout the body for staging disease; this is because extra-ocular SCs cause widespread metastatic disease. In our opinion, SLN should be used in conjunction with wide local excision of the primary tumour to investigate regional subclinical metastases. In the presence of a positive sentinel node, early lymphadenectomy with or without radiotherapy could be used to reduce tumour-related morbidity and mortality. The histopathologic differential diagnosis of SC is wide-ranging, including virtually all other malignant clear cell tumours of the skin. The proliferative pattern, immunostaining and cytologic features permit exclusion of neoplasms that mimic SC, but a diagnosis of SC should be rendered only if the overall attributes of the lesion are appropriate for such a interpretation.
Longitudinal patterns of β-amyloid deposition in nondemented older adults.

BACKGROUND High levels of β-amyloid (Aβ) characterize Alzheimer disease. OBJECTIVE To investigate whether longitudinal changes in Aβ deposition can be detected in vivo in older adults without dementia (hereafter referred to as nondemented). DESIGN Prospective study. SETTING Community-dwelling older adults. PARTICIPANTS Twenty-four nondemented participants (4 with a baseline Clinical Dementia Rating Scale score of 0.5; mean [SD] age, 79.2 [8.1] years) in the Baltimore Longitudinal Study of Aging underwent serial carbon 11-labeled Pittsburgh Compound B-positron emission tomography ([(11)C]PiB-PET) (follow-up at a mean [SD] of 1.5 [0.5] years), with 5 participants undergoing a third [(11)C]PiB-PET examination. MAIN OUTCOME MEASURES Annual changes in distribution volume ratio (DVR) were evaluated using a global index of cortical DVR (cDVR) and region-of-interest analyses. Given the variability of cDVR at the initial PiB-PET, annual changes in cDVR in those with minimal vs those with elevated initial cDVR were compared. RESULTS In nondemented older adults, annual increase in [(11)C]PiB retention is 0.011 DVR per year (0.9%; P = .01), which localizes to the prefrontal, parietal, lateral temporal, occipital, and anterior and posterior cingulate cortices. Annual change in cDVR is greater in older adults with elevated cDVR than in those with a minimal initial cDVR (P = .006). CONCLUSIONS Fibrillar Aβ detected by [(11)C]PiB-PET increases over time even in nondemented older adults. Individuals with higher initial [(11)C]PiB retention have greater rates of Aβ deposition, providing evidence of differential rates of Aβ deposition. Moreover, regional vulnerabilities to Aβ deposition allow for more targeted investigation of early Aβ changes.
Residual Stress Evolution during the Manufacturing Process of Bearing Rings

An innovative X-ray diffractometer was used to measure the residual stress being the source of a typical deformation failure called ovality on bearing rings. The equipment performs the measurements without sample cutting making it possible to measure the stress state of the same rings after each processing step. Thus, the stress state evolution during the complete manufacturing scenario was monitored on the same rings and the manufacturing process was revised.
Security Analysis of OpenID

OpenID is a user-centric and decentralized Single Sign-On system. It enables users to sign into Relying Partiesby providing an authentication assertion from an OpenID Provider. It is supported by many leading internet companies and there are over a billion accounts capable of using OpenID. We present a security analysis of OpenID and the corresponding extensions and reveal several vulnerabilities. This paper demonstrates how identity information sent within the OpenID protocol can be manipulated, due to an improper verification of OpenID assertions and no integrity protection of the authentication request.