Miracle-dz/UniFAR-FTUs huggingface dataset:
How Does Deep Brain Stimulation Work? Present Understanding and Future Questions

Abstract: High-frequency deep brain stimulation (DBS) of the thalamus or basal ganglia represents an effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson’s disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been vaulted forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address the present knowledge of the effects of high frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS. Four general hypotheses have been developed to explain the mechanism(s) of DBS: depolarization blockade, synaptic inhibition, synaptic depression, and stimulation-induced modulation of pathologic network activity. Using the results from microdialysis, neural recording, functional imaging, and neural modeling experiments, the authors address the main hypotheses and attempt to reconcile what have been considered conflicting results from different research modalities.
Cost minimization of service deployment in a multi-cloud environment

Public cloud computing allows one to rent virtual servers on a hourly basis. This raises the problematic of being able to decide which server offers to take, which providers to use, and how to use them to acquire sufficient service capacity, while maintaining a cost effective platform. This article proposes a new realistic model to tackle the problem, placing services into IAAS virtual machines from multiple providers. A flexible protocol is defined to generate real-life instances, and applied on two industrial cases with four real cloud providers. An evolutionary approach, with new specific operators, is introduced and compared to a MIP formulation. Experiments conducted on two data-sets show that the evolutionary approach is viable to tackle real-size instances in reasonable amount of time.
Financial Incentives to Promote Health Care Quality: The Hospital Acquired Conditions Nonpayment Policy

Over a decade ago it was estimated that in the United States 98,000 patients die each year from hospital acquired conditions (HAC). Recently it has been reported that this many patients now die annually from hospital acquired infections (HAI) alone. Currently, HAI affects 1.7 million U.S. citizens each year. Although these conditions are often called “preventable errors,” some are associated with particular hospital and physician cultures, and many of these conditions, such as pressure ulcer formation and infections, may be a sign of low facility staffing levels. Protocols have been developed that have been shown to lower the incidence of many HAC, but these have been slow to be adopted. Voluntary reporting mechanisms to ensure health care quality are reported as having reduced effectiveness by the Joint Commission and U.S. Department of Health and Human Services, Office of Inspector General reports. Transparency and public education have also met with resistance, but in the case of infections now have the support of major national medical organizations. As a further initiative to promote quality, financial incentives have been implemented by the Centers for Medicare and Medicaid Services. Surgeons have lived under stringent financial incentives since the mid-1980s when they were placed under global surgical fees. Medicare currently must make expenditure reductions because it is at risk of becoming insolvent within the decade. Implementation of financial incentives should depend upon a balance between the nonpayment of providers for nonpreventable HAC verses the promotion of health care quality and patient safety, the reduction in patient morbidity and mortality, the spurring of mechanisms to further reduce HAC, and the recouping of taxpayer dollars for HAC that could have been prevented.
Correction for age, education and other demographic variables in the use of the Mini Mental State Examination in Finland

The population‐based Helsinki Aging Study was comprised of three age groups: 75‐, 80‐ and 85‐year‐olds. A random sample of 511 subjects completed the Mini Mental State Examination (MMSE) and were assessed on the Clinical Dementia Rating ‐ scale (CDR). According to the CDR results 446 subjects were screened as non‐demented. Of these subjects 30% scored below or at 24 MMSE points. Age, education and social group had a significant effect on the MMSE scores, even after excluding the demented cases. Together they explained 10% of the total variance within the MMSE. Social group correlated with education. The MMSE scores were corrected according to age and education. Adjustment of the originally used cutpoint of 24 resulted in cutpoints of 25 and 26 among the 75‐year‐olds, in the low and high education groups respectively; 23 and 26 in the 80‐year‐olds; 22 and 23 in the 85‐year‐olds.
Expression of an ATP-binding cassette transporter-encoding gene (YOR1) is required for oligomycin resistance in Saccharomyces cerevisiae

Semidominant mutations in the PDR1 or PDR3 gene lead to elevated resistance to cycloheximide and oligomycin. PDR1 and PDR3 have been demonstrated to encode zinc cluster transcription factors. Cycloheximide resistance mediated by PDR1 and PDR3 requires the presence of the PDR5 membrane transporter-encoding gene. However, PDR5 is not required for oligomycin resistance. Here, we isolated a gene that is necessary for PDR1- and PDR3-mediated oligomycin resistance. This locus, designated YOR1, causes a dramatic elevation in oligomycin resistance when present in multiple copies. A yor1 strain exhibits oligomycin hypersensitivity relative to an isogenic wild-type strain. In addition, loss of the YOR1 gene blocks the elevation in oligomycin resistance normally conferred by mutant forms of PDR1 or PDR3. The YOR1 gene product is predicted to be a member of the ATP-binding cassette transporter family of membrane proteins. Computer alignment indicates that Yor1p shows striking sequence similarity with multidrug resistance-associated protein, Saccharomyces cerevisiae Ycf1p, and the cystic fibrosis transmembrane conductance regulator. Use of a YOR1-lacZ fusion gene indicates that YOR1 expression is responsive to PDR1 and PDR3. While PDR5 expression is strictly dependent on the presence of PDR1 or PDR3, control of YOR1 expression has a significant PDR1/PDR3-independent component. Taken together, these data indicate that YOR1 provides the link between transcriptional regulation by PDR1 and PDR3 and oligomycin resistance of yeast cells.
Design, synthesis, and biological evaluation of bifunctional thyrointegrin inhibitors: new anti-angiogenesis analogs

Context: Inhibition of pathological angiogenesis. Objective: Obtaining new transactivator, bifunctional, thyroid antagonist, non-toxic anti-angiogenic compounds. Materials and methods: In silico drug design, synthesis in bulk and biological evaluation in chick chorioallantoic membrane (CAM) model. Results: Significant inhibition (range 65–73%) at 0.25–2.0 µg/ml doses. Discussion and conclusion: The synthesis of compounds (9), (10), and (11) incorporating long-chain moieties guanidine, urea, methyl amine and, propyl amine substitutions, respectively, into the core molecular framework of tetrac (tetraiodothyroacetic acid) were undertaken. The evaluation of the anti-angiogenic bioactivity of these compounds in the CAM model revealed no loss of activity in comparison with tetrac and XT199, which showed nearly 86% inhibition at dose levels of 1 and 0.5 µg/ml, respectively, and validated the concept.
Oligomerization is involved in pore formation by Bordetella adenylate cyclase toxin

The Bordetella adenylate cyclase‐hemolysin (CyaA, ACT, or AC‐Hly) is a multifunctional toxin. Simultaneously with promoting calcium ion entry, CyaA delivers into host cells an adenylate cyclase enzyme (AC) and permeabilizes cell membrane by forming small cation‐selective pores. Indirect evidence suggested that these two activities were accomplished by different membraneinserted CyaA conformers, one acting as an AC‐delivering monomer and the other as an uncharacterized poreforming oligomer. We tested this model by directly detecting toxin oligomers in cell membrane and by assessing oligomerization of specific mutants with altered poreforming properties. CyaA oligomers were revealed in sheep erythrocyte membranes by immunogold labeling and directly demonstrated by pulldown of membraneinserted CyaA together with biotinylated CyaAAC‐ toxoid. Membrane oligomers of CyaAcould also be resolved by nondenaturing electrophoresis of mild detergent extracts of erythrocytes. Furthermore, CyaA mutants exhibiting enhanced (E581K) or reduced (E570K+E581P) specific hemolytic and pore‐forming activity were found to exhibit also a correspondingly enhanced or reduced propensity to form oligomers in erythrocyte membranes. On the other hand, processed CyaA, with the AC domain cleaved off by erythrocyte proteases, was detected only in a monomeric form excluded from the oligomers of unprocessed CyaA. These results provide the first direct evidence that oligomerization is involved in formation of CyaApores in target membranes and that translocation of the AC domain across cell membrane may be accomplished by monomelic CyaA. —Vojtova‐Vodolanova, J., Basler, M. , Osicka, R. , Knapp, O. , Maier, E. , Cerny, J., Benada, O. , Benz, R. , Sebo, P. Oligomerization is involved in pore formation by Bordetella adenylate cyclase toxin. FASEB J. 23, 2831–2843 (2009). www.fasebj. org
Transient Stability Analysis of Distribution Network with Dispersed Generation

In this paper transient stability of an existing 10 kV distribution network with combined heat and power plants, microturbinesand wind turbines is analyzed. In order to do this, dynamic models of the network and generators have been created and simulations for faults at different network locations have been done. From the analysis it appears that the most critical parameter, which influences transient stability in the test network, is the inertia of a microturbine. Simulations have shown that there is linear relationship between inertia constant of microturbine and critical clearing time. After that it has been checked that the protection of DG satisfies transient stability requirements. In the end, the possibility for providing DG support to the network during and after disturbances using fault ride-through concept has been considered and simulations illustrate that DG protection can guarantee transient stability in this case as well.
Glucocorticoid‐induced tumour necrosis factor receptor family related protein (GITR) mediates inflammatory activation of macrophages that can destabilize atherosclerotic plaques

Glucocorticoid‐induced tumour necrosis factor receptor family related protein (GITR) is the 18th member of the tumour necrosis factor receptor superfamily (TNFRSF18) and is known to interact with its cognate ligand GITRL (TNFSF18). We investigated the potential role of GITR in the pro‐inflammatory activation of macrophages. Immunohistochemistry and in situ hybridization analyses of human atherosclerotic plaques demonstrated that GITR and its ligand are expressed mainly in lipid‐rich macrophages. We then investigated the role of GITR in human and mouse monocyte/macrophage functions. Stimulation of GITR caused nuclear factor (NF)‐κB‐dependent activation of matrix metalloproteinase‐9 (MMP‐9) and pro‐inflammatory cytokine expression in both the human and mouse monocytic/macrophage cell lines, THP‐1 and RAW264.7, respectively. These cellular responses were also observed when the THP‐1 cells were treated with phorbol‐12 myristate‐13 acetate (PMA), which is known to induce macrophage differentiation. To demonstrate that these responses are not restricted to cultured cell lines, we tested primary macrophages. Both peritoneal and bone marrow‐derived macrophages responded to GITR stimulation with induction of MMP‐9 and tumour necrosis factor‐α (TNF‐α). Furthermore, the GITR staining pattern overlapped with those of MMP‐9 and TNF‐α in atherosclerotic plaques. These data indicate that GITR‐mediated macrophage activation may promote atherogenesis via the induction of pro‐atherogenic cytokines/chemokines, and destabilize the atherosclerotic plaques via the induction of the matrix‐degrading enzyme, MMP‐9.
Cytometry of ATM activation and histone H2AX phosphorylation to estimate extent of DNA damage induced by exogenous agents

This review covers the topic of cytometric assessment of activation of Ataxia telangiectasia mutated (ATM) protein kinase and histone H2AX phosphorylation on Ser139 in response to DNA damage, particularly the damage that involves formation of DNA double‐strand breaks. Briefly described are molecular mechanisms associated with activation of ATM and the downstream events that lead to recruitment of DNA repair machinery, engagement of cell cycle checkpoints, and activation of apoptotic pathway. Examples of multiparameter analysis of ATM activation and H2AX phosphorylation vis‐a‐vis cell cycle phase position and induction of apoptosis that employ flow‐ and laser scanning‐cytometry are provided. They include cells treated with a variety of exogenous genotoxic agents, such as ionizing and UV radiation, DNA topoisomerase I (topotecan) and II (mitoxantrone, etoposide) inhibitors, nitric oxide‐releasing aspirin, DNA replication inhibitors (aphidicolin, hydroxyurea, thymidine), and complex environmental carcinogens such as present in tobacco smoke. Also presented is an approach to identify DNA replicating (BrdU incorporating) cells based on selective photolysis of DNA that triggers H2AX phosphorylation. Listed are strategies to distinguish ATM activation and H2AX phosphorylation induced by primary DNA damage by genotoxic agents from those effects triggered by DNA fragmentation that takes place during apoptosis. While we review most published data, recent new findings also are included. Examples of multivariate analysis of ATM activation and H2AX phosphorylation presented in this review illustrate the advantages of cytometric flow‐ and image‐analysis of these events in terms of offering a sensitive and valuable tool in studies of factors that induce DNA damage and/or affect DNA repair and allow one to explore the linkage between DNA damage, cell cycle checkpoints and initiation of apoptosis. © 2007 International Society for Analytical Cytology
Pharmacognostical standardization and antidiabetic activity of Syzygium cumini (Linn.) barks (Myrtaceae) on streptozotocin-induced diabetic rats

Abstract Background: The objectives of the present study were phytochemical and pharmacological screening of bark of Syzygium cumini on streptozotocin (STZ)-induced diabetic Wistar albino rats. Methods: Dose selection was made on the basis of acute oral toxicity study (300–5,000 mg/kg b.w.) as per OECD guidelines. Rats were made diabetic by a single dose of STZ at 50 mg/kg b.w. intraperitoneally. The effect of Syzygium cumini extracts (500 mg/kg) on postprandial blood glucose level was determined in fasted diabetic and normal rats. Blood glucose levels were measured at 0, 30, and 90 min after the glucose administration in the OGTT study. The bark extracts were administered orally at the dose of 500 mg/kg for 21 days in the chronic study. Glibenclamide (2.5 mg/kg) was used as a standard drug for activity comparison. Statistical analyses were performed using one-way ANOVA followed by Bonferroni’s multiple comparison tests. Results: The phytochemical screening showed positive results for triterpenes/steroids, glycosides, carbohydrates, alkaloids, flavonoids, saponins, tannins and amino acids. Administration of Syzygium cumini extracts 30 min before oral glucose loading significantly suppressed (p<0.001) the rise in postprandial blood glucose levels in treated rats compared to control rats but less significant than glibenclamide. Daily, continuous oral treatment of STZ-induced diabetic with various extract of Syzygium cumini for 3 weeks resulted in significant reductions in fasting blood glucose levels compared with diabetic controls. The ethanol and aqueous extracts were most active. Conclusions: This study brings out the evidence regarding phytochemistry and pharmacological activities of Syzygium cumini.
A Novel On-Eye Wettability Analyzer for Soft Contact Lenses

Purpose. To develop novel methodology to assess two in vivo wettability parameters, contact angle and index of liquid spreading (ILS), for hydrogel contact lenses and to provide a comprehensive investigation of the measurement errors (repeatability) associated with these two parameters. Methods. A Novel On-eye Wettability Analyzer (NOWA) was constructed which delivered a drop of 0.4% sodium hyaluronate mixed with sodium fluorescein directly on to a lens surface in vivo while a two-camera digital system recorded both the resultant contact angle and liquid spreading. Ten subjects each wore a different etafilcon A lens (−0.50 DS) in the right eye for 30 min before measurement on three separate occasions. For contact angles, the coefficient of repeatability (COR) associated with three measurement conditions (image analysis COR, intrasubject COR, and intersubject COR) was determined. For ILS, the COR associated with two measurement conditions (intrasubject COR and intersubject COR) was also determined. Results. The in vivo contact angle for the etafilcon A lens was 19.8° ± 2.9° (mean ± standard deviation). COR values for contact angle were 3.2°, 5.2°, and 8.0° for image analysis, intrasubject measures, and intersubject measures, respectively. The mean ± standard deviation ILS was 2.0 ± 0.3 mm, and COR values were 0.4 and 0.8 mm for intrasubject and intersubject measures, respectively. Conclusions. This research demonstrates that it is possible to obtain hydrogel lens contact angles in vivo and to provide a new wettability parameter (ILS) with the NOWA instrumentation. The COR values obtained were considered to be acceptable. Intersubject COR values were greater than intrasubject COR values for both contact angle and ILS; this is likely to be due to greater variability of tear film characteristics between subjects than within an individual. The use of this novel methodology and its associated clinical parameters across a wider range of lens types in various clinical situations warrants further investigation.
Effects of water on cortical excitability in humans

The effects of water on cortical excitability, measured using magnetoencephalographic recordings, were investigated in a sample of 19 healthy volunteers in a double‐blind, placebo experiment comparing water with saline solution. Spontaneous magnetoencephalogram as well as auditory‐evoked magnetic fields were recorded before and after the drinking of 750 mL water (9 subjects) or saline solution (10 subjects) and during and after hyperventilation following the drinking conditions. Hyperventilation was used to enhance the hypothesized synchronizing effect of water on spontaneous magnetoencephalographic activity. In addition, the magnetic fields were measured during a dichotic listening task under attended and unattended conditions. The prediction, that intake of water, because of induced cell swelling, will increase neuronal excitability and lead to an increased synchronization of the spontaneous magnetoencephalogram during hyperventilation was confirmed. Hyperventilation induced an increase of spectral power in all frequency bands particularly theta and delta power after water drinking. Furthermore, there was an increase of magnetic mismatch negativity (MMNm) amplitude in attended conditions and a simultaneous decrease in unattended conditions after water drinking. N1m (magnetic N1 wave) revealed significant changes during experimental conditions: increase after drinking and decrease after hyperventilation in both groups. MMNm for attended conditions showed a high positive correlation with osmolality changes (difference in the mol solute per kg water before and after drinking); N1m and PNm (magnetic processing negativity) as well as MMNm for unattended conditions showed significant correlations with subjective ratings of thirst and mood state.
Knockout of the AtCESA2 Gene Affects Microtubule Orientation and Causes Abnormal Cell Expansion in Arabidopsis1[C][OA]

Complete cellulose synthesis is required to form functional cell walls and to facilitate proper cell expansion during plant growth. AtCESA2 is a member of the cellulose synthase A family in Arabidopsis (Arabidopsis thaliana) that participates in cell wall formation. By analysis of transgenic seedlings, we demonstrated that AtCESA2 was expressed in all organs, except root hairs. The atcesa2 mutant was devoid of AtCESA2 expression, leading to the stunted growth of hypocotyls in seedlings and greatly reduced seed production in mature plants. These observations were attributed to alterations in cell size as a result of reduced cellulose synthesis in the mutant. The orientation of microtubules was also altered in the atcesa2 mutant, which was clearly observed in hypocotyls and petioles. Complementary expression of AtCESA2 in atcesa2 could rescue the mutant phenotypes. Together, we conclude that disruption of cellulose synthesis results in altered orientation of microtubules and eventually leads to abnormal plant growth. We also demonstrated that the zinc finger-like domain of AtCESA2 could homodimerize, possibly contributing to rosette assemblies of cellulose synthase A within plasma membranes.
Condition-based reliability modeling for systems with partial and standby redundancy

In this paper, we introduce a temporal approach for assessing the reliability of systems with components that are subject to change their conditions over time. Such changes could be due to poor working conditions, improper maintenance, or any unexpected malformations throughout the system's useful life. This approach is mainly based on adopting time-dependent reliability functions for assessing condition-based reliability. Our approach can be applied to common situations where the failure rates of the system components have dissimilar distributions.
Monocular Perception of Biological Motion in Johansson Displays

Computer perception of biological motion is key to developing convenient and powerful human? computer interfaces. Algorithms have been developed for tracking the body; however, initialization is done by hand. We propose a method for detecting a moving human body and for labeling its parts automatically in scenes that include extraneous motions and occlusion. We assume a Johansson display, i.e., that a number of moving features, some representing the unoccluded body joints and some belonging to the background, are supplied in the scene. Our method is based on maximizing the joint probability density function (PDF) of the position and velocity of the body parts. The PDF is estimated from training data. Dynamic programming is used for calculating efficiently the best global labeling on an approximation of the PDF. Detection is performed by hypothesis testing on the best labeling found. The computational cost is on the order of N4 where N is the number of features detected. We explore the performance of our method with experiments carried on a variety of periodic and nonperiodic body motions viewed monocularly for a total of approximately 30,000 frames. The algorithm is demonstrated to be accurate and efficient.