Miracle-dz/UniFAR-FTUs huggingface dataset:
Changes in the Extracellular Concentrations of Amino Acids in the Rat Striatum During Transient Focal Cerebral Ischemia

Abstract: Although considerable evidence supports a role for amino acids in transient global cerebral ischemia and permanent focal cerebral ischemia, effects of transient focal cerebral ischemia on the extracellular concentrations of amino acids have not been reported. Accordingly, our study was undertaken to examine the patterns of changes of extracellular glutamate, aspartate, GABA, taurine, glutamine, alanine, and phosphoethanolamine in the striatum of transient focal cerebral ischemia, as evidence to support their pathogenic roles. Focal ischemia was induced using the middle cerebral artery occlusion model, with no need for craniotomy. Microdialysis was used to sample the brain's extracellular space before, during, and after the ischemic period. One hour of middle cerebral artery occlusion followed by recirculation caused neuronal damage that was common in the frontoparietal cortex and the lateral segment of the caudate nucleus. During 1 h of ischemia, the largest increase occurred for GABA and moderate increases were observed for taurine, glutamate, and aspartate. Alanine, which is a nonneuroactive amino acid, increased little. After recirculation, the levels of glutamate and aspartate reverted to normal baseline values right after reperfusion. Despite these rapid normalizations, neuronal damage occurred. Therefore, uptake of excitatory amino acids can still be restored after 1 h of middle cerebral artery occlusion, and tissue damage occurs even though high extracellular levels of glutamate are not maintained.
SIGCAS in the early days: a history from 1967 to 1985

This article is an excerpt from a chapter in a forthcoming book, Communities of Computing: Computer Science and Society in ACM. The chapter covers the debates that went on within ACM during the 1960s and 1970s about the organization's stance on issues such as the Vietnam War, the women's movement and the human rights of Soviet computer scientists. As the special interest group on Computers and Society, SIGCAS had a leading role to play in influencing ACM's position on social issues. This excerpt charts the emergence of SIGCAS as a special interest group and explores the SIGs relationship with ACM management. The article also considers the changing focus of SIGCAS members' interests over the first twenty years.
Constrained pole-zero linear prediction: An efficient and near-optimal method for multi-tone frequency estimation

Constrained pole-zero linear prediction (CPZLP) is proposed as a new method for parametric frequency estimation of multiple real sinusoids buried in noise. The method is based on a signal model that consists of a cascade of second-order constrained pole-zero models, thereby exploiting the linear prediction property of sinusoidal signals. The signal model is parametrized directly with the unknown frequencies, which are then estimated using a numerical optimization approach. By independently optimizing each second-order stage in the cascade model, a computationally efficient algorithm is obtained with a complexity that is linear in both the data record length and the number of sinusoids. The linear complexity allows for using relatively long data records, leading to high accuracy even at low signal-to-noise ratios (SNR). Simulation results confirm that the CPZLP algorithm nearly achieves the Cramér-Rao lower bound for SNR as low as 5 dB.
Mechanisms of Translocation of ER Chaperones to the Cell Surface and Immunomodulatory Roles in Cancer and Autoimmunity

Endoplasmic reticulum (ER) chaperones (e.g., calreticulin, heat shock proteins, and isomerases) perform a multitude of functions within the ER. However, many of these chaperones can translocate to the cytosol and eventually the surface of cells, particularly during ER stress induced by e.g., drugs, UV irradiation, and microbial stimuli. Once on the cell surface or in the extracellular space, the ER chaperones can take on immunogenic characteristics, as mostly described in the context of cancer, appearing as damage-associated molecular patterns recognized by the immune system. How ER chaperones relocate to the cell surface and interact with other intracellular proteins appears to influence whether a tumor cell is targeted for cell death. The relocation of ER proteins to the cell surface can be exploited to target cancer cells for elimination by immune mechanism. Here we evaluate the evidence for the different mechanisms of ER protein translocation and binding to the cell surface and how ER protein translocation can act as a signal for cancer cells to undergo killing by immunogenic cell death and other cell death pathways. The release of chaperones can also exacerbate underlying autoimmune conditions, such as rheumatoid arthritis and multiple sclerosis, and the immunomodulatory role of extracellular chaperones as potential cancer immunotherapies requires cautious monitoring, particularly in cancer patients with underlying autoimmune disease.
Attenuated heart rate response in REM sleep behavior disorder and Parkinson's disease

The objective of this study was to determine whether patients with Parkinson's disease with and without rapid‐eye‐movement sleep behavior disorder and patients with idiopathic rapid‐eye‐movement sleep behavior disorder have an attenuated heart rate response to arousals or to leg movements during sleep compared with healthy controls. Fourteen and 16 Parkinson's patients with and without rapid‐eye‐movement sleep behavior disorder, respectively, 11 idiopathic rapid‐eye‐movement sleep behavior disorder patients, and 17 control subjects underwent 1 night of polysomnography. The heart rate response associated with arousal or leg movement from all sleep stages was analyzed from 10 heartbeats before the onset of the sleep event to 15 heartbeats following onset of the sleep event. The heart rate reponse to arousals was significantly lower in both parkinsonian groups compared with the control group and the idiopathic rapid‐eye‐movement sleep behavior disorder group. The heart rate response to leg movement was significantly lower in both Parkinson's groups and in the idiopathic rapid‐eye‐movement sleep behavior disorder group compared with the control group. The heart rate response for the idiopathic rapid‐eye‐movement sleep behavior disorder group was intermediate with respect to the control and the parkinsonian groups. The attenuated heart rate response may be a manifestation of the autonomic deficits experienced in Parkinson's disease. The idiopathic rapid‐eye‐movement sleep behavior disorder patients not only exhibited impaired motor symptoms but also incipient autonomic dysfunction, as revealed by the attenuated heart rate response. © 2012 Movement Disorder Society
Trends in chlorinated hydrocarbon levels in Hudson River basin sediments.

Analysis of sections from dated sediment cores were used to establish geographic distributions and temporal trends of chlorinated hydrocarbon contaminant levels in sediments from natural waters of the Hudson River basin. Radiometric dating was based primarily on the depth distribution of 137(Cs) in the cores and on the occurrence of detectable levels of 7(Be) in surface sediment samples. Eighteen sampling sites included several along the main stem of the Hudson, its major tributaries, and components of the New York/New Jersey (NY/NJ) harbor complex. Drinking-water reservoirs were sampled to place upper limits on atmospheric inputs. Core sections were analyzed for polychlorinated biphenyls (PCBs), 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane (DDT)-derived compounds, chlordane, and dioxins. Sediment concentrations of most contaminants at most sites have decreased significantly since the mid-1960s. The data provide a basinwide perspective on major point-source inputs of PCBs to the upper Hudson River and of 2,3,7,8-tetrachlorodibenzo-p-dioxin and DDT to the lower Passaic River. Evidence was found for significant but poorly characterized sources of PCBs and chlordane to the western NY/NJ harbor, and of highly chlorinated dioxins to the upstream sites on the main stem of the Hudson. The results indicate that analysis of dated sediment samples is a most effective and efficient monitoring tool for the study of large-scale geographic and temporal trends in levels of particle-associated contaminants. ImagesFigure 1Figure 3Figure 4Figure 5Figure 6Figure 7
Repurposing Drugs in Oncology (ReDO)—itraconazole as an anti-cancer agent

Itraconazole, a common triazole anti-fungal drug in widespread clinical use, has evidence of clinical activity that is of interest in oncology. There is evidence that at the clinically relevant doses, itraconazole has potent anti-angiogenic activity, and that it can inhibit the Hedgehog signalling pathway and may also induce autophagic growth arrest. The evidence for these anticancer effects, in vitro, in vivo, and clinical are summarised, and the putative mechanisms of their action outlined. Clinical trials have shown that patients with prostate, lung, and basal cell carcinoma have benefited from treatment with itraconazole, and there are additional reports of activity in leukaemia, ovarian, breast, and pancreatic cancers. Given the evidence presented, a case is made that itraconazole warrants further clinical investigation as an anti- cancer agent. Additionally, based on the properties summarised previously, it is proposed that itraconazole may synergise with a range of other drugs to enhance the anti-cancer effect, and some of these possible combinations are presented in the supplementary materials accompanying this paper.
Genetic Risk for Violent Behavior and Environmental Exposure to Disadvantage and Violent Crime

Despite mounds of evidence to suggest that neighborhood structural factors predict violent behavior, almost no attention has been given to how these influences work synergistically (i.e., interact) with an individual’s genetic propensity toward violent behavior. Indeed, two streams of research have, heretofore, flowed independently of one another. On one hand, criminologists have underscored the importance of neighborhood context in the etiology of violence. On the other hand, behavioral geneticists have argued that individual-level genetic propensities are important for understanding violence. The current study seeks to integrate these two compatible frameworks by exploring gene–environment interactions (GxE). Two GxEs were examined and supported by the data (i.e., the National Longitudinal Study of Adolescent Health). Using a scale of genetic risk based on three dopamine genes, the analysis revealed that genetic risk had a greater influence on violent behavior when the individual was also exposed to neighborhood disadvantage or when the individual was exposed to higher violent crime rates. The relevance of these findings for criminological theorizing was considered.
Effect of Flow Split on Separation and Stagnation in A Model Vascular Bifurcation

This is a study of the flow disturbance in a plastic model of an asymmetric vascular bifurcation. A sidearm was attached to the mainlimb at an angle of 15° to the inlet flow axis. Water at steady flow was used and flow patterns were demonstrated by a dye injection technique. The proportion of inlet flow (Qi) exiting from the sidearm (Qs) was railed and flow patterns were recorded photographically. A laser Doppler anemometer (LDA) was used to measure near-wall velocity. At a physiologic Reynolds' number of 500, no flow disturbance occurred in the mainlimb when the sidearm was completely occluded. When the fraction of flow exiting from the sidearm (Qs/QI) reached 0.19, a region of boundary layer separation developed along the wall of the mainlimb opposite the flow divider. This region of nearly static fluid spread circumferentially around the mainlimb as Qs/Qi increased. Near-wall velocity within the separation decreased and became negative when Qs/Qi = 0J1. When Qs/Qi reached 0.38, the separation enveloped the wall of the entire bifurcation with a shell of slowly moving fluid. At the same time, the rapidly moving mainstream impinged directly on the flow divider. There is a similarity between the region of separation seen in this model and the site of formation of atherosclerotic plaque at me carotid bifurcation. Separation may contribute to atherogenesls by creating a region of low wall shear at bifurcations.
Compact Relaxations for MAP Inference in Pairwise MRFs with Piecewise Linear Priors

Label assignment problems with large state spaces are important tasks especially in computer vision. Often the pairwise interaction (or smoothness prior) between labels assigned at adjacent nodes (or pixels) can be described as a function of the label difference. Exact inference in such labeling tasks is still difficult, and therefore approximate inference methods based on a linear programming (LP) relaxation are commonly used in practice. In this work we study how compact linear programs can be constructed for general piecwise linear smoothness priors. The number of unknowns is O(LK) per pairwise clique in terms of the state space size $L$ and the number of linear segments K. This compares to an O(L^2) size complexity of the standard LP relaxation if the piecewise linear structure is ignored. Our compact construction and the standard LP relaxation are equivalent and lead to the same (approximate) label assignment.
Genome-Wide Analysis of Nucleotide-Level Variation in Commonly Used Saccharomyces cerevisiae Strains

Ten years have passed since the genome of Saccharomyces cerevisiae–more precisely, the S288c strain–was completely sequenced. However, experimental work in yeast is commonly performed using strains that are of unknown genetic relationship to S288c. Here, we characterized the nucleotide-level similarity between S288c and seven commonly used lab strains (A364A, W303, FL100, CEN.PK, ∑1278b, SK1 and BY4716) using 25mer oligonucleotide microarrays that provide complete and redundant coverage of the ∼12 Mb Saccharomyces cerevisiae genome. Using these data, we assessed the frequency and distribution of nucleotide variation in comparison to the sequenced reference genome. These data allow us to infer the relationships between experimentally important strains of yeast and provide insight for experimental designs that are sensitive to sequence variation. We propose a rational approach for near complete sequencing of strains related to the reference using these data and directed re-sequencing. These data and new visualization tools are accessible online in a new resource: the Yeast SNPs Browser (YSB; http://gbrowse.princeton.edu/cgi-bin/gbrowse/yeast_strains_snps) that is available to all researchers.
Minimum PCB footprint point-of-load DC-DC converter realized with Switched-Capacitor architecture

This work reports on the design and test of a CMOS-based Switched Capacitor (SC) DC-DC conversion integrated circuit (IC) for the point-of-load (POL) application conventionally addressed with the buck converter. A 12V-to-1.5V converter is fabricated in a 0. 18µm technology, with an active die area of 3mm2. There is a significant reduction in printed circuit board (PCB) footprint, passive component height and cost when compared to surveyed buck converters. The converter achieves 93% peak efficiency and an efficiency of 80% over an output current range of 7mA to 1A. This work demonstrates the vast potential of SC converters for wide-range voltage conversion in deep-submicron CMOS technologies, when cost and efficiency are of critical importance.
Mortality in Emergency Department Sepsis (MEDS) score predicts 1‐year mortality*

Objective: To assess the predictive performance for 1‐yr mortality of the previously derived and validated Mortality in Emergency Department Sepsis (MEDS) score. Design: Prospective cohort study. Patients: Consecutive adult (aged ≥18 yrs) emergency department patients presenting to an urban, tertiary care, university hospital were eligible if they had a clinically suspected infection as indicated by the decision to obtain a blood culture. The enrollment period was between February 1, 2000, and February 1, 2001. Of 3,926 eligible patient visits, 3,762 (96%) were enrolled and 3,102 unique first visits were analyzed. Interventions: None. Measurements and Main Results: A total of 667 patients (21.5%) died within 1 yr. The unadjusted 1‐yr mortality rates for the MEDS risk groups were: very low risk, 7%; low risk, 20%; moderate risk, 37%; high risk, 64%; very high risk, 80%. Using a Cox proportional hazard model that controlled for age, sex, and Charlson co‐morbidity index, the 1‐yr hazard ratios compared with the baseline very low–risk group were: low risk, 2.2 (1.7–2.9); moderate risk, 3.5 (2.7–4.6); high risk, 6.7 (4.9–9.3); and very high risk, 10.5 (7.2–15.4). The groups were significantly different (p < .0001). Conclusions: Although the score was initially derived for 28‐day in‐hospital mortality, our results indicate that the MEDS score also predicts patient survival at 1 yr after index hospital visit with suspected infection. The score needs external validation before widespread use.
Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir.

AIMS To compare the inhibitory potential of the HIV protease inhibitors saquinavir, ritonavir and indinavir against CYP1A2, CYP2C9, CYP2E1 and CYP3A4 catalysed metabolic reactions in human liver microsomes in vitro. METHODS Microsomes from six human livers were utilized in this study. The probe substrates were phenacetin (CYP1A2), tolbutamide (CYP2C9), chlorzoxazone (CYP2E1) and testosterone (CYP3A4). Metabolites were analysed by high performance liquid chromatography. IC50 (concentration of inhibitor giving 50% decrease in enzyme activity) and, where appropriate, K(i) values were calculated. RESULTS Ritonavir was a very potent inhibitor of CYP3A4 mediated testosterone 6beta-hydroxylation (mean K(i) = 0.019 +/- 0.004 microM, mean +/- s.d. ; n = 6) and also inhibited tolbutamide hydroxylation (IC50 = 4.2 +/- 1.3 microM, mean +/- s.d.; n = 6). Inhibition of phenacetin O-deethylation and chlorzoxazone 6-hydroxylation was negligible. Indinavir was an order-of-magnitude less potent in inhibiting CYP3A4 (K(i) = 0.17 +/- 0.01 microM) and did not produce appreciable inhibition of the CYP1A2, CYP2C9 or CYP2E1 catalysed reactions. Saquinavir was the least potent CYP3A4 inhibitor (K(i) = 2.99 +/- 0.87 microM) and produced some inhibition of CYP2C9 (approximately 50% at 50 microM). CONCLUSIONS The HIV protease inhibitors have differential effects on CYP isozymes. There is obvious potential for clinically significant drug interactions particularly with ritonavir. Pharmacokinetic drug interaction studies are crucial to gain an overall understanding of the beneficial and potentially harmful effects of this important group of drugs.
Local Coordinates Alignment With Global Preservation for Dimensionality Reduction

Dimensionality reduction is vital in many fields, and alignment-based methods for nonlinear dimensionality reduction have become popular recently because they can map the high-dimensional data into a low-dimensional subspace with the property of local isometry. However, the relationships between patches in original high-dimensional space cannot be ensured to be fully preserved during the alignment process. In this paper, we propose a novel method for nonlinear dimensionality reduction called local coordinates alignment with global preservation. We first introduce a reasonable definition of topology-preserving landmarks (TPLs), which not only contribute to preserving the global structure of datasets and constructing a collection of overlapping linear patches, but they also ensure that the right landmark is allocated to the new test point. Then, an existing method for dimensionality reduction that has good performance in preserving the global structure is used to derive the low-dimensional coordinates of TPLs. Local coordinates of each patch are derived using tangent space of the manifold at the corresponding landmark, and then these local coordinates are aligned into a global coordinate space with the set of landmarks in low-dimensional space as reference points. The proposed alignment method, called landmarks-based alignment, can produce a closed-form solution without any constraints, while most previous alignment-based methods impose the unit covariance constraint, which will result in the deficiency of global metrics and undesired rescaling of the manifold. Experiments on both synthetic and real-world datasets demonstrate the effectiveness of the proposed algorithm.
A Modular Implementation Scheme for Nonsingleton Type-2 Fuzzy Logic Systems With Input Uncertainties

Using nonsingleton (NS) input fuzzifiers along with type-2 fuzzy systems to handle uncertainties in inputs has received some attention in recent years. However, the NS fuzzification schemes proposed so far have a limited impact because they are restricted to a particular kind of fuzzy sets only. This paper proposes a modular implementation scheme for NS type-2 fuzzy logic systems with input uncertainties. The proposed implementation scheme constitutes a generalized fuzzification which is independent of the forms/shapes of the fuzzy sets, i.e., both the NS fuzzifiers and the membership functions. To investigate the effectiveness of the proposed scheme, type-2 fuzzy logic controllers for three different applications, airplane altitude control, obstacle avoidance for a mobile robot, and a wall following robot, are developed. Additionally, for mapping NS fuzzifiers for real sensors, a sensory noise pattern recognition stage is also developed. Despite encountering various kinds of membership functions and input uncertainties along these three applications, the proposed scheme is able to successfully deal with all three applications. Moreover, the performance results in all three application setups show that NS fuzzification can improve the robustness of type-2 fuzzy logic systems against input uncertainties.
Challenges and Approaches in Large-Scale P2P Media Streaming

Large-scale multimedia streaming over the Internet requires an enormous amount of server and network resources. Traditional client-server approaches allocate a dedicated stream from the server for each client request, which is expensive and doesn't scale well. By using end hosts' huge bandwidth and computational capacity, peer-to-peer technologies shed new light on media streaming applications' development. Yet, locating supplying peers and content delivery path maintenance are two major challenges in this area