Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Degradation of Different Benzodiazepine Binding Proteins by Incubation of Membranes from Cerebellum or Hippocampus with Trypsin

Abstract: When rat brain membranes were incubated with [3H]flunitrazepam in the presence of UV light, predominantly one protein (P5I) was irreversibly labeled in cerebellum and at least two proteins (P51 and P55) were labeled in hippocampus. On digestion of membranes with increasing concentrations of trypsin up to 40% of radioactivity irreversibly bound to proteins was removed from the membranes. In addition, P51 was nearly completely degraded to a peptide with apparent molecular weight 39,000 and this peptide was further degraded to a peptide with apparent molecular weight 25,000. In contrast, protein P55 was only partially degraded by trypsin and yielded two proteolytic peptides with apparent molecular weights 42,000 and 45,000 which seemed to be rather stable against further attack by trypsin. Membranes treated with trypsin still had the capacity to bind [3H]‐flunitrazepam reversibly with an affinity similar to that of membranes not previously treated with trypsin. When these membranes were irradiated with UV light, the same proteolytic peptides were detected as in membranes first photolabeled and then digested with trypsin. These results suggest a close association between reversible and irreversible benzodiazepine binding sites and indicate that membrane‐associated proteins P51 and P55 are differentially protected against degradation by trypsin.
Behavioral-state modulation of inhibition is context-dependent and cell type specific in mouse visual cortex

Cortical responses to sensory stimuli are modulated by behavioral state. In the primary visual cortex (V1), visual responses of pyramidal neurons increase during locomotion. This response gain was suggested to be mediated through inhibitory neurons, resulting in the disinhibition of pyramidal neurons. Using in vivo two-photon calcium imaging in layers 2/3 and 4 in mouse V1, we reveal that locomotion increases the activity of vasoactive intestinal peptide (VIP), somatostatin (SST) and parvalbumin (PV)-positive interneurons during visual stimulation, challenging the disinhibition model. In darkness, while most VIP and PV neurons remained locomotion responsive, SST and excitatory neurons were largely non-responsive. Context-dependent locomotion responses were found in each cell type, with the highest proportion among SST neurons. These findings establish that modulation of neuronal activity by locomotion is context-dependent and contest the generality of a disinhibitory circuit for gain control of sensory responses by behavioral state. DOI: http://dx.doi. org/10.7554/eLife.14985. 001
Effects of electromyography-driven robot-aided hand training with neuromuscular electrical stimulation on hand control performance after chronic stroke

Abstract Purpose: An electromyography-driven robot system integrated with neuromuscular electrical stimulation (NMES) was developed to investigate its effectiveness on post-stroke rehabilitation. Methods: The performance of this system in assisting finger flexion/extension with different assistance combinations was evaluated in five stroke subjects. Then, a pilot study with 20-sessions training was conducted to evaluate the training’s effectiveness. Results: The results showed that combined assistance from the NMES–robot could improve finger movement accuracy, encourage muscle activation of the finger muscles and suppress excessive muscular activities in the elbow joint. When assistances from both NMES and the robot were 50% of their maximum assistances, finger-tracking performance had the best results, with the lowest root mean square error, greater range of motion, higher voluntary muscle activations of the finger joints and lower muscle co-contraction in the finger and elbow joints. Upper limb function improved after the 20-session training, indicated by the increased clinical scores of Fugl-Meyer Assessment, Action Research Arm Test and Wolf Motor Function Test. Muscle co-contraction was reduced in the finger and elbow joints reflected by the Modified Ashworth Scale. Conclusions: The findings demonstrated that an electromyography-driven NMES–robot used for chronic stroke improved hand function and tracking performance. Further research is warranted to validate the method on a larger scale. Implications for Rehabilitation The hand robotics and neuromuscular electrical stimulation (NMES) techniques are still separate systems in current post-stroke hand rehabilitation. This is the first study to investigate the combined effects of the NMES and robot on hand rehabilitation. The finger tracking performance was improved with the combined assistance from the EMG-driven NMES–robot hand system. The assistance from the robot could improve the finger movement accuracy and the assistance from the NMES could reduce the muscle co-contraction on finger and elbow joints. The upper limb functions were improved on chronic stroke patients after the pilot study of 20-session hand training with the combined assistance from the EMG-driven NMES–robot. The muscle spasticity on finger and elbow joints was reduced after the training.
Dissection of the asynchronous transport of intestinal microvillar hydrolases to the cell surface

Novel subcellular fractionation procedures and pulse-chase techniques were used to study the intracellular transport of the microvillar membrane hydrolases sucrase-isomaltase and dipeptidylpeptidase IV in the differentiated colon adenocarcinoma cell line Caco-2. The overall rate of transport to the cell surface was two fold faster for dipeptidylpeptidase IV than for sucrase-isomaltase, while no significant differences were observed in transport rates from the site of complex glycosylation to the brush border. The delayed arrival of sucrase-isomaltase in the compartment where complex glycosylation occurs was only in part due to exit from the endoplasmic reticulum. A major slow-down could be ascribed to maturation in and transit of this enzyme through the Golgi apparatus. These results suggest that the observed asynchronism is due to more than one rate-limiting step along the rough endoplasmic reticulum to trans-Golgi pathway.
Quantum walk algorithm for element distinctness

We use quantum walks to construct a new quantum algorithm for element distinctness and its generalization. For element distinctness (the problem of finding two equal items among N given items), we get an O(N/sup 2/3/) query quantum algorithm. This improves the previous O(N/sup 3/4/) quantum algorithm of Buhrman et al. and matches the lower bound by Shi. We also give an O(N/sup k/(k+1)/) query quantum algorithm for the generalization of element distinctness in which we have to find k equal items among N items.
Facilitated transport and diffusion take distinct spatial routes through the nuclear pore complex

Transport across the nuclear envelope is regulated by nuclear pore complexes (NPCs). Much is understood about the factors that shuttle and control the movement of cargos through the NPC, but less has been resolved about the translocation process itself. Various models predict how cargos move through the channel; however, direct observation of the process is missing. Therefore, we have developed methods to accurately determine cargo positions within the NPC. Cargos were instantly trapped in transit by high-pressure freezing, optimally preserved by low-temperature fixation and then localized by immunoelectron microscopy. A statistical modelling approach was used to identify cargo distribution. We found import cargos localized surprisingly close to the edge of the channel, whereas mRNA export factors were at the very centre of the NPC. On the other hand, diffusion of GFP was randomly distributed. Thus, we suggest that spatially distinguished pathways exist within the NPC. Deletion of specific FG domains of particular NPC proteins resulted in collapse of the peripheral localization and transport defects specific to a certain karyopherin pathway. This further confirms that constraints on the route of travel are biochemical rather than structural and that the peripheral route of travel is essential for facilitated import.
On sparse reconstruction from Fourier and Gaussian measurements

This paper improves upon best‐known guarantees for exact reconstruction of a sparse signal f from a small universal sample of Fourier measurements. The method for reconstruction that has recently gained momentum in the sparse approximation theory is to relax this highly nonconvex problem to a convex problem and then solve it as a linear program. We show that there exists a set of frequencies Ω such that one can exactly reconstruct every r‐sparse signal f of length n from its frequencies in Ω, using the convex relaxation, and Ω has size $$ k(r,n) = O(r \log(n) \cdot \log^{2}(r) \log(r \log n) ) = O(r \log^{4} n). $$ A random set Ω satisfies this with high probability. This estimate is optimal within the log logn and log3r factors. We also give a relatively short argument for a similar problem with k(r, n) ≈ r[12 + 8 log(n/r)] Gaussian measurements. We use methods of geometric functional analysis and probability theory in Banach spaces, which makes our arguments quite short. © 2007 Wiley Periodicals, Inc.
Immunoglobulin Subclass Distribution and Diagnostic Value of Leishmania donovani Antigen-Specific Immunoglobulin G3 in Indian Kala-Azar Patients

ABSTRACT Visceral leishmaniasis, or kala-azar, a fatal tropical disease, remains problematic, as early diagnosis is difficult and treatment often results in drug resistance and relapse. We have developed a sensitive enzyme-linked immunosorbent assay (ELISA), using leishmanial membrane antigenic extracts (LAg) to detect specific antibody responses in 25 untreated Indian visceral leishmaniasis patients. To investigate the pathogenetic significance of isotype markers in kala-azar, relative levels of specific immunoglobulin G (IgG), IgM, IgA, IgE, and IgG subclasses were analyzed under clinically established diseased conditions. Since LAg showed higher sensitivity for specific IgG than lysate, the immunoglobulin isotype responses were evaluated, with LAg as antigen. Compared to 60 controls, which included patients with malaria, tuberculosis, leprosy, and typhoid and healthy subjects, visceral leishmaniasis patients showed significantly higher IgG (100% sensitivity, 85% specificity), IgM (48% sensitivity, 100% specificity), and IgE (44% sensitivity, 98.3% specificity) responses. Low levels of IgA in visceral leishmaniasis patients contrasted with a 13-fold-higher reactivity in sera from patients with leprosy. Among IgG subclasses, IgG1, -3, and -4 responses were significantly higher in visceral leishmaniasis patients than in the controls. IgG2 response, however, was significantly higher (twofold) in leprosy than even visceral leishmaniasis patients. The rank orders for sensitivity (IgG = IgG1 = IgG3 = IgG4 > IgG2 > IgM > IgE > IgA) and specificity (IgM = IgG3 > IgE > IgG4 > IgG2 > IgG > IgG1 > IgA) for LAg-specific antibody responses suggest the potentiality of IgG3 as a diagnostic marker for visceral leishmaniasis.
Sex Determination and Individual Identification of American Minks (Neovison vison) on Hokkaido, Northern Japan, by Fecal DNA Analysis

To determine the sex and identity of individual American minks (Neovison vsion), a species Introduced into Japan, molecular genetic methods were employed on fecal samples collected from the Kushiro Wetland, eastern Hokkaido. We examined the sex chromosome-linked genes ZFX and ZFY and 11 microsatellite loci to identify individuals. From microsatellite genotypes, the probability of identity was calculated to distinguish between individuals with 99% certainty. To evaluate the accuracy of the genotyping results, we used two approaches for several randomly selected samples. In the first approach, we genotyped all samples from the results of a maximum of three independent polymerase chain reactions (PCRs). In the second approach, we genotyped 10% of the samples from the results of five independent PCRs. Samples subsequent genotypings disagreed with the first genotype were counted as one of three categories of error. The results indicated that genotyping more than 10 microsatellite loci was required to reduce the probability of error in identity to less than 0.01. Twenty of 72 fecal samples were genotyped at 10 or 11 microsatellite loci and sex-determined by ZFX/ZFY genes, resulting in identification of five males and nine females. In assessing the accuracy of the results, genotyping errors were found to have occurred in 20% of the first genotypes. The main type of error was ‘missing data’, which can be prevented by increasing the number of replicate PCRs.
Misspecified and Asymptotically Minimax Robust Quickest Change Detection

We investigate the quickest detection of an unknown change in the distribution of a stochastic process generating independent and identically distributed observations. We develop new bounds on the performance of misspecified cumulative sum (CUSUM) rules, and pose minimax robust versions of the popular Lorden and Pollak criteria with polynomial (or higher order moment) detection delay penalties. By exploiting our results for misspecified CUSUM rules, we identify solutions to our robust quickest change detection problems in the asymptotic regime of few false alarms. In contrast to previous robust quickest change detection treatments, our asymptotic results hold under relaxed conditions on the uncertainty sets of possible prechange and postchange distributions. We illustrate our results in simulations and apply them to the problem of detecting target manoeuvres in low signal-to-noise ratio settings (i.e., dim-target manoeuvre detection).
Quantifying Fluid Infusions and Tissue Expansion in Brain

The technique of direct infusions into brain tissue of therapeutic molecules that would otherwise not adequately cross the blood-brain barrier (BBB) continues to be used in clinical trials. As part of our research into understanding the transport of fluids and molecules in brain tissue, we performed infusions of a saline solution of the magnetic resonance (MR) marker Gadodiamide( Omniscan) into porcine brains. We use quantitative concentration measurements of contrast reagents from MR images to both measure the distribution profile of the infusate and to elucidate important determinants of fluid flow during infusions into brain parenchyma. Based on this, and from other MRI data collected during infusion, we give preliminary results for the quantification of the expansion of the volume fraction of the interstitium particularly in white matter regions of brain during infusion-induced edema. We claim this expansion, rather than an anisotropy of fluid conductivity, makes white matter tracts a preferred pathway for flow. We also comment briefly on other determinants that are currently being pursued such as the influence of the cerebrospinal fluid and perivascular spaces that may be elucidated with quantitative tracking of tracer, but which need further studies.
The magnitude of acute serum creatinine increase after cardiac surgery and the risk of chronic kidney disease, progression of kidney disease, and death.

BACKGROUND Long-term outcomes after acute kidney injury remain poorly defined. We determined the association between the magnitude of creatinine increase after cardiac surgery and the risk of incident chronic kidney disease (CKD), CKD progression, and death. METHODS We identified 29,388 individuals who underwent cardiac surgery at Veterans Affairs hospitals between November 1999 and September 2005. The magnitude of creatinine increase was defined by the percent change from baseline to peak creatinine levels after cardiac surgery and categorized as none (≤0%) or as class I, (1%-24%), II (25%-49%), III (50%-99%), or IV (≥100%). Cox proportional hazard models were used to examine the association between the magnitude of creatinine increase and outcomes. RESULTS The relative hazards for outcomes increased monotonically with greater increases in creatinine levels compared with no change in creatinine levels. The relative hazards for adverse outcomes were significantly higher immediately after the creatinine increase and attenuated over time. Three months after surgery, creatinine increase classes I, II, III, and IV were associated with a greater risk of incident CKD (hazard ratios [HRs] 2.1, 4.0, 5.8, and 6.6, respectively; all P<.01), progression of CKD stage (HRs 2.5, 3.8, 4.4, and 8.0; all P<.01), and long-term mortality (HRs 1.4, 1.9, 2.8, and 5.0; all P<.01). At 5 years, the associations were lower in magnitude: incident CKD (HRs 1.4, 1.9, 2.3, and 2.3; all P<.01), CKD progression (HRs 1.5, 1.7, 1.7, and 2.4; all P<.01), and mortality (HRs 1.0, 1.2, 1.4, and 1.8; all P<.01, except class I). CONCLUSION The magnitude of creatinine increase after cardiac surgery is associated in a graded manner with an increased risk of incident CKD, CKD progression, and mortality.
Identification of Actinobacillus pleuropneumoniae Genes Important for Survival during Infection in Its Natural Host

ABSTRACT Actinobacillus pleuropneumoniae is a strict respiratory tract pathogen of swine and is the causative agent of porcine pleuropneumonia. We have used signature-tagged mutagenesis (STM) to identify genes required for survival of the organism within the pig. A total of 2,064 signature-tagged Tn10 transposon mutants were assembled into pools of 48 each, and used to inoculate pigs by the endotracheal route. Out of 105 mutants that were consistently attenuated in vivo, only 11 mutants showed a >2-fold reduction in growth in vitro compared to the wild type, whereas 8 of 14 mutants tested showed significant levels of attenuation in pig as evidenced from competitive index experiments. Inverse PCR was used to generate DNA sequence of the chromosomal domains flanking each transposon insertion. Only one sibling pair of mutants was identified, but three apparent transposon insertion hot spots were found—an anticipated consequence of the use of a Tn10-based system. Transposon insertions were found within 55 different loci, and similarity (BLAST) searching identified possible analogues or homologues for all but four of these. Matches included proteins putatively involved in metabolism and transport of various nutrients or unknown substances, in stress responses, in gene regulation, and in the production of cell surface components. Ten of the sequences have homology with genes involved in lipopolysaccharide and capsule production. The results highlight the importance of genes involved in energy metabolism, nutrient uptake and stress responses for the survival of A. pleuropneumoniae in its natural host: the pig.
Urinary and plasma magnesium and risk of ischemic heart disease.

BACKGROUND Previous studies on dietary magnesium and risk of ischemic heart disease (IHD) have yielded inconsistent results, in part because of a lack of direct measures of actual magnesium uptake. Urinary excretion of magnesium, an indicator of dietary magnesium uptake, might provide more consistent results. OBJECTIVE The objective was to investigate whether urinary magnesium excretion and plasma magnesium are associated with IHD risk. DESIGN We examined 7664 adult participants free of known cardiovascular disease in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study-a prospective population-based cohort study. Urinary magnesium excretion was measured in 2 baseline 24-h urine collections. RESULTS Mean ± SD urinary magnesium excretion was 4.24 ± 1.65 mmol/24 h for men and 3.54 ± 1.40 mmol/24 h for women. During a median follow-up of 10.5 y (IQR: 9.9-10.8 y), 462 fatal and nonfatal IHD events occurred. After multivariable adjustment, urinary magnesium excretion had a nonlinear relation with IHD risk (P-curvature = 0.01). The lowest sex-specific quintile (men: <2.93 mmol/24 h; women: <2.45 mmol/24 h) had an increased risk of fatal and nonfatal IHD (multivariable HR: 1.60; 95% CI: 1.28, 2.00) compared with the upper 4 quintiles of urinary magnesium excretion. A similar increase in risk of the lowest quintile was observed for mortality related to IHD (HR: 1.70; 95% CI: 1.10, 2.61). No associations were observed between circulating magnesium and risk of IHD. CONCLUSIONS Low urinary magnesium excretion was independently associated with a higher risk of IHD incidence. An increased dietary intake of magnesium, particularly in those with the lowest urinary magnesium, could reduce the risk of IHD.
Music Undergraduates' Usefulness and Importance Expectations: The Bologna Process from an Australian University Perspective

The Bologna Process model of higher education has been introduced into some Australian universities since 2008. This model promoted university study through a liberal arts philosophy that advanced a worldview approach at the undergraduate level. The model generalized the student experience and eliminated undergraduate specialization. An interesting situation for music undergraduate study thus arose. Expertise and expert performance research has argued an opposing educational approach, namely: Extensive long-term commitment through focused practical engagement and specialized tuition as prerequisites to achieving musical mastery, especially in performance. Motivation research has shown that the majority of this specialized development in pre-university years would be accessed and reinforced predominantly through private music tuition. Drawing on this contextual literature, commencing university music undergraduates would have expectations of their prospective study founded from two historical influences. The first: How undergraduates had accessed pre-university music tuition. The second: How and in what ways undergraduates' pre-university musical activities were experienced and reinforced. Using usefulness and importance measures, the study observed the expectations of students about to commence music undergraduate studies at three representative Australian university music schools. One of these universities operated the Bologna styled model. No other known Australian study has investigated this implementation for any effects upon music undergraduate expectations. How much commencing music undergraduates would draw on their pre-university music instruction and experiences to predict their usefulness and importance expectations formed the basis for this investigation. Strong relationships between usefulness and importance were found across all units of study. Despite strong correlations across all units of study between usefulness and importance, there was a reluctance to be outwardly positive toward units of study that were not practical and performance-related, such as Music History. The educational model did not appear to affect music undergraduate expectations.