Miracle-dz/UniFAR-FTUs huggingface dataset:
Metastable tolerance in nonhuman primates and humans

It is clear that both humans and nonhuman primates can do without immunosuppression for long periods of time before rejecting their allogeneic organ transplants. Immune cell depletion, particularly lymphocyte depletion, is an effective clinical strategy for achieving a tolerant state. Based on nonhuman primate and human studies, evidence suggests that metastable tolerance develops over time in a donor-specific manner and is mediated at least in part by donor antigen-specific regulatory T cells. Suppression of effector T cells by CD8+ and CD4+ T-regulatory cells is mediated by transforming growth factor (TGF)-&bgr; or interleukin 10, and the presence of CD4+ TGF&bgr;(latent)+ T-cell infiltrates may be a useful diagnostic marker for metastable tolerance. Loss of these cells has been shown to correlate with loss of tolerance. Future efforts to withdraw immunosuppressive drugs and establish a tolerant state will depend importantly on development of such diagnostic immunologic monitoring tools. Some of the reasons that tolerance remains such a challenging goal in clinical transplantation are discussed herein.
Screening for the presence of FMR1 premutation alleles in women with parkinsonism.

BACKGROUND Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive, late-onset neurodegenerative disease that affects older carriers of premutation (CGG) repeat expansions of the fragile X mental retardation 1 (FMR1) gene. Clinical features include intention tremor, gait ataxia, memory loss, peripheral neuropathy, autonomic dysfunction, and parkinsonism. The presence of parkinsonism in FXTAS raises the possibility that some individuals who have Parkinson disease are actually carriers of a premutation FMR1 allele. OBJECTIVE To screen DNA samples from a large cohort of females with Parkinson disease for an excess of expanded alleles of the FMR1 gene. DESIGN AND PATIENTS We screened a cohort of 595 women with parkinsonism, the largest screening of a parkinsonism-associated group to date, for the presence of an FMR1 premutation allele (55-200 CGG repeats). The screening protocol uses an enhanced polymerase chain reaction method capable of flagging any FMR1 expanded CGG repeat in women as well as in men. SETTING Diagnostic assessments were performed at an outpatient tertiary clinic (Parkinson Institute, Milan). Genotyping was conducted at the University of California, Davis. MAIN OUTCOME MEASURES CGG repeat number and clinical/neuroimaging assessments of patients with Parkinson disease were conducted. Two premutation carriers were identified. RESULTS Two individuals possessed an FMR1 allele in the premutation range (CGG repeats: 30 and 75; 30 and 115). This carrier frequency (2 of 595 [0.34%]) is not significantly different from estimates of the allele frequency among women in the general population (0.4%-0.8%). Clinical and radiologic features of these 2 patients were similar to those of the general Parkinson disease population; however, 1 patient (115 CGG repeats) had a family history of 2 sons with the fragile X syndrome. CONCLUSION Screening of women within the parkinsonism clinical spectrum is unlikely to be productive in the absence of additional medical or family history suggestive of involvement of the FMR1 gene.
A Stochastic Geometry Model for Vehicular Communication near Intersections

Many traffic-related applications require the nodes in a vehicular ad-hoc network (VANET) to periodically broadcast their state information. As measurements campaigns or simulations to evaluate the reliability of packet transmission are slow and scenario-specific, we present an analytic performance assessment tool that accounts for the spatial statistics of the nodes on a road, in a scenario of crossing roads and fast fading. Based on stochastic geometry, our tool is able to capture a static two-dimensional road geometry and the effect of interference due to node clustering in the vicinity of an intersection. Numerical results reveal how packet transmission is affected as the receiver gets closer to the intersection.
Coincidence detection in the cochlear nucleus: implications for the coding of pitch

The spatio-temporal pattern in the auditory nerve (AN), i.e. the temporal pattern of AN fiber activity across the tonotopic axis, provides cues to important features in sounds such as pitch, loudness, and spatial location. These spatio-temporal cues may be extracted by central neurons in the cochlear nucleus (CN) that receive inputs from AN fibers innervating different cochlear regions and are sensitive to their relative timing. One possible mechanism for this extraction is cross-frequency coincidence detection (CD), in which a central neuron converts the degree of cross-frequency coincidence in the AN into a rate response by preferentially firing when its AN inputs across the tonotopic axis discharge in synchrony. We implemented a CD model receiving AN inputs from varying extents of the tonotopic axis, and compared responses of model CD cells with those of single units recorded in the CN of the anesthetized cat. We used Huffman stimuli, which have flat magnitude spectra and a single phase transition, to systematically manipulate the relative timing across AN fibers and to evaluate the sensitivity of model CD cells and CN units to the spatiotemporal pattern of AN discharges. Using a maximum likelihood approach, we found that certain unit types (primary-like-with-notch and some phase lockers) had responses consistent with cross-frequency CD cell. Some of these CN units provide input to neurons in a binaural circuit that process cues for sound localization and are sensitive to interaural level differences. A possible functional role of a cross-frequency CD mechanism in the CN is to increase the dynamic range of these binaural neurons. However, many other CN units had responses more consistent with AN fibers than with CD cells. We hypothesized that CN units resembling cross-frequency CD cells (as determined by their responses to Huffman stimuli) would convert spatio-temporal cues to pitch in the AN into rate cues that are robust with level. We found that, in response to harmonic complex tones, cross-frequency CD cells and some CN units (primary-like-with-notch and choppers) maintained robust rate cues at high levels compared to AN fibers, suggesting that at least some CN neurons extend the dynamic range of rate representations of pitch beyond that found in AN fibers. However, there was no obvious correlation between robust rate cues in individual CN units and similarity to cross-frequency CD cells as determined by responses to Huffman stimuli. It is likely that a model including more realistic inputs, membrane channels, and spiking mechanism, or other mechanisms such as lateral inhibition or spatial and temporal summation over spatially distributed inputs would provide insight into the neural mechanisms that give rise to the robust rate cues observed in some CN units.
A Comparison of Laboratory and Field Research in the Study of Electronic Meeting Systems

Abstract:Research into the use of Electronic Meeting Systems (ems) has rapidly increased over the past few years. However, ems laboratory experiments have often drawn very different conclusions about the effects of ems use than have ems field studies—conclusions that at first appear inconsistent. By examining the differences in the design of prior ems studies, we attempt to better understand the factors that affect the use of ems technology. It is our contention that these differences in findings are not inconsistent, but rather they reflect different situations that researchers have studied. We identify 24 potentially important differences in organizational contexts, group characteristics, tasks, and ems environments. In planning future research, ems researchers need to make explicit design decisions for each of these aspects, and to consider how those choices may affect research results. An analysis of these differences suggests several approaches to enhance the design of future laboratory experiments a.
Association between biomarkers and clinical characteristics in chronic subdural hematoma patients assessed with lasso regression

Chronic subdural hematoma (CSDH) is characterized by an “old” encapsulated collection of blood and blood breakdown products between the brain and its outermost covering (the dura). Recognized risk factors for development of CSDH are head injury, old age and using anticoagulation medication, but its underlying pathophysiological processes are still unclear. It is assumed that a complex local process of interrelated mechanisms including inflammation, neomembrane formation, angiogenesis and fibrinolysis could be related to its development and propagation. However, the association between the biomarkers of inflammation and angiogenesis, and the clinical and radiological characteristics of CSDH patients, need further investigation. The high number of biomarkers compared to the number of observations, the correlation between biomarkers, missing data and skewed distributions may limit the usefulness of classical statistical methods. We therefore explored lasso regression to assess the association between 30 biomarkers of inflammation and angiogenesis at the site of lesions, and selected clinical and radiological characteristics in a cohort of 93 patients. Lasso regression performs both variable selection and regularization to improve the predictive accuracy and interpretability of the statistical model. The results from the lasso regression showed analysis exhibited lack of robust statistical association between the biomarkers in hematoma fluid with age, gender, brain infarct, neurological deficiencies and volume of hematoma. However, there were associations between several of the biomarkers with postoperative recurrence requiring reoperation. The statistical analysis with lasso regression supported previous findings that the immunological characteristics of CSDH are local. The relationship between biomarkers, the radiological appearance of lesions and recurrence requiring reoperation have been inclusive using classical statistical methods on these data, but lasso regression revealed an association with inflammatory and angiogenic biomarkers in hematoma fluid. We thus suggest that lasso regression should be a recommended statistical method in research on biological processes in CSDH patients.
Intracerebral infusion of 3H‐dopamine and 3H‐mannitol in the striatum of halothane‐anaesthetized male rats.A dual‐probe microdialysis study of long‐distance diffusion

This report characterizes an in vivo intracerebral long‐distance diffusion model using dual‐probe microdialysis. Two probes 1 mm apart were implanted into the striatum of control and 6‐hydroxydopamine (6‐OHDA)‐lesioned halothane‐anaesthetized male rats. Either tritiated dopamine (500 n m3H‐DA) or mannitol (1.5 μm3H‐mannitol) was infused continuously for 5 h, while samples were collected from the other probe. Samples (10 μl) were counted by liquid scintillation. For the DA‐infused rats, another 10 μL was separated with high‐pressure liquid chromatography (HPLC)–electrochemical detection into individual fractions containing 3,4‐dihydroxy phenylacetic acid (DOPAC) and homovanillinic acid (HVA), and counted for β‐decay. The total transfer of 3H‐labelled compounds described the overall effect of cellular uptake, metabolism and clearance into the microcirculation, and was compared with that of an extracellular marker, 3H‐mannitol. The migration reached steady‐state levels, generating an equilibrium between delivery and removal from the extracellular space. The half‐time of the steady‐state values, t50%, was in all cases lower in 6‐OHDA‐treated rats compared with control. In addition, the t50% values of 3H‐mannitol were lower than those following the 3H‐dopamine infusion in both control or 6‐OHDA‐lesioned rats. However, it was not possible to detect any unmetabolized 3H‐dopamine at the 1 mm distance. In conclusion, the dual‐probe microdialysis approach proved to be a valid method to study in vivo diffusion and migration in the brain, and the intracerebral spread of compounds highly depends on the nature of the compound infused.
Pax6 transcription factor is required for the interkinetic nuclear movement of neuroepithelial cells

The mammalian cerebral cortex develops from proliferative neuroepithelial cells that exhibit a cell cycle‐dependent nuclear movement (interkinetic nuclear migration; INM). Pax6 transcription factor plays pivotal roles in various aspects of corticogenesis. From live observation using cultured cortical slices from the Pax6 mutant rat, we identified the premature descent of S phase cells, the unsteady ascent or descent of G2 phase cells, and ectopic cell division within the basal side of the ventricular zone (VZ). The centrosome normally stayed at the most apical side, apart from the nucleus, in the neuroepithelial cell during the S to G2 phase, while the Pax6 mutant showed unstable movement of the centrosome associated with an abnormal INM. Our results suggest the possibility that Pax6 regulates the INM by stabilizing the centrosome at the apical side.
Development of endogenous orienting of attention in school-age children

Orienting of attention was investigated in 6-, 8-, and 10-year-olds and in young adults, in a spatial cueing experiment comparing nonpredictive, predictive, and counterpredictive cues (in different blocks). A larger positive orienting effect (advantage of valid over invalid cues) in the predictive than in the nonpredictive condition occurred in all groups, showing efficient endogenous orienting of attention. However, this effect was larger in 6-year-olds, as if the ability to distribute attention between the different locations (and not only to orient to the most probable location) developed between 6 and 8 years. Moreover, only 10-year-olds and adults showed a significant negative orienting effect (advantage of invalid cues) in the counterpredictive condition, indicating inhibition of attentional capture by goal-irrelevant stimuli. Therefore, our results indicate a large change in the modulation of endogenous orienting between 6 and 10 years.
Prevalence of dyspeptic symptoms and heartburn of adults in Belo Horizonte, Brazil.

BACKGROUND - Medical literature has shown dyspepsia and heartburn-related symptoms occur among 15% to 40% of the population. These symptoms can occur at any age and are more prevalent in women. OBJECTIVE - Investigate the prevalence of dyspeptic symptoms and heartburn among individuals over 18. METHODS - Individuals over 18 were randomly selected in public venues in Belo Horizonte/MG to participate. A standardized questionnaire that included questions related to social-demographic characteristics, eating habits, digestive symptoms, medical appointments, medications, exams, previous surgeries and comorbidities was applied. A questionnaire about functional dyspepsia diagnosis (Rome III) was also applied. RESULTS - A total of 548 individuals were interviewed. Among these, 58.4% were women, 59.3% were white, 55.9% were single and the average age was 36 years. Within this group, 376 individuals (68.6%) declared to have some symptom and/or use medication to relieve dyspepsia symptoms, and for these patients were applied the Rome III questionnaire. Based on the diagnostic criteria for the questionnaire proposed by the Rome III consensus, the symptom of postprandial fullness was reported by 6.7% of the individuals, early satiety (3.5%) and epigastric pain (10.6%). The overlap of these symptoms was very frequent. The prevalence of functional dyspepsia was 10.6% (postprandial discomfort syndrome (8.2%) and epigastric pain syndrome (2.4%). Among all participants, 52.5% reported heartburn, and 11.1% presented this symptom at least once a week. The most used drug was omeprazole. CONCLUSION - The prevalence of dyspeptic symptoms and heartburn among a Brazilian adult urban population is similar to those described in other countries.
Finite-time consensus for multi-agent systems with globally bounded convergence time under directed communication graphs

ABSTRACT In this paper, we study the finite-time consensus problems with globally bounded convergence time also known as fixed-time consensus problems for multi-agent systems subject to directed communication graphs. Two new distributed control strategies are proposed such that leaderless and leader-follower consensus are achieved with convergence time independent on the initial conditions of the agents. Fixed-time formation generation and formation tracking problems are also solved as the generalizations. Simulation examples are provided to demonstrate the performance of the new controllers.
Prefrontal Goal Codes Emerge as Latent States in Probabilistic Value Learning

The prefrontal cortex (PFC) supports goal-directed actions and exerts cognitive control over behavior, but the underlying coding and mechanism are heavily debated. We present evidence for the role of goal coding in PFC from two converging perspectives: computational modeling and neuronal-level analysis of monkey data. We show that neural representations of prospective goals emerge by combining a categorization process that extracts relevant behavioral abstractions from the input data and a reward-driven process that selects candidate categories depending on their adaptive value; both forms of learning have a plausible neural implementation in PFC. Our analyses demonstrate a fundamental principle: goal coding represents an efficient solution to cognitive control problems, analogous to efficient coding principles in other (e.g., visual) brain areas. The novel analytical–computational approach is of general interest because it applies to a variety of neurophysiological studies.
A 3-Mb high-resolution BAC/PAC contig of 12q22 encompassing the 830-kb consensus minimal deletion in male germ cell tumors.

Cytogenetic and molecular genetic analyses have shown that the 12q22 region is recurrently deleted in male germ cell tumors (GCTs), suggesting that this site may harbor a tumor suppressor gene (TSG). Previous loss of heterozygosity (LOH) analyses identified a consensus minimal deleted region between the markers D12S377 and D12S296, and a YAC clone contig covering the region was generated. Here, we describe a high-resolution sequence-ready physical map of this contig covering a 3-Mb region. The map comprised of 52 cosmids, 49 PACs, and 168 BACs that were anchored to the previous YAC contig; 99 polymorphic, nonpolymorphic, EST, and gene-based markers are now placed on this map in a unique order. Of these, 61 markers were isolated in the present study, including one that was polymorphic. In addition, we have narrowed the minimal deletion to approximately 830 kb between D12S1716 (proximal) and P382A8-AG (distal) by LOH analysis of 108 normal-tumor DNAs from GCT patients using 21 polymorphic STSs. These physical and deletion maps should prove useful for identification of the candidate TSG in GCTs, provide framework to generate complete DNA sequence, and ultimately generate a gene map of this segment of the chromosome 12. [The sequence data described in this paper have been submitted to the Genome Survey Sequence under accession nos. AQ254896-AQ254955 and AQ269251-AQ269266. Online supplementary material is available at http://www.genome. org]
Effect of surface tension of mucosal lining liquid on upper airway mechanics in anesthetized humans.

Upper airway (UA) patency may be influenced by surface tension (gamma) operating within the (UAL). We examined the role of gamma of UAL in the maintenance of UA patency in eight isoflurane-anesthetized supine human subjects breathing via a nasal mask connected to a pneumotachograph attached to a pressure delivery system. We evaluated 1). mask pressure at which the UA closed (Pcrit), 2). UA resistance upstream from the site of UA collapse (RUS), and 3). mask pressure at which the UA reopened (Po). A multiple pressure-transducer catheter was used to identify the site of airway closure (velopharyngeal in all subjects). UAL samples (0.2 microl) were collected, and the gamma of UAL was determined by using the "pull-off force" technique. Studies were performed before and after the intrapharyngeal instillation of 5 ml of exogenous surfactant (Exosurf, Glaxo Smith Kline). The gamma of UAL decreased from 61.9 +/- 4.1 (control) to 50.3 +/- 5.0 mN/m (surfactant; P < 0.02). Changes in Po, RUS, and Po - Pcrit (change = control - surfactant) were positively correlated with changes in gamma (r2 > 0.6; P < 0.02) but not with changes in Pcrit (r2 = 0.4; P > 0.9). In addition, mean peak inspiratory airflow (no flow limitation) significantly increased (P < 0.04) from 0.31 +/- 0.06 (control) to 0.36 +/- 0.06 l/s (surfactant). These findings suggest that gamma of UAL exerts a force on the UA wall that hinders airway opening. Instillation of exogenous surfactant into the UA lowers the gamma of UAL, thus increasing UA patency and augmenting reopening of the collapsed airway.
Countergradient Variation in Temperature Preference in Populations of Killifish Fundulus heteroclitus

Behavioral thermoregulation can allow ectotherms to buffer the effects of changes in environmental temperature, and thus an organism’s preferred temperature is thought to be under strong selection. However, this contention has seldom been tested. We used common killifish Fundulus heteroclitus from high‐latitude (northern) and low‐latitude (southern) populations to investigate intraspecific variation in thermal preference and its relationship to habitat temperature. We quantified the preferred temperatures of northern and southern killifish populations acclimated to three temperatures (5°, 15°, and 25°C) to evaluate two alternative hypotheses for the evolution of differences in thermal preference among latitudinally separated populations: local thermal adaptation, which predicts that organisms from high latitudes should prefer lower temperatures than individuals from lower latitudes, versus countergradient variation, which predicts that high‐latitude organisms should prefer higher temperatures to compensate for shorter growing seasons. All killifish selected their final thermal preferendum within 4 h. Southern killifish and killifish acclimated to warmer temperatures had greater variability in selected temperature. This increase in variability was the result of an increase in interindividual variation in preferred temperature rather than a reduction in the precision of temperature selection in these groups. Northern killifish preferred significantly higher temperatures than southern fish (30.6° vs. 29.0°C, respectively, when calculated on the basis of the temperature selected consistently for at least 30 min; 28.4° vs. 26.5°C, respectively, when calculated on the basis of the mean temperature occupied), regardless of acclimation temperature. These data are not consistent with local adaptation in thermal preference but instead can be better explained by countergradient variation in thermal preference in killifish.