Miracle-dz/UniFAR-FTUs huggingface dataset:
Collateralization of cerebellar output to functionally distinct brainstem areas. A retrograde, non-fluorescent tracing study in the rat

The organization of the cerebellum is characterized by a number of longitudinally organized connection patterns that consist of matching olivo-cortico-nuclear zones. These entities, referred to as modules, have been suggested to act as functional units. The various parts of the cerebellar nuclei (CN) constitute the output of these modules. We have studied to what extent divergent and convergent patterns in the output of the modules to four, functionally distinct brain areas can be recognized. Two retrograde tracers were injected in various combinations of the following nuclei: the red nucleus (RN), as a main premotor nucleus; the prerubral area, as a main supplier of afferents to the inferior olive (IO); the nucleus reticularis tegmenti pontis (NRTP), as a main source of cerebellar mossy fibers; and the IO, as the source of climbing fibers. For all six potential combinations three cases were examined. All nine cases with combinations that involved the IO did not, or hardly, resulted in double labeled neurons. In contrast, all other combinations resulted in at least 10% and up to 67% of double labeled neurons in cerebellar nuclear areas where both tracers were found. These results show that the cerebellar nuclear neurons that terminate within the studied areas represent basically two intermingled populations of projection cells. One population corresponds to the small nucleo-olivary neurons whereas the other consists of medium- to large-sized neurons which are likely to distribute their axons to several other areas. Despite some consistent differences between the output patterns of individual modules we propose that modular cerebellar output to premotor areas such as the RN provides simultaneous feedback to both the mossy fiber and the climbing fiber system and acts in concert with a designated GABAergic nucleo-olivary circuit. These features seem to form a basic characteristic of cerebellar operation.
Childhood remembered: Reports of both unique and repeated events

To explore the significance of repeated memories for individuals' personal histories, we compared the characteristics of young adults' unique and repeated memories of childhood experiences. Memory type (unique vs. repeated) was a within-participant variable. In Experiment 1, college-age participants generated as many early memories as possible in 4 minutes; in Experiment 2, another sample provided complete reports of five early memories in each condition. In both experiments, participants rated the vividness, biographical importance and personal meaning of each memory and labelled the accompanying emotion. Unique memories were more vivid than repeated memories as well as more likely to include negative emotion, regardless of the method of reporting. Most importantly, college students rated their memories for unique and repeated events as equivalently infused with personal meaning. Analysis of the content of the memories reported in Experiment 2 established that unique and repeated memories did not differ in word count or percentages of perceptual terms or words indicating positive affect, although unique memories contained a greater percentage of negative affect. Additional analyses of content provided evidence for differences in the functions served by unique and repeated memories. The results have implications for the study of autobiographical memory and for identifying over-general memories.
Real Time Lung Imaging for the Detection of Lung Injury and Alveolar Fluid Movement During Mechanical Ventilation

Experimental ventilator-induced lung injury (VILI) is characterized by alterations in alveolar epithelial and microvascular permeability that favors the systemic dissemination of lung borne cytokines or bacteria. Animal models of VILI have been shown relevant to patient care and outcome and help explaining why most patients with the acute respiratory distress syndrome do not die from respiratory failure but from multiple organ dysfunction. Recent experimental studies also showed that adverse ventilator patterns may propel airway secretions and bacteria to previously healthy lung regions. Noninvasive imaging techniques were used for years to study the net rate of protein flow across the pulmonary microvascular endothelium and the alveolar epithelium in vivo, during normal breathing and lung inflation. More recently, the two-way protein fluxes across the alveolo-capillary barrier and the intra-pulmonary dispersion of alveolar edema have been monitored during mechanical ventilation. These experiments have provided new insights on the mechanisms of experimental VILI that may be of clinical value. This review will describe the evolution of these techniques and their main physiological and pharmacological applications in the era of VILI.
Optimal Filtering of Malicious IP Sources

How can we protect the network infrastructure from malicious traffic, such as scanning, malicious code propagation, and distributed denial-of-service (DDoS) attacks? One mechanism for blocking malicious traffic is filtering: access control lists (ACLs) can selectively block traffic based on fields of the IP header. Filters (ACLs) are already available in the routers today but are a scarce resource because they are stored in the expensive ternary content addressable memory (TCAM). In this paper, we develop, for the first time, a framework for studying filter selection as a resource allocation problem. Within this framework, we study five practical cases of source address/prefix filtering, which correspond to different attack scenarios and operator's policies. We show that filter selection optimization leads to novel variations of the multidimensional knapsack problem and we design optimal, yet computationally efficient, algorithms to solve them. We also evaluate our approach using data from Dshield.org and demonstrate that it brings significant benefits in practice. Our set of algorithms is a building block that can be immediately used by operators and manufacturers to block malicious traffic in a cost-efficient way.
A Disc-based Approach to Data Summarization and Privacy Preservation

Data summarization has been recognized as a fundamental operation in database systems and data mining with important applications such as data compression and privacy preservation. While the existing methods such as CF-values and DataBubbles may perform reasonably well, they cannot provide any guarantees on the quality of their results. In this paper, we introduce a summarization approach for numerical data based on discs formalizing the notion of quality. Our objective is to find a minimal set of discs, i.e. spheres satisfying a radius and a significance constraint, covering the given dataset. Since the proposed problem is NP-complete, we design two different approximation algorithms. These algorithms have a quality guarantee, but they do not scale well to large databases. However, the machinery from approximation algorithms allows a precise characterization of a further, heuristic algorithm. This heuristic, efficient algorithm exploits multi-dimensional index structures and can be well-integrated with database systems. The experiments show that our heuristic algorithm generates summaries that outperform the state-of-the-art data bubbles in terms of internal measures as well as in terms of external measures when using the data summaries as input for clustering methods
Isavuconazole Population Pharmacokinetic Analysis Using Nonparametric Estimation in Patients with Invasive Fungal Disease (Results from the VITAL Study)

ABSTRACT Isavuconazonium sulfate (Cresemba; Astellas Pharma Inc.), a water-soluble prodrug of the triazole antifungal agent isavuconazole, is available for the treatment of invasive aspergillosis (IA) and invasive mucormycosis. A population pharmacokinetic (PPK) model was constructed using nonparametric estimation to compare the pharmacokinetic (PK) behaviors of isavuconazole in patients treated in the phase 3 VITAL open-label clinical trial, which evaluated the efficacy and safety of the drug for treatment of renally impaired IA patients and patients with invasive fungal disease (IFD) caused by emerging molds, yeasts, and dimorphic fungi. Covariates examined were body mass index (BMI), weight, race, impact of estimated glomerular filtration rate (eGFR) on clearance (CL), and impact of weight on volume. PK parameters were compared based on IFD type and other patient characteristics. Simulations were performed to describe the MICs covered by the clinical dosing regimen. Concentrations (n = 458) from 136 patients were used to construct a 2-compartment model (first-order absorption compartment and central compartment). Weight-related covariates affected clearance, but eGFR did not. PK parameters and intersubject variability of CL were similar across different IFD groups and populations. Target attainment analyses demonstrated that the clinical dosing regimen would be sufficient for total drug area under the concentration-time curve (AUC)/MIC targets ranging from 50.5 for Aspergillus spp. (up to the CLSI MIC of 0.5 mg/liter) to 270 and 5,053 for Candida albicans (up to MICs of 0.125 and 0.004 mg/liter, respectively) and 312 for non-albicans Candida spp. (up to a MIC of 0.125 mg/liter). The estimations for Candida spp. were exploratory considering that no patients with Candida infections were included in the current analyses. (The VITAL trial is registered at ClinicalTrials.gov under number NCT00634049.)
Interactions, Starbursts, and Star Formation

We study how interactions between galaxies affect star formation within them by considering a sample of almost 1500 of the nearest galaxies, all within a distance of ∼45 Mpc. We use the far-IR emission to define the massive star formation rate (SFR), and then normalise the SFR by the stellar mass of the galaxy to obtain the specific star formation rate (SSFR). We explore the distribution of (S)SFR with morphological type and with stellar mass. We calculate the relative enhancement of SFR and SSFR for each galaxy by normalising them by the median SFR and SSFR values of individual control samples of similar non-interacting galaxies. We find that both the median SFR and SSFR are enhanced in interacting galaxies, and more so as the degree of interaction is higher. The increase is moderate, reaching a maximum of a factor of 1.9 for the highest degree of interaction (mergers). While the SFR and SSFR are enhanced statistically by interactions, in many individual interacting galaxies they are not enhanced at all. Our study is based on a representative sample of nearby galaxies and should be used to place constraints on studies based on samples of galaxies at larger distances.
Global Gene Expression in Staphylococcus aureus Biofilms

ABSTRACT We previously demonstrated that mutation of the staphylococcal accessory regulator (sarA) in a clinical isolate of Staphylococcus aureus (UAMS-1) results in an impaired capacity to form a biofilm in vitro (K. E. Beenken, J. S. Blevins, and M. S. Smeltzer, Infect. Immun. 71:4206-4211, 2003). In this report, we used a murine model of catheter-based biofilm formation to demonstrate that a UAMS-1 sarA mutant also has a reduced capacity to form a biofilm in vivo. Surprisingly, mutation of the UAMS-1 ica locus had little impact on biofilm formation in vitro or in vivo. In an effort to identify additional loci that might be relevant to biofilm formation and/or the adaptive response required for persistence of S. aureus within a biofilm, we isolated total cellular RNA from UAMS-1 harvested from a biofilm grown in a flow cell and compared the transcriptional profile of this RNA to RNA isolated from both exponential- and stationary-phase planktonic cultures. Comparisons were done using a custom-made Affymetrix GeneChip representing the genomic complement of six strains of S. aureus (COL, N315, Mu50, NCTC 8325, EMRSA-16 [strain 252], and MSSA-476). The results confirm that the sessile lifestyle associated with persistence within a biofilm is distinct by comparison to the lifestyles of both the exponential and postexponential phases of planktonic culture. Indeed, we identified 48 genes in which expression was induced at least twofold in biofilms over expression under both planktonic conditions. Similarly, we identified 84 genes in which expression was repressed by a factor of at least 2 compared to expression under both planktonic conditions. A primary theme that emerged from the analysis of these genes is that persistence within a biofilm requires an adaptive response that limits the deleterious effects of the reduced pH associated with anaerobic growth conditions.
Data extraction from the web using wild card queries

This paper presents an overview of our work for searching and retrieving facts and relationships within natural language text sources. In this work, an extraction task over a text collection is expressed as a query that combines text fragments with wild cards, and the query result is a set of facts in the form of unary, binary and general n-ary tuples. Despite being both simple and declarative, the framework can be applied to a wide range of extraction tasks. This paper presents an overview of the work and its various components. We also report some of our experiments and an evaluation of the proposed querying framework in extracting relevant information to a task.
Tail structure is formed when blastocoel roof contacts blastocoel floor in Xenopus laevis

The tail organizer has been assessed by such transplantation methods as the Einsteck procedure. However, we found that simple wounding of blastocoel roof (BCR) made it possible to form secondary tails without any transplantation in Xenopus laevis. We revealed that the ectopic expression of Xbra was blocked by inhibiting the contact between BCR and blastocoel floor (BCF), and wounding per se seemed to be not directly related to the secondary tail formation. Therefore, the secondary tail might be induced by the contact between BCR and BCF due to the leak of blastocoel fluid from the wound. This secondary tail was similar to the original tail in the expression pattern of tail genes, and in the fact that the inhibition of fibroblast growth factor signaling prevented the secondary tail induction. Our results imply that the secondary tail formation reflects the developmental processes of the original tail, indicating that simple wounding of BCR is useful for the analysis of tail formation in normal development.
Anti-diabetic drug use and the risk of motor vehicle crash in the elderly.

BACKGROUND Studies of the risk of motor vehicle crash associated with diabetes have produced conflicting results. OBJECTIVES To assess whether the use of anti-diabetic drugs among the elderly increases the risk of motor vehicle crash. METHODS The computerized databases of the various universal insurance programs of Québec were linked to form a cohort of all 224,734 elderly drivers that was followed from 1990-1993. Using a nested case-control approach, all 5,579 drivers involved in an injurious crash (cases) and a random sample of 13,300 control subjects were identified. Exposure to anti-diabetic drugs was assessed in the year preceding the index date, namely the date of the crash for the cases and a randomly selected date during follow-up for the controls. RESULTS The adjusted rate ratio of an injurious crash was 1.4 (95% CI: 1.0-2.0) for current users of insulin monotherapy relative to non-users and 1.3 (95% CI: 1.0-1.7) for sulfonylurea and metformin combined. Monotherapy, using either a sulfonylurea or metformin, was not associated with an increased risk. There was a dose-response effect in subjects using high doses of combined oral therapy (RR 1.4; 95% CI: 1.0-2.0). For users of insulin monotherapy or of high doses of combined oral therapy, the increase corresponds to an excess rate of 32 crashes per 10,000 elderly drivers per year. CONCLUSIONS L Elderly drivers treated with insulin monotherapy or a combination of sulfonylurea and metformin, especially at high doses, have a small increased risk of injurious crashes. There is no increased risk associated with any regimen of oral monotherapy.
Outpatient Marijuana Treatment for Adolescents

An economic evaluation of five outpatient adolescent treatment approaches (12 total site-by-conditions) was conducted. The economic cost of each of the 12 site-specific treatment conditions was determined by the Drug Abuse Treatment Cost Analysis Program (DATCAP). Economic benefits of treatment were estimated by first monetizing a series of treatment outcomes and then analyzing the magnitude of these monetized outcomes from baseline through the 12-month follow-up. The average economic costs ranged from $90 to $313 per week and from $839 to $3,279 per episode. Relative to the quarter before intake, the average quarterly cost to society for the next 12 months (including treatment costs) significantly declined in 4 of the 12 site-by-treatment conditions, remained unchanged in 6 conditions, and increased in 2 treatment conditions (both in the same site). These results suggest that some types of substance-abuse intervention for adolescents can reduce social costs immediately after treatment.
Essential Role of Bone Marrow for Microvascular Endothelial and Metabolic Functions in Mice

Rationale: We have previously demonstrated that the importance of endothelium-derived hyperpolarizing factor (EDHF) increases as the vessel size decreases and that endothelium-derived hydrogen peroxide (H2O2) is an EDHF in animals and humans, for which endothelial nitric oxide synthase (eNOS) is the major source. Recent studies have suggested the important role of the bone marrow (BM) in modulating cardiovascular and metabolic functions. Objective: We aimed to examine whether BM plays a role in modulating microvascular endothelial and metabolic functions in mice, and if so, to elucidate the mechanisms involved. Methods and Results: Male eNOS−/− mice were transplanted with BM cells from wild-type (WT) or eNOS−/− mice and were maintained for 6 weeks. Endothelium-dependent relaxations and hyperpolarizations of mesenteric arteries to acetylcholine were reduced in eNOS−/− mice and were markedly improved when transplanted with WT-BM but not with eNOS−/−-BM. The enhanced component of endothelium-dependent relaxations was abolished by catalase, indicating that the improved responses were mediated by H2O2. In contrast, no such beneficial effect was noted in the aorta. Reduced plasma adiponectin levels and impaired glucose tolerance in eNOS−/− mice were also improved by WT-BM transplantation. Neuronal nitric oxide synthase (nNOS) in mesenteric arteries of eNOS−/− mice was significantly upregulated only when transplanted with WT-BM. Importantly, the beneficial effects of WT-BM transplantation were absent in eNOS−/−/adiponectin−/− or eNOS−/−/nNOS−/− mice. Conclusions: These results provide the first evidence that BM plays an important role in modulating microvascular endothelial and metabolic functions, for which adiponectin and nNOS may be involved.
Impaired transit and tolerance of intestinal gas in the irritable bowel syndrome

Abstract Background—Patients with irritable bowel syndrome (IBS) frequently complain of excessive gas but their fasting volume of intestinal gas is apparently normal. We hypothesised that the pathophysiological mechanism involved may be impairment of intestinal gas transit. Aim—To investigate intestinal gas transit and tolerance in IBS patients compared with healthy subjects. Methods—A gas mixture (N2, O2, and CO2 in venous proportions) was infused into the jejunum of 20 patients with IBS and 20 healthy controls at 12 ml/min for four hours. Gas evacuation, initially flatus from the anus (two hours) and then intrarectally (two hours), was continuously recorded. Symptom perception (0–6 scale) and abdominal distension were measured at 10 minute intervals. Results—After two hours of external gas (flatus) collection, 18 of 20 IBS patients had developed gas retention (>400 ml), increased gastrointestinal symptoms (score >3), or abdominal distension (>3 mm girth increment) compared with only four of 20 control subjects. During intrarectal gas collection, 13 of 17 patients still exhibited abnormal responses. Conclusion—A large proportion of patients with IBS can be shown to have impaired transit and tolerance of intestinal gas loads. This anomaly may represent a possible mechanism of IBS symptoms, specifically pain and bloating.
HITOSHI OttMORI AND

It has been reported by many authors that a variety of thiol compounds augment various lymphocyte reactions in vitro, including antibody responses (1, 2), induction of cytotoxic T cells in the mixed lymphocyte culture (3, 4), and the DNA synthetic response to mitogens (5-7). 2-Mercaptoethanol (2-ME), 1 one of the most effective thiols, was shown to be a polyclonal activator of both T cells (8) and B cells (9). Although 2-ME is widely used as an effective additive to lymphocyte cultures to elicit in vitro antibody responses, its mechanism of action still remains to be elucidated, particularly at the molecular level. Opitz et al. (10) have proposed that 2-ME does not act directly on lymphocytes, but interacts with fetal calf serum (FCS) to convert its component(s) into activated form, which in turn is directly involved in the augmentation of the primary antibody response to sheep erythrocytes (SRBC) (11). Sidman and Unanue (12) also demonstrated that the enhancing effect of 2-ME was mediated by 2-ME-activated serum factor(s) in anti-Ig antibody-induced proliferation of murine B cells. The chemical nature of these 2-ME-activated factor(s), however, has not been investigated in detail. On the other hand, Goodman et al. (9, 13, 14) have reported that 2-ME could act directly on late-maturing, resting murine lymphocytes, including both T cells and B cells, to trigger their proliferation and differentiation. They have reported (15) that synergistic cooperation between T and B cells was involved in the activation process by 2-ME. It has been recently proposed by Hoffeld and Oppenheim (16) that a major role of 2-ME in the augmentation of antibody response in vitro is to convert oxidized glutathione (GSSG) in the serum into reduced glutathione (GSH). The former compound had inhibitory effect on antibody response, whereas 2-ME was found to reverse its inhibition. Thus, we have no final conclusion as to the mechanism of action of 2-ME. In a previous paper (7), we compared the enhancing activities of various thiol compounds and found that antibody response was markedly augmented by cysteine, which has higher reduction potential than