Miracle-dz/UniFAR-FTUs huggingface dataset:
Deep Sequencing and High-Resolution Imaging Reveal Compartment-Specific Localization of Bdnf mRNA in Hippocampal Neurons

High-resolution analysis reveals that Bdnf transcripts are weakly but selectively localized to the cell body, not dendrites, of hippocampal neurons. Finding the Site of Translation Studies using exogenous, man-made gene reporter constructs can provide insight into the induction and localization of gene expression; however, they have the caveat of artificiality. Furthermore, the 3′ untranslated region (3′UTR) can influence the localization, stability, and translation efficiency of an mRNA. Will et al. used a suite of quantitative imaging techniques and automated analysis to examine the abundance and localization of two mRNA isoforms (containing a short or long 3′UTR) of endogenous Bdnf, which encodes a neuronal growth factor, in distinct compartments of unstimulated or stimulated adult rat hippocampal neurons. Their findings show how sensitive quantitative techniques may be applied to measure endogenous gene expression in situ and reveal that Bdnf transcripts are predominantly localized to the neuronal cell body, not the dendrites. Brain-derived neurotrophic factor (BDNF) is a small protein of the neurotrophin family that regulates various brain functions. Although much is known about how its transcription is regulated, the abundance of endogenous BDNF mRNA and its subcellular localization pattern are matters of debate. We used next-generation sequencing and high-resolution in situ hybridization in the rat hippocampus to reexamine this question. We performed 3′ end sequencing on rat hippocampal slices and detected two isoforms of Bdnf containing either a short or a long 3′ untranslated region (3′UTR). Most of the Bdnf transcripts contained the short 3′UTR isoform and were present in low amounts relative to other neuronal transcripts. Bdnf mRNA was present in the somatic compartment of rat hippocampal slices or the somata of cultured rat hippocampal neurons but was rarely detected in the dendritic processes. Pharmacological stimulation of hippocampal neurons induced Bdnf expression but did not change the ratio of Bdnf isoform abundance. The findings indicate that endogenous Bdnf mRNA, although weakly abundant, is primarily localized to the somatic compartment of hippocampal neurons. Both Bdnf mRNA isoforms have shorter half-lives compared with other neuronal mRNAs. Furthermore, the findings show that using complementary high-resolution techniques can provide sensitive measures of endogenous transcript abundance.
Robust Learning and Segmentation for Scene Understanding

Abstract : This thesis demonstrates methods useful in learning to understand images from only a few examples, but they are by no means limited to this application. Boosting techniques are popular because they learn effective classification functions and identify the most relevant features at the same time. However, in general, they overfit and perform poorly on data sets that contain many features, but few examples. A novel stochastic regularization technique is presented, based on enhancing data sets with corrupted copies of the examples to produce a more robust classifier. This regularization technique enables the gentle boosting algorithm to work well with only a few examples. It is tested on a variety of data sets from various domains, including object recognition and bioinformatics, with convincing results. In the second part of this work, a novel technique for extracting texture edges is introduced, based on the combination of a patch-based approach, and non-parametric tests of distributions. This technique can reliably detect texture edges using only local information, making it a useful preprocessing step prior to segmentation. Combined with a parametric deformable model, this technique provides smooth boundaries and globally salient structures.
Descriptive set theory over hyperfinite sets

Abstract The separation, uniformization, and other properties of the Borel and projective hierarchies over hyperfinite sets are investigated and compared to the corresponding properties in classical descriptive set theory. The techniques used in this investigation also provide some results about countably determined sets and functions, as well as an improvement of an earlier theorem of Kunen and Miller.
Prevalence and Clinical Significance of Staphylococcus aureus Small-Colony Variants in Cystic Fibrosis Lung Disease

ABSTRACT Small-colony variants (SCVs) of Staphylococcus aureus can be isolated from the chronically infected airways of patients suffering from cystic fibrosis (CF). These slow-growing morphological variants have been associated with persistent and antibiotic-resistant infections, such as osteomyelitis and device-related infections, but no information is available to date regarding the clinical significance of this special phenotype in CF lung disease. We therefore investigated the prevalence of S. aureus SCVs in CF lung disease in a 12-month prospective study and correlated the microbiological culture results with the patients' clinical data. A total of 252 patients were screened for the presence of SCVs. The prevalence rate was determined to be 17% (95% confidence interval, 10 to 25%) among S. aureus carriers. S. aureus isolates with the SCV phenotype showed significantly higher antibiotic resistance rates than those with the normal phenotype. Patients positive for SCVs were significantly older (P = 0.0099), more commonly cocolonized with Pseudomonas aeruginosa (P = 0.0454), and showed signs of more advanced disease, such as lower forced expiratory volume in 1 s (P = 0.0148) than patients harboring S. aureus with a solely normal phenotype. The logistic regression model determined lower weight (P = 0.016), advanced age (P = 0.000), and prior use of trimethoprim-sulfamethoxazole (P = 0.002) as independent risk factors for S. aureus SCV positivity. The clinical status of CF patients is known to be affected by multiple parameters. Nonetheless, the independent risk factors determined here point to the impact of S. aureus SCVs on chronic and persistent infections in advanced CF lung disease.
Adaptive Model Predictive Control for Constrained Nonlinear Systems

Abstract A true adaptive nonlinear model predictive control (MPC) algorithm must address the issue of robustness to model uncertainty while the estimator is evolving. Unfortunately, this may not be achieved without introducing extra degree of conservativeness and/or computational complexity in the controller calculations. To attenuate this problem, we employ a finite time identifier and propose an adaptive predictive control structure that reduces to a nominal MPC problem when exact parameter estimates are obtained. The adaptive MPC is formulated in such a way that useful excitation is automatically injected into the closed loop system to decrease the identification period.
In vitro susceptibilities of the AIDS-associated microsporidian Encephalitozoon intestinalis to albendazole, its sulfoxide metabolite, and 12 additional benzimidazole derivatives

Recent reports have described the successful treatment of Encephalitozoon intestinalis infection in AIDS patients with albendazole. However, this compound is rapidly metabolized in vivo to albendazole sulfoxide, and furthermore it is only 1 of about 15 commercially developed benzimidazole derivatives. To compare the activities of albendazole, albendazole sulfoxide, and other benzimidazoles, an in vitro system involving infection of green monkey kidney cell (E6) monolayers with E. intestinalis spores was developed. After 14 days, the effects of benzimidazoles on spore production were determined. Ten of fourteen derivatives tested, including albendazole, were inhibitory at concentrations of 1 to 10 ng/ml. Derivatives modified at the 1 or 2 position were less active. Albendazole sulfoxide was 1.7-fold more inhibitory than albendazole but significantly less toxic to E6 cells, a finding that explains the clinical efficacy of this compound. Potential alternatives to albendazole are discussed. No albendazole-resistant E. intestinalis mutants were obtained following in vitro selection.
Edge Principal Components and Squash Clustering: Using the Special Structure of Phylogenetic Placement Data for Sample Comparison

Principal components analysis (PCA) and hierarchical clustering are two of the most heavily used techniques for analyzing the differences between nucleic acid sequence samples taken from a given environment. They have led to many insights regarding the structure of microbial communities. We have developed two new complementary methods that leverage how this microbial community data sits on a phylogenetic tree. Edge principal components analysis enables the detection of important differences between samples that contain closely related taxa. Each principal component axis is a collection of signed weights on the edges of the phylogenetic tree, and these weights are easily visualized by a suitable thickening and coloring of the edges. Squash clustering outputs a (rooted) clustering tree in which each internal node corresponds to an appropriate “average” of the original samples at the leaves below the node. Moreover, the length of an edge is a suitably defined distance between the averaged samples associated with the two incident nodes, rather than the less interpretable average of distances produced by UPGMA, the most widely used hierarchical clustering method in this context. We present these methods and illustrate their use with data from the human microbiome.
A new image navigation system for MR-guided cryosurgery.

PURPOSE To evaluate the feasibility of Interactive Scan Control (ISC), a new MR image navigation system, during percutaneous puncture in cryosurgery. MATERIALS AND METHODS With the ISC system in place, percutaneous MR-guided cryosurgery was performed in 26 cases, with the ISC system being used in 11 cases (five renal tumors, three uterine fibroids and three metastatic liver tumors). The ISC system comprised infrared cameras and an MR-compatible optical tracking tool that was directly connected to a cryoprobe. Tumor sizes ranged from 1.2 cm (metastatic liver tumor) to 9.0 cm (uterine fibroid), for a mean size of 3.9 cm. With ISC, one to three cryoprobes with a diameter of 2 mm or 3 mm were advanced into the tumors with the guidance of an MR fluoroscopic image. Two freeze-thaw cycles were used for cryosurgery. During the cryosurgery, the formation of iceballs was monitored on MR images. Follow-up dynamic CT or MRI as well as physical examinations were conducted after two weeks and six weeks. RESULTS Placement of probes was successfully performed under the control of the ISC system. During cryosurgery, engulfment of the tumors by iceballs was carefully monitored by MRI. Necrosis of the cryoablated area was confirmed in all renal tumors by follow-up dynamic CT. The size regression of the uterine fibroids was observed through follow-up MRI. Two of the three cases of metastatic liver tumor were ablated completely. Additional therapy for a residual tumor was performed on one patient with a metastatic liver tumor. A small amount of pneumothorax was the only complication found in a patient with a metastatic liver tumor. CONCLUSION MR-guided cryosurgery with this new navigation system was feasible with low morbidity and allowed for safe and accurate puncture with a cryoprobe.
Two distinct congenital arrhythmias evoked by a multidysfunctional Na(+) channel.

The congenital long-QT syndrome (LQT3) and the Brugada syndrome are distinct, life-threatening rhythm disorders linked to autosomal dominant mutations in SCN5A, the gene encoding the human cardiac Na(+) channel. It is believed that these two syndromes result from opposite molecular effects: LQT3 mutations induce a gain of function, whereas Brugada syndrome mutations reduce Na(+) channel function. Paradoxically, an inherited C-terminal SCN5A mutation causes affected individuals to manifest electrocardiographic features of both syndromes: QT-interval prolongation (LQT3) at slow heart rates and distinctive ST-segment elevations (Brugada syndrome) with exercise. In the present study, we show that the insertion of the amino acid 1795insD has opposite effects on two distinct kinetic components of Na(+) channel gating (fast and slow inactivation) that render unique, simultaneous effects on cardiac excitability. The mutation disrupts fast inactivation, causing sustained Na(+) current throughout the action potential plateau and prolonging cardiac repolarization at slow heart rates. At the same time, 1795insD augments slow inactivation, delaying recovery of Na(+) channel availability between stimuli and reducing the Na(+) current at rapid heart rates. Our findings reveal a novel molecular mechanism for the Brugada syndrome and identify a new dual mechanism whereby single SCN5A mutations may evoke multiple cardiac arrhythmia syndromes by influencing diverse components of Na(+) channel gating function. The full text of this article is available at http://www.circresaha. org.
A New Daily Observational Record from Grytviken, South Georgia: Exploring Twentieth-Century Extremes in the South Atlantic

AbstractThe sparse nature of observational records across the mid- to high latitudes of the Southern Hemisphere limits the ability to place late-twentieth-century environmental changes in the context of long-term (multidecadal and centennial) variability. Historical records from subantarctic islands offer considerable potential for developing highly resolved records of change. In 1905, a whaling and meteorological station was established at Grytviken on subantarctic South Georgia in the South Atlantic (54°S, 36°W), providing near-continuous daily observations through to present day. This paper reports a new, daily observational record of temperature and precipitation from Grytviken, which is compared to regional datasets and historical reanalysis. The authors find a shift toward increasingly warmer daytime extremes commencing from the mid-twentieth century and accompanied by warmer nighttime temperatures, with an average rate of temperature rise of 0.13°C decade−1 over the period 1907–2016 (p < 0.0001). A.
Asthma from the patient’s perspective

Abstract Background: Asthma is a chronic disease with considerable burden on health and economy. Despite growing knowledge about causes and treatment, many patients have uncontrolled asthma, activity and social limitations and reduced quality of life (QOL). Coping with asthma could be developed in a social and scientific context and influenced by personal experience. Objective: To investigate the asthmatic’s perspective on asthma and how coping mechanisms with this disease were influenced by health professionals and networks. Methods: Asthma and QOL questionnaires were sent to 1191 individuals, who had participated in a population-based clinical study in 2004. Of the 7271 responders (72.7%), 10 chronic asthmatics (4 males and 6 females) with different asthma severity grades were recruited to in-depth interviews. The results were interpreted according to selected theories, especially Antonovsky’s salutogenic theory on how comprehensibility, manageability and meaningfulness contribute to sense of coherence and successful coping with stressor/disease. Results and conclusion: Asthma comprehensibility was limited by both the lack of structured information about asthma diagnosis, treatment and prognosis and insufficient follow-up. The informants experimented with what worked and developed individual ways to accomplish satisfactory management. They adjusted their own medication and sometimes stopped prophylactic medicine as they did not detect an immediate effect. Many informants put their asthma into perspective, comparing it to what could have been worse. The unnoticeable development of asthma had probably triggered a gradual adaptation making it more complex for asthmatics to estimate severity. This together with their relative view of asthma might have led to gradual and uncritical accept of bothersome symptoms and reduced the need to seek professional advice or make important changes, e.g. eliminating exposure to irritating agents at work. Avoidance was a recurrent phenomenon as the asthmatics tended to drop physical activities with others instead of improving treatment. Several stated that they did not like to flash their asthma. They had concerns about being labelled as ‘inadequate’. Physicians are urged to consider these tendencies and underlying the some of the mechanisms of ‘living with asthma’ in order to achieve proper asthma treatment and insure their patients’ wellbeing.
Bayesian image separation with natural image prior

Image separation from a set of observed mixtures has important applications in many fields such as intrinsic image extraction. We investigate in this work a natural image prior based image separation algorithm. The natural image prior is modeled via a high-order Markov Random Field (MRF) and is integrated into a Bayesian framework for estimating all the component images. Due to the usage of the natural image prior, which typically leading to non-convex optimization problems, there is no closed form solution for estimating the component images. Therefore, a Markov chain Monte-Carlo based sampling algorithm is developed for solution. Based on this, a Minimum Mean Square Error (MMSE) estimation can be achieved. The proposed method exploits both the mixing observations and the prior distribution of natural images, modeled via an MRF model. Experimental results indicate that the proposed method can generate better results than state-of-the-art image separation algorithms.
Guidelines for Coverage-Based Comparisons of Non-Adequate Test Suites

A fundamental question in software testing research is how to compare test suites, often as a means for comparing test-generation techniques that produce those test suites. Researchers frequently compare test suites by measuring their coverage. A coverage criterion C provides a set of test requirements and measures how many requirements a given suite satisfies. A suite that satisfies 100% of the feasible requirements is called C-adequate. Previous rigorous evaluations of coverage criteria mostly focused on such adequate test suites: given two criteria C and C′, are C-adequate suites on average more effective than C′-adequate suites? However, in many realistic cases, producing adequate suites is impractical or even impossible. This article presents the first extensive study that evaluates coverage criteria for the common case of non-adequate test suites: given two criteria C and C′, which one is better to use to compare test suites? Namely, if suites T1, T2,…,Tn have coverage values c1, c2,…,cn for C and c1′, c2′,…,cn′ for C′, is it better to compare suites based on c1, c2,…,cn or based on c1′, c2′,…,cn′? We evaluate a large set of plausible criteria, including basic criteria such as statement and branch coverage, as well as stronger criteria used in recent studies, including criteria based on program paths, equivalence classes of covered statements, and predicate states. The criteria are evaluated on a set of Java and C programs with both manually written and automatically generated test suites. The evaluation uses three correlation measures. Based on these experiments, two criteria perform best: branch coverage and an intraprocedural acyclic path coverage. We provide guidelines for testing researchers aiming to evaluate test suites using coverage criteria as well as for other researchers evaluating coverage criteria for research use.
Heritability of Coronary Artery Calcium Quantity Measured by Electron Beam Computed Tomography in Asymptomatic Adults

Background—Electron beam computed tomography is an accurate, noninvasive method to detect and quantify coronary artery calcification (CAC), a marker of subclinical and clinical coronary artery atherosclerosis. CAC quantity predicts future coronary artery disease end points in asymptomatic adults, but measured risk factors explain less than half the variability in CAC quantity. Although several candidate genes for CAC have been identified, the relative importance of genetic influences on CAC quantity has not been assessed in asymptomatic adults in a community. Methods and Results—We quantified the relative contributions of measured risk factors and genetic influences on CAC quantity measured by electron beam computed tomography in 698 asymptomatic white adults from 302 families. Before adjusting for any risk factors, 43.5% of the variation in CAC quantity was attributable to genetic factors (P =0.0007). Independent predictors of CAC quantity were identified with stepwise linear regression. After adjusting for these risk factors, including age, sex, fasting glucose level, systolic blood pressure, pack-years of smoking, and LDL cholesterol, 41.8% of the residual variation in CAC quantity was attributable to genetic factors (P =0.0003). Conclusions—These results demonstrate the importance of genetic factors in subclinical coronary atherosclerosis variation as measured by CAC quantity. The presence of genetic effects suggests that unknown genes that influence CAC quantity are yet to be identified.
Combined CD8+ and CD4+ adenovirus hexon-specific T cells associated with viral clearance after stem cell transplantation as treatment for adenovirus infection

Background Human adenovirus can cause morbidity and mortality in immunocompromised patients after allogeneic stem cell transplantation. Reconstitution of adenovirus-specific CD4+ T cells has been reported to be associated with sustained protection from adenovirus disease, but epitope specificity of these responses has not been characterized. Since mainly CD4+ T cells and no CD8+ T cells specific for adenovirus have been detected after allogeneic stem cell transplantation, the relative contribution of adenovirus-specific CD4+ and CD8+ T cells in protection from adenovirus disease remains to be elucidated. Design and Methods The presence of human adenovirus hexon-specific T cells was investigated in peripheral blood of pediatric and adult allogeneic stem cell transplant recipients, who showed spontaneous resolution of disseminated adenovirus infection. Subsequently, a clinical grade method was developed for rapid generation of adenovirus-specific T-cell lines for adoptive immunotherapy. Results Clearance of human adenovirus viremia coincided with emergence of a coordinated CD8+ and CD4+ T-cell response against adenovirus hexon epitopes in patients after allogeneic stem cell transplantation. Activation of adenovirus hexon-specific CD8+ and CD4+ T cells with a hexon protein-spanning peptide pool followed by interferon-γ-based isolation allowed rapid expansion of highly specific T-cell lines from healthy adults, including donors with very low frequencies of adenovirus hexon-specific T cells. Adenovirus-specific T-cell lines recognized multiple MHC class I and II restricted epitopes, including known and novel epitopes, and efficiently lysed human adenovirus-infected target cells. Conclusions This study provides a rationale and strategy for the adoptive transfer of donor-derived human adenovirus hexon-specific CD8+ and CD4+ T cells for the treatment of disseminated adenovirus infection after allogeneic stem cell transplantation.