Miracle-dz/UniFAR-FTUs huggingface dataset:
An Ongoing Role of &agr;-Calcitonin Gene–Related Peptide as Part of a Protective Network Against Hypertension, Vascular Hypertrophy, and Oxidative Stress

&agr;-Calcitonin gene–related peptide (&agr;CGRP) is a vasodilator, but there is limited knowledge of its long-term cardiovascular protective influence. We hypothesized that &agr;CGRP protects against the onset and development of angiotensin II–induced hypertension and have identified protective mechanisms at the vascular level. Wild-type and &agr;CGRP knockout mice that have similar baseline blood pressure were investigated in the angiotensin II hypertension model for 14 and 28 days. &agr;CGRP knockout mice exhibited enhanced hypertension and aortic hypertrophy. &agr;CGRP gene expression was increased in dorsal root ganglia and at the conduit and resistance vessel level of wild-type mice at both time points. &bgr;CGRP gene expression was also observed and shown to be linked to plasma levels of CGRP. Mesenteric artery contractile and relaxant responses in vitro and endothelial NO synthase expression were similar in all groups. The aorta exhibited vascular hypertrophy, increased collagen formation, and oxidant stress markers in response to angiotensin II, with highest effects observed in &agr;CGRP knockout mice. Gene and protein expression of endothelial NO synthase was lacking in the aortae after angiotensin II treatment, especially in &agr;CGRP knockout mice. These results demonstrate the ongoing upregulation of &agr;CGRP at the levels of both conduit and resistance vessels in vascular tissue in a model of hypertension and the direct association of this with protection against aortic vascular hypertrophy and fibrosis. This upregulation is maintained at a time when expression of aortic endothelial NO synthase and antioxidant defense genes have subsided, in keeping with the concept that the protective influence of &agr;CGRP in hypertension may have been previously underestimated.
A structural and functional analogue of a Bowman–Birk-type protease inhibitor from Odorrana schmackeri

Frog skin secretions contain complex peptidomes and peptidic protease inhibitors that are one of the biologically and structurally described groups of components. In the present study, by use of molecular ‘shotgun’ cloning and LC MS/MS fractionation sequencing, a novel Bowman–Birk-type heptadecapeptide (AALKGCWTKSIPPKPCF-amide), named Odorrana schmackeri Trypsin Inhibitor (OSTI), with a canonical Cys6–Cys16 disulfide bridge, was isolated and identified in piebald odorous frog (O. schmackeri) skin secretion. A synthetic replicate of OSTI-exhibited trypsin inhibitory activity with a Ki value of 0.3 ± 0.04 nM and also a tryptase inhibitory effect with a Ki of 2.5 ± 0.6 μM. This is the first time that this property has been reported for a peptide originating from amphibian sources. In addition, substituting lysine (K) with phenylalanine (F) at the presumed P1 position, completely abrogated the trypsin and tryptase inhibition, but produced a strong chymotrypsin inhibition with a Ki of 1.0 ± 0.1 μM. Thus, the specificity of this peptidic protease inhibitor could be optimized through modifying the amino acid residue at the presumed P1 position and this novel native OSTI, along with its analogue, [Phe9]-OSTI, have expanded the potential drug discovery and development pipeline directed towards alleviation of serine protease-mediated pathologies.
Supervisory control of concurrent discrete event systems

This disclosure relates to a vehicle seat construction which comprises a seat frame that has cushion and back support portions, a padded cushion trim assembly, and a padded back trim assembly. The cushion trim assembly is peripherally secured to the cushion support portion of the frame and is suspended thereacross. The cushion trim assembly has a rearward portion which is contoured upwardly adjacent the back support portion of the frame and is connected therewith with resilient means to provide for the cushion trim assembly to conform to the shape of an occupant. The back trim assembly is positioned upon the back support portion of the frame and has a lower portion which depends forwardly over and engages the upwardly contoured rearward portion of the cushion trim assembly. The cushion and back trim assemblies, when the seat construction is occupied, conform to the shape of the occupant with the rearward portion of the cushion trim assembly and the lower portion of the back trim assembly firmly supporting the lower back of the seat occupant.
Learning the weight of the query term from the relevance feedback

We address the problem of assigning each query word an appropriate weight in the retrieval function. Term weight assignment is important, which depends on the relationship among the query words and also impacts the retrieval performance directly. However, various retrieval models can be adopted by the system, which requires different approaches to set term weight and those empirical settings can not ensure to improve the retrieval quality. We propose an unified approach for different retrieval functions to set a unique weight to each individual word. We explore the popular retrieval functions and propose to regard the retrieval function as a linear classification model, which is aimed to predicate the relevance of the document. Thus the parameters in the learning model can be explained as the term weight in the retrieval model. For each query topic, we adopt the generative model and the discriminative model to estimate the term weight by taking the relevance feedback information as the training data. Our analysis gives more insight into the Rocchio's framework on relevance feedback, which can be taken as a special case in the generative model. Experimental results on the benchmark datasets show that by estimating proper weight to each query word, our approach can outperform the baseline methods of BM25 and obtain an equivalent performance with the probability language model.
Modern pollen rain raises doubts about the intensity and extension of the Last Glacial Cycle in Carajás: A reply to D’Apolito et al.

In this paper, we presented a reply to the comments on modern pollen rain and interpretations about the Last Glacial Maximum (LGM) by D’Apolito et al. Carajás may be considered as a micro-hotspot of plant endemism, mainly related to edaphic conditions and presence of different micro-habitats for canga vegetation into ironstone domains. These plants developed several survival strategies, including morphological and physiological adaptations, which is difficult for comparisons with any other distinct biomes or ecosystems. Furthermore, inaccurate interpretation of pollen taxa and habitat types by the previous palynological studies in Carajás, which are keys points presented in Guimarães et al., were not questioned by D’Apolito et al. Therefore, incomplete pollen database, uncertainties about pollen descriptions and plant–pollen habitat, poor knowledge about pollen production and dispersion in edaphically conditioned areas, as well as missing of multiproxy evidences about geology, geomorphology, faciology, and geochemistry can make LGM interpretations a very challenging task. This can produce more noises than reliable signals of paleoclimate changes.
An Integrated Multiomics Approach to Identify Candidate Antigens for Serodiagnosis of Human Onchocerciasis*

Improved diagnostic methods are needed to support ongoing efforts to eliminate onchocerciasis (river blindness). This study used an integrated approach to identify adult female Onchocerca volvulus antigens that can be explored for developing serodiagnostic tests. The first step was to develop a detailed multi-omics database of all O. volvulus proteins deduced from the genome, gene transcription data for different stages of the parasite including eight individual female worms (providing gene expression information for 94.8% of all protein coding genes), and the adult female worm proteome (detecting 2126 proteins). Next, female worm proteins were purified with IgG antibodies from onchocerciasis patients and identified using LC-MS with a high-resolution hybrid quadrupole-time-of-flight mass spectrometer. A total of 241 immunoreactive proteins were identified among those bound by IgG from infected individuals but not IgG from uninfected controls. These included most of the major diagnostic antigens described over the past 25 years plus many new candidates. Proteins of interest were prioritized for further study based on a lack of conservation with orthologs in the human host and other helminthes, their expression pattern across the life cycle, and their consistent expression among individual female worms. Based on these criteria, we selected 33 proteins that should be carried forward for testing as serodiagnostic antigens to supplement existing diagnostic tools. These candidates, together with the extensive pan-omics dataset generated in this study are available to the community (http://nematode.net) to facilitate basic and translational research on onchocerciasis.
Peripheral Nerve Blockade for Primary Total Knee Arthroplasty: A Population-based Cohort Study of Outcomes and Resource Utilization

Background: Although peripheral nerve blocks decrease pain after total knee arthroplasty, the population-level impact of nerve blocks on arthroplasty resource utilization is unknown. Methods: We conducted a population-based cohort study using linked administrative data from Ontario, Canada. We identified all adults having their first primary knee arthroplasty between 2002 and 2013. Using propensity scores to adjust for measureable confounders, we matched nerve block patients to a patient who did not receive a block. Within the matched cohort, we estimated the independent association of blocks with outcomes (length of hospital stay [primary]; and readmissions, emergency department visits, and falls [secondary]). Results: One hundred seventy-eight thousand two hundred fourteen patients were identified; 61,588 (34.6%) had a block. The mean hospital stay was 4.6 days with a block compared to 4.8 without. After matching, there was a statistically significant decrease in the length of stay in the block group (relative risk, 0.98; 95% CI, 0.97 to 0.99; P < 0.001). Blocks were associated with a significant decrease in readmissions (relative risk, 0.87; 95% CI, 0.79 to 0.88; P < 0.001) but not emergency department visits (relative risk, 1.02; 95% CI, 0.98 to 1.05) or falls (relative risk, 1.37; 95% CI, 0.90 to 2.08). The association of blocks with length of stay after 2008 was inconsistent; overall, they were associated with longer stays; however, single-shot blocks were associated with shorter stays, while continuous techniques prolonged the length of stay. Conclusions: Nerve blocks in total knee arthroplasty patients were associated with statistically significant reductions in length of stay and readmissions, but not emergency department visits or falls. The significance of these findings at the patient level and in contemporary practice requires further exploration in prospective randomized studies at low risk of indication bias.
Multi-Task Learning for Classification with Dirichlet Process Priors

Consider the problem of learning logistic-regression models for multiple classification tasks, where the training data set for each task is not drawn from the same statistical distribution. In such a multi-task learning (MTL) scenario, it is necessary to identify groups of similar tasks that should be learned jointly. Relying on a Dirichlet process (DP) based statistical model to learn the extent of similarity between classification tasks, we develop computationally efficient algorithms for two different forms of the MTL problem. First, we consider a symmetric multi-task learning (SMTL) situation in which classifiers for multiple tasks are learned jointly using a variational Bayesian (VB) algorithm. Second, we consider an asymmetric multi-task learning (AMTL) formulation in which the posterior density function from the SMTL model parameters (from previous tasks) is used as a prior for a new task: this approach has the significant advantage of not requiring storage and use of all previous data from prior tasks. The AMTL formulation is solved with a simple Markov Chain Monte Carlo (MCMC) construction. Experimental results on two real life MTL problems indicate that the proposed algorithms: (a) automatically identify subgroups of related tasks whose training data appear to be drawn from similar distributions; and (b) are more accurate than simpler approaches such as single-task learning, pooling of data across all tasks, and simplified approximations to DP.
The unsolved challenge to phylogenetic correlation tests for categorical characters.

1Departments of Zoology and Botany and Beaty Biodiversity Museum, University of British Columbia, 6270 University Boulevard, Vancouver, British Columbia, Canada V6T 1Z4; 2Departments of Zoology and Biodiversity Research Centre, University of British Columbia, 6270 University Boulevard, Vancouver, British Columbia, Canada V6T 1Z4 and 3Department of Biological Sciences, Macquarie University, Sydney NSW 2109, Australia ∗Correspondence to be sent to: Department of Zoology, University of British Columbia, 6270 University Boulevard, Vancouver, British Columbia, Canada V6T 1Z4; E-mail: wayne.maddison@ubc.ca.
Using Unfixed, Frozen Tissues to Study Natural Mucin Distribution

Mucins are complex and heavily glycosylated O-linked glycoproteins, which contain more than 70% carbohydrate by weight1-3. Secreted mucins, produced by goblet cells and the gastric mucosa, provide the scaffold for a micrometers-thick mucus layer that lines the epithelia of the gut and respiratory tract3,4. In addition to mucins, mucus layers also contain antimicrobial peptides, cytokines, and immunoglobulins5-9. The mucus layer is an important part of host innate immunity, and forms the first line of defense against invading microorganisms8,10-12. As such, the mucus is subject to numerous interactions with microbes, both pathogens and symbionts, and secreted mucins form an important interface for these interactions. The study of such biological interactions usually involves histological methods for tissue collection and staining. The two most commonly used histological methods for tissue collection and preservation in the clinic and in research laboratories are: formalin fixation followed by paraffin embedding, and tissue freezing, followed by embedding in cryo-protectant media. Paraffin-embedded tissue samples produce sections with optimal qualities for histological visualization including clarity and well-defined morphology. However, during the paraffin embedding process a number of epitopes become altered and in order to study these epitopes, tissue sections have to be further processed with one of many epitope retrieval methods13. Secreted mucins and lipids are extracted from the tissue during the paraffin-embedding clearing step, which requires prolong incubation with organic solvents (xylene or Citrisolv). Therefore this approach is sub-optimal for studies focusing on the nature and distribution of mucins and mucus in vivo. In contrast, freezing tissues in Optimal Cutting Temperature (OCT) embedding medium avoids dehydration and clearing of the sample, and maintains the sample hydration. This allows for better preservation of the hydrated mucus layer, and thus permits the study of the numerous roles of mucins in epithelial biology. As this method requires minimal processing of the tissue, the tissue is preserved in a more natural state. Therefore frozen tissues sections do not require any additional processing prior to staining and can be readily analyzed using immunohistochemistry methods. We demonstrate the preservation of micrometers-thick secreted mucus layer in frozen colon samples. This layer is drastically reduced when the same tissues are embedded in paraffin. We also demonstrate immunofluorescence staining of glycan epitopes presented on mucins using plant lectins. The advantage of this approach is that it does not require the use of special fixatives and allows utilizing frozen tissues that may already be preserved in the laboratory.
Cure of cancer for seven cancer sites in the Flemish Region

Cumulative relative survival curves for many cancers reach a plateau several years after diagnosis, indicating that the cancer survivor group has reached “statistical” cure. Parametric mixture cure model analysis on grouped relative survival curves provide an interesting way to determine the proportion of statistically cured cases and the mean survival time of the fatal cases in particular for population‐based cancer registries. Based on the relative survival data from the Belgian Cancer Registry, parametric cure models were applied to seven cancer sites (cervix, colon, corpus uteri, skin melanoma, pancreas, stomach and oesophagus), at the Flemish Regional level for the incidence period 1999–2011. Statistical cure was observed for the examined cancer sites except for oesophageal cancer. The estimated cured proportion ranged from 5.9% [5.7, 6.1] for pancreatic cancer to 80.8% [80.5, 81.2] for skin melanoma. Cure results were further stratified by gender or age group. Stratified cured proportions were higher for females compared to males in colon cancer, stomach cancer, pancreas cancer and skin melanoma, which can mainly be attributed to differences in stage and age distribution between both sexes. This study demonstrates the applicability of cure rate models for the selected cancer sites after 14 years of follow‐up and presents the first population‐based results on the cure of cancer in Belgium.
Fecal Amino Acid Analysis Can Discriminate De Novo Treatment-Naïve Pediatric Inflammatory Bowel Disease From Controls

Objectives: Endoscopy remains mandatory in the diagnostic work-up of inflammatory bowel disease (IBD), but is a costly and invasive procedure. Identification of novel, noninvasive, diagnostic biomarkers remains a priority. The aim of the present study was to explore the potential of fecal amino acid composition as diagnostic biomarker for pediatric IBD. Methods: In this case-control study, treatment-naïve, de novo pediatric patients with IBD from two tertiary centers were included. Endoscopic severity of ulcerative colitis (UC) and Crohn's disease (CD) was based on physician global assessment scores, substantiated by levels of fecal calprotectin and C-reactive protein at study inclusion. Patients were instructed to collect a fecal sample prior to bowel cleansing. Healthy controls (HCs) were recruited from primary schools in the same region. Dedicated amino acid analysis was performed on all samples. Results: Significant differences between 30 IBD patients (15 UC, 15 CD) and 15 age and sex-matched HCs were found in six amino acids (histidine, tryptophan, phenylalanine, leucine, tyrosine, and valine; all area under the curve >0.75 and P < 0.005), displaying higher levels in IBD. When distributing the patients according to type of IBD, a similar spectrum of amino acids differed between UC and HC (histidine, tryptophan, phenylalanine, leucine, valine, and serine), whereas three amino acids were different between CD and HC (histidine, tryptophan, and phenylalanine). Conclusions: Significantly increased levels of six different fecal amino acids were found in patients with IBD compared to controls. Whether these differences reflect decreased absorption or increased loss by inflamed intestines needs to be elucidated.
Calretinin and parvalbumin in schizophrenia and affective disorders: a mini-review, a perspective on the evolutionary role of calretinin in schizophrenia, and a preliminary post-mortem study of calretinin in the septal nuclei

Objective: The septal nuclei are important limbic regions that are involved in emotional behavior and connect to various brain regions such as the habenular complex. Both the septal nuclei and the habenular complex are involved in the pathology of schizophrenia and affective disorders. Methods: We characterized the number and density of calretinin-immunoreactive neurons in the lateral, medial, and dorsal subregions of the septal nuclei in three groups of subjects: healthy control subjects (N = 6), patients with schizophrenia (N = 10), and patients with affective disorders (N = 6). Results: Our mini-review of the combined role of calretinin and parvalbumin in schizophrenia and affective disorders summarizes 23 studies. We did not observe significant differences in the numbers of calretinin-immunoreactive neurons or neuronal densities in the lateral, medial, and dorsal septal nuclei of patients with schizophrenia or patients with affective disorders compared to healthy control subjects. Conclusions: Most post-mortem investigations of patients with schizophrenia have indicated significant abnormalities of parvalbumin-immunoreactive neurons in various brain regions including the hippocampus, the anterior cingulate cortex, and the prefrontal cortex in schizophrenia. This study also provides an explanation from an evolutionary perspective for why calretinin is affected in schizophrenia.
Expertise paradigms for investigating the neural substrates of stable memories

One of the hallmarks of acquiring expertise in any area of life is the ability to maintain relevant information over a long period of time (i.e., years or decades). Understanding the neural implementations of this ability requires the elucidation of two issues. First, the processes whereby recently acquired pieces of information become stable over time (i.e., memory consolidation); and second, the localization of these stable memories in the brain. Unlike neurobiological and neuropsychological memory research, brain imaging research has paid little attention to these issues. Instead, most memory research in brain imaging has focused on the processes of memory encoding and retrieval. In this article we first succinctly present the current debate on the localization of stable memories in neurobiology and neuropsychology. We then discuss the difficulties in studying the localization of stable memories in human neuroimaging. After presenting the most traditional paradigm in studying long-term memory and the autobiographical memory paradigm, we present three expertise brain imaging paradigms. We also discuss how the latter help overcome the technical difficulties to investigate the neural localization of stable memories.