Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptional Profiling of Equine Endometrium During the Time of Maternal Recognition of Pregnancy1

Establishment and maintenance of pregnancy are critically dependent on embryo-maternal communication during the preimplantation period. To gain new insights into this complex process in the horse, transcriptional profiling of Day 13.5 pregnant and cyclic endometrial tissue samples was carried out using custom-designed microarrays. Selected array data were validated using quantitative RT-PCR, and proteins of interest were localized using immunohistochemistry. One hundred and six transcripts were up-regulated, whereas 47 transcripts showed lower expression levels in pregnant mares, that is, were down-regulated in pregnant mares. Half of the genes with known or inferred function are classically regulated by estrogens. Elevated transcript levels were found for genes involved in cell-cell signaling, heat shock response, and secretory proteins, among others. Solute carrier family 36 (proton/amino acid symporter), member 2, SLC36A2, was one of the most highly up-regulated genes, potentially reflecting the nutritional needs of the rapidly developing embryo. Among the genes showing lower expression in pregnant mares, estrogen receptor 1 was of particular interest because of its potential involvement in the initiation of luteolysis in cyclic mares. We hypothesize that either conceptus' estrogens or luteinizing hormone of uterine origin is involved in the observed down-regulation of estrogen receptor 1. Several of the genes identified in the current study are known to play a role in early pregnancy in species other than the horse. Thus, products of these commonly expressed genes likely contain universal activities for controlling endometrial receptivity to the conceptus, whereas other factors play unique roles within specific species in ensuring ongoing corpus luteum function. This is the first systematic study of endometrial transcriptome changes in response to the presence of an embryo during maternal recognition of pregnancy and an important step toward deciphering the embryo-maternal dialogue in equids.
Feeling severely affected by Multiple Sclerosis: What does this mean?

Background: The situation for people feeling severely affected by Multiple Sclerosis (MS) remains largely unexamined and the term ‘severe MS’ is not clearly defined. Aim: Our study describes this sub-group of patients utilizing exclusively a subjective inclusion criterion to analyse their reasons for feeling severely affected and document their perceived unmet needs. Design: A questionnaire with open- and closed-ended items addressing only patients feeling severely affected was sent out nationwide. Expanded Disability Status Score (EDSS) and subjectively severe affectedness were analysed for correlation. After dichotomizing both scores by a median split, the answers were allocated to these groups and tested for significant differences. Setting/participants: 1,110 questionnaires were analysed regarding the closed-ended questions while a subsample of 40% (n = 445) was analysed regarding the open-ended questions. Average age of participants was 51.87 years. Average time since diagnosis was 16.6 years. Main course of the disease was secondary progressive (35.5%). Results: The most frequently mentioned reasons for feeling severely affected were lack of mobility (56.4%) and fatigue (27.4%). Significant percentages for unmet needs were seen in the categories of funding services (31.0%), better social integration (24.7%) and medical support (25.2%). A significant correlation was observed between EDSS and subjectively felt affectedness (p ≤ 0.01). Motor disorders explained differences in patient needs behind a higher EDSS score; higher severe affectedness referred to other issues like dependency and immobility. Conclusions: EDSS is insufficient for usage as the sole instrument for measuring severe affectedness as it does not take into account other potential reasons. Complex patient needs necessitate multi-professional care as offered by palliative medicine.
An Overview of PWGL, a Visual Programming Environment for Music

This article provides an overview of our free Lispbased, cross-platform, visual programming environment called PWGL (the name is an acronym for PatchWork Graphical Language). PWGL can be used for computer-aided composition, music analysis, and sound synthesis. Our work is influenced by our past experience with PatchWork (Laurson 1996; Assayag et al. 1999). However, PWGL has been completely rewritten and redesigned in our attempt to develop and improve many of the useful concepts behind PatchWork. PWGL and several of its applications have already been discussed in our previous work, including Laurson and Kuuskankare (2002, 2006), Kuuskankare and Laurson (2006), and Laurson, Norilo, and Kuuskankare (2005). Since 2002, PWGL has undergone several revisions and additions including the public release, launching of the PWGL home page, inclusion of the tutorials and new programming interfaces, etc.; each of these have been attempts to make our system more available and more easily approachable within the computer music community. The main purpose of the present article is to give a general overview of the current state of the system with an emphasis on features that are useful for potential PWGL users, such as composers, music analysts, and researchers. PWGL is programmed ANSI Common Lisp (Steele 1990) from LispWorks (www.lispworks.com), which is source-code compatible across several different operating systems, such as Macintosh OS X, Microsoft Windows, and Linux. LispWorks provides support for Foreign Language Interfaces, by which a program written in one programming language can call routines or make use of services written in another. LispWorks also supports the OpenGL graphics library API. (The graphics part
Promoter methylation and transgene copy numbers predict unstable protein production in recombinant chinese hamster ovary cell lines

Mammalian cell lines for recombinant protein production need to maintain productivity over extended cultivation times. Long‐term stability studies are time and resource intensive, but are widely performed to identify and eliminate unstable candidates during cell line development. Production instability of manufacturing cell lines can be associated with methylation and silencing of the heterologous promoter. We have identified CpG dinucleotides within the human cytomegalovirus major immediate early promoter/enhancer (hCMV‐MIE) that are frequently methylated in unstable antibody‐producing Chinese hamster ovary (CHO) cell lines. We have established methylation‐specific real‐time qPCR for the rapid and sensitive measurement of hCMV‐MIE methylation in multiple cell lines and provide evidence that hCMV‐MIE methylation and transgene copy numbers can be used as early markers to predict production instability of recombinant CHO cell lines. These markers should provide the opportunity to enrich stable producers early in cell line development and allow developers to put more emphasis on other criteria, such as product quality and bioprocess robustness. Biotechnol. Bioeng. 2011;108: 2670–2681. © 2011 Wiley Periodicals, Inc.
Apoptosis of regulatory T lymphocytes is increased in chronic inflammatory bowel disease and reversed by anti-TNFα treatment

Background and aims Inappropriate immune responses contribute to the continuous stimulation of the intestinal immune system in chronic inflammatory bowel disease (IBD). Among several pathogenic factors, a numerical deficiency of regulatory T (Treg) cells has been suggested to lead to an insufficient compensation of chronically activated T lymphocytes. This study was conducted to investigate whether increased apoptosis contributes to Treg cell deficiency in IBD and whether successful treatment with antitumour necrosis factor α (TNFα) is achieved by reducing of Treg cell apoptosis. Methods Apoptosis of CD4+Foxp3+ Treg cells in tissue sections of patients with active IBD was analysed by immunohistochemistry and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling) staining. Apoptosis of peripheral blood CD4+CD25+Foxp3+ Treg cells was investigated by flow cytometry and annexin-V staining. In addition, caspase activity and apoptosis were measured in sera of patients with IBD treated with anti-TNFα by a luminometric caspase enzyme assay. Results It is demonstrated that patients with active IBD revealed increased apoptosis of local CD4+Foxp3+ Treg cells in the inflamed mucosa compared with non-inflamed control colon tissue. Moreover, in peripheral blood a reduced frequency and increased apoptosis of Treg cells were found and accompanied by elevated caspase activity in the serum. During anti-TNFα treatment, Treg cell apoptosis declined in close correlation with elevated peripheral Treg cell numbers and a decrease of caspase activation and disease activity. Conclusions These data suggest that increased apoptosis of Treg cells plays a potentially important role in the pathogenesis of IBD and can be reversed by anti-TNFα treatment. Measurement of Treg cell apoptosis and serum caspase activity might therefore represent promising tools for monitoring disease activity and treatment response in patients with IBD.
Slow-binding inhibition of acetylcholinesterase by an alkylammonium derivative of 6-methyluracil: mechanism and possible advantages for myasthenia gravis treatment.

Inhibition of human AChE (acetylcholinesterase) and BChE (butyrylcholinesterase) by an alkylammonium derivative of 6-methyluracil, C-547, a potential drug for the treatment of MG (myasthenia gravis) was studied. Kinetic analysis of AChE inhibition showed that C-547 is a slow-binding inhibitor of type B, i.e. after formation of the initial enzyme·inhibitor complex (Ki=140 pM), an induced-fit step allows establishment of the final complex (Ki*=22 pM). The estimated koff is low, 0.05 min(-1) On the other hand, reversible inhibition of human BChE is a fast-binding process of mixed-type (Ki=1.77 μM; Ki'=3.17 μM). The crystal structure of mouse AChE complexed with C-547 was solved at 3.13 Å resolution. The complex is stabilized by cation-π, stacking and hydrogen-bonding interactions. Molecular dynamics simulations of the binding/dissociation processes of C-547 and C-35 (a non-charged analogue) to mouse and human AChEs were performed. Molecular modelling on mouse and human AChE showed that the slow step results from an enzyme conformational change that allows C-547 to cross the bottleneck in the active-site gorge, followed by formation of tight complex, as observed in the crystal structure. In contrast, the related non-charged compound C-35 is not a slow-binding inhibitor. It does not cross the bottleneck because it is not sensitive to the electrostatic driving force to reach the bottom of the gorge. Thus C-547 is one of the most potent and selective reversible inhibitors of AChE with a long residence time, τ=20 min, longer than for other reversible inhibitors used in the treatment of MG. This makes C-547 a promising drug for the treatment of this disease.
An Imprecision-based Language for the Web

Abstract In this paper, we introduce a fuzzy language to extract information from the web extending the web query language WebSQL [1]. These extensions are based on two observations: the inadequacy of traditional Boolean query languages for web documents, and the need to move beyond the notion of query providing just a set of answers in order to provide a better data presentation through answers' restructuring. In order to address the first issue, we consider fuzzy sets to express imprecision in data, queries and answers. In our case, data imprecision comes from the data classification provided by several search engines. Query imprecision occurs in weighting values provided at query definition time. Answer imprecision allows to filter and rank the answers. To address the second point, we provide an answer restructuring language to model the restructuring phase that follows the query phase. The restructuring language allows creation/deletion of links and page creation. Thus several answer organizations are possible as a result to the same query. The resulting language extends in a uniform framework WebSQL. Then we provide a mapping for the language constructs into an extended relational algebra called SAME W [2] expressing similarity-based queries over imprecisely classified data, queries involving navigation among web pages and answer restructurings. Finally, we study the optimization of similarity-based queries using equivalence and containment rules holding for SAME W and presenting several algorithms for query evaluation.
High Pressure Extraction of Antioxidants from Solanum stenotomun Peel

In the work described here, two techniques for the recovery of anthocyanins from potato peel were studied and compared. One of the techniques employed was supercritical fluid extraction (SFE) with pure CO2 or with CO2 and ethanol as cosolvent and the other technique was pressurized liquid extraction (PLE), where the solvent used was ethanol in water acidified to pH 2.6. The effects of pressure and temperature were studied and the anthocyanin contents obtained were statistically analyzed. In SFE the use of low pressure (100 bar) and high temperature (65 °C) was desirable for the anthocyanin extraction. With PLE the anthocyanin contents are increased considerably, and the best yields were obtained at 100 bar and 80 °C. This result is in correspondence with antioxidant activity index values (1.66) obtained in a DPPH antioxidant activity assay. In the extracts obtained with PLE the phenolic compounds were also determined, but the main compounds presented in the extract are anthocyanins.
Nitrogen fixation: Anthropogenic enhancement‐environmental response

In the absence of human activities, biotic fixation is the primary source of reactive N, providing about 90–130 Tg N yr−1 (Tg = 1012 g) on the continents. Human activities have resulted in the fixation of an additional ≈140 Tg N yr−1 by energy production (≈20 Tg N yr−1 ), fertilizer production (≈80 Tg N yr−1), and cultivation of crops (e.g., legumes, rice) (≈40 Tg N yr−1 ). We can only account for part of this anthropogenic N. N2O is accumulating in the atmosphere at a rate of 3 Tg N yr−1. Coastal oceans receive another 41 Tg N yr−1 via rivers, much of which is buried or denitrified. Open oceans receive 18 Tg N yr−1 by atmospheric deposition, which is incorporated into oceanic N pools (e.g., NO3−, N2). The remaining 80 Tg N yr−1 are either retained on continents in groundwater, soils, or vegetation or denitrified to N2. Field studies and calculations indicate that uncertainties about the size of each sink can account for the remaining anthropogenic N. Thus although anthropogenic N is clearly accumulating on continents, we do not know rates of individual processes. We predict the anthropogenic N-fixation rate will increase by about 60% by the year 2020, primarily due to increased fertilizer use and fossil-fuel combustion. About two-thirds of the increase will occur in Asia, which by 2020 will account for over half of the global anthropogenic N fixation.
Ontology based personalized search

With the exponentially growing amount of information available on the Internet, the task of retrieving documents of interest has become increasingly difficult. Search engines usually return more than 1,500 results per query, yet out of the top twenty results, only one half turn out to be relevant to the user. One reason for this is that Web queries are in general very short and give an incomplete specification of individual users' information needs. This paper explores ways of incorporating users' interests into the search process to improve the results. The user profiles are structured as a concept hierarchy of 4,400 nodes. These are populated by 'watching over a user's shoulder' while he is surfing. No explicit feedback is necessary. The profiles are shown to converge and to reflect the actual interests quite well. One possible deployment of the profiles is investigated: re-ranking and filtering search results. Increases in performance are moderate but noticeable and show that fully automatic creation of large hierarchical user profiles is possible.
Drug treatments in upper gastrointestinal bleeding: value of endoscopic findings as surrogate end points

INTRODUCTION Pharmacotherapy for upper gastrointestinal bleeding has been difficult to evaluate because clinical end points are infrequent and affected by other factors. AIMS To evaluate whether blood in the stomach at endoscopy reflected severity of bleeding, predicted clinical outcomes, and could be altered by therapeutic agents. METHODS We studied 414 consecutive admissions with suspected upper gastrointestinal bleeding. Patients were randomised to receive lansoprazole 60 mg followed by 30 mg four times daily, tranexamic acid 2 g followed by 1 g four times daily, both drugs, or placebo for four days, until discharge or a clinical end point occurred. Logistic regression analysis was used to determine predictors of endoscopic changes and clinical outcomes, and to investigate the effects of drug treatments on blood in the stomach. RESULTS Of 414 patients with suspected upper gastrointestinal bleeding, 379 were endoscoped. Upper gastrointestinal bleeding was confirmed in 316. Sixteen required surgery within 30 days and 16 died on the index admission. Trial treatments were evaluable on a per protocol basis in 228 patients. The amount of blood in the stomach was found to reflect initial risk, with significant associations with high risk categorisation (odds ratio 3.7 (95% confidence interval 1.5–9.4) for more than a trace v none/trace), age (1.5 (1.1–1.9) per decade), and initial pulse (1.02 (1.00–1.04) per beat), and to predict rebleeding (9.2 (4.6–18.7)) and surgery (8.2 (2.9–22.9)). Other stigmata were less significant in these respects. The amount of blood in the stomach at endoscopy was reduced significantly by both lansoprazole (0.22 (0.07–0.63)) and tranexamic acid (0.27 (0.09–0.81)), although there was no evidence of synergy. CONCLUSIONS Blood in the stomach reflects clinical features in patients with acute upper gastrointestinal bleeding and is reduced by treatment with lansoprazole and tranexamic acid.
Azilsartan medoxomil in the treatment of hypertension: the definitive angiotensin receptor blocker?

Introduction: Azilsartan medoxomil is the newest angiotensin receptor blocker marketed for the treatment of arterial hypertension. The aim of this article was to review the available evidence about this drug alone or combined with other antihypertensive agents in the treatment of hypertensive population. Areas covered: For this purpose, a search on MEDLINE and EMBASE databases was performed. The MEDLINE and EMBASE search included both medical subject headings (MeSHs) and keywords including azilsartan or azilsartan medoxomil or angiotensin receptor blockers or renin angiotensin system or chlorthalidone and hypertension. References of the retrieved articles were also screened for additional studies. There were no language restrictions. Expert opinion: Azilsartan medoxomil has a potent and persistent ability to inhibit binding of angiotensin II to AT1 receptors, which may play a role in its superior blood pressure (BP) -lowering efficacy compared with other drugs, including ramipril, candesartan, valsartan or olmesartan, without an increase of side effects. Chlortalidone is a diuretic which significantly differs from other classic thiazides and has largely demonstrated clinical benefits in outcome trials. The fixed-dose combination of azilsartan and chlorthalidone has been shown to be more effective than other potent combinations of angiotensin receptor blockers plus hydrochlorothiazide, with a good tolerability profile.
Use cases of heterogeneous learning ontologies

The emergence of new repositories of learning resources based on semantic technology raises the problem of ontologies interoperability. Learning resources are described by a set of metadata which may use different ontologies as referential. To handle the increasing number of heterogeneous ontologies it becomes necessary to develop automatic mapping approach. In this paper we propose to study technical solutions for ontologies handling through two use cases: (1) the comparison between a current learner profile and a target profile and (2) the search of learning resources among distributed repositories.
Prototyping of biodegradable flat stents in pure zinc by laser microcutting and chemical etching

Cardiovascular stents are biomedical devices, which restore normal blood flow in the case of coronary artery obstructions. Biodegradable metals provide the possibility of a less-invasive treatment, where the stent is dissolved in body fluids after remodelling of the artery. Compared to Mg- and Fe-alloys, Zn and its alloys provide optimal corrosion rates as a more recent option. New Zn-alloys are under development and often need to be tested for corrosion and biological properties. However, Zn and its alloys still require further investigation in terms of the production routes involved for stent manufacturing. Especially at a prototyping stage, the extrusion of thin biodegradable tubes is an expensive and difficult process. This work investigates a novel manufacturing route consisting of laser microcutting and chemical etching of pure Zn sheets to develop inflatable devices that can take a tubular form. Initially, laser microcutting parameters were studied to understand the dross formation on a low melting point material. Chemical etching of the material with low corrosion resistance was investigated for the dross removal. Prototype flat stents were produced and expanded using a medical catheter.