Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of DNA damage and repair accompanying differentiation in the intestinal crypt.

The ability to process damaged DNA may vary between cells depending on their differentiated status. However, there is little in vivo data available and it is not intuitively obvious how the activity of specific repair pathways may vary between different subpopulations (e.g. stem cells and proliferative, committed and differentiated cells) of a particular tissue. To obtain such information for the intestinal epithelium, we have developed an assay that detects differences in the way different regions of the crypt (stem, proliferative and maturation zones) respond to DNA damage. The assay is a variant of the 'comet' assay, which detects DNA strand breaks by measuring the proportion of DNA migrating from individual cells, or in this case intact isolated crypts, in an electrophoretic field. The method is quantitative, with the amount of migrating DNA being proportional to the number of strand breaks. Isolated crypts are repair competent and spatial differences are apparent with some agents. The assay has the potential to characterize the repair properties of cells at different stages of differentiation within the crypt, determine the characteristics that might predispose them to damage and may help in understanding the route of stem cell mutation.
Content based Image Retrieval based on Histogram

visual content and find images in the database. this paper has been propose a novel approach to CBIR system based on prime’s histogram of the color image . This paper describe a project that implements by using Matlab and test three techniques depend on the simple color histogram based search and retrieve algorithm for images. The study find the technique to be effective between the three techniques that used.
Hemodynamic Thresholds for Precapillary Pulmonary Hypertension.

BACKGROUND Hemodynamic differentiation between pulmonary arterial hypertension (PAH) and postcapillary pulmonary hypertension (PH) is important because treatment options are strikingly different for the two disease subsets. Whereas patients with PAH can be treated effectively with targeted therapies, their use in postcapillary PH is currently not recommended. Our aim was to establish an algorithm to identify patients who are likely to experience a significant hemodynamic treatment response. METHODS We determined hemodynamic cutoffs to discriminate between idiopathic PAH and postcapillary PH in a large database of 4,363 stable patients undergoing first diagnostic right and left heart catheterizations. In a second step, we performed a patient-level pooled analysis of four randomized, placebo-controlled trials including 541 patients with PAH who received treprostinil or placebo, to validate hemodynamic cutoffs with regard to treatment response. RESULTS Receiver operating characteristic analysis identified mean pulmonary arterial wedge pressure (mPAWP) < 12 mm Hg and diastolic pulmonary vascular pressure gradient (DPG) ≥ 7 mm Hg as the best hemodynamic discriminators between idiopathic PAH and postcapillary PH. In our treatment study, only patients with mPAWP < 12 mm Hg, DPG > 20 mm Hg or a combination of both had a significant placebo-corrected improvement in hemodynamics. CONCLUSIONS mPAWP < 12 mm Hg and DPG > 20 mm Hg identify patients with PAH who are likely to have significant hemodynamic improvement with prostacyclin treatment.
EphB4 Promotes Osteogenesis of CTLA4-Modified Bone Marrow-Derived Mesenchymal Stem Cells Through Cross Talk with Wnt Pathway in Xenotransplantation.

BACKGROUND Cytotoxic T lymphocyte-associated antigen 4-Ig (CTLA4-Ig)-modified bone marrow-derived mesenchymal stem cells (MSCs-CTLA4) have excellent osteogenic function in xenografts, but their mechanism of action remains to be elucidated. As bidirectional signaling between erythropoietin-producing hepatocyte receptors B4 (EphB4) and ephrinB2 is vital for bone remodeling, this study aimed to fully characterize the role of MSCs-CTLA4 in promoting bone regeneration in xenotransplantation through EphB4/ephrinB2 and their cross talk with the Wnt/beta-catenin pathway. METHODS MSCs-CTLA4 were investigated for their osteogenic capacity through xenotransplantation in vivo. MSCs-CTLA4 were treated with ephrinB2-FC or FC under conditions of osteogenic induction and cultured with or without immune activation conditions established by phytohemagglutinin and peripheral blood mononuclear cells in vitro. Osteogenesis markers and the Wnt pathway-related molecules such as EphB4, runt-related transcription factor 2 (Runx2), collagen 1 (COL1), osteocalcin (OCN), alkaline phosphatase (ALP), calcium nodus, β-catenin, phospho-glycogen synthase kinase 3-beta (p-GSK-3β)-Ser9, and glycogen synthase kinase 3-beta (GSK-3β) were detected. RESULTS MSCs-CTLA4-based xenografts show better osteogenic capacity compared with MSC-based xenografts. EphB4 expression was reduced in MSCs compared with MSCs-CTLA4 under immune activation conditions. In ephrinB2-FC-treated cells, levels of osteogenesis markers were increased compared with FC-treated cells. The activity of GSK-3 was inhibited and the expression of β-catenin in MSCs was increased by ephrinB2-FC treatment. CONCLUSIONS CTLA4 modification maintains EphB4 expression in MSCs under immune activation conditions, and EphB4 cross talk with the Wnt pathway promotes osteogenic differentiation of MSCs-CTLA4.
Mammographic screening for breast cancer : an ounce of prevention worth a pound of harm ?

Introduction Although breast cancer screening by means of mammography was implemented almost 20 years ago it is still a subject of much controversy. Recent systematic reviews suggest a significant reduction in breast cancer related mortality due to screening. There are however reasons for skepticism. The incidence of advanced breast cancer has not decreased. Apart from the dubious benefits of screening, a myriad of adverse effects has been reported. Overdiagnosis results in unnecessary mastectomies, lumpectomies, chemotherapy and radiotherapy which all cause undue physical harm and squander of resources and specialist care. False-positive mammograms cause unnecessary psychological distress. In scientific literature, particularly by interested parties, these drawbacks tend to be underexposed. From an ethical point of view there are firm objections to breast cancer screening in its current mode. To live up to the principle of beneficence the principle of non-maleficence should not be neglected. Recent evidence suggests an alternative way of screening in which adverse effects are diminished. This paper looks to explore whether mammographic screening is still the best approach in view of the above points and to contrive the answer to a question that affects hundreds of thousands of women: ‘Should mammographic screening be reconsidered? ’
EXPECTED VALUE AND VARIANCE OF GEOMETRIC LIU PROCESS

A normally distributed fuzzy variable is defined by a unimodal and symmetric membership function, and is proved to be the most uncertain one when expected value and variance are given. In this note, a lognormally distributed fuzzy variable is defined and the membership function, expected value and variance of this variable are discussed. Based on these results, some properties about geometric Liu process are given.
QUALITY ASSESSMENT OF COFALE : AN AUTHORING TOOL FOR ADAPTIVE EDUCATIONAL HYPERMEDIA SYSTEMS

E-learning has become more learners centred because of adaptation. It is very difficult process to develop adaptive educational hypermedia systems because of complex nature of adaptation mechanism. There are several authoring tools through which it becomes very easy for everybody to develop such kind of systems. COFALE is also used for this purpose. It is an open source adaptive learning content management system. In this paper, we have assessed its quality through evaluating its object oriented design in terms of complexity, cohesion and coupling along with its usability in terms of adaptation features.
Conduit artery structure and function in lowlanders and native highlanders: relationships with oxidative stress and role of sympathoexcitation

Information describing alterations in vascular function during either acute or prolonged normobaric or hypobaric hypoxia is sparse and often confounded by pathology and methodological limitations. We show that high altitude exposure in lowlanders is associated with impairments in both endothelial and smooth muscle function, and with increased central arterial stiffness; furthermore, in all of these respects, lowlanders’ vasculature becomes comparable to that of natives born and raised at altitude. Changes in endothelial function occur very rapidly in normobaric hypoxia, and partly under the influence of sympathetic nerve activity. Thus, a lifetime of high‐altitude exposure neither attenuates nor intensifies the impairments in vascular function observed with short‐term exposure in lowlanders; such impairment and altered structure likely translate into an elevated cardiovascular risk.
Theory and Design of a Novel Wideband DC Isolated Wilkinson Power Divider

In this letter, a novel wideband 3-dB Wilkinson power divider (WPD) is presented. It employs port matching using coupled lines to achieve wider isolation bandwidth, without modifying the isolation network. Due to the presence of parallel coupled lines, the design enjoys complete DC isolation. Analysis leading to closed-form design equations shows freedom in choosing design parameters. Many design case studies are provided to show the capabilities of the proposed design. The designed and fabricated prototype shows promising results.
Sequence of heat-labile enterotoxin of Escherichia coli pathogenic for humans

We determined the complete nucleotide sequence of the toxB gene (375 base pairs in length), which encodes the B subunit of heat-labile enterotoxin produced from Escherichia coli pathogenic for humans (hLT). The amino acid sequence of the B subunit of hLT was deduced from the nucleotide sequence. Consequently, it has become possible to study the homology between the B subunits of three similar toxins: hLT, LT produced from E. coli pathogenic for piglets (pLT), and cholera toxin (the latter two sequences have been reported by others). The three B subunits are all 103 amino acids in length. A comparison of the toxB gene and the eltB gene, which encodes the B subunit of pLT, showed a 98% homology at the nucleotide level and a 95% homology at the amino acid (of a precursor) level, indicating the possibility that the two genes share a common ancestor. With respect to the B-subunit sequences, the homologies between hLT and pLT, between hLT and cholera toxin, and between pLT and cholera toxin were 96, 81, and 79%, respectively. Several large common sequences are conserved by the three peptides. In contrast, no sequences are present in both pLT and cholera toxin but missing in hLT.
Health Care Use and the Canadian Immigrant Population

Set within the “determinants of health” framework and drawing on Statistics Canada's longitudinal National Population Health Survey, this article explores health care utilization by Canada's immigrant population. Given the observed “healthy immigrant effect,” whereby the health status of immigrants at the time of arrival is high but subsequently declines and converges toward that of the native-born population, does the incidence of use of health care facilities reflect greater need for care? Similarly, does the use of health care facilities by the native- and the foreign-born differ, and if so, are these differences explained primarily by socioeconomic, sociodemographic, or lifestyle factors, which may point to problems in the Canadian health care system? This study identifies trends in the incidence of physician and hospital use, the factors that contribute to health care use, and differences in health care use between the native- and foreign-born.
A Novel Type of limulus Lectin-L6. PURIFICATION, PRIMARY STRUCTURE, AND ANTIBACTERIAL ACTIVITY (*)

Lipopolysaccharide (LPS)-binding protein(s) was first screened in the detergent extract of horseshoe crab (limulus) hemocytes, using LPS-immobilized agarose. A protein, designated L6 (Mr = 27,000), was found to bind to LPS-agarose and was eluted with EDTA or o-phenanthroline. The L6 protein, however, did not inhibit the LPS-mediated activation of a limulus serine protease zymogen factor C. L6 had an affinity to the matrix of Sepharose CL-6B itself, and it could be eluted with high concentrations of monosaccharides (0.5-1.0 M), such as glucose, mannose, and galactose, suggesting a lectin-like nature. The entire amino acid sequence of L6 was determined by sequencing peptides derived from CNBr and enzymatic cleavages. L6 contained 7 half-cystines, and 1 cysteine residue at position 201 had a free SH-group. In addition, positions of the remaining three intrachain disulfide bonds were assigned by amino acid and sequence analyses of three cystinyl peptides produced by lysyl endopeptidase digestion. These results indicated that the entire sequence of L6 consisted of 221 residues with no N-linked sugar and was composed of six tandem repeats, each consisting of 33-38 amino acid residues. Inductively coupled plasma spectrometry of L6 indicated the presence of 0.75 mol zinc/mol of protein. No significant sequence homology was observed between L6 and other proteins, including various animal lectins and LPS-binding proteins. However, L6 showed agglutinating activity on LPS-coated sheep erythrocytes and Gram-negative and Gram-positive bacteria, it inhibited the growth of Gram-negative bacteria, and thus it presumably recognizes carbohydrate components in the cell wall of bacteria.
A Qualitative Investigation of Averted School Shooting Rampages

The recent rash of school violence has again brought to the fore a need to investigate ways to enhance the safety of America’s children. With its emphases on prevention and collaboration with schools, a counseling psychology perspective can add much to the growing body of research on lethal school violence. This article aims to understand school violence prevention from the perspectives of school personnel who intervened to avert deadly shootings. As such, this study used consensual qualitative research methodology. Six primary domains emerged from the data, including school conditions, intervention, crisis planning, relationship, prevention efforts, and problematic issues. A seventh other domain captured important data that did not fit with the aforementioned six domains. From all domains, data were collapsed into 42 core ideas.
Solid-state nanopore localization by controlled breakdown of selectively thinned membranes

We demonstrate precise positioning of nanopores fabricated by controlled breakdown (CBD) on solid-state membranes by spatially varying the electric field strength with localized membrane thinning. We show 100 × 100 nm2 precision in standard SiNx membranes (30–100 nm thick) after selective thinning by as little as 25% with a helium ion beam. Control over nanopore position is achieved through the strong dependence of the electric field-driven CBD mechanism on membrane thickness. Confinement of pore formation to the thinned region of the membrane is confirmed by TEM imaging and by analysis of DNA translocations. These results enhance the functionality of CBD as a fabrication approach and enable the production of advanced nanopore devices for single-molecule sensing applications.
Network of inflammatory cytokines and correlation with disease activity in ulcerative colitis

Objective:The inflammatory component of most human inflammatory chronic diseases implicates the production of proinflammatory cytokines. Tumor necrosis factor α (TNFα) and interleukin 1β (IL1β) seem to play an important role in ulcerative colitis (UC) in relevant experimental models. Moreover, antiTNF therapy seems promising experimentally and clinically. However, these cytokines, and TNFα more particularly, are hardly seen in vivo in such patients. The mediators of choice, correlated with disease activities or drug efficacy, remain unclear. To characterize in vivo the network of colonic cytokines in patients with UC, and the contribution of the various cytokines to disease activity we performed this study, using the colonic perfusion method.Methods:A 20-cm colon length was perfused. Perfusate samples were collected for cytokine determination by enzyme-linked immnoassays. Nineteen perfusions were performed in mild to moderate UC, including two successive perfusions in four patients. Six healthy control patients and four having Crohn's disease (CD) with rectal involvement were studied. Endoscopic score, leukocyte scintigraphy, and systemic markers of inflammation were simultaneously quantified.Results:Large amounts of IL1β, TNFα, IL6, and IL8 were produced in UC patients with a highly significant correlation between TNFα, IL1β and IL8 two by two. Multivariate factorial analysis indicated that IL1β showed the best correlation with disease activity. Locally produced IL6 was strongly associated with circulating platelet counts. Moreover, production of inflammatory cytokines was associated with similar variations of disease activity in the four patients with two successive perfusions performed. The level of inflammatory cytokines in CD was lower than in UC; TNFα, IL1β, and IL6 were not found in any control patients.Conclusions:UC appears to be a chronic inflammatory disease characterized by high production of all four proinflammatory cytokines (IL1β, TNFα, IL6, and IL8). These results suggest that colonic perfusion may be a suitable method to evaluate the local anticytokine properties of new drugs, in correlation with disease activity and systemic markers of inflammation.
Colonic perforation: An unusual complication of therapy with high‐dose lnterleukin‐2

The majority (85%) of patients receiving high dose Interleukin‐2 (IL‐2) experience gastrointestinal side effects, namely nausea, vomiting and diarrhea. In this article we describe four cancer patients that developed localized necrosis or perforation of the colon during IL‐2 treatment. They represent 1.3% of patients (n = 315) or 0.9% of treatment courses (n = 452). All underwent surgical intervention and survived to leave the hospital. No common etiologic factor was apparent. Two patients were subsequently retreated with IL‐2 without complication. Localized colonic necrosis or perforation is a rare complication associated with high dose IL‐2 treatments. Aggressive surgical intervention is advocated and retreatment following recovery is safe.
Data issues in the life sciences

Abstract We review technical and sociological issues facing the Life Sciences as they transform into more data-centric disciplines - the “Big New Biology”. Three major challenges are: 1) lack of comprehensive standards; 2) lack of incentives for individual scientists to share data; 3) lack of appropriate infrastructure and support. Technological advances with standards, bandwidth, distributed computing, exemplar successes, and a strong presence in the emerging world of Linked Open Data are sufficient to conclude that technical issues will be overcome in the foreseeable future. While motivated to have a shared open infrastructure and data pool, and pressured by funding agencies in move in this direction, the sociological issues determine progress. Major sociological issues include our lack of understanding of the heterogeneous data cultures within Life Sciences, and the impediments to progress include a lack of incentives to build appropriate infrastructures into projects and institutions or to encourage scientists to make data openly available.
Differentiation-Dependent Interactions between RUNX-1 and FLI-1 during Megakaryocyte Development

ABSTRACT The transcription factor RUNX-1 plays a key role in megakaryocyte differentiation and is mutated in cases of myelodysplastic syndrome and leukemia. In this study, we purified RUNX-1-containing multiprotein complexes from phorbol ester-induced L8057 murine megakaryoblastic cells and identified the ets transcription factor FLI-1 as a novel in vivo-associated factor. The interaction occurs via direct protein-protein interactions and results in synergistic transcriptional activation of the c-mpl promoter. Interestingly, the interaction fails to occur in uninduced cells. Gel filtration chromatography confirms the differentiation-dependent binding and shows that it correlates with the assembly of a complex also containing the key megakaryocyte transcription factors GATA-1 and Friend of GATA-1 (FOG-1). Phosphorylation analysis of FLI-1 with uninduced versus induced L8057 cells suggests the loss of phosphorylation at serine 10 in the induced state. Substitution of Ser10 with the phosphorylation mimic aspartic acid selectively impairs RUNX-1 binding, abrogates transcriptional synergy with RUNX-1, and dominantly inhibits primary fetal liver megakaryocyte differentiation in vitro. Conversely, substitution with alanine, which blocks phosphorylation, augments differentiation of primary megakaryocytes. We propose that dephosphorylation of FLI-1 is a key event in the transcriptional regulation of megakaryocyte maturation. These findings have implications for other cell types where interactions between runx and ets family proteins occur.
Recalibration of the Klales et al. (2012) method of sexing the human innominate for Mexican populations.

OBJECTIVES The aim of this study was to test the accuracy of the Klales et al. (2012) equation for sex estimation in contemporary Mexican population. MATERIALS AND METHODS Our investigation was carried out on a sample of 203 left innominates of identified adult skeletons from the UNAM-Collection and the Santa María Xigui Cemetery, in Central Mexico. The Klales' original equation produces a sex bias in sex estimation against males (86-92% accuracy versus 100% accuracy in females). Based on these results, the Klales et al. (2012) method was recalibrated for a new cutt-of-point for sex estimation in contemporary Mexican populations. RESULTS AND DISCUSSION The results show cross-validated classification accuracy rates as high as 100% after recalibrating the original logistic regression equation. Recalibration improved classification accuracy and eliminated sex bias. This new formula will improve sex estimation for Mexican contemporary populations.
Roles of p53 in Herpes Simplex Virus 1 Replication

ABSTRACT p53 is a critical factor in the cellular response to a broad range of stress factors through its ability to regulate various cellular pathways. In this study, tandem affinity purification of transiently expressed herpes simplex virus 1 (HSV-1) regulatory protein ICP22 coupled with mass spectrometry-based proteomics technology and subsequent analyses showed that ICP22 interacted with p53 in HSV-1-infected cells. In p53−/− cells, replication of wild-type HSV-1 was reduced compared to that in parental p53+/+ cells, indicating that p53 had a positive effect on HSV-1 replication. In contrast, the levels of viral replication of an ICP22-null mutant virus were similar in both p53−/− and p53+/+ cells. At 2 h postinfection, the level of expression of ICP27, an essential viral regulatory protein, in p53−/− cells infected with wild-type HSV-1 or the ICP22-null mutant virus was lower than in p53+/+ cells. In contrast, at 18 h postinfection, the level of expression of ICP0, a critical viral regulatory protein, in p53−/− cells infected with the ICP22-null mutant virus was higher than in p53+/+ cells, although the levels of ICP0 expression in p53−/− and p53+/+ cells infected with wild-type HSV-1 were almost identical. These results suggested that p53 overall promoted HSV-1 replication and that p53 played both positive and negative roles in HSV-1 replication: upregulating ICP27 expression very early in infection and downregulating ICP0 expression later in infection, which was antagonized by ICP22.