Miracle-dz/UniFAR-FTUs huggingface dataset:
Colitis-associated variant of TLR2 causes impaired mucosal repair because of TFF3 deficiency.

BACKGROUND & AIMS Goblet cells (GC) facilitate mucosal protection and epithelial barrier repair, yet the innate immune mechanisms that selectively drive GC functions have not been defined. The aim of this study was to determine whether Toll-like receptor (TLR) 2 and modulation of GC-derived trefoil factor (TFF) 3 are functionally linked in the intestine. METHODS GC modulation was assessed using quantitative real-time polymerase chain reaction analysis (qRT-PCR), Western blotting, and confocal microscopy. Dextran sulfate sodium (DSS) colitis was induced in wild-type, TFF3(-/-), and TLR2(-/-) mice. Recombinant TLR2 ligand or TFF3 peptide were orally administered after DSS termination. Caco-2 cells overexpressing full-length TLR2 or mutant TLR2-R753Q were tested for TFF3 synthesis and functional-related effects in a wounding assay. RESULTS Data from in vitro (Ls174T) and ex vivo models of murine and human GC reveal that TLR2 activation selectively induces synthesis of TFF3. In vivo studies using TFF3(-/-) or TLR2(-/-) mice demonstrate the ability for oral treatment with a TLR2 agonist to confer antiapoptotic protection of the intestinal mucosa against inflammatory stress-induced damage through TFF3. Recombinant TFF3 rescues TLR2-deficient mice from increased morbidity and mortality during acute colonic injury. Severe ulcerative colitis (UC) has recently been found to be associated with the R753Q polymorphism of the TLR2 gene. The relevance of the observed functional effect of TLR2 in regulating GC is confirmed by the finding that the UC-associated TLR2-R753Q variant is functionally deficient in the ability to induce TFF3 synthesis, thus leading to impaired wound healing. CONCLUSIONS These data demonstrate a novel function of TLR2 in intestinal GC that links products of commensal bacteria to innate immune protection of the host via TFF3.
Effects of Two Different Doses of Amino Acid Supplementation on Growth and Blood Amino Acid Levels in Premature Neonates Admitted to the Neonatal Intensive Care Unit: A Randomized, Controlled Trial

OBJECTIVES. The goal was to measure the effects of 2 distinct strategies for parenteral nutrition on neonatal growth and blood amino acid profiles. METHODS. In a multicenter trial (n = 11 sites), we randomly allocated premature (23–29 weeks and 6 days of gestation) neonates to 1 of 2 approaches to intravenous amino acid administration. In one group, amino acid supplementation was started at 1.0 g/kg per day and advanced by 0.5 g/kg per day to a maximum of 2.5 g/kg per day (2.5 g/kg per day group). The other group received amino acids starting at 1.5 g/kg per day and advancing by 1.0 g/kg per day to a maximum of 3.5 g/kg per day (3.5 g/kg per day group). Filter paper blood spots were obtained from each infant on the day of random assignment and on days 7 and 28 of age, to monitor blood amino acid levels. RESULTS. We enrolled 122 neonates (64 in the 3.5 g/kg per day group and 58 in the 2.5 g/kg per day group). There were no differences in demographic or baseline characteristics between the 2 treatment groups. There was no significant difference in growth by day 28 after birth (median weight gain: 12.9 and 11.4 g/kg per day for the 3.5 and 2.5 g/kg per day groups, respectively), and the incidences of secondary morbidities were similar in the 2 groups. On day 7, blood levels of several amino acids and the serum urea nitrogen level were higher in the 3.5 g/kg per day group, compared with the 2.5 g/kg per day group; none of the amino acid levels were lower. CONCLUSIONS. Higher doses of amino acid supplementation did not improve neonatal growth and were associated with increased blood amino acid and urea nitrogen levels.
Exact Controllability for Fuzzy Differential Equations in Credibility Space

With reasonable control selections on the space of functions, various application models can take the shape of a well-defined control system on mathematics. In the credibility space, controlability management of fuzzy differential equation is as much important issue as stability. This paper addresses exact controllability for abstract fuzzy differential equations in the credibility space in the perspective of Liu process. This is an extension of the controllability results of Park et al. (Controllability for the semilinear fuzzy integro-differential equations with nonlocal conditions) to fuzzy differential equations driven by Liu process.
Development of a modified perturb and observe algorithm based on the characteristic of the V-D curve and the P-V curve

This paper introduces a step size selector to enhance tracking performance of the conventional P&O algorithm. The characteristic of the V-D curve is analyzed extensively in order to develop the selector. The ideal buck-boost converter is applied in the MATLAB/Simulink simulation model. Simulation results suggest that the proposed algorithm responses to the abrupt change in solar irradiance much faster than three reference algorithms and they show that average efficiency of the PV system is increased by 6% approximately. Moreover, the oscillation of output power in steady state is reduced.
Outcome evaluation of a zero-profile implant for anterior cervical diskectomy with fusion.

AIM Supplementing anterior cervical diskectomy and fusion (ACDF) with plates enhances stabilization, increases fusion and reduces failure rates. Zero-P implant for stand-alone anterior interbody fusion procedures of the cervical spine was recently developed to avoid complications associated with anterior cervical plates. We evaluate the outcome of its use in our patients undergoing ACDF. MATERIAL AND METHODS 84 patients were selected to undergo ACDF with Zero-P implant of whom 75 (52 male and 23 female) were followed up for 12 to 16 months (mean 14.2 months) with a total of 94 operated levels (54 single, 21 double level). Patients underwent pre- and postoperative clinical evaluation with full neurological examination, visual analogue scale (VAS), Neck Pain and Disability Scale (NPAD) and Bazaz-Yoo dysphagia index for postoperative dysphagia. Postoperative plain X-ray evaluation of fusion and implant-associated complications was done. REAULTS: All patients had significant reduction in arm and neck pain and NPAD maintained over 12 months, no implant-associated complications during follow-up, and radiological fusion by 3 months. None had dysphagia after 3 months postoperatively. CONCLUSION The Zero-P implant is a valid alternative to anterior cervical plating after ACDF with a very low incidence of postoperative dysphagia and no implant-related complications.
Identification and functional analysis of the novel S179R POU1F1 mutation associated with combined pituitary hormone deficiency.

CONTEXT The pituitary-specific transcription factor 1 plays a key role in the development and differentiation of three pituitary cell types: somatotrophs, lactotrophs, and thyrotrophs. Several mutations of the human gene (called POU1F1) have been shown to be responsible for a phenotype of combined pituitary hormone deficiency involving GH, prolactin (PRL), and TSH. OBJECTIVE We have identified a novel homozygous C to G mutation in exon 4 of the POU1F1 gene (S179R) in a patient with this rare phenotype. We analyzed the functional consequences of this S179R mutation associated with a single-amino acid change in the POU-specific domain. METHODS Consequences of this mutation on transcriptional activities by transfection studies in alphaT3 cells, DNA binding ability by EMSA, structural properties, and nuclear accumulation of POU1F1 were investigated. RESULTS The transactivation capacity of this mutant was markedly decreased on the GH1, PRL, TSHbeta, and POU1F1 genes. Interestingly, this mutation abolished the functional interaction of POU1F1 on the PRL promoter with the coactivator cAMP response element-binding protein-binding protein but not with the transcription factor LIM homeodomain transcription factor 3. The S179R mutant displayed normal nuclear accumulation but a markedly decreased binding to a DNA response element in keeping with crystallographic data, suggesting that the S179R mutation might interfere with DNA binding. CONCLUSIONS Together with previous data, our study indicates that both DNA binding and interaction with cofactors like cAMP response element-binding protein-binding protein are critical for POU1F1 function and that functional and structural properties of abnormal POU1F1 proteins are variously influenced by the type of mutations.
Structure of the double‐stranded RNA‐binding domain of the protein kinase PKR reveals the molecular basis of its dsRNA‐mediated activation

Protein kinase PKR is an interferon‐induced enzyme that plays a key role in the control of viral infections and cellular homeostasis. Compared with other known kinases, PKR is activated by a distinct mechanism that involves double‐stranded RNA (dsRNA) binding in its N‐terminal region in an RNA sequence‐independent fashion. We report here the solution structure of the 20 kDa dsRNA‐binding domain (dsRBD) of human PKR, which provides the first three‐dimensional insight into the mechanism of its dsRNA‐mediated activation. The structure of dsRBD exhibits a dumb‐bell shape comprising two tandem linked dsRNA‐binding motifs (dsRBMs) both with an α‐β‐β‐β‐α fold. The structure, combined with previous mutational and biochemical data, reveals a highly conserved RNA‐binding site on each dsRBM and suggests a novel mode of protein–RNA recognition. The central linker is highly flexible, which may enable the two dsRBMs to wrap around the RNA duplex for cooperative and high‐affinity binding, leading to the overall change of PKR conformation and its activation.
B RINGING P ROFESSIONALS ON B OARD : L ESSONS ON E XECUTING IT-ENABLED O RGANIZATIONAL T RANSFORMATION 1,2

IT-enabled organizational change has not always succeeded. But this paper traces a successful case – the Gemini project – at the University of Illinois Medical Center (UIMC), a leading public healthcare institution in the United States. This effort, which took place from 1996 to 2002, exemplifies the multitude of challenges faced in large-scale IT projects. The main distinguishing factor is that the dominant players were the healthcare professionals.
Need for a framework for the assessment, evaluation and measurement of System Maturity, System Readiness and Capability Readiness

This study has identified the need for a Framework for the assessment, evaluation and measurement of System Maturity, System Readiness and Capability Readiness for Systems and Networked System of Systems. The advantages and disadvantages of existing maturity and readiness assessments are presented; after undertaking a literature review to examine relevant research papers from both academia and industry.
Emergence of Novel Streptococcus iniae Exopolysaccharide-Producing Strains following Vaccination with Nonproducing Strains

ABSTRACT Streptococcus iniae is a major pathogen of fish, producing fatal disease among fish species living in very diverse environments. Recently, reoccurrences of disease outbreaks were recorded in rainbow trout (Oncorhynchus mykiss, Walbaum) farms where the entire fish population was routinely vaccinated. New strains are distinguished from previous strains by their ability to produce large amounts of extracellular polysaccharide that is released into the medium. Present findings indicate that the extracellular polysaccharide is a major antigenic factor, suggesting an evolutionary selection of strains capable of extracellular polysaccharide production.
Incident Chlamydia trachomatis Infections Among Inner-city Adolescent Females

Between January 1994 and September 1996, 3,202 adolescent women aged 12-19 years (mean 16.9) making 5,360 patient visits that were are least 30 days apart were screened for Chlamydia trachomatis at two family planning clinics, two sexually transmitted disease (STD) clinics, or five schoolbased clinics in Baltimore, MD, as part of the Region III Chlamydia project of the Centers for Disease Control (CDC). Ninety-eight percent of the subjects were African-American. Subjects underwent screening for Chlamydia because of symptoms suggestive of an STD, a history of partner exposure, or as part of routine screening during pelvic examination. Specimens for Chlamydia were cervical if a pelvic examination
Femtosecond spectroscopic studies of the ultrafast relaxation process in the charge-transfer state of insulating cuprates.

We have investigated the transient absorption spectra of insulating ${\mathrm{YBa}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{\mathit{y}}$ and ${\mathrm{Nd}}_{2}$${\mathrm{CuO}}_{4}$ thin films by the pump and probe method from 1.3 to 2.8 eV with a time resolution of 100 fs. For both insulating samples, a bleaching signal with a 0.6\char21{}0.9 ps initial decay time was observed in the spectral range of the ${\mathrm{O}}_{2\mathit{p}}$ to ${\mathrm{Cu}}_{3\mathit{d}}$ charge-transfer transition at around 1.8 eV. This initial decay can be explained as a nonradiative transition through the successive emission of magnons having a comparably large energy quantum. In the photon-energy region lower than the bleaching signal, an induced absorption signal is observed. The origin of the induced absorption by pumping pulses has not necessarily been resolved, but the in-gap states induced by the photodoping effect is suggested as a reason.
Comparative virulence of Candida albicans yeast and filamentous forms in orally and intravenously inoculated mice

ObjectiveCandida albicans, a dimorphic fungus that switches from yeast to filamentous forms, is a major cause of complicating systemic infection in intensive care patients. The aim of this study was to compare the pathogenic potential of C. albicans yeast and filamentous forms. DesignSeparate groups of mice were inoculated either intravenously or orally with C. albicans CAF2 (wild type), HLC54 (yeast forms defective in filament formation), or BCa2-10 (constitutively filamentous). Mice were killed 1, 7, 14, and 21 days after intravenous C. albicans and kidneys and liver were quantitatively cultured; cohort groups were observed for mortality. Mice were pretreated with antibiotics for 3 days before oral inoculation with C. albicans, and killed 3 days later with dexamethasone administered for the latter 3 days; at sacrifice, the mesenteric lymph nodes and kidneys were cultured to monitor extraintestinal dissemination of C. albicans. SettingUniversity teaching hospital research laboratory. SubjectsFemale, Swiss Webster, adult mice. Measurements and Main ResultsIn intravenously inoculated mice, mortality was highest with wild-type C. albicans CAF2 (92%), intermediate with HLC54 (56%), and not detected with constitutively filamentous BCa2-10 (0%); BCa2-10 was cleared from the kidney and liver, but CAF2 and HLC54 were recovered at approximately 105–7/g kidney and 104–5/g liver. There was only occasional mortality in orally inoculated mice and the numbers of cecal C. albicans CAF2 and HLC54 were similarly high (approximately 10/g), whereas numbers of cecal BCa2-10 were at least 100-fold lower. Extraintestinal dissemination was greatest with HLC54, intermediate with CAF2, and undetectable with BCa2-10. ConclusionsOf the three C. albicans strains studied, wild-type CAF2 was most virulent in intravenously inoculated mice and HLC54 (defective in filament formation) was most virulent in orally inoculated mice. The constitutively filamentous BCa2-10 was avirulent in both models, suggesting that filamentous forms by themselves might not be critically important for C. albicans virulence.
Reducing barriers to interprofessional training: Promoting interprofessional cultural competence

The need to train health professionals who can work across disciplines is essential for effective, competent, and culturally sensitive health care delivery. By its very nature, the provision of health service requires communication and coordination between practitioners. However, preparation for interdisciplinary practice within the health care setting is rare. The authors argue that the primary reason students are not trained across disciplines is related to the diverse cultural structures that guide and moderate health education environments. It is further argued that this profession specific “cultural frame” must be addressed if there is any hope of having interprofessional education accepted as a valued and fully integrated dimension of our curriculum. Each health discipline possess its own professional culture that shapes the educational experience; determines curriculum content, core values, customs, dress, salience of symbols, the meaning, attribution, and etiology of symptoms; as well as defines what constitutes health, wellness and treatment success. Most importantly, professional culture defines the means for distributing power; determines how training should proceed within the clinical setting; and the level and nature of inter-profession communication, resolution of conflicts and management of relationships between team members and constituents. It might be said that one factor limiting interdisciplinary training is profession-centrism. If we are to achieve effective and fully integrated interdisciplinary education, we must decrease profession-centrism by crafting curriculum that promotes interprofessional cultural competence. The article explores how to promote interprofessional cultural competence within the health education setting.
Supportive friendships moderate the association between stressful life events and sexual risk taking among African American adolescents.

OBJECTIVE This study examined whether uncontrollable stressful life events were associated with sexual risk taking among adolescents across a 1-year period, and whether supportive friendships modified associations. DESIGN Participants were 159 sexually active African American adolescents (57% male; mean age [SD] = 17.0 [1.5] years at baseline). Participants were recruited for in-person interviews through random digit dialing in one inner-city neighborhood characterized by high rates of poverty and crime relative to the surrounding city. MAIN OUTCOME MEASURES Dependent variables included substance use before sexual activity and inconsistent condom use. RESULTS Among adolescents who reported low levels of supportive friendships, uncontrollable stressors were associated with greater levels of sexual risk taking over time. In contrast, uncontrollable stressors were not associated with sexual risk taking among adolescents who reported high social support from friends; risk taking was typically moderate to high among these adolescents. CONCLUSION Different processes may explain sexual risk taking among adolescents with varying levels of social support from friends. Adolescents with low support may be prone to engagement in health risk behavior as a stress response, while adolescents with high support may engage in risk behavior primarily due to peer socialization of risk.
The effects of hand force variation on shoulder muscle activation during submaximal exertions

Upper limb injuries are highly prevalent in the workplace and new tools are needed to proactively design workstations to reduce injury risk. The objective was to characterize spatial, load and direction dependency of muscle activity for hand exertions in the upper limb workspace. Electromyographic signals were collected from 14 upper limb muscles during exertions for all combinations of 4 submaximal hand forces (20/30/50/60 N) in 6 cardinal (up/down/left/right/forward/backward) directions at 5 hand locations. Linear muscle activity increases accompanied increased hand forces. Total muscle activity increases between 20 and 60 N hand forces ranged by direction from 92% (downward) to 189% (right). Prediction equations for all muscles depended on hand force, and linear, quadratic and interaction permutations of hand location. Muscle activity associated with manual tasks is load, direction and spatially dependent. Equations developed to describe these complex relationships can be used to better design future and evaluate current occupational activities.
Inactivation of the MAL Gene in Breast Cancer Is a Common Event That Predicts Benefit from Adjuvant Chemotherapy

Dysregulation of MAL (myelin and lymphocyte protein) has been implicated in several malignancies including esophageal, ovarian, and cervical cancers. The MAL protein functions in apical transport in polarized epithelial cells; therefore, its disruption may lead to loss of organized polarity characteristic of most solid malignancies. Bisulfite sequencing of the MAL promoter CpG island revealed hypermethylation in breast cancer cell lines and 69% of primary tumors analyzed compared with normal breast epithelial cells. Differential methylation between normal and cancer DNA was confined to the proximal promoter region. In a subset of breast cancer cell lines including T47D and MCF7 cells, promoter methylation correlated with transcriptional silencing that was reversible with the methylation inhibitor 5-aza-2′-deoxycytidine. In addition, expression of MAL reduced motility and resulted in a redistribution of lipid raft components in MCF10A cells. MAL protein expression measured by immunohistochemistry revealed no significant correlation with clinicopathologic features. However, in patients who did not receive adjuvant chemotherapy, reduced MAL expression was a significant predictive factor for disease-free survival. These data implicate MAL as a commonly altered gene in breast cancer with implications for response to chemotherapy. (Mol Cancer Res 2009;7(2):199–209)
In vitro free radical scavenging activity of platinum nanoparticles

A polyacrylic acid (PAA)-protected platinum nanoparticle species (PAA-Pt) was prepared by alcohol reduction of hexachloroplatinate. The PAA-Pt nanoparticles were well dispersed and homogeneous in size with an average diameter of 2.0 ± 0.4 nm (n = 200). We used electron spin resonance to quantify the residual peroxyl radical () generated from 2,2-azobis (2-aminopropane) dihydrochloride (AAPH) by thermal decomposition in the presence of O2 and a spectrophotometric method to quantify the residual 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. PAA-Pt scavenged these two radicals in a dose-dependent manner. Platinum was the functional component. PAA-Pt reduced the rate of oxygen consumption required for linoleic acid peroxidation initiated by generated from AAPH, indicating inhibition of the propagation of linolate peroxidation. A thiobarbituric acid test also revealed dose-dependent inhibition of the linolate peroxidation by PAA-Pt. Fifty micromolar platinum, as PAA-Pt, completely quenched 250 µM DPPH radical for 5 min. Even when twice diluted in half, the PAA-Pt still quenched 100% of the 250 µM DPPH radical. The scavenging activity of PAA-Pt is durable. These observations suggest that PAA-Pt is an efficient scavenger of free radicals.
Dendritic cell immunotherapy in uterine cancer

Uterine cancer is the most common pelvic gynecological malignancy. Uterine sarcomas and relapsed uterine carcinomas have limited treatment options. The search for new therapies is urgent. Dendritic cell (DC) immunotherapy holds much promise, though has been poorly explored in uterine cancer. This commentary gives an insight in existing DC immunotherapy studies in uterine cancer and summarizes the possibilities and the importance of the loading of tumor antigens onto DC and their subsequent maturation. However, the sole application of DC immunotherapy to target uterine cancer will be insufficient because of tumor-induced immunosuppression, which will hamper the establishment of an effective anti-tumor immune response. The authors give an overview on the limited existing immunosuppressive data and propose a novel approach on DC immunotherapy in uterine cancer.