Miracle-dz/UniFAR-FTUs huggingface dataset:
Developmental expression of SLC26A4 (Pendrin) during amelogenesis in developing rodent teeth

Ameloblasts need to regulate pH during formation of enamel crystals, a process that generates protons. Solute carrier family 26A member 4 (SLC26A4, or pendrin) is an anion exchanger for chloride, bicarbonate, iodine and formate. It is expressed in apical membranes of ion-transporting epithelia in kidney, inner ear and thyroid where it regulates luminal pH and fluid transport. We hypothesized that maturation ameloblasts express SLC26A4 to neutralize acidification of enamel fluid in forming enamel. In rodents, secretory and maturation ameloblasts were immunopositive for SLC26A4. Staining was particularly strong in apical membranes of maturation ameloblasts facing forming enamel. RT-PCR confirmed the presence of mRNA transcripts for Slc26a4 in enamel organs. SLC26A4 immunostaining was also found in mineralizing connective tissues including odontoblasts, osteoblasts, osteocytes, osteoclasts, bone lining cells, cellular cementoblasts and cementocytes. However, Slc26a4-null mutant mice had no overt dental phenotype. The presence of SLC26A4 in apical plasma membranes of maturation ameloblasts is consistent with a potential function as pH regulator. SLC26A4 does not appear critical for ameloblast functioning and is likely compensated by other pH regulators.
TEACHERS’ TOPICS An Anticoagulation Therapy Elective for Third-Year Pharmacy Students

Objective. To develop an anticoagulation elective course for third-year pharmacy students to enhance their knowledge and skills for providing anticoagulation services. Design. Content developed for the course focused on standards of care, evaluation of primary literature, clinical application, billing and regulatory issues, written and verbal communication, and patient education. Teaching methods included lectures, discussions, demonstrations, and self-directed learning. Assessment. Assessment methods included multiple-choice examinations, evaluation of patient cases, student presentations, and a practical examination. Students demonstrated competencies in multiple areas and rated the course favorably. Students who completed the elective reported being more prepared for anticoagulation activities than those who did not. Confidence levels regarding participation in anticoagulation services postgraduation were similar. Conclusion. The elective provided valuable experience in anticoagulation therapy and increased students’ perception of their preparedness related to dealing with anticoagulation issues while on advanced pharmacy practice experiences (APPEs). More exposure to management topics and the logistics of initiating anticoagulation services should be incorporated.
Mapping of the functional determinants of the integrin *, cytoplasmic domain by site-directed mutagenesis

We describe here the expression of deletion mutants of the cytoplasmic domain of the avian integrin , subunit. These mutants, which contain termination codons at positions 767, 776, 791, and 800, were transfected into mouse 3T3 cells to determine which sequences were essential for localization of integrins into focal contact sites. In all cases, high-level expression of the truncated avian integrins was obtained. Heterodimers were formed between the exogenous truncated avian f,B subunits and endogenous mouse a subunits, and these heterodimers were efficiently exported to the cell surface. The longest flI subunit tested, which is only four amino acids shorter than the wild type, to focal contacts. In ,81 subunits long truncations domain contacts, including which the consensus for tyrosine phosphorylation. a mutant subunit which the of the the segment nearest the including dibasic (RR) focal the peptide segment nearest to the transmembrane region in focal contact In mutant subunits that this segment a of the localize as the shorter form, that of abnormal folding. and analyzed by SDS-PAGE. Thus, the mutant integrins efficiently form het- erodimers with endogenous mouse a subunits and are expressed on the cell surface.
Effect of Acyclovir on HIV-1 Set Point among HSV-2 Seropositive Persons during Early HIV-1 Infection

We evaluated whether acyclovir suppression during human immunodeficiency virus type 1 (HIV-1) acquisition reduces HIV-1 set point, increases CD4 cell counts, and selects reverse-transcriptase mutations among 76 HIV-1 seroconverters identified in a placebo-controlled trial of twice-daily acyclovir (400 mg) for the prevention of HIV acquisition in herpes simplex virus type 2 (HSV-2)– seropositive persons (HIV Prevention Trials Network study 039). We found no significant difference in plasma HIV-1 RNA levels ( P <.30)or CD4 cell counts ( P <.85) between the acyclovir and placebo recipients. V75I and other mutations in HIV-1 reverse transcriptase reported from in vitro acyclovir studies were not observed. In conclusion, acyclovir suppression during HIV-1 seroconversion and the subsequent 6 months does not affect HIV-1 set point.
Modelling and simulation of the drivetrain of an omnidirectional mobile robot

ABSTRACT The main contribution of this paper is to present the state-space model of an omnidirectional drivetrain (Kiwi drive) for mobile robots. Holonomy or omnidirectional movement of mobile robots is important in applications where navigation through tight space is required. Besides the already available literature regarding either dynamic or kinematic models, this paper presents the complex analysis of a mechatronic system and shows a coherent model that takes into account both the kinematics and the dynamics of a coupled electromechanical system. The model was developed based on two holonomic mobile robots: the Festo Robotino® and the MOGI Ethon. A simulation software developed by the authors is also presented for numerical evaluation of the model. The simulation results qualitatively confirm the model by fulfilling the empirical requirements. Both the model and the simulation software are expandable in order to improve the accuracy of the model describing actual mobile robots. Compared to other models which are based only on the kinematics of the Kiwi drivetrain, in accordance to one's technical instinct, the presented model shows that there is a cross effect between the motors of the drivetrain, where the motors affect each other.
Comparison of Monovalent Glycoprotein B with Bivalent gB/ pp65 (GP83) Vaccine for Congenital Cytomegalovirus Infection in a Guinea Pig Model: Inclusion of GP83 Reduces Antibody Response but Provides Equivalent Protection Against Mortality

Cytomegalovirus (CMV) subunit vaccine candidates include glycoprotein B (gB), and phosphoprotein ppUL83 (pp65). Using a guinea pig cytomegalovirus (GPCMV) model, this study compared immunogenicity, pregnancy outcome, and congenital viral infection following pre-pregnancy immunization with a three-dose series of modified vaccinia virus Ankara (MVA)-vectored vaccines consisting either of gB administered alone, or simultaneously with a pp65 homolog (GP83)-expressing vaccine. Vaccinated and control dams were challenged at midgestation with salivary gland-adapted GPCMV. Comparisons included ELISA and neutralizing antibody responses, maternal viral load, pup mortality, and congenital infection rates. Strikingly, ELISA and neutralization titers were significantly lower in the gB/GP83 combined vaccine group than in the gB group. However, both vaccines protected against pup mortality (60.5% in controls vs. 11.4% and 8.3% in gB and gB/GP83 combination groups, respectively; p<0.0001). Reductions in pup viral load were noted for both groups compared to control, but preconception vaccine resulted in a significant reduction in GPCMV transmission in the monovalent gB group only (26/44, 59 % v. 27/34, 79 % in controls; p<0.05). We conclude that, in the MVA platform, adding GP83 to a gB subunit vaccine interferes with antibody responses and diminishes protection against congenital GPCMV infection, but does not decrease protection against pup mortality.
III Secondary hypertension D. Obstructive Sleep Apnea

Sleep disordered breathing includes obstructive and central sleep apnea (CSA), obesity hypoventilatory syndrome, snoring and Cheyne-Stokes breathing. Obstructive sleep apnea (OSA) is usually diagnosed via polysomnography (PSG) and quantified by the number of episodes of cessation (apnea) or reduction (hypopneas) of airflow, lasting ≥ 10 seconds per hour of sleep [1]. An apnea-hypopnea index (AHI) of ≥ 5 per hour is considered significant for OSA. A diagnosis of OSA syndrome (OSAS) is made when patients have OSA and symptoms. CSA has similar clinical features, but is due to reduced central drive vs OSA which is usually due to anatomical obstruction. PSG testing distinguishes between CSA and OSA.
Combination of Controllably Released Platelet Rich Plasma Alginate Beads and Bone Morphogenic Protein-2 Gene-Modified Mesenchymal Stem Cells for Bone Regeneration

, Abstract Background— Platelet rich plasma (PRP) consists of platelet derived growth factor (PDGF) and Transforming growth factor-beta (TGF- β ) that increase cell proliferation of mesenchymal stem cells (MSCs), whereas, bone morphogenic Protein-2 (BMP2) promotes osteogenic differentiation of MSCs. However, the high degradation rate of fibrin leads to the dissociation of cytokines even before the process of bone regeneration has begun. Hence, for the first time, we studied the combined effect of sustained released PRP from alginate beads on BMP2 modified MSCs osteogenic differentiation in vitro and of sustained PRP alone on a fracture defect model ex vivo as well as its effect on the calvarial suture closure. Methods— After optimizing the concentration of alginate for the microspheres, the osteogenic and mineralization effect of PRP and BMP2 in combinations on MSCs was studied. A self-setting alginate hydrogel carrying PRP was tested on a femur defect model ex-vivo. The effect of PRP was studied on the closure of the embryonic (E15) mouse calvaria sutures ex vivo. Results— Increase of PRP concentration promoted cellular proliferation of MSCs. 2.5%–10% of PRP displayed gradually increased ALP activity on the cells in a dose dependent manner. Sustained release PRP and BMP2 demonstrated a significantly higher ALP and mineralization activity (p<0.05). The radiographs of alginate hydrogel with PRP treated bone demonstrated a nearly complete healing of the fracture and the histological sections of the embryonic calvaria revealed that PRP leads to suture fusion. Conclusions— Sustained release of PRP along with BMP2 gene modified MSCs can significantly promote bone regeneration.
Wind turbine generator and method of controlling the same

In the wind power generator (1), and an object thereof is to reduce the down time of the wind turbine generator (1) due to icing of the wind turbine blade (10). By having an icing detector 7 for detecting ice accumulation amount of the wind turbine blade 10, when the amount of the detected icing by icing detector 7 exceeds a first predetermined value, no-load operation mode, which does not perform the power generation switching to the operation mode, and provides a wind power generator (1) for detecting ice accumulation amount by a state in which the operation in the no-load operation mode to the icing detection unit (7).
Statin Users Without an APOE- ε 4 Allele have Increased Insulin Resistance

The present study examined the relationships among statin use, APOE genotype, and insulin resistance as measured by the homeostasis model assessment of insulin resistance (HOMA-IR) in healthy older adults. APOE ε 4- (i.e., not having an ε 4 allele) statin users had higher HOMA-IR values compared with ε 4+/statin users ( p = 0.0169), and with non-users who were ε 4- ( p = 0. 0003) or ε 4+ ( p = 0.0006). These results suggest that statin use may modulate insulin levels for individuals without an APOE ε 4 allele.
The effects of prepubertal gonadectomy and binge-like ethanol exposure during adolescence on ethanol drinking in adult male and female rats

The pubertal surge in gonadal hormones that occurs during adolescence may impact the long-term effects of early alcohol exposure and sex differences in drinking behavior in adulthood. We investigated this hypothesis by performing sham or gonadectomy surgeries in Long Evans rats around postnatal day (P) 20. From P35–45, males and females were given saline or 3.0 g/kg ethanol using a binge-like model of exposure (8 injections total). As adults (P100), they were trained to self-administer ethanol via a sucrose-fading procedure and then given access to different unsweetened concentrations (5–20% w/v) for 5 days/concentration. We found that during adolescence, ethanol-induced intoxication was similar in males and females that underwent sham surgery. In gonadectomized males and females, however, the level of intoxication was greater following the last injection compared to the first. During adulthood, females drank more sucrose per body weight than males and binge-like exposure to ethanol reduced sucrose consumption in both sexes. These effects were not seen in gonadectomized rats. Ethanol consumption was higher in saline-exposed females compared to males, with gonadectomy reversing this sex difference by increasing consumption in males and decreasing it in females. Exposure to ethanol during adolescence augmented ethanol consumption in both sexes, but this effect was statistically significant only in gonadectomized females. Together, these results support a role for gonadal hormones during puberty in the short- and long-term effects of ethanol on behavior and in the development of sex differences in consummatory behavior during adulthood.
Molybdenum cofactor-dependent resistance to N -hydroxylated base analogs in E. coli is independent of MobA function

Lack of molybdenum cofactor (MoCo) in Escherichia coli and related microorganisms was found to cause hypersensitivity to certain N -hydroxylated base analogs, such as HAP (6- N -hydroxylaminopurine). This observation has lead to a previous proposal that E. coli contains a molybdoenzyme capable of detoxifying such N -hydroxylated analogs. Here, we show that, unexpectedly, deletion of all known or putative molybdoenzymes in E. coli failed to reveal any base-analog sensitivity, suggesting that a novel type of MoCo-dependent activity is involved. Further, we establish that protection against the analogs does not require the common molybdopterin guanine-dinucleotide (MGD) form of the cofactor, but instead the guanosine monophosphate (GMP)-free version of MoCo (MPT) is sufficient.
A Map of Human Mitochondrial Protein Interactions Linked to Neurodegeneration Reveals Molecular Determinants of Redox Homeostasis and NF- κ B Signaling

SUMMARY Mitochondrial protein (MP) dysfunction has been linked to neurodegenerative disorders (NDs), however, the discovery of the molecular mechanisms underlying NDs has been impeded by the limited characterization of interactions governing MP function. Here, using mass spectrometry (MS) based analysis of 210 affinity-purified mitochondrial (mt) fractions isolated from 27 epitope-tagged human ND-linked MPs in HEK293 cells, we report a high-confidence MP network including 1,964 interactions among 772 proteins (>90% previously unreported). Nearly three-fourths of these interactions were confirmed in mouse brain and multiple human differentiated neuronal cell lines by primary antibody immunoprecipitation and MS, with many linked to NDs and autism. We show that the SOD1-PRDX5 interaction, critical for mt redox homeostasis, can be perturbed by amyotrophic lateral sclerosis-linked SOD1 allelic variants, and establish a functional role for ND-linked factors coupled with I κ B ε in NF-kB activation. Our results identify mechanisms for ND-linked MPs, and expand the human mt interaction landscape.
An examination of SNP selection prioritisation strategies for tests of gene-gene interaction

Background— Given that genome wide association studies (GWAS) of psychiatric disorders have identified only a small number of convincingly associated variants, there is interest in seeking additional evidence for associated variants using tests of gene-gene interaction. Comprehensive pair-wise SNP-SNP interaction analysis is computationally intensive and the penalty for multiple testing is severe given the number of interactions possible. Aiming to minimize these statistical and computational burdens, we have explored approaches to prioritise SNPs for interaction analyses. Methods— Primary interaction analyses were performed using the Wellcome Trust Case Control Consortium Bipolar Disorder GWAS (1868 cases, 2938 controls). Replication analyses were performed using the Genetic Association Information Network BD dataset (1001 cases, 1033 controls). SNPs were prioritized for interaction analysis that showed evidence for association that surpassed a number of nominally significant thresholds, are within genome-wide significant genes, or are within genes that are functionally related. Results— For no set of prioritized SNPs did we obtain evidence to support the hypothesis that the selection strategy identified pairs of variants that were enriched for true (statistical) interactions. Conclusions— SNPs prioritized according to a number of criteria do not have a raised prior probability for significant interaction that is detectable in samples of this size. As is now widely accepted for single SNP analysis, we argue the use of significance levels reflecting only the number of tests performed does not offer an appropriate degree of protection against the potential for GWAS studies to generate an enormous number of false positive interactions.
Type I IFN response and innate immune sensing of cancer

Unexpectedly, many cancers appear to induce a spontaneous adaptive T cell response. The presence of a T cell infiltrate has been linked to favorable clinical outcome in multiple cancer types. However, the innate immune pathways that bridge to an adaptive immune response under sterile conditions are poorly understood. Recent data have indicated that tumors can induce type I IFN production by host antigen-presenting cells which is required for a spontaneous T cell response in vivo. The innate immune sensing pathways that trigger type I IFN production are being elucidated. Host type I IFNs are also required for optimal therapeutic efficacy with radiation. This recently uncovered role for host type I IFNs for anti-tumor immunity has important fundamental and clinical implications.
Validation of Electronic Health Record Phenotyping of Bipolar Disorder and Controls

Objective— To validate the use of electronic health records (EHRs) for the diagnosis of bipolar disorder (BD) and controls. Methods— EHR data were obtained from a healthcare system of more than 4.2 million patients spanning more than 20 years. Chart review by experienced clinicians was used to identify text features and coded data consistent or inconsistent with a diagnosis of BD. Natural language processing (NLP) was used to train a diagnostic algorithm with 95% specificity for classifying BD. Filtered coded data were used to derive three additional classification rules for cases and one for controls. The positive predictive value (PPV) of EHR-based BD and subphenotype diagnoses was calculated against direct semi-structured interview diagnoses by trained clinicians blind to EHR diagnosis in a sample of 190 patients. Results— The PPV of NLP-defined BD was 0.85. A coded classification based on strict filtering achieved a PPV of 0.79, but BD classifications based on less stringent criteria performed less well. None of the EHR-classified controls was given a diagnosis of BD on direct interview (PPV = 1.0). For most subphenotypes, PPVs exceeded 0.80. The EHR-based classifications were used to accrue 4500 BD cases and 5000 controls for genetic analyses. Conclusions— Semi-automated mining of EHRs can be used to ascertain BD cases and controls with high specificity and predictive value compared to a gold-standard diagnostic interview. EHRs provide a powerful resource for high-throughput phenotyping for genetic and clinical research.
Antibiotic Resistance in NICU Pathogens: Mechanisms, Clinical Impact, and Prevention including Antibiotic Stewardship

Antibiotic resistance is a public health crisis. The Institute of Medicine has listed control and reduction of infections caused by antibiotic resistant pathogens in acute care settings as one of the most important issues facing the medical community. [1] The prevalence of antimicrobial resistant pathogens is higher in other intensive care unit (ICU) populations than in the neonatal ICU, but the experience in other populations is useful and can serve to warn NICU providers of the potential future threat. Thus, it is critical to understand the implications of the epidemiology of resistance to craft strategies to reduce antimicrobial resistance (AMR) in the NICU population.
Software Safety - A journey across domains and safety standards

: The position of software regarding the global system safety is subject to significant variations among the various application domains and their safety standards. As a consequence, the position regarding whether, how and to which extent software safety analyses could or should contribute to the global safety assessment also varies. In Civil Aviation [ARP 4754A; ARP 4761; DO 178C], Nuclear [IEC 61513, IEC 60880] and to some extent Space [ECSS Q40; ECSS Q80], safety analyses are performed at system level and on functions, sub-systems and equipment, but not under the form of dedicated safety analyses applied to software. In these domains, the rationale is that software contributes to system safety through adherence to software development and validation rules i.e. through an argument on confidence in software correctness to an extent adapted to the consequences of failures. However it is worth noting that the assessment of the consequences of failures, and hence the determination of the Development Assurance Level, or Software Criticality Category, etc., result from safety analyses performed at system and not at software level. Conversely in domains such as railway [EN 50129] or automotive [ISO 26262], whereas the overall safety rationale is very similar, it is still required to perform in addition dedicated safety analyses applied to software. In the Base Safety Standard
A Learning Framework for Project Management

The contribution of this paper is a framework for understanding and practicing learning in a project environment. The framework includes the goals, processes, and tools for learning. The project management and learning processes are described using the plan-do-study-act (PDSA) cycle from quality management. The PDSA cycle is used to define the learning process that occurs within and between projects. Data from a survey of practicing project managers supports the learning framework by providing an assessment of project management practices. Four implications are provided for project managers to use in focusing the learning activities of a project team.