Miracle-dz/UniFAR-FTUs huggingface dataset:
Induction of Cytotoxic Granules in Human Memory CD8+ T Cell Subsets Requires Cell Cycle Progression1

Memory CD8+ T cell responses are thought to be more effective as a result of both a higher frequency of Ag-specific clones and more rapid execution of effector functions such as granule-mediated lysis. Murine models have indicated that memory CD8+ T cells exhibit constitutive expression of perforin and can lyse targets directly ex vivo. However, the regulated expression of cytotoxic granules in human memory CD8+ T cell subsets has been underexplored. Using intracellular flow cytometry, we observed that only a minor fraction of CD45RA−CD8+ T cells, or of CD8+ T cells reactive to EBV-HLA2 tetramer, expressed intracellular granzyme B (GrB). Induction of GrB-containing cytotoxic granules in both CD45RA+ and CD45RA− cells was achieved by stimulation with anti-CD3/anti-CD28 mAb-coated beads, required at least 3 days, occurred after several rounds of cell division, and required cell cycle progression. The strongest GrB induction was seen in the CCR7+ subpopulations, with poorest proliferation being observed in the CD45RA−CCR7− effector-memory pool. Our results indicate that, as with naive T cells, induction of cytotoxic granules in human Ag-experienced CD8+ T cells requires time and cell division, arguing that the main numerical advantage of a memory T cell pool is a larger frequency of CTL precursors. The fact that granule induction can be achieved through TCR and CD28 ligation has implications for restoring lytic effector function in the context of antitumor immunity.
Exploring the relationship between IT governance practices and business/IT alignment through extreme case analysis in Belgian mid-to-large size financial enterprises

Purpose – Many thought leaders are promoting information technology (IT) governance and its supporting practices as an approach to improve business/IT alignment. This paper aims to further explore this assumed positive relationship between IT governance practices and business/IT alignment.Design/methodology/approach – This paper explores the relationship between the use of IT governance practices and business/IT alignment, by creating a business/IT alignment maturity benchmark and qualitatively comparing the use of IT governance practices in the extreme cases.Findings – The main conclusion of the research is that all extreme case organisations are leveraging a broad set of IT governance practices, and that IT governance practices need to obtain at least a maturity level 2 (on a scale of 5) to positively influence business/IT alignment. Also, a list of 11 key enabling IT governance practices is identified.Research limitations/implications – This research adheres to the process theory, implying a limited de.
The epidemiologic relationship between tuberculosis and non-tuberculous mycobacterial disease: a systematic review.

SETTING Tuberculosis (TB) rates are decreasing in many areas, while non-tuberculous mycobacteria (NTM) infection rates are increasing. The relationship between the epidemiology of TB and NTM infections is not well understood. OBJECTIVE To understand the epidemiologic relationship between TB and NTM disease worldwide. DESIGN A systematic review of Medline (1946-2014) was conducted to identify studies that reported temporal trends in NTM disease incidence. TB rates for each geographic area included were then retrieved. Linear regression models were fitted to calculate slopes describing changes over time. RESULTS There were 22 studies reporting trends in rates of NTM disease, representing 16 geographic areas over four continents: 75% of areas had climbing incidence rates, while 12.5% had stable rates and 12.5% had declining rates. Most studies (81%) showed declining TB incidence rates. The proportion of incident mycobacterial disease caused by NTM was shown to be rising in almost every geographic area (94%). CONCLUSION We found an increase in the proportion of mycobacterial disease caused by NTM in many parts of the world due to a simultaneous reduction in TB and increase in NTM disease. Research into the interaction between mycobacterial infections may help explain this inverse relationship.
Language mode vs. L2 interference: Evidence from L1 Polish

Only a small amount of research has been devoted to the phonetics of code-switching in the speech of bilinguals. The studies that do exist have shown conflicting results with regard to the appearance and direction of cross-language interaction, and are limited in the types of participants and phonetic parameters that have been investigated. This paper presents both monolingual data and insertional code-switches from L1 Polish speakers that are highly proficient in English. The phonetic parameter of interest is glottalization vs. sandhi-linking of vowel-initial words. Linking is common in English, but rare in Polish, where glottalization is more prevalent. Results show that suggest that English style sandhi-linking does not interfere with boundary realization in the L1 in both monolingual and bilingual modes. Implications are discussed for models of L2 speech and the phonological status of the boundary effects under study.
Factors that impact on the safety of patient handovers: An interview study

Aims: Improvement of clinical handover is fundamental to meet the challenges of patient safety. The primary aim of this interview study is to explore healthcare professionals’ attitudes and experiences with critical episodes in patient handover in order to elucidate factors that impact on handover from ambulance to hospitals and within and between hospitals. The secondary aim is to identify possible solutions to optimise handovers, defined as “situations where the professional responsibility for some or all aspects of a patient’s diagnosis, treatment or care is transferred to another person on a temporary or permanent basis”. Methods: We conducted 47 semi-structured single-person interviews in a large university hospital in the Capital Region in Denmark in 2008 and 2009 to obtain a comprehensive picture of clinicians’ perceptions of self-experienced critical episodes in handovers. We included different types of handover processes that take place within several specialties. A total of 23 nurses, three nurse assistants, 13 physicians, five paramedics, two orderlies, and one radiographer from different departments and units were interviewed. Results: We found eight central factors to have an impact on patient safety in handover situations: communication, information, organisation, infrastructure, professionalism, responsibility, team awareness, and culture. Conclusions: The eight factors identified indicate that handovers are complex situations. The organisation did not see patient handover as a critical safety point of hospitalisation, revealing that the safety culture in regard to handover was immature. Work was done in silos and many of the handover barriers were seen to be related to the fact that only few had a full picture of a patient’s complete pathway.
Actin Network Architecture Can Determine Myosin Motor Activity

Actin Up Actomyosin interactions lie at the heart of fundamental cellular processes—including morphogenesis, establishment of polarity, and overall motility—but the general principles driving the spatiotempotal orchestration of these interactions have remained elusive. Working in vitro, using micropatterned substrates, Reymann et al. (p. 1310) demonstrate that myosins can use a “selection orientation” mechanism to pull selectively on actin filaments, contract the actin network and disassemble it, or walk on the filaments, align them, allow their growth, and control filament orientation. Myosin crumples up antiparallel actin fibers and leaves parallel bundles intact. The organization of actin filaments into higher-ordered structures governs eukaryotic cell shape and movement. Global actin network size and architecture are maintained in a dynamic steady state through regulated assembly and disassembly. Here, we used experimentally defined actin structures in vitro to investigate how the activity of myosin motors depends on network architecture. Direct visualization of filaments revealed myosin-induced actin network deformation. During this reorganization, myosins selectively contracted and disassembled antiparallel actin structures, while parallel actin bundles remained unaffected. The local distribution of nucleation sites and the resulting orientation of actin filaments appeared to regulate the scalability of the contraction process. This “orientation selection” mechanism for selective contraction and disassembly suggests how the dynamics of the cellular actin cytoskeleton can be spatially controlled by actomyosin contractility.
Turn-Taking with Improvisational Co-Creative Agents

Turn-taking is the ability for agents to lead or follow in social interactions. Turn-taking between humans and intelligent agents has been studied in human-robot interaction but has not been applied to improvisational, dance-based interactions. User understanding and experience of turn-taking in an improvisational, dance-based system known as LuminAI was investigated in a preliminary study of 11 participants. The results showed a trend towards users understanding the difference between turn-taking and non-turn-taking versions of LuminAI but reduced user experience in the turn-taking version.
Sequence of the amino-terminal part of enterotoxin from Clostridium perfringens type A: identification of points of trypsin activation

The sequence of the first 66 amino acids of the amino-terminal part of the enterotoxin from Clostridium perfringens type A is presented. The trypsin activation of the enterotoxin involves hydrolysis of Lys15-Glu16 and Lys25-Thr26 bonds. The N-terminal sequence of the trypsin-activated enterotoxin has limited homology with the sequence of the N-terminal region of the cholera toxin B subunit.
Bone marrow‐derived mesenchymal cells can rescue osteogenic capacity of devitalized autologous bone

In clinical cases, many orthopaedists have been troubled with bone fragility, such as fractures after devitalization therapy for bone tumour, pathological fractures and metastatic tumours. The aim of this study was to determine whether loss of osteogenic capacity of devitalized autologous bones can be rescued using cultured bone marrow‐derived mesenchymal cells. A devitalized bone model was produced from rat femur by irradiation and three groups were prepared: intact bone, irradiated bone and irradiated bone combined with cultured mesenchymal cells. Each bone was transplanted subcutaneously into a syngeneic rat. At 2 or 4 weeks after transplantation, biochemical analyses [alkaline phosphatase (ALP) activity and osteocalcin mRNA expression] and histological measurement were performed. Moreover, we verified the origin of newly formed bone, using the sex‐determining region Y (sry) gene as a marker to distinguish between donor and recipient. In both intact bone and irradiated bone with mesenchymal cells, ALP activity and osteocalcin mRNA expression were detected and living osteoblasts together with newly formed bone were clearly seen histologically. Furthermore, analysis of the origin of de novo formed bone indicated that newly formed bone in irradiated bone with mesenchymal cells was derived from cultured bone marrow‐derived mesenchymal cells. These results proved that the osteogenic capacity of devitalized autologous bone can be rescued using tissue‐engineering techniques. This procedure should contribute to various clinical treatments, such as local metastatic tumours, pathological fracture after devitalization therapy and reconstruction after wide‐margin tumour resection. The benefits would be applicable to all types of devitalized bone. Copyright © 2008 John Wiley & Sons, Ltd.
Polymorphisms in the Transcription Factor 7-Like 2 (TCF7L2) Gene Are Associated With Type 2 Diabetes in the Amish

Transcription factor 7-like 2 (TCF7L2) regulates genes involved in cell proliferation and differentiation. The TCF7L2 gene is located on chromosome 10q25 in a region of replicated linkage to type 2 diabetes. Recently, a microsatellite marker in intron 3 (DG10S478) and five correlated single nucleotide polymorphisms (SNPs) were identified in Icelandic individuals that showed strong association with type 2 diabetes, which was replicated in Danish and European-American cohorts. We genotyped four of the SNPs (rs7901695, rs7903146, rs11196205, and rs12255372) in Amish subjects with type 2 diabetes (n = 137), impaired glucose tolerance (IGT; n = 139), and normal glucose tolerance (NGT; n = 342). We compared genotype frequencies in subjects with type 2 diabetes with those with NGT and found marginal association for rs7901695 (P = 0.05; odds ratio [OR] 1.51); comparison between NGT control subjects and the combined type 2 diabetes/IGT case group showed strong association with rs7901695 and rs7903146 (P = 0.008–0.01; OR 1.53–1.57) and marginal association with rs11196205 and rs12255372 (P = 0.07 and P = 0.04, respectively). In an expanded set of 698 Amish subjects without diabetes, we found no association with insulin and glucose levels during a 3-h oral glucose tolerance test. We also genotyped these SNPs in nondiabetic, non-Amish subjects (n = 48), in whom intravenous glucose tolerance tests were performed, and found an association between rs7901695 and rs7903146 and insulin sensitivity (P = 0.003 and P = 0.005, respectively) and disposition index (P = 0.04 and P = 0.007, respectively). These data provide replicating evidence that variants in TCF7L2 increase the risk for type 2 diabetes and novel evidence that the variants likely influence both insulin secretion and insulin sensitivity.
Seventeen-point dermal ultrasound scoring system--a reliable measure of skin thickness in patients with systemic sclerosis.

OBJECTIVE Our objective was to develop a 17-site ultrasound method of measuring skin thickness in patients with systemic sclerosis (SSc) and to assess its inter- and intra-observer variability. METHODS Dermal thickness (using a 22 MHz ultrasound probe) was measured at 17 sites (corresponding to those assessed in the modified Rodnan skin score) in 39 patients with SSc (26 limited cutaneous, 13 diffuse) and 34 healthy controls. The sum of the thicknesses (at the 17 sites) and the maximal thickness were also documented. Because skin thickness varies between sites, each measurement was converted to a z-score. Inter- and intra-observer variability were assessed in 35 patients/33 controls, and 20 patients/15 controls respectively. RESULTS Measurement precision was good for the dermal measurements-intraclass correlation coefficients at the 17 sites ranged from 0.65 to 0.94 for the inter-observer variability (0.86 for maximum thickness) and from 0.55 to 0.96 for the intra-observer variability (0.92 for maximum thickness). CONCLUSION Our results suggest that the 17-point dermal ultrasound scoring system is extremely reliable and may therefore be a useful measure of outcome, including in clinical trials.
Practice as the Site of Knowing: Insights from the Field of Telemedicine

This paper aims to shift the unit of analysis in the study of organisational knowledge from individuals and their actions to practices and their relationships. It introduces the concept of “site” to help advance an understanding of the relationship between practice and knowing. The notion of site supports the intuition that knowing is both sustained in practice and manifests itself through practice. It also evokes the idea of knowledge as being rooted in an extended pattern of interconnected activities that only when taken in its living and pulsating entirety constitutes the site of knowing. In this paper, I review the different ways to conceptualise the relationships between knowing and practice, and I show how the idea of site adds to the existing body of work. Building on the results of a longitudinal study in the field of telemedicine, I then offer suggestions on aspects of practice where knowing manifests itself, and I use the concepts of “translation by contact” and “at distance” to explain how dispersed knowings are woven together and the power effect that can derive from these. I conclude by reflecting on the implications of this radical view and the direction for future research.
Oxidative DNA Base Damage, Antioxidant Enzyme Activities and Selenium Status in Highly Iodine-deficient Goitrous Children

The objective of this study was to investigate oxidative DNA damage, and the levels of antioxidant enzymes (AOE) and selenium (Se) in relation to iodine deficiency and/or goiter in children. The study was performed in a group of goitrous high school children (15-18 years of age) ( n =14) with severe or moderate iodine deficiency. Thyroid hormones (TSH, FT 4 , TT 4 , FT 3 , TT 3 ), urinary iodine (UI) and plasma Se levels, and erythrocyte glutathione peroxidase (GSHPx), superoxide dismutase (SOD) and catalase (CAT) activities were determined and compared with those of a control group consisting of non-goitrous high school children ( n =14) with normal UI levels or mild iodine deficiency. In the goitrous group, concentrations of FT 4 , TT 4 , plasma Se and UI, and activities of GSHPx and SOD were found to be significantly lower. Six typical hydroxyl radical-induced base lesions in genomic DNA of peripheral blood were identified and quantified by gas chromatography/isotope-dilution mass spectrometry (GC/IDMS), and higher levels of DNA base lesions were observed in the goitrous group. The results suggest that highly iodine-deficient goitrous children may be under oxidative stress, which may lead to greater level of oxidative damage to DNA. This study supports the evidence for the reported relationship between iodine deficiency and the increased incidence of thyroid malignancies.
Effects of pneumoperitoneum on hemodynamic and systemic immunologic responses to peritonitis in pigs.

BACKGROUND Experimental evidence supporting the safety of laparoscopic intervention during sepsis is limited. The purpose of this study was to evaluate the effects of pneumoperitoneum on immunologic and hemodynamic responses to peritoneal sepsis. MATERIALS AND METHODS A porcine model of peritonitis was created using an intraperitoneal autologous fecal inoculum. Pigs were then subjected to one of four procedures 24 h postinoculation (n = 6 per group): laparotomy, CO(2) laparoscopy, helium laparoscopy, and anesthesia only (1.5% isoflurane in 100% O(2), mechanical ventilation). Venous blood samples were obtained prior to inoculation, and at 24 (prior to procedure), 30, 48, 72, and 96 h postinoculation to determine white blood count (WBC) with differential, C-reactive protein (CRP), tumor necrosis factor, and bacteremia. Heart rate, end-tidal CO(2) (ETCO(2)), mean arterial blood pressure (MAP), and arterial blood gas variables were also measured at baseline and every 30 min throughout the procedure. RESULTS Postoperative blood cultures confirmed systemic bacteremia in all groups at all time periods postinoculation. Following inoculation, WBC, band cell count, and CRP remained elevated above baseline in all groups throughout the study (P < 0.01). However, no significant differences in these parameters were observed among groups. In the CO(2) laparoscopy group, MAP, ETCO(2), and arterial pCO(2) were increased above baseline, while pH was decreased throughout the procedure (P < 0.01). CONCLUSIONS In this animal model of peritonitis, CO(2) pneumoperitoneum induced hypercapnia, acidemia, and systemic hypertension intraoperatively, without a discernable effect on systemic immune function.
An Outbreak of Food‐borne Illness Due to Methomyl Contamination

Abstract Background. On December 26, 2002, 124 dinners took ill while eating lunch at a seafood restaurant in the town of Chiching in Kaohsiung municipality of Taiwan. Sixty‐nine people were sent to the emergency departments of the Municipal Chiching Hospital and Yuan's General Hospital. Methods. We analyzed the clinical symptoms, detailed food history, and ingested amount of each food from 59 hospitalized adult patients and identified the source of the outbreak. Results. The median latency period from beginning eating to first symptoms was 5 min. Twenty‐six symptoms and signs were recorded. The most commonly reported clinical effects were general weakness (84%), ataxia (82%), dizziness (82%), vomiting (80%), sweating (75%), floating sensation (71%), headache (69%), dyspnea (69%), and blurred vision (67%). Thirty‐one patients had residual symptoms 7 days after ingestion. Of the six residual symptoms reported, the most frequent ones were dizziness (40%), poor appetite and dry mouth (11%), and gastrointestinal disturbance (11%). The presence of residual symptoms correlated with the severity of the initial complaints (p < 0.01). Almost all patients ate cooked rice (93%) and leaf vegetable stir‐fried with crab claw (93%). The amount of each food eaten by the patients was not associated with the severity of symptoms (p > 0.05). High levels of methomyl in leaf vegetables of “leaf vegetables stir‐fried with crab claws” (380 ppm) and fried mussels (1113 ppm) were found by the Food Inspection Center at the Department of Health. The food history and chemical analysis of the poison indicated methomyl was the cause of this outbreak. Twenty‐four patients recovered completely within 7 days. Conclusion. Food‐related methomyl intoxication produced a rapid onset of significant clinical toxicity in 124 individuals. Based on the analysis of 55 adult patients, the most common effects were gait ataxia, dizziness, generalized weakness, and vomiting.
Governing for Agility and Innovation in Data-Rich Environments: the Role of Data Analytics Capabilities

While previous studies agree that governance of information technology (IT) capabilities is an enabler of organizational agility and innovation, scant attention has been paid to exploring capabilities that are antecedents of agility and successful innovation in data-rich environments. By drawing on IT capabilities literature, in this research in progress paper we conceptualize a three-dimensional secondorder construct of data analytics capabilities and propose to test its enabling effect on agility and consequently on innovation success in an environment with a copious amount of data. Our proposition is that data analytics capabilities consisting of the dimensions of infrastructure, personnel expertise, and inter-unit social infrastructure, can lead to organizational agility, which in turn leads to successful innovation. In this study, we develop a theoretical model and present hypotheses for empirical testing. The methodology for conducting a web-based survey and anticipated theoretical as well as practical contributions are presented.