Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxidative Stress and the Ovary

Superoxide (O2-), hydrogen preoxide (H2O2), and lipid peroxides are generated in luteal tissue during natural and prostaglandin-induced regression in the rat, and this response is associated with reversible depletion of ascorbic acid. Reactive oxygen species immediately uncouple the luteinizing hormone receptor from adenylate cyclase and inhibit steroideogenesis by interrupting transmitochondrial cholesterol transport. The cellular origin of oxygen radicls in regressing corpora lutea is predominately from resident and infiltrated leukocytes, notably neutrophils. Reactive oxygen species are also produced within the follicle at ovulation and, like the corpus luteum, leukocytes are the major source of the products. Antioxidants block the resumption of meiosis, whereas the generation of reactive oxygen induces oocyte maturation in the follicle. Although oxygen radicals may serve important physiologic roles within the ovary, the cyclic production of these damaging agents over years may lead to an increased cumulative risk of ovarian pathology that would probably be exacerbated under conditions of reduced antioxidant status.
CT and MRI in Detection of Intrahepatic Portosystemic Shunts in Patients with Liver Cirrhosis

Objective Our goal was to determine the prevalence and anatomic location of intrahepatic portosystemic shunts (IPSs) in patients with hepatic cirrhosis as shown by CT and MRI. Materials and Methods We retrospectively reviewed CT and MR scans of 33 cirrhotic patients who had IPSs. In addition, two series of 100 consecutive CT or MR were reviewed to determine the prevalence of IPSs and the percentage of intrahepatic and extrahepatic paraumbilical veins. Results Intrahepatic portosystemic shunts were divided into three groups according to the intrahepatic course: paraumbilical shunt between the left portal vein and the paraumbilical vein anterior to the liver (n = 29); inferior vena caval shunt between the posterior branch of the right portal vein and the inferior vena cava (n = 2); and miscellaneous (n = 2). Shunts of the paraumbilical type ran through the medial (n = 23), lateral (n = 3), or both medial and lateral (n = 3) segments of the left lobe of the liver. Twenty-five patients had one shunt, and four had more than one. Six cases were also associated with extrahepatic paraumbilical veins. Conclusion Intrahepatic portosystemic shunts, especially the paraumbilical type, were not infrequently visualized in patients with hepatic cirrhosis.
The retrotrapezoid nucleus stimulates breathing by releasing glutamate in adult conscious mice

The retrotrapezoid nucleus (RTN) is a bilateral cluster of neurons located at the ventral surface of the brainstem below the facial nucleus. The RTN is activated by hypercapnia and stabilises arterial Pco2 by adjusting lung ventilation in a feedback manner. RTN neurons contain vesicular glutamate transporter‐2 (Vglut2) transcripts (Slc17a6), and their synaptic boutons are Vglut2‐immunoreactive. Here, we used optogenetics to test whether the RTN increases ventilation in conscious adult mice by releasing glutamate. Neurons located below the facial motor nucleus were transduced unilaterally to express channelrhodopsin‐2 (ChR2)–enhanced yellow fluorescent protein, with lentiviral vectors that employ the Phox2b‐activated artificial promoter PRSx8. The targeted population consisted of two types of Phox2b‐expressing neuron: non‐catecholaminergic neurons (putative RTN chemoreceptors) and catecholaminergic (C1) neurons. Opto‐activation of a mix of ChR2‐expressing RTN and C1 neurons produced a powerful stimulus frequency‐dependent (5–15 Hz) stimulation of breathing in control conscious mice. Respiratory stimulation was comparable in mice in which dopamine‐β‐hydroxylase (DβH)‐positive neurons no longer expressed Vglut2 (DβHCre/0;;Vglut2fl/fl). In a third group of mice, i.e. DβH+/+;;Vglut2fl/fl mice, we injected a mixture of PRSx8‐Cre lentiviral vector and Cre‐dependent ChR2 adeno‐associated virus 2 unilaterally into the RTN; this procedure deleted Vglut2 from ChR2‐expressing neurons regardless of whether or not they were catecholaminergic. The ventilatory response elicited by photostimulation of ChR2‐positive neurons was almost completely absent in these mice. Resting ventilatory parameters were identical in the three groups of mice, and their brains contained similar numbers of ChR2‐positive catecholaminergic and non‐catecholaminergic neurons. From these results, we conclude that RTN neurons increase breathing in conscious adult mice by releasing glutamate.
Dietary energy substrates reverse early neuronal hyperactivity in a mouse model of Alzheimer's disease

Deficient energy metabolism and network hyperactivity are the early symptoms of Alzheimer's disease (AD). In this study, we show that administration of exogenous oxidative energy substrates (OES) corrects neuronal energy supply deficiency that reduces the amyloid‐beta‐induced abnormal neuronal activity in vitro and the epileptic phenotype in AD model in vivo. In vitro, acute application of protofibrillar amyloid‐β1–42 (Aβ1–42) induced aberrant network activity in wild‐type hippocampal slices that was underlain by depolarization of both the neuronal resting membrane potential and GABA‐mediated current reversal potential. Aβ1–42 also impaired synaptic function and long‐term potentiation. These changes were paralleled by clear indications of impaired energy metabolism, as indicated by abnormal NAD(P)H signaling induced by network activity. However, when glucose was supplemented with OES pyruvate and 3‐beta‐hydroxybutyrate, Aβ1–42 failed to induce detrimental changes in any of the above parameters. We administered the same OES as chronic supplementation to a standard diet to APPswe/PS1dE9 transgenic mice displaying AD‐related epilepsy phenotype. In the ex‐vivo slices, we found neuronal subpopulations with significantly depolarized resting and GABA‐mediated current reversal potentials, mirroring abnormalities we observed under acute Aβ1‐42 application. Ex‐vivo cortex of transgenic mice fed with standard diet displayed signs of impaired energy metabolism, such as abnormal NAD(P)H signaling and strongly reduced tolerance to hypoglycemia. Transgenic mice also possessed brain glycogen levels twofold lower than those of wild‐type mice. However, none of the above neuronal and metabolic dysfunctions were observed in transgenic mice fed with the OES‐enriched diet. In vivo, dietary OES supplementation abated neuronal hyperexcitability, as the frequency of both epileptiform discharges and spikes was strongly decreased in the APPswe/PS1dE9 mice placed on the diet. Altogether, our results suggest that early AD‐related neuronal malfunctions underlying hyperexcitability and energy metabolism deficiency can be prevented by dietary supplementation with native energy substrates.
Identification and analysis of PH domain‐containing targets of phosphatidylinositol 3‐kinase using a novel in vivo assay in yeast

Phosphatidylinositol 3‐kinase (PI3K) mediates a variety of cellular responses by generating PtdIns(3,4)P2 and PtdIns(3,4,5)P3. These 3‐phosphoinositides then function directly as second messengers to activate downstream signaling molecules by binding pleckstrin homology (PH) domains in these signaling molecules. We have established a novel assay in the yeast Saccharomyces cerevisiae to identify proteins that bind PtdIns(3,4)P2 and PtdIns(3,4,5)P3 in vivo which we have called TOPIS (Targets of PI3K Identification System). The assay uses a plasma membrane‐targeted Ras to complement a temperature‐sensitive CDC25 Ras exchange factor in yeast. Coexpression of PI3K and a fusion protein of activated Ras joined to a PH domain known to bind PtdIns(3,4)P2 (AKT) or PtdIns(3,4,5)P3 (BTK) rescues yeast growth at the non‐permissive temperature of 37°C. Using this assay, we have identified several amino acids in the β1–β2 region of PH domains that are critical for high affinity binding to PtdIns(3,4)P2 and/or PtdIns(3,4,5)P3, and we have proposed a structural model for how these PH domains might bind PI3K products with high affinity. From these data, we derived a consensus sequence which predicts high‐affinity binding to PtdIns(3,4)P2 and/or PtdIns(3,4,5)P3, and we have identified several new PH domain‐containing proteins that bind PI3K products, including Gab1, Dos, myosinX, and Sbf1. Use of this assay to screen for novel cDNAs which rescue yeast at the non‐permissive temperature should provide a powerful approach for uncovering additional targets of PI3K.
Patterns and trends in clinically recognized HIV seroconversions among all newly diagnosed HIV‐infected homo‐/bisexual men in Denmark, 1991–1994

ObjectiveTo analyse patterns and trends in recently acquired HIV infections among newly diagnosed homo-/bisexual men. Design and methodsAll newly diagnosed HIV-positive homo-/bisexual men reported to the mandatory national HIV reporting system in Denmark in 1991–1994. ResultsA total of 495 homo-/bisexual men were diagnosed with HIV infection for the first time; 45% had previously been tested HIV-negative, among whom 68% were known to have seroconverted 4 years or less prior to the positive diagnosis. Both proportions increased significantly from 1991 to 1994. Among men previously tested negative, the median interval between last negative and first positive HIV test was 902 days (range, 14–4459 days); 21.3% had seroconverted within 1 year and 55.1% within 3 years. Men previously tested negative were significantly younger than men never tested. Sex with a known HIV-positive partner was associated with having had a previous negative test and with being young. Half of the men had HIV-associated symptoms when diagnosed with HIV. Using a logistic regression model the following variables were associated with being a clinically recognized recent seroconverter: young age, no HIV-associated symptoms when diagnosed as HIV-infected, and ever having sex with an HIV-infected man. ConclusionAn increasing proportion of homo-/bisexual men diagnosed with HIV in Denmark in the early 1990s had had a negative HIV test 4 years or less before being diagnosed as HIV-positive. These men were younger and had HIV-associated symptoms less often than men not previously tested. The national HIV reporting system provides valuable information for planning primary HIV prevention programmes.
Dynamic Asset Allocation under Disappointment Aversion Preferences

We study the impact of Disappointment Aversion (DA) preferences of Gul (1991) over portfolio allocation in a dynamic setting by updating the certainty equivalent endogenously. In our paper, particular emphasis is given to the effects of return predictability and parameter uncertainty on long-term portfolio allocation. By calibrating relevant data generating processes, we find that horizon effects persist, even in the case of i.i. d. returns, with stocks appearing progressively more attractive at longer horizons. These effects intensify when investors become more disappointment averse, thus confirming the role of DA as an explanatory factor underlying the non-participation puzzle in the stock market. JEL classification: G11; G12
Changes in pain and physical function during waiting time and 3 months after knee joint arthroplasty.

OBJECTIVE To determine changes in physical and social function during a prolonged preoperative waiting period and at 3 months after total knee arthroplasty. SUBJECTS Forty-three patients were evaluated on the day that surgery was decided, the day before surgery, and 3 months afterwards. METHODS Knee pain and function were assessed using a visual analogue scale and a functional assessment system. Isometric knee flexion extension strength and mobility were measured. RESULTS Knee pain and muscle strength remained unchanged during the mean waiting time of 10 (standard deviation 8) months. On the affected side, knee extension strength was 19% weaker than on the contralateral side and did not change pre-operatively. Post-operatively, knee pain decreased by 50%. Knee extension strength decreased by 26% and flexion strength by 12% compared with the initial assessments. Knee extension strength of the operated side was 42% lower than on the non-operated side. Knee flexion mobility was decreased by 8%, while the initially detected knee extension deficit of 10 degrees (SD 7) remained unchanged. The functional assessment system did not detect any changes in function. CONCLUSION Waiting time did not affect knee pain or isometric knee extension/flexion strength. Three months post-operatively, knee pain had decreased significantly, but the strength of the operated knee was significantly lower than the pre-operative level.
Controlling lean manufacturing in multidivisional organisations: Highlighting local interests and constraints

Purpose The purpose of this paper is to address the impact of a multidivisional structure on the implementation of lean manufacturing. It investigates how the controls employed by the corporate level impact the local implementation of lean manufacturing. Design/methodology/approach The paper reports on case studies in three subsidiaries in different multidivisional organisations. Findings The paper finds that lean manufacturing can be severely constrained by the accounting-based controls which are commonly in place in a multidivisional structure. Depending on the degree of centralisation, subsidiaries may be restricted to implementing lean tools in a fragmented way, rather than acting according to a coherent set of principles. Practical implications Companies may have to accept that being part of a multidivisional organisation can imply that their lean implementation is more gradual and piecemeal than they prefer. The paper proposes several ways to mitigate the constraints that may arise from incompatibilities between accounting-based controls and lean controls. Originality/value This study contributes to the literature about external constraints on production innovations, such as lean manufacturing. It highlights how the organisational context creates local conditions that may be detrimental to the implementation of lean manufacturing.
Bioinformatics analysis of gene expression in peripheral blood mononuclear cells from children with type 1 diabetes in 3 periods.

To explore the expression changes of potential key genes and relevant biological processes in peripheral blood mononuclear cells of children with newly diagnosis of type 1 diabetes (T1D). Microarray data GSE9006 were downloaded from Gene Expression Omnibus (GEO) database, including peripheral blood mononuclear cells samples from 43 children with newly diagnosed T1D (NEW), 19 one-month (1-MO) follow-up samples, 19 4-month (4-MO) follow-up samples and 24 healthy controls. The differentially expressed genes (DEGs) were identified using Affy package in R, and cluster analysis of DEGs were performed following functional enrichment analysis with Database for Annotation, Visualization and Integrated Discovery (DAVID) and construction of protein-protein interaction (PPI) network with STRING database.We identified 73, 73, 96 DEGs in NEW group, 1-MO group and 4-MO group, respectively by comparing with healthy controls with |logFC|>0.58 and P-value<0.05. The cluster analysis of these DEGs showed that 4 genes, including human leukocyte antigen (HLA-DQA1), HLA-DRB4, integrin 3 (ITGB3) and killer cell lectin-like receptor subfamily F member 1 (KLRF1) were all significantly expressed in 3 groups, which were significantly enriched in asthma, T1D and intestinal immune network for IgA production pathway. And 57 genes enriched in cluster 5, which were only differentially expressed in NEW group, were involved in response to wounding, inflammatory response and blood coagulation as well as chemokine signaling pathway. Besides, the hub genes in PPI network of cluster 5 were identified, containing FOS, pro-platelet basic protein (PPBP), interleukin 8 (IL8), formyl peptide receptor-like 2 (FPR2) and platelet factor 4 (PF4). HLA-DQA1, HLA-DRB4, ITGB3 and KLRF1 might be targets for treatment of T1D, and 5 hub proteins, FOS, PPBP, IL8, FPR2 and PF4, were likely to be new markers for diagnosis of T1D.
Enthusiastic Educators and Interested Visitors: Investigating the Relationships between Museum Educators' Enthusiasm and Visitors' Situational Interest

Author: Liu, ChangChia, J. PhD Institution: Purdue University Degree Received: August 2018 Title: Enthusiastic Educators and Interested Visitors: Investigating the Relationships between Museum Educators’ Enthusiasm and Visitors’ Situational Interest Major Professor: P. Youli Mantzicopoulos Informal education environments like museums have become some of the most important educational resources. Although much attention has been paid to museum settings and programs, little is known about how museum educators support visitors’ learning and intrinsic motivation. In particular, there is a need to investigate museum educators’ enthusiasm, considering that enthusiasm is a powerful way of creating an engaging learning experience across various subjects and environments. In this study, I investigate museum educators’ enthusiasm as perceived by adult visitors through the lens of interest development. The results I found (N = 209) indicate a strong positive relationship between museum educators’ enthusiasm and visitors’ situational interest. Visitors’ reports of educators’ enthusiasm were directly related to catch interest (β = .74) and indirectly to hold interest (β = .46). In addition, educators’ enthusiasm mediated the connection between prior individual interest and catch interest. Visitors’ prior individual interest was also moderately related to both their catch (β = .28) and hold interest (β = .37). Limitations and directions for future studies are discussed.
The Study of Glioma by Xenotransplantation in Zebrafish Early Life Stages

Zebrafish (Danio rerio) and their transparent embryos are becoming an increasingly popular tool for studying processes involved in tumor progression and in the search for novel tumor treatment approaches. The xenotransplantation of fluorescently labeled mammalian cancer cells into zebrafish embryos is an approach enabling relatively high-throughput in vivo analyses. The small size of the embryos as well as the relative simplicity of their manipulation and maintenance allow for large numbers of embryos to be processed efficiently in a short time and at low cost. Furthermore, the possibility of fluorescence microscopic imaging of tumor progression within zebrafish embryos and larvae holds unprecedented potential for the real-time visualization of these processes in vivo. This review presents the methodologies of xenotransplantation studies on zebrafish involving research on tumor invasion, proliferation, tumor-induced angiogenesis and screening for antitumor therapeutics. We further focus on the application of these zebrafish to the study of glioma; in particular, its most common and malignant form, glioblastoma.
Control of matrix metalloproteinase production in human intestinal fibroblasts by interleukin 21

Background: T cell-mediated immunity plays a central part in the pathogenesis of tissue damage in inflammatory bowel disease (IBD). The mechanism by which T cells mediate tissue damage during IBD remains unclear, but evidence indicates that T cell-derived cytokines stimulate fibroblasts to synthesise matrix metalloproteinases (MMPs), which then mediate mucosal degradation. We have previously shown that, in IBD, there is high production of interleukin (IL) 21, a T cell-derived cytokine, which enhances Th1 activity. Aim: To investigate whether IL21 controls MMP production by intestinal fibroblasts. Methods: IL21 receptor (IL21R) was evaluated in intestinal fibroblasts by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting. Fibroblasts were stimulated with IL21 and MMPs were evaluated by RT-PCR and western blotting. The effect of a neutralising IL21R fusion protein (IL21R/Fc) on the induction of MMPs in fibroblasts stimulated with IBD lamina propria mononuclear cell (LPMC) supernatants was also evaluated. Results: Intestinal fibroblasts constitutively express both IL21R and the common γ chain receptor, which are necessary for IL21-driven signalling. IL21 enhances fibroblast production of MMP-1, MMP-2, MMP-3 and MMP-9, but not tissue inhibitors of MMP-1 and MMP-2. Moreover, IL21 synergises with tumour necrosis factor α to increase synthesis of MMP synthesis. IL21 enhances MMP secretion without affecting gene transcription and protein synthesis. IBD LPMC supernatants stimulate MMP secretion by intestinal fibroblasts, and this effect is partly inhibited by IL21R/Fc. Conclusions: These results suggest that fibroblasts are a potential target of IL21 in the gut and that IL21 controls MMP secretion by fibroblasts.
Migrant acculturation: An exploration of the early work experiences of Indian professionals working in skilled occupations in New Zealand

The Indian migrant group in New Zealand has been growing rapidly in the recent past, and a significant number of Indian migrants who relocate into the country are skilled professionals (Ministry of Business Innovation and Employment, 2016; Statistics New Zealand, 2014). Skilled migrants contribute towards increasing the human capital of the host country, by bringing with them skills, knowledge and expertise that can be harnessed to create economic advantage for their employers and the larger community (Ben-Gad, 2008; Ortega & Peri, 2014). Smooth adaptation of skilled migrants at the workplace could therefore, prove beneficial to not just the migrant individuals, but also to their employers and the larger economy. This research aims to examine the workplace acculturation experiences of skilled, first generation Indian migrants in New Zealand, and how intercultural interactions at the workplace influence their adaptation process. Interpretive descriptive methodology (Smythe, 2012) was adopted to address the research question and one-on-one, in-depth interviews with five professional, first generation Indian migrants in the city of Auckland formed the basis of this study. Analysis of the findings was done using the theoretical concepts of culture shock, acculturation and culture distance. This research finds that workplace acculturation experiences of professional Indian migrants are greatly influenced by their background and individual contexts; key factors being previous exposure to a foreign environment, financial liabilities and visa type. Visa conditions in particular, are found to have a crucial relationship with the employment choices of migrants, influencing their career choices and affecting their early workplace experiences. The lack of New Zealand work experience was a key barrier faced by participants while seeking employment in New Zealand, but once this initial hurdle was crossed, their workplace acculturation was smooth and swift. This seamless adaptation at work was attributed to the support of supervisors and colleagues, although the participants’ employers did not have formally established diversity policies and practices. This research provides practical insights to organisations that can help them formulate effective inclusion practices to support new migrants, particularly Indian professional migrants in the workplace. It also adds to the existing academic knowledge in this area, considering that there is a scarcity of studies centered on the adaptation experiences of skilled Indian migrants in New Zealand.