Miracle-dz/UniFAR-FTUs huggingface dataset:
Short‐period hypoxia increases mouse embryonic stem cell proliferation through cooperation of arachidonic acid and PI3K/Akt signalling pathways

Abstract. Hypoxia plays important roles in some early stages of mammalian embryonic development and in various physiological functions. This study examined the effect of arachidonic acid on short‐period hypoxia‐induced regulation of G1 phase cell‐cycle progression and inter‐relationships among possible signalling molecules in mouse embryonic stem cells. Hypoxia increased the level of hypoxia‐inducible factor‐1α (HIF‐1α) expression and H2O2 generation in a time‐dependent manner. In addition, hypoxia increased the levels of cell‐cycle regulatory proteins (cyclin D1, cyclin E, cyclin‐dependent kinase 2 (CDK2) and CDK4). Maximum increases in the level of these proteins and retinoblastoma phosphorylation were observed after 12–24 h of exposure to hypoxic conditions, and then decreased. Alternatively, the level of the CDK inhibitors, p21Cip1 and p27Kip1 were decreased. These results were consistent with the results of [3H]‐thymidine incorporation and cell counting. Hypoxia also increased the level of [3H]‐arachidonic acid release and inhibition of cPLA2 reduced hypoxia‐induced increase in levels of the cell‐cycle regulatory proteins and [3H]‐thymidine incorporation. The level of cyclooxygenase‐2 (COX‐2) was also increased by hypoxia and inhibition of COX‐2 decreased the levels of cell‐cycle regulatory proteins and [3H]‐thymidine incorporation. Indeed, the percentage of cells in S phase, levels of cell cycle regulatory proteins, and [3H]‐thymidine incorporation were further increased in hypoxic conditions with arachidonic acid treatment compared to normoxic conditions. Hypoxia‐induced Akt and mitogen‐activated protein kinase (MAPK) phosphorylation was inhibited by vitamin C (antioxidant, 10−3 M). In addition, hypoxia‐induced increase of cell‐cycle regulatory protein expression and [3H]‐thymidine incorporation were attenuated by LY294002 (PI3K inhibitor, 10−6 M), Akt inhibitor (10−6 M), rapamycin (mTOR inhibitor, 10−9 M), PD98059 (p44/42 inhibitor, 10−5 M), and SB203580 (p38 MAPK inhibitor, 10−6 M). Furthermore, hypoxia‐induced increase of [3H]‐arachidonic acid release was blocked by PD98059 or SB203580, but not by LY294002 or Akt inhibitor. In conclusion, arachidonic acid up‐regulates short time‐period hypoxia‐induced G1 phase cyclins D1 and E, and CDK 2 and 4, in mouse embryonic stem cells through the cooperation of PI3K/Akt/mTOR, MAPK and cPLA2‐mediated signal pathways.
Organization of Hyaluronan and Versican in the Extracellular Matrix of Human Fibroblasts Treated With the Viral Mimetic Poly I:C

We have examined structural details of hyaluronan- and versican-rich peri-cellular matrices in human lung fibroblasts, as well as fixation effects after treatment with the viral mimetic, poly I:C. Lateral aggregation of hyaluronan chains was promoted by acid-ethanol-formalin fixation compared with a network appearance with formalin alone. However, hyaluronidase-sensitive cable structures were seen in live cells, suggesting that they are not a fixation artifact. With all fixatives, versican and hyaluronan probes bound alternately along strands extending from the plasma membrane. However, a yellow colocalization signal required aggregation/overlap of several hyaluronan/versican strands and was more pronounced after acid-ethanol-formalin fixation. In addition to the main cell surface, hyaluronan and versican were also associated with fine actin-positive membrane protrusions, retraction fibers, and surface blebs. After wounding plus treatment with poly I:C, cells displayed larger hyaluronan coats and cable-like structures, as well as more membrane protrusions. However, treated cells did not migrate and had increased stress fibers compared with control wounded cells. Deposition of hyaluronan into cable-like structures in response to poly I:C was diminished but still apparent following actin filament disruption with cytochalasin D, suggesting that the protrusions only partially facilitate cable formation. As seen by scanning electron microscopy, the membrane protrusions may participate in poly I:C-induced binding of monocytes to hyaluronan- and versican-rich matrices. These results suggest that poly I:C-induced hyaluronan- and versican-rich cable structures are not deposited during migration, and that cellular protrusions partially contribute to hyaluronan cable formation. This manuscript contains online supplemental material at http://www.jhc. org. Please visit this article online to view these materials.
Brostallicin, a novel anticancer agent whose activity is enhanced upon binding to glutathione.

Brostallicin (PNU-166196) is a synthetic alpha-bromoacrylic, second-generation DNA minor groove binder structurally related to distamycin A, presently in Phase II trials in Europe and the United States. The compound shows broad antitumor activity in preclinical models and dramatically reduced in vitro myelotoxicity in human hematopoietic progenitor cells compared with that of other minor groove binders. Brostallicin showed a 3-fold higher activity in melphalan-resistant L1210 murine leukemia cells than in the parental line (IC(50) = 0.46 and 1.45 ng/ml, respectively) under conditions in which the cytotoxicity of conventional antitumor agents was either unaffected or reduced. This melphalan-resistant cell line has increased levels of glutathione (GSH) in comparison with the parental cells. Conversely, GSH depletion by buthionine sulfoximine in a human ovarian carcinoma cell line (A2780) significantly decreased both the cytotoxic and the proapoptotic effects of brostallicin. In one experiment, human glutathione S-transferase pi (GST-pi) cDNA was transfected into A2780 cells, and four clones of A2780 with different expression levels of GST-pi were generated (i.e., two clones with high and two clones with low GST-pi expression). A 2-3-fold increase in GST-pi levels resulted in a 2-3-fold increase in cytotoxic activity of brostallicin. Similar results were obtained for GST-pi-transfected human breast carcinoma cells (MCF-7). Brostallicin showed 5.8-fold increased cytotoxicity in GST-pi-transfected versus empty vector-transfected cells with low GST-pi expression. In an in vivo experiment, A2780 clones were implanted into nude mice. The antitumor activity of brostallicin was higher in the GST-pi-overexpressing tumors without increased toxicity. Regarding the mechanism of action, brostallicin interacts reversibly with the DNA minor groove TA-rich sequences but appears unreactive in classical in vitro DNA alkylation assays. We speculated that an intracellular reactive nucleophilic species, e.g., GSH, could react with the alpha-bromoacrylamide moiety functions. Experiments on the interaction with plasmid DNA showed a change of the DNA topology from supercoiled to circular form (nicking) in the presence of GSH, whereas no change was found in its absence. In vitro incubations of brostallicin were performed with the human recombinant GST isoenzymes A1-1, M1-1, and P1-1 (alpha, mu and pi isoenzymes, respectively) in the presence of GSH. The decrease in brostallicin levels was monitored in these incubations; the rate of loss (and therefore brostallicin metabolism) was significantly higher for the M1-1 and P1-1 isoenzymes than for the A1-1 isoenzyme.
Epidemiological problems associated with studies of the safety of oral contraceptives.

Most segments of American society agree that excessive and disproportionate population growth is a social, economic, and health threat, and there is a consensus, reflected in the stated policy of the federal government 1 that every family should have easy access to family planning information and services so that each may make an intelligent and uninhibited choice concerning the number of children desired. This consensus has increased the need for family planning services and efforts to develop improved techniques of contraception. New methods have been developed because the old ones are not suitable for all populations. It is difficult for a single method to satisfy all the criteria of the ideal contraceptive: efficacy, safety, reversibility, low cost, simplicity, and acceptability. Advances in reproductive biology supported and conducted by private foundations, industry, and the government have resulted in several unique and effective techniques in the last decade, the most noteworthy being oral
THIRST AND SODIUM APPETITE IN MICE : ANGIOTENSIN , BRAIN

of Thesis Presented to the Graduate School of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Master of Science THIRST AND SODIUM APPETITE IN MICE: ANGIOTENSIN, BRAIN Fos, BLOOD PLASMA HORMONES AND FLUID INTAKE By Bradley E. Goldstein May 2003 Chair: Donna Duckworth Cochair: Neil Rowland Major Department: Molecular Genetics and Microbiology Questions regarding the role of angiotensin (Ang) were examined in mice. In contrast to rats, CD-1 male mice failed to drink water or sodium after exogenous Ang injection. Fos-IR in these mice was prevalent in the subfornical organ (SFO) and there were no differences in Fos-IR among different strains or gender of mice. Like rats, mice drank both sodium and water after furosemide treatment. Mice given furosemide were also hypovolemic (increased plasma protein and hematocrit ratios) and had increased plasma renin activity (PRA). Fos-IR in these mice was similar to that seen after exogenous Ang treatment. Whereas rats drink both sodium and water after polyethylene glycol treatment, mice did not show a clear sodium appetite. However, these mice were hypovolemic, had increased PRA, had modestly increased aldosterone, and drank water. Fos-IR was prevalent in almost all brain regions examined after this treatment. Thus, our results revealed several differences between rats and mice with regard to responses after procedures that mimic the renin-angiotensin-system (RAS).
A case study of algorithm-assisted decision making in child maltreatment hotline screening decisions

Every year there are more than 3.6 million referrals made to child protection agencies across the US. The practice of screening calls is left to each jurisdiction to follow local practices and policies, potentially leading to large variation in the way in which referrals are treated across the country. Whilst increasing access to linked administrative data is available, it is diﬃcult for welfare workers to make systematic use of historical information about all the children and adults on a single referral call. Risk prediction models that use routinely collected administrative data can help call workers to better identify cases that are likely to result in adverse outcomes. However, the use of predictive analytics in the area of child welfare is contentious. There is a possibility that some communities— such as those in poverty or from particular racial and ethnic groups—will be disadvantaged by the reliance on government administrative data. On the other hand, these analytics tools can augment or replace human judgments, which themselves are biased and imperfect. In this paper we describe our work on developing, validating, fairness auditing, and deploying a risk prediction model in Allegheny County, PA, USA. We discuss the results of our analysis to-date, and also highlight key problems and data bias issues that present challenges for model evaluation and deployment.
Comparison of salivary antioxidants in healthy smoking and non-smoking men.

BACKGROUND Tobacco use is known as a serious global public health problem, and is also an important risk factor for oral diseases. Saliva is the first biological medium encountered during inhalation of cigarette smoke. Therefore, the main aim of this study was to compare the levels of salivary antioxidants between healthy smoking and non-smoking men. METHODS Unstimulated whole saliva samples were collected from 80 men. Forty subjects were smokers with a daily consumption of 20 cigarettes for at least 10 years and 40 subjects were non-smokers. The salivary levels of uric acid, superoxide dismutase, glutathione peroxidase, and peroxidase were measured and compared between studied groups. RESULTS The mean levels of salivary superoxide dismutase, glutathione peroxidase, and peroxidase were significantly lower in smokers than non-smokers. There was no statistically significant difference in the salivary uric acid level between smokers and non-smokers. CONCLUSIONS Measurement of antioxidant agents in human saliva might be useful for estimating the level of oxidative stress caused by cigarette smoke.
Reversal effect of Jagged1 signaling inhibition on CCl4-induced hepatic fibrosis in rats

The role of the Notch ligand Jagged1 in hepatic fibrosis remains to be elucidated. In the current study, we investigated the role of Jagged1 in the activation of hepatic stellate cells (HSCs) and development of hepatic fibrosis in rats. In vitro, Jagged1 in HSCs was downregulated and upregulated by Jagged1 siRNA and pcDNA3.1 Jagged1, respectively. The levels of epithelial-mesenchymal transition (EMT) markers and HSC activation markers were assessed using western blot analysis. The proliferation and migration capacity of HSCs were assessed using 5-ethynyl-2′-deoxyuridine (EdU) incorporation and Transwell migration assays. In vivo, a recombinant adeno-associated virus type 1 (rAAV1) vector carrying Jagged1 shRNA (rAAV1-Jagged1-shRNA) was constructed and transferred to rat livers via the tail vein. Reversion of liver fibrosis and the effect of Jagged1 signaling on EMT were studied using pathological, immunohistochemical and immunofluorescence methods. Our findings revealed that downregulation and upregulation of Jagged1 inhibited and promoted, respectively, HSC activation. The migratory capacity of HSCs was markedly restrained by Jagged1 siRNA. Furthermore, downregulation of Jagged1 suppressed EMT in HSCs. rAAV1-Jagged1-shRNA was generated to treat CCl4-induced hepatic fibrosis in rats. Treatment with rAAV1-Jagged1-shRNA reversed hepatic fibrosis by decreasing EMT. The results of the present study suggest that inhibition of Jagged1 is a potential treatment to ameliorate liver fibrosis.
A distributed control strategy for connectivity preservation of multi-agent systems subject to actuator saturation

In this paper a connectivity preserving consensus protocol for single-integrator agents is presented subject to actuator saturation. In contrast to the previously proposed methods not only the control laws are shown to remain bounded, but also the actuators remain within their available actuating constraints. We have shown that by using our proposed control algorithm agents converge to the same position, while connectivity of the entire network is preserved. The effectiveness of the proposed control strategy is illustrated through numerical simulations.
Influence of Culture on Tripartite Self-Concept Development in Adolescence: A Comparison between Han and Uyghur Cultures

This study investigated the development of cultural variability in interdependent self-construal by comparing the differences in the tripartite self-concept of adolescent samples from the Han and Uyghur cultures. Participants (460 males, 522 females; M age = 16.3 yr., SD = 4.8) in the sub-phases of pre-, early-, mid-, late- and post-adolescence were asked to completed the revised Twenty Statements Test, and the items generated by the participants were coded into private, relational, and collective self-statements. The private self-statements were further differentiated by personal and social orientation, and the relational self-statements were further coded into family and friend focus. The relational aspect of an individual's self, or personal relationship, became increasingly important with age in the Han cultural groups, whereas the collective aspect of an individual's self, or social identity, became increasingly important with age in the Uyghur cultural groups. These findings seem to show the development of differences between relational and collective interdependent self-construals. Furthermore, these findings emphasize the need for further research into the development of within-cultural differences in self-construal.
The Safety and Efficacy of Antivenin Latrodectus mactans

Latrodectus species of spiders are ubiquitous throughout the world. The United States is home to at least five varieties, and the North American native Latrodectus mactans can now be found around the world by virtue of hitchhiking with travelers from this continent. Bites from Latrodectus spiders continue to be a health problem. There are over 10,000 reports to poison centers annually of patients bitten by these arachnids, with probably hundreds or thousands more unreported. The neurotoxic alpha-latrotoxin is likely responsible for most of the signs and symptoms witnessed after bites by these spiders, and is thought to exert its activity through calcium-mediated release of neurotransmitters from nerve terminals. Clinical effects reported following Latrodectus envenomation include hypertension, diaphoresis, muscle cramps, weakness, and gastrointestinal complaints. However, the most common reason for victims of Latrodectus envenomation to present to health care facilities is for intractable pain. Many individuals describe the pain as nonspecific cramping of the extremities, back, and abdomen, and some compare the intensity to pain associated with nephrolithiasis or childbirth. Most patients will see a resolution of symptoms within 48 to 72 hours of onset, but symptoms in some cases can last for several days.
Volt-time curves of 24 kV porcelain insulators under non-standard impulse waveshapes

This paper presents an application of novel method in order to assess the characteristic of volt-time curves based on Disruptive Effect Model. The tests were performed on a pin-type, porcelain insulator of 24 kV class. Besides the standard 1.2/50 μs impulse voltage waveshape, four non-standard impulse waveshapes, of both polarities, were adopted in the tests, namely 1.2/4 ms, 1.2/10 ms, 3/10 μs, and 7.5/30 μs. The volt-time characteristics obtained from the tests were compared with those predicted by three different procedures related to the Disruptive Effect Model. The results show that the methods by Darveniza and Vlastos and by Hileman do not predict insulator breakdown for the lower peak voltage levels in some cases. On the other hand, a good agreement was found between theoretical and experimental results for the calculations performed using the method proposed by the authors.
Language friction and multilingual policies in higher education: the stakeholders' view

The learning of prestigious international languages becomes a process fraught with tensions in multilingual settings. The process of internationalisation in many universities has led to the spread of English-medium instruction (EMI), which tends to raise linguistic debates particularly in the case of bilingual institutions. However, and despite a few exceptions, there is scant research into the effect of EMI on the different bodies that make up the university community, especially in the case of teaching staff and administration personnel (as most studies focus on students). The participants in this study were 648 students, teachers and administration personnel who filled out a questionnaire. The analyses of the data revealed the existence of language tensions among the different languages in contact. Parallelisms and differences were found among the three different bodies, which led us to put forward a series of implications related to the implementation of EMI courses, as well as to multilingual language policies at university.
Seeking Newborn Information as a Resource for Maternal Support

The purpose of this descriptive, longitudinal study was to identify topics and sources of information sought by new mothers. Eighty-nine mothers were recruited from prenatal classes conducted at two health-care systems located in the Midwest region of the United States. Telephone contact was made with the mothers between 2 and 3 weeks postpartum. Each mother completed prenatal and postpartum questionnaires addressing mothers’ perceived support systems. Findings indicated that, despite attending prenatal classes and receiving child and postpartum care instruction, mothers often want additional information after they bring their baby home. The study’s results contribute to nursing knowledge by confirming that new mothers seek and receive information regarding childcare from multiple sources. Nurse-initiated contacts with postpartum mothers provide support and information that can assist mothers in caring for their newborns.
Development of verbal abilities in retarded and normal children as measured by Stroop test.

The Stroop Test was administered to 102 low-grade retardates and 208 normal school children in age-groups of 10 to 15 years in order to bring out developmental differences. The retardates could name colours faster than reading words, and showed relatively less interference than normals in naming the colours of words. In these they functioned like the normal children at Grade 1 level. The reading speed and interference measures appeared to reflect stable individual differences which might be related to those in learning.
HIV status of sexual partners is more important than antiretroviral treatment related perceptions for risk taking by HIV positive MSM in Montreal, Canada

Objective: To examine the role of antiretroviral treatment related perceptions relative to other clinical and psychosocial factors associated with sexual risk taking in HIV positive men who have sex with men (MSM). Methods: Participants were recruited from ambulatory HIV clinics in Montreal. Information on sociodemographic factors, health status, antiretroviral treatment related perceptions, and sexual behaviours was collected using a self administered questionnaire. At-risk sexual behaviour was defined as at least one occurrence of unprotected insertive or receptive anal intercourse in the past 6 months. Multivariate logistic regression was performed to evaluate the associations between at-risk sexual behaviour and covariates. Results: 346 subjects participated in the study. Overall, 34% of subjects were considered at risk; 43% of sexually active subjects (n = 274). At-risk sexual behaviour was associated with two antiretroviral treatment related perceptions: (1) taking antiretroviral treatment reduces the risk of transmitting HIV (adjusted odds ratio (OR), 2.10; 95% confidence interval (CI), 1.16 to 3.80); and (2) there is less safer sex practised by MSM because of HIV treatment advances (OR, 1.82; CI, 1.14 to 2.90). Other factors, however, were more strongly associated with risk. These were: (1) safer sex fatigue (OR, 3.23; CI, 1.81 to 5.78); (2) use of “poppers” during sexual intercourse (OR, 6.28; CI, 2.43 to 16.21); and (3) reporting a greater proportion of HIV positive anal sex partners, compared with reporting no HIV positive anal sex partners: (a) <50% HIV positive (OR, 16.79; CI, 4.70 to 59.98); (b) ⩾50% HIV positive (OR, 67.67; CI, 15.43 to 296.90). Conclusion: Despite much emphasis on HIV treatment related beliefs as an explanation for sexual risk taking in MSM, this concern may play a relatively minor part in the negotiation of risk by HIV positive MSM. Serosorting, safer sex fatigue, and the use of poppers appear to be more important considerations in understanding the sexual risk behaviours of HIV positive MSM.