Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel mechanism of vasoregulation: ADP‐induced relaxation of the porcine isolated coronary artery is mediated via adenosine release

In this study, we have investigated the mechanism of ADP‐induced relaxation of porcine coronary artery (PCA) rings. The P2Y receptor agonists ADP and ADPβS produced concentration‐dependent relaxation of endothelium‐denuded PCA smooth muscle with pD2 values of 5.3 and 4.9, respectively. RT‐polymerase chain reaction (RT‐PCR) and immunoblotting demonstrated mRNA and protein expression of P2Y1 and A2A adenosine receptors in the PCA. The nonselective P2 antagonist PPADS or the P2Y1‐selective antagonist MRS2179 failed to alter ADP‐ or ADPβS‐induced relaxations. Relaxations to ADP were, however, blocked by the A2A adenosine receptor‐selective antagonists ZM241385 and SCH58261 (apparent pKB values of 9.2 and 8.9, respectively). We excluded roles for direct occupancy of A2A adenosine receptors by ADP or ADPβS as well as metabolism to adenosine as mechanisms for ADP‐evoked relaxations. However, ADP responses were significantly enhanced in the presence of the ENT1 nucleoside transporter inhibitors dipyridamole and NBTI and were significantly inhibited by adenosine deaminase, indicating a role for extracellular adenosine. Suprafusion of [3H]‐adenine‐labeled PCA segments showed that ADP induced the release of a number of purines, including adenosine. These data suggest that ADP mediates relaxation of the PCA via a novel mechanism that involves adenine nucleotide‐evoked adenosine release and the subsequent activation of A2A receptors. —Rayment, S. J., Ralevic, V. , Barrett, D. A. , Cordell, R. and Alexander, S. P. H. A novel mechanism of vasoregulation: ADP‐induced relaxation of the porcine isolated coronary artery is mediated via adenosine release FASEB J. 21, 577–585 (2007)
Lower pain and higher muscular strength in immigrant women with vitamin D deficiency following vitamin D treatment

ABSTRACT Background: Vitamin D deficiency is common among immigrants in the Nordic region. It may lead to osteomalacia with severe musculoskeletal pain. There are reports that vitamin D deficiency without osteomalacia may lead to pain but little is known of the effect of treatment. Objective: To investigate whether a moderate dose of cholecalciferol and calcium improves strength and pain in a group of vitamin D deficient women. Design: Twentyfive immigrant women with vitamin D deficiency diagnosed during pregnancy were treated postpartum with a daily dose of 1,600 IU cholecalciferol and 1,000 mg of calcium. They were examined at the start of treatment and again after 3 months of treatement and the results were statistically compared. Setting: Southern parts of Stockholm. Main outcome measures: Serum 25-hydroyvitamin D (25(OH)D), serum-parathyroid hormone (PTH), pain measured by a visual analogue scale (VAS), musculoskeletal strength by performance on a chair stand test (seconds), and bone tenderness by pressure algometer (kilo-Pascal). Results: Following the treatment, the 21 women attending had lowered cm in VAS, improved musculoskeletal strength, - and 25(OH)D levels were normalized. Conclusions: A moderate dose of vitamin D normalized l vitamin D levels, improved muscular strength and reduced pain in this group of vitamin D deficient immigrant women.
Passing Messages Between Disciplines

Problems in computer science, such as error correction in information transfer and "satisfiability" in optimization, show phase transitions familiar from solid-state physics. In his Perspective, Mezard explains how recent advances in these three fields originate in similar "message passing" procedures. The exchange of elaborate messages between different variables and constraints, used in the study of phase transitions in physical systems, helps to make error correction and satisfiability codes more efficient.
Andes virus stimulates interferon‐inducible MxA protein expression in endothelial cells

MxA is a cellular protein activated in cells treated with type I interferons. MxA protein is a member of the dynamin superfamily of large guanosine triphosphatases. A unique property of Mx1 GTPases is their antiviral activity against a wide range of RNA viruses. Replication of several hantavirus strains is inhibited in cells constitutively expressing MxA protein. We have found that Andes virus (ANDV) infection up regulates transcription of MxA RNA and expression of MxA protein in human endothelial cells in vitro. Activation of MxA gene expression requires virus replication. Up‐regulation of MxA gene expression in hantavirus infected cells varies depending on the cell type. The degree of activation of MxA gene expression is inversely correlated with the efficiency of hantavirus replication. Additionally, MxA protein is co‐localized with hantavirus nucleocapsid protein in infected cell. Our data suggest that MxA by interacting with the virus nucleocapsid protein inhibits production of new infectious virus particles. J. Med. Virol. 75:267–275, 2005. © 2004 Wiley‐Liss, Inc.
Phase I Clinical Trial of Topotecan and Pegylated Liposomal Doxorubicin

Background: The objective of this study was to determine the feasibility and maximum tolerated dose (MTD) of combination topotecan and pegylated liposomal doxorubicin (PLD) administered in 4- or 3-week cycles in patients with advanced or refractory solid tumors. Patients and Methods: Patients were treated with intravenous topotecan (0.75–1.25 mg/m2) for 3 days followed by PLD (25–40 mg/m2) on Day 4. The following dose combinations (topotecan/PLD, mg/m2) were explored: 0.75/40, 1.0/40, and 1.25/40 every 28 days; and 1.0/25 and 1.0/30 every 21 days. Results: Thirty-two patients were enrolled, and all had received prior chemotherapy. Most (84 percent) patients had ovarian cancer. A total of 157 cycles (median, 4 cycles; range, 1–19 cycles) of chemotherapy were administered. Dose-limiting toxicities were Grade 4 neutropenia and death at dose level 3 (1.25/40 mg/m2 every 28 days), and neutropenic fever, Grade 3 stomatitis, and Grade 3 peripheral neuropathy (all in one patient) at dose level 5 (1/30 mg/m2 every 21 days). Myelosuppression was the most common serious toxicity. Twenty-six patients were evaluable for response and 7 (27 percent) had partial responses. All responses were seen in patients with ovarian cancer. Conclusions: This combination is feasible and well tolerated; encouraging activity was observed in heavily pretreated patients with ovarian cancer. The recommended regimens for a Phase II study are topotecan 1.0 mg/m2 on Days 1–3 followed by PLD 40 mg/m2 on Day 4 of a 28-day cycle, and topotecan 1.0 mg/m2 on Days 1–3 and PLD 30 mg/m2 on Day 4 of a 21-day cycle.
An unanticipated copy number variant of chromosome 15 disrupting SMAD3 reveals a three‐generation family at serious risk for aortic dissection

Several genes involved in the familial appearance of thoracic aortic aneurysms and dissections (FTAAD) have been characterized recently, one of which is SMAD3. Mutations of SMAD3 cause a new syndromic form of aortic aneurysms and dissections associated with skeletal abnormalities. We discovered a small interstitial deletion of chromosome 15, leading to disruption of SMAD3, in a boy with mild mental retardation, behavioral problems and revealed features of the aneurysms‐osteoarthritis syndrome (AOS). Several family members carried the same deletion and showed features including aortic aneurysms and a dissection. This finding demonstrates that haploinsufficiency of SMAD3 leads to development of both thoracic aortic aneurysms and dissections, and the skeletal abnormalities that form part of the aneurysms‐osteoarthritis syndrome. Interestingly, the identification of this familial deletion is an example of an unanticipated result of a genomic microarray and led to the discovery of important but unrelated serious aortic disease in the proband and family members.
Health, disease, mortality and survival in wild and rehabilitated harbor seals (Phoca vitulina) in San Francisco Bay and along the central California coast

xvi Acknowledgements xviii Chapter 1: General Introduction 1 Harbor seals as sentinels of ocean health 1 Harbor seals in San Francisco Bay 2 Harbor seal survival and dispersal 5 Disease in harbor seals: overview 6 Disease in harbor seals in the San Francisco Bay Area 10 Some methods to assess seal health 11 Contaminants 13 Interactions among health, infectious diseases, and contaminants 15 Thesis structure 16 Chapter 2: Sampling overview: study sites and capture methods 19 Study sites 19 Capture and sampling 23 Chapter 3: Hematology and serum chemistry in stranded and wild-caugh harbor seals in central California: reference intervals, predictors of survival, and parameters affecting blood variables 27 Introduction 27 Methods 29
Effect of cytokines and lipopolysaccharide on CD14 antigen expression in human monocytes and macrophages

The 52 kD myeloid membrane glycoprotein CD14 represents the receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein (LBP); it is involved in LPS induced tumor necrosis factor‐alpha production. Expression of CD14 increases in monocytes differentiating into macrophages, and it is reduced by rIFNg in monocytes in vitro. In the present study CD14 membrane antigen expression was investigated in cultures of human mononuclear leucocytes (PBL), in elutriated, purified monocytes, and in blood monocyte derived Teflon cultured macrophages. Cells were incubated for 15 or 45 h with rIL‐1, rIL‐2, rIL‐3, rIL‐4, rIL‐5, rIL‐6, rTNFa, rGM‐CSF, rM‐CSF, rTGFb1, rIFNa, lipopolysaccharide (LPS), and, as a control, rIFNg. The monoclonal antibodies Leu‐M3 and MEM 18 were used for labelling of CD14 antigen by indirect immunofluorescence and FACS analysis of scatter gated monocytes or macrophages. IFNg concentrations were determined in PBL culture supernatants by ELISA. rIFNa and rIL‐2 reduced CD14 in 15 and 45 h PBL cultures, an effect mediated by endogenous IFNg, since it was abolished by simultaneous addition of an anti‐IFNg antibody. rIFNa and rIL‐2 were ineffective in purified monocytes or macrophages. rIL‐4 strongly reduced CD14 in PBL and purified monocytes after 45 h, whereas in macrophages the decrease was weak, although measurable after 15 h. The other cytokines investigated did not change CD14 antigen expression. Cycloheximide alone reduced CD14, but when added in combination with rIFNg the effect on CD14 downregulation was more pronounced. The effect of rIFNg on CD14 in PBL cultures was dose‐dependently inhibited by rIL‐4 and this inhibition is probably due to an IL‐4 mediated blockade of IFNg secretion. LPS at a low dose increased CD14, at a high dose it produced a variable decrease of CD14 in PBL, which was probably due to LPS induced IFNg secretion. LPS strongly enhanced CD14 in 45 h cultures of purified monocytes. The results, showing that CD14 antigen expression is upregulated by LPS and downregulated by rIFNg and rIL‐4, suggest that the LPS‐LBP receptor is involved in the feedback response of IFNg and IL‐4 to LPS stimulation.
Pitch and spectral analysis of speech based on an auditory synchrony model

There has been a substantial interest in the last few decades in the problem of training computers to recognize human speech. In spite of the concentrated efforts of conscientious teams of researchers, however, the solution remains elusive, unless the task is kept so restricted as to be uninteresting. These discouraging results may be due in part to the fact that researchers in the past paid little attention to models for human processing of auditory signals to guide in the design of speech frontend processing strategies. The picture is rapidly changing at the present time, although we have not yet realized any direct benefits from the available models. Voiced speech sounds are characterized in the spectral domain by prominent peaks at specific frequencies that correspond to certain resonances in the vocal tract. The frequencies of these formants" convey most of the information necessary to identify the phonetic content. The peripheral level of the auditory system performs a frequency analysis, but also compresses the dynamic range of input stimuli. The net effect is to reduce the prominence of spectral peaks, relative to those obtained through standard Fourier analysis. Recent research on the response of a large population of auditory nerve fibers in the cat's ear to speech-like stimuli [Sachs and Young, 1979, 19801 has demonstrated that mean rate response alone does not in general convey adequate information to show clearly the frequencies of the formants. However, a significant amount of information is retained in the patterns of firing which is lost when a simple count of number of spikes per unit time is derived. Sachs and Young, and others, have suggested that a form of processing that measures the synchrony in the response to certain periodicites may be able to accentuate peaks in the spectrum. This thesis concerns the development of a specific strategy for such synchrony detection, and its application to the two separate tasks of spectral analysis and estimation of the fundamental frequency of voicing. The approach of the thesis is to process the incoming speech signal through a system which models what is known about peripheral auditory processing, and then to apply a synchrony measure to accentuate the spectral attributes that are known to be important for the identification of the phonetic content of speech. The design of the synchrony measure is motivated in large part by a preconceived notion of what represents a good' result. The main criteria were that peaks in the original speech spectrum should be preserved, but amplitude information, particularly general
Facilitating Self-Transcendence: An Intervention to Enhance Well-Being in Late Life

This randomized controlled pilot study evaluated the effects of the Psychoeducational Approach to Transcendence and Health (PATH) Program, an 8-week intervention hypothesized to increase self-transcendence and improve well-being in community-dwelling women aged 60 years and older (N = 20). The PATH combined mindfulness exercises, group processes, creative activities, and at-home practice using community engaged research methods. Findings provided some support for the effectiveness of PATH. Although there was no significant Group × Time interaction, self-transcendence, psychological well-being, and life satisfaction differed significantly pre- and postintervention in the wait-listed control group, which received a revised version of the program. Further study is needed with a larger sample to determine the effectiveness of PATH. Potentially, PATH may be a convenient and affordable activity to support personal development and improve well-being among older adults at senior centers, retirement communities, nursing homes, church groups, and other places where older adults gather.
Can the Government Deter Discrimination? Evidence from a Randomized Intervention in New York City

Racial discrimination persists despite established antidiscrimination laws. A common government strategy to deter discrimination is to publicize the law and communicate potential penalties for violations. We study this strategy by coupling an audit experiment with a randomized intervention involving nearly 700 landlords in New York City and report the first causal estimates of the effect on rental discrimination against blacks and Hispanics of a targeted government messaging campaign. We uncover discrimination levels higher than prior estimates indicate, especially against Hispanics, who are approximately 6 percentage points less likely to receive callbacks and offers than whites. We find suggestive evidence that government messaging can reduce discrimination against Hispanics but not against blacks. The findings confirm discrimination’s persistence and suggest that government messaging can address it in some settings, but more work is needed to understand the conditions under which such appeals are most effective.
Nuclear changes in oral mucosa of alcoholics and crack cocaine users

The effects of drugs of abuse on oral mucosa are only partly understood. The aims of the present study were to: (1) evaluate the frequency of nuclear changes in normal-appearing oral mucosa of alcoholics and crack cocaine users and (2) assess their association with cell proliferation rate. Oral smears were obtained from the border of the tongue and floor of the mouth of 26 crack cocaine users (24 males and 2 females), 29 alcoholics (17 males and 12 females), and 35 controls (17 males and 18 females). Histological slides were submitted to Feulgen staining to assess the frequency of micronuclei (MN), binucleated cells (BN), broken eggs (BE), and karyorrhexis (KR). A significant increase in the frequency of MN was observed in cells exfoliated from the tongue of crack cocaine users (p = 0.01), and alcoholics showed a higher frequency of KR in cells obtained from the floor of the mouth (p = 0.01). Our findings suggest that the use of crack cocaine induces clastogenic effects, whereas alcoholism is associated with higher degrees of keratinization in the floor of the mouth.
17-β-Estradiol Induces Heat Shock Proteins in Brain Arteries and Potentiates Ischemic Heat Shock Protein Induction in Glia and Neurons

Estradiol reduces brain injury from many diseases, including stroke and trauma. To investigate the molecular mechanisms of this protection, the effects of 17-β-estradiol on heat shock protein (HSP) expression were studied in normal male and female rats and in male gerbils after global ischemia. 17-β-Estradiol was given intraperitoneally (46 or 460 ng/kg, or 4.6 μg/kg) and Western blots performed for HSPs. 17-β-Estradiol increased hemeoxygenase-1, HSP25/27, and HSP70 in the brain of male and female rats. Six hours after the administration of 17-β-estradiol, hemeoxygenase-1 increased 3.9-fold (460 ng/kg) and 5.4-fold (4.6 μg/kg), HSP25/27 increased 2.1-fold (4.6 μg/kg), and Hsp70 increased 2.3-fold (460 ng/kg). Immunocytochemistry showed that hemeoxygenase-1, HSP25/27,and HSP70 induction was localized to cerebral arteries in male rats, possibly in vascular smooth muscle cells. 17-β-Estradiol was injected intraperitoneally 20 minutes before transient occlusion of both carotids in adult gerbils. Six hours after global cerebral ischemia, 17-β-estradiol (460 ng/kg) increased levels of hemeoxygenase-1 protein 2.4-fold compared with ischemia alone, and HSP25/27 levels increased 1.8-fold compared with ischemia alone. Hemeoxygenase-1 was induced in striatal oligodendrocytes and hippocampal neurons, and HSP25/27 levels increased in striatal astrocytes and hippocampal neurons. Finally, Western blot analysis confirmed that estrogen induced heat shock factor-1, providing a possible mechanism by which estrogen induces HSPs in brain and other tissues. The induction of HSPs may be an important mechanism for estrogen protection against cerebral ischemia and other types of injury.
Inducible immune factors of the vector mosquito Anopheles gambiae: biochemical purification of a defensin antibacterial peptide and molecular cloning of preprodefensin cDNA

Larvae of the mosquito vector of human malaria, Anopheles gambiae, were inoculated wlth bacteria and extracts were biochemically fractionated by reverse‐phase HPLC. Multiple induced polypeptides and antibacterial activities were observed following bacterial infection, including a member of the Insect defensin family of antibacterial proteins. A cDNA encoding An. gambiae preprodefensin was isolated using PCR primers based on phyiogeneticaiiy conserved sequences. The mature peptide is highly conserved, but the signal and propeptide segments are not, relative to corresponding defensin sequences of other insects. Defensin expression is Induced in response to bacterial infection, in both adult and larval stages. in contrast, pupae express defensin mRNA constitutively. Defensin expression may prove a valuable molecular marker to monitor the An. gambiae host response to infection by parasitic protozoa of medical importance.
Stressors, Academic Performance, and Learned Resourcefulness in Baccalaureate Nursing Students

High stress levels in nursing students may affect memory, concentration, and problem-solving ability, and may lead to decreased learning, coping, academic performance, and retention. College students with higher levels of learned resourcefulness develop greater self-confidence, motivation, and academic persistence, and are less likely to become anxious, depressed, and frustrated, but no studies specifically involve nursing students. This explanatory correlational study used Gadzella’s Student-life Stress Inventory (SSI) and Rosenbaum’s Self Control Scale (SCS) to explore learned resourcefulness, stressors, and academic performance in 53 baccalaureate nursing students. High levels of personal and academic stressors were evident, but not significant predictors of academic performance (p = .90). Age was a significant predictor of academic performance (p = < .01) and males and African-American/Black participants had higher learned resourcefulness scores than females and Caucasians. Studies in larger, more diverse samples are necessary to validate these findings.
Effect of a Polycyclic Aromatic Hydrocarbon on the Phytoremediation of Zinc by Two Plant Species (Brassica Juncea and Festuca Arundinacea)

The redevelopment of contaminated land is becoming increasingly necessary under sustainable-development legislation; however, many of the contaminated sites are “orphan” sites and therefore require a low-cost remediation technology. These sites often contain a cocktail of pollutants including organics and inorganics. Phytoremediation provides a possible solution, but there is little information available on the tolerance of plant species to multiple pollutants and their ability to remediate in mixed-contaminant soils. The effect of a polycyclic aromatic hydrocarbon (pyrene) in soil upon the remediation of zinc by Brassica juncea and Festuca arundinacea was investigated under normal climatic conditions in the United Kingdom. Zinc was effectively removed from mixed-contaminant soils in the presence of both species, in comparison to a control treatment. Both species accumulated zinc in plant tissues in the presence of pyrene, but the growth of B. juncea was significantly reduced when zinc and pyrene were supplied in combination. Zinc was predominantly associated with root tissues for F. arundinacea, whereas B. juncea contained higher concentrations in shoot tissues. F. arundinacea provides a possible species to be used for the phytoremediation of brownfield sites, but further research is required to determine a range of species that may be used and their applicability to different contaminants.
The Use of Exploratory Factor Analysis in Public Health: A Note on Parallel Analysis as a Factor Retention Criterion

Purpose. Exploratory factor analysis is used to identify latent factors for public health interventions. The most popular factor retention criterion, the eigenvalue greater than one (EVG1) rule, leads to the retention of more factors than warranted. The use of parallel analysis (PA) as a factor retention criterion is recommended. Design. Environmental factors that are likely to affect the propensity of individuals to walk are identified. Results from PA are compared with those obtained by using the EVG1 rule. Setting. Telephone survey data were collected from three communities (spanning 12 counties) in the Appalachian region. Participants. The sample was composed of adults between the ages of 40 and 65 years. There were 1019 completed surveys. Measures. The data on 14 variables, including measures of neighborhood safety, beauty, and access to walking facilities were collected. Analysis. A principal components analysis was performed. The factors retained after using the EVG1 rule were compared with the factors retained after using PA. Varimax rotation was used to aid factor interpretation. Results. The EVG1 rule led to the retention of nearly twice the number of latent factors as did the PA criterion. Conclusion. The use of the EVG1 rule in research may mislead policy makers to focus on trivial interventions. They are urged to use PA to obtain more parsimonious and externally valid interventions.