Miracle-dz/UniFAR-FTUs huggingface dataset:
Signaling of Prostaglandin E Receptors, EP3 and EP4 Facilitates Wound Healing and Lymphangiogenesis with Enhanced Recruitment of M2 Macrophages in Mice

Lymphangiogenesis plays an important role in homeostasis, metabolism, and immunity, and also occurs during wound-healing. Here, we examined the roles of prostaglandin E2 (PGE2) receptor (EP) signaling in enhancement of lymphangiogenesis in wound healing processes. The hole-punch was made in the ears of male C57BL/6 mice using a metal ear punch. Healing process and lymphangiogenesis together with macrophage recruitment were analyzed in EP knockout mice. Lymphangiogenesis was up-regulated in the granulation tissues at the margins of punched-hole wounds in mouse ears, and this increase was accompanied by increased expression levels of COX-2 and microsomal prostaglandin E synthase-1. Administration of celecoxib, a COX-2 inhibitor, suppressed lymphangiogenesis in the granulation tissues and reduced the induction of the pro-lymphangiogenic factors, vascular endothelial growth factor (VEGF) -C and VEGF-D. Topical applications of selective EP receptor agonists enhanced the expressions of lymphatic vessel endothelial hyaluronan receptor-1 and VEGF receptor-3. The wound-healing processes and recruitment of CD11b-positive macrophages, which produced VEGF-C and VEGF-D, were suppressed under COX-2 inhibition. Mice lacking either EP3 or EP4 exhibited reduced wound-healing, lymphangiogenesis and recruitment of M2 macrophages, compared with wild type mice. Proliferation of cultured human lymphatic endothelial cells was not detected under PGE2 stimulation. Lymphangiogenesis and recruitment of M2 macrophages that produced VEGF-C/D were suppressed in mice treated with a COX-2 inhibitor or lacking either EP3 or EP4 during wound healing. COX-2 and EP3/EP4 signaling may be novel targets to control lymphangiogenesis in vivo.
Birth order and child cognitive outcomes: an exploration of the parental time mechanism

ABSTRACT Higher birth order positions are associated with poorer outcomes due to smaller shares of resources received within the household. Using a sample of Panel Study of Income Dynamics-Child Development Supplement children, we investigate if the negative birth order effect we find in cognitive outcomes is due to unequal allocation of mother and father time investments. Exploiting the presence of siblings in the sample, we show that birth order differences in parental time are mostly driven by between-families variation rather than within-family variation. This finding suggests that birth order effects are unlikely to be driven by differences in quality time spent with either parent.
A randomized phase II trial of gemcitabine plus treosulfan versus treosulfan alone in patients with metastatic uveal melanoma.

BACKGROUND Several trials demonstrated efficacy of the gemcitabine/treosulfan (GeT) combination in metastatic uveal melamoma. This randomized phase II trial compared the GeT combination versus treosulfan alone (T) in this rare disease. PATIENTS AND METHODS Chemotherapy-naive patients with proven metastatic uveal melanoma were randomly assigned to receive 1000 mg/m(2) of gemcitabine plus 3500 mg/m(2) of treosulfan (GeT) or 3500 mg/m(2) of T. Chemotherapy was administered on days 1 and 8 in both arms, cycles were repeated on day 29. Primary end point was rate of responses and disease stabilizations. RESULTS Forty-eight patients were randomized. Seven confirmed stable diseases (SDs) and one partial remission (PR) were observed in 24 patients treated with the GeT regimen, whereas no PR and only three SDs were observed in the T arm (P = 0.08). Median progression-free survival (PFS) was 3 months (95% CI 1.1-4.9) and 2 months (95% CI 1.7-2.3) in the GeT and T arm (P = 0.008, log-rank). Six and 12 months PFS was 34.8% and 17.9% and 16.7% and 0% always favoring the GeT arm. CONCLUSIONS This first randomized trial in metastatic uveal melanoma showed a superior PFS and a trend for a higher response/stabilization rate of the GeT combination over T.
Future pharmacological treatments for substance use disorders

Substance use disorders represent a serious public health and social issue worldwide. Recent advances in our understanding of the neurobiological basis of the addictive processes have led to the development of a growing number of pharmacological agents to treat addictions. Despite this progress, there are no approved pharmacological treatments for cocaine, methamphetamine and cannabis addiction. Moving treatment development to the next stage will require novel ways of approaching substance use disorders. One such novel approach is to target individual vulnerabilities, such as cognitive function, sex differences and psychiatric comorbidities. This review provides a summary of promising pharmacotherapies for alcohol, opiate, stimulant and nicotine addictions. Many medications that target positive and negative reinforcement of drugs, as well as individual vulnerabilities to addiction, are in different phases of development. Clinical trials testing the efficacy of these medications for substance use disorder are warranted.
Illness perceptions mediate the relationship between depression and quality of life in patients with epilepsy

The current study examined whether negative illness perceptions help explain the link between depression and quality of life. Seventy patients with epilepsy completed standardized self‐report questionnaires measuring depression, illness perception, and quality of life (QOL). Illness perception statistically mediated the relationship between depression and QOL (Indirect effect (CI; confidence interval) = −. 72, lower limit = −1.7, upper limit = −. 22, p < . 05). Results held with and without adjusting for potential confounding variables (age, sex, ethnicity, income, and seizure frequency) and when operationalizing depression as a continuous variable that indexed severity of symptoms or as a dichotomous variable that indexed criteria consistent with a diagnosis of major depressive disorder. This study is the first to suggest that illness perceptions may be a useful target in screening and intervention approaches in order to improve QOL among low‐income, racially/ethnically diverse patients with epilepsy.
The effect of middle and lower trapezius strength exercises and levator scapulae and upper trapezius stretching exercises in upper crossed syndrome

[Purpose] The purpose of this study was to determine the effectiveness of strength and stretching exercises on upper crossed syndrome. [Subjects and Methods] After measuring cervical alignment using the Global Posture System, 30 students with forward head posture were selected and divided into two groups. The experimental group (n=15) participated in strength and stretching exercises, three times per week for 4 weeks. The control group (n=15) did not participate in the exercises. The exercise program comprised middle and lower trapezius strength exercises and levator scapulae and upper trapezius stretching exercises. The temperature of the posterior neck was then measured using digital infrared thermographic imaging. [Results] There was a significant difference between the pretest and posttest results in the experimental group, and a significant difference in posterior neck temperature between the two groups. [Conclusion] This study showed that middle and lower trapezius strength exercises and levator scapulae and upper trapezius stretching exercises are more effective for upper crossed syndrome.
Unstable Operation of Francis Pump-Turbine at Runaway: Rigid and Elastic Water Column Oscillation Modes

This paper presents a numerical simulation study of the transient behavior of a 2x340MW pump-turbine power plant, where the results show an unstable behavior at runaway. First, the modeling of hydraulic components based on equivalent schemes is presented. Then, the 2 pump-turbine test case is presented. The transient behavior of the power plant is simulated for a case of emergency shutdown with servomotor failure on Unit 1. Unstable operation at runaway with a period of 15 seconds is properly simulated using a 1-dimensional approach. The simulation results points out a switch after 200 seconds of the unstable behavior between a period of oscillations initially of 15 seconds to a period of oscillation of 2.16 seconds corresponding to the hydraulic circuit first natural period. The pressure fluctuations related to both the rigid and elastic water column mode are presented for oscillation mode characterization. This phenomenon is described as a switch between a rigid and an elastic water column oscillation mode. The influence of the rotating inertia on the switch phenomenon is investigated through a parametric study.
Antiviral immunity of Anopheles gambiae is highly compartmentalized, with distinct roles for RNA interference and gut microbiota

Significance It is important to understand antiviral mechanisms in potential new arbovirus vectors, such as Anopheles mosquitoes, in order to assess risks associated with arbovirus spread. Using an arbovirus naturally transmitted by Anopheles, we find that important immune mechanisms involved in the first bottleneck to Anopheles infection, the midgut, have distinct effects on arbovirus or malaria. This result is, to our knowledge, the first concrete evidence of protection tradeoffs for different human pathogens in a human disease vector, and it suggests that design of genetically immune-modified mosquitoes could result in unexpected outcomes. These results also indicate that different mosquito tissues display distinct antiviral protection that probably imposes divergent selection pressures upon viral replication during different stages of the infection. Arboviruses are transmitted by mosquitoes and other arthropods to humans and animals. The risk associated with these viruses is increasing worldwide, including new emergence in Europe and the Americas. Anopheline mosquitoes are vectors of human malaria but are believed to transmit one known arbovirus, o’nyong-nyong virus, whereas Aedes mosquitoes transmit many. Anopheles interactions with viruses have been little studied, and the initial antiviral response in the midgut has not been examined. Here, we determine the antiviral immune pathways of the Anopheles gambiae midgut, the initial site of viral infection after an infective blood meal. We compare them with the responses of the post-midgut systemic compartment, which is the site of the subsequent disseminated viral infection. Normal viral infection of the midgut requires bacterial flora and is inhibited by the activities of immune deficiency (Imd), JAK/STAT, and Leu-rich repeat immune factors. We show that the exogenous siRNA pathway, thought of as the canonical mosquito antiviral pathway, plays no detectable role in antiviral defense in the midgut but only protects later in the systemic compartment. These results alter the prevailing antiviral paradigm by describing distinct protective mechanisms in different body compartments and infection stages. Importantly, the presence of the midgut bacterial flora is required for full viral infectivity to Anopheles, in contrast to malaria infection, where the presence of the midgut bacterial flora is required for protection against infection. Thus, the enteric flora controls a reciprocal protection tradeoff in the vector for resistance to different human pathogens.
Erratum: Locality and inequality: Farm and Industry Structure and Socioeconomic Conditions

John Hagan and Alberto Palloni wish to clarify two equations that appeared in their article, "The Social Reproduction of a Criminal Class in Working-Class London, circa 1950-1980" (AJS 96[2]:265-99). In equation (A2), a superscript "n" should replace the superscript "m"; in equation (A4), " + U" should appear between the closing parenthesis and the closing bracket to the first set of fences. The two equations are thus:
Running economy and distance running performance of highly trained athletes.

The purpose of the study was to determine the relationship between running economy and distance running performance in highly trained and experienced distance runners of comparable ability. Oxygen uptake (Vo2) during steady-state and maximal aerobic power (Vo2max) were measured during treadmill running using the open-circuit method. Distance running performance was determined in a nationally prominent 10 km race; all subjects (12 males) placed among the top 19 finishers. The subjects averaged 32.1 min on the 10 km run, 71.7 ml.kg-1.min-1 for Vo2max, and 44.7, 50.3, and 55.9 ml.kg-1.min-1 for steady-state Vo2 at three running paces (241, 268, and 295 m.min-1). The relationship between Vo2max and distance running performance was r = -0.12 (p = 0.35). The relationship between steady-state Vo2 at 241, 268 and 295 m.min-1 and 10 km time were r = 0.83, 0.82, and 0.79 (p < 0.01), respectively. Within this elite cluster of finishers, 65.4% of the variation observed in race performance time on the 10 km run could be explained by variation in running economy. It was concluded that among highly trained and experienced runners of comparable ability and similar Vo2max, running economy accounts for a large and significant amount of the variation observed in performance on a 10 km race.
Observations of H α emission profiles in Aditya tokamak

Emissions from the hydrogen Balmer alpha (λ = 656.28 nm) has been recorded for a large number of plasma discharges in the Aditya tokamak using a 1m Czerny-Turner spectrometer equipped with an 1800 grooves/mm reflection grating [5]. Eight simultaneous vertically collimated line-of-sights, using individual lens – fiber combination from a top port of the tokamak view a poloidal cross-section of the plasma. The line-of-sights can be moved along the major radius to obtain emissions from different major-radial positions on a shot–to–shot basis. Abel-like matrix inversion has been performed to obtain radial profile of volume emissivities from these chord-integrated intensities. Considerable Hα emission is observed in the bulk plasma indicating a considerable neutral penetration. Further, a second peak in the Hα radial profile has been observed at ρ(r/a) ~ +/0.3 -+/0.5 in majority of discharges irrespective of the plasma column position. This observation suggests a considerable accumulation of neutrals in the region of ρ(r/a) ~ +/0.3 -+/0.5. CV to CIII line ratio variations at the same location also suggest a substantial presence of neutrals explained by the charge-exchange, involving collisions between H-like carbon ions and neutral hydrogen atoms.
Advanced Modes of Mechanical Ventilation: Introduction for the Critical Care Pharmacist

Mechanical ventilation continues to be an evolving modality in the critical care environment. Technological advances in microprocessor-controlled ventilation integrated with the complexity of new ventilator modes has provided the multidisciplinary team opportunities to further improve the care of the critically ill ventilator patients. As members of the critical care multidisciplinary team, pharmacists require a basic understanding of both conventional and advanced modes of mechanical ventilation in order to assist in optimizing medication use and ultimately patient health-care outcomes. Pharmacists have a key responsibility to practice vigilance to maintain safe drug therapy use by preventing drug–drug or drug–disease interactions and optimal dose selection based upon pharmacokinetics and pharmacodynamics principles. Pharmacists also assist in the development of drug utilization guidelines and pharmacological ventilator-weaning protocols based upon evidence-based practice. The result of these responsibilities must include the continued longitudinal assessment and reporting of quality measures to assess ventilator weaning, time to liberation of mechanical ventilation, and length of care in intensive care unit. The purpose of this article is to provide the clinical pharmacist a guide to a basic understanding of advanced modes of mechanical ventilation in adults and to apply the knowledge gained to assist in the care of the critical care patients.
Costimulation of Naive CD8+ Lymphocytes Induces CD4 Expression and Allows Human Immunodeficiency Virus Type 1 Infection

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection requires cell surface expression of CD4. Costimulation of CD8+/CD4− T lymphocytes by anti-CD3 and anti-CD28 antibodies or by allogeneic dendritic cells induced expression of CD4 and rendered these CD8 cells susceptible to HIV-1 infection. Naive CD45RA+ cells responded with greater expression of CD4 than did CD45RO+ cells. CD8+lymphocytes derived from fetal or newborn sources exhibited a greater tendency to express CD4, consistent with their naive states. This mechanism of infection suggests HIV-induced perturbation of the CD8 arm of the immune response and could explain the generally rapid disease progression seen in HIV-infected children.
Formalization of real analysis: a survey of proof assistants and libraries †

In the recent years, numerous proof systems have improved enough to be used for formally verifying non-trivial mathematical results. They, however, have different purposes and it is not always easy to choose which one is adapted to undertake a formalization effort. In this survey, we focus on properties related to real analysis: real numbers, arithmetic operators, limits, differentiability, integrability and so on. We have chosen to look into the formalizations provided in standard by the following systems: Coq, HOL4, HOL Light, Isabelle/HOL, Mizar, ProofPower-HOL, and PVS. We have also accounted for large developments that play a similar role or extend standard libraries: ACL2(r) for ACL2, C-CoRN/MathClasses for Coq, and the NASA PVS library. This survey presents how real numbers have been defined in these various provers and how the notions of real analysis described above have been formalized. We also look at the methods of automation these systems provide for real analysis.
Resilient First-Generation College Students: A Multiple Regression Analysis Examining the Impact of Optimism, Academic Self-Efficacy, Social Support, Religiousness, and Spirituality on Perceived Resilience

First-generation college students (FGCS) have been identified as an at-risk population as evidenced by higher attrition rates, lower socio-economic backgrounds, and are less engaged in the college environment when compared to their college peers. Yet despite these stressors, many will graduate college demonstrating their resilience. This study examined optimism, academic self-efficacy, social support, religiousness, and spirituality as potential protective factors for FGCS who perceive themselves to be resilient. Two-way effects were examiined in order to determine if any two-way combination of the five protective factors explored in this study explained more of the variance in perceived resilience of FGCS. Demographic varaibles were also taken into consideration. The study surveyed 249 FGCS from a small rural state university. The regression model revealed a significant positive relationship between the protective factors of academic self-efficacy, social support, and optimism on perceived resilience. FGCS who indicated having more social support, believed themselves to be optimistic and academically self-efficacious, also perceived themselves to be highly resilient. Furthermore, male FGCS reported higher perceived resiliency scores when compared to female FGCS. The implications, limitations, and the future direction of the research were discussed.
The Sensitivity Of 173 Sydney Isolates Of Neisseria Gonorrhoeae To Cefpodoxime And Other Antibiotics Used To Treat Gonorrhea

&NA; One hundred and thirty seven consecutive isolates of Neisseria gonorrhoeae and a further 36 selected gonococci with either chromosomal (CMRNG) or plasmid mediated (PPNG) resistance to penicillin, all cultured in Sydney in 1993, were found to be sensitive to cefpodoxime, an oral third generation cephalosporin antibiotic (MIC range < 0.001–0.25 mg/L). All isolates were also sensitive to ceftriaxone and spectinomycin. Six gonococci showed high level resistance to tetracycline (TRNG, MIC = 32 mg/L) and 12 had decreased susceptibility to quinolone antibiotics (MIC range 0.06–0.5 mg/L). The MIC50 and MIC90 for both cefpodoxime and ceftriaxone were highest amongst CMRNG and ceftriaxone was 2 to 4 times as active as cefpodoxime weight for weight. Cefpodoxime may be a valuable additional oral agent for the treatment of gonorrhea in Australia. The sensitivity of gonococci to cefpodoxime can probably be inferred from values obtained for ceftriaxone.
Involvement of protein kinase CK2 in angiogenesis and retinal neovascularization.

PURPOSE The purpose of the study was to characterize signaling intermediates involved in angiogenic responses of retinal endothelial cells (RECs) to the extracellular matrix and growth factors, by using specific inhibitors. METHODS Tubelike structure formation and the development of secondary sprouts on a basement membrane (BM) matrix, cell proliferation, and cell migration were studied in cultures of bovine and human RECs. Specific inhibitors were tested for inhibition of retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). RESULTS In initial experiments, the broad-spectrum protein kinase inhibitors, H7 and H89, stabilized REC tubes on BM matrix and inhibited secondary sprouting, cell migration, and cell proliferation. Among more specific kinase inhibitors tested, only inhibitors of protein kinase CK2 (formerly, casein kinase II), such as emodin and DRB, were able to duplicate the effects of H7 and H89. Actinomycin D caused only minor changes in angiogenic assays, suggesting that CK2's effects on REC did not involve its known impact on transcription. The extent of retinal neovascularization in a mouse OIR model was reduced >70% (versus untreated or vehicle-treated groups) after treatment with emodin (6 days at 60 mg/kg per day) and by approximately 60% after treatment at the same dose with TBB, the most specific CK2 inhibitor known. In the treated retinas, the main vascular tree had minimal changes, but the neovascular tufts were greatly reduced in number or absent. CONCLUSIONS This is the first demonstration of the involvement of ubiquitous protein kinase CK2 in angiogenesis. Naturally derived CK2 inhibitors may be useful for treatment of proliferative retinopathies.
‘Circling the wagons’ and community formation: interpreting circular villages in the archaeological record

Abstract In some respects, the circular village layout might appear to be the ultimate expression of an egalitarian and highly integrated communal society, one in which individual needs are clearly subsumed to the needs of the community as a whole. Cross-cultural studies in Amazonia and the eastern United States, however, suggest that this form of village organization may not be tied so closely to internal social organization as to regional context. The circular village layout may have been important in creating an uneasy but workable group identity vis-à-vis outsiders within a specific social context: that of regional demographic change, social uncertainty and violent inter-village conflict. Recent research in central New Mexico indicates that this regional context may also have been an important factor behind the construction of the little-known circular pueblo at Gran Quivira, Salinas Pueblo Missions National Monument.