Miracle-dz/UniFAR-FTUs huggingface dataset:
Naloxone excites oxytocin neurones in the supraoptic nucleus of lactating rats after chronic morphine treatment.

1. Lactating rats were implanted with a cannula in a lateral cerebral ventricle to deliver morphine (up to 50 micrograms/h) chronically from a subcutaneous osmotically driven mini‐pump. After infusion of morphine for 5 days the rats were anaesthetized with urethane and prepared with ventral surgery for recording the electrical activity of single, antidromically identified neurones in the supraoptic nucleus. 2. A single I.V. injection of naloxone (5 mg/kg) in these rats provoked a long‐lasting, large increase in intramammary pressure, but in control rats had negligible effects. Concentrations in plasma of oxytocin, measured by radioimmunoassay in samples of femoral arterial blood, rose from 44.7 +/‐ 2.5 to 1072.1 +/‐ 89.5 pg/ml (means +/‐ S.E.M.) 6 min after naloxone in the morphine‐treated rats. In control rats, the concentration of oxytocin in plasma rose only from 42.1 +/‐ 2.9 to 125.1 +/‐ 28.2 pg/ml after naloxone. 3. Naloxone produced a transient increase in arterial blood pressure in morphine‐treated but not control rats. Concentrations in plasma of vasopressin, measured by radioimmunoassay in samples of femoral arterial blood, rose in morphine‐treated rats from 7.4 +/‐ 2.4 to 29.2 +/‐ 3.7 pg/ml after naloxone, but did not rise significantly in control rats. 4. Naloxone (1‐5 mg/kg) produced a prompt and prolonged increase in the discharge rate of each of ten continuously active (putative oxytocin) cells recorded from ten morphine‐treated rats. The discharge rate of the six cells tested at the highest dose (5 mg/kg) increased by an average of 6.3 Hz (360%) within 5 min, and the firing rate remained elevated for at least 30 min; the discharge rate of six continuously active supraoptic neurones recorded in control rats was not affected by naloxone. 5. The firing activity of five phasic (putative vasopressin) supraoptic neurones in morphine‐treated rats was increased for at least 30 min by the injection of naloxone; these increases were the result of a raised intraburst firing rate with no change in burst duration or frequency. One phasic neurone was inhibited for 15 min, and one phasic neurone was unaffected. 6. The excitatory effects of naloxone on neurones in the supraoptic nucleus of morphine‐treated rats were not explained by changes in blood pressure or osmolarity and did not depend on suckling or a cholinergic pathway. 7. The concentrations of oxytocin in plasma and the operation of the milk‐ejection reflex were similar in the controls and morphine‐treated rats, prior to naloxone. These findings indicate tolerance to initial inhibitory effects of morphine on oxytocin secretion. (ABSTRACT TRUNCATED AT 400 WORDS)
Attainment of optional low-density lipoprotein cholesterol goal of less than 70 mg/dl and impact on prognosis of very high risk stable coronary patients: a 3-year follow-up

Objectives: We aimed to investigate the proportion of very high-risk patients with coronary heart disease (CHD) who achieve the optional low-density lipoprotein cholesterol (LDL-C) target of < 70 mg/dl (1.8 mmol/liter), the factors that influence the success rate and the impact on their prognosis. Research design and methods: We enrolled 1337 consecutive patients with stable CHD. Fasting lipids were determined and all cardiovascular events were recorded during a median follow-up of 33 months. Results: The majority (86.5%) of patients were taking lipid-lowering medication (95.5% statins), but only 50.6% had LDL-C levels of < 100 mg/dl (2.6 mmol/liter). In total, 941 (70.4%) patients were considered very high risk and only 15.1% of them had LDL-C levels of < 70 mg/dl. Τhe use of intensive lipid-lowering medication was associated with 12-fold (95% CI 6.98 – 20.76; p < 0.001) higher possibility in achieving LDL-C levels of < 70 mg/dl. Attainment of LDL-C levels of < 70 mg/dl by patients at very high risk were independent predictors of all cardiovascular events (HR = 0.34, 95% CI 0.17 – 0.70; p = 0.003). Conclusions: The vast majority of very high-risk patients do not achieve the optional LDL-C goal; this is mainly due to the suboptimal uptitration of statin dose and is translated into loss of clinical benefits.
The Holocene temperature conundrum

Significance Marine and terrestrial proxy records suggest global cooling during the Late Holocene, following the peak warming of the Holocene Thermal Maximum (∼10 to 6 ka) until the rapid warming induced by increasing anthropogenic greenhouses gases. However, the physical mechanism responsible for this global cooling has remained elusive. Here, we show that climate models simulate a robust global annual mean warming in the Holocene, mainly in response to rising CO2 and the retreat of ice sheets. This model-data inconsistency demands a critical reexamination of both proxy data and models. A recent temperature reconstruction of global annual temperature shows Early Holocene warmth followed by a cooling trend through the Middle to Late Holocene [Marcott SA, et al., 2013, Science 339(6124):1198–1201]. This global cooling is puzzling because it is opposite from the expected and simulated global warming trend due to the retreating ice sheets and rising atmospheric greenhouse gases. Our critical reexamination of this contradiction between the reconstructed cooling and the simulated warming points to potentially significant biases in both the seasonality of the proxy reconstruction and the climate sensitivity of current climate models.
The relation between objective and subjective exposure to traffic noise around two suburban highway viaducts in Ghent: lessons for urban environmental policy

ABSTRACT A growing empirical evidence base identifies environmental noise exposure as an important health problem. While the health effects depend for a great part on personal noise sensitivity and contextual factors, in environmental policy, generic noise standards and procedures based on objective sound levels are used. In this article, the relation between objective and subjective noise exposure variables is further explored by carrying out a residents’ survey in a highly noise polluted area along two highways south of the city centre of Ghent, Belgium. The survey results show only a weak correlation between objective and subjective exposure variables, with both variables demonstrating different associations with the respondents’ background characteristics. While lower-educated and lower-income people are generally higher exposed according to the models, they do not report a higher subjective exposure. People who have been living longer in the area are not necessarily higher exposed according to the models but do report a higher subjective exposure. Most strikingly, owners of a comfortable detached house report a higher subjective exposure than renters of an apartment or small house, while the latter group is significantly higher exposed according to the models. The results support a plea for the joint evaluation of both objective and subjective noise exposure variables in environmental policy and environmental assessments. In addition, the results argue for specific attention for noise exposure of socio-economically vulnerable people and the establishment of a shared knowledge base on noise exposure with both objective and subjective information.
Damage, Reorganization, and Abnormal Neocortical Hyperexcitability in the Pilocarpine Model of Temporal Lobe Epilepsy

Summary: Purpose: Clinical, neuropathological, and electrophysiological data have shown that limbic structures are involved in the pathogenesis of temporal lobe epilepsy (TLE). In most cases, limbic‐originated seizures frequently spread to extrahippocampal areas. It is unclear whether such distant circuitries, especially the neocortex, exhibit abnormal electrophysiology as consequences of a chronic epileptogenic process. The present research studied neuropathological abnormalities and in vitro electrophysiological properties of sensorimotor neocortex in pilocarpine‐treated epileptic rats.
Bacteriological agents of neonatal sepsis in NICU at Nishtar Hospital Multan.

OBJECTIVE To find clinical features and bacteriological agents of neonatal sepsis and to determine their antibiotic sensitivity pattern. DESIGN An observational study. PLACE AND DURATION OF STUDY Paediatric Medicine Unit II, Nishtar Hospital, Multan, from July 2003 to January 2004. PATIENTS AND METHODS Neonates admitted with, or clinically suspected to develop neonatal sepsis during their hospital stay, for another reason, were included in this study. Common clinical features were noted and blood culture reports were analyzed for etiological microorganisms and their antibiotic sensitivity pattern. RESULTS Among the total 115 cases of clinically suspected neonatal sepsis, 62 (54%) had culture proven sepsis. Out of these 26(42%) presented as early onset sepsis and 36(58%) as late-onset sepsis. Among the bacteriological isolates, gram negative organisms (58%) were slightly more common in both early-onset and late-onset sepsis. Among the Gram-negative isolates E.coli (37%) was the commonest organism followed by Klebsiella (9.6%). Among the gram +ve organisms Staphylococcus aureus (32%) was most frequent. All the microorganisms were resistant to ampicillin. E.coli were mostly sensitive to ceftriaxone(75%), ceftazidime (78%), meropenem (88%), imipenem (80%), and ciprofloxacin (52%). Staphylococcus aureus were more sensitive to ciprofloxacin (85%), meropenem (87%), imipenem (82%) as compared to cephalosporins and aminoglycosides. CONCLUSION E.coli and Staph. aureus are the most common organisms causing neonatal sepsis and there is high degree of resistance to commonly used first line antibiotics.
Joint Audit Engagements and Client Tax Avoidance: Evidence from the Italian Statutory Audit Regime

Under the Italian statutory audit regime, three individual accountants are jointly appointed to audit each client's annual financial statements and sign off on the tax return. These individuals can belong to the same or different accounting firms and through multiple and repeated collaborations they form a professional network. We use network measures of centrality to capture individuals' ability to acquire and apply tax expertise across clients. We demonstrate that clients engaging better-connected individual auditors have comparatively lower effective tax rates. Our results are robust to controlling for a number of client, individual, and accounting firm characteristics, as well as for alternative network connections between clients. We also use instrumental variables, individual fixed effects, and matching to mitigate the effect of endogenous pairing of clients and auditors. Our findings demonstrate that in a joint audit environment, individual auditor professional networks have consequences for tax outcomes. Data Availability: Data are obtainable from the public sources cited in the text and are available upon request.
A Rank-Size Rule Analysis of The City System at The Country and Province Level in Turkey

The present study investigates the rank-size distribution of cities above 10,000 in Turkey for the years 2000 and 2012, and the results are compared with the findings related to 1945 and 1975. The results show that despite the political and economic transformations of the last decade, there is a perfect adjustment of the city size distribution to the rank-size rule at the country level due to existence of a well-established urban system. A regression analysis is employed to reveal the relationships between the slopes of city size distribution and the characteristics of provinces.
Alterations in tyrosine protein phosphorylation induced by antibody-mediated cross-linking of the CD4 receptor of T lymphocytes

Accumulating data suggest that the CD4 T-cell surface antigen transduces an independent intracellular signal during antigen-mediated T-cell activation. CD4 is physically associated with the internal membrane tyrosine protein kinase p56lck and can mediate, after antibody-mediated cross-linking, the rapid enzymatic activation of Lck, implying that CD4 signalling may involve changes in tyrosine protein phosphorylation. In this report, we describe that cross-linking of CD4 results in a series of rapid changes in intracellular tyrosine protein phosphorylation. The most prominent CD4-induced tyrosine phosphorylation change involved p56lck, which became extensively phosphorylated on the carboxy-terminal tyrosine residue 505 and, to a lesser extent, lymphocytes can transduce an intracellular signal resulting in tyrosine protein phosphorylation and strongly suggest that this property of CD4 is mediated through p56lck.
Intraischemic mild hypothermia prevents neuronal cell death and tissue loss after neonatal cerebral hypoxia–ischemia

The effectiveness of hypothermia in preventing ischemic brain damage depends on when it is started. The purpose of this study was to investigate the effects of temperature reduction during a hypoxic–ischemic (HI) insult on brain injury and signalling pathways of neuronal cell death and survival. Seven‐day‐old mice were subjected to left common carotid artery ligation and hypoxia (10% oxygen) at different temperatures (37, 36 or 34 °C) for 50 min. Brain injury at 7 days post‐HI was significantly reduced from 67.4% at 37 °C to 31.6% at 36 °C and 10% at 34 °C, with no observable injury in the cortex of the 34 °C group. Cytochrome c release, caspase‐3 activation and apoptosis‐inducing factor translocation from mitochondria to nuclei were all significantly inhibited after intraischemic temperature reduction. Concurrently, the cell survival signalling pathway involving Akt was significantly sustained (the phosphorylated form of Akt was maintained) when the hypoxia temperature was decreased. These results indicate that intraischemic hypothermia diminished apoptosis through inhibition of both caspase‐dependent and caspase‐independent neuronal cell death pathways and promoted cell survival by inhibition of phosphorylated Akt dephosphorylation in the neonatal brain, thereby preventing neuronal cell death.
Unrequited: Asymmetry in interorganizational trust

Many studies of interorganizational relationships assume that trust between organizations is symmetric. In this essay, we explore the origins of this assumption and examine relevant quantitative and qualitative evidence from the literatures on strategy, marketing, supply chain management, and information systems. We conclude that no systematic evidence currently exists to support the assumption that interorganizational trust is typically symmetric. We explore how the possibility of asymmetry complicates interpretation of previous research on the effects of interorganizational trust. We encourage further research to identify conditions under which symmetry is likely, and offer a variety of strategies that scholars may use to deal with potential asymmetry.
Fatty acid transport protein 1 regulates retinoid metabolism and photoreceptor development in mouse retina

In retinal pigment epithelium (RPE), RPE65 catalyzes the isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol in the visual cycle and controls the rhodopsin regeneration rate. However, the mechanisms by which these processes are regulated are still unclear. Fatty Acid Transport Protein 1 (FATP1) is involved in fatty acid uptake and lipid metabolism in a variety of cell types. FATP1 co-localizes with RPE65 in RPE and inhibits its isomerase activity in vitro. Here, we further investigated the role of FATP1 in the visual cycle using transgenic mice that overexpress human FATP1 specifically in the RPE (hFATP1TG mice). The mice displayed no delay in the kinetics of regeneration of the visual chromophore 11-cis-retinal after photobleaching and had no defects in light sensitivity. However, the total retinoid content was higher in the hFATP1TG mice than in wild type mice, and the transgenic mice also displayed an age-related accumulation (up to 40%) of all-trans-retinal and retinyl esters that was not observed in control mice. Consistent with these results, hFATP1TG mice were more susceptible to light-induced photoreceptor degeneration. hFATP1 overexpression also induced an ~3.5-fold increase in retinosome autofluorescence, as measured by two-photon microscopy. Interestingly, hFATP1TG retina contained ~25% more photoreceptor cells and ~35% longer outer segments than wild type mice, revealing a non-cell-autonomous effect of hFATP1 expressed in the RPE. These data are the first to show that FATP1-mediated fatty acid uptake in the RPE controls both retinoid metabolism in the outer retina and photoreceptor development.
A Phase I/II study of external beam radiation, brachytherapy, and concurrent chemotherapy for patients with localized carcinoma of the esophagus (Radiation Therapy Oncology Group Study 9207)

A multiinstitutional, prospective study of the Radiation Therapy Oncology Group (RTOG) was designed to determine the feasibility and toxicity of chemotherapy, external beam radiation, and esophageal brachytherapy (EB) in a potentially curable group of patients with adenocarcinoma or squamous cell carcinoma of the esophagus. A preliminary analysis indicated a 17% 1‐year actuarial risk of treatment‐related fistulas. A final analysis of this study was considered important to determine the median survival time, local control, and late toxicity associated with this treatment regimen.
One Shot Joint Colocalization and Cosegmentation

This paper presents a novel framework in which image cosegmentation and colocalization are cast into a single optimization problem that integrates information from low level appearance cues with that of high level localization cues in a very weakly supervised manner. In contrast to multi-task learning paradigm that learns similar tasks using a shared representation, the proposed framework leverages two representations at different levels and simultaneously discriminates between foreground and background at the bounding box and superpixel level using discriminative clustering. We show empirically that constraining the two problems at different scales enables the transfer of semantic localization cues to improve cosegmentation output whereas local appearance based segmentation cues help colocalization. The unified framework outperforms strong baseline approaches, of learning the two problems separately, by a large margin on four benchmark datasets. Furthermore, it obtains competitive results compared to the state of the art for cosegmentation on two benchmark datasets and second best result for colocalization on Pascal VOC 2007.
Re-evaluating the Efficacy of Targeted Killing

The purposeful killing of select individuals is a cornerstone of modern counter-terror and insurgency doctrine. The CIA’s drone fleet strikes targets across the globe, while Israeli strikes on Hamas leadership have become so routine as to be compared to “mowing the grass” (Inbar & Shamir, 2014). Despite the ubiquity of targeted killing, the academic community is divided as to its effectiveness. This article seeks to demonstrate that, as the literature on targeted killing has matured and become more rigorous, the consensus has shifted from seeing targeted killings as an ineffective or counterproductive measure to viewing them as an effective tool. After reviewing the early arguments against targeted killing, this article assesses these claims in light of more recent research. It explores why and how targeted killings aid security forces and concludes with four policy lessons.
Residues of calcium hydroxide‐based intracanal medication associated with different vehicles: A scanning electron microscopy evaluation

This study evaluated the presence of residues after removal of calcium hydroxide [Ca(OH)2] associated with different vehicles. Thirty single‐rooted teeth were instrumented to a master apical file #25 using 2.5% NaOCl as main irrigant and 17% trisodium EDTA (ethylenediaminetetraacetic acid) as final agent irrigant. Then, the root canals were dressed with Ca(OH)2 associated with silicone oil (Group 1), 2% chlorhexidine gluconate (Group 2), or propylene glycol (Group 3). After coronal sealing, all teeth were kept in a moist environment at room temperature. After 7 days, the teeth were reopened and medicaments were removed using 5 mL of saline solution and instrumentation with master apical file followed by new irrigation with 5 mL of 2.5% NaOCl. Subsequently, teeth were split longitudinally and assessed by scanning electron microscopy. The wall cleanliness of the cervical and apical thirds of the roots were evaluated and scored by three blinded examiners. Statistical analysis was performed using Kruskal–Wallis and Wilcoxon tests at 5% level of significance. All roots had residues of Ca(OH)2 on the canal walls. All experimental groups had similar results (P > 0.05) regardless of the third evaluated. There was significant difference between the apical and cervical thirds only in Group 3 (P < 0.05). Association of different vehicles to Ca(OH)2 does not influence the persistence of residues on the root canal walls. Microsc. Res. Tech. 2012. © 2012 Wiley Periodicals, Inc.
Pentoxifylline does not prevent the cytokine-induced first dose reaction following OKT3--a randomized, double-blind placebo-controlled study.

The use of OKT3 as an immunosuppressive agent is accompanied by increased cytokine production and constellation of side effects collectively termed cytokine release syndrome (CRS). Pentoxifylline (PTF) inhibits synthesis of some cytokines, and has been shown to attenuate CRS when administered before OKT3. In this double-blinded, placebo-controlled study, 46 renal allograft recipients were randomized to receive either PTF (800 mg q 8 hr for at least 24 h) p.o. or placebo, along with methylprednisolone (7 mg/kg), diphenhydramine, and acetaminophen, prior to beginning OKT3 as therapy for acute rejection. Patients were observed, and symptoms scored semiquantitatively. Despite the presence of therapeutic PTF levels (721 +/- 726 ng/ml), the frequency and severity of side effects (fever, chills, headache, neurocortical symptoms, dyspnea, nausea, vomiting, diarrhea) did not differ between treatment groups. Likewise PTF did not affect renal function or immunologic response to OKT3, with similar graft and patient survival in both groups. Plasma levels of TNF alpha, IFN gamma, IL-6, and IL-8 increased as predicted following OKT3 administration, without significant differences between PTF and placebo groups. In this controlled, multicenter trial, pretreatment with oral PTF was ineffective in attenuating OKT3-related CRS in renal allograft recipients.