Miracle-dz/UniFAR-FTUs huggingface dataset:
Orexin Neurons Respond Differentially to Auditory Cues Associated with Appetitive versus Aversive Outcomes

Orexin (Orx) neurons are known to be involved in the promotion and maintenance of waking because they discharge in association with cortical activation and muscle tone during waking and because, in their absence, waking with muscle tone cannot be maintained and narcolepsy with cataplexy ensues. Whether Orx neurons discharge during waking in association with particular conditions, notably with appetitive versus aversive stimuli or positive versus negative emotions, is debated and considered important in understanding their role in supporting particular waking behaviors. Here, we used the technique of juxtacellular recording and labeling in head-fixed rats to characterize the discharge of Orx neurons during the performance of an associative discrimination task with auditory cues for appetitive versus aversive outcomes. Of 57 active, recorded, and neurobiotin-labeled neurons in the lateral hypothalamus, 11 were immunohistochemically identified as Orx-positive (Orx+), whereas none were identified as melanin-concentrating hormone-positive. Orx+ neurons discharged at significantly higher rates during the tone associated with sucrose than during the tone associated with quinine delivered upon licking. They also discharged at high rates after the tone associated with sucrose. Across periods and outcomes, their discharge was positively correlated with EEG gamma activity and EMG activity, which is indicative of cortical activation and behavioral arousal. These results suggest that Orx neurons discharge in a manner characteristic of reward neurons yet also characteristic of arousal neurons. Accordingly, the Orx neurons may respond to and participate in reward processes while modulating cortical activity and muscle tone to promote and maintain arousal along with learned adaptive behavioral responses. SIGNIFICANCE STATEMENT Orexin neurons play a critical role in promoting and maintaining a waking state because, in their absence, narcolepsy with cataplexy ensues. Known to discharge during waking and not during sleep, they have also been proposed to be selectively active during appetitive behaviors. Here, we recorded and labeled neurons in rats to determine the discharge of immunohistochemically identified orexin neurons during performance of an associative discrimination task. Orexin neurons responded differentially to auditory cues associated with appetitive sucrose versus aversive quinine, indicating that they behave like reward neurons. However, correlated discharge with cortical and muscle activity indicates that they also behave like arousal neurons and can thus promote cortical activation with behavioral arousal and muscle tone during adaptive waking behaviors.
An empirical analysis of market efficiency

The objective of electricity restructuring is to produce reliable electricity efficiently. Even though a perfectly competitive market is the objective of restructuring, there is no such perfect market in practice. Many issues can contribute to market inefficiency, such as market design flaws, market power, and inherent engineering features of power system operations. This paper focuses on the effects of engineering features on market efficiency. Models are developed to estimate the competitive benchmark with transmission constraints and how transmission and operational constraints affect market prices based on the submitted bids of market participants. The models are applied to the Electric Reliability Council of Texas (ERCOT) market, which is now undertaking a market redesign rulemaking process. Evaluation of the performance of its current market is helpful for this policy process.
Identification of Phosphatin, a Drug Alleviating Phosphate Starvation Responses in Arabidopsis1[C][W][OPEN]

A family of drugs reduces the growth response, the lipid modifications, and the pattern of gene expression triggered by inorganic phosphate starvation. Inorganic phosphate (Pi) is present in most soils at suboptimal concentrations, strongly limiting plant development. Plants have the ability to sense and adapt to the surrounding ionic environment, and several genes involved in the response to Pi starvation have been identified. However, a global understanding of the regulatory mechanisms involved in this process is still elusive. Here, we have initiated a chemical genetics approach and isolated compounds that inhibit the response to Pi starvation in Arabidopsis (Arabidopsis thaliana). Molecules were screened for their ability to inhibit the expression of a Pi starvation marker gene (the high-affinity Pi transporter PHT1;4). A drug family named Phosphatin (PTN; Pi starvation inhibitor), whose members act as partial suppressors of Pi starvation responses, was thus identified. PTN addition also reduced various traits of Pi starvation, such as phospholipid/glycolipid conversion, and the accumulation of starch and anthocyanins. A transcriptomic assay revealed a broad impact of PTN on the expression of many genes regulated by low Pi availability. Despite the reduced amount of Pi transporters and resulting reduced Pi uptake capacity, no reduction of Pi content was observed. In addition, PTN improved plant growth; this reveals that the developmental restrictions induced by Pi starvation are not a consequence of metabolic limitation but a result of genetic regulation. This highlights the existence of signal transduction pathway(s) that limit plant development under the Pi starvation condition.
Combining goal-directed, reactive and reflexive navigation in autonomous mobile robots

This paper describes a simple fuzzy navigation system for autonomous mobile robots. The navigation system achieves three different behaviours: obstacle-free navigation, reactive obstacle-avoidance, and a reflex; the executive monitors sensory inputs and activates the appropriate behavioural rules of navigation. The obstacle-free navigation rules drive the mobile robot on straight-line path segments, generated by a visibility graph planner in a polygonal world. The obstacle-avoidance rules navigate the robot away from unmapped obstacles, while keeping the attraction of the (sub)goal. The reflex performs an overriding emergency brake when the robot is confronted by sudden obstacles appearing at a close range. The system was tested on a realistic (kinematic and dynamic) simulation of a mobile robot base. The navigation system exhibited 'intelligent' human-like behaviour.
Ribonucleotide reductase subunits M2 and p53R2 are potential biomarkers for metastasis of colon cancer.

BACKGROUND Ribonucleoside diphosphate reductase plays a key role in converting ribonucleoside diphosphate to 2'-deoxyribonucleoside diphosphate, which is necessary for DNA repair and replication. To determine if human ribonucleotide reductase small subunit M2 (hRRM2) and p53-dependent human ribonucleotide reductase small subunit R2 (p53R2) play roles on invasion ability of cancer cells, the gene transferring technique was used to construct stable hRRM2 and p53R2 overexpression transfectants. Increase of hRRM2 dramatically enhanced the cell migration in KB and PC-3 cells, but p53R2 overexpression reduced cellular invasion potential to 50% and 40% in KB and PC-3 cells, respectively. Furthermore, hRRM2 enhanced cancer cells to induce the cell migration of Human Umbilical Vein Endothelial Cells, but p53R2 reduced this ability in transfectants. PATIENTS AND METHODS To further determine the role of human ribonucleotide reductase subunits on cancer metastasis, a tissue array, including 59 primary and 49 metastatic colon adenocarcinoma samples, was used. Immunohistochemistry was used to evaluate the relationship between human ribonucleotide reductase subunits and metastasis. RESULTS Univariate and multivariate analysis revealed that p53R2 is negatively related to the metastasis of colon adenocarcinoma samples (odds ratio, 0.23; P < 0.05); hRRM2 increases the risk of metastasis in colon cancer, but did not show significantly. Thus, opposing regulation of hRRM2 and p53R2 in invasion potential might play a critical role in determining the invasion and metastasis phenotype in cancer cells. CONCLUSION The expression level of ribonucleotide reductase small subunits could serve as biomarkers to predict the malignancy potential of human cancers in the future.
Delirium risk factors in elderly hospitalized patients

OBJECTIVE: Delirium is frequent in elderly hospitalized patients. Many studies have examined its risk factors, but results have been quite variable. Thus, the goal of this study is to identify through systematic literature review the risk factors associated with the development of delirium in hospitalized geriatric patients.MEASUREMENTS AND MAIN RESULTS: First, MEDLINE/CURRENT contents databases were screened for relevant articles published from 1966 to December 1995, and from bibliographies of identified articles additional reports were selected. Second, the reports were screened by two different investigators and retained only if meeting the five following criteria: (1) original research in French or English; (2) prospective study; (3) patients over age 50; (4) minimum of one risk factor examined; (5) acceptable definition of delirium. Third, the methodology of each study was graded according to specific criteria for risk factor studies. Fourth, risk factors were identified and tabulated, unadjusted odds ratios (ORs) were computed, and where appropriate a combined OR with the Mantel-Haenszel estimator was calculated. Twenty-seven articles were retained meeting all of the above criteria. Among these studies, 11 were done on medical patients, 9 on surgical patients, 2 on medical and surgical patients, and 5 on psychiatric patients. In total 1,365 subjects with delirium were studied. Sixty-one different risk factors were examined, the five most common being dementia, medication, medical illness, age, and male gender. Mantel-Haenszel estimator was calculated for 10 risk factors, the most strongly associated being dementia (OR 5.2; 95% confidence interval [CI] 4.2, 6.3), medical illness (OR 3.8; 95% CI 2.2, 6.4), alcohol abuse (OR 3.3; 95% CI 1.9, 5.5), and depression (OR 1.9; 95% CI 1.3, 2.6). Methodologic weaknesses were present in many studies.CONCLUSIONS: Despite methodologic limitations, certain risk factors for delirium seem to be consistent and could help identify high-risk patients. These risk factors include dementia, advanced age, and medical illness. Other risk factors appear to play a contributory role in the development of delirium in elderly hospitalized patients.
Harsh parent–child conflict is associated with decreased anti-inflammatory gene expression and increased symptom severity in children with asthma

Abstract Asthma is a chronic respiratory disorder that affects over 7 million children in the United States. Evidence indicates that family stressors are associated with worsening of asthma symptoms, and some research suggests that these stressful experiences engender changes in children's immune systems in ways that exacerbate airway inflammation and contribute to both acute and chronic asthma symptoms. We examined the association between observed experiences of parent–child conflict and the expression of signaling molecules involved in the transduction of anti-inflammatory signals that regulate airway inflammation and obstruction. Fifty-seven children and their parents participated in a conflict task, and coders rated interactions for evidence of harsh and supportive behaviors. Children reported on their perceptions of parental support and reported on their daily asthma symptoms for 2 weeks. We collected peripheral blood in children to measure leukocyte expression of messenger RNA for the glucocorticoid receptor and the β2-adrenergic receptor. Analyses revealed that harsh conflict behaviors were associated with decreased expression of both messenger RNAs and more severe asthma symptoms. Neither supportive behaviors nor perceived parental support was associated with gene expression or asthma symptoms. These findings suggest that harsh interactions with parents are associated with downregulation of key anti-inflammatory signaling molecules and difficulties breathing in children with asthma. Children with asthma who are also victims of maltreatment may be particularly susceptible to transcriptional changes in immune cells that could worsen asthma over time.
Two‐phase liquid culture system models normal human adult erythropoiesis at the molecular level

Abstract: We have studied the patterns of expression of various genes during maturation of normal human adult erythroid precursors cultured in a two‐phase liquid culture method. In the first phase, peripheral blood mononuclear cells are cultured for one week in the presence of a combination of growth factors, but not erythropoietin (Epo). In Phase II, Epo is included in the medium. Cell samples were taken throughout phase II, and expression of globins, transcription factors, and cytokine receptors was assayed by RT‐PCR and quantified by phosphor imaging. We have divided phase II into stages: early (days 0–5), intermediate (days 6–10) and late (days 11–15) and measured maximum expression of each gene. During early phase II, γ‐globin, Sp1, and GATA‐2 mRNAs were expressed at their highest levels. As the cells matured during the intermediate period, GATA‐2 levels remained high, and then declined, while the transcription factors GATA‐1, EKLF, NF‐E2, and the Epo receptor (EpoR) reached maximum expression. In late phase II, β‐globin increased and reached its maximum level of expression. This erythroid culture system appears to recapitulate normal adult erythropoiesis at the molecular level, and thus may be a suitable model to examine the molecular basis of severe congenital or acquired disorders oferythropoiesis.
Association of ATG16L1 gene haplotype with inflammatory bowel disease in Indians

Inflammatory bowel disease (IBD) is characterized by multigenic inheritance. Defects in autophagy related genes are considered to show genetic heterogeneity between populations. We evaluated the association of several single nucleotide polymorphisms (SNPs) in the autophagy related 16 like 1 (ATG16L1) gene with IBD in Indians. The ATG16L1 gene was genotyped for ten different SNPs using DNA extracted from peripheral blood of 234 patients with Crohn’s disease (CD), 249 patients with ulcerative colitis (UC) and 393 healthy controls The SNPs rs2241880, rs4663396, rs3792106, rs10210302, rs3792109, rs2241877, rs6737398, rs11682898, rs4663402 and rs4663421 were genotyped using the Sequenom MassArray platform. PLINK was used for the association analysis and pairwise linkage disequilibrium (LD) values. Haplotype analysis was done using Haploview. All SNPs were in Hardy Weinberg equilibrium in cases and controls. The G allele at rs6737398 exhibited a protective association with both CD and UC. The T allele at rs4663402 and C allele at rs4663421 were positively associated with CD and UC. The T allele at rs2241877 exhibited protective association with UC only. The AA genotype at rs4663402 and the GG genotype at rs4663421 were protectively associated with both CD and UC. Haplotype analysis revealed that all the SNPs in tight LD (D’ = 0.76–1.0) and organized in a single haplotype block. Haplotype D was positively associated with IBD (P = 5.8 x 10−6 for CD and 0.002 for UC). SNPs in ATG16L1 were associated with IBD in Indian patients. The relevance to management of individual patients requires further study.
Antisense oligodeoxynucleotide to delta opioid receptors attenuates morphine dependence in mice.

The effect of intracerebroventricular (i.c.v.) treatment with antisense oligodeoxynucleotide (A-oligo) to delta opioid receptor mRNA on the morphine-induced place preference and naloxone-precipitated jumping was examined in morphine-dependent mice. Morphine (5 mg/kg, s.c.) produced a significant place preference. I.c. v. pretreatment with A-oligo (0.01-1 microg/mouse) dose-dependently attenuated this morphine (5 mg/kg, s.c.)-induced place preference, while mismatched oligodeoxynucleotide (M-oligo; 1 microg/mouse, i.c.v.) was ineffective. Naloxone (3 mg/kg, s.c.) precipitated jumping in morphine-dependent mice. I.c. v. pretreatment with A-oligo (1 microg/mouse) attenuated this naloxone (3 mg/kg, s.c.)-precipitated jumping in morphine-dependent mice, while M-oligo (1 microg/mouse, i.c.v.) was ineffective. These data demonstrate that the selective reduction in supraspinal delta opioid receptor function caused by pretreatment with A-oligo attenuated the morphine-induced place preference and naloxone-precipitated jumping in morphine-dependent mice, suggesting that the rewarding effect of and physical dependence on morphine may be modulated by central delta opioid receptors.
Migraine in Childhood and Its Prognosis

In 1955 a population study in Uppsala comprising about 9,000 school children showed that migraine increased from 1.4% at the age of seven to 5.3% at fifteen. With increasing age there was an increasing predominance of girls. A matched comparison between 73 children with more pronounced migraine and 73 control children showed a greater tendency in the migraine group to abdominal pain, motion sickness, sleep disturbance and orthostatic symptoms. In a longitudinal study lasting 23 years the 73 migraine children were followed-up until all were over 30 years of age. During puberty and as young adults 62% were free from migraine for at least two years. Of these, 22% again suffered migraine regularly. Thus, 60% had migraine attacks at 30. Girls seem to have a greater relapse rate than boys. Most of the girls with classical migraine were headache free during pregnancy. Every third family with one parent belonging to the migraine group and with children over four years of age had one child with migraine symptoms. Migraine seems to be more frequently inherited via the mother, and to girls.
In Vitro and In Vivo Activities of a Triterpenoid Saponin Extract (PX-6518) from the Plant Maesa balansae against Visceral Leishmania Species

ABSTRACT The in vitro and in vivo activities of a mixture of six oleane triterpene saponins, recovered from the methanolic extract of the leaves of the Vietnamese plant Maesa balansae (PX-6518), were evaluated against drug-sensitive visceral Leishmania strains. The in vitro 50% inhibitory concentration (IC50) against intracellular Leishmania infantum amastigotes was 0.04 μg/ml. The cytotoxic concentrations causing 50% cell death (CC50s) were about 1 μg/ml in murine macrophage host cells and >32 μg/ml in human fibroblasts (MRC-5 cell line). Evaluation in the Leishmania donovani BALB/c mouse model indicated that a single subcutaneous administration of 0.4 mg/kg at 1 day after infection reduced liver amastigote burdens by about 95% in all treated animals. If treatment was delayed until 14 days after infection, a dose of 1.6 mg/kg of body weight was required to maintain the same level of activity. Single 250-mg/kg doses of sodium stibogluconate (Pentostam) 1 and 14 days after infection produced comparable efficacies. A single dose of PX-6518 at 2.5 mg/kg administered 5 days before infection was still 100% effective in preventing liver infection, suggesting a particularly long residual action. Spleen and bone marrow could not be cleared by PX-6518 nor sodium stibogluconate. PX-6518 did not show activity after oral dosing at up to 200 mg/kg for 5 days. This study concludes that triterpenoid saponins from M. balansae show promising in vitro and in vivo antileishmanial potential and can be considered as new lead structures in the search for novel antileishmanial drugs.
Factor analysis with finite data

Factor analysis aims to describe high dimensional random vectors by means of a small number of unknown common factors. In mathematical terms, it is required to decompose the covariance matrix Σ of the random vector as the sum of a diagonal matrix D — accounting for the idiosyncratic noise in the data — and a low rank matrix R — accounting for the variance of the common factors — in such a way that the rank of R is as small as possible so that the number of common factors is minimal. In practice, however, the matrix Σ is unknown and must be replaced by its estimate, i.e. the sample covariance, which comes from a finite amount of data. This paper provides a strategy to account for the uncertainty in the estimation of Σ in the factor analysis problem.
The relationship between tourism, foreign direct investment and economic growth: evidence from Iran

Tourism is one of the world's largest industries and an increasingly important source of foreign currency that is used to finance economic growth. The purpose of this study is to examine the long-term and short-term relationships between tourism and economic growth in Iran, by using annual data covering the 1985–2013 period and autoregressive distributed lag and the Error Correction model to examine the relationships between variables. The findings showed that there is a positive relationship between tourism expenditure and economic growth in the long term and short term. The result indicate that there is also positive relationship between the real effective exchange rate (REER), foreign direct investment (FDI) and economic growth. The Granger causality test shows a bidirectional causality running between tourism expenditure and economic growth.
Optic Nerve Head Blood Flow Response to Reduced Ocular Perfusion Pressure by Alteration of Either the Blood Pressure or Intraocular Pressure

Abstract Purpose: To test the hypothesis that blood flow autoregulation in the optic nerve head has less reserve to maintain normal blood flow in the face of blood pressure-induced ocular perfusion pressure decrease than a similar magnitude intraocular pressure-induced ocular perfusion pressure decrease. Materials and methods: Twelve normal non-human primates were anesthetized by continuous intravenous infusion of pentobarbital. Optic nerve blood flow was monitored by laser speckle flowgraphy. In the first group of animals (n = 6), the experimental eye intraocular pressure was maintained at 10 mmHg using a saline reservoir connected to the anterior chamber. The blood pressure was gradually reduced by a slow injection of pentobarbital. In the second group (n = 6), the intraocular pressure was slowly increased from 10 mmHg to 50 mmHg by raising the reservoir. In both experimental groups, optic nerve head blood flow was measured continuously. The blood pressure and intraocular pressure were simultaneously recorded in all experiments. Results: The optic nerve head blood flow showed significant difference between the two groups (p = 0.021, repeat measures analysis of variance). It declined significantly more in the blood pressure group compared to the intraocular pressure group when the ocular perfusion pressure was reduced to 35 mmHg (p < 0.045) and below. There was also a significant interaction between blood flow changes and the ocular perfusion pressure treatment (p = 0.004, adjusted Greenhouse & Geisser univariate test), indicating the gradually enlarged blood flow difference between the two groups was due to the ocular perfusion pressure decrease. Conclusions: The results show that optic nerve head blood flow is more susceptible to an ocular perfusion pressure decrease induced by lowering the blood pressure compared with that induced by increasing the intraocular pressure. This blood flow autoregulation capacity vulnerability to low blood pressure may provide experimental evidence related to the hemodynamic pathophysiology in glaucoma.