Miracle-dz/UniFAR-FTUs huggingface dataset:
Developmentally regulated neurosteroid synthesis enhances GABAergic neurotransmission in mouse thalamocortical neurones

During neuronal development synaptic events mediated by GABAA receptors are progressively reduced in their duration, allowing for rapid and precise network function. Here we focused on ventrobasal thalamocortical neurones, which contribute to behaviourally relevant oscillations between thalamus and cortex. We demonstrate that the developmental decrease in the duration of inhibitory phasic events results predominantly from a precisely timed loss of locally produced neurosteroids, which act as positive allosteric modulators of the GABAA receptor. The mature thalamus retains the ability to synthesise neurosteroids, thus preserving the capacity to enhance both phasic and tonic inhibition, mediated by synaptic and extrasynaptic GABAA receptors, respectively, in physiological and pathophysiological scenarios associated with perturbed neurosteroid levels. Our data establish a potent, endogenous mechanism to locally regulate the GABAA receptor function and thereby influence thalamocortical activity.
Is major depressive disorder or dysthymia more strongly associated with bulimia nervosa?

OBJECTIVE Research on adult samples has found that the comorbidity between depression and eating disorders exceeds the comorbidity of any other Axis I disorder and eating disorders. Few studies have investigated the specific associations of major depression versus dysthymia with eating disorders. METHOD This sample consisted of 937 adolescents who were repeatedly assessed until the age of 24. RESULTS Analyses revealed that dysthymia was a stronger correlate with bulimia than major depression, even while controlling for other mood disorders and a history of depression and dysthymia. CONCLUSIONS The presence of dysthymia in adolescence might be a possible risk factor for the development of bulimia nervosa.
Predictors of abnormal heart rate recovery in patients with heart failure reduced and preserved ejection fraction

Background Heart rate recovery (HRR) is becoming an important prognostic maker in heart failure (HF), but very little is known about the underlying mechanisms responsible for its clinical efficacy. Therefore, we examined echocardiographic and exercise (submaximal and maximal) characteristics to gain a better appreciation of HRR and factors responsible for the development of abnormal HRR in patients with both heart failure reduced ejection fraction (HFrEF) and heart failure preserved ejection fraction (HFpEF). Methods Cardiopulmonary exercise testing (CPX), a 6-minute walk test (6MWT), and resting 2D echocardiography were randomly performed in 240 HF patients (200 HFrEF, 40 HFpEF) after which HRR was measured. HRR was defined as the difference between heart rate at peak exercise and 1 minute following test termination. Results Bivariate correlation analyses found significant relationships among most CPX and 6MWT measurements with the highest correlations between 6MWT HRR and 6MWT peak HR (r = 0.65; p < 0.001) and CPX HRR and CPX HRreserve (r = 0.63; p < 0.001). The relationship between 6MWT HRR and CPX HRR was very good (r = 0.91; p < 001). Multivariate logistic regression of submaximal and maximal exercise found 6MWT peak HR and exercise oscillatory ventilation (EOV), respectively, were the strongest predictors (p < 0.001) of abnormal HRR. The E/E′ was a significant predictor (p < 0.001) of abnormal HRR, but EOV was the strongest predictor of abnormal HRR (OR = 6.5). Conclusions HRR after both CPX and the 6MWT is significantly related to many exercise and echocardiographic measures with the most significant predictors of abnormal HRR being related to indices of cardiorespiratory performance in patients with HFrEF and HFpEF.
CEOs and Earnings Management: the Distributional Anomalies of Discretionary Accruals in Post-SOX Era

This thesis examines anomalies related to the discretionary accruals usage during the tenures of CEOs in listed U.S. companies since the implementation of Sarbanes-Oxley Act. The approach used in this thesis is quantitative in nature. Four well-known discretionary accruals models: Healy model, DeAngelo model, Jones model and modified Jones are used in to separate discretionary accruals from the total accruals. The sample consists of financial and executive data of listed U.S. companies between the years 2003-2013. The results of this study strongly support the idea that income-increasing accruals are used in the final year of the average CEO’s tenure. Furthermore, support for the usage of income-increasing discretionary accruals during the early years of CEO’s tenure was found. In addition, in the transition year between two CEOs, weak evidence for the downwards management of discretionary accruals was observed.
In-vitro and in-vivo antagonistic action of an anti-amylin Spiegelmer

The anorectic and dipsogenic effects of the pancreatic hormone amylin are mediated by the area postrema and the subfornical organ. We tested the effectiveness of a new amylin antagonist, a so-called RNA Spiegelmer, by electrophysiological in-vitro recordings from the rat subfornical organ and by immunohistological c-Fos studies in the area postrema. Amylin's excitatory effect on subfornical organ neurons was blocked by the anti-amylin Spiegelmer. Peripheral administration 5 h prior to amylin also suppressed the amylin-induced activation (c-Fos expression) in the area postrema. The biostable anti-amylin Spiegelmer may be therapeutically beneficial in conditions associated with high plasma amylin levels, such as cancer anorexia occurring during certain pancreatic tumors.
The temperature characteristics of synaptic membrane ATPases from immature and adult rat brain

SYNAPTIC membranes isolated from adult brain homogenates are known to be rich in Na+-K+-ATPase (EC 3.6.1.3) following the work of ALBERS et al. (1965), H o s l ~ (1965), KUROKAWA et al. (1965), WHITTAKER (1965) and BRADFORD et al. (1966). More recent workers report highly purified preparations of synaptosomal membranes with a higher specific activity for the Na+-K+-ATPase (LEVITAN et al., 1972; MORGAN et al., 1971). SAMSON et al. (1964) and SAMSON & QUINN (1967) have shown the Na+-K'-ATPase activity rises dramatically in the I s 2 0 day postnatal period in rat brain. It has been reported that this occurs in the synaptosomal as well as microsomal Na+-K+-ATPase activity (ABDEL-LATIF & ABOOD, 1964; ABDEL-LATIF et al., 1967, 1970) and furthermore parallels the appearance of electrical activity and the known changes in synaptic morphology (HUTTENLOCHER & RAWSON, 1968). During this early postnatal period young rats are not easily able to regulate body temperature and so they experience and tolerate lower body temperatures than do adults (ADOLPH, 1957). Several workers have shown that the Nai-Kt-ATPase present in microsomal fractions obtained from mammalian brain (CHARNOCK et al., 1971; BOWLER & DUNCAN, 1968, 1969), kidney cortex (WILLIS & LI, 1969) and also red cell cation transport (WIETH, 1970) are dramatically reduced at temperatures below 15"Cand virtually absent below 5°C. The purpose of this present study is to determine whether synaptic membrane ATPases are qualitatively different in preparations from immature and adult rat brains, with respect to their temperature sensitivity.
A numerical study of transcranial focused ultrasound beam propagation at low frequency

The feasibility of transcranial ultrasound focusing with a non-moving phased array and without skull-specific aberration correction was investigated using computer simulations. Three cadaver skull CT image data sets were incorporated into an acoustic wave transmission model to simulate transskull ultrasound wave propagation. Using a 0.25 MHz hemispherical array (125 mm radius of curvature, 250 mm diameter, 24 255 elements), the simulated beams could be focused and steered with transducer element driving phases and amplitude adjusted for focal beam steering in water (water-path). A total of 82 foci, spanning wide ranges of distance in the three orthogonal dimensions, were simulated to test the focal beam steering capability inside the three skulls. The acoustic pressure distribution in a volume of 20 × 20 × 20 mm3 centred at each focus was calculated with a 0.5 mm spacing in each axis. Clearly defined foci were retained through the skulls (skull-path) in most cases. The skull-path foci were on average 1.6 ± 0.8 mm shifted from their intended locations. The −3 dB skull-path beam width and length were on average 4.3 ± 1.0 mm and 7.7 ± 1.8 mm, respectively. The skull-path sidelobe levels ranged from 25% to 55% of the peak pressure values. The skull-path peak pressure levels were about 10%–40% of their water-path counterparts. Focusing low-frequency beam through skull without skull-specific aberration correction is possible. This method may be useful for applying ultrasound to disrupt the blood–brain barrier for targeted delivery of therapeutic or diagnostic agents, or to induce microbubbles, or for other uses of ultrasound in brain where the required power levels are low and the sharp focusing is not needed.
Insulin and insulinlike growth factor 1 (IGF-1) receptors during central nervous system development: expression of two immunologically distinct IGF-1 receptor beta subunits

Insulin and insulinlike growth factor 1 (IGF-1) receptors are present in brain, yet their function remains obscure. Expression of these tyrosine kinase-bearing growth factor receptors during rat brain development was examined by using three antipeptide antibodies directed against epitopes in the beta subunits (AbP2, AbP4, and AbP5). All three antibodies recognized both insulin and IGF-1 receptors. Membranes were prepared from fetal brains (14 to 21 days of gestation), neonatal brain (postnatal day 1), and adult brain. Immunoblot analyses using AbP4 and AbP5 revealed a 92-kilodalton (kDa) protein that corresponded to the beta subunit of the insulin and IGF-1 receptors. Densitometric scanning of immunoblots indicated that receptor proteins were 4- to 10-fold more abundant in fetal brain membranes than in membranes from adult brain. Expression was highest during 16 to 18 days of gestation and declined thereafter to the relatively low level found in adult brain. Immunoblot analyses with AbP2 as well as ligand-activated receptor autophosphorylation revealed an additional protein of 97 kDa. This protein was phosphorylated in response to IGF-1 and was not directly recognized by AbP4 or AbP5. The covalent association of the 97-kDa protein with the 92-kDa beta subunit was indicated by the ability of AbP4 and AbP5 to immunoprecipitate both proteins under nonreducing conditions but only the 92-kDa protein after reduction. In contrast, AbP2 immunoprecipitated both proteins regardless of their association. This immunospecificity remained unchanged after deglycosylation of the isolated proteins. Two-dimensional tryptic phosphopeptide analysis showed that the 92- and 97-kDa subunits of the IGF-1 receptor are related but distinct proteins. Taken together, the data suggest that the 92- and 97-kDa subunits differ in primary amino acid sequence. Thus, two distinct beta subunits may be present in a single IGF-1 receptor in brain. These subunits have in common an epitope recognized by an antibody to the tyrosine kinase domain (AbP2) but differ in regions thought to be important in receptor kinase regulation and signal transduction.
Fatal blunt injuries possibly resulting from sexual abuse of a calf

We report a case of a calf-related fatality on a farm. The victim was a 60-year-old man who was possibly attempting to sexually approach the animal from behind when he was struck by it, sustaining fatal blunt injuries, mostly to the thorax. This case is reported because of its rarity and because of the particular circumstances of death. Fatal trauma associated with bovines is rare on the whole, and when it does occur it is usually caused by kicking or pushing during regular agricultural activity. Although the cause of death in our case could be determined, the circumstances and the manner of death remain speculative to some degree.
Genetical studies on the skeleton of the mouse. XXII. The development of Danforth's short-tail.

The semi-dominant gene for Danforth's short-tail in the mouse (symbol Sd ; linkage group V) was first described by Dunn, Gluecksohn-Schoenheimer, & Bryson (1940). The most conspicuous abnormality of Sd /+ heterozygotes is a shortening of the tail the extent of which varies with the genetic background (Dunn, 1942; Fisher & Holt, 1944; Dunn & Gluecksohn-Schoenheimer, 1945). Reduction or absence of kidneys is common on some genetic backgrounds, but rare or absent on others (Gluecksohn-Schoenheimer, 1943). Reduction or absence of the dens epistrophei (odontoid process of the axis) with formation of an anomalous articulation between atlas and epistropheus (axis) was later described by Theiler (1951 a, b ; 1952; 1954) and by Gruneberg (1953). The reduction of the dens epistrophei is part and parcel of a general reduction of the vertebral bodies which is most marked in the cervical region, but which can be traced throughout the whole length of the axial skeleton.
Thermodilution and Fick cardiac outputs differ: impact on pulmonary hypertension evaluation.

BACKGROUND The relationship between thermodilution and indirect Fick cardiac output determination methods has not been well described. OBJECTIVE To describe the relationship between these two cardiac output determination methods in patients evaluated for pulmonary hypertension and to highlight potential clinical implications. METHODS A retrospective review of charts of all adult patients who underwent a right heart catheterization (RHC) between January 1, 2007 and November 10, 2010, and participated in the pulmonary hypertension program of the pulmonary division at an academic institution was conducted. For validation, the charts of all patients who underwent RHC during the same period within the cardiology division were reviewed. RESULTS A total of 198 patients underwent 213 RHCs, 79 (40%) of whom had pulmonary arterial hypertension, were included. Forty-three per cent of patients had >20% difference between thermodilution and Fick. The average difference (thermodilution - Fick ±SD) was -0.39±2.03 L⁄min (n=213; P=0.006). There was no significant difference in bias or variability between thermodilution and Fick among patients with tricuspid regurgitant jet velocity (TRJ) of <3 m⁄s versus those with TRJ >3 m⁄s (-0.41±2.10 L⁄min versus -0.36±1.93 L⁄min, respectively; P=0.87). In a multivariable analysis, the thermodilution-Fick difference increased with age (P=0.001). DISCUSSION The presence of such discrepancy in 36% of patients evaluated for heart failure and⁄or heart transplant validated the results. In total, 37% of the 1315 procedures (213 performed by pulmonologists and 1102 performed by cardiologists) had a difference of >20% between thermodilution and Fick. CONCLUSION Significant discrepancy exists between thermodilution and indirect Fick methods. This discrepancy potentially impacts pulmonary arterial hypertension prognostication and diagnosis, and is independent of TRJ.
English Bacon: Copartisan Bias in Intergovernmental Grant Allocation in England

The literature on distributive politics suggests that politicians have incentives to engage in targeted spending especially in decentralized political systems with weak parties and candidate-centered elections. We argue that in centralized political systems with party-centered elections parties use intergovernmental transfers to advance their electoral fortune via performance spillovers across different levels of government. On the basis of a new data set on partisan composition of local councils in England and grants allocated by the central government during 1992–2012, and using a difference-in-difference approach, we provide evidence that governments allocate up to 17% more money to local councils controlled by their “own” party. Furthermore, we show that the effect is strongest closer to local election years, in local councils where institutions facilitate credit claiming, and in swing councils.
Molecular cloning of chemotaxis genes and overproduction of gene products in the bacterial sensing system

The chemotaxis genes cheR, cheB, cheY, cheZ, and tar of Salmonella typhimurium were cloned into bacteriophage lambda vectors and onto pBR322 plasmids by recombinant DNA techniques. The genes were linearly arranged in the order tar-cheR-cheB-cheY-cheZ (and were read from a promoter on the upstream side of the tar or cheR gene). However, their stoichiometries of expression were found to be 4:1:1:18:3, respectively. The overexpression of the cheY gene appeared to be a function of translational control. These five che genes were placed on a multicopy plasmid, and the gene products were overproduced in the cells, as shown by enzyme assays. The overproduction of the products of these five genes relative to those of the other che genes caused some changes in chemotactic properties, but no dramatic destruction of sensing ability.
Designing durable icephobic surfaces

Researchers successfully design materials with extremely low ice adhesion. Ice accretion has a negative impact on critical infrastructure, as well as a range of commercial and residential activities. Icephobic surfaces are defined by an ice adhesion strength τice < 100 kPa. However, the passive removal of ice requires much lower values of τice, such as on airplane wings or power lines (τice < 20 kPa). Such low τice values are scarcely reported, and robust coatings that maintain these low values have not been reported previously. We show that, irrespective of material chemistry, by tailoring the cross-link density of different elastomeric coatings and by enabling interfacial slippage, it is possible to systematically design coatings with extremely low ice adhesion (τice < 0.2 kPa). These newfound mechanisms allow for the rational design of icephobic coatings with virtually any desired ice adhesion strength. By using these mechanisms, we fabricate extremely durable coatings that maintain τice < 10 kPa after severe mechanical abrasion, acid/base exposure, 100 icing/deicing cycles, thermal cycling, accelerated corrosion, and exposure to Michigan wintery conditions over several months.
Inhalant use, abuse, and dependence among adolescent patients: commonly comorbid problems.

OBJECTIVE Little is known about adolescents with DSM-IV-defined inhalant abuse and dependence. The aim of this study was to compare comorbidity among (1) adolescents with inhalant use disorders, (2) adolescents who reported using inhalants without inhalant use disorder, and (3) other adolescent patients drawn from an adolescent drug and alcohol treatment program. METHOD The authors examined 847 admissions of patients who had completed structured diagnostic assessments. The three groups were compared for noninhalant substance use disorders, posttraumatic stress disorder, conduct disorder, major depression, previous suicide attempts, and physical/sexual abuse and neglect. RESULTS Adolescents with inhalant abuse or dependence (group 1; n = 28) were significantly more likely to meet lifetime criteria for abuse or dependence on alcohol, hallucinogens, nicotine, cocaine, and amphetamines, to have had major depression, and to have attempted suicide compared with other adolescent patients who reported never using inhalants (group 3); adolescents with inhalant use disorders also reported significantly more abuse and neglect. Adolescents with inhalant abuse or dependence (group 1) did not differ significantly on any measure compared with adolescents who reported using inhalants without an inhalant use disorder (group 2). CONCLUSIONS Adolescent patients with a history of inhalant use, abuse, or dependence entering treatment should be carefully screened for noninhalant substance use disorders, major depression, suicidality, and abuse and neglect.
A Deep Architecture for Content-based Recommendations Exploiting Recurrent Neural Networks

In this paper we investigate the effectiveness of Recurrent Neural Networks (RNNs) in a top-N content-based recommendation scenario. Specifically, we propose a deep architecture which adopts Long Short Term Memory (LSTM) networks to jointly learn two embeddings representing the items to be recommended as well as the preferences of the user. Next, given such a representation, a logistic regression layer calculates the relevance score of each item for a specific user and we returns the top-N items as recommendations. In the experimental session we evaluated the effectiveness of our approach against several baselines: first, we compared it to other shallow models based on neural networks (as Word2Vec and Doc2Vec), next we evaluated it against state-of-the-art algorithms for collaborative filtering. In both cases, our methodology obtains a significant improvement over all the baselines, thus giving evidence of the effectiveness of deep learning techniques in content-based recommendation scenarios and paving the way for several future research directions.
Comment on: Daily 300 mg dose of linezolid for the treatment of intractable multidrug-resistant and extensively drug-resistant tuberculosis.

Background: Although previous studies have suggested that linezolid may be effective for treating multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), the optimal dose of linezolid for intractable MDR/XDR-TB is not clear. Methods: Twenty-four patients with intractable MDR/XDR-TB were treated with a daily 300 mg dose of linezolid as part of their anti-TB drug regimen. Results: The patients were treated with linezolid for a median duration of 359 days [interquartile range (IQR) 268―443 days]. Seventeen (71%) patients received 300 mg of linezolid once daily from the beginning of treatment for a median duration of 289 days (IQR 233―405 days). Of these patients, four developed peripheral neuropathy, one of whom discontinued linezolid. In seven (29%) patients, 600 mg/day linezolid was administered initially for a median duration of 104 days (IQR 26―145 days) followed by 300 mg/day linezolid for a median duration of 348 days (IQR 298―427 days). In five of these seven patients, the reason for changing from 600 to 300 mg/day was due to side effects of 600 mg/day linezolid (peripheral neuropathy in four patients and leucopenia in one patient). After reducing the dose to 300 mg/day, linezolid could be continued in six of the seven patients. Negative sputum conversion was achieved in 22 (92%) patients after a median of 89 days from the start of linezolid treatment (IQR 48―160 days). Conclusions: A daily 300 mg dose of linezolid may be useful for increasing the chances of culture conversion in the treatment of patients with intractable MDR/XDR-TB and might have fewer side effects, especially neurotoxicity, compared with a daily 600 mg dose of linezolid therapy. The present results encourage further research into the use of a 300 mg dose of linezolid for MDR/XDR-TB patients.