Miracle-dz/UniFAR-FTUs huggingface dataset:
Towards a “canonical” agranular cortical microcircuit

Based on regularities in the intrinsic microcircuitry of cortical areas, variants of a “canonical” cortical microcircuit have been proposed and widely adopted, particularly in computational neuroscience and neuroinformatics. However, this circuit is founded on striate cortex, which manifests perhaps the most extreme instance of cortical organization, in terms of a very high density of cells in highly differentiated cortical layers. Most other cortical regions have a less well differentiated architecture, stretching in gradients from the very dense eulaminate primary cortical areas to the other extreme of dysgranular and agranular areas of low density and poor laminar differentiation. It is unlikely for the patterns of inter- and intra-laminar connections to be uniform in spite of strong variations of their structural substrate. This assumption is corroborated by reports of divergence in intrinsic circuitry across the cortex. Consequently, it remains an important goal to define local microcircuits for a variety of cortical types, in particular, agranular cortical regions. As a counterpoint to the striate microcircuit, which may be anchored in an exceptional cytoarchitecture, we here outline a tentative microcircuit for agranular cortex. The circuit is based on a synthesis of the available literature on the local microcircuitry in agranular cortical areas of the rodent brain, investigated by anatomical and electrophysiological approaches. A central observation of these investigations is a weakening of interlaminar inhibition as cortical cytoarchitecture becomes less distinctive. Thus, our study of agranular microcircuitry revealed deviations from the well-known “canonical” microcircuit established for striate cortex, suggesting variations in the intrinsic circuitry across the cortex that may be functionally relevant.
MRI of the cervical nerve roots in the diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy: a single-institution, retrospective case–control study

Objective To systematically evaluate the usefulness of assessing the cervical nerve roots by MRI for the diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Design Single-institution, retrospective case–control study. Setting A regional referral hospital. Participants We retrospectively enrolled 15 consecutive patients with CIDP who satisfied the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) typical and definite criteria and underwent cervical MRI. 30 control patients who had also undergone cervical MRI were included, matched with regard to sex, age and MRI system. The diagnoses of the control patients included cervical spondylosis (n=19), cervical spine trauma (n=2), infection (n=1), malignancies (n=4), demyelinating disorders (n=2) and neurodegenerative disorders (n=2). Measurement A radiologist determined the C5–C8 root diameters on the coronal short tau inversion recovery (STIR) images. Signal intensities of these roots were quantified as nerve-to-muscle contrast-to-noise ratios (CNRs), which were calculated using mean signal intensities of the roots and sternocleidomastoid muscle as well as SD of background noise. Statistical analyses were performed to determine the diagnostic accuracy of the diameters and nerve-to-muscle CNRs. Another radiologist reviewed MRI for ensuring reproducibility. Results The root diameters showed no significant differences between the patients with CIDP and control patients. The nerve-to-muscle CNRs were significantly higher in the patients with CIDP. We defined the sum of nerve-to-muscle CNRs of C5–C8 roots as the CNR score to serve as an index of overall signal intensity. The area under the receiver operating characteristic curve of CNR scores was 0.731. The reproducibility of the assessment procedure was satisfactory. Conclusions Our results suggest that assessment of the cervical nerve roots by MRI is useful for CIDP diagnosis when the signal intensities, rather than the diameters, are paid more attention on STIR images.
Autoregulation of the 26S proteasome by in situ ubiquitination

The 26S proteasome is ubiquitinated by proteasome-associating ubiquitination enzymes. Proteasome ubiquitination impairs proteasomal degradation and is regulated by deubiquitination, substrate binding, and cellular stress. It is proposed that in situ ubiquitination autoregulates proteasomal activity in cells.
The Debt-contracting Value of Accounting Numbers, Renegotiation, and Investment Efficiency

This paper investigates the impact of the debt-contracting value (DCV) of borrowers’ accounting information on the likelihood of private debt renegotiation and the implication of renegotiation for borrowing firms’ investment efficiency. DCV captures the inherent ability of firms’ accounting numbers to predict future credit quality. Building on incomplete contract theory, I hypothesize that lower DCV of a borrower’s accounting numbers creates ex post incentives for both parties to renegotiate the terms of the initial contract, leading to higher probability of renegotiation. During the renegotiation, the lenders can extract partial gains from the borrowers’ investment according to their relative bargaining power. Anticipating the high-probability of renegotiation reduces the ex ante investment incentives of borrowers, inducing underinvestment. Using a sample of 3,720 private debt contracts, I find that firms with higher DCV have a lower probability of renegotiation and less underinvestment. Moreover, the impact of DCV on investment increases with lenders’ relative bargaining power.
Antidopaminergic effects of dietary tyrosine depletion in healthy subjects and patients with manic illness

Background In rats, amino acid mixtures lacking tyrosine and its precursor phenylalanine decrease the release of dopamine produced by the psychostimulant drug amphetamine. Amphetamine has been proposed as a model for clinical mania. Aims To assess whether dietary tyrosine depletion attenuates the psychostimulant effects of methamphetamine in healthy volunteers and diminishes the severity of mania in acutely ill patients. Method Sixteen healthy volunteers received a tyrosine-free amino acid mixture and a control mixture in a double-blind crossover design 4 h before methamphetamine (0.15 mg/kg). Twenty in-patients meeting DSM–IV criteria for mania were allocated blindly and randomly to receive either the tyrosine-free mixture or the control mixture. Results The tyrosine-free mixture lowered both subjective and objective measures of the psychostimulant effects of methamphetamine. Ratings of mania were lower in the patients who received the tyrosine-free mixture. Conclusions Decreased tyrosine availability to the brain attenuates pathological increases in dopamine neurotransmission following methamphetamine administration and putatively in mania.
Labour and Racism

Race is a political raw nerve — best avoided, rather than touched. The Tory government's proposed British Nationality Bill is the latest in a long line of racist immigration policies that, we are told, has nothing to do with race. It's the same old game — but with different categories; define degrees of 'Britishness' that bear an uncanny resemblance to black and white skins and call it 'nationality'. Sidestepping the issue of race is not new, it provides a way around the emotional minefield of race relations. Runnymede Trust (and the Radical Statistics Race Group) are prepared to tackle the issue head on. Britain's Black Population cuts a hard, statistical path through the minefield to provide a factual picture of the position of black people in this country. The opening chapter sets the groundwork for the ensuing discussion of racial disadvantage and the Government's response, by providing a detailed demographic account — size, births, deaths, age, sex — of the black population. The stereotype that all black people are immigrants is quickly exorcised, to give the reader in the following chapters, a detailed account of the material disadvantages black people experience in comparison to whites in the fields of employment, housing, education and social services. Well written and illustrated, this sober account provides a useful antidote to the myths of racist propaganda. (A wealth of further publications and statistical sources relating to race are included in the appendices for those wishing to develop a more comprehensive picture.)
Effects of dyadic work organization on realism in confidence judgments

This study examines the effect of three regimens (organizations of activities) on the realism in dyad’s confidence judgments. The effect of letting the pair members first work alone when selecting an answer and/or when confidence rating the correctness of this answer was compared with working directly in pairs. No improvement in the realism of the dyads’ final confidence judgments was found as an effect of the work regimens involving preparatory work, compared with pairs having no such preparation. In fact, carrying out a confidence judgment acting as an individual after a dyadic decision about the selection of answer alternative, led to increased overconfidence in the pairs. Improved realism was found when pair members worked individually when selecting and confidence judging the answer, before collectively deciding on an answer but again giving individual confidence ratings, but this effect did not reach significance. It is suggested that these results might at least partly be explained by increased confidence as an effect of explaining one’s belief. Finally, each pair’s final judgment of the total number of questions answered correctly was not improved by individual preparatory work.
Tuberculosis incidence after 36 months’ isoniazid prophylaxis in HIV-infected adults in Botswana: a posttrial observational analysis

Objective:Thirty-six months of isoniazid preventive therapy (36IPT) was superior to 6 months of IPT (6IPT) in preventing tuberculosis (TB) among HIV-infected adults in Botswana. We assessed the posttrial durability of this benefit. Design:A 36-month double-blind placebo controlled trial (1 : 1 randomization) with recruitment between November 2004 and July 2006 and observation until June 2011. Methods:One thousand, nine hundred and ninety-five participants were followed in eight public health clinics. Twenty-four percent had a tuberculin skin test ≥5 mm (TST-positive). A minimum CD4+ lymphocyte count was not required for enrolment. Antiretroviral therapy (ART) was provided in accordance with Botswana guidelines; 72% of participants retained by June 2011 had initiated ART. Multivariable analysis using Cox regression analysis included treatment arm, TST status, ART as a time-dependent variable and CD4+ cell count at baseline and updated at 36 months. Results:In the posttrial period, 2.13 and 2.14 per 100 person-years accumulated, whereas 0.93 and 1.13% TB incidence rates were observed in the 36IPT and 6IPT arms, respectively (P = 0.52). The crude hazard ratio of TB during the trial and posttrial was 0.57 [95% confidence intervals (CI) 0.33, 0.99] and 0.82 (95% CI 0.46, 1.49), and when restricted to TST-positive participants was 0.26 (95% CI 0.08, 0.80) and 0.40 (95% CI 0.15, 1.08), respectively. Multivariable analysis showed that ART use was associated with reduced death (adjusted hazard ratio 0.36, 95% CI 0.17–0.75) but not TB (0.92, 95% CI 0.55–1.53) in the posttrial period. Conclusion:The benefit of 36IPT for TB prevention declined posttrial in this cohort. Adjunctive measures are warranted to prevent TB among HIV-infected persons receiving long-term ART in TB-endemic settings.
The Apparent Voltage Dependence of GABAA Receptor Activation and Modulation Is Inversely Related to Channel Open Probability

The GABA type A receptor (GABAAR) is expressed ubiquitously throughout the brain and is a target for many therapeutic agents, including general anesthetics and benzodiazepines, which enhance receptor function by increasing the open probability (Po) of the ion channel. It is commonplace for in vitro studies of receptor pharmacological characteristics to use negative membrane holding potentials to mimic the resting potential of neurons and symmetrical chloride to eliminate Goldman rectification, which results in chloride flow in the opposite direction, compared with in vivo conditions. This critical difference is usually overlooked because the GABAAR has been reported to behave as an ohmic pore, but our results show that the current-voltage relationship is nonlinear with respect to Po. Specifically, we found that currents were outwardly rectifying at low Po and linear at high Po. We confirmed the correlation between Po and rectification with a partial agonist, piperidine-4-sulfonic acid, and a gating-impaired mutation, α1(L277A); both exhibited enhanced outward rectification. Furthermore, this correlation was independent of Goldman rectification and persisted under altered chloride gradient conditions, which suggests that rectification is linked to the direction of chloride flux. Finally, our results showed that the degree of potentiation by general anesthetics (etomidate, propofol, and isoflurane) was greater at negative membrane potentials. Traditional in vitro experiments thus overestimate the action of positive allosteric modulators of the GABAAR. Our results show that the direction of the driving force on the permeant ion, as well as Po, must be considered together for a complete understanding of drug actions on ligand-gated ion channels.
The dimensionality of discourse

The paragraph spaces of five text corpora, of different genres and intended audiences, in four different languages, all show the same two-scale structure, with the dimension at short distances being lower than at long distances. In all five cases the short-distance dimension is approximately eight. Control simulations with randomly permuted word instances do not exhibit a low dimensional structure. The observed topology places important constraints on the way in which authors construct prose, which may be universal.
Detecting Stealthy False Data Injection Using Machine Learning in Smart Grid

Aging power industries, together with the increase in demand from industrial and residential customers, are the main incentive for policy makers to define a road map to the next-generation power system called the smart grid. In the smart grid, the overall monitoring costs will be decreased, but at the same time, the risk of cyber attacks might be increased. Recently, a new type of attacks (called the stealth attack) has been introduced, which cannot be detected by the traditional bad data detection using state estimation. In this paper, we show how normal operations of power networks can be statistically distinguished from the case under stealthy attacks. We propose two machine-learning-based techniques for stealthy attack detection. The first method utilizes supervised learning over labeled data and trains a distributed support vector machine (SVM). The design of the distributed SVM is based on the alternating direction method of multipliers, which offers provable optimality and convergence rate. The second method requires no training data and detects the deviation in measurements. In both methods, principal component analysis is used to reduce the dimensionality of the data to be processed, which leads to lower computation complexities. The results of the proposed detection methods on IEEE standard test systems demonstrate the effectiveness of both schemes.
The more the merrier? Fertility and food insecurity among older Senegalese women

ABSTRACT The number of children women have is a critical determinant of their future wellbeing. Often, adult children confer some protection against adverse conditions in their older ages. In many sub-Saharan African societies, it is expected that older women who typically have had many children, will benefit from their investment in children. Yet it is unclear if this is really the case. Using data from the 10 per cent micro-sample of the 2002 Senegalese Population and Housing Census, this study investigates the effect of the childbearing histories of older women (aged 60–85) on the likelihood that their households experienced food insecurity in the past year. Women who had had no children and those who had ever had two or more, were not significantly different from those who had had five or more – only those who had had one child were adversely affected. Based on principles of intergenerational altruism and moral obligation, I expected that food insecurity would decrease with increases in the number of surviving children. This pattern was generally found. However, among women in the bottom 40 per cent of the wealth distribution, the relationship was, at best, weak with respect to all of the fertility variables (children ever had, living, co-resident). The benefits of high fertility seem to accrue to relatively richer women – those in the top 60 per cent of the wealth distribution. Yet among these richer women, having fewer than three children and co-resident adult children were significant risk factors of food insecurity.
The myelin proteolipid plasmolipin forms oligomers and induces liquid-ordered membranes in the Golgi complex

ABSTRACT Myelin comprises a compactly stacked massive surface area of protein-poor thick membrane that insulates axons to allow fast signal propagation. Increasing levels of the myelin protein plasmolipin (PLLP) were correlated with post-natal myelination; however, its function is unknown. Here, the intracellular localization and dynamics of PLLP were characterized in primary glial and cultured cells using fluorescently labeled PLLP and antibodies against PLLP. PLLP localized to and recycled between the plasma membrane and the Golgi complex. In the Golgi complex, PLLP forms oligomers based on fluorescence resonance energy transfer (FRET) analyses. PLLP oligomers blocked Golgi to plasma membrane transport of the secretory protein vesicular stomatitis virus G protein (VSVG), but not of a VSVG mutant with an elongated transmembrane domain. Laurdan staining analysis showed that this block is associated with PLLP-induced proliferation of liquid-ordered membranes. These findings show the capacity of PLLP to assemble potential myelin membrane precursor domains at the Golgi complex through its oligomerization and ability to attract liquid-ordered lipids. These data support a model in which PLLP functions in myelin biogenesis through organization of myelin liquid-ordered membranes in the Golgi complex. Summary: Investigation of the intracellular dynamics of plasmolipin reveals that it assembles potential myelin membrane precursor domains at the Golgi complex by oligomerizing and attracting liquid-ordered lipids.
Index-CloseMiner: An improved algorithm for mining frequent closed itemset

The set of frequent closed itemsets determines exactly the complete set of all frequent itemsets and is usually much smaller than the latter. This paper proposes an improved algorithm for mining frequent closed itemsets. Firstly, the index array is proposed, which is used for discovering those items that always appear together. Then, by using bitmap, an algorithm for computing index array is presented. Thirdly, based on the heuristic information provided by index array, frequent items, which co-occur together and share the same support, are merged together. Thus, initial generators are calculated. Finally, based on index array, reduced pre-set and reduced post-set are proposed. It is proved that the reduced pre-set and reduced post-set not only retain the function of pre-set and post-set, but also have smaller sizes. Therefore, the redundant items in pre-set and post-set are deleted, thus making it possible to save a lot of work related to inclusion check. The experimental results show that the proposed algorithm is efficient especially on dense dataset.
Arginase regulates red blood cell nitric oxide synthase and export of cardioprotective nitric oxide bioactivity

Significance Nitric oxide from endothelial cells is important for regulating cardiovascular function. Recent data suggest that red blood cells are a source for nitric oxide. We examined the function of red blood cell nitric oxide and the regulation of its formation by the enzyme arginase. We show that red blood cells contain arginase that inhibits nitric oxide export. The function was tested in a heart model subjected to ischemia. The recovery of heart function after ischemia was improved following inhibition of red blood cell arginase. This effect depended on the specific protein producing nitric oxide. The results demonstrate an important function by red blood cells in regulating heart function during ischemia via nitric oxide production under tight control by arginase. The theory that red blood cells (RBCs) generate and release nitric oxide (NO)-like bioactivity has gained considerable interest. However, it remains unclear whether it can be produced by endothelial NO synthase (eNOS), which is present in RBCs, and whether NO can escape scavenging by hemoglobin. The aim of this study was to test the hypothesis that arginase reciprocally controls NO formation in RBCs by competition with eNOS for their common substrate arginine and that RBC-derived NO is functionally active following arginase blockade. We show that rodent and human RBCs contain functional arginase 1 and that pharmacological inhibition of arginase increases export of eNOS-derived nitrogen oxides from RBCs under basal conditions. The functional importance was tested in an ex vivo model of myocardial ischemia-reperfusion injury. Inhibitors of arginase significantly improved postischemic functional recovery in rat hearts if administered in whole blood or with RBCs in plasma. By contrast, arginase inhibition did not improve postischemic recovery when administered with buffer solution or plasma alone. The protective effect of arginase inhibition was lost in the presence of a NOS inhibitor. Moreover, hearts from eNOS−/− mice were protected when the arginase inhibitor was given with blood from wild-type donors. In contrast, when hearts from wild-type mice were given blood from eNOS−/− mice, the arginase inhibitor failed to protect against ischemia-reperfusion. These results strongly support the notion that RBCs contain functional eNOS and release NO-like bioactivity. This process is under tight control by arginase 1 and is of functional importance during ischemia-reperfusion.