Miracle-dz/UniFAR-FTUs huggingface dataset:
How Many Cell Types Does It Take to Wire a Brain?

Microglia play an important role in the maturation of synaptic circuits in newborn mice. Microglia, highly mobile immune cells that reside in the central nervous system, are traditionally viewed as “barometers” of the brain because they rapidly respond to cellular damage caused by injury and disease by engulfing and cleaning up debris (1). Imaging studies, however, have revealed that microglia are also ceaselessly active in healthy brains, and other studies have shown that this activity is often associated with synapses, which move signals between neurons (2–4). Despite these intriguing observations, the function of microglia at healthy synapses has been elusive. On page 1456 of this issue, Paolicelli et al. (5) help pin it down. They demonstrate that micro glia are involved in the development of brain wiring in newborn mice and that disrupting micro gliasynapse interactions delays the maturation of synaptic circuits. The finding offers insight into the mechanisms underlying synapse maturation and into brain diseases in which synaptic connectivity is altered.
Deep hedging

We present a framework for hedging a portfolio of derivatives in the presence of market frictions such as transaction costs, liquidity constraints or risk limits using modern deep reinforcement machine learning methods. We discuss how standard reinforcement learning methods can be applied to non-linear reward structures, i.e. in our case convex risk measures. As a general contribution to the use of deep learning for stochastic processes, we also show in Section 4 that the set of constrained trading strategies used by our algorithm is large enough to ε-approximate any optimal solution. Our algorithm can be implemented efficiently even in high-dimensional situations using modern machine learning tools. Its structure does not depend on specific market dynamics, and generalizes across hedging instruments including the use of liquid derivatives. Its computational performance is largely invariant in the size of the portfolio as it depends mainly on the number of hedging instruments available. We illustrate our approach by an experiment on the S&P500 index and by showing the effect on hedging under transaction costs in a synthetic market driven by the Heston model, where we outperform the standard ‘complete-market’ solution.
Design for Robust Controls Having Almost Minimum Time Response

The problem of proximate time-optimal control of third-order systems is considered. Two third-order proximate time-optimal servomechanisms, PTOS3 and PTOS3¿, are proposed for type-3 and type-2 third-order plants, respectively. The approach used here to develop the controllers is that of constructing a 'slab' in 3-dimensional state space that describes the 'switching' structure of the control. The technique relies on 3-dimensional phase-space analysis which is rarely applied to systems of order 3 or higher. Simulation results demonstrate the performance of the developed algorithms.
Naloxone Blockade of (‐)Pentazocine‐Induced Changes in Auditory Function

Objective: In a previous report, we found that intravenous (IV) (‐)pentazocine improved auditory sensitivity and significantly altered compound action potential (CAP) amplitudes. Its sigma (σ)‐receptor‐selective optical isomer (+)pentazocine administered at the same dose was without effect, suggesting that the observed auditory neural effects might be mediated by an opioid receptor. To directly test this hypothesis, in the present investigation we attempted to antagonize the auditory neural effects of(‐)pentazocine using the pure, nonspecific drug antagonist naloxone. Design: In 25 normal‐hearing, male, pigmented chinchillas, amplitude and latency changes in the click‐evoked auditory nerve CAP (N1) and cochlear microphonic (CM) were tracked at six stimulus intensities during a baseline period and after the postbaseline administration of the opioid drug agonist(‐)pentazocine (16 mg/kg; IV). In separate groups of chinchillas,(‐)pentazocine was given alone or administered in combination with the standard opioid receptor antagonist naloxone administered at two doses. Results: Robust changes in CAP amplitudes after (‐)pentazocine occurred in the absence of measurable alterations in CAP response latencies, CM amplitudes, or blood chemistries and were significantly antagonized when naloxone (5 mg/kg) was added to the IV infusion. Conclusions: The observed blockade clearly indicates that the agonist effects of(‐)pentazocine are opioid receptor‐mediated and suggests a connection between opioid receptors and auditory neural function. Mechanisms of action and the connection between an opioid modulation of auditory function and stress, hyperacusis, and tinnitus are discussed.
Cost comparison between the atraumatic and cutting lumbar puncture needles

Objective: The aim of this study was to determine which type of spinal needle is preferred from a cost perspective, taking into account costs of the spinal needle and treatment of postlumbar puncture headache. Methods: A decision-analytic model was created to determine the cost of diagnostic lumbar punctures using atraumatic and cutting needles. We assumed a health care system perspective and based the analysis on the treatment of a patient facing event probabilities derived from prior studies. The economic outcome measure was the difference in estimated costs between the 2 needles. One-way and probabilistic sensitivity analyses tested the robustness of the model. Results: Lumbar puncture performed with the atraumatic needle is associated with an average cost savings of $26.07 per patient. Average total health care costs are $166.08 with the atraumatic needle, compared to $192.15 with the cutting needle. There is 94% certainty that the atraumatic needle is cost-saving compared to the cutting needle based on probabilistic sensitivity analysis. Use of the atraumatic needle over the cutting needle by neurologists alone may result in $10.4 million in cost savings to the US health care system per year. Conclusion: The atraumatic spinal needle is associated with an overall cost savings to the US health care system. The balance of costs and benefits favors the use of the atraumatic needle over the cutting needle for diagnostic lumbar puncture.
Phase III comparison of depomedroxyprogesterone acetate to venlafaxine for managing hot flashes: North Central Cancer Treatment Group Trial N99C7.

PURPOSE Vasomotor hot flashes are a common problem in menopausal women. Given concerns regarding estrogen and/or combined hormonal therapy, other treatment options are desired. Prior trials have confirmed that progestational agents and newer antidepressants effectively reduce hot flashes. This current trial compared a single intramuscular dose of medroxyprogesterone acetate (MPA), depot preparation, versus daily oral venlafaxine as treatment for hot flashes. METHODS Women with bothersome hot flashes were entered onto this trial, were randomly assigned to treatment, and then had a baseline week where hot flash scores were recorded without treatment. They were then treated and observed for 6 weeks; daily diaries were used to measure hot flash frequencies and severities. There were 109 patients per each arm randomly assigned to receive MPA 400 mg intramuscularly for a single dose versus venlafaxine 37.5 mg per day for a week, then 75 mg per day. RESULTS During the sixth week after random assignment, hot flash scores were reduced by 55% in the venlafaxine arm versus 79% in the MPA arm (P < .0001). In an intention-to-treat analysis, 46% of venlafaxine patients (50 of 109) compared with 74% of the MPA patients (81 of 109) had a decrease in hot flashes by more than 50% from baseline (P < .0001). Less toxicity was reported in the MPA arm. CONCLUSION A single MPA dose seems to be well tolerated and more effectively reduces hot flashes than does venlafaxine.
Isolation and Characterization of RNA Polymerase rpoB Mutations That Alter Transcription Slippage during Elongation in Escherichia coli*

Background: The domains in RNA polymerase involved in elongation slippage are unknown. Results: We isolated E. coli RNA polymerase rpoB mutants with altered transcriptional slippage. Conclusion: The fork domain of RNA polymerase controls slippage. Biochemical analysis of the mutants validates the genetic schemes. Significance: Our work sheds light on the mechanism for maintenance of RNA-DNA register during transcription. Transcription fidelity is critical for maintaining the accurate flow of genetic information. The study of transcription fidelity has been limited because the intrinsic error rate of transcription is obscured by the higher error rate of translation, making identification of phenotypes associated with transcription infidelity challenging. Slippage of elongating RNA polymerase (RNAP) on homopolymeric A/T tracts in DNA represents a special type of transcription error leading to disruption of open reading frames in Escherichia coli mRNA. However, the regions in RNAP involved in elongation slippage and its molecular mechanism are unknown. We constructed an A/T tract that is out of frame relative to a downstream lacZ gene on the chromosome to examine transcriptional slippage during elongation. Further, we developed a genetic system that enabled us for the first time to isolate and characterize E. coli RNAP mutants with altered transcriptional slippage in vivo. We identified several amino acid residues in the β subunit of RNAP that affect slippage in vivo and in vitro. Interestingly, these highly clustered residues are located near the RNA strand of the RNA-DNA hybrid in the elongation complex. Our E. coli study complements an accompanying study of slippage by yeast RNAP II and provides the basis for future studies on the mechanism of transcription fidelity.
A Specific Shifting Deficit in Parkinson's Disease: A Reversal Shift of Consistent Stimulus-Response Mappings

Two experiments were designed to investigate effects of cueing upon aptitude for shifting by patients with Parkinson's disease. Subjects executed in alternation two different components of a task set over successive items in a list. We compared the costs of shifting when the stimulus ensemble remained constant from trial to trial (“uniform” lists), with the case in which a change of stimulus ensemble cued each shift of task (“mixed” lists). Shift costs with mixed lists were significantly smaller than those with uniform lists (Exp. 1, ns=12). This suggests that patients with Parkinson's disease can benefit from cues about the stimulus ensemble in performing tasks. Patients' shifting performance was different from that of controls only in a reversalshift condition of the previously consistent stimulus-response mappings (Exp. 2, ns = 12). This result suggests that patients with Parkinson's disease suffer from a specific but not a general deficit in ability to shift.
History of affective disorder and the experience of fatigue in rheumatoid arthritis.

OBJECTIVE To evaluate how a prior affective disorder (major depression or generalized anxiety disorder) affects current fatigue among individuals with rheumatoid arthritis (RA). To determine whether that relationship is mediated by self-efficacy expectations. METHODS Forty-eight RA patients with a prior affective disorder and 74 without a history of affective disorder completed a mailed questionnaire that included the Multidimensional Assessment of Fatigue and indicators of neuroticism and self efficacy. RESULTS RA patients with a history of affective disorder reported higher levels of fatigue than those with no previous affective disturbance. Controlling for neuroticism and self efficacy, affective disorder history continued to predict current fatigue. Mediational analyses revealed both direct and indirect effects (via self efficacy) of history of affective disorder on the experience of fatigue in RA. CONCLUSION History of affective disorder independently predicts higher levels of fatigue in RA patients, and self efficacy plays a mediating role in this relationship.
Bridging the gap: the roles of social capital and ethnicity in medical student achievement

Within medical education, there is a discrepancy between the achievement level of White students and that of their ethnic minority peers. The processes underlying this disparity have not been adequately investigated or explained. This study utilises social network analysis to investigate the impact of relationships on medical student achievement by ethnicity, specifically by examining homophily (the tendency to interact with others in the same group) by ethnicity, age and role.
Improved clinical outcome using polytetrafluoroethylene-coated stents for TIPS: results of a randomized study.

BACKGROUND & AIMS A 50% dysfunction rate at 1 year is one of the main drawbacks of the transjugular intrahepatic portosystemic shunt procedure. Preliminary experimental and clinical studies suggest that the use of stents covered with polytetrafluoroethylene could tremendously decrease this risk. METHODS Eighty patients with cirrhosis and uncontrolled bleeding (n = 23), recurrent bleeding (n = 25), or refractory ascites (n = 32) were randomized to be treated by transjugular intrahepatic portosystemic shunts with either a polytetrafluoroethylene-covered stent (group 1; 39 patients) or a usual uncovered prosthesis (group 2; 41 patients). Follow-up Doppler ultrasound was scheduled at day 7, at 1 month, and then every 3 months for 2 years. Angiography and portosystemic pressure gradient measurements were performed 6, 12, and 24 months after the transjugular intrahepatic portosystemic shunt procedure and whenever dysfunction was suspected. Dysfunction was defined as a >50% reduction of the lumen of the shunt at angiography or a portosystemic pressure gradient >12 mm Hg. RESULTS After a median follow-up of 300 days, 5 patients (13%) in group 1 and 18 (44%) in group 2 experienced shunt dysfunction (P < 0.001). Clinical relapse occurred in 3 patients (8%) in group 1 and 12 (29%) in group 2 (P < 0.05). Actuarial rates of encephalopathy were 21% in group 1 and 41% in group 2 at 1 year (not significant). Estimated probabilities of survival were 71% and 60% at 1 year and 65% and 41% at 2 years in groups 1 and 2, respectively (not significant). CONCLUSIONS The use of polytetrafluoroethylene-covered prostheses improves transjugular intrahepatic portosystemic shunt patency and decreases the number of clinical relapses and reinterventions without increasing the risk of encephalopathy.
Arabidopsis SHY 2 / IAA 3 Inhibits Auxin-Regulated Gene Expression

In Arabidopsis, SHY2 encodes IAA3 , a member of the auxin-induced Aux/IAA family. Gain-of-function mutations in SHY2/IAA3 cause enlarged cotyledons, short hypocotyls, and altered auxin-regulated root development. Here we show that the gain-of-function mutation shy2-2 decreases both the induction and repression of auxin-regulated genes, suggesting that SHY2/IAA3 acts as a negative regulator in auxin signaling. shy2-2 affects auxin induction of many previously characterized primary response genes, implying that it might repress primary auxin responses. In addition, shy2-2 also affects expression of multiple auxin-nonresponsive genes. Light regulates expression of SHY2/IAA3 , suggesting a possible link between light and auxin response pathways.
Evaluation of motion and realignment for functional magnetic resonance imaging in real time

Functional magnetic resonance imaging in real time is an emerging tool for the assessment of dynamic changes in brain activation. The short response latency (tens of seconds) renders the technique more sensitive to motion artifacts. Motion correction in real time requires computationally efficient algorithms which can be executed on a complete 3D data set within a single time of repetition cycle. In this study, a method to evaluate motion and realign functional images in real time implemented on standard imaging hardware is introduced. The detection of activity in correlation maps is improved, and artifactual edge enhancements are reduced. As the estimation of large movements is stable, this algorithm is attractive for clinical studies with uncooperative patients. Magn Reson Med 45:167–171, 2001. © 2001 Wiley‐Liss, Inc.
Calcium Dependence of Settlement and Nematocyst Discharge in Actinulae of the Hydroid Tubularia mesembryanthemum.

The influence of Ca2+ and Mg2+ ions on both atrichous isorhiza (AI) discharge and settlement of actinular larvae of the hydroid Tubularia mesembryanthemum was investigated. Mg2+-supplemented artificial seawater (ASW) completely inhibited both events at a concentration of 206 mM, whereas lowered Mg2+ concentrations enhanced them. Ca2+ ions in the bathing solution highly regulated AI discharge and settlement, and Mg2+ ions may down-regulate these events. The effect of inorganic Ca2+-channel blockers, including Gd3+ and La3+, was also examined. Larval settlement was inhibited by Co2+, Ni2+, Cd2+, La3+, and Gd3+, with half inhibitory concentrations (IC50) of 5800, 260, 53, 45, and 7 {mu}M, respectively; AI discharge was also inhibited by these ions, with IC50 values of 6600, 500, 78, 41, and 5 {mu}M, respectively. These results suggest possible involvement of stretch-activated Ca2+ channels in the signal transmission of both AI discharge and larval settlement.
Unbinding of oxidized cytochrome c from photosynthetic reaction center of Rhodobacter sphaeroides is the bottleneck of fast turnover.

To understand the details of rate limitation of turnover of the photosynthetic reaction center, photooxidation of horse heart cytochrome c by reaction center from Rhodobacter spheroides in detergent dispersion has been examined by intense continuous illumination under a wide variety of conditions of cytochrome concentration, ionic strength, viscosity, temperature, light intensity, and pH. The observed steady-state turnover rate of the cytochrome was not light intensity limited. In accordance with recent findings [Larson, J. W. , Wells, T. A. , and Wraight, C. A. (1998) Biophys. J. 74 (2), A76], the turnover rate increased with increasing bulk ionic strength in the range of 0-40 mM NaCl from 1000 up to 2300 s(-)(1) and then decreased at high ionic strength under conditions of excess cytochrome and ubiquinone and a photochemical rate constant of 4500 s(-)(1). Furthermore, we found the following: (i) The contribution of donor (cytochrome c) and acceptor (ubiquinone) sides as well as the binding of reduced and the release of oxidized cytochrome c could be separated in the observed kinetics. At neutral and acidic pH (when the proton transfer is not rate limiting) and at low or moderate ionic strength, the turnover rate of the reaction center was limited primarily by the low release rate of the photooxidized cytochrome c (product inhibition). At high ionic strength, however, the binding rate of the reduced cytochrome c decreased dramatically and became the bottleneck. The observed activation energy of the steady-state turnover rate reflected the changes in limiting mechanisms: 1.5 kcal/mol at 4 mM and 5.7 kcal/mol at 100 mM ionic strength. A similar distinction was observed in the viscosity dependence of the turnover rate: the decrease was steep (eta(-)(1)) at 40 and 100 mM ionic strengths and moderate (eta(-)(0.2)) under low-salt (4 mM) conditions. (ii) The rate of quinone exchange at the acceptor side with excess ubiquinone-30 or ubiquinone-50 was higher than the cytochrome exchange at the donor side and did not limit the observed rate of cytochrome turnover. (iii) Multivalent cations exerted effects not only through ionic strength (screening) but also by direct interaction with surface charge groups (ion-pair production). Heavy metal ion Cd(2+) bound to the RC with apparent dissociation constant of 14 microM. (iv) A two-state model of collisional interaction between reaction center and cytochrome c together with simple electrostatic considerations in the calculation of rate constants was generally sufficient to describe the kinetics of photooxidation of dimer and cytochrome c. (v) The pH dependence of cytochrome turnover rate indicated that the steady-state turnover rate of the cytochrome under high light conditions was not determined by the isoelectric point of the reaction center (pI = 6. 1) but by the carboxyl residues near the docking site.
Serum antibody and opsonic responses after immunization with pneumococcal vaccine in kidney transplant recipients and controls

We immunized 31 renal transplant patients and 6 control subjects with a pneumococcal vaccine containing 14 capsular polysaccharides. Antibody levels to Streptococcus pneumoniae types 3 and 6A were measured by a radioimmunoassay, and opsonic activity to S. pneumoniae types 3 and 6B was determined by using a luminol-enhanced chemiluminescence phagocytic assay on serum samples obtained before and 1 month after immunization. There was a 10.2-fold and a 2.9-fold increase in antibody to S. pneumoniae type 3 (P less than 0.005) and type 6A (P less than 0.01), respectively, but only a 1.3-fold (P greater than 0.05) and 1.1-fold (P greater than 0.05) increase in opsonic activity. For S. pneumoniae type 3, changes in opsonic activity correlated well with antibody concentration (P less than 0.05). However, for S. pneumoniae type 6, these two tests correlated poorly (P greater than 0.05). This poor correlation suggests that concentrations of antibody to type 6A polysaccharide which are achieved after immunization may not be opsonically active in vitro against S. pneumoniae type 6B.
Low Contrast Detectability and Contrast/Detail Analysis in Medical Ultrasound

Abstruct-The first- and second-order statistics of envelope detected ultrasound (US)B-mode images for the case of a scattering phantom with many scatteiers per resolution cell have been previously derived. These characteristics are integrated over the region of a simulated focal (disk) lesion and the signal-to-noise ratio (SNR) for lesion detectability is obtained. This SNR requires the average number of independent speckle cells over the lesion area (analogous to the number of x-ray photons over the lesion area in incoherent light or x-ray imaging). This number is obtained from our autocorrelation analysis (second-order statistics). By setting the SNR expression equal to the threshold value SNRT required to detect a lesion in the presence of speckle noise, the dependence of lesion contrast on lesion diameter at threshold is found, i.e., the contrast/detail function. This is a simple inverse relation for ideal observers of US B-scans. It is also found that the contrast/detail results for envelope detectionin diagnostic ultrasound are almost identical with the results for square law detection (the usual laser case) with the latter serving as an upper limit for performance in lesion detection. Finally, the results of human observer performance using a contrast/ detail phantom are compared with the predictions for optimal or ideal 2cm Fig. 1. Schematic of contrast/detail phantom for diagnostic ultrasound. performance. The results are comparable with results for photon imaging systems, with valuesof the SNR at threshold in the neighborhood of 2-3.