Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroanatomical predictors of response to donepezil therapy in patients with dementia.

BACKGROUND Patients with dementia of the Alzheimer type (DAT) respond variably to treatment with acetylcholinesterase inhibitors. OBJECTIVE To determine whether measures of hippocampal volume and shape predict the response to donepezil in patients with DAT. DESIGN T1-weighted, magnetic resonance images were obtained from patients with DAT, who subsequently underwent treatment with donepezil. Brain-mapping algorithms were used to quantify hippocampal volume and shape, and growth curves were used to estimate clinical outcome. SETTING A referral outpatient center specializing in treatment of dementia. PATIENTS Thirty-seven patients with very mild or mild DAT received donepezil therapy for up to 4 weeks before magnetic resonance imaging and for 24 to 96 weeks after magnetic resonance imaging. INTERVENTION Donepezil, 10 mg/d. MAIN OUTCOME MEASURE Rate of change in the cognitive portion of the Alzheimer's Disease Assessment Scale total scores. RESULTS Smaller hippocampal volume and inward variation of the lateral and inferomedial portions of the hippocampal surface were correlated with a poorer response to donepezil therapy. CONCLUSIONS Measures of hippocampal volume and surface variation can be used to predict the response of patients with DAT to the acetylcholinesterase inhibitor donepezil.
An integral battery charger with Power Factor Correction for electric scooter

An integral battery charger is proposed for an electric scooter with Li-Ion batteries and Interior-Permanent-Magnet (IPM) traction motor. The battery charger is integrated in the power hardware of the scooter, with the IPM traction drive that operates as three-phase dc-dc converter with Power Factor Correction (PFC) capability. The control of the PFC battery charger is also integrated into the traction control code that is performed by a fixed-point DSP controller. Current-controlled and voltage-controlled battery charge are actuated according to the requirements of the Battery Management System (BMS), that is embedded in the battery pack. Respect to other on-board chargers, the AC current is absorbed at unitary power factor with no harmonic distortion and no particular filtering is needed since the PWM ripple is minimized by interleaving the three phases of the converter. Other type of motors are also considered (IM, SMPM) and commented. The feasibility of the integral battery charger is demonstrated on a prototype electric scooter with high voltage battery (260V nominal).
Widespread Weathered Glass on the Surface of Mars

Low albedo sediments cover >10 7 km 2 in the northern lowlands of Mars, but the composition and origin of these widespread deposits have remained ambiguous despite many previous investigations. Here we use near-infrared spectra acquired by the Mars Express OMEGA (Observatoire pour la Mineralogie, l9Eau, les Glaces, et l9Activite) imaging spectrometer to show that these sediments exhibit spectral characteristics that are consistent with both high abundances of iron-bearing glass and silica-enriched leached rinds on glass. This interpretation is supported by observations of low-albedo soil grains with possible rinds at the Phoenix Mars Lander landing site in the northern lowlands. By comparison with the extensive glass-rich dune fields and sand sheets of Iceland, we propose an explosive volcanic origin for these glass-rich sediments. We also propose that the glassy remnant rinds on the sediments are the result of postdepositional alteration, as these rinds are commonly formed in arid terrestrial volcanic environments during water-limited, moderately acidic leaching. These weathered, glass-rich deposits in the northern lowlands are also colocated with the strongest concentrations of a major global compositional surface type previously identified in mid-infrared spectra, suggesting that they may be representative of global processes. Our results provide potential confirmation of models suggesting that explosive volcanism has been widespread on Mars, and also raise the possibilities that glass-rich volcaniclastics are a major source of eolian sand on Mars and that widespread surficial aqueous alteration has occurred under Amazonian climatic conditions.
Ultrasound imaging-guided noninvasive ultrasound thrombolysis: preclinical results.

BACKGROUND Catheter-based therapeutic ultrasound thrombolysis was recently shown to be effective and safe. The purpose of this work was to study the safety and efficacy of external high-intensity focused ultrasound thrombolysis guided by ultrasound imaging in experimental settings. METHODS AND RESULTS A therapeutic transducer was constructed from an acoustic lens and integrated with an ultrasound imaging transducer. In vitro clots were inserted into bovine arterial segments and sonicated under real-time ultrasound imaging guidance in a water tank. With pulsed-wave (PW) ultrasound, the total sonication time correlated with thrombolysis efficiency (r(2)=0.7666). A thrombolysis efficiency of 91% was achieved with optimal PW parameters (1:25 duty cycle, 200-micros pulse length) at an intensity (I(spta)) of >35+/-5 W/cm(2). Ultrasound imaging during sonication showed the cavitation field as a spherical cloud of echo-dense material. Within <2 minutes, the vessel lumen evidenced neither residual clot nor damage to the arterial wall. On serial filtration, 93+/-1% of the lysed clot became subcapillary in size (<8 microm). In vitro safety studies, however, showed arterial damage when an I(spta) of 45 W/cm(2) was used for periods of >/=300 seconds. CONCLUSIONS External high-intensity focused ultrasound thrombolysis using optimal PW parameters for periods of </=300 seconds appears to be a safe and effective method to induce thrombolysis. The procedure can be guided by ultrasound imaging, thereby allowing the monitoring of therapy.
Incretin mimetics and dipeptidyl peptidase 4 inhibitors in clinical trials for the treatment of type 2 diabetes.

BACKGROUND Exenatide is an incretin mimetic, while sitagliptin and vildagliptin are incretin enhancers used as adjunctive therapy in patients with type 2 diabetes failing oral agents. Sitagliptin and vildagliptin can also be used as monotherapy in patients with type 2 diabetes uncontrolled by diet. OBJECTIVE To provide a critical review of clinical trials of exenatide, sitagliptin and vildagliptin. METHOD Review of Phase III clinical trials based on Medline search published up to April 2008. RESULTS The use of exenatide is associated with reduction in average hemoglobin A1c (HbA1c) levels of approximately 0.8% compared with baseline. The corresponding reduction with either sitagliptin or vildagliptin is 0.7%. The actions of incretin-based drugs predominantly target postprandial hyperglycemia. Treatment-related hypoglycemia is generally mild, and mainly occurs when used with sulfonylureas (SUs). Exenatide treatment leads to a mild weight loss of around 2 kg after 30 weeks, whereas sitagliptin and vildagliptin have generally neutral effect on weight. Sitagliptin and vildagliptin are well tolerated in trials lasting up to 52 weeks. Meanwhile, 5 - 10% of patients cannot tolerate exenatide due to adverse effects, mainly nausea and vomiting. The three drugs are limited by the lack of long-term safety and efficacy data, as well as by their high cost. CONCLUSION Exenatide, sitagliptin and vildagliptin are useful add-on therapy for type 2 diabetes that is suboptimally controlled on oral agents, particularly when there is concern about weight gain and hypoglycemia, or when postprandial hyperglycemia is the major cause of inadequate glycemic control. Sitagliptin and vildagliptin may be used as monotherapy in patients who cannot tolerate metformin or SU, and sitagliptin may be used as alternative to metformin in renal insufficiency.
Anatomy of Risk Premium in UK Natural Gas Futures

In many futures markets, trading is concentrated in the front contract and positions are rolled-over until the strategy horizon is attained. In this paper, a pair-wise comparison between the conventional risk premium and the accrued risk premium in rolled-over positions in the front contract is carried out for UK natural gas futures. Several novel results are obtained. Firstly, and most importantly, the accrued risk premium in rollover strategies is significatively larger than conventional risk premiums and increases with the time to delivery. Specifically, for strategy horizons between three and six months, this difference increases from 1% to 10%. Secondly, it is the first time that risk premium in day-ahead futures has been measured in this market. The average value of the day-ahead risk premium is 0.5% per day and it is statistically significant. Thirdly, all risk premiums are significantly larger and more volatile in winter. Finally, risk premium time-variation is analyzed using a regression model. It is shown that reservoirs, weather, liquidity, volatility, skewness, and seasons are able in all cases to explain between 21% and 59% of the risk premium time-variation (depending on the futures maturity and sub-period).
Altering Effects of Antigenic Variations in HIV-1 on Antiviral Effectiveness of HIV-Specific CTLs1

The mutational escape of HIV-1 from established CTL responses is becoming evident. However, it is not yet clear whether antigenic variations of HIV-1 may have an additional effect on the differential antiviral effectiveness of HIV-specific CTLs. Herein, we characterized HIV-specific CTL responses toward Pol, Env, and Nef optimal epitopes presented by HLA-B*35 during a chronic phase of HIV-1 infection. We found CTL escape variants within Pol and Nef epitopes that affected recognition by TCRs, although there was no mutation within the Env epitope. An analysis of peptide-HLA tetrameric complexes revealed that CD8 T cells exclusively specific for the Nef variant were generated following domination by the variant viruses. The variant-specific cells were capable of killing target cells and producing antiviral cytokines but showed impaired Ag-specific proliferation ex vivo, whereas wild-type specific cells had potent activities. Moreover, clonotypic CD8 T cells specific for the Pol variant showed diminished proliferation, whereas Env-specific ones had no functional heterogeneity. Taken together, our data indicate that antigenic variations that abolished TCR recognition not only resulted in escape from established CTL responses but also eventually generated another subset of variant-specific CTLs having decreased antiviral activity, causing an additional negative effect on antiviral immune responses during a chronic HIV infection.
Effect of a New Imidazolium-based Silver Nanoparticle Irrigant on the Bond Strength of Epoxy Resin Sealer to Root Canal Dentine

Introduction: The aim of this study was to evaluate the effect of a new imidazolium-based silver nanoparticle (ImSNP) root canal irrigant on the bond strength of AH-Plus sealer to root canal dentine. Methods and Materials: Forty single-rooted extracted human teeth were used in this study. The crowns were resected and according to the irrigation solutions used during root canal preparation, the roots were divided into 5 groups (n=8): Group 1: normal saline (control group), Group 2: 2.5% Sodium Hypochlorite (NaOCl), Group 3: 2.5% NaOCl+17% ethylene diamin tetracetic acid (EDTA), Group 4: silver nanoparticles (AgNPs), Group 5: AgNPs +17% EDTA. After root canal instrumentation, the canals were filled with AH-Plus. Then, after 7 days, 2 or 3 dentine disks were obtained from the mid-root of each sample. Bond strength was measured by the push-out test. Additionally, failure patterns were classified as adhesive, cohesive and mixed. Data were statistically analyzed by one-way ANOVA and Tamhane post hoc tests. The level of significance was set at 0.05. Results: There was no statistically significant differences between groups (P>0.05). Groups 4 (AgNPs), 3 (2.5% NaOCl+17% EDTA) and 2 (2.5% NaOCl) showed statistically higher bond strength compared to group 1 (control group) (P<0.05). Also, Group 4 showed a significant difference with group 5 (AgNPs+17% EDTA) (P=0.017). The failure patterns were mainly cohesive. Conclusion: This in vitro study showed that, when used without EDTA, AgNPs improved the bond strength of AH-Plus to radicular dentine.
Polycystin-1 Negatively Regulates Polycystin-2 Expression via the Aggresome/Autophagosome Pathway*

Background: PC1 and PC2 function as a complex, but their interrelations are not completely understood. Results: Expression of PC1 accelerates degradation of PC2. Conclusion: PC1 negatively regulates PC2 expression, presumptively by enhancing degradation via the aggresome/autophagosome pathway. Significance: Understanding how PC1 regulates PC2 within a critical range may help elucidate the pathogenesis of cyst formation. Mutations of the PKD1 and PKD2 genes, encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively, lead to autosomal dominant polycystic kidney disease. Interestingly, up-regulation or down-regulation of PKD1 or PKD2 leads to polycystic kidney disease in animal models, but their interrelations are not completely understood. We show here that full-length PC1 that interacts with PC2 via a C-terminal coiled-coil domain regulates PC2 expression in vivo and in vitro by down-regulating PC2 expression in a dose-dependent manner. Expression of the pathogenic mutant R4227X, which lacks the C-terminal coiled-coil domain, failed to down-regulate PC2 expression, suggesting that PC1-PC2 interaction is necessary for PC2 regulation. The proteasome and autophagy are two pathways that control protein degradation. Proteins that are not degraded by proteasomes precipitate in the cytoplasm and are transported via histone deacetylase 6 (HDAC6) toward the aggresomes. We found that HDAC6 binds to PC2 and that expression of full-length PC1 accelerates the transport of the HDAC6-PC2 complex toward aggresomes, whereas expression of the R4227X mutant fails to do so. Aggresomes are engulfed by autophagosomes, which then fuse with the lysosome for degradation; this process is also known as autophagy. We have now shown that PC1 overexpression leads to increased degradation of PC2 via autophagy. Interestingly, PC1 does not activate autophagy generally. Thus, we have now uncovered a new pathway suggesting that when PC1 is expressed, PC2 that is not bound to PC1 is directed to aggresomes and subsequently degraded via autophagy, a control mechanism that may play a role in autosomal dominant polycystic kidney disease pathogenesis.
Glutamatergic Regulation of Basal and Stimulus‐Activated Dopamine Release in the Prefrontal Cortex

Abstract: The present study was undertaken to determine whether basal and stimulus‐activated dopamine release in the prefrontal cortex (PFC) is regulated by glutamatergic afferents to the PFC or the ventral tegmental area (VTA), the primary source of dopamine neurons that innervate the rodent PFC. In awake rats, blockade of NMDA or α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) receptors in the VTA, or blockade of AMPA receptors in the PFC, profoundly reduced dopamine release in the PFC, suggesting that the basal output of dopamine neurons projecting to the PFC is under a tonic excitatory control of NMDA and AMPA receptors in the VTA, and AMPA receptors in the PFC. Consistent with previous reports, blockade of cortical NMDA receptors increased dopamine release, suggesting that NMDA receptors in the PFC exert a tonic inhibitory control on dopamine release. Blockade of NMDA or AMPA receptors in the VTA as well as blockade of AMPA receptors in the PFC reduced the dopaminergic response to mild handling, suggesting that activation of glutamate neurotransmission also regulates stimulus‐induced increase of dopamine release in the PFC. In the context of brain disorders that may involve cortical dopamine dysfunction, the present findings suggest that abnormal basal or stimulus‐activated dopamine neurotransmission in the PFC may be secondary to glutamatergic dysregulation.
Repeated Piperacillin-Tazobactam Plasma Concentration Measurements in Severely Obese Versus Nonobese Critically Ill Septic Patients and the Risk of Under– and Overdosing*

Objective: Obesity and critical illness modify pharmacokinetics of antibiotics, but piperacillin-tazobactam continuous IV infusion pharmacokinetics has been poorly studied in obese critically ill patients. We aimed to compare pharmacokinetics of piperacillin in severely obese and nonobese patients with severe sepsis or septic shock. We hypothesized that plasma concentration variability would expose the critically ill to both piperacillin under and overdosing. Methods: Prospective comparative study. Consecutive critically ill severely obese (body mass index, > 35 kg/m2) and nonobese patients (body mass index, < 30 kg/m2) were treated with 16 g/2 g/24 hr continuous piperacillin-tazobactam infusion. Piperacillin plasma concentration was measured every 12 hours over a 7-day period by high-pressure liquid chromatography. Unbound piperacillin plasma concentration and fractional time of plasma concentration spent over 64 mg/L (4-fold the minimal inhibitory concentration for Pseudomonas aeruginosa) were compared between the two groups. We performed 5,000 Monte Carlo simulations for various dosing regimens and minimal inhibitory concentration and calculated the probability to spend 100% of the time over 64 mg/L. Results: We enrolled 11 severely obese and 12 nonobese patients and obtained 294 blood samples. We did not observe a statistically significant difference in piperacillin plasma concentrations over time between groups. The fractional time over 64 mg/L was 64% (43–82%) and 93% (85–100%) in obese and nonobese patients, respectively, p = 0.027 with intra- and intergroup variability. Five nonobese and two obese patients experienced potentially toxic piperacillin plasma concentrations. When 64 mg/L was targeted, Monte Carlo simulations showed that 12 g/1.5 g/24 hr was inadequate in both groups and 16 g/2 g/24 hr was adequate only in nonobese patients. Conclusion: Using a conventional dosing of 16 g/2 g/24 hr continuous infusion, obese patients were more likely than nonobese patients to experience piperacillin underdosing when facing high minimal inhibitory concentration pathogens. The present study suggests that piperacillin drug monitoring might be necessary in the sickest patients who are at the highest risk of unpredictable plasma concentration exposing them to overdose, toxicity, underdosing, and treatment failure.
Equity home bias : a global perspective

This paper provides a global perspective on equity home bias using MSCI country and world index (returns) data for 39 countries for the period 2000 – 2009. Two measures of home bias, namely, diffuse priors based I-CAPM measure, and, BayesStein shrinkage based mean-variance measure are used. The I-CAPM is tested and holds for the country sample. The estimated optimal equity investment weights arising from the single factor ICAPM prove highly sensitive to the world market excess returns. The Bayes-Stein shrinkage estimator reduces parameter uncertainty through Bayesian shrinkage of the equity investment allocation parameters. Shrinkage estimation results in more acceptable values of home bias, particularly for the USA. We find that developed economies in the Euro zone display lower equity investment home bias compared to the emerging economies. Australia displays moderately high equity home bias which is similar to that of Canada, Japan and USA, and higher than that of the developed Euro zone economies. The system GMM procedure of panel analysis reveals that country idiosyncratic risk, country financial structure and country institutional quality constitute the three most important determinants of global equity home bias over the last decade. Policy options and their implications are discussed.
General Structure of the Causal and Stable Inverses of MIMO Systems with ISI

This paper, gives a general framework to investigate the existence and the general structure of causal inverse filters for multiple-input multiple-output (MIMO) systems with intersymbol interference (ISI). It gives necessary and sufficient conditions for the existence of causal and stable inverse filters allowing for further properties of the receive filters such as stability and smoothness of its transfer function. Furthermore, a parametrization and the general structure of all causal inverses are given
A STOCK-ADJUSTMENT INVESTMENT MODEL'

Firms' investment in plant and equipment is explained by a stock-adjustment model in which the coefficient of adjustment is allowed to vary. It is assumed that firms partially close the gap between desired and actual capital stock, but that the speed of adjustment depends on the firm's ability to procure funds at reasonable cost. A panel of individual firm responses to the McGraw-Hill plant and equipment survey is the principal data source, supplemented by financial statement information for the firms and two indices representing costs of debt and equity financing. The predictions generated by the regressions are aggregated for comparison with the observed aggregates. 1. A STOCK-ADJUSTMENT INVESTMENT MODEL THE PURPOSE of this paper is to develop and test a model to explain firms' investment in plant and equipment. The model incorporates features which recent research on the investment decision suggests are significant. The basic framework is a stock-adjustment model, in which each year the firm moves partially toward its desired position, with the coefficient of adjustment (reaction coefficient) allowed to vary by firm and year. The model has the form
Structure, scaling, and phase transition in the optimal transport network.

The structure and properties of optimal networks depend on the cost functional being minimized and on constraints to which the minimization is subject. We show here two different formulations that lead to identical results: minimizing the dissipation rate of an electrical network under a global constraint is equivalent to the minimization of a power-law cost function introduced by Banavar et al. [Phys. Rev. Lett. 84, 4745 (2000)10.1103/PhysRevLett.84. 4745]. An explicit scaling relation between the currents and the corresponding conductances is derived, proving the potential flow nature of the latter. Varying a unique parameter, the topology of the optimized networks shows a transition from a tree topology to a very redundant structure with loops; the transition corresponds to a discontinuity in the slope of the power dissipation.
Objective Outcome After Functional Endoscopic Sinus Surgery: Prediction Factors

Objectives/Hypothesis: After failure of medical treatment, chronic rhinosinusitis and nasal polyposis require surgical management. However, little is known about the predictive factors for objective outcome after sinus surgery. The aims of the study were to correlate preoperative, intraoperative, and postoperative clinical factors to healing outcome and to establish their respective predictive values.