Miracle-dz/UniFAR-FTUs huggingface dataset:
Potassium currents responsible for inward and outward rectification in rat neostriatal spiny projection neurons

Many of the nonlinear membrane properties displayed by neostriatal spiny projection neurons are conferred by their voltage-gated potassium (K+) currents, including an inwardly rectifying current (IKir), fast (IAt), and slowly (IAs)-inactivating A-currents, and a slow, noninactivating current. The relative contribution of these K+ currents to the pronounced inward and outward rectification of the current- voltage (I-V) relationship of spiny neurons was investigated in a neostriatal slice preparation. Manipulation of the equilibrium potential for K+ (EK) showed that the voltage dependence of activation of inward rectification was identical to that of IKir. In addition, application of barium (100 microM), which is known to reduce IKir in a time- and voltage-dependent manner, had equivalent effects on inward rectification. Subsequent application of cesium (3 mM) or tetraethylammonium (TEA, 25 mM) blocked inward rectification in a solely voltage-dependent fashion consistent with the action of these blockers on IKir. Administration of 4-aminopyridine (4-AP, 100 microM) at concentrations that selectively depress IAs, reduced outward rectification of spiny neurons at subthreshold membrane potentials. Higher concentrations of 4-AP (2 mM), which block both IAs and IAt, revealed an early transient overshoot in voltage deflections at potentials near spike threshold, but rectification persisted at the end of the responses. The transient overshoot and the residual rectification were eliminated by TEA (25 mM), a blocker of the slow, noninactivating K+ current. Collectively, these results indicate that all three depolarization-activated K+ currents contribute to outward rectification at different times and membrane potentials defined by their voltage dependence of activation and kinetics of inactivation. The spontaneous activity of neostriatal spiny neurons recorded in intact animals is characterized by sustained and limited shifts in membrane potential from relatively hyperpolarized potentials to depolarized potentials near spike threshold. The present data suggest that the hyperpolarized state is determined principally by IKir and the limits on the depolarized state are defined by IAf, IAs, and the noninactivating current. These outward K+ currents also are hypothesized to govern the spike discharge characteristics once the depolarized state has been reached.
The role of vicariance vs. dispersal in shaping genetic patterns in ocellated lizard species in the western Mediterranean

The schism between North Africa and Southern Europe caused by the opening of the Strait of Gibraltar and the consequent refilling of the Mediterranean basin at the end of Messinian salinity crisis (MSC), 5.33 million years ago, has been advocated as the main event shaping biogeographical patterns in the western Mediterranean as exemplified by the distribution of species and subspecies and genetic variation within the ocellated lizard group. To reassess the role of the MSC, partial sequences of three mitochondrial DNA genes (cytochrome b, 12S and 16S ribosomal RNA) and two nuclear genes (β‐fibrinogen and C‐mos) from species of the ocellated lizard group were analysed. Three alternative hypotheses were tested: that divergence was initiated (i) by post‐MSC vicariance as the basin filled, (ii) when separate populations established either side of the strait by pre‐MSC overseas dispersal, and (iii) by post‐MSC overseas dispersal. The pattern and level of divergence detected clearly refute the post‐MSC vicariance hypothesis, and support a model of divergence initiated by earlier overseas dispersal. Indeed, our best estimate is that the basal Euro‐African divergence predates the MSC event by several million years. The estimated divergence times among the populations in former Miocene Mediterranean islands, the current Betic and Rifian mountains, from adjacent mainland populations suggest overseas dispersal for the former and overland dispersal, or perhaps vicariance, for the latter. These results suggest that the MSC may have played a much less important role in shaping the current western Mediterranean biogeographical patterns than might have been anticipated from the dramatic nature of the episode.
Density functional theory study on electron and hole transport properties of organic pentacene derivatives with electron‐withdrawing substituent

Attaching electron‐withdrawing substituent to organic conjugated molecules is considered as an effective method to produce n‐type and ambipolar transport materials. In this work, we use density functional theory calculations to investigate the electron and hole transport properties of pentacene (PENT) derivatives after substituent and simulate the angular resolution anisotropic mobility for both electron and hole transport. Our results show that adding electron‐withdrawing substituents can lower the energy level of lowest unoccupied molecular orbital (LUMO) and increase electron affinity, which are beneficial to the electron injection and ambient stability of the material. Also the LUMO electronic couplings for electron transport in these pentacene derivatives can achieve up to a hundred meV which promises good electron transport mobility, although adding electron‐withdrawing groups will introduce the increase of electron transfer reorganization energy. The final results of our angular resolution anisotropic mobility simulations show that the electron mobility of these pentacene derivatives can get to several cm2 V−1s−1, but it is important to control the orientation of the organic material relative to the device channel to obtain the highest electron mobility. Our investigation provide detailed information to assist in the design of n‐type and ambipolar organic electronic materials with high mobility performance. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Redefining the Higher Education Landscape through Problem-Based Learning

Problem-Based Learning (PBL) is a pedagogical approach impacting instructional delivery in all tiers of K-20 education. The introduction of PBL in higher education first occurred in the medical school setting. Several decades later PBL is widely utilized as a popular teaching and learning strategy in colleges of education, specifically in graduate programs. Adult Learning Theory (Knowles, 1984), Transformative Learning Theory (Mezirow & Associates, 2000), and Information Processing Theory (Schmidt, 1983; Norman & Schmidt, 1992) all contribute to a theoretical understanding of PBL. This chapter identifies the key ideas, supporting learning theories, and principles of PBL. It then proposes a practical model that instructors can use to improve the quality of teaching and learning in academia.
Identification of Three New Autoantibodies Associated with Systemic Lupus Erythematosus Using Two Proteomic Approaches

Our objective was to identify new serum autoantibodies associated with systemic lupus erythematosus (SLE), focusing on those found in patients with central nervous system (CNS) syndromes. Autoantigens in human brain proteins were screened by multiple proteomic analyses: two-dimensional polyacrylamide gel electrophoresis/Western blots followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis and immunoprecipitation followed by liquid chromatography-tandem mass spectrometry shotgun analysis. The presence of serum IgG autoantibodies against 11 selected recombinant antigens was assessed by Western blot and enzyme-linked immunosorbent assay (ELISA) in the sera of 106 SLE patients and 100 normal healthy controls. The O.D. values in sera from SLE patients were significantly higher than those of controls for the antigens crystallin αB (p = 0.0002), esterase D (p = 0.0002), APEX nuclease 1 (p < 0.0001), ribosomal protein P0 (p < 0.0001), and PA28γ (p = 0.0005); the first three are newly reported. The anti-esterase D antibody levels were significantly higher in the CNS group than in the non-CNS group (p = 0.016). Moreover, when the SLE patients were categorized using CNS manifestations indicating neurologic or psychiatric disorders, the anti-APEX nuclease 1 antibody levels were significantly elevated in SLE patients with psychiatric disorders (p = 0.037). In conclusion, the association of SLE with several new and previously reported autoantibodies has been demonstrated. Statistically significant associations between anti-esterase D antibodies and CNS syndromes as well as between anti-APEX nuclease 1 antibodies and psychiatric disorders in SLE were also demonstrated. The combined immunoproteomic approaches used in this study are reliable and effective methods for identifying SLE autoantigens.
Association of serum chemerin concentrations with the presence of atrial fibrillation

Objective Chemerin, a newly discovered adipokine, is correlated with hypertension, diabetes and coronary heart disease. The aim of this study is to investigate the association of serum chemerin concentrations with the presence of atrial fibrillation. Methods Serum chemerin concentrations were determined in 256 patients with atrial fibrillation and 146 healthy subjects. Atrial fibrillation patients were then divided into paroxysmal, persistent and permanent atrial fibrillation. Results Serum chemerin concentrations were significantly higher in atrial fibrillation patients compared with healthy controls. In subgroup studies, patients with permanent atrial fibrillation had higher serum chemerin concentrations than those with persistent and paroxysmal atrial fibrillation. Furthermore, significant higher serum chemerin concentrations were observed in persistent atrial fibrillation patients compared with paroxysmal atrial fibrillation subjects. Serum chemerin concentrations were associated with the presence of atrial fibrillation after logistic regression analysis. Pearson correlation analysis revealed a positive relation of serum chemerin concentrations with body mass index, systolic blood pressure, diastolic blood pressure, triglycerides, low-density lipoprotein cholesterol, blood urea nitrogen, creatinine, C-reactive protein and left atrial diameter. Conclusion Serum chemerin concentrations are associated with the presence of atrial fibrillation and atrial remodelling.
Approximate Random Allocation Mechanisms

We generalize the scope of random allocation mechanisms, in which the mechanism first identifies a feasible “expected allocation” and then implements it by randomizing over nearby feasible integer allocations. The previous literature has shown that the cases in which this is possible are sharply limited. We show that if some of the feasibility constraints can be treated as goals rather than hard constraints, then, subject to weak conditions that we identify, any expected allocation that satisfies all the constraints and goals can be implemented by randomizing among nearby integer allocations that satisfy all the hard constraints exactly and the goals approximately. By defining ex post utilities as goals, we are able to improve the ex post properties of several classic assignment mechanisms, such as the random serial dictatorship. We use the same approach to prove the existence of $\epsilon$-competitive equilibrium in large markets with indivisible items and feasibility constraints.
Identification of the valine 408 to methionine mutation in the LDL receptor in a Greek patient with homozygous familial hypercholesterolemia

We have identified the cytosine to thymine change in the codon for amino acid 408 which causes valine to be replaced by methionine in exon 9 of the LDL receptor gene in a 12‐year‐old Greek boy living in Germany, with homozygous familial hypercholesterolemia, by using polymerase chain reaction‐amplified genomic DNA and subsequent restriction digestion. Homozygosity was confirmed by direct DNA sequencing. The mutation was present in both his parents, and his brother, grandmother, uncle and cousin. Six restriction fragment length polymorphisms of the LDL receptor gene were used to determine the haplotype of the defective allele. The haplotype was different from the one reported earlier in African Afrikaners and from Holland. We conclude that the mutation in the Greek boy probably occurred as an independent mutation. Because the parents are from different areas in Greece, this mutation may be common in Greeks.
Dysphagia in Parkinson's Disease: Assessment by Solid Phase Radionuclide Scintigraphy

Patients with Parkinson's disease often experience dysphagia, in which case food seems to be blocked in the throat. The patient must swallow over and over to get it down. A radionuclide solid phase esophageal motility study was conducted to evaluate esophageal function of patients with Parkinson's disease. Twenty-seven patients and 27 age-matched normal volunteers were studied. Each subject was placed in the supine position above a gamma camera linked to a computer and was given a 4 mL bolus of solid gelatin containing 75 MBq Tc-99m pertechnetate. Data were acquired in the list mode. A computer routine was used to calculate the total mean transit time, the residual fraction after the first swallow, and the retrograde index. The preliminary results suggest: 1) patients with Parkinson's disease display significantly slowed transit time when compared with normal age-matched controls, and 2) dysphagia of Parkinson's disease may improve with medication. A solid phase esophageal motility study may be used as a monitor of dysphagia in patients with Parkinson's disease in our future studies.
A Two-Year Clinical Experience with Lithium *

A two year clinical experience with lithium has been described. Our results can be summarized as follows: Effect on active mania Over seventy per cent of the manic patients in this study were controllable with lithium alone. An additional twenty per cent with severe mania had to be stabilized by haloperidol, but were maintained by lithium once the acute phase subsided. When a patient maintained on lithium shows prodromal symptoms of hypomania an increase in the dose of lithium is often, and for some patients regularly, an effective control for the incipient manic attack. Some patients required periodic treatment for residual depression. Decreasing the dose of lithium, and adding an anti-depressant has been found to be effective, even in some cases where an antidepressant alone had previously failed to prevent repeated depressions. Merely decreasing the dose of lithium was not found to be effective. Those who relapsed completely tended to be more hostile and suspicious, and in the authors' experience, ultimately showed schizophrenic features. One relapse, especially when subsequent to the patient's discontinuing his own medication, does not mean that the patient cannot thereafter, be stabilized on lithium. One relapse should not be taken to mean ultimate failure, when a decrease in severity or frequency of attacks would be a worthwhile goal.
The architecture and task scheduling design for the video analysis center

The deployment of the large-scale video analysis center that provides comprehensive video applications is the developing trend of video surveillance systems. It integrates intelligent video information analysis, the mass video image content retrieval, and the associated data mining of structural video data. In this paper, we present the hierarchical architecture of the video analysis center by discussing key design issues of the data storage layer, the video analysis layer, the application layer and the task scheduling system. The design of task scheduling mechanisms in the video analysis center is the key issue that affects the system performance, which needs the consideration on both the partition of server resource pool and the capacity constrained assignment of video streams. The effective operation of the video analysis center can be guaranteed through the adaptive task planning and the cooperation among different layers of the system.
The Changes in Quantitative HCV RNA Titers During Interferon Alpha 2B Therapy in Patients With Chronic Hepatitis C Infection

Objective:Our aim was to analyze the outcomes and the patterns of response to interferon treatment in patients with chronic hepatitis C using serum HCV RNA as the primary endpoint of therapy.Methods:Seventy anti-HCV–positive patients were treated with 3 million U of interferon-α-2b thrice weekly for 24 wk and followed for an additional 24 wk after cessation of therapy (wk 48). Serum HCV RNA was measured by a reverse transcriptase-polymerase chain reaction method that has a sensitivity of < 100 viral copies per ml.Results:The mean pretreatment HCV RNA was 2.8 ± 2.2 × 106 viral copies per ml. Genotype 1 patients had significantly higher mean baseline viral titers than those with genotype 2 (p= 0.03). At wk 48, 12 (17%) patients were HCV RNA negative and considered virological complete responders (CR) to treatment. The remaining patients were HCV RNA positive at wk 48 and were considered nonresponders to therapy. There were two types of virological nonresponder patients, responder relapse (RR) and no response (NR). The mean baseline HCV RNA level was significantly lower in the virological CR patients (p= 0.0004). At wk 12 and 24 of interferon treatment, both the virological CR and RR patients had lower serum HCV RNA concentrations than the patients in the NR category (p= 0.0001), while at wk 48, only the virological CR patients had undetectable HCV RNA when compared to the RR and NR patients (p= 0.04). Transient decreases in the HCV RNA titers of ≥ 1 log in magnitude were observed in 49% of the NR patients, which rose to pretreatment levels either during or after interferon therapy. Conclusions: Our findings indicate that measurement of serum HCV RNA precisely defined the responses to interferon therapy. Because the goal is to eliminate virus in patients with chronic hepatitis C infection, then HCV RNA should be used as the primary endpoint of treatment.
Exploring Eucladoceros Ecomorphology Using Geometric Morphometrics

An increasingly common method for reconstructing paleoenvironmental parameters of hominin sites is ecological functional morphology (ecomorphology). This study provides a geometric morphometric study of cervid rearlimb morphology as it relates to phylogeny, size, and ecomorphology. These methods are then applied to an extinct Pleistocene cervid, Eucladoceros, which is found in some of the earliest hominin‐occupied sites in Eurasia. Variation in cervid postcranial functional morphology associated with different habitats can be summarized as trade‐offs between joint stability versus mobility and rapid movement versus power‐generation. Cervids in open habitats emphasize limb stability to avoid joint dislocation during rapid flight from predators. Closed‐adapted cervids require more joint mobility to rapidly switch directions in complex habitats. Two skeletal features (of the tibia and calcaneus) have significant phylogenetic signals, while two (the femur and third phalanx) do not. Additionally, morphology of two of these features (tibia and third phalanx) were correlated with body size. For the tibial analysis (but not the third phalanx) this correlation was ameliorated when phylogeny was taken into account. Eucladoceros specimens from France and Romania fall on the more open side of the habitat continuum, a result that is at odds with reconstructions of their diet as browsers, suggesting that they may have had a behavioral regime unlike any extant cervid. Anat Rec, 298:291–313, 2015. © 2014 Wiley Periodicals, Inc.
SPATIAL POPULATION STRUCTURE IN THE WHIRLIGIG BEETLE DINEUTUS ASSIMILIS: EVOLUTIONARY INFERENCES BASED ON MITOCHONDRIAL DNA AND FIELD DATA

The spatial population structure of the pond‐living water beetle Dineutus assimilis (Coleoptera: Gyrinidae) was investigated through a field study of population dynamics and dispersal, with a concurrent assessment of the spatial distribution of mitochondrial DNA (mtDNA) restriction‐fragment‐length polymorphism (RFLP). A comprehensive 2‐yr survey within a 60‐km2 study area revealed pronounced fluctuations in local abundances, including extinctions and colonizations. The recapture of marked individuals showed that dispersal among ponds is frequent in both males and females and connects populations on a large geographic scale (maximum observed flight distance: 20 km). The population structure of D. assimilis is thus characterized by both pronounced genetic drift and frequent gene flow. Together, these two forces generate a pattern of very local and transient genetic differentiation. Mitochondrial DNA samples collected within a few kilometers indicate highly significant spatial structure, if newly founded demes or those that experienced recent bottlenecks are included. These results based on four demes within the study area were placed into a regional context by further samples collected at distances of 100 km and 200 km. Fst estimates computed on increasing spatial scales were variable but showed no increasing trend. Thus, gene flow exerts a strong homogenizing force over a wide geographic range but is counteracted locally by genetic drift. These findings highlight the need to supplement estimates of Fst with additional data to arrive at valid interpretations of the genetic information. More generally, this study raises questions about how to capture the relevant features of dynamic, subdivided populations to understand their evolutionary dynamics.
Pharmaceutical nanocrystals by nanomilling: critical process parameters, particle fracturing and stabilization methods

Objectives Wet milling is a common technique to produce drug nanocrystals. Stability of the nanocrystals is a critical question, and different kinds of stabilizers, e.g. polymers, celluloses, surfactants and lipids, have been tested for various drugs. Still, the question about how to select the best stabilizer to a certain drug material and also to a selected process is open.
Dietary risk factors for incidence or progression of chronic kidney disease in individuals with type 2 diabetes in the European Union.

BACKGROUND Although the prevalence of chronic kidney disease (CKD) is ∼ 30% in the group of people with diabetes, data on interventions in the very early stage of the disease are still missing. Furthermore, the effects of modifiable lifestyle factors such as nutrition on incidence and progression of CKD in patients with diabetes in Europe remain elusive. METHODS We analyzed whether diet quality and adherence to dietary guidelines using the modified Alternate Healthy Eating Index (mAHEI) score was associated with CKD incidence or progression after 5.5 years in 3088 European participants of the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) with type 2 diabetes and baseline normo- or micro-albuminuria. Death was considered as a competing risk in the multinomial logit regression models, which were adjusted for age, gender, duration of diabetes, ONTARGET randomization, baseline albuminuria and glomerular filtration rate (GFR). We also estimated the potential impact on population health of improvement in diet quality. RESULTS At study end, 450 (14.6%) participants had died and 926 (30%) had experienced the renal endpoint of incidence or progression of CKD, of which 422 (13.7%) participants had progressed to micro- or macro-albuminuria, 596 (19.3%) had a GFR-decline of >5% per year and 18 (0.6%) had developed end-stage renal disease. Participants in the healthiest tertile of the mAHEI score had a decreased risk of incidence or progression of CKD (odds ratio 0.8, 95% confidence interval 0.68-0.94) and death (0.65, 0.52-0.81) compared with participants in the least healthy tertile. If individuals with a suboptimal dietary quality (e.g. mAHEI < 28) were able to improve their diet to an mAHEI of 28, 3.2% of CKD incidence or progression and 10.0% of deaths might be avoided in 5.5 years. CONCLUSIONS If the association between diet and these endpoints is causal, then optimizing diet quality in individuals with diabetes who have no CKD or very early CKD would have substantial population benefits in terms of prevention of CKD incidence or progression and mortality in this high-risk population.