Miracle-dz/UniFAR-FTUs huggingface dataset:
E2F4 Actively Promotes the Initiation and Maintenance of Nerve Growth Factor-Induced Cell Differentiation

ABSTRACT E2F transcription factors play a critical role in cell cycle progression through the regulation of genes required for G1/S transition. They are also thought to be important for growth arrest; however, their potential role in the cell differentiation process has not been previously examined. Here, we demonstrate that E2F4 is highly upregulated following the neuronal differentiation of PC12 cells with nerve growth factor (NGF), while E2F1, E2F3, and E2F5 are downregulated. Immunoprecipitation and subcellular fractionation studies demonstrated that both the nuclear localization of E2F4 and its association with the Rb family member p130 increased following neuronal differentiation. The forced expression of E2F4 markedly enhanced the rate of PC12 cell differentiation induced by NGF and also greatly lowered the rate at which cells lost their neuronal phenotype following NGF removal. Importantly, this effect occurred in the absence of any significant change in the growth regulation of PC12 cells by NGF. Further, the downregulation of E2F4 expression with antisense oligodeoxynucleotides inhibited NGF-induced neurite outgrowth, indicating an important role for this factor during PC12 cell differentiation. Finally, E2F4 expression was found to increase dramatically in the developing rat cerebral cortex and cerebellum, as neuroblasts became postmitotic and initiated terminal differentiation. These findings demonstrate that, in addition to its effects on cell proliferation, E2F4 actively promotes the neuronal differentiation of PC12 cells as well as the retention of this state. Further, this effect is independent of alterations in cell growth and may involve interactions between E2F4 and the neuronal differentiation program itself. E2F4 may be an important participant in the terminal differentiation of neuroblasts.
Inference of Population Structure of Leishmania donovani Strains Isolated from Different Ethiopian Visceral Leishmaniasis Endemic Areas

Background Parasites' evolution in response to parasite-targeted control strategies, such as vaccines and drugs, is known to be influenced by their population genetic structure. The aim of this study was to describe the population structure of Ethiopian strains of Leishmania donovani derived from different areas endemic for visceral leishmaniasis (VL) as a prerequisite for the design of effective control strategies against the disease. Methodology/Principal Findings Sixty-three strains of L. donovani newly isolated from VL cases in the two main Ethiopian foci, in the north Ethiopia (NE) and south Ethiopia (SE) of the country were investigated by using 14 highly polymorphic microsatellite markers. The microsatellite profiles of 60 previously analysed L. donovani strains from Sudan, Kenya and India were included for comparison. Multilocus microsatellite typing placed strains from SE and Kenya (n = 30) in one population and strains from NE and Sudan (n = 65) in another. These two East African populations corresponded to the areas of distribution of two different sand fly vectors. In NE and Sudan Phlebotomus orientalis has been implicated to transmit the parasites and in SE and Kenya P. martini. The genetic differences between parasites from NE and SE are also congruent with some phenotypic differences. Each of these populations was further divided into two subpopulations. Interestingly, in one of the subpopulations of the population NE we observed predominance of strains isolated from HIV-VL co-infected patients and of strains with putative hybrid genotypes. Furthermore, high inbreeding irreconcilable from strict clonal reproduction was found for strains from SE and Kenya indicating a mixed-mating system. Conclusions/Significance This study identified a hierarchical population structure of L. donovani in East Africa. The existence of two main, genetically and geographically separated, populations could reflect different parasite-vector associations, different ecologies and varying host backgrounds and should be further investigated.
Understanding the Sparsity: Augmented Matrix Factorization with Sampled Constraints on Unobservables

An important problem of matrix completion/approximation based on Matrix Factorization (MF) algorithms is the existence of multiple global optima; this problem is especially serious when the matrix is sparse, which is common in real-world applications such as personalized recommender systems. In this work, we clarify data sparsity by bounding the solution space of MF algorithms. We present the conditions that an MF algorithm should satisfy for reliable completion of the unobservables, and we further propose to augment current MF algorithms with extra constraints constructed by compressive sampling on the unobserved values, which is well-motivated by the theoretical analysis. Model learning and optimal solution searching is conducted in a properly reduced solution space to achieve more accurate and efficient rating prediction performances. We implemented the proposed algorithms in the Map-Reduce framework, and comprehensive experimental results on Yelp and Dianping datasets verified the effectiveness and efficiency of the augmented matrix factorization algorithms.
Investigating Holocene mountain glaciations: a plea for the supremacy of glacial geomorphology when reconstructing glacier chronologies

Investigating Holocene glacier chronologies constitutes a valuable approach within palaeoclimatic research. Recent progress of numerical dating techniques, in particular terrestrial cosmogenic nuclide dating (TCND), has given it new momentum. Highly increased precision and improved methodological procedures of data calibration seem, however, to have gradually pushed previous rigorous geomorphological analysis of the investigated glacier forelands aside. By using a well-known key site in the Southern Alps/New Zealand it is demonstrated that even alleged benchmark studies are not immune to geomorphological uncertainties. Considerable potential misinterpretations are alerting and reinforce the demand for an unaltered ‘supremacy’ of geomorphology in this context. Especially with global compilations aiming at wider palaeoclimatic conclusions critical re-assessment of glacier chronologies may occasionally seem necessary.
LCM-DS: A novel approach of predicting drug-drug interactions for new drugs via Dempster-Shafer theory of evidence

There is an urgent need to discover or predict DDIs, which would cause serious adverse drug reactions. However, preclinical detection of DDIs bear high cost. Similarity-based computational approaches can be the assistance of experimental approaches. Utilizing pre-market drug similarities, they are able to predict DDIs on a large scale. However, they neglect the topological structure among DDIs and non-DDIs and have a burden of slow training and much memory. Or, they bear the bias that the pairs between a newly-given drug and the drugs having many DDIs tend to obtain high ranks. More importantly, they lack an effective combination of multiple predictions. To address these issues, we develop a local classification-based model (LCM), which has the advantages of faster training, less memory requirement as well as no that bias. We further design a novel supervised algorithm of fusion based on Dempster-Shafer (DS) theory of evidence for combine multiple predictions. Finally, the experiments demonstrate that our LCM-DS is significantly superior to three state-of-the-art approaches and outperforms both individual LCMs and classical fusion algorithms.
Radiation effects on a radiation-tolerant CMOS active pixel sensor

A comprehensive cobalt60, proton, and heavy ion evaluation of the Fillfactory STAR-250 CMOS active pixel sensor has been performed for space applications up to 100 krd(Si). It was possible to eliminate image lag by adjustment of the bias voltage and this allowed a reduction in proton-induced dark signal. Both cobalt60 and proton irradiation produced a decrease in responsivity, which is thought to be due to total dose effects. There was also an increase in photoresponse nonuniformity (PRNU). No major single event effects (latch-up or functional interrupt) where seen at the maximum linear energy transfer (LET) of 68MeV/(mg/cm/sup 2/).
Immunohistochemical Studies of Metastatic Germ-Cell Tumors in Retroperitoneal Dissection Specimens

Germ-cell tumors (GCTs) are the most common malignancies in adolescent and young men. These tumors are highly treatable, even at an advanced stage; therefore, accurate diagnosis is imperative. In this study, we evaluated immunohistochemical stains for SALL4, NANOG, glypican-3 (GPC3), D2-40, and CD30 with adequate control in retroperitoneal dissection specimens under the same laboratory conditions. The study groups included 31 cases of metastatic testicular GCTs with the following components: 11 seminomas, 14 embryonal carcinoma (ECs), 12 yolk sac tumor (YSTs), 8 teratomas, 10 cases of metastatic melanomas, 14 cases of malignant lymphomas, and 11 cases of metastatic, poorly differentiated carcinoma. SALL4 showed diffuse nuclear labeling for all seminomas, ECs, and YSTs. NANOG showed diffuse nuclear positivity in all seminomas and ECs. Metastatic carcinomas, melanomas, and malignant lymphomas were negative for these 2 markers. Gypican-3, D2-40, and CD30 showed sensitive staining for YSTs, seminomas, and ECs, respectively. In conclusion, SALL4 and NANOG are sensitive and specific markers for GCTs. GPC3, D2-40, and CD30 are sensitive but not specific for individual components of GCTs and may be useful in aiding in the differential diagnosis for the individual component of GCTs when the identity of GCT is established.
Adding liraglutide to lifestyle changes, metformin and testosterone therapy boosts erectile function in diabetic obese men with overt hypogonadism

The aim of this retrospective observational study was to evaluate whether adding liraglutide to lifestyle changes, metformin (Met) and testosterone replacement therapy (TRT), by means of improving weight and glycaemic control, could boost erectile function in type 2 diabetic obese men with overt hypogonadism and erectile dysfunction (ED) in a ‘real‐life setting’. Forty‐three obese, diabetic and hypogonadal men (aged 45–59 years) were evaluated because of complaining about the recent onset of ED. They were subdivided into two groups according to whether hypogonadism occurred after puberty (G1; n = 30: 25 with dysfunctional hypogonadism and 5 with acquired hypogonadotropic hypogonadism) or before puberty (G2; n = 13: 10 with Klinefelter's syndrome and 3 with idiopathic hypogonadotropic hypogonadism). Both G1 and G2 patients were given a combination of testosterone (T) [testosterone undecanoate (TU) 1000 mg/every 12 weeks] and Met (2000–3000 mg/day) for 1 year. In the poor responders (N) to this therapy in terms of glycaemic target (G1N: n = 16; G2N: n = 10), liraglutide (L) (1.2 μg/day) was added for a second year, while the good responders (Y) to T + Met (G1Y: 14/30 and G2Y: 3/13) continued this two drugs regimen therapy for another year. All patients were asked to fill in the International Index of Erectile Function (IIEF 15) questionnaire before starting TU plus Met (T1) and after 12 months (T2) and 24 months (T3) of treatment. Patients underwent a clinical examination and a determination of serum sex hormone binding globulin (SHBG), total testosterone (T) and glycosylated haemoglobin (HbA1c) at T1, T2 and T3. At T2, each patient obtained an improvement of ED (p < 0.01) and of the metabolic parameters without reaching, however, the glycaemic goals [HbA1c = >7.5% (>58 mmol/mol)], while T turned out to be within the range of young men. L added to TU and Met regimen in G1N and G2N allowed these patients to reach not only the glycaemic target [HbA1c = <7.5% (<58 nmol/mol)] and a significant reduction in body weight (p < 0.01), but also a further increase in SHBG (p < 0.05) and T (p < 0.01) plasma levels as well as a significant increment of IIEF score (T3). Conversely, at T3 G1Y and G2Y, who received the combined therapy with TRT and Met for the second year, showed a partial failure of that treatment given that there was no improvement of the IIEF score and they showed a significant rise in serum HbA1c (p < 0.05) and weight (p < 0.04) compared with the assessments at T2. These results suggest that TRT could improve clinical and metabolic parameters in obese, type 2 diabetic men with ED and overt hypogonadism (independently of when T deficit occurred). Furthermore, in case of insufficient metabolic control the addition of L to TRT and Met regimen allows to achieve serum T levels in the range of healthy men, as well as to reach glycaemic target and to lower weight, leading to a considerable improvement of ED.
Androgen Receptors in Bone-Forming Tissue

Androgen receptors (AR) were stained in sections of normal human growth plate of the costo sternal junction obtained at postmortem from one 4-day-old and two 5-day-old male infants, and in osteoblasts, grown in culture obtained from the femora of 3 male patients undergoing orthopaedic surgery for osteoarthritis. In the growth plate AR were found mostly in a narrow band of chondrocytes occupying an area about midway between the proximal and distal end of the epiphysis. Nearly all AR were in the cytoplasm and appeared in a granular form; there was no diffuse staining and the nuclei were either completely devoid of AR or only contained a few. Less-differentiated chondroblasts, perichondrial cells and hypertrophic chondrocytes contained few or no AR. Osteoblasts (and osteocytes) contained numerous AR and almost all were in the cytoplasm. Normal human osteoblasts, in their second or third passage, were grown on coverslips either in a medium with no added androgen or in the presence of 5α-dihydrotestosterone or methyltrienolone for a period of 24 h or longer. In control cultures, with vehicle and no added androgen, nearly all AR were found in the cytoplasm, with hardly any in the nucleus. In the presence of added androgen some osteoblasts from two of the specimens demonstrated a clear translocation of AR into the nucleus, whilst osteoblasts from a third specimen failed to translocate. These preliminary results indicate that AR translocation to the nucleus occurs in osteoblastic cells derived from osteoarthritic subjects. However, the ability to translocate may depend on the state of differentiation of the osteoblast and on culture conditions.
Association˚˚ of˚˚ Glycemic˚˚ Indexes,˚˚ Hyposalivation, and˚˚ Xerostomia˚˚ Type˚˚ 1˚˚ Diabetic˚˚ Patients Asociación˚˚ de˚˚ los˚˚ Œndices˚˚ de˚˚ Glucemia,˚˚ Hiposalivación y˚˚ Xerostomía˚˚ en˚˚ Pacientes˚˚ Diabéticos˚˚ Tipo˚˚ 1

The aim of this study was to assess the relationship between glycemic control of type 1 diabetic (DM1) patients and hyposalivation and xerostomia. This observational transversal study used a quantitative approach with a sample of 25 DM1 patients enrolled at the Diabetes Association of Joinville (ADIJO) in 2008. Variables assessed were sialometry through stimulated salivary flow, complaints of xerostomia, and testing for glycemic control: fasting capillary glycemia (FCG) and glycated hemoglobin (HbA1c). The Mann-Whitney U test, chi-square test, and Fisher's exact test were used to verify a possible association among the variables. Most subjects (64%; 16/25) showed concomitant hyposalivation and xerostomia. No significant statistical difference between glycemic control (FCG and HbA1c), hyposalivation, and xerostomia (p=0.54) was found. A high prevalence of hyposalivation and xerostomia was found to be more closely related to higher FCG values at the moment of blood testing than to higher values of HbA1c. ˚
LACUNAE

Context: While it is known that the risk of unintentional drowning varies with age, the manner in which drowning episode characteristics vary by age has not been well described. Such information might be useful for prevention. Objective: To describe characteristics of drowning by age group. Design: Retrospective review of the characteristics of drowning victims and their drowning incidents obtained from death certificates, medical examiner, pre-hospital, emergency department, and hospital records. Setting: Three counties in Western Washington state. Subjects: Residents who died (n=709) of unintentional drowning within the study region during 1980 through 1995. Outcomes: Age specific counts, proportions, and rates per million person years were estimated for and compared among six age groups. Results: Rates varied by age group: 0–4 (30.5), 5–14 (11.6), 15–19 (29.9), 20–34 (21.5), 35–64 (12.5), and 65 years or older (21.2). Among those 0–4 years, the proportions that drowned in pools, bathtubs, and open water were nearly equal. But from age 5–64 years, over 69% of deaths were in open water. Among those 65 years and older, the deaths were almost evenly divided between bathtub and open water; bathtub drowning rates were highest in this age group, 10.9. Pre-drowning activities were divided into boating, swimming, car passenger, bathing, and fell in while doing something else. Most (64/89, 76%) victims aged 0–4 years drowned while bathing or after falling in. Among those 15–19 years, most occurred while swimming (24/79, 34%) or boating (22/79, 31%). The drowning event was least often witnessed among those 0–4 years (10/36, 28%), and most often witnessed (44/58, 76%) among those 15–19 years. Medical care (pre-hospital, emergency department, or hospital) was most often involved in drownings of those 0–4 years (70/89, 79%) and least among those over 65 years (11/86, 13%). Conclusion: The characteristics of drowning episodes vary greatly by age. Different prevention strategies may be needed for different age groups.
Post-traumatic stress disorder: supportive evidence from an eighteenth century natural disaster

Synopsis Post-traumatic stress disorder was first recognized as a diagnostic category embracing reactions in response to overwhelming environmental stress ‘outside the range of usual human experience’ in DSM-III (APA, 1980). Such abnormal stressors are by no means a product of the twentieth century but have featured, sporadically, in all societies from the earliest civilizations. Longitudinal investigations of traumatic stress have rarely gone further back than the nineteenth century, and have been concerned, almost exclusively, with adverse effects following railway accidents and military combat. The present study, utilizing a mid-eighteenth century medical source, presents an analysis of the impact of a natural disaster on members of a peasant family trapped in an avalanche in the Italian Alps in 1755.
Keratoconus patients at Jordan University Hospital: a descriptive study

Purpose To study a sample of keratoconus patients, who were referred to Jordan University Hospital for possible penetrating keratoplasty (PKP), and provide basic epidemiological analysis. Method A descriptive study; we reviewed the medical records of 308 keratoconus patients referred for possible PKP. The following parameters were collected and analyzed: sex predilection, age at presentation, best corrected visual acuity, severity, bilaterality of the disease, and its association with vernal catarrh. Results Males constituted 61.6% while females constituted 38.4% of the study group. The mean age at presentation for males and females was 19.1 and 19.9 years, respectively. The best corrected visual acuity on evaluation was ≤6/60 in 60.4% of males’ eyes and 57.9% of females’ eyes; >6/60 and <6/12 in 30% of males’ eyes and 28.5% of females’ eyes; and ≥6/12 in 9.6% of males’ eyes and 13.6% of females’ eyes. Regarding the severity, 72.3% of males’ eyes and 71.8% of females’ eyes had severe keratoconus; 17.3% of males’ and 28.2% of females’ eyes had moderate keratoconus; and 10.4% of males’ eyes had mild keratoconus, which was not recorded in females. 90.5% of male patients and 93.2% of female patients had bilateral disease and vernal catarrh was recorded in 33.7% of males and 35.6% of females. Conclusion Keratoconus was found to be more prevalent in Jordanian males referred for PKP than females, keeping in mind that this doesn’t reflect the real sex predilection in the general population. Males also presented at a younger age. We didn’t find any association between gender and bilaterality, nor association with vernal catarrh.
Exploring the possibilities and limitations of multitarget SSVEP-based BCI applications

Steady state visual evoked potentials (SSVEPs) are the brain signals induced by gazing at a constantly flickering target. Frame-based frequency approximation methods can be implemented in order to realize a high number of visual stimuli for SSVEP-based Brain-Computer Interfaces (BCIs) on ordinary computer screens. In this paper, we investigate the possibilities and limitations regarding the number of targets in SSVEP-based BCIs. The BCI-performance of seven healthy subjects was evaluated in an online experiment with six differently sized target matrices. Our results confirm previous observations, according to which BCI accuracy and speed are dependent on the number of simultaneously displayed targets. The peak ITR achieved in the experiment was 130.15 bpm. Interestingly, it was achieved with the 15 target matrix. Generally speaking, the BCI performance dropped with an increasing number of simultaneously displayed targets. Surprisingly, however, one subject even gained control over a system with 84 flickering targets, achieving an accuracy of 91.30%, which verifies that stimulation frequencies separated by less than 0.1 Hz can still be distinguished from each other.
Awareness predicts the magnitude of single‐cue trace eyeblink conditioning

Studies of differential eyeblink conditioning (CS+ and CS‐) have demonstrated that successful conditioning requires awareness of the stimulus contingencies and that delay conditioning does not. Two experiments were carried out to determine whether awareness is also important for single‐cue trace eyeblink conditioning. In experiment 1, participants who performed a secondary, attention‐demanding task emitted significantly fewer conditioned eyeblink responses than participants who watched a silent movie during the conditioning session. In experiment 2, participants who became aware of the stimulus contingencies early in the conditioning session emitted significantly more conditioned responses during the remainder of the session than participants who became aware later in the session or who never became aware. These results indicate that awareness is important for single‐cue trace eyeblink conditioning, just as it is for differential trace conditioning. The relationship between awareness and trace eyeblink conditioning is discussed in the light of these and other recent findings. Hippocampus 10:181–186, 2000 © 2000 Wiley‐Liss, Inc.
Natural block data decomposition for heterogeneous clusters

We propose general purposes natural heuristics for static block and block-cyclic heterogeneous data decomposition over processes of parallel program mapped into multidimensional grid. This heuristics is an extension of the intuitively clear heterogeneous data distribution for one-dimensional case. It is compared to advanced heuristics for heterogeneous data decomposition proposed for solving linear algebra problems on two-dimensional process grid. We experimentally show that for typical local network (12 Windows 2000 PCs interconnected via Fast Ethernet switch) and for typical linear algebra problems these two heuristics have almost the same efficiency. We demonstrate efficiency of the proposed natural decomposition for case of three-dimensional process grid on the example of 3D modeling of supernova explosion.