Miracle-dz/UniFAR-FTUs huggingface dataset:
The POU Domain Transcription Factor POU3F1 Is an Important Intrinsic Regulator of GDNF-Induced Survival and Self-Renewal of Mouse Spermatogonial Stem Cells1

Continual spermatogenesis relies on a pool of spermatogonial stem cells (SSCs) that possess the capacity for self-renewal and differentiation. Maintenance of this pool depends on survival of SSCs throughout the lifetime of a male. Response to extrinsic stimulation from glial cell line-derived neurotrophic factor (GDNF), mediated by the PIK3/AKT signaling cascade, is a key pathway of SSC survival. In this study, we found that expression of the POU domain transcription factor POU3F1 in cultured SSCs is up-regulated via this mechanism. Reduction of Pou3f1 gene expression by short interfering RNA (siRNA) treatment induced apoptosis in cultured germ cell populations, and transplantation analyses revealed impaired SSC maintenance in vitro. POU3F1 expression was localized to spermatogonia in cross-sections of prepubertal and adult testes, implying a similar role in vivo. Through comparative analyses, we found that expression of POU5F1, another POU transcription factor implicated as essential for SSC self-renewal, is not regulated by GDNF in cultured SSCs. Transplantation analyses following siRNA treatment showed that POU5F1 expression is not essential for SSC maintenance in vitro. Additionally, expression of NODAL, a putative autocrine regulator of POU5F1 expression in mouse germ cells, could not be detected in SSCs isolated from testes or cultured SSCs. Collectively, these results indicate that POU3F1, but not POU5F1, is an intrinsic regulator of GDNF-induced survival and self-renewal of mouse SSCs.
Tonotopic organization and parcellation of auditory cortex in the FM‐bat Carollia perspicillata

In the short‐tailed fruit bat (Carollia perspicillata), the auditory cortex was localized autoradiographically and studied electrophysiologically in detail by using metal microelectrodes and 10‐ms tone stimuli. Because, in the weakly‐anaesthetized preparation, neuronal responses to pure‐tones were even found throughout the non‐primary auditory cortex, characteristic frequencies and minimum thresholds of neuron clusters (multiunits) could be mapped consistently and used to define auditory cortical fields conventionally (i.e. as in studies of auditory cortex of non‐echolocating mammals). Thus, within the electrophysiologically demarcated auditory cortex, six auditory fields were defined by criteria, as for example a gradient of characteristic frequencies (primary auditory cortex, AI; anterior auditory field, AAF; secondary auditory cortex, AII), reversal of the gradient across the field border (AI, AAF), uniform representation of a restricted band of frequencies (i.e. > 60 kHz; high‐frequency fields I and II, HFI and HFII), and transition from low to high minimum thresholds or vice versa [dorsoposterior field (DP), AII, HFI, HFII]. As supportive evidence for the distinction of these auditory cortical fields, differences in neuronal response properties were also used. In comparison with other mammals (e.g. cat and mouse), both the relative position of the auditory fields (mainly AI, AAF, DP and AII) and the representational principles for sound parameters within these forebrain areas seem to reflect a ‘fundamental plan’ (discussion below) of mammalian auditory cortical organization. Two coherent dorsally displaced high‐frequency representations (HFI, HFII) covering ∼ 40% of the total auditory cortical surface seem particularly suited for the processing of the dominant biosonar second and third harmonic of this species, and hence can be regarded as an adaptation for echolocation.
Microgrids energy trading in islanding mode

In this paper, we address the case where two microgrids are isolated from the main power grid but can exchange energy with each other in a peer-to-peer (P2P) manner. The goal is to minimize the total cost resulting from energy generation and transportation, while each microgrid satisfies its local power demand. We first propose a centralized solution. In this approach, a central controller must have access to all the information. For those situations where privacy must be protected, we propose a distributed approach, in which each microgrid solves a local optimization problem in an iterative fashion by exchanging some information with the other one.
Combination therapy for invasive mycoses: evaluation of past clinical trial designs.

BACKGROUND Despite the availability of new antifungals, single-agent therapy frequently falls short of high cure rates. Combination therapy offers potentially higher cure rates, especially for resistant organisms. In vitro studies and experimental animal models have provided conflicting data. METHODS Retrospective, randomized, controlled clinical studies were reviewed. RESULTS Results indicate a clear advantage for polyene and flucytosine combination therapy in cryptococcal meningitis and a possible advantage for combination amphotericin B and fluconazole for candidemia. Unfortunately, the few studies published have been flawed by design problems that have compromised the determination of outcome. Study review allows investigators the opportunity to design future studies to ensure optimal evaluation of efficacy. CONCLUSION Combination antifungal therapy is advantageous in cryptococcal diseases and may have a role in the treatment of invasive candidiasis. The greatest potential exists for combination therapy against aspergillosis and resistant fungi in patients with refractory mycotic disease who experience failure of monotherapy.
Survivin study: An update of “What is the next wave?”

Studies on survivin over the past 2–3 years have shown that survivin possesses multiple subcellular localizations and is a multi‐functional molecule involved in many aspects of cellular processes and/or behaviors. The subcellular localization and function of the survivin splice variants, however, have not yet been well elucidated. We have, therefore, provided additional observations on several survivin splice variants for further exploration. This review article will update the role of survivin, and its splice variants in the mitosis/cell cycle, apoptosis, tumorigenesis, chemoprevention, drug/radiation resistance, and cancer therapeutics. J. Cell. Physiol. 208: 476–486, 2006. © 2006 Wiley‐Liss, Inc.
Loss of smooth muscle cell hypoxia inducible factor‐1α underlies increased vascular contractility in pulmonary hypertension

Pulmonary arterial hypertension (PAH) is an often fatal disease with limited treatment options. Whereas current data support the notion that, in pulmonary artery endothelial cells (PAECs), expression of transcription factor hypoxia inducible factor‐1a (HIF‐1a) is increased, the role of HIF‐1a in pulmonary artery smooth muscle cells (PASMCs) remains controversial. This study investigates the hypothesis that, in PASMCs from patients with PAH, decreases in HIF‐1a expression and activity underlie augmented pulmonary vascular contractility. PASMCs and tissues were isolated from nonhypertensive control patients and patients with PAH. Compared with controls, HIF‐1a and Kv1.5 protein expression were decreased in PAH smooth muscle cells (primary culture). Myosin light chain (MLC) phosphorylation and MLC kinase (MLCK) activity‐major determinants of vascular tone‐were increased in patients with PAH. Cofactors involved in prolyl hydroxylase domain activity were increased in PAH smooth muscle cells. Functionally, PASMC contractility was inversely correlated with HIF‐1a activity. In PASMCs derived from patients with PAH, HIF‐1a expression is decreased, and MLCK activity, MLC phosphorylation, and cell contraction are increased. We conclude that compromised PASMC HIF‐1a expression may contribute to the increased tone that characterizes pulmonary hypertension. —Barnes, E. A. , Chen, C. ‐H. , Sedan, O. , Cornfield, D. N. Loss of smooth muscle cell hypoxia inducible factor‐1a underlies increased vascular contractility in pulmonary hypertension. FASEB J. 31, 650–662(2017). www.fasebj. org
Knee joint function and the energy cost of level walking in soccer players.

OBJECTIVES: To study self reported knee joint problems and the energy costs of level walking in soccer players. METHODS: Seventeen soccer players and twelve control subjects between 18 and 27 years old participated in the study. A questionnaire was used to establish the amount of participation in soccer and the frequency and extent of knee injuries. The physiological cost index (PCI) was used as an index of the energy costs of level walking. RESULTS: Soccer players had a significantly higher PCI than control subjects (p = 0.0001). Control subjects had a mean (SD) PCI of 0.23 (0.06) beats/m and soccer players had a mean PCI of 0.42 (0.12) beats/m. Some 82% of the soccer players experienced knee joint problems, whereas only 25% of the control group had problems. CONCLUSIONS: This study shows that college soccer players have a higher rate of self reported knee problems and higher energy costs of level walking than people who do not play soccer.
Acitretin for chemoprevention of non‐melanoma skin cancers in renal transplant recipients

A prospective, open randomized crossover trial was conducted to evaluate the efficacy of acitretin for chemoprevention of squamous cell carcinomas and basal cell carcinomas in renal allograft recipients. Analysis was performed according to the intention‐to treat principle. Twenty‐three patients with previous history of non‐melanoma skin cancer enrolled into the study and were randomly allocated into two groups. They crossed over at the end of 1 year. Eleven (47.8%) patients completed the 2‐year trial. Twelve (52.2%) patients withdrew from the trial. Nine of these withdrew because of side‐effects of acitretin. The majority of the patients who continued with the acitretin could tolerate 25 mg of acitretin daily or on alternate days. The number of squamous cell carcinomas (SCC) observed in patients while on acitretin was significantly lower than that in the drug‐free period (P = 0.002). A similar trend was observed in patients with basal cell carcinomas, but this was not significant and the numbers were small. Side‐effects were a major limiting factor. A severe rebound increase in SCC occurred in one patient after the acitretin was ceased.
Expression of Ly‐6, a marker for highly malignant murine tumor cells, is regulated by growth conditions and stress

Ly‐6E.1 is highly expressed in murine tumor cells with a high malignancy phenotype and may serve as a marker for such a phenotype. In this study, we examined the effects of various growth conditions and stress on the expression levels of Ly‐6E.1 by tumor cells. Previous preliminary results have shown that murine DA3 mammary tumor cells expressing high levels of Ly‐6E.1 (Ly‐6hi) are more highly tumorigenic than the same tumor cells expressing low levels of this membrane protein (Ly‐6lo). In this study, we demonstrate that mice bearing Ly‐6hi DA3 tumors have a significantly higher burden of spontaneous pulmonary metastasis than mice bearing Ly‐6lo DA3 tumors. Furthermore, the survival time of the former mice was significantly shorter than that of the latter ones. We further show that certain other members of the Ly‐6 gene family such as Ly‐6C.1 and Ly‐6G.1 are coregulated with Ly‐6E.1. This was shown to occur with respect to both DA3 cells as well as A3 tumor cells which are of fibroblast origin. However, these 2 cells differ with respect to regulation of Sca‐2 (TSA1, another member of the Ly‐6 family) expression on these cells. Levels of Sca‐2 on A3 cells appear to be coregulated with Ly‐6E.1 (i.e., Ly‐6hi A3 cells express high levels of Sca‐2 and Ly‐6lo A3 cells express low levels of Sca‐2). These 2 Ly‐6 proteins were, however, not coregulated on DA3 cells. Both Ly‐6hi as well as Ly‐6lo DA3 cells express equal levels of Sca‐2. Levels of Thy‐1, another glycosylphosphatidylinositol (GPI)‐anchored protein expressed by A3 tumor cells, were equally expressed by both Ly‐6hi and Ly‐6lo A3 tumor cells. Levels of Ly‐6 (but not those of CD44) on A3 tumor cells were upregulated on cells from dense cultures but were not influenced by the position of the cells in the cell cycle. Stress conditions such as serum starvation or heat shock upregulated the expression of Ly‐6 by the 2 types of tumor cells but did not induce apoptosis in these cells. The kinetics of the stress‐dependent upregulation of Ly‐6 expression differed, however, between the epithelial and fibroblastic tumor cells. Int. J. Cancer 77:306–313, 1998. © 1998 Wiley‐Liss, Inc.
Medically unexplained symptoms and pain: misunderstanding and myth

Purpose of reviewThe recent resurgence of the notion of psychosomatic disorders, grouping together as ‘medically unexplained symptoms’ all those without organic diagnosis and associated with distress, has included all chronic (persistent) pain within its remit. As pain is reasonably well explained, within an integrated biopsychosocial model, critical analysis of the position is required. Recent findingsNeuroscientific and translational studies of pain mechanisms have strengthened the understanding of pain, providing stronger connections between abstract psychological concepts corresponding to observation and studies of human clinical populations, neuroscientific findings in clinical and analogue studies, and animal research. This situation is contrasted with even the most recent reviews of medically unexplained symptoms providing only vague and patchily supported mechanisms, with little cognate human analogue or animal research. SummaryThe implication of subsuming chronic pain under medically unexplained symptoms is that the primary care/community physician will try to persuade the patient that the symptoms indicate underlying depression, which her or she may offer to treat. When pain is instead recognized as a problem in its own right, it would be referred for specialist opinion and care, or treated directly with evidence-based pain interventions.
Trisomy in man.

Trisomy, occurring in at least 4% of pregnancies, is the most common chromosome abnormality in humans. The majority of trisomies are associated with single additional chromosome. The presence of an additional sex chromosome is often associated with physical, behavioral, and intellectual impairment. The presence of an additional autosome is even more serious, being associated with severe mental and physical retardation and frequently with death in infancy. This review discusses the incidence, parental origin, and etiology of human trisomy. The incidence of trisomy varies widely among different chromosomes. This variation appears to reflect a real difference in the frequency of the primary event leading to trisomy as well as in differential selection. Studies of parental origin have shown a 1st maternal meiotic division error to be the most frequent source of the additional chromosome, regardless of the chromosome involved or the maternal age. Although the magnitude of risk varies among chromosomes, increased maternal age is an important risk factor in trisomy. The incidence of trisomy 21 increases from . 05% of livebirths at maternal age 20 years to over 3% of all livebirths at age 45 years. The effect of maternal age is most pronounced in double trisomies. It has been hypothesized that the relationship between increasing maternal age and trisomy is due to a gradient in the fetal ovary that affects chiasma freequency. While the basis for the maternal age effect remains unknown, it is almost certainly due to factors acting at or before conception. Epidemiologic studies suggest that maternal irradiation exposure may also lead to trisomy; however, the effective dosage level and the relationship to maternal age remain unknown. No effect of oral contraceptives, spermicides, or fertility drugs on the incidence of trisomy has been documented to date. Understanding of the mechanisms by which trisomies are produced represents a major challenge for human cytogenetics.
Expression of insulin/insulin‐like signalling and TOR pathway genes in honey bee caste determination

The development of queen and worker castes in honey bees is induced by differential nutrition, with future queens and workers receiving diets that are qualitatively and quantitatively different. We monitored the gene expression of 14 genes for components of the insulin/insulin‐like signalling and TOR pathways in honey bee larvae from 40–88 h after hatching. We compared normally fed queen and normally fed worker larvae and found that three genes showed expression differences in 40‐h‐old larvae. Genes that show such early differences in expression may be part of the mechanism that transduces nutrition level into a hormone signal. We then compared changes in expression after shifts in diet with those in normally developing queens and workers. Following a shift to the worker diet, the expression of 9/14 genes was upregulated in comparison with queens. Following a shift to the queen diet, expression of only one gene changed. The honey bee responses may function together as a homeostatic mechanism buffering larvae from caste‐disrupting variation in nutrition. The different responses would be part of the canalization of both the queen and worker developmental pathways, and as such, a signature of advanced sociality.
Exercise Training eduction in C-Reactive Protein Through ardiac Rehabilitation and Exercise Training

OBJECTIVES This study was designed to assess the effects of three-month formal phase II cardiac rehabilitation and exercise training programs on high-sensitivity C-reactive protein (HSCRP) levels in patients with coronary heart disease (CHD). BACKGROUND High-sensitivity C-reactive protein is associated with abdominal adiposity and other CHD risk factors and is a potent independent predictor of CHD events. Although weight reduction and statin therapy reduce HSCRP levels, the independent effects of cardiac rehabilitation programs on HSCRP are not well established. METHODS We analyzed plasma levels of HSCRP in 277 patients with CHD (235 consecutive patients before and after formal phase II cardiac rehabilitation and exercise training programs and 42 “control” patients who did not attend cardiac rehabilitation). Additionally, we determined the effects of cardiac rehabilitation on HSCRP independent of statin therapy and weight loss. RESULTS Rehabilitation patients improved significantly in body fat, obesity indices, exercise capacity, and other cardiac risk factors. Mean (5.9 7.7 to 3.8 5.8 mg/l; 36%; p 0.0001) and median levels of HSCRP ( 41%; p 0.002) decreased significantly in the rehabilitation group but not in the control population. Similar significant reductions in HSCRP occurred in the rehabilitation patients regardless of whether they received statin therapy or lost weight. CONCLUSIONS Therapeutic lifestyle changes effected through a three-month cardiac rehabilitation program significantly improved numerous cardiac risk factors. Through this holistic approach to secondary prevention, we observed significant reductions in HSCRP levels. These findings identify another clinical modality of reducing HSCRP beyond use of statin drugs and suggest an additional benefit of formal phase II cardiac rehabilitation and exercise training programs. (J Am Coll Cardiol 2004;43:1056–61) © 2004 by the American College of Cardiology Foundation
Regional brain volumes and their later neurodevelopmental correlates in term and preterm infants.

OBJECTIVE To compare regional brain volumes measured in term and preterm infants, and to correlate regional volumes with measures of neurodevelopmental outcome. METHODS High-contrast, high-resolution magnetic resonance imaging scans were acquired in 10 preterm and 14 term infants who were scanned near term. The cerebrum was segmented into cortical gray matter, white matter, cerebral ventricles, subcortical gray matter, cerebellum, and brainstem. The cortical gray matter, white matter, and ventricles were further divided into specific anatomic subregions, and the volumes were compared across groups. Measures of cognitive and motor development were acquired between 18 and 20 months of corrected age. Correlations of regional brain volumes with developmental outcome were assessed in the preterm group. RESULTS Volumes in preterm infants were reduced in parieto-occipital gray matter and increased in the midbody, occipital horn, and temporal horns of the lateral ventricles. Gray matter volumes were also less prominently reduced in the sensorimotor and inferior occipital cortices. Normal lateralization of white matter volumes were altered in the parieto-occipital region in the preterm infants, who had significantly larger left-sided and smaller right-sided structures. White matter volumes in the sensorimotor and midtemporal regions correlated strongly with measures of neurodevelopmental outcome. CONCLUSIONS These findings of reduced volumes in sensorimotor and parieto-occipital regions in preterm infants, and the prospective correlations of regional volumes with cognitive outcome, confirm and extend findings previously reported in a cross-sectional study of 8-year-old prematurely born children. The data suggest that regional brain volumes near term are a promising marker for predicting disturbances of cognitive outcome in preterm infants. Further prospective, longitudinal studies of neonatal brain volumes and developmental indices into later childhood are required to confirm the utility of regional brain volumes as predictors of longer term outcome.
An Economic Analysis of 5 G Superfluid Networks

We target the evaluation of a Superfluid 5G network from an economic point of view. The considered 5G architecture has notably features, such as flexibility, agility, portability and high performance, as shown by the H2020 SUPERFLUIDITY project. The proposed economic model, tailored to the Superfluid network architecture, allows to compute the CAPEX, the OPEX, the Net Present Value (NPV) and the Internal Rate of Return (IRR). Specifically, we apply our model to estimate the impact for the operator of migrating from a legacy 4G to a 5G network. Our preliminary results, obtained over two realistic case studies located in Bologna (Italy) and San Francisco (CA), show that the monthly subscription fee for the subscribers can be kept sufficiently low, i.e., typically around 5 [USD] per user, while allowing a profit for the operator.