Miracle-dz/UniFAR-FTUs huggingface dataset:
Activating JAK1 mutation may predict the sensitivity of JAK-STAT inhibition in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common type of cancers worldwide. However, current therapeutic approaches for this epidemic disease are limited, and its 5-year survival rate hasn't been improved in the past decades. Patient-derived xenograft (PDX) tumor models have become an excellent in vivo system for understanding of disease biology and drug discovery. In order to identify new therapeutic targets for HCC, whole-exome sequencing (WES) was performed on more than 60 HCC PDX models. Among them, four models exhibited protein-altering mutations in JAK1 (Janus Kinase 1) gene. To explore the transforming capability, these mutations were then introduced into HEK293FT and Ba/F3 cells. The results demonstrated that JAK1S703I mutation was able to activate JAK-STAT (Signal Transducer and Activator of Transcription) signaling pathway and drive cell proliferation in the absence of cytokine stimulation in vitro. Furthermore, the sensitivity to the treatment of a JAK1/2 inhibitor, ruxolitinib, was observed in JAK1S703I mutant PDX model, but not in other non-activating mutant or wild type models. Pharmacodynamic analysis showed that phosphorylation of STAT3 in the Ruxolitinib-treated tumor tissues was significantly suppressed. Collectively, our results suggested that JAK1S703I is an activating mutation for JAK-STAT signaling pathway in vitro and in vivo, and JAK-STAT pathway might represent a new therapeutic approach for HCC treatment. Monotherapy using a more potent and specific JAK1 inhibitor and combinatory therapy should be further explored in JAK1 mutant PDX models.
Role of Cathepsin D in U18666A-induced Neuronal Cell Death

Background: Cathepsin D has been implicated in Niemann-Pick type C (NPC) disease, which is associated with intracellular cholesterol accumulation. Results: Increased cytosolic and extracellular levels of cathepsin D enhanced neuronal death via different mechanisms. Conclusion: Leakage of cathepsin D within and outside the cell can cause cell death. Significance: Cathepsin D may be involved in the degeneration of neurons in NPC pathology. Cathepsin D is an aspartyl protease that plays a crucial role in normal cellular functions and in a variety of neurodegenerative disorders, including Niemann-Pick type C (NPC) disease, which is characterized by intracellular accumulation of cholesterol and glycosphingolipids in many tissues, including the brain. There is evidence that the level and activity of cathepsin D increased markedly in vulnerable neurons in NPC pathology, but its involvement in neurodegeneration remains unclear. In the present study, using mouse hippocampal cultured neurons, we evaluated the significance of cathepsin D in toxicity induced by U18666A, a class II amphiphile, which triggers cell death by impairing the trafficking of cholesterol, as observed in NPC pathology. Our results showed that U18666A-mediated toxicity is accompanied by an increase in cathepsin D mRNA and enzyme activity but a decrease in the total peptide content. The cytosolic level of cathepsin D, on the other hand, was increased along with cytochrome c and activated caspase-3 in U18666A-treated neurons. The cathepsin D inhibitor, pepstatin A, partially protected neurons against toxicity by attenuating these signaling mechanisms. Additionally, down-regulation of cathepsin D level prevented, whereas overexpression of the protease increased, vulnerability of cultured N2a cells to U18666A-induced toxicity. We also showed that extracellular cathepsin D from U18666A-treated neurons or application of exogenous enzyme can induce neurotoxicity by activating the autophagic pathway. These results suggest that increased release/activation of cathepsin D can trigger neurodegeneration and possibly development of NPC pathology. Thus, targeting cathepsin D level/activity may provide a new therapeutic opportunity for the treatment of NPC pathology.
What Makes a Successful Export?

We analyse a very rich and unique panel database which provides information on exports at the firm-product level. A stylised fact in the data is that many firms add as well as drop products from the export mix in any given year. Motivated by recent theory we investigate what determines the survival of products in the export mix. Estimating hazard models we find evidence that is consistent with the view that characteristics of the product as well as that of the firm matter. This suggests, in line with theory, that there are firm- as well as firm-product specific competencies that are important for shaping firms’ export mix.
Mobility impact on mode selection map in D2D networks — An analytical approach

Device-to-Device (D2D) transmission is a promising technology which enables the User Equipments (UE) in 5G cellular networks to directly communicate without going through the evolved Node-B (eNB). In such networks UEs should select a Transmission Mode (TM) amongst reuse, dedicated, and cellular modes by maximizing the overall transmission throughput or referring to a mode selection map. The selection map identifies the mode which results in the highest data rate given the current state of the network. This paper presents a new analytical framework for the derivation of the selection map of D2D enabled cellular networks. While this problem was treated in the literature through numerical simulations, our approach is analytical and consequently fast and precise.
Single Row vs. Twin Row Digging Losses for Two Virginia Type Peanut Varieties

Abstract. Twin row peanut production was initially introduced to take advantage of production benefits noted in narrow, single row studies, while still accommodating typical machinery involved in peanut production. Studies on twin row peanut production have been conducted since at least the early 1980s and many report increased yields and reduced weed pressure when compared to single row studies. Because the conventional peanut harvest is a two stage process where the plants are first dug and then combined several days later, there are two opportunities for yield losses. This study compares the yield losses at digging for twin row and single row peanuts of two virginia type varieties, Bailey and Champs. Digging losses were quantified as â€œabove groundâ€ and â€œbelow groundâ€ losses. Peanuts were planted and dug using RTK navigation to reduce operator induced errors. Mean above ground, below ground, and total digging losses were higher for twin row than for single row configurations across both varieties, but only statistically different for percent above ground losses and percent total digging losses in the Champs variety. Single row mean pod production was higher than that for twin row, but single row mean harvested yield was lower than that for twin row, although not statistically different. The results of this study were not statistically conclusive, but indicate that despite greater pod production and lower digging losses for single row than that for twin row peanuts. This suggests that combining losses for the single row peanuts in this study may be dominant in accounting for total harvest losses. Further study is needed to verify.
Re-assessing the formation of the inner Oort cloud in an embedded star cluster – II. Probing the inner edge

The detached object Sedna is likely at the inner edge of the Oort cloud, more precisely the inner Oort cloud (IOC). Until recently it was the sole member of this population. The recent discovery of the detached object 2012 VP113 has confirmed that there should be more objects in this region. Three additional IOC candidates with orbits much closer to Neptune have been proposed in the past decade since Sedna's discovery: 2000 CR105, 2004 VN112 and 2010 GB174. Sedna and 2012 VP113 have perhelia near 80 AU and semi-major axes over 250 AU. The latter three have perihelia between 44 AU and 50 AU and semi-major axes between 200 AU and 400 AU. Here we determine whether the latter three objects belong to the IOC or are from the Kuiper Belt's Extended Scattered Disc (ESD) using numerical simulations. We assume that the IOC was formed when the Sun was in its birth cluster. We analyse the evolution of the IOC and the Scattered Disc (SD) during an episode of late giant planet migration. We examine the impact of giant planet migration in the context of four and five planets. We report that the detached objects 2004 VN112 and 2010 GB174 are likely members of the IOC that were placed there while the Sun was in its birth cluster or during an episode of Solar migration in the Galaxy. The origin of 2000 CR105 is ambiguous but it is likely it belongs to the ESD. Based on our simulations we find that the maximum perihelion distance of SD objects is 41 AU when the semi-major axis is higher than 250 AU. Objects closer in are subject to mean motion resonances with Neptune that may raise their perihelia. The five planet model yields the same outcome. We impose a conservative limit and state that all objects with perihelion distance q>45 AU and semi-major axis a>250 AU belong to the inner Oort cloud.
Comparison of Two Bandwidth Selectors with Dependent Errors

For nonparametric regression. in the case of dependent observations. cross-validation is known to be severely affected by dependence. This effect is precisely quantified through a limiting distribution for the cross-validated bandwidth. The performance of two methods. the "leave-(2e+1)-out" version of cross-validation and partitioned cross-validation. which adjust for the dependence effect on bandwidth selection is investigated. The bandwidths produced by these two methods are analyzed by further limiting distributions which reveal significantly different characteristics. Simulations demonstrate that the asymptotic effects hold for reasonable sample sizes.
Leukocytosis of Unknown Origin: Gangrenous Cholecystitis

There have been case reports where patients admitted with acute cholecystitis, who were managed conservatively, had subsequently developed GC (gangrenous cholecystitis). The current case is unique, since our patient denied any prior episodes of abdominal pain and the only tip off was leukocytosis. A high index of suspicion is essential for the early diagnosis and treatment of GC. GC has a mortality rate of up to 22% and a complication rate of 16–25%. Complications associated with GC include perforation, which has been reported to occur in as many as 10% of cases of acute cholecystitis. The radiological investigations may not be conclusive. Ultrasonography usually serves as the first-line imaging modality for the evaluation of patients with clinically suspected acute cholecystitis. However, CT can play an important role in the evaluation of these patients if sonography is inconclusive. There is a need for an early (if not urgent) surgical intervention in acute cholecystitis (whether laparoscopic or open surgery) in order to decrease the time elapsed from the start of symptoms to admission and treatment.
High Expression of 17β-hydroxysteroid Dehydrogenase Type 2 is Associated with a Better Prognosis in Urothelial Carcinoma of the Urinary Tract

Object: To identify associations between 17β-hydroxysteroid dehydrogenase type 2 (HSD17B2) expression and clinicopathological variables and prognoses in patients with urothelial carcinoma of the urinary tract. Materials and Methods: We analyzed one public transcriptome dataset (GSE31684) from the Gene Expression Omnibus. HSD17B2 showed the highest log2-transformed fold-change in expression, and it was therefore further analyzed. We enrolled 340 upper urinary tract and 295 urinary bladder tissue samples that were obtained from patients with urothelial carcinoma between 1996 and 2004 to evaluate the expression of HSD17B2 using immunohistochemistry. The endpoints were disease-specific survival and metastasis-free survival. Univariate and multivariate analyses were performed to assess the relationships between HSD17B2, survival and clinicopathological parameters. Results: High expression of HSD17B2 was significantly associated with better clinicopathological parameters, including the following parameters in urothelial carcinoma of upper urinary tracts: Ta (non-invasive papillary carcinoma) and T1 (invaded subepithelial connective tissue) disease, without nodal metastasis, without vascular invasion, without perineal invasion and with a low histological grade, and the following parameters specifically in urothelial carcinoma of the urinary bladder: Ta (noninvasive papillary carcinoma) and T1 (invaded into the lamina propria but not into the muscularis propria) disease, without nodal metastasis (all P<0.05). Additionally, HSD17B2 high expression predicted a better prognosis, including improved disease-specific survival and metastasis-free survival in urothelial carcinomas of the urinary tract system. Conclusions: High expression of HSD17B2 is associated with a better prognosis and is therefore a prognostic biomarker that can be used to predict favorable survival in patients with urothelial carcinoma of the urinary tract system.
How Does Government Policy Affect Equity Risk Premium

This study examines the effect of country-level governance quality on equity risk premium using a panel dataset of 122 developed, emerging and developing economies over the period 2000-2012. Governance quality is measured by worldwide governance indicators. We use other determinants of equity risk premium as independent variables in the model which are inflation, consumption preferences, economic risk, international financial integration and binary variable 'Crisis'. Our results show that better governance quality translates into lower equity risk premium. This paper has strong policy implications for policy makers. In fact, a good government policy is essential in order to attract foreign investors.
A Neuronal Model of Predictive Coding Accounting for the Mismatch Negativity

The mismatch negativity (MMN) is thought to index the activation of specialized neural networks for active prediction and deviance detection. However, a detailed neuronal model of the neurobiological mechanisms underlying the MMN is still lacking, and its computational foundations remain debated. We propose here a detailed neuronal model of auditory cortex, based on predictive coding, that accounts for the critical features of MMN. The model is entirely composed of spiking excitatory and inhibitory neurons interconnected in a layered cortical architecture with distinct input, predictive, and prediction error units. A spike-timing dependent learning rule, relying upon NMDA receptor synaptic transmission, allows the network to adjust its internal predictions and use a memory of the recent past inputs to anticipate on future stimuli based on transition statistics. We demonstrate that this simple architecture can account for the major empirical properties of the MMN. These include a frequency-dependent response to rare deviants, a response to unexpected repeats in alternating sequences (ABABAA…), a lack of consideration of the global sequence context, a response to sound omission, and a sensitivity of the MMN to NMDA receptor antagonists. Novel predictions are presented, and a new magnetoencephalography experiment in healthy human subjects is presented that validates our key hypothesis: the MMN results from active cortical prediction rather than passive synaptic habituation.
A unified context activation mechanism

With the increase of research interest in context-oriented programming (COP), several COP languages with different characteristics have been proposed. Although they share common language features to modularize context-dependent variations of behavior, they take quite different ways to realize them. Because of such differences, each language cannot solely cover all use cases of implementing context-dependent behavioral variations. In this paper, we propose a new COP language Javanese that unifies several COP mechanisms into general linguistic constructs. Specifically, it provides context declarations to identify context and its specification of the range of execution sequences where this context is active, activate declarations to define the relation between contexts and layers, and context group declarations that modularize these declarations and specify the set of instances where they are applied. This paper describes design of Javanese and an implementation strategy.
Imams’ Experience With and Response to Mosque-Goers With OCD Scrupulosity

Abstract The experience of obsessive-compulsive disorder (OCD) symptoms that have a religious theme is common. Recent research has found that religious participants with religious OCD symptoms frequently turn to religious advisors, such as imams or clergy, for help to understand and alleviate their symptoms. As such, the advice provided by imams or clergy may have an important impact on the response of the person seeking help. This study examined the attitudes, beliefs and experiences of 64 Muslim imams with mosque-goers who had religious OCD symptoms, particularly scrupulosity. This study also examined imams’ familiarity with first-line psychological treatments for OCD such as Exposure and Response Prevention (ERP). Sunni imams from Australia and Shia imams from Iran completed an online survey based on the research of Deacon, Vincent, and Zhang (2012), which was conducted with Christian clergy in the United States. Results showed that the majority of imams were unfamiliar with scrupulosity as a possible symptom of a mental health problem, such as OCD, and with ERP as a recognised treatment for OCD. While 37% of participants reported having been approached by mosque-goers for help with scrupulosity, only 9% referred mosque-goers to mental health professionals, and only one imam reported having referred a mosque-goer for ERP. Sunni imams located in Australia were more likely to provide advice inconsistent with the ERP approach and were also significantly less likely than Shia imams located in Iran to recommend referral to a mental health professional who was not affiliated with their own religious denomination. Finally, Sunni imams had significantly higher scores than Shia imams on Thought Action Fusion (TAF) subscales. Results of multiple regression analysis revealed that TAF explained a considerable amount of the variance related to ERP-inconsistent advice. Research implications and limitations are discussed.
Homogeneous photometry and metal abundances for a large sample of Hipparcos metal-poor stars★

Homogeneous photometric data (Johnson V, B-V, V-K, Cousins V-I and Stromgren b-y), radial velocities, and abundances of Fe, O, Mg, Si, Ca, Ti, Cr and Ni are presented for 99 stars with high-precision parallaxes measured by the Hipparcos satellite. These data have been previously used to assist the derivation of accurate distances and ages of Galactic globular clusters. Magnitudes and colours for the programme stars were obtained by combining and standardizing carefully selected literature data available in the Simbad data base, and V and B-V values measured by the Hipparcos/Tycho mission. Comparison of colours for our targets suggests: (i) ground-based and Tycho B-V values agree well for colours bluer than 0.75 mag, but have a lot of scatter for redder colours; (ii) the Hipparcos V-I colours have a very large scatter and a zero-point offset of +0.02 mag compared to the literature values. The programme stars have metal abundances in the range −2.5 200) spectra obtained at the Asiago and McDonald Observatories for 66 stars. The analysis is carried out following the same precepts as those used in previous papers of this series, and includes corrections for departures from LTE in the formation of the O lines. The main results are: (i) the equilibrium of ionization of Fe is well satisfied in late F--early K dwarfs; (ii) oxygen and α-elements are overabundant by ∼0.3 dex. This large homogeneous abundance data set has been used to recalibrate the abundance scales of Schuster & Nissen, Ryan & Norris and Carney et al. (1994).
Evaluating the energy benefit of dynamic optical bypass for content delivery

We evaluate the energy efficiency of dynamic optical bypass for decentralized content delivery networks (CDNs). We build energy models based on the energy consumption of current network equipment and devices and analyze the energy tradeoff among key networking resources. Our results show that, due to the under-utilization associated with signaling and reconfiguration overhead, a CDN with dynamic optical bypass achieves the largest savings in delivering very large files (100 Gb (gigabit) and above) with high download rate (a few hundred downloads per hour). We also derive a threshold for a file size, which is approximately the bandwidth-overhead product scaled by the ratio between the power density of WDM equipment and routers: CλT°pwdmd/pr1d. We show that, only for the delivery of content of sizes larger than this size threshold, a CDN with dynamic optical bypass is more energy efficient than CDN without bypass.
Causative Factors behind an Efficacious Teacher: Evaluating Teacher Efficacy

In the third world school dropout rates are the highest, which is largely attributable to a dearth of efficacious teachers. The present research is an analysis of the teacher efficacy based on the teaching milieu. The Ohio State Teacher Efficacy Scale was used for data collection. Probability sampling design was used to select 171 secondary school teachers. As per the results, subject specialization affects teacher efficacy the most whereas, institution type influences teacher efficacy the least. The less experienced teachers have a greater self-efficacy than the experienced teachers, teachers teaching uncrowded classes are more efficacious than those teaching crowded classes.
Mathematik in den Naturwissenschaften Leipzig Simultaneous Blowup and Mass Separation During Collapse in an Interacting System of Chemotactic Species

We study an interacting system of chemotactic species in two-space dimension. First, we show that there is a parameter region which ensures simultaneous blowup also for non-radially symmetric solutions. If the existence time of the solution is finite, there is a formation of collapse (possibly degenerate) for each component, total mass quantization, and formation of subcollapses. For radially symmetric solutions we can rigorously prove that the collapse concentrates mass on one component if the total masses of the other components are relatively small. Several related results are also shown.
A Regulated Interaction of Syntaxin 1A with the Antidepressant-Sensitive Norepinephrine Transporter Establishes Catecholamine Clearance Capacity

Norepinephrine (NE) transporters (NETs) terminate noradrenergic synaptic transmission and represent a major therapeutic target for antidepressant medications. NETs and related transporters are under intrinsic regulation by receptor and kinase-linked pathways, and clarification of these pathways may suggest candidates for the development of novel therapeutic approaches. Syntaxin 1A, a presynaptic soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein, interacts with NET and modulates NET intrinsic activity. NETs colocalize with and bind to syntaxin 1A in both native preparations and heterologous systems. Protein kinase C activation disrupts surface NET/syntaxin 1A interactions and downregulates NET activity in a syntaxin-dependent manner. Syntaxin 1A binds the NH2 terminal domain of NET, and a deletion of this domain both eliminates NET/syntaxin 1A associations and prevents phorbol ester-triggered NET downregulation. Whereas syntaxin 1A supports the surface trafficking of NET proteins, its direct interaction with NET limits transporter catalytic function. These two contradictory roles of syntaxin 1A on NET appear to be linked and reveal a dynamic cycle of interactions that allow for the coordinated control between NE release and reuptake.