Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of group-I metabotropic glutamate receptors protects against prion toxicity

Prion infections cause inexorable, progressive neurological dysfunction and neurodegeneration. Expression of the cellular prion protein PrPC is required for toxicity, suggesting the existence of deleterious PrPC-dependent signaling cascades. Because group-I metabotropic glutamate receptors (mGluR1 and mGluR5) can form complexes with the cellular prion protein (PrPC), we investigated the impact of mGluR1 and mGluR5 inhibition on prion toxicity ex vivo and in vivo. We found that pharmacological inhibition of mGluR1 and mGluR5 antagonized dose-dependently the neurotoxicity triggered by prion infection and by prion-mimetic anti-PrPC antibodies in organotypic brain slices. Prion-mimetic antibodies increased mGluR5 clustering around dendritic spines, mimicking the toxicity of Aβ oligomers. Oral treatment with the mGluR5 inhibitor, MPEP, delayed the onset of motor deficits and moderately prolonged survival of prion-infected mice. Although group-I mGluR inhibition was not curative, these results suggest that it may alleviate the neurological dysfunctions induced by prion diseases.
The p38-MK2/3 Module Is Critical for IL-33–Induced Signaling and Cytokine Production in Dendritic Cells

IL-33 is an IL-1 cytokine superfamily member. Binding of IL-33 to the IL-33R induces activation of the canonical NF-κB signaling and activation of MAPKs. In bone marrow–derived dendritic cells, IL-33 induces the production of IL-6, IL-13, and TNF-α. However, the signaling pathways resulting in IL-33–induced effector functions of dendritic cells are unknown. In this article, we show that the IL-33–induced cytokine production is only partly dependent on p65. Thereby, p65 mediates the production of IL-6, but not of IL-13, whereas the p38–Mapk-activated protein kinases 2/3 (MK2/3) signaling module mediates the IL-13, but not the IL-6, production. In addition, GM-CSF, which is critical for the differentiation and proliferation of bone marrow–derived dendritic cells, potentiates the p65-dependent IL-6 and the p38-MK2/3–dependent IL-13 production. Furthermore, we found that effective TNF-α production is only induced in the presence of GM-CSF and IL-33 via the p38-MK2/3 signaling module. Taken together, we found that the p38-MK2/3 signaling module is essential to mediate IL-33–induced cytokine production in dendritic cells.
Evaluation and selection of LiNbO/sub 3/ and LiTaO/sub 3/ substrates for SAW devices by the LFB ultrasonic material characterization system

This paper demonstrates the evaluation and selection of commercially available LiNbO/sub 3/ and LiTaO/sub 3/ single crystals and wafers for surface acoustic wave (SAW) devices using the line-focus-beam ultrasonic material characterization (LFB-UMC) system. This system enables measuring leaky-SAW (LSAW) propagation characteristics precisely and efficiently for a number of specimens. The wafers are prepared from the top, middle, and bottom parts of four 128/spl deg/YX LiNbO/sub 3/ and seven X-112/spl deg/Y LiTaO/sub 3/ single crystals. For both series of crystals, the measured LSAW velocities increase from top to bottom in the crystals and with the increasing crystal growth number. The velocity changes for all wafers are 0.036% for 128/spl deg/YX LiNbO/sub 3/ and 0.035% for X-112/spl deg/Y LiTaO/sub 3/, corresponding to changes of 0.038 mol% and 0.075 mol% in Li/sub 2/O concentration, respectively. Moreover, the inhomogeneity in the first X-112/spl deg/Y LiTaO/sub 3/ single crystal caused by some undesirable wafer fabrication processes can be detected precisely, although it is difficult for the conventional methods to obtain such information.
Arabidopsis thaliana isoprenyl diphosphate synthases produce the C25 intermediate geranylfarnesyl diphosphate.

Isoprenyl diphosphate synthases (IDSs) catalyze some of the most basic steps in terpene biosynthesis by producing the prenyl diphosphate precursors of each of the various terpenoid classes. Most plants investigated have distinct enzymes that produce the short-chain all-trans (E) prenyl diphosphates geranyl diphosphate (GDP, C10 ), farnesyl diphosphate (FDP, C15 ) or geranylgeranyl diphosphate (GGDP, C20 ). In the genome of Arabidopsis thaliana, 15 trans-product-forming IDSs are present. Ten of these have recently been shown to produce GGDP by genetic complementation of a carotenoid pathway engineered into Escherichia coli. When verifying the product pattern of IDSs producing GGDP by a new LC-MS/MS procedure, we found that five of these IDSs produce geranylfarnesyl diphosphate (GFDP, C25 ) instead of GGDP as their major product in enzyme assays performed in vitro. Over-expression of one of the GFDP synthases in A. thaliana confirmed the production of GFDP in vivo. Enzyme assays with A. thaliana protein extracts from roots but not other organs showed formation of GFDP. Furthermore, GFDP itself was detected in root extracts. Subcellular localization studies in leaves indicated that four of the GFDP synthases were targeted to the plastoglobules of the chloroplast and one was targeted to the mitochondria. Sequence comparison and mutational studies showed that the size of the R group of the 5th amino acid residue N-terminal to the first aspartate-rich motif is responsible for C25 versus C20 product formation, with smaller R groups (Ala and Ser) resulting in GGDP (C20 ) as a product and a larger R group (Met) resulting in GFDP (C25 ).
Photonic MEMS: From Laser Physics to Cell Biology

This paper reviews the recent progress from optical MEMS to photonic MEMS, nano- photonics and biophotonic MEMS, which represents a latest trend of the expansion and penetration of the MEMS technology to the nano and bio areas. Different types of devices are demonstrated as the examples of the natural synergy of MEMS with the photonics, including thermo-optic switches, tunable lasers, injection-locked laser systems, nano-photonic bandgap devices and biophotonic cell chips. The use of MEMS not only produces better integration, robustness and compactness, but also improves the functionalities and specifications of the devices.
Economic Growth and Banking Credit in India

The interdependence between credit expansion and economic growth has been a subject of some debate. While some economists contest that the development of the financial system is a byproduct of economic growth others assert that credit expansion is critical for growth itself. India’s impetus on expanding its banking reach and recent changes in the way transactions are being done begs the question whether such changes directly affect the growth trajectory. This paper aims to examine and understand the relationship between credit and growth in India in the last few decades. Different metrics for credit and output is used to test the relationship at an overall as well as sectoral level. The findings indicate a strong relationship between the two variables.
Human Adeno-Associated Virus Type 5 Is Only Distantly Related to Other Known Primate Helper-Dependent Parvoviruses

ABSTRACT We have characterized 95% (4,404 nucleotides) of the genome of adeno-associated virus type 5 (AAV5), including part of the terminal repeats and the terminal resolution site. Our results show that AAV5 is different from all other described AAV serotypes at the nucleotide level and at the amino acid level. The sequence homology to AAV2, AAV3B, AAV4, and AAV6 at the nucleotide level is only between 54 and 56%. The positive strand contains two large open reading frames (ORFs). The left ORF encodes the nonstructural (Rep) proteins, and the right ORF encodes the structural (Cap) proteins. At the amino acid level the identities with the capsid proteins of other AAVs range between 51 and 59%, with a high degree of heterogeneity in regions which are considered to be on the exterior surface of the viral capsid. The overall identity for the nonstructural Rep proteins at the amino acid level is 54.4%. It is lowest at the C-terminal 128 amino acids (10%). There are only two instead of the common three putative Zn fingers in the Rep proteins. The Cap protein data suggest differences in capsid surfaces and raise the possibility of a host range distinct from those of other parvoviruses. This may have important implications for AAV vectors used in gene therapy.
Improving the Naive Portfolio Strategy

In this paper, I consider four approaches to improve the naive strategy, of which one is newly proposed in this paper. The new approach attempts to minimize the difference from a reference portfolio while satisfying risk and return targets. Other well known strategies such as variance minimization are also compared. Empirical results show that the new approach consistently outperforms the naive strategy. However, the best performance comes from the minimum variance portfolios. It is also worth noting that optimal strategies appear to perform well for factor portfolios, which implies careful construction of asset universe could have a large impact on portfolio optimization performance.
Learning English Literacy as an Aspect of Social Practice

This paper aims to examine students’ English language learning as an aspect of social practice. The focus is on two groups of undergraduates who studied in the English Department at a university in Taiwan. The research is ethnographic, combining intensive interviews, observation, and systematic collection and analysis of documents and students’ assignments in English. The results reveal that English literacy learning was shaped by the institutional contexts, which include the course contents, the task requirements and the teaching approaches. These students seem to adopt a low-level or a high-level transmission model of learning, depending on the levels of their English language proficiency. Specifically, the process of individual students’ learning appears to be dynamic and ongoing culturally embedded in the educational settings in Taiwan. Consequently, the paper proposes that teachers of English as a foreign language should consider the use of an ecological approach to needs analysis and encourage students to take an ethnographic stance towards their language learning. This may assist teachers in designing appropriate curricula and, in the long run, improve the quality of student learning both inside and outside academic institutions.
Traffic dynamics estimation by using raw floating car data

Massive datasets of Floating Car Data (FCD) are collected and thereafter processed to estimate and predict traffic conditions. In the framework of short-term traffic forecasting, machine learning techniques have become very popular. However, the big datasets available today contain for the most part easily predictable data, that are data observed during recurrent conditions. Integration of different machine learning techniques with traffic engineering notions must contribute to obtain new transportation-oriented data-driven methods. In this paper we address traffic dynamics estimation by using individual FCD in order to develop an integrative framework able to recognize and select the suitable method for traffic forecasting. Taking into account the spatial distributions of individual FCD positions we retrieve a new spatial-based criterion for the integration of models.
The relative spatial distribution of in vitro‐CFCs in the bone marrow, responding to specific growth factors

Haemopoietic progenitor cells are stimulated by a range of growth factors which promote colony growth in culture. The progenitors are a part of an age‐structured developmental hierarchy in the tissue. The growth factors, although overlapping in their effects, stimulate cells preferentially at different stages in this programme. Femoral bone marrow was fractionated into axial (close to the central venous sinus) and marginal (close to the bone surface) cells. Progenitors which responded to IL‐3, GM‐CSF, G‐CSF, M‐CSF and SCF were then assayed in soft agar cultures. Consequent plots of their spatial distributions showed that the more primitive cells in vitro (responding to IL‐3) were concentrated close to the bone surface. The peak concentrations of cells responding primarily to growth factors with progressively more affinity to more mature progenitor cells correspondingly appeared progressively further from the bone surface and closer to the point of release at the central venous sinus. This suggests that the developmental/maturational process in haemopoiesis is accompanied by a progressive movement of cells from the bone surface towards the central axial regions of the bone cavities. The most primitive cells are however exposed, close to the centre of the cavity, by a combination of SCF and G‐CSF (or by a 50‐fold increase in G‐CSF concentration alone). These results corroborate earlier data which indicate a developmental movement of cells from the centre of the marrow tissue towards the bone surface and back again, sequentially encountering a series of growth factors which promote their differentiation into mature cells, for release at the central venous sinus.
Three-dimensional Structure of Steroid 21-Hydroxylase (Cytochrome P450 21A2) with Two Substrates Reveals Locations of Disease-associated Variants*

Background: Steroid 21-hydroxylase deficiency accounts for ∼95% of individuals with congenital adrenal hyperplasia (CAH). Results: The bovine cytochrome P450 21A2 (CYP21A2) crystal structure complexed with the substrate 17-hydroxyprogesterone was determined to 3.0 Å resolution. Conclusion: The structure reveals the binding mode of two molecules of the steroid substrate and accurate residue locations in the protein. Significance: The structure of CYP21A2 enhances our understanding of CAH. Steroid 21-hydroxylase (cytochrome P450 21A2, CYP21A2) deficiency accounts for ∼95% of individuals with congenital adrenal hyperplasia, a common autosomal recessive metabolic disorder of adrenal steroidogenesis. The effects of amino acid mutations on CYP21A2 activity lead to impairment of the synthesis of cortisol and aldosterone and the excessive production of androgens. In order to understand the structural and molecular basis of this group of diseases, the bovine CYP21A2 crystal structure complexed with the substrate 17-hydroxyprogesterone (17OHP) was determined to 3.0 Å resolution. An intriguing result from this structure is that there are two molecules of 17OHP bound to the enzyme, the distal one being located at the entrance of the substrate access channel and the proximal one bound in the active site. The substrate binding features locate the key substrate recognition residues not only around the heme but also along the substrate access channel. In addition, orientation of the skeleton of the proximal molecule is toward the interior of the enzyme away from the substrate access channel. The 17OHP complex of CYP21A2 provides a good relationship between the crystal structure, clinical data, and genetic mutants documented in the literature, thereby enhancing our understanding of congenital adrenal hyperplasia. In addition, the location of certain CYP21A2 mutations provides general understanding of structure/function relationships in P450s.
Toward a phylogenetic classification of Primates based on DNA evidence complemented by fossil evidence.

A highly resolved primate cladogram based on DNA evidence is congruent with extant and fossil osteological evidence. A provisional primate classification based on this cladogram and the time scale provided by fossils and the model of local molecular clocks has all named taxa represent clades and assigns the same taxonomic rank to those clades of roughly equivalent age. Order Primates divides into Strepsirhini and Haplorhini. Strepsirhines divide into Lemuriformes and Loriformes, whereas haplorhines divide into Tarsiiformes and Anthropoidea. Within Anthropoidea when equivalent ranks are used for divisions within Platyrrhini and Catarrhini, Homininae divides into Hylobatini (common and siamang gibbon) and Hominini, and the latter divides into Pongina for Pongo (orangutans) and Hominina for Gorilla and Homo. Homo itself divides into the subgenera H. (Homo) for humans and H. (Pan) for chimpanzees and bonobos. The differences between this provisional age related phylogenetic classification and current primate taxonomies are discussed.
The expression of thyroid hormone transporters in the human fetal cerebral cortex during early development and in N‐Tera‐2 neurodifferentiation

Non‐technical summary Thyroid hormones are important in brain development and they enter cells through thyroid hormone transporters at the cell membrane. Thyroid hormone transporters are thought to play an important role since gene defects in one of these transporters, MCT8, have been associated with severe mental retardation. This paper describes the expression of a range of thyroid hormone transporters in the human fetal brain during early pregnancy, and suggests that these transporters could regulate the supply of thyroid hormones into brain cells from very early in development. Surprisingly, the reduction of thyroid hormones and MCT8 expression do not affect the differentiation of an unspecialised cell to a specialised human nerve cell in the brain. Thyroid hormones and MCT8 are thus likely to affect other processes during human brain development. To find out how thyroid hormones influence human fetal brain development requires further research.
Are exchange rates interdependent? Evidence using wavelet analysis

ABSTRACT We examine the co-movement in daily returns of USD–INR, EUR–INR, GBP–INR, and JPY–INR currency pair futures contracts traded on the National Stock Exchange of India (NSE) using the wavelet cohesion approach. This study contributes to the literature by examining the scantly studied area of co-movement in exchange rates and using the wavelet approach, which allows us to analyse time–frequency-wise co-movement of the time series. The empirical results indicate that the currency futures markets are nearly perfectly integrated in the long run (monthly, quarterly and biannual scales) offering little potential gains from international portfolio diversification. The discrepancies between currency futures markets are small and almost fade away within 3–6 months. Moreover, international currency diversification might offer relatively higher potential gains at intraweek, weekly, and fortnightly time horizons owing to lower correlations among the currencies under consideration. Finally, our multiple-wavelet correlation and cross-correlation analysis shows that GBP acts as a potential leader/follower across scales. The results of our analysis indicate the dynamic pattern of co-movement among the major currency futures contracts, which provides several implications for portfolio managers and international investors participating in the Indian market.
An Operational Semantic Basis for OpenMP Race Analysis

OpenMP is the de facto standard to exploit the on-node parallelism in new generation supercomputers.Despite its overall ease of use, even expert users are known to create OpenMP programs that harbor concurrency errors, of which one of the most insidious of errors are {\em data races}. OpenMP is also a rapidly evolving standard, which means that future data races may be introduced within unfamiliar contexts.A simple and rigorous operational semantics for OpenMP can help build reliable race checkers and ward off future errors through programmer education and better tooling.This paper's key contribution is a simple operational semantics for OpenMP, with primitive events matching those generated by today's popular OpenMP runtimes and tracing methods such as OMPT.This makes our operational semantics more than a theoretical document for intellectual edification; it can serve as a blueprint for OpenMP event capture and tool building.We back this statement by summarizing the workings of a new data race checker for OpenMP being built based on this semantics.The larger purpose served by our semantics is to serve the needs of the OpenMP community with regard to their contemplated extensions to OpenMP, as well as future tooling efforts.
Recall initiation strategies must be controlled in training studies that use immediate free recall tasks to measure the components of working memory capacity across time

There has been great interest in using working memory (WM) training regimens as an alternative treatment for ADHD, but it has recently been concluded that existing training regimens may not be optimally designed because they target the primary memory component but not the secondary component of WM capacity. This conclusion requires the ability to accurately measure changes in primary and secondary memory abilities over time. The immediate free recall task has been used in previous studies to measure these changes; however, one concern with these tasks is that the recall order required on training exercises may influence the recall strategy used during free recall, which may in turn influence the relative number of items recalled from primary and secondary memory. To address this issue, previous training studies have explicitly controlled recall strategy before and after training. However, the necessity of controlling for recall strategies has not been explicitly tested. The present study investigated the effects of forward-serial-order training on free recall performance under conditions in which recall strategy was not controlled using a sample of adolescents with ADHD. Unlike when recall order was controlled, the main findings showed selective improvement of the secondary memory component (as opposed to the primary memory component) when recall order was uncontrolled. This finding advances our understanding of WM training by highlighting the importance of controlling for recall strategies when free recall tasks are used to measure changes in the primary and secondary components of WM across time.
Ectopic expression of the coxsackievirus and adenovirus receptor increases susceptibility to adenoviral infection in the human cervical cancer cell line, SiHa.

The expression level of the coxsackievirus and adenovirus receptor (CAR) gene in human cervical cancer cell lines (Hela, Caski, HT-3, and SiHa) appears to be correlated with their susceptibility to adenoviral vector-based gene transfer. Hela, Caski, and HT-3 cells, which express the CAR molecule on the cell surface, showed a higher susceptibility to infection of AdCMVGFP than SiHa cells with no detectable level of CAR expression. Transient expression of the CAR gene in SiHa cells dramatically enhanced the susceptibility to adenoviral infection. Furthermore, SiHa-CAR, a stable transfectant which expresses the CAR gene showed a highly increased susceptibility to adenoviral infection in contrast to SiHa. These results demonstrate that the low susceptibility of SiHa to adenoviral infection is closely related to its loss of the CAR gene expression. In addition, the low infection efficacy can be overcome by the ectopic expression of the CAR gene. These results also give insight into a possible application of the CAR gene to adenovirus-mediated gene delivery.