Miracle-dz/UniFAR-FTUs huggingface dataset:
From fat fighter to risk factor: the zigzag trek of leptin.

Obesity is a major risk factor for a number of cardiovascular diseases, and causes cardiac and vascular disease through well-known mediators including arterial hypertension, hyperlipidemia, and type-2 diabetes. Obesity is characterized by an excess of adipose tissue, which efficiently stores energy for times of starvation. In addition, multiple reports in the last decade have underlined the importance of white adipose tissue (WAT) as an endocrine organ.1 Several peptide hormones commonly referred to as adipokines are secreted by WAT, including leptin, adipsin, acylation-stimulating protein (ASP), angiotensinogen, plasminogen activator inhibitor-1 (PAI-1), adiponectin, resistin, various cytokines including GM-CSF and G-CSF, and steroid hormones.1 Consequently, WAT peptide hormones and cytokines are involved in energy homeostasis, glucose and lipid metabolism, immune response, reproduction, and vascular homeostasis. See page 112 The exact molecular mechanisms of increased adipogenesis and its relation to the development of atherosclerotic lesions still remain unclear. One focus of research has been leptin, which was discovered in 1994 and is considered one of the important peripheral signals affecting food intake and body weight balance.2 Leptin reduces appetite and can reduce obesity in leptin deficient (ob/ob) knock-out mice. However, the initial enthusiasm over the discovery of leptin and its potential as fat-fighter for the obese has been absorbed by the facts, which reveal that in obese humans leptin levels are increased and mutations of the leptin receptor gene are rare events. There is a strong correlation of plasma leptin concentrations in humans with total body fat mass and body mass index.3,4 Leptin production is about two-fold higher in females than in males and is affected by growth and energy consumption.2 The majority of obese humans with high levels of plasma leptin show a leptin insensitivity on the leptin receptor level.5 Increased plasma leptin concentrations are an independent predictor …
Rhizobia catabolize nod gene-inducing flavonoids via C-ring fission mechanisms

Gas chromatographic and mass spectrometric analyses of derivatized culture medium extracts were used to identify the products of flavonoid metabolism by rhizobia. A number of Rhizobium species and biovars degraded their nod gene-inducing flavonoids by mechanisms which originated in a cleavage of the C-ring of the molecule and which yielded conserved A- and B-ring products among the metabolites. In contrast, Pseudomonas putida degraded quercetin via an initial fission in its A-ring, and Agrobacterium tumefaciens displayed a nonspecific mode of flavonoid degradation which yielded no conserved A- or B-ring products. When incubated with rhizobia, flavonoids with OH substitutions at the 5 and 7 positions yielded phloroglucinol as the conserved A-ring product, and those with a single OH substitution at the 7 position yielded resorcinol. A wider range of structures was found among the B-ring derivatives, including p-coumaric, p-hydroxybenzoic, protocatechuic, phenylacetic, and caffeic acids. The isoflavonoids genistein and daidzein were also degraded via C-ring fission by Rhizobium fredii and Rhizobium sp. strain NGR234, respectively. Partially characterized aromatic metabolites with potential nod gene-inducing activity were detected among the products of naringenin degradation by Rhizobium leguminosarum bv. viciae. The initial structural modification of nod gene-inducing flavonoids by rhizobia can generate chalcones, whose open C-ring system may have implications for the binding of inducers to the nodD gene product.
New scan attacks against state-of-the-art countermeasures and DFT

Scan attack has been known as a threat to Design for Testability (DFT). All the existing attacks require both the normal mode and the test mode of the device. In normal mode the intermediate results of a crypto-hardware are captured in scan chains and in the test mode the results are shifted out. One simple countermeasure for this kind of attacks is to reset the device whenever there is a switch of the mode. A recent test-mode-only attack shows that the mode-reset countermeasure is insecure against scan attack. An attack is still possible using only the test mode of the device. However, the attack was presented without the presence of an on-chip test compactor. In this paper we propose a new test-mode-only attack on AES hardware which works in the presence of an on-chip response compactor. The proposed attack retrieves the secret key with negligible time complexity. The attack results show that DFT infrastructures with response compactor are vulnerable to scan attack even in the presence of mode-reset countermeasure.
Mutation in the factor VII hepatocyte nuclear factor 4&agr;-binding site contributes to factor VII deficiency

Severe coagulant factor VII (FVII) deficiency in postpubertal dizygotic twin males results from two point mutations in the FVII gene, a promoter region T→C transition at −60 and a His-to-Arg substitution at amino acid 348; both mutations prevent persistence of plasma functional FVII. This report documents longitudinal laboratory measurements from infancy to adulthood of FVII coagulant activity (FVII:C) in the twin FVII-deficient patients; it also details specific biochemical analyses of the −60 T→C mutation. The results revealed FVII:C levels of less than 1% in infancy that remain severely decreased through puberty and into adulthood. In-vitro analyses utilizing hepatocyte nuclear factor 4&agr; (HNF4&agr;) co-transfection and a chromatin immunoprecipitation assay indicate that the −60 T→C mutation severely diminishes functional interaction between the FVII promoter and transcription factor HNF4&agr;. The importance of interaction between the FVII gene and HNF4&agr; in normal FVII expression provides an in-vivo illustration of the regulated expression of an autosomal gene encoding a coagulation protein. The constancy of FVII:C and peripubertal patient symptomatology reported here illustrates androgen-independent expression in contrast to expression with an analogous mutation in the promoter region of the gene encoding coagulation FIX.
Individual differences in responses to ethanol and d-amphetamine: a within-subject study.

BACKGROUND In some individuals, ethanol (EtOH) produces marked stimulant-like subjective effects resembling those of stimulant drugs, like d-amphetamine (AMP). In this study, we examined the neurochemical basis of these individual differences by examining the same subjects' responses to both EtOH and AMP. A positive correlation between subjects' responses to the two drugs may suggest that AMP and EtOH produce their stimulant-like subjective effects by a shared mechanism. METHODS Twenty-seven volunteers (17 male, 10 female), aged 21-35, received beverages or capsules containing EtOH 0.8 g/kg, AMP 10 or 20 mg, or placebo on four separate sessions in random order and under double-blind conditions. Various self-reported and objective drug effects were measured, including measures sensitive to subjective and cognitive stimulant-like effects. RESULTS EtOH and AMP produced their prototypical subjective and behavioral effects, including increased ratings of stimulant-like subjective effects, increased heart rate and blood pressure, and improved vigilance performance after AMP and increased ratings of sedative-like subjective effects, increased heart rate and blood pressure, and impaired vigilance performance after EtOH. Consistent with previous reports, there was substantial intersubject variability in subjective responses to EtOH: some subjects reported primarily stimulant-like effects, whereas others reported primarily sedative-like effects. To examine the relationship between these responses to EtOH and subjects' responses to AMP, correlations were examined between effects of EtOH and AMP. For all subjects together, there was a significant positive correlation between responses to EtOH and 20 mg AMP on the ARCI A scale (a measure of stimulant-like subjective effects; r = 0.41, p < 0.05). Among only those subjects who reported primarily stimulant-like effects from EtOH, the correlation between EtOH and AMP was 0.64 (p < 0.05). CONCLUSIONS Subjects who experience pronounced stimulant-like effects from EtOH also report greater stimulant effects from AMP, suggesting that these effects may be mediated through similar mechanisms. These correlations between the drugs' effects were not observed on other measures, such as DSST or vigilance task performance or heart rate. This may indicate that these other effects are mediated by separate mechanisms. The study illustrates a novel approach to studying the neurochemical basis of drug effects.
Toward an MT System without Pre-Editing: Effects of a New Method in ALT-J/E

Recently, several types of Japanese to English MT (machine translation) systems have been developed, but prior to using such systems, they have required a pre-editing process of re-writing the original text into Japanese that could be easily translated. For communication of translated information requiring speed in dissemination, application of these systems would necessarily pose problems. To overcome such problems, a Multi-Level Translation Method based on Constructive Process Theory had been proposed. In this paper, the benefits of this method in ALT-J/E will be described. In comparison with the conventional elementary composition method, the Multi-Level Translation Method, emphasizing the importance of the meaning contained in expression structures, has been ascertained to be capable of conducting translation according to meaning and context processing with comparative ease. We are now hopeful of realizing machine translation omitting the process of pre-editing.
Characterization of Osterix Protein Stability and Physiological Role in Osteoblast Differentiation

Osterix (Osx/SP7) is a C2H2 zinc finger-containing transcription factor of the SP gene family. Osx knockout mice indicate that the gene plays an essential role in osteoblast differentiation and bone formation. However, the mechanisms involved in the regulation of Osx are still poorly understood. Here, we report a novel post-translational mechanism for the regulation of Osx in mammalian cells. We found that the stability of endogenous and exogenous Osx reduced after cycloheximide treatment. In cells treated with the proteasome inhibitors MG-132 or lactacystin, both endogenous and exogenous Osx protein expression increased in a time-dependent manner. Co-immunoprecipitation (Co-IP) assays showed that both endogenous and exogenous Osx were ubiquitinated. Six lysine residues of Osx were identified as candidate ubiquitination sites by construction of point mutant plasmids and luciferase reporter assays. Furthermore, we confirmed that K58 and K230 are the ubiquitination sites of Osx by Co-IP assays and protein stability assays. Moreover, the Osx K58R and K230R mutations promoted the expression of osteoblast differentiation markers (alkaline phosphatase, collagen I and osteocalcin) and enhanced osteogenic differentiation in C2C12 cells. Taken together, our data indicate that Osx is an unstable protein, and that the ubiquitin-proteasome pathway is involved in the regulation of Osx and thereby regulates osteoblast differentiation.
JIAD: a tool to infer design patterns in refactoring

Refactoring in object-orientation has gained increased attention due to its ability to improve design quality. Refactoring using design patterns (DPs) leads to production of high quality software systems. Although numerous tools related to refactoring exist, only a few of them apply design patterns in refactoring. Even these do not clearly specify where refactoring can be applied and when to apply appropriate design patterns.In this paper, we propose a tool, JIAD (Java based Intent-Aspects Detector) which addresses the refactoring issues such as, the scope for applying DPs in the code and the appropriate selection of DPs. The tool automates the identification of Intent-Aspects (IAs) which helps in applying suitable design patterns while refactoring the Java code. By automating the process of identifying IAs, the whole process of refactoring using DPs can be automated which enables rapid development of software systems. Also, the tool minimizes the number of possible errors while inferring the suitable DPs to apply refactoring. Our approach primarily focuses on Java code refactoring using declarative programming and AspectJ compiler. Finally, the tool is validated using two applications namely, JLex and Java2Prolog written in Java.
Interactive programming in Agda – Objects and graphical user interfaces

Abstract We develop a methodology for writing interactive and object-based programs (in the sense of Wegner) in dependently typed functional programming languages. The methodology is implemented in the ooAgda library. ooAgda provides a syntax similar to the one used in object-oriented programming languages, thanks to Agda's copattern matching facility. The library allows for the development of graphical user interfaces (GUIs), including the use of action listeners. Our notion of interactive programs is based on the IO monad defined by Hancock and Setzer, which is a coinductive data type. We use a sized coinductive type which allows us to write corecursive programs in a modular way. Objects are server-side interactive programs that respond to method calls by giving answers and changing their state. We introduce two kinds of objects: simple objects and IO objects. Methods in simple objects are pure, while method calls in IO objects allow for interactions before returning their result. Our approach also allows us to extend interfaces and objects by additional methods. We refine our approach to state-dependent interactive programs and objects through which we can avoid exceptions. For example, with a state-dependent stack object, we can statically disable the pop method for empty stacks. As an example, we develop the implementation of recursive functions using a safe stack. Using a coinductive notion of object bisimilarity, we verify basic correctness properties of stack objects and show the equivalence of different stack implementations. Finally, we give a proof of concept that our interaction model allows to write GUI programs in a natural way: we present a simple drawing program, and a program which allows the users to move a small spaceship using a button.
Prevalence of autosomal dominant cerebellar ataxia in Aomori, the northernmost prefecture of Honshu, Japan.

OBJECTIVE The frequency of autosomal dominant cerebellar ataxia (ADCA) varies between different regions of Japan. This is the first report on the prevalence of ADCA subtypes in Aomori, Japan. METHODS AND PATIENTS Sixty-five familial spinocerebellar ataxia (SCA) patients and 15 sporadic SCA patients were genetically examined. For only the SCA2 patients (n = 8), the magnetic resonance imaging (MRI) data were analyzed in detail. RESULTS Spinocerebellar ataxia (SCA) type 6 was often observed (77.7% of cases), with SCA2 (10.6% of cases) being the next most common form. In contrast, only one of the eighty patients had SCA1. Among the 15 sporadic SCA patients, genetic mutations for SCA2, SCA6, SCA17, and SCA31 were identified, indicating that ADCAs should be considered in sporadic cases of ataxia. Furthermore, in SCA2 cases, brainstem atrophy, pontine midline linear hyperintensity, and atrophy of the frontal lobes were frequently observed using MRI. CONCLUSION The present data indicate that the prevalence of ADCA in Aomori differs from other prefectures in the Tohoku District. MRI findings are very similar between SCA2 and multiple system atrophy (MSA), and thus care must be taken to prevent the misdiagnosis of sporadic SCA2 as MSA.
Graph Regularized and Locality-Constrained Coding for Robust Visual Tracking

Visual tracking is complicated due to factors, such as occlusion, background clutter, abrupt target motion, and illumination variations, among others. In recent years, subspace representation and sparse coding techniques have demonstrated significant improvements in tracking. However, performance gain in tracking has been at the expense of losing locality and similarity attributes among the instances to be encoded. In this paper, a graph regularized and locality-constrained coding (GRLC) technique that encapsulates local manifold structure of the data in order to preserve locality and similarity information among instances is proposed. The GRLC methodology incorporates a similarity-preserving term within the objective function of the locality-constrained linear coding model, thereby overcoming some of the inherent instability issues common to such coding methods. In the proposed GRLC scheme, a graph Laplacian regularizer is chosen as a smoothing operator to learn both the representation dictionary and the coefficients by preserving the local structure of the data. This graph Laplacian smoothing operator ensures that the representations vary smoothly along the geodesics of the data manifold. Thus, by deriving the objective function of the GRLC method, a discriminative dictionary of instances can be iteratively obtained and the corresponding coefficients for each candidate can be computed using this learned dictionary. Finally, an effective observation likelihood function based on reconstruction error and a simple dictionary update scheme for visual target tracking are also proposed. Experimental results on the CVPR2013 visual tracker benchmark have demonstrated a favorable performance of the proposed technique both in terms of accuracy and robustness.
Before it is too late: professional responsibilities in late-onset Alzheimer’s research and pre-symptomatic prediction

The development of a wide array of molecular and neuroscientific biomarkers can provide the possibility to visualize the course of Alzheimer’s disease (AD) at early stages. Many of these biomarkers are aimed at detecting not only a preclinical, but also a pre-symptomatic state. They are supposed to facilitate clinical trials aiming at treatments that attack the disease at its earliest stage or even prevent it. The increasing number of such biomarkers currently tested and now partly proposed for clinical implementation calls for critical reflection on their aims, social benefits, and risks. This position paper summarizes major challenges and responsibilities. Its focus is on the ethical and social problems involved in the organization and application of dementia research, as well as in healthcare provision from a cross-national point of view. The paper is based on a discussion of leading dementia experts from neuroscience, neurology, social sciences, and bioethics in the United States and Europe. It thus reflects a notable consensus across various disciplines and national backgrounds. We intend to initiate a debate on the need for actions within the researchers’ national and international communities.
Principal polar spectral indices for mapping mangroves forest in South East Asia: study case Indonesia

ABSTRACT Identification and monitoring of species composition and richness is needed to formulate effective mangrove management and conservation priorities. Prior studies have used commercial satellite images which are cost prohibitive for national and global applications. Here, we used freely available Landsat satellite data and new indices to discriminate mangrove species in Maros Regency, South Sulawesi, Indonesia and Segara Anakan, West Java, Indonesia. We use sensitive algorithm of the principal polar spectral (PPS) indices to discriminate mangroves species. PPS Indices were produced from a set of 3-dimensional Landsat 8 Operational Land Imager (OLI) spectral indices (PPS Brightness, PPS Greenness, and PPS Wetness) determined by a polar change of the principal component axes of a spectral image of reference scene. We qualitatively compare this set of PPS indices with the set of conventional RGB multi-bands image composition and conventional Normalized Difference Vegetation Indices (NDVI) for mangroves species discrimination. The comparisons indicate that the set of PPS indices have the potential for regional and possibly global applications in mangroves species mapping and monitoring.
Objects and Agents : How do they differ ? by

Just how different are objects and agents? Some developers consider agents to be objects, but with more bells and whistles. This approach tends to define agents beginning with the phrase, "An agent is an object that . "—where the definers add their favorite discriminating features. Then, there are those who see agents and objects as different even though they share many things in common. Both approaches envision using both objects and agents together in the development of software systems. This article discusses both the differences and similarities between agents and objects and lets you decide which viewpoint you want to choose. Whichever viewpoint you choose, I hope you will find that the agent-based way of thinking brings a useful and important perspective for system development.
Structure of a myosin•adaptor complex and pairing by cargo

Significance To navigate large cargo through the viscous cytoplasm, cells use a variety of energy-consuming machines that, akin to ropewalkers, move on intracellular “tracks” in a stepwise “bipedal” fashion. To prevent waste of energy by futile walking, several control mechanisms have evolved. In the case described here for one group of yeast myosins, crystallographic and biophysical analyses revealed that a single myosin molecule associates with an intertwined middle region of two “adaptor” molecules. The adaptor also contains distinct binding sites for cargo. Only when cargo is attached to the myosin-bound adaptor are two of the myosin–adaptor complexes joined into a pair, akin to converting a uniped (unable to walk) into a biped (able to walk). Myosin 4 protein (Myo4p), one of five distinct myosins of yeast, is dedicated to cytoplasmic transport of two types of cargos, zipcoded messenger ribonucleoprotein particles (mRNPs) and tubular endoplasmic reticulum (tER). Neither cargo binds directly to Myo4p. Instead, swi5p-dependent HO expression 3 protein (She3p) serves as an “adaptor” that contains three binding modules, one for Myo4p and one each for zipcoded mRNP and tER. The assembly of a transport-competent motor complex is poorly understood. Here, we report that Myo4p•She3p forms a stable 1:2 heterotrimer in solution. In the Myo4p•She3p crystal structure, Myo4p’s C-terminal domain (CTD) assumes a lobster claw-shaped form, the minor prong of which adheres to a pseudocoiled-coil region of She3p. The extensive Myo4p•She3p interactome buries 3,812 Å2 surface area and is primarily hydrophobic. Because the Myo4p•She3p heterotrimer contains only one myosin molecule, it is not transport-competent. By stepwise reconstitution, we found a single molecule of synthetic oligonucleotide (representing the mRNA zipcode element) bound to a single tetramer of zipcode binding protein She2p to be sufficient for Myo4p•She3p dimerization. Therefore, cargo initiates cross-linking of two Myo4p•She3p heterotrimers to an ensemble that contains two myosin molecules obligatory for movement. An additional crystal structure comprising an overlapping upstream portion of She3p showed continuation of the pseudocoiled-coil structure and revealed another highly conserved surface region. We suggest this region as a candidate binding site for a yet unidentified tER ligand. We propose a model whereby zipcoded mRNP and/or tER ligands couple two Myo4p•She3p heterotrimers and thereby generate a transport-competent motor complex either for separate transport or cotransport of these two cargos.