Miracle-dz/UniFAR-FTUs huggingface dataset:
The dopamine D4 receptor in schizophrenia: an update

The dopamine D2 receptor as defined in classical pharmacological terms (not linked to adenylate cyclase) is historically the site of action of psychotropic drugs and the prime neurochemical candidate for schizophrenia. Molecular genetic studies of dopamine receptors have now shown that they belong to a genetically similar superfamily of receptors that are characterized by having seven transmembrane protein domains and are coupled to G-protein regulated second messenger systems. On the basis of sequence homology and pharmacological characteristics, they remain in two categories broadly similar to, and named after, traditional Dl and D2 receptors (Sibley & Monsma, 1992). The subfamily of D2 receptor is further divided on the basis of sequence into D3 and D4 receptors, which overall have the characteristics of D2 receptors but with interesting anatomical distributions and one or two crucial differences in pharmacology, such as the high affinity of clozapine for the D4 receptor (Van Tol et al. 1992). The overall D2 characteristics, plus the anomalous divergence from these characteristics, make the D4 receptor a highly attractive candidate for the dopamine receptor abnormality of schizophrenia. This editorial assesses progress to date in this rapidly evolving story.
Sexual risk behaviors among apps-using young men who have sex with men in Hong Kong

ABSTRACT This study is among the first to examine the sexual risk behaviors and attendant factors of young men who have sex with men (YMSM) in Hong Kong using location-aware gay social networking mobile applications (“gay apps”). Among the 213 YMSM (Mage = 21.52, SD = 2.29 years, range 17–25) who reported their recent (past six months) sexual history with male partners and gay apps use, inconsistent condom use (ICU) during anal sex was fairly common (60.2% regular partners, 45.8% non-regular partners). One-fifth of the sample reported condomless internal ejaculation (CIE) during anal sex (19.3% insertive, 19.8% receptive). Frequent “Grindr” and “Jack'd” users were less likely to report anal sex, and hence ICU, with regular [adjusted odds ratio (AOR) = 0.72] and non-regular (AOR = 0.62) partners, respectively. Sexual partnering via apps doubled the odds of ICU with both regular (AOR = 1.99) and non-regular (AOR = 2.17) partners. The odds of ICU with regular partners also increased with relationship status (AOR = 2.86 exclusive, AOR = 3.23 non-exclusive) but reduced for those who never had STI/HIV testing (AOR = 0.27). With non-regular partners, YMSM's likelihood of ICU increased with more recent partners (AOR = 3.25) and drug use (AOR = 3.79), but reduced with group sex (AOR = 0.15). The odds of receptive CIE increased with alcohol consumption (AOR = 4.04), non-exclusive relationship (AOR = 4.10), and more recent partners (AOR = 2.47), but reduced with group sex (AOR = 0.15) and older age (AOR = 0.84). For insertive CIE, the odds increased with bisexual YMSM (AOR = 2.89), exclusive relationship (AOR = 3.97), and longtime apps-use (AOR = 1.81). The findings identify meaningful differences among YMSM app-users that inform sexual health intervention and suggest attention on alcohol or drug use during sex and condomless sex with non-exclusive regular partners.
Trouble in the second year: three questions about family interaction.

3 questions regarding family interaction in the second year of life are addressed in this report on 69 families rearing firstborn sons. Question 1 concerns the identification, via cluster analysis, of families having difficulty managing their child, using codings of narrative records of family interaction when children were 15 and 21 months of age. Parents in families identified as "troubled" at each age tried to control their toddlers most often, were least likely to rely upon control-plus-guidance management strategies, had children who defied them most frequently, and experienced the greatest escalation of negative affect in these control encounters. Families identified as "troubled" at both 15 and 21 months had children who received the highest "externalizing" problem scores at 18 months and mothers who experienced the most daily hassles during the second year. Question 2 concerns the antecedents of "trouble in the second year. " Discriminant function analyses indicated that membership in the groups of families that appeared troubled at both ages of measurement (n = 15), at only one age (n = 28), or never (n = 26) could be reliably predicted (hit rate = 71%) using a set of 9 measurements of parent personality, child emotionality/temperament, marital quality, work-family relations, and social support, suggested by Belsky's model of the determinants of parenting, and social class. Question 3 concerns the proposition that extensive nonmaternal care in the first year is a risk factor for troubled family functioning in the second year. As hypothesized, prediction analysis showed that families at moderate and high contextual risk (based on 10 antecedent variables pertaining to Question 2), were significantly more likely to experience trouble in the second year when children experienced 20 or more hours per week of nonmaternal care in their first year, and these results could not be attributed to "selection effects. "
A Novel Cation-Dependent O-Methyltransferase Involved in Anthocyanin Methylation in Grapevine1[C][W][OA]

Anthocyanins are major pigments in colored grape (Vitis vinifera) berries, and most of them are monomethoxylated or dimethoxylated. We report here the functional characterization of an anthocyanin O-methyltransferase (AOMT) from grapevine. The expression pattern in two cultivars with different anthocyanin methylation profiles (Syrah and Nebbiolo) showed a peak at start ripening (véraison), when the concentrations of all methylated anthocyanins begin to increase. The purified recombinant AOMT protein was active on both anthocyanins and flavonols in vitro, with Km in the micromolar range, and was dependent on divalent cations for activity. AOMT showed a preference for 3′,5′ methylation when a 3′,4′,5′ hydroxylated anthocyanin substrate was tested. In order to assess its in planta activity, we performed transient expression of AOMT in tobacco (Nicotiana benthamiana) leaves expressing the Production of Anthocyanin Pigment1 (PAP1) transcription factor from Arabidopsis (Arabidopsis thaliana). PAP1 expression in leaves induced the accumulation of the nonmethylated anthocyanin delphinidin 3-rutinoside. The coexpression of PAP1 and AOMT resulted in an accumulation of malvidin 3-rutinoside. We also showed that AOMT localized exclusively in the cytoplasm of tobacco leaf cells. These results demonstrate the ability of this enzyme to methylate anthocyanins both in vitro and in vivo, indicating that AOMT plays a major role in anthocyanin biosynthesis in grape berries.
Effect of Resveratrol on Serum and Liver Lipid Profile and Antioxidant Activity in Hyperlipidemia Rats

The antioxidant activity of resveratrol in cholesterol-fed rats, along with its hypolipidemic effects was determined. Thirty two male Sprague-Dawley (SD) rats were randomly divided into three groups (Control, Res30 and Res70) and fed a hyperlipidemic diet for 4 weeks. Resveratrol was suspended in 0.3% carboxymethyl cellulose (CMC) solution and given to rats of the Res30 and Res70 groups once a day for 4 weeks by oral intubation at a dose of 30 and 70 mg/kg body weight, respectively. The control group received 0.3% CMC solution alone. Resveratrol significantly lowered serum lipid, hepatic cholesterol (TC) and triglyceride (TG) levels compared to the control. Excretion of bile acids was significantly enhanced by resveratrol. The overall potential of the antioxidant system was significantly enhanced by the resveratrol as plasma and hepatic thiobarbituric acid reactive substances (TBARS) levels were lowered while serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were increased in the cholesterol-fed rats. These findings suggest that resveratrol maintains an antioxidant efficacy as well as its anti-hyperlipidemic effect.
A General Framework for Multi-agent Search with Individual and Global Goals: Stakeholder Search

Stakeholder search is a general framework for an extension to the improving on the competition approach paradigm for cooperative search that allows for additional individual goals of the search agents. This framework defines a whole spectrum of possibilities for search systems. Based on a scheme defining interactions, search agents use a given strategy (ranging from cooperative to competitive) to find good solutions for the global search goal that are also good for their individual goals. A stakeholder search system was created to solve instances of the package delivery problem. Experiments with search agents using either a cooperative, a competitive or a stakeholder strategy, between the two extremes, showed that the stakeholder strategy was effective at finding solutions which satisfied both the global goal and many of the individual agent's goals.
An analysis of the regulation of DNA synthesis by cdk2, Cip1, and licensing factor

The activation of DNA replication appears to involve at least four steps. These include origin recognition, origin unwinding, primer synthesis, and a switching step to a continuous elongation mode. Moreover, in higher eukaryotes a number of studies have shown that much of the DNA replication which occurs is restricted to specific sites within the nuclei. It has been proposed that these replication foci are composed of a large number of origin sites which are clustered together into an aggregate. The molecular basis for this aggregation is currently not well understood. Regulation of the activation of DNA replication is a complicated process. The G1-S kinase cdk2 is a positive regulator of replication. The p21 protein is a negative regulator of replication both by inhibiting cdk2 kinase and the replication protein PCNA. Moreover, it has been proposed that origin usage is restricted to a single firing per cell cycle by a "licensing factor. " Using a cell-free replication system derived from Xenopus eggs we have investigated at what step in the replication process these regulators participate. We present evidence that the clustered organization of DNA into foci is not a transient arrangement, but rather, it persists following DNA replication. We also find that foci form on both sperm chromatin and bacteriophage lambda DNA incubated in extracts depleted of cdk2 kinase. Therefore, our data support the conclusion that organization of chromatin into foci is an early event in the replication pathway preceding activation of cdk2 kinase. With respect to the role of cdk2 during activation of DNA replication we find that in cdk2-depleted extracts primer synthesis does not occur and RP-A remains tightly associated with foci. This strongly suggests that cdk2 kinase is required for activating the origin unwinding step of the replication process. Consistent with this interpretation we find that addition of rate limiting quantities of the cdk2 inhibitor p21 protein to an extract delays primer synthesis. Interestingly, in the presence of p21 primer synthesis does occur after a delay and then replication arrests. This is consistent with the published demonstration that p21 can inhibit PCNA, a protein required for replication beyond the priming step. Therefore, our results provide additional support to the proposal that the post-priming switching step is a key regulatory step in replication. With respect to the role of licensing factor during DNA replication it has recently been shown that treatment of mitotic extracts with kinase inhibitor DMAP inactivates "licensing factor. "(ABSTRACT TRUNCATED AT 400 WORDS)
Robust Sequential Data Modeling Using an Outlier Tolerant Hidden Markov Model

Hidden Markov (chain) models using finite Gaussian mixture models as their hidden state distributions have been successfully applied in sequential data modeling and classification applications. Nevertheless, Gaussian mixture models are well known to be highly intolerant to the presence of untypical data within the fitting data sets used for their estimation. Finite Student's t-mixture models have recently emerged as a heavier-tailed, robust alternative to Gaussian mixture models, overcoming these hurdles. To exploit these merits of Student's t-mixture models in the context of a sequential data modeling setting, we introduce, in this paper, a novel hidden Markov model where the hidden state distributions are considered to be finite mixtures of multivariate Student's t-densities. We derive an algorithm for the model parameters estimation under a maximum likelihood framework, assuming full, diagonal, and factor-analyzed covariance matrices. The advantages of the proposed model over conventional approaches are experimentally demonstrated through a series of sequential data modeling applications.
Efficient Detection of Zero-day Android Malware Using Normalized Bernoulli Naive Bayes

According to a recent F-Secure report, 97% of mobile malware is designed for the Android platform which has a growing number of consumers. In order to protect consumers from downloading malicious applications, there should be an effective system of malware classification that can detect previously unseen viruses. In this paper, we present a scalable and highly accurate method for malware classification based on features extracted from Android application package (APK) files. We explored several techniques for tackling independence assumptions in Naive Bayes and proposed Normalized Bernoulli Naive Bayes classifier that resulted in an improved class separation and higher accuracy. We conducted a set of experiments on an up-to-date large dataset of APKs provided by F-Secure and achieved 0.1% false positive rate with overall accuracy of 91%.
Stability of Multi-Path Dual Congestion Control Algorithms

This paper investigates fair, scalable, stable congestion controls which achieve high bandwidth utilization over networks operating multi-path routing. It aims to take advantage of path diversity to achieve efficient bandwidth allocation without causing instability. We develop a multi-path extension to the dual algorithm, which takes into consideration path diversity when evaluating fairness. This algorithm is shown to be globally stable in the absence of propagation delays and a sufficient condition for local stability, for the case when heterogeneous propagation delays are present, is found. The sufficient condition we present is decentralized in the following sense: the gain parameter for each dynamic variable is restricted by the average round-trip time of packets passing through the link or source it represents, but not by the round-trip times of any other packets. This leads to a highly scalable parameter choice scheme. Gain parameters are calculated from local information which is independent of the state of the algorithm, and our delay stability condition is satisfied. The models considered apply to networks consisting of arbitrary interconnections of sources and links with arbitrary heterogeneous propagation delays.
Mowat–Wilson syndrome and mutation in the zinc finger homeo box 1B gene: a well defined clinical entity

Mowat et al in 1998 delineated a new syndrome characterised by a distinct facial phenotype, Hirschsprung disease (HSCR), microcephaly, and mental retardation; they also identified a locus at chromosome 2q21-q23.1 The six children described were sporadic cases, and the authors suggested a contiguous gene syndrome or a dominant single gene disorder. Three further sporadic cases published earlier as having unclassified syndromic HSCR, Goldberg–Shprintzen syndrome, or 2q22-23 deletion,2–4 were recognised by Mowat et al having the same distinctive facial appearance as their patients. Kaariainen et al reported five patients with a similar phenotype.5 Mutations in ZFHX1B ( SIP1 ) were identified by Wakamatsu et al in a patient with a translocation t(2;13)(q22;q22) and in another three patients, all with syndromic HSCR.6 Mutations in ZFHX1B (SIP1) were also identified by Cacheux et al 7 in two patients of Kaariainen et al 5: patient 1 with a t(2;11)(q22.2;q21) and in patient 3; and in patients 1,2, and 3 of Mowat et al. 1 Subsequently Yamada et al reported ZFHX1B mutations in other patients with complex developmental disorders,8 as did Amiel et al in patients with syndromic Hirschsprung disease.9 Investigation of four patients by Zweier et al 10 and one patient by Garavelli et al 11 showed the distinct phenotype and the mutation in ZFHX1B ( SIP1 ) and confirmed the syndrome described by Mowat et al . 1 Recently an article by Wilson et al reported 15 new patients with ZFHX1B mutations, and a review of Mowat–Wilson syndrome was published by Mowat et al. 12,13 Although in total 45 cases with deletions or mutations in ZFHX1B ( SIP1 ) have been recorded,4–14 detailed clinical descriptions are rare. We report two new patients from Northern Italy with all the typical signs of the syndrome and with mutations in ZFHX1B …
Attracting Dynamics of Frontal Cortex Ensembles during Memory-Guided Decision-Making

A common theoretical view is that attractor-like properties of neuronal dynamics underlie cognitive processing. However, although often proposed theoretically, direct experimental support for the convergence of neural activity to stable population patterns as a signature of attracting states has been sparse so far, especially in higher cortical areas. Combining state space reconstruction theorems and statistical learning techniques, we were able to resolve details of anterior cingulate cortex (ACC) multiple single-unit activity (MSUA) ensemble dynamics during a higher cognitive task which were not accessible previously. The approach worked by constructing high-dimensional state spaces from delays of the original single-unit firing rate variables and the interactions among them, which were then statistically analyzed using kernel methods. We observed cognitive-epoch-specific neural ensemble states in ACC which were stable across many trials (in the sense of being predictive) and depended on behavioral performance. More interestingly, attracting properties of these cognitively defined ensemble states became apparent in high-dimensional expansions of the MSUA spaces due to a proper unfolding of the neural activity flow, with properties common across different animals. These results therefore suggest that ACC networks may process different subcomponents of higher cognitive tasks by transiting among different attracting states.
ACDC: A Structured Efficient Linear Layer

The linear layer is one of the most pervasive modules in deep learning representations. However, it requires $O(N^2)$ parameters and $O(N^2)$ operations. These costs can be prohibitive in mobile applications or prevent scaling in many domains. Here, we introduce a deep, differentiable, fully-connected neural network module composed of diagonal matrices of parameters, $\mathbf{A}$ and $\mathbf{D}$, and the discrete cosine transform $\mathbf{C}$. The core module, structured as $\mathbf{ACDC^{-1}}$, has $O(N)$ parameters and incurs $O(N log N )$ operations. We present theoretical results showing how deep cascades of ACDC layers approximate linear layers. ACDC is, however, a stand-alone module and can be used in combination with any other types of module. In our experiments, we show that it can indeed be successfully interleaved with ReLU modules in convolutional neural networks for image recognition. Our experiments also study critical factors in the training of these structured modules, including initialization and depth. Finally, this paper also provides a connection between structured linear transforms used in deep learning and the field of Fourier optics, illustrating how ACDC could in principle be implemented with lenses and diffractive elements.
Extracorporeal photochemotherapy for secondary chronic progressive multiple sclerosis: a pilot study

Background/purpose: Extracorporeal photochemotherapy (ECP) has been proposed for the treatment of various auto‐ and allo‐immune reactions. However, a standard ECP regimen did not significantly alter the course of chronic progressive multiple sclerosis (MS). We tested whether an intensive ECP treatment can affect the course of secondary chronic progressive form of MS.
Dietary Protein: An Essential Nutrient For Bone Health

Nutrition plays a major role in the development and maintenance of bone structures resistant to usual mechanical loadings. In addition to calcium in the presence of an adequate vitamin D supply, proteins represent a key nutrient for bone health, and thereby in the prevention of osteoporosis. In sharp opposition to experimental and clinical evidence, it has been alleged that proteins, particularly those from animal sources, might be deleterious for bone health by inducing chronic metabolic acidosis which in turn would be responsible for increased calciuria and accelerated mineral dissolution. This claim is based on an hypothesis that artificially assembles various notions, including in vitro observations on the physical-chemical property of apatite crystal, short term human studies on the calciuric response to increased protein intakes, as well as retrospective inter-ethnic comparisons on the prevalence of hip fractures. The main purpose of this review is to analyze the evidence that refutes a relation of causality between the elements of this putative patho-physiological “cascade” that purports that animal proteins are causally associated with an increased incidence of osteoporotic fractures. In contrast, many experimental and clinical published data concur to indicate that low protein intake negatively affects bone health. Thus, selective deficiency in dietary proteins causes marked deterioration in bone mass, micro architecture and strength, the hallmark of osteoporosis. In the elderly, low protein intakes are often observed in patients with hip fracture. In these patients intervention study after orthopedic management demonstrates that protein supplementation as given in the form of casein, attenuates post-fracture bone loss, increases muscles strength, reduces medical complications and hospital stay. In agreement with both experimental and clinical intervention studies, large prospective epidemiologic observations indicate that relatively high protein intakes, including those from animal sources are associated with increased bone mineral mass and reduced incidence of osteoporotic fractures. As to the increased calciuria that can be observed in response to an augmentation in either animal or vegetal proteins it can be explained by a stimulation of the intestinal calcium absorption. Dietary proteins also enhance IGF-1, a factor that exerts positive activity on skeletal development and bone formation. Consequently, dietary proteins are as essential as calcium and vitamin D for bone health and osteoporosis prevention. Furthermore, there is no consistent evidence for superiority of vegetal over animal proteins on calcium metabolism, bone loss prevention and risk reduction of fragility fractures.