Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic association and brain morphology studies and the chromosome 8p22 pericentriolar material 1 (PCM1) gene in susceptibility to schizophrenia.

CONTEXT There is evidence of linkage to a schizophrenia susceptibility locus on chromosome 8p21-22 found by several family linkage studies. OBJECTIVES To fine map and identify a susceptibility gene for schizophrenia on chromosome 8p22 and to investigate the effect of this genetic susceptibility on an endophenotype of abnormal brain structure using magnetic resonance imaging. DESIGN Fine mapping and identification of a chromosome 8p22 susceptibility gene was carried out by finding linkage disequilibrium between genetic markers and schizophrenia in multiply affected families, a case-control sample, and a trio sample. Variation in brain morphology associated with pericentriolar material 1 (PCM1) alleles was examined using voxel-based morphometry and statistical parametric mapping with magnetic resonance imaging. Setting and Patients A family sample of 13 large families multiply affected with schizophrenia, 2 schizophrenia case-control samples from the United Kingdom and Scotland, and a sample of schizophrenic trios from the United States containing parents and 1 affected child with schizophrenia. MAIN OUTCOME MEASURES Tests of transmission disequilibrium between PCM1 locus polymorphisms and schizophrenia using a family sample and tests of allelic association in case-control and trio samples. Voxel-based morphometry using statistical parametric mapping. RESULTS The family and trio samples both showed significant transmission disequilibrium between marker D85261 in the PCM1 gene locus and schizophrenia. The case-control sample from the United Kingdom also found significant allelic association between PCM1 gene markers and schizophrenia. Voxel-based morphometry of cases who had inherited a PCM1 genetic susceptibility showed a significant relative reduction in the volume of orbitofrontal cortex gray matter in comparison with patients with non-PCM1-associated schizophrenia, who, by contrast, showed gray matter volume reduction in the temporal pole, hippocampus, and inferior temporal cortex. CONCLUSIONS The PCM1 gene is implicated in susceptibility to schizophrenia and is associated with orbitofrontal gray matter volumetric deficits.
A Tyrosine Kinase Inhibitor–Based High-Affinity PET Radiopharmaceutical Targets Vascular Endothelial Growth Factor Receptor

Tyrosine kinase receptors including vascular endothelial growth factor receptor (VEGFR) have gained significant attention as pharmacologic targets. However, clinical evaluation of small-molecule drugs or biologics that target these pathways has so far yielded mixed results in a variety of solid tumors. The reasons for response variability remain unknown, including the temporal and spatial patterns of receptor tyrosine kinase expression. Methods to detect and quantify the presence of such cellular receptors would greatly facilitate drug development and therapy response assessment. We aimed to generate specific imaging agents as potential companion diagnostics that could also be used for targeted radionuclide therapy. Here, we report on the synthesis and initial preclinical performance of 64Cu-labeled probes that were based on the kinase inhibitor already in clinical use, vandetanib (ZD6474), as a VEGFR-selective theranostic radiopharmaceutical. Methods: A monomeric (ZD-G1) and a dimeric (ZD-G2) derivative of ZD6474 were synthesized and conjugated with DOTA for chelation with 64Cu to produce the probes 64Cu-DOTA-ZD-G1 and 64Cu-DOTA-ZD-G2. The binding affinity and specificity to VEGFR were measured using U-87 MG cells known to overexpress VEGFR. Small-animal PET and biodistribution studies were performed with 64Cu-labeled probes (3–4 MBq) intravenously administered in U-87 MG tumor–bearing mice with or without coinjection of unlabeled ZD-G2 for up to 24 h after injection. Results: Receptor-binding assays yielded a mean equilibrium dissociation constant of 44.7 and 0.45 nM for monomeric and dimeric forms, respectively, indicating a synergistic effect in VEGFR affinity by multivalency. Small-animal PET/CT imaging showed rapid tumor accumulation of 64Cu-DOTA-ZD-G2, with excellent tumor–to–normal tissue contrast by 24 h. Coinjection of the 64Cu-DOTA-ZD-G2 with 50 nmol (60 μg) of nonradioactive ZD-G2 effectively blocked tumor uptake. Conclusion: A 64Cu-labeled probe derived from an approved oncologic drug selective for VEGFR demonstrates excellent tumor targeting, particularly for the dimeric form. The multivalent probe yielded a 100-fold improvement in receptor affinity while maintaining pharmacokinetic and biodistribution properties well suited for PET imaging in our preclinical model. These results indicate that a clinically relevant theranostic platform can be rapidly developed from known small molecules that target key cellular receptors.
The effect of collusion games on the profit of primary networks and secondary heterogeneous cognitive radio networks with femtocells

This paper studies the effect of the different pricing games played by the primary user (PU) operators on the profit of both the PU networks and the cognitive base station (CBS). We show that the price achieved by the PU operators in the collusion game (called the Pareto point) is the maximum price that can be achieved in the competitive game when the substitutability parameter is higher than zero. However, for negative values of the substitutability parameter, the Pareto point represents the minimum price that can be offered by the PU operators. Moreover, the effect of the collusion game on the profit of the CBS has also been investigated, and the simulations show that the worst case for the CBS in terms of profit is not associated with the highest price that can be offered by the PU networks.
Low power MPEG-4 ASP codec IP macro for high quality mobile video applications

This work presents a low power MPEG-4 ASP (advanced simple profile) codec IP macro suitable for high quality mobile video applications. By introducing a motion estimation algorithm suitable for low power applications and a field/frame mode estimation algorithm for interlaced video, this IP macro achieves higher compression efficiency and image quality than previous SP (simple profile) codec LSIs.
Unsatisfactory glycemic control in type 2 Diabetes mellitus patients: predictive factors and negative clinical outcomes with the use of antidiabetic drugs

Many factors can interfere with glycemic control in patients with type 2 diabetes mellitus and this patient group has an increased risk of experiencing drug-related negative outcomes (DNO). The aim of this study was to identify the predictive factors of unsatisfactory glycemic control and DNO in this group of patients. A cross-sectional study was conducted collecting data from prescriptions and interviews with 100 patients of the Endocrinology Clinic of the Hospital Complex of Sorocaba, Sao Paulo, Brazil. Variables associated with unsatisfactory glycemic control were determined and the DNO associated with antidiabetic drugs identified. Age ( ;0.05). Characterization of the profile of patients with uncontrolled diabetes and of aspects associated with drug treatment can contribute to the planning of interventions to improve patient care.
NEMO: Next Career Move Prediction with Contextual Embedding

With increased globalization and labor mobility, human resource reallocation across firms, industries and regions has become the new norm in labor markets. The emergence of massive digital traces of such mobility offers a unique opportunity to understand labor mobility at an unprecedented scale and granularity. While most studies on labor mobility have largely focused on characterizing macro-level (e.g., region or company) or micro-level (e.g., employee) patterns, the problem of how to accurately predict an employee's next career move (which company with what job title) receives little attention. This paper presents the first study of large-scale experiments for predicting next career moves. We focus on two sources of predictive signals: profile context matching and career path mining and propose a contextual LSTM model, NEMO, to simultaneously capture signals from both sources by jointly learning latent representations for different types of entities (e.g., employees, skills, companies) that appear in different sources. In particular, NEMO generates the contextual representation by aggregating all the profile information and explores the dependencies in the career paths through the Long Short-Term Memory (LSTM) networks. Extensive experiments on a large, real-world LinkedIn dataset show that NEMO significantly outperforms strong baselines and also reveal interesting insights in micro-level labor mobility.
Downward Nominal Wage Rigidity in the OECD

Recent microeconomic studies have documented extensive downward nominal wage rigidity (DNWR) for job stayers in many OECD countries, but critics argue that the effect might be undone by compositional changes and flexibility in wages of new entrants. Using data for hourly nominal wages at industry level, we explore the existence of DNWR on industry wages in 19 OECD countries, over the period 1973-1999. We propose a novel method to detect DNWR. We reject the hypothesis of no DNWR in the overall sample. The fraction of wage cuts prevented due to DNWR has fallen over time, from 61 percent in the 1970s to 16 percent in the late 1990s, but the number of industries affected by DNWR has increased. DNWR is more prevalent when unemployment is low and union density is high. Strict employment protection legislation also leads to fewer wage cuts.
Reduced inhibition of Candida albicans adhesion by saliva from patients receiving oral cancer therapy

The effect of saliva on the adhesion of Candida albicans to epithelial cells was examined in vitro by using saliva from healthy controls and patients with oral squamous cell carcinoma. The adhesion of C. albicans to established epithelial tumor cells was reduced by 40% by salivary treatment of the C. albicans or epithelial cells. The inhibitory activity of saliva was almost completely abolished by anti-secretory immunoglobulin A antibody, concanavalin A, and mannose. Compared with saliva from healthy individuals, that from patients who had received chemoradiotherapy for oral carcinoma showed reduced suppression of C. albicans adhesion, which accompanied decreased salivary secretory immunoglobulin A and lactoferrin concentrations. A greater number of C. albicans cells adhered to buccal cells obtained from patients who had received chemoradiotherapy than to those from healthy individuals. Treatment of either epithelial cells or C. albicans with anticancer drugs induced an increase in adherence of epithelial cells and yeast cells. In contrast, concanavalin A- and mannose-pretreated C. albicans exhibited reduced adhesion to epithelial cells. No further decrease of C. albicans adhesion was observed when both epithelial cells and yeast phase C. albicans were treated with mannose. In conclusion, the inhibition of C. albicans adhesion by saliva depends largely on mannose residues on salivary glycoproteins and mannose is one of the binding ligands on both C. albicans and epithelial cells. In addition, anticancer therapy may induce oral C. albicans overgrowth by decreasing salivation and the concentrations of glycoproteins in saliva inhibiting C. albicans adhesion and by increasing the adhesive properties of both C. albicans and oral epithelial cells.
Designing a Sub-RISC Multi-Gigabit Regular Expression Processor

ABSTRACT Increasingly, embedded system designers must exploit application-speciﬁc concurrency in order to obtain high performance. Oftenan application will exhibit several different styles and granular-ities of concurrency. An average embedded RISC processor isa poor platform when concurrency is a ﬁrst-class concern. TheSub-RISC paradigm, on the other hand, allows designers to cre-ate programmable architectures with application-speciﬁc process-,data-, and datatype-level concurrency. This paper describes a Sub-RISC processor that accelerates regular expression matching fornetwork intrusion detection. This processor is lightweight and canbe tiled to search multiple packet streams in parallel. Unlike typi-cal application-speciﬁc processors, designers are not burdened withassembly language programming. Instead, the language of regularexpressions is used as a high-level programming abstraction. Re-sults are shown for ASIC and FPGA implementations using regexprules from the Snort database. 1. INTRODUCTION
Collision resolution algorithms in multistation packet-radio networks

The performance of a multistation packet-radio network in which the nodes of the network employ some collision resolution algorithm (CRA) for accessing a shared radio channel is analyzed. The two CRAs considered here are the binary-tree CRA (BTCRA) and the clipped binary-tree CRA (CBTCRA). The exact analysis of a multistation network with these access schemes is intractable. Therefore, the authors present an approximate method that captures the interactions among the nodes of different stations. The mean idea is to view the interference among the nodes of different stations as independent random noises and compute the probabilities of these noises, taking into account the interactions between the nodes. Numerical results of the approximate analysis are presented and compared with the results of simulations. >
Spatially tuned auditory responses in area LIP of macaques performing delayed memory saccades to acoustic targets.

1. The lateral intraparietal area (area LIP) of the macaque's posterior parietal cortex (PPC) lies in the dorsal stream of extrastriate visual areas. It receives extensive visual inputs and sends outputs to several eye movement centers. It contains neurons with visual and saccade-related responses suggesting a role of area LIP in programming saccadic eye movements to visual targets. Because primates can also orient to nonvisual stimuli, we investigated whether LIP neurons process stimuli of other modalities besides the visual one by comparing their activity in auditory and visual saccade tasks. 2. We recorded the activity of single neurons of Macaca mulatta monkeys while they performed memory saccades to acoustic and visual targets. We analyzed the activity during stimulus presentation (stimulus period, S) and during the delay (memory period, M) between stimulus presentation and the saccade to its remembered location. 3. Among 80 area LIP neurons tested, we found 44 that had S period and/or M period responses following presentation of the auditory stimulus. Most of these responses were spatially tuned, i.e., selective for the left or right stimulus location (27 of 29 S responses; 25 of 29 M responses). 4. The majority of neurons with responses in the auditory memory saccade task also responded in the visual version of the task. Eighty-nine percent (24/27) were clearly bimodal in the S period, and 88% (23/26) were bimodal in the M period. 5. Almost all the neurons with spatially tuned auditory responses that were bimodal were also spatially tuned in their visual responses (20/22 for S responses; 18/19 for M responses). The spatial tuning for the two modalities was the same in 85% (17/20) of the tested neurons for the S responses, and in 83% (15/18) of the tested neurons for the M responses. 6. Area LIP contains a population of neurons that respond to both visual and auditory stimuli. This result is consistent with our finding that the memory activity of many LIP cells encodes the next planned saccade. If cells are coding planned movements, they should be active independently of the sensory modality of the target for the movement, as was the case for most of the neurons described in the present study.
Localization of periodic orbits of autonomous systems based on high-order extremum conditions

This paper gives localization and nonexistence conditions of periodic orbits in some subsets of the state space. Mainly, our approach is based on high-order extremum conditions, on high-order tangency conditions of a nonsingular solution of a polynomial system with an algebraic surface, and on some ideas related to algebraically-dependent polynomials. Examples of the localization analysis of periodic orbits are presented including the Blasius equations, the generalized mass action (GMA) system, and the mathematical model of the chemical reaction with autocatalytic step.
Efficient Control of raf Gene Expression by CAP and Two Raf Repressors that Bend DNA in Opposite Directions

Abstract The plasmid-borne raf operon of Escherichia coli encodes proteins involved in the uptake and utilisation of the trisaccharide raffinose. The operon is subject to dual regulation; to negative control by the binding of RafR repressor to twin operators, O1 and O2, and to positive control by the cAMP-binding protein, CAP. We have identified the CAP binding site (CBS) as a 22 bp palindromic sequence with incomplete dyad symmetry by deletion analysis, DNaseI footprinting and electrophoretic mobility shift assays (EMSA) of CAP-DNA complexes. The CBS is centred 60.5 bp upstream of the transcription start point and partially overlaps O1. In vivo, CAP increases rafA (α-galactosidase) gene expression up to 50-fold. The 28 bp spacing between the centres of CBS and the—35 box is essential, since insertions of 4, 8, 12 or 16 bp completely eliminated rafA gene expression. In vitro binding studies revealed that the CBS, O1 and O2 sites, can be simultaneously occupied by their cognate proteins. However, no cooperativity between binding of CAP and RafR was detected. EMSA with circularly permuted DNA fragments demonstrated that CAP and RafR proteins bend raf promoter (rafP) DNA by 75° ± 5° and 95° ± 5°, respectively, in opposite directions. Among sugar catabolic operons, the compact arrangement of three protein-binding sites, a CBS and two operators bounding the—35 promoter box, is unique and provides a sensitive and highly efficient device for transcriptional control.
Human herpesvirus 6 DNA in peripheral blood cells and saliva from immunocompetent individuals

Human herpesvirus 6 (HHV-6) genome equivalents were quantitated in peripheral blood mononuclear cells (PBMCs) and saliva from 20 healthy individuals by the polymerase chain reaction (PCR). Nineteen of 20 subjects (95%) harbored HHV-6 DNA: 18 (90%) had HHV-6 in their PBMCs and 18 had HHV-6 in their saliva. Quantitative PCR revealed HHV-6 DNA levels ranging from negative to 4,000 HHV-6 genome equivalents per 10(6) PBMCs and from negative to 200,000 HHV-6 genome equivalents per ml of saliva. Longitudinal saliva samples from 15 HHV-6-seropositive subjects revealed salivary HHV-6 DNA persistence in 13 subjects. HHV-6 antibodies were detected in 17 of 19 subjects, with titers ranging from 1:400 to 1:51,200 (geometric mean titer, 1:2,500). Antibody titers did not correlate with HHV-6 DNA levels in PBMCs or saliva (P = 0.27 and P = 0.44, respectively). One subject with persistent HHV-6 DNA lacked detectable HHV-6 antibodies. The high prevalence of HHV-6 DNA in PBMCs and saliva supports the concept that HHV-6 exists at these sites in normal individuals.
A direction-adaptive in-loop deartifacting filter for video coding

Recent video coding strategies, such as H.264/AVC, incorporate an in-loop deblocking filter in order to reduce the effects of quantization noise. These techniques are limited to treating blocky artifacts on smooth regions. In order to solve this, sparsity-based filtering techniques have been recently proposed for efficient filtering of edge and textured areas. More recently, direction-adaptive sparsity-based filtering has also allowed to exploit directional features on intra encoded pictures. This paper proposes a high-performance in-loop filter for deartifacting intra and inter encoded video data. This work extends for Inter frames the use of direction-adaptive sparsity-based filtering techniques and it improves performance by adaptively selecting filtering thresholds consistent with quantization noise statistics, local encoding conditions, compression requirements and the original signal. Thresholds are both spatially and temporally adapted to optimize video quality and/or coding cost. Selected thresholds are encoded and transmitted as side information to the decoder. Experimental results show significant bit rate savings and visual quality enhancement when compared to the state-of-the- art H.264/AVC codec using in-loop deblocking filtering.
Low-complexity linear array multiplier for normal basis of type-II

In many cryptographic applications, the finite field is usually defined as the normal basis representation, and accordingly, much research on fast implementation of such a basis are reported. By restricting the characteristics of an optimal normal basis (ONB) of type-II, we used the palindromic representation of type-II ONB to derive a linear array multiplier with a low-complexity architecture. The space complexity of the proposed multiplier can be reduced from O(m2) to O(m) as compared with the related normal basis multipliers
Synthetic Pathway for Production of Five-Carbon Alcohols from Isopentenyl Diphosphate

ABSTRACT Synthetic biological pathways could enhance the development of novel processes to produce chemicals from renewable resources. On the basis of models that describe the evolution of metabolic pathways and enzymes in nature, we developed a framework to rationally identify enzymes able to catalyze reactions on new substrates that overcomes one of the major bottlenecks in the assembly of a synthetic biological pathway. We verified the framework by implementing a pathway with two novel enzymatic reactions to convert isopentenyl diphosphate into 3-methyl-3-butenol, 3-methyl-2-butenol, and 3-methylbutanol. To overcome competition with native pathways that share the same substrate, we engineered two bifunctional enzymes that redirect metabolic flux toward the synthetic pathway. Taken together, our work demonstrates a new approach to the engineering of novel synthetic pathways in the cell.
Spontaneous and UV-induced mutations in Escherichia coli K-12 strains with altered or absent DNA polymerase I

The induction of mutations to valine resistance and to rifampin resistance occurs after UV irradiation in bacteria carrying a deletion through the polA gene (delta polA), showing that DNA polymerase I (PolI) is not an essential enzyme for this process. The PolI deletion strain showed a 7- to 10-fold-higher spontaneous mutation frequency than the wild type. The presence in the deletion strain of the 5'----3' exonuclease fragment on an F' episome caused an additional 10-fold increase in spontaneous mutation frequency, resulting in mutation frequencies on the order of 50- to 100-fold greater than wild type. The mutator effect associated with the 5'----3' exonuclease gene fragment together with much of the effect attributable to the polA deletion was blocked in bacteria carrying a umuC mutation. The mutator activity therefore appears to reflect constitutive SOS induction. Excision-proficient polA deletion strains exhibited increased sensitivity to the lethal effect of UV light which was only partially ameliorated by the presence of polA+ on an F' episome. The UV-induced mutation rate to rifampin resistance was marginally lower in delta polA bacteria than in bacteria carrying the polA+ allele. This effect is unlikely to be caused by the existence of a PolI-dependent mutagenic pathway and is probably an indirect effect caused by an alteration in the pattern of excision repair, since it did not occur in excision-deficient (uvrA) bacteria. An excision-deficient polA deletion strain possessed UV sensitivity similar to that of an isogenic strain carrying polA+ on an F' episome, showing that none of the functions of PolI are needed for postreplication repair in the absence of excision repair. Our data provide no evidence for a pathway of UV mutagenesis dependent on PolI, although it remains an open question whether PolI is able to participate when it is present.