Miracle-dz/UniFAR-FTUs huggingface dataset:
Galactosylated magnetic nanovectors for regulation of lipid metabolism based on biomarker-specific RNAi and MR imaging

The specific delivery of ribonucleic acid (RNA) interfering molecules to disease-related cells is still a critical blockade for in vivo systemic treatment. Here, this study suggests a robust delivery carrier for targeted delivery of RNA-interfering molecules using galactosylated magnetic nanovectors (gMNVs). gMNVs are an organic–inorganic polymeric nanomaterial composed of polycationics and magnetic nanocrystal for delivery of RNA-interfering molecules and tracking via magnetic resonance (MR) imaging. In particular, the surface of gMNVs was modified by galactosylgluconic groups for targeted delivering to asialoglycoprotein receptor (ASGPR) of hepatocytes. Moreover, the small interfering RNAs were used to regulate target proteins related with low-density lipoprotein level and in vivo MR imaging was conducted for tracking of nanovectors. The obtained results show that the prepared gMNVs demonstrate potential as a systemic theragnostic nanoplatform for RNA interference and MR imaging.
PHASE-RESOLVED NuSTAR AND SWIFT-XRT OBSERVATIONS OF MAGNETAR 4U 0142+61

We present temporal and spectral analysis of simultaneous 0.5–79 keV Swift-XRT and Nuclear Spectroscopic Telescope Array observations of the magnetar 4U 0142+61. The pulse profile changes significantly with photon energy between 3 and 35 keV. The pulse fraction increases with energy, reaching a value of ≈20%, similar to that observed in 1E 1841–045 and much lower than the ≈80% pulse fraction observed in 1E 2259+586. We do not detect the 55 ks phase modulation reported in previous Suzaku-HXD observations. The phase-averaged spectrum of 4U 0142+61 above 20 keV is dominated by a hard power law (PL) with a photon index Γ H ∼ 0.65 ? > , and the spectrum below 20 keV can be described by two blackbodies, a blackbody plus a soft PL, or by a Comptonized blackbody model. We study the full phase-resolved spectra using the e ± ? > outflow model of Beloborodov. Our results are consistent with the parameters of the active j-bundle derived from INTEGRAL data by Hascoët et al. We find that a significant degeneracy appears in the inferred parameters if the footprint of the j-bundle is allowed to be a thin ring instead of a polar cap. The degeneracy is reduced when the footprint is required to be the hot spot inferred from the soft X-ray data.
Sons or Daughters: a Cross-Cultural Study of Sex Ratio Biasing and Differential Parental Investment

ABSTRACT Survivorship of children is dependent upon numerous variables, including the role that preferential treatment may play in biasing the birth and survival of sons and daughters across cultures. This study draws upon an evolutionary approach by examining a theory referred to as the “Trivers-Willard hypothesis” concerning condition-dependent sex allocation and differential parental investment. Previous research on humans concerning this hypothesis tends to be restricted to one cultural group and thereby limited in sample size. For this study, nationally representative household survey data collected by the Demographic and Health Surveys (DHS+) program across 35 countries was used to test biological, resource-oriented, and behavioral aspects affecting maternal condition, sex allocation, and parental investment in humans. The units of analysis for this study were the mothers and their lastborn child (N = 128,039 woman-child pairs). A series of hierarchical regressions were executed to empirically investigate the TW hypothesis in humans. Scales were developed for maternal socioeconomic resources (MSR), maternal biological condition (MBC), prenatal care for the lastborn child (PCL), and health-seeking for the lastborn child (HSL). MSR was measured by relative household economic status, woman's and partner's education, and residence in an urban/rural setting. MBC was defined by body mass index, pregnancy status and duration, and breast-feeding status. PCL was an index for type of prenatal care received, number of prenatal visits, and assistance during delivery of the lastborn child. Lastly, HSL measured indicators of treatment for diarrhea and immunizations received by the lastborn child. Across the 35 countries, the analyses did not support the Trivers-Willard hypothesis. However, there is evidence of regional and country level differences.
Sampling for Approximate Maximum Search in Factorized Tensor

Factorization models have been extensively used for recovering the missing entries of a matrix or tensor. However, directly computing all of the entries using the learned factorization models is prohibitive when the size of the matrix/tensor is large. On the other hand, in many applications, such as collaborative filtering, we are only interested in a few entries that are the largest among them. In this work, we propose a sampling-based approach for finding the top entries of a tensor which is decomposed by the CANDECOMP/PARAFAC model. We develop an algorithm to sample the entries with probabilities proportional to their values. We further extend it to make the sampling proportional to the k-th power of the values, amplifying the focus on the top ones. We provide theoretical analysis of the sampling algorithm and evaluate its performance on several real-world data sets. Experimental results indicate that the proposed approach is orders of magnitude faster than exhaustive computing. When applied to the special case of searching in a matrix, it also requires fewer samples than the other state-of-the-art method.
Physiologically based pharmacokinetic and pharmacodynamic model for the inhibition of acetylcholinesterase by diisopropylfluorophosphate.

Organophosphate (OP) exposure can be lethal at high doses while lower doses may impair performance of critical tasks. The ability to predict such effects for realistic exposure scenarios would expedite OP risk assessment. To this end, a physiologically based model for diisopropylfluorophosphate (DFP) pharmacokinetics and acetylcholinesterase (AChE) inhibition was developed in mammals. DFP tissue:blood partition coefficients, rates of DFP hydrolysis by esterases, and DFP-esterase bimolecular inhibition rate constants were determined in rat tissue homogenates. Other model parameters were scaled for rats and mice using standard allometric relationships. These DFP-specific parameter values were used with the model to simulate expected in vivo pharmacokinetic data from mice and rats. Literature data were used for model validation. DFP concentrations in mouse plasma and brain were successfully simulated after a single iv injection (B.R. Martin, 1985, Toxicol. Appl. Pharmacol. 77, 275-284). AChE inhibition and AChE resynthesis data from this study were also simulated. Effects of repeated, subcutaneous DFP dosing on AChE activity in rat plasma and brain (H. Michalek, A. Meneguz, and G.M. Bisso, 1982, Arch. Toxicol., Suppl. 5, 116-119; M.E. Traina and L.A. Serpietri, 1984, Biochem. Pharmacol. 33, 645-653) were also simulated well, but the return of brain AChE activity to basal levels after cessation of repeated dosing was not as well described. The initial model structure returned brain AChE activity to the original level, while in the laboratory studies brain AChE never returned to basal levels, even at 35 days after the last dose. These data suggest modulation of AChE synthesis with prolonged DFP exposure. This study demonstrated the possibility of using a model based on mammalian physiology and biochemistry to simulate in vivo data on DFP pharmacokinetics and AChE inhibition. Scaling of the model between rats and mice was also successful. The approach holds promise for predictive simulation of organophosphate-mediated AChE inhibition in humans.
Differences in oxygen‐dependent nitric oxide metabolism by cytoglobin and myoglobin account for their differing functional roles

The endogenous vasodilator nitric oxide (NO) is metabolized in tissues in an oxygen‐dependent manner. In skeletal and cardiac muscle, high concentrations of myoglobin (Mb) function as a potent NO scavenger. However, the Mb concentration is very low in vascular smooth muscle, where low concentrations of cytoglobin (Cygb) may play a major role in metabolizing NO. Questions remain regarding how low concentrations of Cygb and Mb differ in terms of NO metabolism, and the basis for their different cellular roles and functions. In this study, electrode techniques were used to perform comparative measurements of the kinetics of NO consumption by Mb and Cygb. UV/Vis spectroscopic methods and computer simulations were performed to study the reaction of Mb and Cygb with ascorbate (Asc) and the underlying mechanism. It was observed that the initial rate of Cygb3+ reduction by Asc was 415‐fold greater than that of Mb3+. In the low [O2] range (0–50 μm), the Cygb‐mediated NO consumption rate is ~ 500 times more sensitive to changes in O2 concentration than that of Mb. The reduction of Cygb3+ by Asc follows a reversible kinetic model, but that of Mb3+ is irreversible. A reaction mechanism for Cygb3+ reduction by Asc is proposed, and the reaction equilibrium constants are determined. Our results suggest that the rapid reduction of Cygb by cellular reductants enables Cygb to efficiently regulate NO metabolism in the vascular wall in an oxygen‐dependent manner, but the slow rate of Mb reduction does not show this oxygen dependence.
Automating Resources Discovery for Multiple Data Stores Cloud Applications

The production of huge amount of data and the emergence of cloud computing have introduced new requirements for data management. Many applications need to interact with several heterogeneous data stores depending on the type of data they have to manage: traditional data types, documents, graph data from social networks, simple key-value data, etc. Interacting with heterogeneous data models via different APIs, multidata store applications imposes challenging tasks to their developers. Indeed, programmers have to be familiar with different APIs. In addition, developers need to master and deal with the complex processes of cloud discovery, and application deployment and execution. Moreover, the execution of join queries over heterogeneous data models cannot, currently, be achieved in a declarative way as it is used to be with mono-data store application, and therefore requires extra implementation effort. In this paper we propose a declarative approach enabling to lighten the burden of the tedious and non-standard tasks of discovering relevant cloud environment and deploying applications on them while letting developers to simply focus on specifying their storage and computing requirements. A prototype of the proposed solution has been developed and is currently used to implement use cases from the OpenPaaS project.
Fuzzy Logic based parameter estimator for variable speed wind generators PI pitch control

The control of mechanical power in wind turbogenerators involves the participation of many subsystems. One of them is related to pitch mechanism, which usually employs conventional PI strategies. This paper presents an alternative for estimating the parameters of this PI controller, using Fuzzy Logic (FL). Matlab-Simulink™ software was used in order to verify the performance of the FL-based parameter estimator in some general cases.
Cyclic AMP-dependent protein kinase inhibits the activity of myogenic helix-loop-helix proteins

Differentiation of skeletal muscle cells is inhibited by the cyclic AMP (cAMP) signal transduction pathway. Here we report that the catalytic subunit of cAMP-dependent protein kinase (PKA) can substitute for cAMP and suppress muscle-specific transcription by silencing the activity of the MyoD family of regulatory factors, which includes MyoD, myogenin, myf5, and MRF4. Repression by the PKA catalytic (C) subunit is directed at the consensus sequence CANNTG, the target for DNA binding and transcriptional activation by these myogenic regulators. Phosphopeptide mapping of myogenin in vitro and in vivo revealed two PKA phosphorylation sites, both within the basic region. However, repression of myogenin function by PKA does not require direct phosphorylation of these sites but instead involves an indirect mechanism with one or more intermediate steps. Regulation of the transcriptional activity of the MyoD family by modulation of the cAMP signaling pathway may account for the inhibitory effects of certain peptide growth factors on muscle-specific gene expression and may also determine the responsiveness of different cell types to myogenic conversion by these myogenic regulators.
Effects of an urban high school-based child care center on self-selected adolescent parents and their children.

This study examined the effects of an urban high school-based child care center on parenting teens and their children enrolled during 1995-1998. Retrospective record review of 52 low-income, urban adolescent parents enrolled at the Celotto Child Care Center (CCCC) during the period of study was conducted from the CCCC and the high school records. Mean age of the student parents was 17 years (s.d. = 1.3) and mean grade level was 11.2 (s.d. = 1). Most parents were female (98%) and African American (62%). Children enrolled at CCCC had a mean age of 10 months (s.d. = 10.8). Students using the services of CCCC showed improvement in overall grade point averages, and 100% were educationally successful as defined by promotion to the next grade or graduating from high school. None of the students experienced a repeat childbirth during the period of CCCC enrollment. Ninety percent of children were up-to-date with pediatric health visits and immunizations. These results lend strong support to the importance of extending child care and social support services to teen parents, and for the implementation of high school-based child care centers as alternative sites for these critically important services.
Impact of intranasal corticosteroids on asthma outcomes in allergic rhinitis: a meta‐analysis

Given the relationship between allergic rhinitis (AR) and asthma, it can be hypothesized that reducing inflammation in the upper airway with intranasal corticosteroid (INCS) medications may improve asthma outcomes. The goal of this study was to perform a systematic review with meta‐analysis of the efficacy of INCS medications on asthma outcomes in patients with AR and asthma. Asthma‐specific outcomes from randomized, controlled studies evaluating INCS medications in patients with AR were evaluated, including studies that compared INCS sprays to placebo, INCS sprays plus orally inhaled corticosteroids to orally inhaled corticosteroids alone, and nasally inhaled corticosteroids to placebo. Sufficient data for meta‐analysis were retrieved for 18 trials with a total of 2162 patients. Asthma outcomes included pulmonary function, bronchial reactivity, asthma symptom scores, asthma‐specific quality of life, and rescue medication use. The subgroup of studies comparing INCS spray to placebo had significant improvements in FEV1 (SMD = 0.31; 95% CI, 0.04–0.58), bronchial challenge (SMD = 0.46; 95% CI, 0.12–0.79), asthma symptom scores (SMD = −0.42; 95% CI, −0.53 to −0.30), and rescue medication use (SMD = −0.29; 95% CI, −0.58 to −0.01). Nasal inhalation of corticosteroids significantly improved morning and evening peak expiratory flow. There were no significant changes in asthma outcomes with the addition of INCS spray to orally inhaled corticosteroids. Thus, the results of this meta‐analysis demonstrated that intranasal corticosteroid medications significantly improve some asthma‐specific outcome measures in patients suffering from both AR and asthma. This effect was most pronounced with INCS sprays when patients were not on orally inhaled corticosteroids, or when corticosteroid medications were inhaled through the nose into the lungs. Overall, intranasal corticosteroid medications improve some asthma‐specific outcome measures in patients with both AR and asthma. Further research is needed to clarify the role of INCS sprays as asthma‐specific therapy, as well as the role of the nasal inhalation technique as a monotherapy in patients suffering from both asthma and AR.
Spin-transfer torque magnetic memory as a stochastic memristive synapse

Spin-transfer torque magnetic memory (STT-MRAM) is currently under intense academic and industrial development, since it features nonvolatility, high write and read speed and high endurance. In this work, we show that when used in an original regime, it can additionally act as a stochastic memristive device, appropriate to implement a “synaptic” function. We introduce basic concepts relating to STT-MRAM cell behavior and its possible use to implement learning-capable synapses. System-level simulations on a problem of car counting highlight the potential of the technology for learning systems. Monte Carlo simulations show its robustness to device variations. These results open the way for unexplored applications of STT-MRAM in robust, low power, cognitive-type systems.
A novel feature selection method for nearest neighbor search in binary embedding codes

We address the issue of search nearest neighbors in binary embedding codes by asymmetric distance computation. Although asymmetric distance computation can obtain a more accurate result than symmetric distance computation, its speed is much slower. Applying multi-index hashing can accelerate asymmetric distance computation. However, it takes more memory to store the index tables. Thus, how to select appropriate binary features for indexing under a certain memory constraint is a key issue to improve asymmetric distance computation. In this paper, we propose a novel feature selection method. When only partial index tables can be loaded into memory, the binary features with the lowest quantization error can be selected as a representative for indexing. Experimental results show that the proposed method improves the accuracy up to 8.35% and outperforms the linear scan approach and other feature selection methods.
Binding of rationally designed non‐natural peptides to the human leukocyte antigen HLA‐B*2705

High‐affinity ligands of non‐peptidic nature, binding to the class I major histocompatibility complex protein HLA B*2705 whose expression is strongly linked to the pathogenesis of the autoimmune disease ankylosing spondylitis, should give way to a selective immunotherapy by blocking or antagonising the interaction with autoreactive T cell clones. Here we present experimental data on the binding of modified peptides, designed to optimally bind to HLA‐B*2705 by filling a hydrophobic binding pocket (pocket D) with nonencoded aromatic amino acids. Three peptides with altered side chains (alpha‐naphthylalanine, beta‐naphthylalanine and homophenylalanine) in position 3 were synthesised. The thermal denaturation profiles of the HLA protein in complex with the modified peptides, monitored by circular dichroism spectroscopy, showed a significant shift towards higher melting temperatures with respect to the parent T cell epitope. The proposed binding mode of the nonnatural peptides was checked by site‐directed mutagenesis of the pocket D, hypothesised to accommodate the large hydrophobic side chains. Reducing the size and depth of the pocket by mutating Leu l56 into Trp only affects the binding of the non‐natural ligands, thus providing experimental evidence that the nonnatural peptide amino acids bind as predicted to the host MHC protein. © 1998 European Peptide Society and John Wiley & Sons, Ltd.
Prognostic sub-grouping of diffuse large B-cell lymphomas into germinal centre and post germinal centre groups by immunohistochemistry after 6 cycles of chemotherapy.

INTRODUCTION Diffuse large B-cell lymphomas (DLBCL) can be divided into germinal centre (GC-DLBCL) and post germinal centre (post GC-DLBCL) groups by applying immunohistochemical antibodies. As these subgroups respond differently to chemotherapy, it is possible at diagnosis to select a poor prognostic subgroup for aggressive treatment. OBJECTIVE To determine the frequencies of GC-DLBCL and post GC-DLBCL in patients by immunohistochemistry (IHC) and the clinical response after six cycles of chemotherapy. SUBJECTS AND METHODS In this descriptive study conducted in AFIP and CMH, Rawalpindi and NORI, Islamabad, from September 2010 to September 2011, a total of 75 pretreatment cases of DLBCL diagnosed during the study period were included. Cases were segregated in to GC-DLBCL and post GC-DLBCL groups according to results of immunohistochemistry markers CD10, BCL6 and MUM1. Immediate clinical response was assessed after 6 cycles of chemotherapy. Response was divided into complete response, partial response, stable disease or relapse or progression. RESULTS The mean age was 54.2 ± 15. Males were 53 (70.7%). Forty (53.3%) cases comprised the GC-DLBCL group; 25(62.5%) of them showed a complete response. Most patients of the post GC-DLBCL 19(54%) showed relapse/progression. Results of immediate clinical response in both prognostic subgroups were significant (p<0.05). Results regarding positivity with immunohistochemical antibodies CD10 (p 0.011), BCL6 (p 0.013) and MUM1 (p 0.000) regarding immediate clinical response were also significant. CONCLUSION GC-DLBCL group shows better response to CHOP chemotherapy regimen. Immunohistochemistry should be used to further classify DLBCL as this can enable us to select aggressive group for aggressive treatment. This manuscript is important because the study is the first to becarried out exclusively in Pakistan or our part of the world.
Changes in cognition following mild stroke

The objective of the study was to determine how performance on cognitive assessments administered in the subacute phase of mild stroke change or remain stable over time. A prospective longitudinal cohort pilot study was used to assess the cognitive status of participants with mild stroke (n = 20) at two time points: (1) within 3 weeks post-discharge from the acute care setting following mild stroke, and (2) approximately 6 months post-mild stroke. Participants were given a battery of cognitive assessments at both time points that included the following measures: (1) Short Blessed Test, (2) California Verbal Learning Test (CVLT), (3) Connor's Continuous Performance Task (CPT), and (4) The Delis-Kaplan Executive Function System (DKEFS) Trail Making subtest. The only significant differences between the test administrations was on the CVLT Short Delay Free Recall (p = .027) and Long Delay Free Recall (p = .002) which was likely due to practice effects associated with this measure. The results of the study show that performance on standardised cognitive testing in the early phases of mild stroke remained stable over a 6 month period. These results help justify the necessity and ability to assess cognition immediately post-mild stroke in order to make accurate and appropriate rehabilitation recommendations.
Genetic relationship between calf livability and calving difficulty of Holsteins.

Multitrait procedure was used to investigate the genetic relationship between calf livability and calving difficulty of Holsteins. The genetic correlation between calf livability and calving difficulty was . 66. Heritabilities were . 9% for calf livability and 4.1% for calving difficulty. The product-moment correlation (.4) between sires' transmitting abilities estimated separately for livability and dystocia, with properties of Best Linear Unbiased Predicator, underestimated the genetic correlation (.66). The correlated response of calf livability is expected to be 41% greater when selection is for dystocia than is expected from direct selection on calf livability.