Miracle-dz/UniFAR-FTUs huggingface dataset:
Uniform asymptotic approximation of diffusion to a small target: Generalized reaction models.

The diffusion of a reactant to a binding target plays a key role in many biological processes. The reaction radius at which the reactant and target may interact is often a small parameter relative to the diameter of the domain in which the reactant diffuses. We develop uniform in time asymptotic expansions in the reaction radius of the full solution to the corresponding diffusion equations for two separate reactant-target interaction mechanisms: the Doi or volume reactivity model and the Smoluchowski-Collins-Kimball partial-absorption surface reactivity model. In the former, the reactant and target react with a fixed probability per unit time when within a specified separation. In the latter, upon reaching a fixed separation, they probabilistically react or the reactant reflects away from the target. Expansions of the solution to each model are constructed by projecting out the contribution of the first eigenvalue and eigenfunction to the solution of the diffusion equation and then developing matched asymptotic expansions in Laplace-transform space. Our approach offers an equivalent, but alternative, method to the pseudopotential approach we previously employed [Isaacson and Newby, Phys. Rev. E 88, 012820 (2013)PLEEE81539-375510.1103/PhysRevE.88. 012820] for the simpler Smoluchowski pure-absorption reaction mechanism. We find that the resulting asymptotic expansions of the diffusion equation solutions are identical with the exception of one parameter: the diffusion-limited reaction rates of the Doi and partial-absorption models. This demonstrates that for biological systems in which the reaction radius is a small parameter, properly calibrated Doi and partial-absorption models may be functionally equivalent.
Fuzzy techniques for trust and reputation management in anonymous peer-to-peer systems

Peer-to-peer (P2P) applications are rapidly gaining acceptance among users of Internet-based services, especially because of their capability of exchanging resources while preserving the anonymity of both requesters and providers. However, concerns have been raised about the possibility that malicious users can exploit the network to spread tampered-with resources (e.g., malicious programs and viruses). A considerable amount of research has thus focused on the development of trust and reputation models in P2P networks. In this article, we propose to use fuzzy techniques in the design of reputation systems based on collecting and aggregating peers' opinions. Fuzzy techniques are used in the evaluation and synthesis of all the opinions expressed by peers. The behavior of the proposed system is described by comparison with probabilistic approaches.
Searching with numbers

A large fraction of the useful web comprises of specification documents that largely consist of hattribute name, numeric valuei pairs embedded in text. Examples include product information, classified advertisements, resumes, etc. The approach taken in the past to search these documents by first establishing correspondences between values and their names has achieved limited success because of the difficulty of extracting this information from free text. We propose a new approach that does not require this correspondence to be accurately established. Provided the data has "low reflectivity", we can do effective search even if the values in the data have not been assigned attribute names and the user has omitted attribute names in the query. We give algorithms and indexing structures for implementing the search. We also show how hints (i. e, imprecise, partial correspondences) from automatic data extraction techniques can be incorporated into our approach for better accuracy on high reflectivity datasets. Finally, we validate our approach by showing that we get high precision in our answers on real datasets from a variety of domains.
Matching Games with Additive Externalities

Two-sided matchings are an important theoretical tool used to model markets and social interactions. In many real life problems the utility of an agent is influenced not only by their own choices, but also by the choices that other agents make. Such an influence is called an externality. Whereas fully expressive representations of externalities in matchings require exponential space, in this paper we propose a compact model of externalities, in which the influence of a match on each agent is computed additively. In this framework, we analyze many-to-many and one-to-one matchings under neutral, optimistic, and pessimistic behaviour, and provide both computational hardness results and polynomial-time algorithms for computing stable outcomes.
Radiolabeled nano‐peptides show specificity for an animal model of human PC3 prostate cancer cells

OBJECTIVES: Cancer has been investigated using various pre‐targeting techniques or models focusing on radiobombesin analogues; however, both are not offered together. In this study, nano‐bombesin labeling by a pre‐targeting system was undertaken to develop an alternative approach for prostate tumor treatment. METHODS: A two‐step pre‐targeting system utilizing a combination of streptavidin (SA), biotinylated morpholino (B‐MORF), biotinylated BBN (B‐BBN) with two different spacers (β‐Ala and PEG), and a radiolabeled cMORF was evaluated in vitro and in vivo. RESULTS: Final conjugation conditions consisted of a 1:1:2 ratio of SA:B‐MORF:B‐BBN, followed by addition of 99mTc‐cMORF to compensate for free MORF. In vitro binding experiments with prostate cancer cells (PC‐3) revealed that total binding was time‐dependent for the Ala spacer but not for the PEG spacer. The highest accumulation (5.06±1.98 %) was achieved with 1 hour of incubation, decreasing as time progressed. Specific binding fell to 1.05±0.35 %. The pre‐targeting biodistribution in healthy Swiss mice was measured at different time points, with the best responses observed for 7‐h and 15‐h incubations. The effector, 99mTc‐MAG3‐cMORF, was administered 2 h later. Strong kidney excretion was always documented. The greatest tumor uptake was 2.58±0.59 %ID/g at 7 h for B‐βAla‐BBN, with a region of interest (ROI) value of 3.9 % during imaging. The tumor/blood ratio was low due to the slow blood clearance; however, the tumor/muscle ratio was 5.95. CONCLUSIONS: The pre‐targeting approach with a peptide was a viable concept. Further evaluation with modified sequences of MORF, including less cytosine, and additional test intervals could be worthwhile.
Factors associated with transition from community settings to hospital as place of death for adults aged 75 years or older : a population-based mortality follow-back survey

http://sro.sussex. ac.uk Bone, Anna E, Gao, Wei, Gomes, Barbara, Sleeman, Katherine E, Maddocks, Matthew, Wright, Juliet, Yi, Deokhee, Higginson, Irene J and Evans, Catherine J (2016) Factors associated with transition from community settings to hospital as place of death for adults aged 75 years or older: a population-based mortality follow-back survey. Journal of the American Geriatrics Society, 64 (11). pp. 2210-2217. ISSN 0002-8614
Generic Maintenance Immunosuppression in Solid Organ Transplant Recipients

Survival after solid organ transplantation has increased in the era of tacrolimus and mycophenolate. This increased survival could be due in part to the broad clinical use of these potent and specific agents for maintenance immunosuppression. These drugs have enhanced specificity and potency for T and B lymphocytes compared with their predecessors, cyclosporine and azathioprine. Between 2008 and 2010, the United States Food and Drug Administration approved several generic formulations of both tacrolimus and mycophenolate mofetil. Deciding whether generic products can be safely substituted for the innovator product is a clinical dilemma similar to that which occurred when generic formulations of cyclosporine became available. We describe the concerns regarding generic immunosuppression use, summarize expert opinion and consensus statements in transplantation, analyze the potential impact of generic substitution, and provide estimates of populations affected based on generic drug market penetration. Formulary considerations such as cost, availability, and potential drug ordering and drug selection errors are described, and transplant coordinator and patient perspectives are reviewed. Finally, general recommendations about the use of generic maintenance immunosuppression in solid organ transplant recipients are provided. Although more research is needed to confirm clinical and therapeutic equivalence and pharmacoeconomic benefit, generic immuno‐suppressants can be safely substituted for innovator products as long as patients consistently receive the same product, patients and clinicians are aware of when substitutions occur, and enhanced therapeutic drug monitoring is provided during the transition.
Diagnostic Case Retrieval Guided by Evaluation and Feedback

In this project we study the effect of a user’s high-level expository goals upon the details of how case-based reasoning (CBR) is performed, and, vice versa the effect of feedback from CBR on them. Our thesis is that case retrieval should reflect the user’s ultimate goals in appealing to cases and that these goals can be affected by the cases actually available in a case base. To examine this thesis, we have designed and built FRANK (Flexible Report and Analysis System), which is a hybrid, blackboard system that integrates case-based, rule-based, and planning components to generate a diagnostic report that reflects a user’s viewpoint and specifications. FRANK’s control module relies on a set of generic hierarchies that provide taxonomies of standard report types and problem-solving strategies in a mixed-paradigm environment. Our second focus in FRANK is on its response to a failure to retrieve an adequate set of supporting cases. We describe FRANK’s planning mechanisms that dynamically re-specify the memory probe or the parameters for case retrieval when an inadequate set of cases is retrieved, and give examples of how the system responds to retrieval failures.
T‐shaped arrangement of the recombinant agrin G3 – IgG Fc protein

Agrin is a large heparin sulphate proteoglycan with multiple domains, which is located in the extracellular matrix. The C‐terminal G3 domain of agrin is functionally one of the most important domains. It harbors an α‐dystroglycan binding site and carries out acetylcholine receptor clustering activities. In the present study, we have fused the G3 domain of agrin to an IgG Fc domain to produce a G3‐Fc fusion protein that we intend to use as a tool to investigate new binding partners of agrin. As a first step of the study, we have characterized the recombinant fusion protein using a multidisciplinary approach using dynamic light scattering, analytical ultracentrifugation and small angle X‐ray scattering (SAXS). Interestingly, our SAXS analysis using the high‐resolution structures of G3 and Fc domain as models indicates that the G3‐Fc protein forms a T‐shaped molecule with the G3 domains extruding perpendicularly from the Fc scaffold. To validate our models, we have used the program HYDROPRO to calculate the hydrodynamic properties of the solution models. The calculated values are in excellent agreement with those determined experimentally.
Multi-relational data mining: an introduction

Data mining algorithms look for patterns in data. While most existing data mining approaches look for patterns in a single data table, multi-relational data mining (MRDM) approaches look for patterns that involve multiple tables (relations) from a relational database. In recent years, the most common types of patterns and approaches considered in data mining have been extended to the multi-relational case and MRDM now encompasses multi-relational (MR) association rule discovery, MR decision trees and MR distance-based methods, among others. MRDM approaches have been successfully applied to a number of problems in a variety of areas, most notably in the area of bioinformatics. This article provides a brief introduction to MRDM, while the remainder of this special issue treats in detail advanced research topics at the frontiers of MRDM.
RAN-Binding Protein 9 is Involved in Alternative Splicing and is Critical for Male Germ Cell Development and Male Fertility

As a member of the large Ran-binding protein family, Ran-binding protein 9 (RANBP9) has been suggested to play a critical role in diverse cellular functions in somatic cell lineages in vitro, and this is further supported by the neonatal lethality phenotype in Ranbp9 global knockout mice. However, the exact molecular actions of RANBP9 remain largely unknown. By inactivation of Ranbp9 specifically in testicular somatic and spermatogenic cells, we discovered that Ranbp9 was dispensable for Sertoli cell development and functions, but critical for male germ cell development and male fertility. RIP-Seq and proteomic analyses revealed that RANBP9 was associated with multiple key splicing factors and directly targeted >2,300 mRNAs in spermatocytes and round spermatids. Many of the RANBP9 target and non-target mRNAs either displayed aberrant splicing patterns or were dysregulated in the absence of Ranbp9. Our data uncovered a novel role of Ranbp9 in regulating alternative splicing in spermatogenic cells, which is critical for normal spermatogenesis and male fertility.
Thiobarbiturates as Sirtuin Inhibitors: Virtual Screening, Free‐Energy Calculations, and Biological Testing

NAD+‐dependent histone deacetylases (sirtuins) are enzymes that cleave acetyl groups from lysine residues in histones and other proteins. Potent selective sirtuin inhibitors are interesting tools for the investigation of the biological functions of these enzymes and may be future drugs for the treatment of cancer or neurodegenerative diseases. Herein we present the results from a protein‐based virtual screen of a commercial database with subsequent biological testing of the most promising compounds. The combination of docking and in vitro experimental testing resulted in the identification of novel sirtuin inhibitors with thiobarbiturate structure. To rationalize the experimental results, free‐energy calculations were carried out by molecular mechanics Poisson–Boltzmann/surface area (MM‐PBSA) calculations. A significant correlation between calculated binding free energies and measured Sirt2 inhibitory activities was observed. The analyses suggested a molecular basis for the interaction of the identified thiobarbiturate derivatives with human Sirt2. Based on the docking and MM‐PBSA calculations we synthesized and tested five further thiobarbiturates. The MM‐PBSA method correctly predicted the activity of the novel thiobarbiturates. The identified compounds will be used to further explore the therapeutic potential of sirtuin inhibitors.
Assessing the term independence assumption in blind relevance feedback

When applying blind relevance feedback for ad hoc document retrieval, is it possible to identify, a priori, the set of query terms that will most improve retrieval performance? Can this complex problem be reduced into the simpler one of making independent decisions about the performance effects of each query term? Our experiments suggest that, for the selection of terms for blind relevance feedback, the term independence assumption may be empirically justified.
Prediction of Poststroke Hemorrhagic Transformation Using Computed Tomography Perfusion

Background and Purpose— Intracerebral hemorrhage is a serious potential complication of stroke thrombolysis. We investigated the optimal computed tomography perfusion (CTP) parameter to predict cerebral parenchymal hematoma (PH) in acute ischemic stroke. Methods— Patients with hyperacute ischemic stroke had whole-brain CTP and follow-up computed tomography/MRI to identify hemorrhagic transformation. The association of the 3 parameters relative cerebral blood flow, relative cerebral blood volume, and time to maximum (Tmax) with PH was examined using receiver operating characteristic analysis and multivariate logistic regression. Results— Of 132 patients, 70 were treated with thrombolysis, and 14 (10.6%) developed PH on follow-up imaging. Baseline National Institutes of Health Stroke Scale score (P=0.033) and thrombolysis (P=0.003) were both predictive of PH. Receiver operating characteristic analysis revealed that Tmax>14 s (area under the curve=0.748; P=0.002) and relative cerebral blood flow <30% of contralateral mean (area under the curve=0.689, P=0.021) were the optimal thresholds, and the Bayesian information criterion (+2.6) indicated that Tmax was more strongly associated with PH than relative cerebral blood flow. Tmax >14 s volumes of >5 mL allowed prediction of PH with sensitivity of 79%, specificity of 68%, and negative likelihood ratio of 3.16. Tmax>14 s volume and thrombolysis were both independently predictive of PH in a multivariate logistic regression model (P<0.05). Conclusions— Tmax >14 s was the CTP parameter most strongly associated with PH. This outperformed relative cerebral blood flow <30%, which closely equates to CTP estimates of ischemic core volume. Although ischemic core volume on CTP is useful in the pretreatment prediction of PH, severe hypoperfusion on Tmax is more strongly associated and may allow better prediction of the likely anatomic location of hemorrhage.
Modelling and simulation of adaptation and degradation in anisotropic biological tissues

This thesis deals with the constitutive modelling of adaptation and degradation processes for the simulation of the material behaviour of anisotropic biological tissues. The modelling is based on the framework of finite deformation continuum mechanics. The constitutive models proposed are motivated by elastic and inelastic physical mechanisms originating from the micro-mechanical structure of the material. With regard to the modelling of soft biological tissues, e.g. arteries, the range of topics covers the investigation of energetic properties of an anisotropic residually stressed non-linear elastic continuum, a gradient-enhanced continuum damage model for the progressive failure of collagen fibres and a remodelling formulation for the deformation-driven evolution of anisotropy. With regard to adaptation processes in hard biological tissues, e.g. bone, a growth model for the energy-driven evolution of density is proposed. The constitutive models are discussed with respect to their numerical implementation. The modelling capabilities of the constitutive formulations are validated by homogeneous deformation cases and illustratively underlined by a variety of different finite element simulations.
Considering testability during high-level design

Considering testability during the early stages of the design flow can have several benefits, including significantly improved fault coverage, reduced test hardware overheads, and reduced design iteration times. This paper presents an overview of high level design methodologies that consider testability during the early (behavior and architecture) stages of the design flow, and their testability benefits. The topics reviewed include behavioral and RTL test synthesis approaches that generate easily testable implementations targeting ATPG (full and partial scan) and BIST methodologies, and techniques to use high-level information for ATPG.
Psychometric assessment of the Neonatal Abstinence Scoring System and the MOTHER NAS Scale.

BACKGROUND AND OBJECTIVES The present study examined the psychometric characteristics of the Neonatal Abstinence Scoring System (NASS; "Finnegan Scale") and the MOTHER NAS Scale (MNS). METHODS Secondary analysis of data from 131 neonates from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a randomized trial in opioid-dependent pregnant women administered buprenorphine or methadone. RESULTS Both the NASS and MNS demonstrated poor psychometric properties, with internal consistency (Cronbach's αs) failing to exceed . 62 at first administration, peak NAS score, and NAS treatment initiation. CONCLUSIONS Findings support the need for development of a NAS measure based on sound psychometric principles. SCIENTIFIC SIGNIFICANCE This study found that two frequently used measures of neonatal abstinence syndrome suffer inadequacies in regard to their basic measurement characteristics. (Am J Addict 2016;25:370-373).
Genetic Variants in the UCP 2-UCP 3 Gene Cluster and Risk of Diabetes Mellitus in the Women ’ s Health Initiative Observational Study

Objective: The mitochondrial uncoupling proteins (UCPs) are involved in body weight regulation and glucose homeostasis. Genetic variants in the UCP2-UCP3 gene cluster, located on chromosome 11q13, may play a significant role in the development of type 2 diabetes (T2D). Research Design And Methods: We conducted a comprehensive assessment of common single nucleotide polymorphisms (SNPs) at the 70-kb UCP2-UCP3 gene cluster in relation to T2D risk in a prospective, case-control study nested in the Women’s Health Initiative Observational Study (WHI-OS), an ethnically diverse cohort of postmenopausal women including Caucasian, African, Hispanic, and Asian Americans. We genotyped 14 tag SNPs in 1,584 incident T2D cases and 2,198 controls matched by age, ethnicity, clinical center, time of blood draw, and length of follow-up. Results: We identified a haplotype set (rs591758-rs668514-rs647126-rs1800006 spanning the UCP2-UCP3 inter-genic and UCP3 regions) to be significantly associated with greater T2D risk (nominal p=0.0011, permutation p=0.046) in Caucasian women, especially among overweight Caucasian (BMI > 25 kg/m) (nominal p=0.0006, permutation p=0.032). Comparing to the most common haplotype (h1010 as the referent), haplotype h0001 (19.5% in controls) had odds ratios of 2.0 (95% CI, 1.13-3.37) in whites, and 3.8 (95% CI, 1.44-9.93) in white overweight women. Similar haplotype-T2D association was also observed among Hispanic women who were overweight. Conclusions: These findings suggest a role of UCP2-UCP3 gene cluster haplotypes in diabetes, and in particular the effects of the high-risk haplotypes appeared more apparent in those overweight Caucasian women. These data warrant further confirmation in future prospective and experimental studies.
Temperature and Pressure Effects of Desalination Using a MFI-Type Zeolite Membrane

Zeolites are potentially a robust desalination alternative, as they are chemically stable and possess the essential properties needed to reject ions. Zeolite membranes could desalinate “challenging” waters, such as saline secondary effluent, without any substantial pre-treatment, due to the robust mechanical properties of ceramic membranes. A novel MFI-type zeolite membrane was developed on a tubular α-Al2O3 substrate by a combined rubbing and secondary hydrothermal growth method. The prepared membrane was characterised by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and single gas (He or N2) permeation and underwent desalination tests with NaCl solutions under different pressures (0.7 MPa and 7 MPa). The results showed that higher pressure resulted in higher Na+ rejection and permeate flux. The zeolite membrane achieved a good rejection of Na+ (~82%) for a NaCl feed solution with a TDS (total dissolved solids) of 3000 mg·L−1 at an applied pressure of 7 MPa and 21 °C. To explore the opportunity for high salinity and high temperature desalination, this membrane was also tested with high concentration NaCl solutions (up to TDS 90,000 mg·L−1) and at 90 °C. This is the first known work at such high salinities of NaCl. It was found that increasing the salinity of the feed solution decreased both Na+ rejection and flux. An increase in testing temperature resulted in an increase in permeate flux, but a decrease in ion rejection.