Miracle-dz/UniFAR-FTUs huggingface dataset:
Dysregulation of dopamine receptor D2 as a sensitive measure for Huntington disease pathology in model mice

The ability to quantitatively evaluate the impact of a potential therapeutic intervention for Huntington disease (HD) in animal models for the disease is a critical step in the pathway to development of an effective therapy for this devastating neurodegenerative disorder. We report here an approach that combines a cell-based assay’s quantitative accuracy and direct relationship to molecular processes with the ability to directly monitor effects in HD model mouse neurons. To accomplish this goal, we have developed an accurate quantitative reporter assay for a transcript known to be down-regulated as an early consequence of mutant huntingtin expression. This system uses mouse strains carrying a GFP reporter for the expression of the dopamine receptor D2, expressed in the medium spiny neurons of the basal ganglion. This receptor consistently demonstrates reduced expression in patients and murine models, and the FACS-based assay gives a highly accurate and quantitative readout of this pathology in mouse neurons expressing mutant huntingtin. For four genetic models and one viral model, a highly reproducible time course of loss of reporter expression is observed. This quantitative measure of HD pathology can be used to measure the effects of HD therapeutics in small cohorts with high confidence. We further demonstrate that the introduction of an shRNA against the huntingtin transgene by virus can improve this pathological status in medium spiny neurons transduced with the construct. We believe this system can be of great utility in the validation of effective therapeutic interventions for HD.
Responsiveness of Mouse Corpora Luteal Cells to Fas Antigen (CD95)-Mediated Apoptosis1

Abstract Regression of the corpus luteum (CL) occurs by apoptosis. The Fas antigen (Fas) is a cell surface receptor that induces apoptosis in sensitive cells when bound to Fas ligand or agonistic anti-Fas monoclonal antibodies (Fas mAb). A potential role for Fas to induce apoptosis in dispersed CL cell preparations was tested in cells isolated from mice on Days 2–4 of pseudopregnancy. Total CL dispersates, containing steroidogenic luteal cells, fibroblasts, and endothelial cells, were cultured. The effect of pretreatment of cultures with cytokines interferon γ (IFN) and tumor necrosis factor α (TNF) was examined because these cytokines demonstrated effects on Fas-mediated apoptosis in other cell types. Fas mAb had no effect on viability of CL cells cultured in 5% fetal bovine serum (FBS) and pretreated with or without IFN or TNF, but Fas mAb did kill 23% of the cells in cultures pretreated with IFN + TNF. Fas mRNA was detectable in cultured CL cells and was increased 2.1-, 2.0-, and 11.8-fold by treatment with TNF, IFN, or IFN + TNF, respectively. CL cells treated with the protein synthesis inhibitor cycloheximide (CX) were killed by Fas mAb in the absence of cytokine pretreatment (34%); pretreatment with IFN or IFN + TNF further potentiated killing (62% and 96%, respectively), whereas pretreatment with TNF had no effect (42%). Cells cultured in medium supplemented with insulin, transferrin, and selenium instead of FBS were killed by Fas mAb in the presence of IFN (23%) or IFN + TNF (29%) but not in the presence of TNF. Cells derived from the mouse CL have a functional Fas pathway that is inhibited by FBS and activated by treatment with CX, IFN, and IFN + TNF.
Screening of SLC26A4, FOXI1, KCNJ10, and GJB2 in Bilateral Deafness Patients with Inner Ear Malformation

Objective. Bilateral nonsyndromic sensorineural hearing loss associated with inner ear malformation is closely related to genetics. SLC26A4 is considered to be the major involved gene. Recently, FOXI1 and KCNJ10 mutations have been linked to enlarged vestibular aqueducts and GJB2 mutations linked to temporal bone malformation. The authors aimed to investigate the mutation spectrums of these genes in Chinese patients with bilateral hearing impairment associated with inner ear malformation. Study Design. Cross-sectional study. Setting. Affiliated hospital of the university. Subjects and Methods. The authors analyzed the GJB2, SLC26A4, FOXI1, and KCNJ10 gene sequences in 43 patients presenting with bilateral hearing impairment associated with inner ear malformation using pyrosequencing and direct DNA sequencing. Results. In total, 74.4% (32/43) of patients carried at least 1 of 14 pathogenic SLC26A4 mutations, including 6 novel mutations and 4 polymorphisms. Patients with enlarged vestibular aqueducts had a higher rate of SLC26A4 mutation than Mondini dysplasia patients. No FOXI1 or KCNJ10 potential pathogenic mutation was present, and GJB2 biallelic pathogenic mutations were uncommon (2.3%; 1/43). No significant correlation was observed between the genotype and phenotype of SLC26A4 mutations. Conclusion. SLC26A4 accounts for 74.4% of inner ear malformations in our cohort, whereas FOXI1, KCNJ10, and GJB2 mutations are not common. Other possible genes or external factors may contribute to this multibranch abnormality.
Unlimited Love: Altruism, Compassion, and Service

What if we could prove that love heals mental illness and is vital to successful therapeutic outcomes in all areas of health care? What if we could prove that people who live more for others than for self have greater psychological well-being? Professor Stephen G. Post, who heads the Institute for Research on Unlimited Love, is developing a new positive scientific program that integrates practice with high-level empirical research and religious-ethical ideas in order to explore these questions. The goal is to understand how our complex brains, unique imaginations, communicative abilities, reasoning powers, moral sense, and spiritual promptings give rise to the remarkable practice of unselfish love for our neighbors--or for those we do not even know. In Unlimited Love, Post examines the question of what we mean by "unlimited love"; his focus is not on "falling" into love, which is "altogether natural, easy, and delusional. " Rather, he focuses on the difficult learned ascent that "begins with insight into the need for tolerance of ubiquitous imperfection, and matures into unselfish concern, gratitude, and compassion. " He considers social scientific and evolutionary perspectives on human altruistic motivations, and he analyzes these perspectives in a wide interdisciplinary context at the interface of science, ethics, and religion. Teilhard de Chardin commented that the scientific understanding of the power of unselfish love would be as significant in human history as the discovery of fire. In Unlimited Love, Stephen Post presents an argument for the creation of a new interdisciplinary field for the study of love and unlimited love, "engaging great minds and hoping to shape the human futureaway from endless acrimony, hatred, and violence. "
Algorithms for abstracting and solving imperfect information games

Game theory is the mathematical study of rational behavior in strategic environments. In many settings, most notably two-person zero-sum games, game theory provides particularly strong and appealing solution concepts. Furthermore, these solutions are efficiently computable in the complexity-theory sense. However, in most interesting potential applications in artificial intelligence, the solutions are difficult to compute using current techniques due primarily to the extremely large state-spaces of the environments. In this thesis, we propose new algorithms for tackling these computational difficulties. In one stream of research, we introduce automated abstraction algorithms for sequential games of imperfect information. These algorithms take as input a description of a game and produce a description of a strategically similar, but smaller, game as output. We present algorithms that are lossless (i.e., equilibrium-preserving), as well as algorithms that are lossy, but which can yield much smaller games while still retaining the most important features of the original game. In a second stream of research, we develop specialized optimization algorithms for finding e-equilibria in sequential games of imperfect information. The algorithms are based on recent advances in non-smooth convex optimization and provide significant improvements over previous algorithms for finding e-equilibria. Combining these two streams, we enable the application of game theory to games much larger than was previously possible. As an illustrative example, we find near-optimal solutions for four-round models of limit and no-limit Texas Hold'em poker, and report that the resulting players won the most chips overall at the 2008 AAAI Computer Poker Competition.
Building large scale ontology networks

Adoptable, high performance, large scale ontologies that can be extended to support multimedia play a crucial role in building effective content and knowledge management systems and applications. In the context of developing a unified taxonomy and ontology network (UTON), we have undertaken the task of developing a technology framework for building large scale ontologies. This paper describes the architecture of UTON and how general purpose resources such as WordNet and open directory project can be used to create large scale ontology networks and how application specific taxonomies or ontologies can be derived from these general purpose tools and resources.
High-Throughput Calculation of Protein-Ligand Binding Affinities: Modification and Adaptation of the MM-PBSA Protocol to Enterprise Grid Computing

We have developed a system for performing computations on an enterprise grid using a freely available package for grid computing that allows us to harvest unused CPU cycles off of employee desktop computers. By modifying the traditional formulation of Molecular Mechanics with Poisson-Boltzmann Surface Area (MM-PBSA) methodology, in combination with a coarse-grain parallelized implementation suitable for deployment onto our enterprise grid, we show that it is possible to produce rapid physics-based estimates of protein-ligand binding affinities that have good correlation to experimental data. This is demonstrated by examining the correlation of our calculated binding affinities to experimental data and also by comparison to the correlation obtained from the binding-affinity calculations using traditional MM-PBSA that are reported in the literature.
Identification of Pyrus Single Nucleotide Polymorphisms (SNPs) and Evaluation for Genetic Mapping in European Pear and Interspecific Pyrus Hybrids

We have used new generation sequencing (NGS) technologies to identify single nucleotide polymorphism (SNP) markers from three European pear (Pyrus communis L.) cultivars and subsequently developed a subset of 1096 pear SNPs into high throughput markers by combining them with the set of 7692 apple SNPs on the IRSC apple Infinium® II 8K array. We then evaluated this apple and pear Infinium® II 9K SNP array for large-scale genotyping in pear across several species, using both pear and apple SNPs. The segregating populations employed for array validation included a segregating population of European pear (‘Old Home’×‘Louise Bon Jersey’) and four interspecific breeding families derived from Asian (P. pyrifolia Nakai and P. bretschneideri Rehd.) and European pear pedigrees. In total, we mapped 857 polymorphic pear markers to construct the first SNP-based genetic maps for pear, comprising 78% of the total pear SNPs included in the array. In addition, 1031 SNP markers derived from apple (13% of the total apple SNPs included in the array) were polymorphic and were mapped in one or more of the pear populations. These results are the first to demonstrate SNP transferability across the genera Malus and Pyrus. Our construction of high density SNP-based and gene-based genetic maps in pear represents an important step towards the identification of chromosomal regions associated with a range of horticultural characters, such as pest and disease resistance, orchard yield and fruit quality.
The location-specific role of proteoglycans in the flexor carpi ulnaris tendon

Abstract Tendons like the flexor carpi ulnaris (FCU) that contain region-specific distributions of proteoglycans (PGs) as a result of the heterogeneous, multi-axial loads they are subjected to in vivo provide valuable models for understanding structure–function relationships in connective tissues. However, the contributions of specific PGs to FCU tendon mechanical properties are unknown. Therefore, the objective of this study was to determine how the location-dependent, viscoelastic mechanical properties of the FCU tendon are impacted individually by PG-associated glycosaminoglycans (GAGs) and by two small leucine-rich proteoglycans (SLRPs), biglycan and decorin. Full length FCU tendons from biglycan- and decorin-null mice were compared to wild-type (WT) mice to evaluate the effects of specific SLRPs, while chondroitinase ABC digestion of isolated specimens removed from the tendon midsubstance was used to determine how chondroitin/dermatan sulfate (CS/DS) GAGs impact mechanics in mature FCU tendons. A novel combined genetic knockout/digestion technique also was employed to compare SLRP-null and WT tendons in the absence of CS/DS GAGs that may impact properties in the mature state. In all genotypes, mechanical properties in the FCU tendon midsubstance were not affected by GAG digestion. Full-length tendons exhibited complex, multi-axial deformation under tension that may be associated with their in vivo loading environment. Mechanical properties were adversely affected by the absence of biglycan, and a decreased modulus localized in the center of the tendon was measured. These results help elucidate the role that local alterations in PG levels may play in processes that adversely impact tendon functionality including injury and pathology.
A K-band low-power CMOS transformer-feedback VCO

A K-band transformer-feedback voltage-controlled oscillator (TF-VCO) is implemented in 90 nm CMOS process and covers the frequency range from 19.39 GHz to 19.99 GHz. Utilizing the complementary cross-coupled structure and transformer-feedback technique, the VCO achieves low phase noise with low power consumption. The measured 1-MHz frequency offset phase noise is -95.37 dBc/Hz at 19.99 GHz and the dc power consumption is 1 mW.
Is cold paresis related to axonal depolarization?

Cold paresis may occur in multifocal motor neuropathy and lower motor neuron disease. It was proposed to reflect nerve lesions where axons are depolarized due to loss of Na/K‐pump activity. In those circumstances, a further decrease in pump activity by cooling may induce extra depolarization, conduction block, and weakness. Evidence for this hypothesis is incomplete because it is unknown if cold induces depolarization in human motor axons and other factors may contribute to the symptoms. To solve these questions, we examined 10 normal subjects. At 37, 25, 20, and 15°C we assessed: excitability in the median nerve, decrement on 3‐Hz stimulation, pulsed Doppler of a wrist artery, and thenar muscle strength. Cooling induced: (1) findings compatible with axonal depolarization on excitability testing (fanning‐in of threshold electrotonus, steepened current threshold relation, increased refractory period, decreased super‐ and subexcitability), (2) decreased Doppler peak systolic velocity without causing ischemia, (3) decreased muscle strength and impaired muscle relaxation. Decrement tests and compound muscle action potential amplitude remained normal. The excitability findings induced by cooling were best explained by axonal depolarization due to the effect of temperature on Na/K‐pump activity. The induced weakness may be explained not only by this mechanism but also by impaired muscle contraction.
Fault Current Interruption by the Dynamic Voltage Restorer

This paper introduces and evaluates an auxiliary control strategy for downstream fault current interruption in a radial distribution line by means of a dynamic voltage restorer (DVR). The proposed controller supplements the voltage-sag compensation control of the DVR. It does not require phase-locked loop and independently controls the magnitude and phase angle of the injected voltage for each phase. Fast least error squares digital filters are used to estimate the magnitude and phase of the measured voltages and effectively reduce the impacts of noise, harmonics, and disturbances on the estimated phasor parameters, and this enables effective fault current interrupting even under arcing fault conditions. The results of the simulation studies performed in the PSCAD/EMTDC software environment indicate that the proposed control scheme: 1) can limit the fault current to less than the nominal load current and restore the point of common coupling voltage within 10 ms; 2) can interrupt the fault current in less than two cycles; 3) limits the dc-link voltage rise and, thus, has no restrictions on the duration of fault current interruption; 4) performs satisfactorily even under arcing fault conditions; and 5) can interrupt the fault current under low dc-link voltage conditions.
An exact algorithm for the O-l collapsing knapsack problem

An exact algorithm is proposed for the O-l collapsing knapsack problem as defined by Guignard and Posner. Bounding of the number of variables equal to 1 in an optimal solution is extensively used, as well as innerand outer-linearization of the nonlinear right-hand side of the constraint. This allows generally a drastic reduction of the feasible domain. An implicit enumeration scheme solves the problem reduced by the preprocessing phase. Computational experiments are reported on.
Hearing voices: coping, resilience and recovery

Introduction: The aim of this study was to explore the experience of people who hear voices and how the support offered to them affects coping, resilience and recovery. Individual factors such as coping, resilience, belief systems and current service provisions are discussed within the developing context of the mental health system and wider society. Method: Seven people who hear voices were recruited from a local hearing voices group and interviewed using a semi-structured interview. Interpretative Phenomenological Analysis was used to analyse the transcripts. Results: Six key themes emerged from the participants’ accounts. These included: Psychiatry: social control; Psychiatry: a clinical model; Trauma, trauma and re-trauma; Voice awareness; Dancing with voices; and Relationships: lack of understanding. Discussion: The participants highlighted the support provided by the Hearing Voices Group and help provided by family and friends. This was considered in contrast with psychiatry which was viewed unfavourably. The primary difference in the experience of support, perceived as either helpful or unhelpful, was linked to the emphasis on specific factors that the interviewees considered to influence their process of recovery. These included being in a safe and non-judgemental environment, being offered hope and validation of their experiences, as well as having a means to socially connect and empower their position so that they can be more active in their own recovery. The research suggests that more training in the conceptual frameworks and models of recovery, a greater focus on working with the family and wider support, enhanced collaborative working, and more tailored outcome measures would help services to better meet these individuals’ needs during the recovery process.
Similarity for Analogical Software Reuse: A Computational Model

This paper describes a computational model of similarity developed to support analogical software reuse. Similarity is computed from conceptual descriptions of software artifacts of any substance (i.e code, design or specification artifacts). This computation is restricted by an axiomatic framework realizing properties of similarity assessments by humans and analogical reasoning and exploits the semantics of three com- mon conceptual modeling abstractions, namely the classification, the gen- eralization and the attribution. An operationalization of the model is presented together with a prototype implementing it. The consistency of the estimates of the operational model with respect to similarity assess- ments of software engineers and its recall performance are evaluated, in a preliminary experiment.
Effects of the weight-to-stress principle in English speakers learning Japanese prosody

Anna Powers: Effects of the Weight-to-Stress Principle in English Speakers Learning Japanese Prosody (Under the direction of Jennifer L. Smith) This thesis explores the effect of the Weight-to-Stress Principle (WSP) in second language transfer of word-level accent from English stress accent to Japanese pitch accent within the framework of Optimality Theory. A model is proposed that predicts some English speakers will be more likely to insert pitch accents into unaccented Japanese words containing heavy syllables (Heavy words) than ones consisting only of light syllables (Light words), due to the effects of WSP. I performed an elicitation experiment on English-speaking learners of Japanese wherein participants produced unaccented Japanese nonce words of varying prosodic structure in a sentence. At least one participant was more likely to insert a pitch accent into Heavy words than Light words, supporting the proposed model. Two other participants showed a preference for inserting pitch accents on three-mora Light words, indicating that additional factors may be at work. iv ACKNOWLEDGEMENTS
Iterative Directional Total Variation Refinement for Compressive Sensing Image Reconstruction

We propose a novel compressive sensing (CS) image reconstruction method based on iterative directional total variation (TV) refinement. As is generally known, classical TV-based CS reconstruction methods tend to produce over-smoothed image edges and texture details, since they favor piece-wise constant solutions. Hence, directional TV is introduced to describe the sparsity of the image gradient in order to overcome this drawback. However, it is difficult to estimate orientation field robustly and accurately from CS measurements. Inspired by vectorial ROF model, orientation field refinement model is presented and introduced into CS reconstruction. Extended experiments show that the proposed CS reconstruction method has a better improvement in the quality of the reconstructed image details over related TV-based CS reconstruction methods.
Cerebrospinal Fluid Immunoglobulin Kappa Light Chain in Clinically Isolated Syndrome and Multiple Sclerosis

Background Oligoclonal bands (OCB) are the most widely used CSF test to support the diagnosis of MS and to predict conversion of clinically isolated syndrome (CIS) to multiple sclerosis (MS). Since OCB tests are based on non-quantitative and difficult to standardise techniques, measurement of immunoglobulin kappa free light chains (KFLC) may represent an easier to use quantitative test. Methods KFLC were measured in CSF and serum of 211 patients using ELISA. These include patients without any inflammatory central nervous system reaction (NIND, n = 77), MS (n = 20), viral CNS infections (V-CNS-I, n = 10), neuroborreliosis (NB, n = 17) and other bacterial CNS infections (B-CNS-I, n = 10). Furthermore a cohort of 77 patients with CIS, including 39 patients that remained CIS over follow-up of two years (CIS-CIS) and 38 patients that developed MS over the same follow-up time (CIS-MS). Results CSF-serum ratio of KFLC (Q KFLC) was elevated in all patients with MS, 86.8% of patients with CIS-MS and 61.5% of patients with CIS-CIS. It was significantly elevated in CIS with presence of OCB (p<0.001). Q KFLC significantly correlated with other CSF variables such as CSF leukocyte count (p<0.001, R = 0.46), CSF CXCL13 levels (p<0.001, R = 0.64) and also intrathecal IgG synthesis (p<0.001, R = 0.74) as determined by nephelometry and quotient diagram. OCB were detected in 66.7% of CIS-CIS and in 92.1% of CIS-MS. Conclusions Although the measurement of CSF KFLC is a rapid and quantitative easy to standardize tool, it is almost equal but not superior to OCB with regard to diagnostic sensitivity and specificity in patients with early MS.