Miracle-dz/UniFAR-FTUs huggingface dataset:
ABL Tyrosine Kinases: Evolution of Function, Regulation, and Specificity

Insights from the regulation of ABL-family tyrosine kinases could facilitate development of therapies for malignancies driven by ABL fusion proteins. ABL-family proteins comprise one of the best conserved branches of the tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3–Src homology 2–tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. This cassette is coupled to an actin-binding and -bundling domain, which makes ABL proteins capable of connecting phosphoregulation with actin-filament reorganization. Two vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain through which it mediates DNA damage-repair functions, whereas ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. Information on ABL regulatory mechanisms is being mined to provide new therapeutic strategies against hematopoietic malignancies caused by BCR-ABL1 and related leukemogenic proteins. ABL-family proteins couple a highly regulated tyrosine kinase domain with an actin-binding and -bundling domain to carry out a set of unique and essential functions. The ABL genes are among the earliest identifiable genes encoding tyrosine kinases, and they show remarkable sequence conservation. Gene duplication produced two vertebrate ABL paralogs with specialized properties. ABL1 evolved nuclear localization signals and a DNA binding domain to mediate damage repair functions. ABL2 developed additional binding domains for actin and microtubules, extending its cytoskeletal remodeling functions. This Review surveys the recent literature and available databases with a focus on ABL evolution and the mechanisms regulating ABL's catalytic activity and substrate specificity. This Review contains 7 figures, 2 tables, and 248 references. A better understanding of these properties could facilitate the design of new treatments for malignancies driven by ABL fusion proteins.
A novel design for an expandable, modular microgrid unit

This paper proposes a modular microgrid unit (MMGU) that can work autonomously but is also capable of connecting to other MMGUs to form an expandable microgrid. Because of various types of resources and power lines, the proposed unit is reliable and robust enough to protect against single failures and generation fluctuation. Storage units are included to enhance the overall performance of the microgrid system by improving reliability, dispatchability, stability, and power quality.
Morphometry in schizophrenia revisited: height and its relationship to pre-morbid function

Background. Morphometry, the measurement of forms, is an ancient practice. In particular, schizophrenic somatology was popular early in this century, but has been essentially absent from the literature for over 30 years. More recently, evidence has grown to support the notion that aberrant neurodevelopment may play a role in the pathophysiology of schizophrenia. Is the body, like the brain, affected by abnormal development in these patients? Methods. To evaluate global deficit in development and its relationship to pre-morbid function, height was compared in a large group (N=226) of male schizophrenics and a group of healthy male controls (N=142) equivalent in parental socio-economic status. Patients in the lower quartile of height were compared to those in the upper quartile of height. Results. The patient group had a mean height of 177·1 cm, which was significantly shorter than the mean height of the control group of 179·4 (P<0·003). Those in the lower quartile had significantly poorer pre-morbid function as measured by: (1) psychosocial adjustment using the pre-morbid adjustment scales for childhood and adolescence/young adulthood, and (2) cognitive function using measures of school performance such as grades and need for special education. In addition, these measures of pre-morbid function correlated significantly with height when analysed using the entire sample. Conclusions. These findings provide further support to the idea that abnormal development may play a key role in the pathophysiology of schizophrenia. Furthermore, this is manifested as a global deficit in growth and function resulting in smaller stature, poorer social skills, and deficits in cognitive abilities.
Hyperfinite type structures

The notion of a hyperfinite set comes from nonstandard analysis. Such a set has the internal cardinality of a nonstandard natural number. By a transfer principle such sets share many properties of finite sets. Here we apply this notion to give a hyperfinite model of the Kleene-Kreisel continuous functionals. We also extend the method to provide a hyperfinite characterisation of certain transfinite type structures, thus, through the work of Waagbø [14], constructing a hyperfinite model for Martin-Löf type theory. This kind of application is not new. Normann [6] gave a characterisation of the Kleene-Kreisel continuous functionals using ‘hyperfinitary’ functionals. The novelty here is that we use a constructive version of hyperfinite functionals and also generalise the method to transfinite types. Many of the results of this paper are constructive, though not the characterisation theorems themselves. Our characterisation of the Kleene-Kreisel continuous functionals is a supplement to a number of previous characterisations of topological and recursion-theoretical nature, see [6] for a brief survey. Altogether these characterisations show that the original concept of Kleene and Kreisel forms the correct mathematical model of the idea of finitely based functions of finite types. There is, however, no a priori reason to believe that there is a canonical way to extend the continuous functionals to cover transfinite objects of transfinite type used in, e.g., type theory. Our characterisation of Waagbø's model indicates that the model is natural, not only seen from domain theory but from a higher perspective. Normann and Waagbø (unpublished) have subsequently obtained a limit-space characterisation that further supports this view.
Study of dose-dependent metabolism of 5,5-diphenyl-hydantoin in the rat using new methodology for isolation and quantitation of metabolites in vivo and in vitro.

A specific extraction procedure for the separation and measurement of 5,5-diphenyihydantoin (DPH), hydroxydiphenyihydantoin (HPPH) and more polar metabolites has been developed using 14C-DPH. The DPH is extracted with 1-chlorobutane, the HPPH with diethyl ether and more polar metabolites with acetone. The half-life ( t /2) of DPH in the blood of the rat (male, Sprague-Dawley) after i.v. injection is dose dependent and is 0.6, 1.2 and 2.5 hours at doses of 10, 25 and 40 mg/kg, respectively. In the isolated perfused rat liver there is an initial rapid decline of DPH in the perfusate caused primarily by hepatic uptake of unchanged drug. Thereafter the decline in the perfusate is slower and the t /2 is 15 and 60 minutes at initial doses of 10 and 92 µg/ml in the perfusate. Under these conditions DPH is converted mainly to p -HPPH which undergoes conjugation. Two isomers of HPPH, p -HPPH and m -HPPH, were isolated from acid hydrolysates of bile but only p -HPPH after enzymic hydrolysis. The conjugate accumulates in the bile and perfusate. The dihydrodiol metabolite is also present in the bile and perfusate. The t /2 of p -HPPH (100 µg/ml) in the perfusate is 12 minutes. Incubations of DPH with microsomes obtained from rat liver results in the production of p -HPPH as well as more polar components. Pretreatment of rats with phenobarbital, chlordane, hydroxyzine and DDT results in an increase in the rate of disappearance of DPH from microsomal incubations and the metabolite pattern remains similar.
Publishing Pilot Intervention Work

Pilot intervention studies can be viewed as rehearsals for subsequent full-scale trials. They can help investigators fine-tune later larger studies as well as explore issues related to project management and budget. Pilot studies permit testing of sampling strategies, participant recruitment, intervention content, delivery methods, data collection, and analysis. They also allow researchers to experience the more practical aspects of implementing a study, such as determining the number of study staff members needed to handle recruitment and data collection or identifying special equipment needs. Because pilot study findings may be generalizable, publication is encouraged as long as the preliminary nature of the work is clearly indicated in both the abstract and the article. The present article provides an overview of the types of information that can be gleaned from pilot intervention studies that are suitable for publication.
Costs of rheumatoid arthritis in Germany: a micro-costing approach based on healthcare payer’s data sources

Objective: To develop a systematic set of German cost data in rheumatoid arthritis (RA) based solely on valid healthcare payer’s cost data sources. Methods: Retrospectively one year cost data of 338 patients with RA were generated and analysed. The cost data were derived from a major statutory health insurance plan (“Allgemeine Ortskrankenkasse Niedersachsen”) and the regional physicians’ association (“Kassenärztliche Vereinigung Niedersachsen”). The recently published matrix of cost domains in RA was applied to structure the analysis. Descriptive statistics were used to analyse the data. Results: The total direct costs for the 338 patients during one year (third quarter 2000 to second quarter 2001) were €3815 per patient-year. RA related direct costs were €2312 per patient-year. Outpatient costs accounted for 73.7%, inpatient costs for 24.0%, and other disease related costs for 2.3% of RA related direct costs. Outpatients cost drivers were RA related drugs (€1019 per patient-year), physician visits (€323 per patient-year), diagnostic and therapeutic procedures and tests (€185 per patient-year), and devices and aids (€168 per patient-year). 98 patients were retired prematurely owing to RA related work disability and incurred costs of €8358 per retired patient-year. 96 patients were gainfully employed and incurred sick leave costs of €2835 per employed patient-year. Conclusion: Micro-costing based on healthcare payer’s data provides a relatively conservative albeit highly accurate estimate of costs in RA. Both RA related and non-RA related costs must be taken into account. In gainfully employed patients and in patients who receive RA related retirement payments productivity costs exceed direct costs.
[Artificial ribonucleases I. Targeted RNA cleavage by 5'-peptidyloligodeoxyribonucleotides containing arginine and leucine residues].

The interaction of DNA and RNA with oligodeoxyribonucleotides and their 3'-terminal N-(2-hydroxyethyl)phenazinium derivatives carrying peptide residues with alternating basic and hydrophobic amino acids at the 5'-terminal phosphate was studied. It was found that the introduction of peptide residues (LeuArg)n-Gly-NH2 (n = 2-4) into an oligodeoxyribonucleotide enhances the latter's hybridization ability: each additional LeuArg pair increases the Tm value of the (5')pd(CACACACAAAAAAC). (3')d(TGTGTGTG)p(-LeuArg)n-Gly- NH2 complex by 1.3 degrees C. The reagents did not destort the DNA structure and were capable of site-specific hydrolysis of the phosphodiester bonds of RNA. It was shown that the location of the cleavage sites and the efficacy of the RNA hydrolysis at n = 2 and 4 and at n = 3 strongly differ. The maximum hydrolysis (80%) of tetradecaribonucleotide (5')p(GAUUGAAAAUCCCC) was achieved using peptidyloligodeoxyribonucleotide (3')d(CTAACT)p(LeuArg)4GlyNH2. The possibility of directed cleavage of phosphodiester bonds in tRNAPhe by peptidyloligodeoxyribonucleotides (3')d(CTAACT)p(LeuArg)nGlyNH2 (n = 3 and 4) was shown.
A 95-dB linear low-power variable gain amplifier

An all-CMOS variable gain amplifier (VGA) that adopts a new approximated exponential equation is presented. The proposed VGA is characterized by a wide range of gain variation, temperature-independence gain characteristic, low-power consumption, small chip size, and controllable dynamic gain range. The two-stage VGA is fabricated in 0.18-mum CMOS technology and shows the maximum gain variation of more than 95 dB and a 90-dB linear range with linearity error of less than plusmn 1 dB. The range of gain variation can be controlled from 68 to 95 dB. The P1dB varies from - 48 to - 17 dBm, and the 3-dB bandwidth is from 32 MHz (at maximum gain of 43 dB) to 1.05 GHz (at minimum gain of - 52 dB). The VGA dissipates less than 3.6 mA from 1.8-V supply while occupying 0.4 mm2 of chip area excluding bondpads
Asymptotic stabilization of nonlinear systems via sign-indefinite damping injection

The problem of asymptotic stabilization of nonlinear, “double integrator”, open-loop stable systems via sign-indefinite damping injection is considered in this paper. A constructive procedure to reduce the problem to the solution of a set of partial differential equations is presented. Particular emphasis is given to mechanical systems, for which it is shown that the proposed approach obviates the usual detectability assumption needed to conclude asymptotic stability via LaSalle's invariance principle.
Pre-Charged Local Bit-Line Sharing SRAM Architecture for Near-Threshold Operation

In this paper, a pre-charged local bit-line sharing (PCLBS) static random access memory (SRAM) for near-threshold operation is proposed. In previous local bit-line sharing SRAMs, such as average-8T and full-swing local bit-line (FSLB) SRAMs, multiple bit-cells share a local bit-line pair with a small capacitance for high read stability. However, the average-8T SRAM has a considerably large delay because the full development of the local bit-line cannot be achieved. On the other hand, the FSLB SRAM reduces the delay but requires a timing constraint of control signals to achieve sufficient read sensing margin. The proposed PCLBS SRAM achieves high read speed by fully developing local bit-line pair without a timing constraint. Furthermore, the proposed PCLBS SRAM enhances the read stability and the write ability by, respectively, applying a pre-charged local bit-line scheme and transmission gates in write paths. Based on a 22-nm FinFET technology, the FSLB and proposed PCLBS SRAM have the minimum operating voltages of 0.44 and 0.4 V, respectively, while achieving the $5\sigma$ target read stability and write ability yields. Compared with the FSLB SRAM, the proposed PCLBS SRAM consumes 21% less energy at each minimum operating voltage and has 57% smaller read delay at the operating voltage of 0.4 V.
Serological and molecular comparisons of coronaviruses

The antigenic interrelationships among viruses of the family Coronaviridae were examined. Four mammalian coronaviruses from two different antigenic groups were compared using serological and molecular techniques. The viruses selected were murine hepatitis virus A59 (A59V), bovine coronavirus (BCV), canine coronavirus (CCV) and transmissible gastroenteritis virus (TGEV). Hyperimmune ascitic fluids were prepared in mice to provide a homogeneous source of antibody. Virus-infected cell lysates were used as immunogens to generate antibodies against intracellular as well as structural proteins. Antibodies directed against cellular proteins were removed by absorption with uninfected cells. The ascitic fluids compared favorably to hyper immune serum in immunofluorescence and virus-neutralization tests. The intracellular, proteins of A59V, BCV, CCV and TGEV were identified by immunoprecipitation of infected-cell lysates with hyperimmune ascitic fluids. Reciprocal cross-immunofluorescence and neutralization tests showed two-way cross-reactions between A59V and BCV, and between CCV and TGEV. Immunoprecipitation of virus-infected cell lysates showed that the serological relatedness was based on common determinants on each of the major viral antigens: the peplomer, nucleocapsid and membrane. Monoclonal antibodies (MAbs) against each virus were isolated using hybridoma technology. The MAbs were tested for virus specificity by immunofluorescence, polypeptide specificity by immunoprecipitation, and virus neutralization activity by a plaque reduction test. They were also tested for cross-reaction with the related virus. Most of the MAbs isolated recognized the nucleocapsid protein, which is the major polypeptide synthesized in infected cells. MAbs which neutralized virus infactivity were directed against the peplomeric proteins. The immunoprecipitation and MAb studies suggest that TGEV and CCV are more closely related than AS9V and BCV. SEROLOGICAL AND MOLECULAR COMPARISONS OF CORONAVIRUSES by Susan Herbert Goss A thesis submitted in partial fulfillment of the requirements for the degree of i Doctor of Philosophy in Microbiology . MONTANA STATE UNIVERSITY Bozeman, Montana December 1984
Hepatic Stellate Cells and Fibrogenesis in Hepatitis C Virus Infection: An Ultrastructural Insight

An ultrastructural quantitative assessment of hepatic stellate cells (HSCs) was made in relation to hepatic fibrosis, apoptotic cellular changes, intracellular fat deposition, circulating inflammatory cells in the sinusoids, and the necroinflammatory activity in liver specimens of 33 patients proven to be positive for hepatitis C virus (HCV)-RNA by polymerase chain reaction with the intention that electron microscopy may throw more light on the role of HSCs in the complicated process of fibrogenesis. A detailed review concerning these parameters and observed evidence suggesting the potential properties of HSCs to recycle cellular debris into collagen fibers are reported.
Protein and RNA engineering to customize microbial molecular reporting

Nature takes advantage of the malleability of protein and RNA sequence and structure to employ these macromolecules as molecular reporters whose conformation and functional roles depend on the presence of a specific ligand (an “effector” molecule). By following nature's example, ligand‐responsive proteins and RNA molecules are now routinely engineered and incorporated into customized molecular reporting systems (biosensors). Microbial small‐molecule biosensors and endogenous molecular reporters based on these sensing components find a variety of applications that include high‐throughput screening of biosynthesis libraries, environmental monitoring, and novel gene regulation in synthetic biology. Here, we review recent advances in engineering small‐molecule recognition by proteins and RNA and in coupling in vivo ligand binding to reporter‐gene expression or to allosteric activation of a protein conferring a detectable phenotype. Emphasis is placed on microbial screening systems that serve as molecular reporters and facilitate engineering the ligand‐binding component to recognize new molecules.
Artificial Intelligence Opportunities and an End-To-End Data-Driven Solution for Predicting Hardware Failures by

Dell’s target to provide quality products based on reliability, security, and manageability, has driven Dell Inc. to become one of the largest PC suppliers. The recent developments in Artificial Intelligence (AI) combined with a competitive market situation have encouraged Dell to research new opportunities. AI research and breakthroughs have risen in the last years, bringing along revolutionary technologies and companies that are disrupting all businesses. Over 30 potential concepts for AI integration at Dell Inc. were identified and evaluated to select the ones with the highest potential. The top-most concept consisted of preventing in real time the failure of hardware. This concept was investigated using a data science process. Currently, there exist a number of machine learning tools that automate the last stages of the proposed data science process to create predictive models. The utilized tools vary in functionality and evaluation standards, but also provide other services such as data and model storage and visualization options. The proposed solution utilizes the deep feature synthesis algorithm that automatically generates features from problem-specific data. These engineered features boosted predictive model accuracy by an average of 10% for the AUC and up to 250% in recall for test (out of sample) data. The proposed solution estimates an impact exceeding $407M in the first five years for Dell Inc. and all of the involved suppliers. Conservatively, the direct impact on Dell Inc. is particular to batteries under warranty and is expected to surpass $2.7M during the first five years. The conclusions show a high potential for implementation. Thesis Supervisor: Kalyan Veeramachaneni Title: Principal Research Scientist in Laboratory for Information and Decision Systems Thesis Supervisor: Tauhid Zaman Title: KDD Career Development Professor in Communications and Technology
Generation of HIV Latency in Humanized BLT Mice

ABSTRACT Here we demonstrate that a combination of tenofovir, emtricitabine, and raltegravir effectively suppresses peripheral and systemic HIV replication in humanized BLT mice. We also demonstrate that antiretroviral therapy (ART)-treated humanized BLT mice harbor latently infected resting human CD4+ T cells that can be induced ex vivo to produce HIV. We observed that the levels of infected resting human CD4+ T cells present in BLT mice are within the range of those observed circulating in patients undergoing suppressive ART. These results demonstrate the potential of humanized BLT mice as an attractive model for testing the in vivo efficacy of novel HIV eradication strategies.
Gene Therapy and Informed Consent Decision Making: Nursing Research Directions

Recent gene therapy clinical trials have demonstrated significant promise for treating a number of genetic neuromuscular disorders. Although nurses are experienced in educating patients and families about the benefits and risks of conventional therapeutics, there are significant challenges for guiding patients through the decision-making phase of gene therapy clinical trial participation. The first part of this review provides an overview and update on neuromuscular gene therapy, including viral delivery principles and historical progress. The second part discusses risk/benefit perception of gene therapy and factors affecting the decision making for patients interested in participating in a trial. Future challenges for gene therapy are targeted high-efficiency delivery, and additional research on developing patient-centered decision support interventions.
A single-to-differential broadband transimpedance amplifier for 12.5 Gb/s optical links

A broadband transimpedance amplifier (TIA) is designed and analyzed based on Regulated Cascode (RGC) configuration with L-matching network and cascode amplifier. A novel single-to-differential amplifier is also designed to simplify the following limiting amplifier (LA) design and increase the immunity of common-mode noise. The TIA is implemented in UMC 0.18 μm standard CMOS process. The measured transimpedance gain is 57 dBΩ with a −3 dB bandwidth of 8.1GHz. The average equivalent input noise current spectral density is 29 pA/√Hz. The chip consumes 68mW DC power under 1.8V and occupies the area of 0.9mm2.