gebhart/patrepeval huggingface dataset:
A point mutation in the integrin beta 3 cytoplasmic domain (S752-->P) impairs bidirectional signaling through alpha IIb beta 3 (platelet glycoprotein IIb-IIIa) (1994)

Abstract Agonist-induced inside-out signaling results in an increased affinity of integrin alpha IIb beta 3 (platelet glycoprotein IIb-IIIa) for soluble ligands (fibrinogen [Fg] and PAC1). Ligand binding to integrins initiates outside-in signaling that leads to cellular responses such as cell spreading and focal adhesion formation. A point mutation in the beta 3 cytoplasmic domain (S752--&gt;P) is associated with blocked inside- out alpha IIb beta 3 signaling in a variant Glanzmann's thrombasthenia. This mutation was introduced into beta 3 and cotransfected into Chinese hamster ovary cells with a chimeric alpha subunit consisting of the alpha IIb extracellular and transmembrane domains and the alpha 6B cytoplasmic domain. The substitution of the alpha IIb cytoplasmic domain with that of alpha 6 led to activation of alpha IIb beta 3 to bind PAC1, mimicking inside-out signaling. This effect was reversed by the S752--&gt;P mutation, indicating a disruption of inside-out signaling by the mutation. In addition, transfectants expressing this beta 3 variant showed reduced alpha IIb beta 3-mediated cell spreading on immobilized Fg, focal adhesion, and fibrin clot retraction, suggesting an impairment in outside-in alpha IIb beta 3 signaling. Therefore, a single point mutation in the beta 3 cytoplasmic domain impaired bidirectional signaling through alpha IIb beta 3.
<title>Volumetric applications for spiral CT in the thorax</title> (1994)

Spiral computed tomography (CT) is a new technique for rapidly acquiring volumetric data within the body. By combining a continuous gantry rotation and table feed, it is possible to image the entire thorax within a single breath-hold. This eliminates the ventilatory misregistration seen with conventional thoracic CT, which can result in small pulmonary lesions being undetected. An additional advantage of a continuous data set is that axial sections can be reconstructed at arbitrary intervals along the spiral path, resulting in the generation of overlapping sections which diminish partial volume effects resulting from lesions that straddle adjacent sections. The rapid acquisition of spiral CT enables up to a 50% reduction in the total iodinated contrast dose required for routine thoracic CT scanning. This can be very important for imaging patients with cardiac and renal diseases and could reduce the cost of thoracic CT scanning. Alternatively, by combining a high flow peripheral intravenous iodinated contrast injection with a spiral CT acquisition, it is possible to obtain images of the vasculature, which demonstrate pulmonary arterial thrombi, aortic aneurysms and dissections, and congenital vascular anomalies in detail previously unattainable without direct arterial access.
Ninety-day readmissions after degenerative cervical spine surgery: A single-center administrative database study (2015)

IV.
Gateless Computing using N-Manakov Solitons (1999)

Despite the fantastic rate at which silicon-based technologies have been progressing, there are several fundamental limitations which suggest that this progress cannot continue without bound. Even within the next decade or two these factors may start to become a real hindrance, and so interest in alternative technologies, such as quantum and DNA computing, has been growing.
Inverse scattering image quality as a function of SNR (2007)

In this paper, we consider Colton-Kirsh regularized sampling (CK-RS), holographic backprojection tomography, and diffraction tomography. The latter of these algorithms are based on the Born approximation, whereas regularized sampling is not. Numerical simulations have been performed for several different scatterer geometries and varying levels of noise in the forward data in order to quantity image quality as a function of SNR.
Genetically Engineered Pig Models for Human Diseases (2013)

Although pigs are used widely as models of human disease, their utility as models has been enhanced by genetic engineering. Initially, transgenes were added randomly to the genome, but with the application of homologous recombination, zinc finger nucleases, and transcription activator-like effector nuclease (TALEN) technologies, now most any genetic change that can be envisioned can be completed. To date these genetic modifications have resulted in animals that have the potential to provide new insights into human diseases for which a good animal model did not exist previously. These new animal models should provide the preclinical data for treatments that are developed for diseases such as Alzheimer's disease, cystic fibrosis, retinitis pigmentosa, spinal muscular atrophy, diabetes, and organ failure. These new models will help to uncover aspects and treatments of these diseases that were otherwise unattainable. The focus of this review is to describe genetically engineered pigs that have resulted in models of human diseases.
Tethering soluble meprin α in an enzyme complex to the cell surface affects IBD‐associated genes (2019)

Biologic activity of proteases is mainly characterized by the substrate specificity, tissue distribution, and cellular localization. The human metalloproteases meprin α and meprin β share 41% sequence identity and exhibit a similar cleavage specificity with a preference for negatively charged amino acids. However, shedding of meprin α by furin on the secretory pathway makes it a secreted enzyme in comparison with the membrane-bound meprin β. In this study, we identified human meprin α and meprin β as forming covalently linked membrane-tethered heterodimers in the early endoplasmic reticulum, thereby preventing furin-mediated secretion of meprin α. Within this newly formed enzyme complex, meprin α was able to be activated on the cell surface and detected by cleavage of a novel specific fluorogenic peptide substrate. However, the known meprin β substrates amyloid precursor protein and CD99 were not shed by membrane-tethered meprin α. On the other hand, being linked to meprin α, activation of or substrate cleavage by meprin β on the cell surface was not altered. Interestingly, proteolytic activity of both proteases was increased in the heteromeric complex, indicating an increased proteolytic potential at the plasma membrane. Because meprins are susceptibility genes for inflammatory bowel disease (IBD), and to investigate the physiologic impact of the enzyme complex, we performed transcriptome analyses of intestinal mucosa from meprin-knockout mice. Comparison of the transcriptional gene analysis data with gene analyses of IBD patients revealed that different gene subsets were dysregulated if meprin α was expressed alone or in the enzyme complex, demonstrating the physiologic and pathophysiological relevance of the meprin heterodimer formation.-Peters, F., Scharfenberg, F., Colmorgen, C., Armbrust, F., Wichert, R., Arnold, P., Potempa, B., Potempa, J., Pietrzik, C. U., Häsler, R., Rosenstiel, P., Becker-Pauly, C. Tethering soluble meprin α in an enzyme complex to the cell surface affects IBD-associated genes.
Dye-doped dual-frequency nematic cells as fast-switching polarization-independent shutters (2019)

We present polarization-independent optical shutters with a sub-millisecond switching time. The approach utilizes dual-frequency nematics doped with a dichroic dye. Two nematic cells with orthogonal alignment are driven simultaneously by a low-frequency or high-frequency electric field to switch the shutter either into a transparent or a light-absorbing state. The switching speed is accelerated via special short pulses of high amplitude voltage. The approach can be used in a variety of electro-optical devices.
Pole-zero approximations for head-related transfer functions using a logarithmic error criterion (1997)

Pole-zero approximations of human free-field-to-eardrum transfer functions-i.e., head-related transfer functions (HRTFs)-can be used to synthesize binaural acoustic fields over headphones with fewer parameters, and therefore, lower computational complexity than is typically achieved by all-zero approximations. While standard pole-zero designs minimize the squared difference between the desired and designed frequency responses, the synthesis of binaural acoustic fields is more likely to be sensitive to relative, rather than absolute, differences in the HRTF approximations. The paper proposes a new design algorithm that minimizes an error criterion based on complex logarithms. As a result, both log-magnitude and phase errors are minimized. Slight modifications to the proposed algorithm result in one for which the phase error can be ignored. A comparison of this modified algorithm to others that have been developed to minimize the log-magnitude error shows implementation advantages without sacrificing performance. In achieving comparable errors, application of the proposed algorithm to the HRTF approximation results in pole-zero model orders smaller than those required for approximating the HRTFs using a least-squares error criterion.
Radioimmunoassay of SP1(Pregnancy-specificβ1-glycoprotein) in maternal blood and in amniotic fluid in normal and pathologic pregnancies (1981)

Sp1, the pregnancy-specific beta 1-glycoprotein, was studied in normal and pathologic pregnancies. We developed a highly specific and sensitive double-antibody-radioimmunoassay by radioiodination of purified placental SP1. This RIA allowed the estimation of SP1 concentrations as low as 2 ng/ml. In a collective of 227 women with normal pregnancies we established the normal distribution curve in maternal plasma from the fifth week of gestation to term. The median value rose steadily from 3 microgram/ml in the 8th week to 140 microgram/ml in the 36th week when a plateau was formed. In more than 400 patients with pregnancies complicated by a variety of pathologic disorders the SP1 levels were controlled by either single assays or serial estimations throughout pregnancy and were compared with the normal distribution range. SP1 was also determined in about 200 samples of amniotic fluid gained by amniocentesis and during parturition of normal pregnant women from the 13th gestational week until term. The normal range was established up to the 20th w.o.p. The concentrations rose from below 0.2 microgram/ml in early pregnancy to 3 microgram/ml and generally amounted to approximately 1% of the respective serum value. Pathologic cases with diverse chromosomal anomalies, Rh-incompatibility, anencephaly, hydramnios and other abnormal conditions were examined. From these only twin-pregnancies with slightly elevated levels and cases with fetal trisomies with reduced SP1 concentrations showed aberrations from the normal distribution. The estimation of serum concentrations in mothers with diabetes or Rh-incompatibility were not significantly different from the normal collective. In diabetes a characteristic course of the follow-up curves was observed. Abortion in early pregnancy was frequently but not always indicated by reduced SP1 values. Threatened abortion with subsequent continuation of pregnancy exhibited SP1 values scattered within the normal range. Since the radioimmunological determination of SP1 is possible in the early stage of gestation (from week 8) it may serve as a useful tool for prediction at times when the determination of placental lactogen is not yet possible. In pregnancies with "small-for-date babies" the correlation between SP1 in maternal plasma and fetal growth retardation was reflected in a pronounced tendency to low SP1 levels. Serial determinations of SP1 in the serum of women with EPH-gestosis were compared with the corresponding HPL determinations and showed the equality of SP1 concerning the assessment of the placental function.
Structure-based Design Technology CONTOUR and its Application to Drug Discovery (2012)

Structure-based design has had a significant impact on the drug discovery process over the past two decades by identifying novel and efficacious molecules for a variety of therapeutic targets. Among the approaches used for structure-based drug design, the de novo design approach has a great potential to generate novel molecules that best complement a protein binding site, but had failed to meet expectations in its initial attempts. More recently this approach has met with success due to algorithmic developments in the methodologies. In this chapter we introduce a state-of-the-art de novo design technology called CONTOUR®, provide details of the algorithmic enhancements we have implemented and show improvements in performance over past methods. CONTOUR was developed to grow novel drug like molecules by assembling fragments in the context of the binding site using a high resolution crystal structure of a protein as a starting point. The technology comprises a sophisticated growth algorithm that works in concert with an effective scoring function. The growth algorithm creates molecules in a context sensitive manner by assembling fragments that are dynamically selected from a fragment library and screened to optimally complement features of a given binding site. The scoring function was developed to capture essential elements of the binding interactions and to rank order grown molecules with a high probability of exhibiting activity against a protein target of interest. The application of CONTOUR to identify inhibitors against human 11β HSD1 enzyme will be discussed here.
Development of neural modules based on Si/PLZT technology for opto-electronic implementations of neural networks (1992)

The objective of the research program was to design opto-electronic neuron modules communicating via free-space optical interconnects, and to develop Si/PLZT opto-electronic integrated circuit technology in order to implement these designs. First, device and system requirements for artificial neural networks were studied. Minimum performance requirements for artificial neural networks implementations were extracted. Next, two opto-electronic neural network architectures were developed. The first achieves reconfigurable optical interconnects using photorefractive crystals. This system was theoretically and experimentally investigated. The second reconfigurable weights based on Si/PLZT technology. A prototype of this system was successfully built and tested. The performance of both systems exceed the minimum requirements. The first year effort involved the design of the optoelectronic architectures, the further development of the Si/PLZT process, the development of optimal neural networks data-encoding methods, and analysis of the system performances. The remaining period entailed the experimental demonstration of the CMTM system, an the development, characterization, and application of the D-STOP prototype system.
Patterned Soft Underlayers for Perpendicular Media (2006)

Perpendicular recording may be the most viable, near future, replacement for the longitudinal core technology in ultrahigh-density magnetic disk storage. Central to this mode of recording is a soft underlayer (SUL) which facilitates flux flow between writer poles, and is responsible for an effective increase in recording field. However, there are controversies concerning the effectiveness and limitations of using soft underlayers; among which are readback noise and inadequate switching torque. Patterned SUL is proposed as a new and viable approach to SUL limitations in perpendicular media, with improved system performance. Numerical models have been developed using commercially available FEM and BEM software suites (ANSYS and Ampere) to demonstrate key advantages of patterned SUL in perpendicular media
A transformant ofAspergillus fumigatusdeficient in the antigenic cytotoxin ASPFI (1993)

The aspfI gene encoding a ribonucleotoxin, a putative virulence factor of Aspergillus fumigatus, was inactivated by gene disruption. Gene replacement through homologous recombination by the disrupted allele tagged by the hygromycin B resistance marker was performed by transformation of a pathogenic strain. One transformant with the disrupted aspfI gene failed to produce the ASPFI protein and was shown to be pathogenic for mice. We concluded that this ribotoxin is not a main factor in the colonization of the lung tissues by A. fumigatus.
Latent semantic modeling for slot filling in conversational understanding (2013)

In this paper, we propose a new framework for semantic template filling in a conversational understanding (CU) system. Our method decomposes the task into two steps: latent n-gram clustering using a semi-supervised latent Dirichlet allocation (LDA) and sequence tagging for learning semantic structures in a CU system. Latent semantic modeling has been investigated to improve many natural language processing tasks such as syntactic parsing or topic tracking. However, due to several complexity problems caused by issues involving utterance length or dialog corpus size, it has not been analyzed directly for semantic parsing tasks. In this paper, we propose extending the LDA by introducing prior knowledge we obtain from semantic knowledge bases. Then, the topic posteriors obtained from the new LDA model are used as additional constraints to a sequence learning model for the semantic template filling task. The experimental results show significant performance gains on semantic slot filling models when features from latent semantic models are used in a conditional random field (CRF).
Translational control of hypoxia sensitive genes by nucleolin (2007)

The first striking cellular response to hypoxia is the suppression of energy consuming processes, such as translation, protein degradation and transcription. Even though the metabolic rate is suppressed, several genes show an increased expression rate against the overall trend. In general, the alteration of gene expression can be modulated at transcriptional or posttranscriptional level. The latter involves alteration in mRNA‐stability, translational efficiency or mRNA‐localization. mRNA translation is a highly controlled process which is sensitive to a variety of cellular stressors. Here we introduce the collagen prolyl 4‐hydroxylase alpha (I) (P4HA1) and MMP‐9 as hypoxia sensitive genes, regulated by modulation of translational efficiency. In both cases the initial step in translational control is the increased binding of the RNA‐binding protein nucleolin (~64 kDa form) at the 5′‐ and/or 3′ untranslated regions (UTR) of the mRNAs. The increased level of ~64 kDa nucleolin under hypoxia can be attributed to an autocatalytic cleavage of a high molecular weight form, without alterations in nucleolin mRNA‐concentration. Thus, the alteration of translational efficiency by nucleolin, which occurs through a hypoxia inducible factor (HIF) independent pathway, is an important step in C‐P4H‐alpha (I) and MMP‐9 regulation and highlights the role of translational control under hypometabolic conditions.
Mechanistic investigations reveal that dibromobimane extrudes sulfur from biological sulfhydryl sources other than hydrogen sulfide (2014)

Hydrogen sulfide (H<sub>2</sub>S) has emerged as an important biological signaling molecule in the last decade. During the growth of this field, significant controversy has arisen centered on the physiological concentrations of H<sub>2</sub>S. Recently, a monobromobimane (mBB) method has been developed for the quantification of different biologically-relevant sulfide pools. Based on the prevalence of the mBB method for sulfide quantification, we expand on this method to report the use of dibromobimane (dBB) for sulfide quantification. Reaction of H<sub>2</sub>S with dBB results in formation of highly-fluorescent bimane thioether (BTE), which is readily quantifiable by HPLC. Additionally, the reaction of sulfide with dBB to form BTE is significantly faster than the reaction of sulfide with mBB to form sulfide dibimane. Using the dBB method, BTE levels as low as 0.6 pM can be detected. Upon use of the dBB method in wild-type and CSE<sup>-/-</sup> mice, however, dBB reports significantly higher sulfide levels than those measured using mBB. Further investigation revealed that dBB is able to extract sulfur from other sulfhydryl sources including thiols. Based on mechanistic studies, we demonstrate that dBB extracts sulfur from thiols with α- or β-hydrogens, thus leading to higher BTE formation than from sulfide alone. Taken together, the dBB method is a highly sensitive method for H<sub>2</sub>S but is not compatible for use in studies in which other thiols are present.
Style Control for Schema-Guided Natural Language Generation (2021)

Alicia Tsai, Shereen Oraby, Vittorio Perera, Jiun-Yu Kao, Yuheng Du, Anjali Narayan-Chen, Tagyoung Chung, Dilek Hakkani-Tur. Proceedings of the 3rd Workshop on Natural Language Processing for Conversational AI. 2021.
Evaluation of standard and semantically-augmented distance metrics for neurology patients (2020)

Although semantic augmentation reduced inter-patient distances, we did not find improved classification accuracy or improved cluster quality with semantically augmented patient distance metrics when applied to a dataset of neurology patients. Further work is needed to assess the utility of semantically augmented patient distances.
Drug Penetration into the Central Nervous System: Pharmacokinetic Concepts and In Vitro Model Systems (2021)

Delivery of most drugs into the central nervous system (CNS) is restricted by the blood-brain barrier (BBB), which remains a significant bottleneck for development of novel CNS-targeted therapeutics or molecular tracers for neuroimaging. Consistent failure to reliably predict drug efficiency based on single measures for the rate or extent of brain penetration has led to the emergence of a more holistic framework that integrates data from various in vivo, in situ and in vitro assays to obtain a comprehensive description of drug delivery to and distribution within the brain. Coupled with ongoing development of suitable in vitro BBB models, this integrated approach promises to reduce the incidence of costly late-stage failures in CNS drug development, and could help to overcome some of the technical, economic and ethical issues associated with in vivo studies in animal models. Here, we provide an overview of BBB structure and function in vivo, and a summary of the pharmacokinetic parameters that can be used to determine and predict the rate and extent of drug penetration into the brain. We also review different in vitro models with regard to their inherent shortcomings and potential usefulness for development of fast-acting drugs or neurotracers labeled with short-lived radionuclides. In this regard, a special focus has been set on those systems that are sufficiently well established to be used in laboratories without significant bioengineering expertise.
LOCATING SYSTEMS FOR HORIZONTAL DIRECTIONAL DRILLING (1998)

This paper describes the challenges of locating underground cables and the evolution of cable locating techniques for the task of locating boring tool heads. It compares the signals emanating from cables and horizontal directional drilling tracking transmitters and the various receiving techniques employed. It provides maps of the magnetic signal fields produced by currents induced in cables and by dipole transmitters. It also compares two locating receiver designs and their differing locating algorithms. Finally, it provides theoretical accuracy limits for determining position and depth.