gebhart/patrepeval huggingface dataset:
Proteases act synergistically with low molecular weight inducers to stimulate mouse erythroleukemia cell differentiation. (1983)

Proteases stimulate mouse erythroleukemia (MEL) cell differentiation and multiplication. The stimulation of differentiation is synergistically increased by low concentrations of dimethyl sulfoxide. Synergism of other low molecular weight inducers with representative proteases, alpha-chymotrypsin and protease V8, was tested. Hemin. hypoxanthine, actinomycin D, aminonucleoside of puromycin, hexamethylene bisacetamide, and 5-azacytidine were also found to act synergistically with this protease to augment MEL cell hemoglobin production, but not cell multiplication. Fatty acids (acetate, propionate, butyrate, isobutyrate, and valerate), prostaglandins A1 and E1, amino acids, and amino acid analogs and metabolites did not act synergistically with chymotrypsin. Some physiologic amino acids were found to be weak inducers. Several of the low molecular weight inducers also acted synergistically with protease V8 in inducing differentiation, and, as with chymotrypsin, did not act synergistically in stimulating cell multiplication. Like chymotrypsin, protease V8 did not act synergistically with butyrate. The earlier finding that proteases, but not low molecular weight inducers, stimulate cell multiplication during the induction of differentiation was confirmed. Carboxypeptidase A also was found to be an inducer.
Elevated serum dipeptidyl peptidase IV (CD26, EC 3.4.14.5) activity in experimental liver cirrhosis (2000)

The significantly higher serum DPP IV activity found in experimental liver cirrhosis is in concordance with human observations. The elevation was probably not due to the enzyme induction effect of phenobarbital. In this experimental model, serum DPP IV seems to be an indicator for chronic liver injury.
On the Auditory Significance of the Term Hearing Loss (1940)

For a number of years hearing impairment has been expressed by the audiogram, which is a measure of the hearing loss for sounds which are just audible to the deafened ear, with the implication that impairment for threshold sounds indicates the impairment for sounds above threshold in the range of interest to the deafened. It is shown that the audiogram is not an accurate indication of hearing impairment for above threshold sounds in cases involving nerve deafness, when the loss in loudness sensation is taken as the criterion; but when the capacity to interpret speech sounds, as indicated by articulation tests, is the criterion, the audiogram does give an approximately correct indication of the hearing impairment. The relation of the audiogram to experiences in interpreting the speech of everyday life and the relation of hearing loss to absolute ear sensitivity are given.
Motion artefact correction for capacitive ECG measurement (2009)

Applications for capacitive ECG measurement that have been demonstrated range from clinical applications like body surface potential mapping to monitoring devices for personal health care. One common drawback in all systems is the susceptibility to motion artefacts caused by relative movement between the capacitive electrodes and the patient. In this paper we describe the setup and experiments that were used to verify the model that simulates time domain behavior of a capacitive electrode. Finally, we show that artefact correction is possible for real world capacitive ECG signals using this model, even for motion artefacts that are within the ECG spectrum.
Actor-Critic Reinforcement Learning with Energy-Based Policies (2012)

We consider reinforcement learning in Markov decision processes with high dimensional state and action spaces. We parametrize policies using energy-based models (particularly restricted Boltzmann machines), and train them using policy gradient learning. Our approach builds upon Sallans and Hinton (2004), who parameterized value functions using energy-based models, trained using a non-linear variant of temporal-difference (TD) learning. Unfortunately, non-linear TD is known to diverge in theory and practice. We introduce the first sound and efficient algorithm for training energy-based policies, based on an actorcritic architecture. Our algorithm is computationally efficient, converges close to a local optimum, and outperforms Sallans and Hinton (2004) in several high dimensional domains. 1.
Epigenetic balance of gene expression by Polycomb and COMPASS families (2016)

Epigenetic regulation of gene expression in metazoans is central for establishing cellular diversity, and its deregulation can result in pathological conditions. Although transcription factors are essential for implementing gene expression programs, they do not function in isolation and require the recruitment of various chromatin-modifying and -remodeling machineries. A classic example of developmental chromatin regulation is the balanced activities of the Polycomb group (PcG) proteins within the PRC1 and PRC2 complexes, and the Trithorax group (TrxG) proteins within the COMPASS family, which are highly mutated in a large number of human diseases. In this review, we will discuss the latest findings regarding the properties of the PcG and COMPASS families and the insight they provide into the epigenetic control of transcription under physiological and pathological settings.
Hybrid Nanoparticles with Block Copolymer Shell Structures (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTHybrid Nanoparticles with Block Copolymer Shell StructuresKeith J. Watson, Jin Zhu, SonBinh T. Nguyen, and Chad A. MirkinView Author Information Department of Chemistry, Northwestern University 2145 Sheridan Road, Evanston, Illinois 60208 Cite this: J. Am. Chem. Soc. 1999, 121, 2, 462–463Publication Date (Web):December 29, 1998Publication History Received4 September 1998Published online29 December 1998Published inissue 1 January 1999https://pubs.acs.org/doi/10.1021/ja983173lhttps://doi.org/10.1021/ja983173lrapid-communicationACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views2837Altmetric-Citations248LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Copolymers,Metal nanoparticles,Nanoparticles,Polymer particles,Polymers Get e-Alerts
Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation (2009)

We show that endothelial cell (EC)-generated vascular guidance tunnels (ie, matrix spaces created during tube formation) serve as conduits for the recruitment and motility of pericytes along EC ablumenal surfaces to facilitate vessel maturation events, including vascular basement membrane matrix assembly and restriction of EC tube diameter. During quail development, pericyte recruitment along microvascular tubes directly correlates with vascular basement membrane matrix deposition. Pericyte recruitment to EC tubes leads to specific induction of fibronectin and nidogen-1 (ie, matrix-bridging proteins that link together basement membrane components) as well as perlecan and laminin isoforms. Coincident with these events, up-regulation of integrins, alpha(5)beta(1), alpha(3)beta(1), alpha(6)beta(1), and alpha(1)beta(1), which bind fibronectin, nidogens, laminin isoforms, and collagen type IV, occurs in EC-pericyte cocultures, but not EC-only cultures. Integrin-blocking antibodies to these receptors, disruption of fibronectin matrix assembly, and small interfering RNA suppression of pericyte tissue inhibitor of metalloproteinase (TIMP)-3 (a known regulator of vascular tube stabilization) all lead to decreased EC basement membrane, resulting in increased vessel lumen diameter, a key indicator of dysfunctional EC-pericyte interactions. Thus, pericyte recruitment to EC-lined tubes during vasculogenesis is a stimulatory event controlling vascular basement membrane matrix assembly, a fundamental maturation step regulating the transition from vascular morphogenesis to stabilization.
Multi-quantum-well electroabsorption modulators (2002)

Electroabsorption modulators (EAMs) based on the quantum confined Stark effect have advantages in applications that require high speed, low drive voltage, and high extinction ratio. They are promising devices for external signal modulation in high-bandwidth optical communication systems. EAMs can be integrated with other devices like laser diodes, semiconductor optical amplifiers, and mode transformers. We have previously fabricated InGaAsP/InP multi-quantum well EAMs with a bandwidth of 25 GHz and a drive voltage of 1.2 V and 20 dB extinction ratio. Further optimization of our devices requires a detailed analysis of internal physical processes and their interaction. In this paper, we employ a two-dimensional electro-optic device model to analyze our EAMs. The model self-consistently combines kp bandstructure and absorption calculations with a carrier drift-diffusion model and optical waveguiding. The required low polarization sensitivity of EAMs leads to strong valence band mixing so that usual effective mass models cannot be applied. Optical transmission characteristics are calculated which are in good agreement with measurements. Modulation efficiency and linearity are analyzed in detail. Optimum operation voltages are identified.
The application of EEG sleep for the differential diagnosis of affective disorders (1978)

On the basis of two EEG sleep criteria, REM latency and REM activity, the authors achieved 81% accuracy in distinguishing between 47 patients with primary depression and 48 patients with secondary depression using discriminant analysis. Sleep efficiency, the percentage of delta sleep, and the percentage of REM sleep discriminated between psychotic and nonpsychotic subgroups in the group with primary depression with 75% accuracy. REM activity and intermittent nocturnal awakening accurately discriminated two subtypes of patients with secondary depression at a level of 81%. These results suggest that EEG sleep measurements can yield significant data to aid in differential diagnosis in psychiatry.
Dynamic mutations: a decade of unstable expanded repeats in human genetic disease (2001)

The term 'dynamic mutation' was introduced to distinguish the unique properties of expanding, unstable DNA repeat sequences from other forms of mutation. The past decade has seen dynamic mutations uncovered as the molecular basis for a growing number of human genetic diseases and for all of the characterized 'rare' chromosomal fragile sites. The common properties of the repeats in different diseases and fragile sites have given insight into this unique form of DNA instability. While the dynamic mutation mechanism explains some unusual genetic characteristics, unexpected findings have raised new questions and challenged some assumptions about the pathways that lead from mutation to disease. This review will address the current understanding of the molecular mechanisms involved in the dynamic mutation process and elaborate on the pathogenic pathways that lead from expanded repeats to the diseases with which they are associated.
Electronic Prognostics Through Advanced Modeling Techniques (2007)

Electronic prognostics is a growing field important to both military and commercial applications. When implemented, this capability will greatly enhance the maintenance management of platforms. Electronic prognostics require extensive use of physics of failure models to predict the remaining useful life of complex electronic failure modes.
An introduction to enzyme kinetics (1974)

The purpose of this paper is to present a simple, intuitive, yet accurate introduction to some of the fundamental concepts of enzyme kinetics. The experimental definitions of competitive, uncompetitive, and noncompetitive inhibition will be given, and a simple mechanistic model will be presented for each case.
Medical image retrieval by spatial features (2003)

A content-based indexing technique is proposed. The image features used are derived from the relative spatial relationships among internal image entities. The similarity measurement is based on causality (probability) which indicates the degree of similarity between a user's query and images. The index structure contains a set of causality-based similarity trees with nodes connected to an information causal net. For a given (weighted) query, the initial set of similar images is identified via similarity trees and then refined through the information causal net. The method is introduced with an example using magnetic resonance chest images.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Somatic mutations of the epidermal growth factor receptor and non-small-cell lung cancer (2006)

Frequent overexpression of epidermal growth factor receptor (EGFR) in non-small-cell lung cancer (NSCLC) makes EGFR a new therapeutic target. Two specific EGFR tyrosine kinase inhibitors, gefitinib (ZD1839, Iressa) and erlotinib (OSI-774, Tarceva), have been developed and approved by the US Food and Drug Administration for second-line and third-line treatment of advanced NSCLC. Clinical trials have shown considerable variability in the response rate between different patients with NSCLC, which led to the discovery of somatic EGFR-activating mutations. This brief review summarises the discovery and functional consequences of the mutations, their clinicopathological features and significant implications in the treatment and prognosis of NSCLC.
Geometric Hitting Set for Segments of Few Orientations (2016)

We study several natural instances of the geometric hitting set problem for input consisting of sets of line segments (and rays, lines) having a small number of distinct slopes. These problems model path monitoring (e.g., on road networks) using the fewest sensors (the "hitting points"). We give approximation algorithms for cases including (i) lines of 3 slopes in the plane, (ii) vertical lines and horizontal segments, (iii) pairs of horizontal/vertical segments. We give hardness and hardness of approximation results for these problems. We prove that the hitting set problem for vertical lines and horizontal rays is polynomially solvable.
The interleukin-8 receptor is encoded by a neutrophil-specific cDNA clone, F3R (1991)

Interleukin-8 (IL-8) is one of the most potent chemotactic agents for neutrophils and has been implicated as a major mediator of inflammation. The IL-8 receptor is expressed exclusively in neutrophils and belongs to the family of G-protein-coupled receptors. In a recent paper we reported the characterization of a cDNA clone, F3R, isolated from a neutrophil cDNA library and showed that it encodes a G-protein-coupled receptor which is exclusively expressed in neutrophils. We also suggested, based on expression studies in Xenopus oocytes, that the F3R protein product is an isoform of the (fMLP) receptor (Thomas, K. M., Pyun, H. Y., and Navarro, J. (1990) J. Biol. Chem. 265, 20061-20064). In this work, the F3R receptor cDNA is expressed in monkey kidney cells (COS-7) and is shown to encode the IL-8 receptor. F3R cDNA does not encode for a fMLP receptor isoform. We show conclusively that the F3R-transfected COS-7 cells express the IL-8 receptor at a density equivalent to that observed in neutrophils. The pharmacological profile of the F3R-transfected cells is the same as that of neutrophils. The apparent Kd values for binding of 125I-IL-8 to neutrophils and F3R-transfected COS-7 cell membranes were 1.2 and 1.4 nM, respectively. Antipeptide antibodies against a partial sequence of the F3R protein product specifically immunoprecipitate the IL-8 receptor from transfected cells as well as neutrophils. The molecular characterization of the IL-8 receptor should provide the basis for further studies on the identification of the binding domain of this inflammatory receptor.
Rapid Identification of Subtype-Selective Agonists of the Somatostatin Receptor Through Combinatorial Chemistry (1998)

Nonpeptide agonists of each of the five somatostatin receptors were identified in combinatorial libraries constructed on the basis of molecular modeling of known peptide agonists. In vitro experiments using these selective compounds demonstrated the role of the somatostatin subtype-2 receptor in inhibition of glucagon release from mouse pancreatic alpha cells and the somatostatin subtype-5 receptor as a mediator of insulin secretion from pancreatic beta cells. Both receptors regulated growth hormone release from the rat anterior pituitary gland. The availability of high-affinity, subtype-selective agonists for each of the somatostatin receptors provides a direct approach to defining their physiological functions.
Androgen receptor gene amplification: A novel molecular mechanism for endocrine therapy resistance in human prostate cancer (1996)

Since the development and growth of the prostate cancer is highly dependent on androgens, androgen deprivation therapy continues to be the treatment of choice for patients with advanced prostate cancer. The therapy is very effective, but responses are often short-lived. We describe here a novel molecular mechanism that may explain why prostate cancer cells become resistant to hormonal therapy. Amplification of the androgen receptor (AR) gene was found to be selected for during androgen deprivation therapy in 23% of prostate cancer patients who experienced local tumor recurrence. Amplification leads to increased expression of the AR gene, which enables the cancer cells to more effectively utilize the residual low levels of androgens for sustaining cell growth. Discovery of AR amplification as a possible molecular mechanism of therapy resistance in prostate cancer should prove useful for development of more effective endocrine therapy regimens as well as diagnostic and predictive tests for therapy failure.
Amino Acid Sequences within the α Subunit of Integrin αMβ2(Mac-1) Critical for Specific Recognition of C3bi (1999)

Phagocytosis of opsonized particles by neutrophils and monocytes plays a central role in host defense mechanisms against foreign pathogens. This process depends on the interaction between C3bi, a degradation product derived from activation of the complement system, and the alpha M beta 2 (CD11b/CD18, Mac-1) receptor, the major integrin on neutrophils. Previous studies had established a central role for the I domain, a stretch of approximately 200 amino acids within the alpha M subunit in the binding of C3bi, as well as many other alpha M beta 2 ligands. The present study was undertaken to establish the molecular basis of C3bi recognition by alpha M beta 2. The strategy employed the use of a series of mutant receptors in which short segments of the I domain of alpha M were switched to the corresponding segments of alpha L, which is structurally very similar but does not bind C3bi. We report three major findings: (1) The C3bi binding pocket is composed of three regions, P147-R152, P201-K217, and K245-R261 of alpha M, which surround the cation binding site within the MIDAS motif of the I domain. (2) Within the latter segment, K245 plays a critical role in mediating C3bi binding to alpha M beta 2. Mutation of K245 to Ala significantly reduced C3bi binding but had no effect on binding of another alpha M beta 2 I domain ligand, NIF. (3) Blocking of C3bi binding to alpha M beta 2 by monoclonal antibodies is achieved through two different mechanisms: direct competition for the ligand binding site or induction of conformational changes. Overall, these studies support the hypothesis that many of the ligands of alpha M beta 2 bind to overlapping but not identical sites within the I domain. Although the same short structural segments within the I domain may be involved in binding, different amino acids within these segments may contact different ligands.
In vitro bone marrow toxicity of nucleoside analogs against human immunodeficiency virus (1989)

3'-Azido-2',3'-dideoxythymidine is known to cause severe anemia and neutropenia. Although these are rare for 2',3'-dideoxycytidine, it frequently impairs thrombocytogenesis. These differential myelossuppressive features correlated well with the in vitro toxicities of the drugs for a megakaryoblastic cell line and for colony formation of erythroid and granulocytic cells.
Antitumor activity of the single-chain immunotoxin BR96 sFv-PE40 against established breast and lung tumor xenografts (1993)

We have constructed a single-chain immunotoxin consisting of the variable H and L chains of the carcinoma-reactive mAb BR96, fused to the binding defective protein toxin, PE40. This molecule, BR96 sFv-PE40, has been shown to be extremely cytotoxic toward a variety of BR96 Ag-expressing tumor cell lines. When administered i.v. into athymic mice carrying L2987 tumor xenografts, BR96 sFv-PE40 was cleared rapidly from the blood with a half-life of approximately 30 min. This is in comparison to a chemical conjugate, chiBR96-LysPE40, that remained in the blood for almost 2 h. In addition, the smaller single-chain immunotoxin (67 kDa) penetrates the tumor faster than the larger chemical conjugate (190 kDa). Using a variety of administration schedules and doses, we treated established human tumor xenografts in athymic mice with both the single-chain immunotoxin BR96 sFv-PE40 and the chemical conjugate chiBR96-LysPE40. In both L2987 lung carcinoma and MCF-7 breast carcinoma models, we found that BR96 sFv-PE40 completely regressed the tumor xenografts. With an administration schedule of q4dx5, the tumors were totally regressed and did not reappear. The chiBR96-LysPE40 conjugate produced partial tumor regressions, although at near maximum tolerated dose. These results show that the single-chain immunotoxin, BR96 sFv-PE40, is a potent antitumor agent.
Identification of structural determinants on tau protein essential for its pathological function: novel therapeutic target for tau immunotherapy in Alzheimer’s disease (2014)

We have discovered defined determinants on mis-disordered truncated tau protein which are responsible for tau oligomerisation leading to neurofibrillary degeneration. Antibody DC8E8 reactive with these determinants is able to inhibit tau-tau interaction in vitro and in vivo. DC8E8 is able to discriminate between the healthy and diseased tau proteome, making its epitopes suitable targets, and DC8E8 a suitable candidate molecule, for AD immunotherapy.