gebhart/patrepeval huggingface dataset:
Site-Directed Mutagenesis Combined with Chemical Modification as a Strategy for Altering the Specificity of the S1 and S1‘ Pockets of Subtilisin Bacillus lentus (1998)

By combining site-directed mutagenesis with chemical modification, we have altered the S1 and S1' pocket specificity of subtilisin Bacillus lentus (SBL) through the incorporation of unnatural amino acid moieties, in the following manner: WT --> Cysmutant + H3CSO2SR --> Cys-SR, where R may be infinitely variable. A paradigm between extent of activity changes and surface exposure of the modified residue has emerged. Modification of M222C, a buried residue in the S1' pocket of SBL, caused dramatic changes in kcat/KM, of an up to 122-fold decrease, while modification of S166C, which is located at the bottom of the S1 pocket and is partially surface exposed, effected more modest activity changes. Introduction of a positive charge at S166C does not alter kcat/KM, whereas the introduction of a negative charge results in lowered activity, possibly due to electrostatic interference with oxyanion stabilization. Activity is virtually unaltered upon modification of S156C, which is located toward the bottom of the S1 pocket and surface exposed and whose side chain is solvated. An unexpected structure-activity relationship was revealed for S166C-SR enzymes in that the pattern of activity changes observed with increasing steric size of R was not monotonic. Molecular modeling analysis was used to analyze this unprecedented structure-activity relationship and revealed that the position of the beta-carbon of Cys166 modulates binding of the P1 residue of the AAPF product inhibitor.
A database centric view of semantic image annotation and retrieval (2005)

We introduce a new model for semantic annotation and retrieval from image databases. The new model is based on a probabilistic formulation that poses annotation and retrieval as classification problems, and produces solutions that are optimal in the minimum probability of error sense. It is also database centric, by establishing a one-to-one mapping between semantic classes and the groups of database images that share the associated semantic labels. In this work we show that, under the database centric probabilistic model, optimal annotation and retrieval can be implemented with algorithms that are conceptually simple, computationally efficient, and do not require prior semantic segmentation of training images. Due to its simplicity, the annotation and retrieval architecture is also amenable to sophisticated parameter tuning, a property that is exploited to investigate the role of feature selection in the design of optimal annotation and retrieval systems. Finally, we demonstrate the benefits of simply establishing a one-to-one mapping between keywords and the states of the semantic classification problem over the more complex, and currently popular, joint modeling of keyword and visual feature distributions. The database centric probabilistic retrieval model is compared to existing semantic labeling and retrieval methods, and shown to achieve higher accuracy than the previously best published results, at a fraction of their computational cost.
Nucleotide Sequence Analysis of Rheumatoid Factors and Polyreactive Antibodies derived from Patients with Rheumatoid Arthritis Reveals Diverse Use of VH and VL Gene Segments and Extensive Variability in CDR‐3 (1992)

The heavy and light chain nucleotide sequences of 17 monoreactive and polyreactive rheumatoid factors largely derived from the inflamed synovial tissue of two patients with rheumatoid arthritis are described. Some of these sequences have been the subject of a previous report from our laboratories. Additionally, a few rheumatoid factors from the peripheral blood of patients with systemic lupus erythematosus and Sjogren's syndrome as well as a normal individual are included. A review of our previous results as well as the new data provided within this paper lead to the following major conclusions: (1) Rheumatoid factors and polyreactive antibodies derive from a diverse array of VH and VL gene segments; (2) While many rheumatoid factors and polyreactive antibodies are direct or nearly direct copies of germline genes, some show clear evidence of somatic mutation; (3) The CDR3 of all of these antibodies is extraordinarily diverse in length and composition. Certain 'restrictions' do appear in this very large sample: (a) the polyreactive antibodies are exclusively lambda, and (b) there seems to be a preponderance of a particular subset of VH3 genes beyond that one would expect based on random utilization.
The use of colonoscopy to follow the inflammatory time course of TNBS colitis in rats. (2011)

Our findings suggest that routine endoscopy is a reliable method for monitoring the development and follow-up of the degree of TNBS colitis in rats.
The use of peptide analogs with improved stability and MHC binding capacity to inhibit antigen presentation in vitro and in vivo. (1990)

The identification of a core region for OVA 323-339, which is critical in determining binding to IAd, has enabled us to generate a series of analog peptides in which this core region was extended at both the N and C termini with different amino acid residues. When assessed for binding capacity, several peptides were shown to have increased affinity for IAd compared with the parent sequence, and in addition, some peptides had acquired binding specificities for class II MHC haplotypes not present for OVA 323-339. These peptides were next examined for their ability to inhibit T cell responses in vitro and in vivo. The correlation between binding and the ability to inhibit T cell activation in vitro was good. However, when assessed in vivo, it was clear that high Ia binding was not sufficient in itself to define the inhibitory capacity of a given peptide. That this discrepancy was due to differences in degradation of the core-extended peptides was suggested by 1) results from an inhibition of Ag presentation assay, in which the pulse period with Ag and inhibitor was extended to 20 h; and 2) direct analysis of peptide stability by using reverse phase HPLC. Finally, by protecting the peptide from degradation with N- and C-terminal substitutions of D-amino acids, the inhibitory capacity of an unstable core-extended peptide in vitro could be greatly enhanced. These data indicate that the core extension approach may be one method by which antagonists for MHC class II molecules may be generated.
Importance of Hepatic Portal Circulation for Insulin Action in Streptozotocin-Diabetic Rats Transplanted with Fetal Pancreases (1979)

The importance of the hepatic portal circulation in the response to insulin was assessed in streptozotocin-diabetic rats transplanted with syngeneic fetal pancreases. Partial reversal of diabetes was accomplished by transplantation of two or three fetal pancreases beneath the capsule of the kidney; complete reversal followed shunting of the venous drainage from the transplants to the liver. Plasma glucose after streptozotocin of 509+/-31 mg/dl (mean+/-SEM) fell after transplantation to 395+/-23 and after the shunt to 143+/-5 mg/dl. Urine volume fell from 84+/-4 to 50+/-5 ml/d and then to normal (17+/-1 ml/d) after the shunt. Glucose excretion which was 8.1+/-0.3 g/d after streptozotocin fell after transplantation to 4.8+/-0.3 g/d and after the shunt completely disappeared from the urine. The disappearance rate of glucose injected into the circulation, which was 0.50+/-0.07%/min in untreated diabetes, increased to 1.39+/-0.38%/min after transplantation and to 2.52+/-0.31%/min after the shunt, not different from normal controls (2.79+/-0.25). Plasma immunoreactive insulin (IRI) was below normal (25-35 muU/ml) and unresponsive to glucose in untreated diabetic rats. After transplantation IRI levels ranged from 73-223 muU/ml and there was no rise after glucose injection. After the shunt both the basal IRI (36+/-5 muU/ml) and the peak response to glucose at 10 min (58+/-7 muU/ml) were the same as in normal controls (42+/-4 and 62+/-7 muU/ml, respectively). The fall in IRI after the shunt is explained by increased extraction of insulin passing into the liver and also diminished secretion. After removal of the transplants plasma glucose and urine values returned almost to pretransplant levels. Secretion of insulin by transplanted pancreases into the liver enhances the effectiveness probably by increased extraction and action and reveals the importance of the normal route for insulin delivery.
A Data-Driven Security Risk Assessment Scheme for Personal Data Protection (2018)

To protect collected personal data, current data protection laws and regulations usually request organizations that accumulate and use personal data to adopt reasonable security safeguards. In this case, risk assessment approaches enable organizations to specify security controls as appropriate risks to their personal data. This paper proposes a data-driven risk assessment approach for personal data protection. In the proposed approach, an organization can model flows of collected personal data using extended data flow diagrams. In addition to recognizing scenarios of personal data collection and usage, the organization can identify components used to process, store, and transmit data. Based on associated components for further risk evaluation, the organization can identify potential incidents to each personal data. Compared to a traditional asset-oriented risk assessment approach, the proposed method diminishes risks to assets associated with sensitive personal data. In addition, compared to a process-oriented risk assessment approach, our approach prevents organizations from overlooking risks to sensitive data that are not used in critical business processes. While the proposed approach can improve the risk assessment accuracy of personal data protection, the study may hopefully help organizations adopt more appropriate security safeguards to protect personal data.
Induction of insulin-like growth factor I messenger RNA in rat aorta after balloon denudation. (1990)

Insulin-like growth factor I (IGF-I) is a widely distributed mitogen that mediates the growth-promoting effects of platelet-derived growth factor in mesenchymal cells. We show that rat aortic IGF-I messenger RNA (mRNA) is induced 24 hours after deendothelialization, at a time when smooth muscle cell proliferation within the intima is still not apparent. After 7 days, IGF-I mRNA induction peaks at about ninefold control levels and then falls to about threefold 14 days after denudation when smooth muscle cell proliferation is at its peak. We also show that, of the 5' untranslated IGF-I mRNA transcripts, only the class C transcript is expressed and regulated in aortic tissue. In contrast, treatment of rats with supraphysiological doses of growth hormone, the major endocrine regulator of IGF-I gene expression, elicited only twofold induction of aortic IGF-I mRNA. Our findings suggest that IGF-I may be an important autocrine or paracrine regulator of smooth muscle cell proliferation and that it may be significant in determining the cellular response to arterial wall injury.
β 2‐Microglobulin and amyloidosis (2000)

Dialysis-associated amyloidosis is a serious complication in chronic dialysis patients. Its clinical expression in terms of arthralgias, destructive arthopathies and carpal tunnel syndrome is often associated with amyloid deposits, which are mainly composed of beta2-microglobulin (beta2-M) fibrils, but in addition contain a number of other compounds. It is probable that beta2-M-amyloid deposition is related, at least in part, to the elevated plasma beta2-M that is characteristic of chronic renal failure. The latter can decrease with high-performance dialysis techniques but cannot be reduced to the normal range. Almost certainly, several other systemic and local factors are involved, including beta2-M transformed by advanced glycation end products and advanced oxidation protein products, serum P component, ubiquitin, calcium crystals, cytokines, immunoglobulin light chains, proteases and antiproteases, as well as modified collagen and glucosaminoglycans. It is also possible that the beta2-M protein, in its native or modified form, exerts noxious effects on bone and joint tissues, in addition to its mere 'passive' presence as amyloid fibrils. Several retrospective studies and one prospective study suggest that dialysis strategies with highly permeable, synthetic membranes and/or ultrapure dialysate may be partially protective or at least delay the onset of dialysis amyloidosis. Successful kidney transplantation generally halts the disease process and leads to rapid relief of osteoarticular pain although regression of beta2-M-amyloid deposits probably does not occur.
raf oncogenes in carcinogenesis. (1990)

There are three active raf genes in man and at least two in Xenopus and Drosophila. The mammalian c- and A-raf genes have 16 coding exons, which span 40 and 20 kb, respectively. B-raf is larger and extends over greater than 46 kb. Human c-raf-1 maps to chromosome 3p25 and A-raf-1 to Xp21. c-raf-1 RNA is present in many tissues, while A-raf and B-raf expression is restricted. A- and c-raf encode cytoplasmic ser/thr protein kinases of 68 and 74 kDa, which contain three conserved regions (CR). CR1 and 2 are in the amino terminal half, CR1 comprises the presumed ligand binding site, and CR3 represents the carboxy terminal kinase domain. All three genes can be artificially activated by deletions, provided CR3 is preserved. However, only c-raf-1 occurs naturally in truncated versions, such as v-raf and v-mil in the acutely transforming retroviruses 3611-MSV and MH2. raf transformation can also be affected by point mutation, suggesting that this mechanism may activate c-raf-1 as an oncogene in carcinogenesis.
Fabrication of SiOC Ceramic Microparts and Patterned Structures from Polysiloxanes via Liquid Cast and Pyrolysis (2009)

SiOC ceramic microparts and patterned microstructures are fabricated from their metal masters using polysiloxanes as a precursor, which consists of polyhydromethylsiloxane (PHMS) and 1,3,5,7‐tetramethyl‐1,3,5,7‐tetravinylcyclotetrasiloxane (D 4 Vi), via mold transfer, liquid cast, crosslink, and pyrolysis. The mixed liquid of PHMS and D 4 V was cast with the polydimethylsiloxane (PDMS) negative molds transferred from the masters and solidified via hydrosilylation of PHMS and D 4 Vi under controlled heating. Because both the precursors and mold materials are polysiloxanes, their chemical similarities ensure the excellent contact between the two phases that allows for the precise duplication of the master microstructures into the polysiloxanes. Strategies were developed for the use of a two‐step controlled heating method and the use of polysiloxane as a support in the processes of demolding, crosslinking, and pyrolysis in order to ensure the bonding qualities of both the crosslinked bodies and the pyrolyzed microstructures. Through this route, we obtained dense and crack‐free SiOC ceramic microngears and arrayed holes of well‐duplicated microstructures with a resolution down to the submicrometers. Moreover, the polysiloxanes allow the direct imprints with the metal masters to form inversed microstructures of SiOC ceramics, as demonstrated by the formation of microchannels and various motifs of SiOC ceramics from their metal counterparts.
Ewing's Sarcoma–Like Tumors Originate from EWS-FLI-1-Expressing Mesenchymal Progenitor Cells (2006)

In Response: 

Our study was directed toward identifying a primary cell that is permissive for EWS-FLI-1-mediated transformation. Following the observation that EWS-FLI-1 transforms primary mouse mesenchymal progenitor cells (MPC) to form Ewing's sarcoma–like tumors ( [1][1]), we tested these
Effect of first-order PMD compensation on the statistics of pulse broadening in a fiber with randomly varying birefringence (1999)

Polarization mode dispersion in standard telecommunication fibers can be compensated to first order by using the concept of principal states of polarization. At the receiver the pulse is decomposed into the two waveforms polarized along the two principal states for the optical link and their delay is removed. We show by Monte Carlo simulation that compensation sharpens the probability distribution function of the pulse durations by a factor that decreases with increasing polarization dispersion.
Semi-Supervised Video Segmentation Using Tree Structured Graphical Models (2013)

We present a novel patch-based probabilistic graphical model for semi-supervised video segmentation. At the heart of our model is a temporal tree structure that links patches in adjacent frames through the video sequence. This permits exact inference of pixel labels without resorting to traditional short time window-based video processing or instantaneous decision making. The input to our algorithm is labeled key frame(s) of a video sequence and the output is pixel-wise labels along with their confidences. We propose an efficient inference scheme that performs exact inference over the temporal tree, and optionally a per frame label smoothing step using loopy BP, to estimate pixel-wise labels and their posteriors. These posteriors are used to learn pixel unaries by training a Random Decision Forest in a semi-supervised manner. These unaries are used in a second iteration of label inference to improve the segmentation quality. We demonstrate the efficacy of our proposed algorithm using several qualitative and quantitative tests on both foreground/background and multiclass video segmentation problems using publicly available and our own datasets.
Inhibition of rhinovirus attachment by neutralizing monoclonal antibodies and their Fab fragments (1989)

Previous molecular and immunological studies have mapped four neutralization sites on human rhinovirus type 14 (B. Sherry, A. G. Mosser, R. J. Colonno, and R. R. Rueckert, J. Virol. 57:246-257, 1986). Eight monoclonal antibodies, one pair for each of the four target sites and all belonging to a single isotype, immunoglobulin G2a, were studied under conditions which resulted in 95% neutralization of infectious viral particles. All eight antibodies shifted the isoelectric point of virions from 6.7 to much more acidic forms, ranging from pI 1.8 to 3.2. In addition, antibodies targeted against three of the four neutralization sites caused significant aggregation of virions under the neutralization conditions employed. Aggregation could be reversed by digesting virus-antibody complexes with papain. Following papain digestion, the acidic pIs of three of the neutralized virus preparations returned to neutral and infectivity was restored. Membrane-binding assays with virus neutralized with a nonaggregating antibody showed a dose-related inhibition of virus attachment to cellular receptors. Purified Fab fragments at a 13- to 61-fold-higher concentration than intact antibodies caused a comparable isoelectric shift, neutralized virions in the absence of aggregation, and interfered with attachment of virions to host cell receptors in a membrane-binding assay. These findings suggest that neutralizing antibodies interfere with the attachment of rhinoviruses to cellular receptors and that bivalent attachment of antibody is not a prerequisite for neutralization.
Efficient Gene Transfer in Primitive CD34 + /CD38 lo Human Bone Marrow Cells Reselected after Long-Term Exposure to GALV-Pseudotyped Retroviral Vector (1997)

Successful retroviral gene transfer into human hematopoietic stem cells was demonstrated in preliminary clinical trials at low efficiency. We have shown previously that gene transfer into committed hematopoietic progenitor cells is more efficient using a gibbon ape leukemia virus (GALV)-pseudotyped retroviral vector instead of an amphotropic retroviral vector. Here, we have conducted a systematic study of human hematopoietic progenitor cells after extended transduction with a GALV-pseudotyped retroviral vector. CD34+/CD38lo Cells were transduced for 5 days and reselected according to phenotype after culture and analyzed for cell cycle status, long-term culture-initiating cell (LTC-IC) activity, and gene transfer. Reselection of rare, very primitive progenitor cells was successful. Equal to fresh CD34+/CD38lo cells, >90% of reselected CD34+/CD38locells were in G0/G1. CD34+/CD38lo reselection enriched for LTC-IC (10-fold), as compared to freshly isolated CD34+/CD38lo cells with excellent specificity (82.7% of total LTC-IC were recovered in the reselected CD34+/CD38lo population) and recovery (62% of initial LTC-IC number in CD34+/CD38lo cells were recovered in the reselected fraction after transduction). Gene transfer into primitive progenitor cells was efficient with 50.5% G418-resistant LTC-IC colonies and more than 40 copies of vector provirus detectable per 100 nuclei of CD34+/CD38lo cells. To our knowledge, this is the first systematic analysis of phenotype, function, and cell cycle demonstrating retroviral gene transfer into rare, very primitive human hematopoietic progenitor cells. The chosen strategy should be of considerable value for analyzing and improving gene therapy of the hematopoietic system. We have performed a systematic study of retroviral gene transfer in primitive human hematopoietic progenitor cells by analyzing the phenotype, function, cell cycle status, and retrovirus transduction after culture. Following extended exposure of CD34+/CD38lo marrow cells to gibbon ape leukemia virus (GALV)-pseudotyped retroviral vector, cells were efficiently reisolated that had characteristics of very primitive progenitor cells, including a CD34+/CD38lo phenotype, a very high content of long-term culture-initiating cells, and a low mitotic activity. In this population, functional and molecular analysis indicate a transduction efficiency of more than 40%. The presented strategy demonstrates the feasibility of efficiently transducing, isolating, and characterizing very primitive hematopoietic progenitor cells and should have interesting implications for hematopoietic gene therapy.
WHERE MIGHT ENHANCED OIL RECOVERY (EOR) METHODS BE SUCCESSFUL IN OHIO IN THE FUTURE (1996)

ABSTRACT The recent Ohio TORIS study indicated that some five billion barrels of crude oil remain in oil reservoirs in the Appalachian Basin portion of Ohio. Economically successful Ohio enhanced oil recovery (EOR) projects have been very limited when compared to activity in other states and few operators and technical personnel in the State have developed working experiences with EOR applications. It is the object of this paper to provide some general ideas and guidelines for oil and gas personnel in Ohio that might be the basis to further consider specific reservoirs in which economically successful EOR projects could be implemented. Waterflooding is the most economical and likely process for consideration at this time due to the lack of other type of EOR success in Ohio and the comparatively low price of crude oil. Therefore, this presentation will focus on water- flooding but many of the items discussed could be applicable to other EOR processes.
Neuromyelitis Optica (NMO) Antibody Positivity in Patients with Transverse Myelitis and No Visual Manifestations (2008)

The aquaporin protein autoimmune disease previously identified as neuromyelitis optica (NMO) may more correctly be identified as neuromyelitis (NM), and future diagnostic criteria should take into account the population of patients with antibody to aquaporin 4 protein, without clinically evident optic nerve pathology. Future research may indicate that the entity of NMO is a subcategory of the NM population.