gebhart/patrepeval huggingface dataset:
Chronic Treatment with the γ-Secretase Inhibitor LY-411,575 Inhibits β-Amyloid Peptide Production and Alters Lymphopoiesis and Intestinal Cell Differentiation (2004)

Inhibition of gamma-secretase, one of the enzymes responsible for the cleavage of the amyloid precursor protein (APP) to produce the pathogenic beta-amyloid (Abeta) peptides, is an attractive approach to the treatment of Alzheimer disease. In addition to APP, however, several other gamma-secretase substrates have been identified (e.g. Notch), and altered processing of these substrates by gamma-secretase inhibitors could lead to unintended biological consequences. To study the in vivo consequences of gamma-secretase inhibition, the gamma-secretase inhibitor LY-411,575 was administered to C57BL/6 and TgCRND8 APP transgenic mice for 15 days. Although most tissues were unaffected, doses of LY-411,575 that inhibited Abeta production had marked effects on lymphocyte development and on the intestine. LY-411,575 decreased overall thymic cellularity and impaired intrathymic differentiation at the CD4(-)CD8(-)CD44(+)CD25(+) precursor stage. No effects on peripheral T cell populations were noted following LY-411,575 treatment, but evidence for the altered maturation of peripheral B cells was observed. In the intestine, LY-411,575 treatment increased goblet cell number and drastically altered tissue morphology. These effects of LY-411,575 were not seen in mice that were administered LY-D, a diastereoisomer of LY-411,575, which is a very weak gamma-secretase inhibitor. These studies show that inhibition of gamma-secretase has the expected benefit of reducing Abeta in a murine model of Alzheimer disease but has potentially undesirable biological effects as well, most likely because of the inhibition of Notch processing.
Hepcidin is decreased in TFR2 hemochromatosis (2004)

The hepatic peptide hepcidin is the key regulator of iron metabolism in mammals. Recent evidence indicates that certain forms of hereditary hemochromatosis are caused by hepcidin deficiency. Juvenile hemochromatosis is associated with hepcidin or hemojuvelin mutations, and these patients have low or absent urinary hepcidin. Patients with C282Y HFE hemochromatosis also have inappropriately low hepcidin levels for the degree of iron loading. The relationship between the hemochromatosis due to transferrin receptor 2 (TFR2) mutations and hepcidin was unknown. We measured urinary hepcidin levels in 10 patients homozygous for TFR2 mutations, all with increased transferrin saturation. Urinary hepcidin was low or undetectable in 8 of 10 cases irrespective of the previous phlebotomy treatments. The only 2 cases with normal hepcidin values had concomitant inflammatory conditions. Our data indicate that TFR2 is a modulator of hepcidin production in response to iron.
Neurobehaviorally Inspired ACT-R Model of Sleep Deprivation: Decreased Performance in Psychomotor Vigilance (2006)

This paper describes how changes in architectural parameters in ACT-R can be used to understand and predict the effects of sleep deprivation on a fundamental aspect of human performance.In a sample task, the parameter manipulations produce changes in the model's performance that closely resemble the neurobehavioral effects seen in human data.The parameter that is manipulated (G) influences a mechanism in ACT-R that is considered to be associated with the thalamus, an area that is sensitive to sleep deprivation.
Computational analysis of deep brain stimulation (2007)

Chronic, high-frequency electrical stimulation of subcortical brain structures (deep brain stimulation [DBS]) is an effective clinical treatment for several medically refractory neurological disorders. However, the clinical successes of DBS are tempered by the limited understanding of the response of neurons to applied electric fields and scientific definition of the therapeutic mechanisms of DBS remains elusive. In addition, it is presently unclear which electrode designs and stimulation parameters are optimal for maximum therapeutic benefit and minimal side effects. Detailed computer modeling of DBS has recently emerged as a powerful technique to enhance our understanding of the effects of DBS and to create a virtual testing ground for new stimulation paradigms. This review summarizes the fundamentals of neurostimulation modeling and provides an overview of some of the scientific contributions of computer models to the field of DBS. We then provide a prospective view on the application of DBS-modeling tools to augment the clinical utility of DBS and to design the next generation of DBS technology.
Market Power in Electricity Markets: Beyond Concentration Measures (1999)

The wave of electricity market restructuring both within the United States and abroad has brought the issue of horizontal market power to the forefront of energy policy. Traditionally, estimation and prediction of market power has relied heavily on concentration measures. In this paper, we discuss the weaknesses of concentration measures as a viable measure of market power in the electricity industry, and we propose an alternative method based oil market simulations that take advantage of existing plant level data. We discuss results from previous studies the authors have performed, and present new results that allow for the detection of threshold demand levels where market power is likely to be a problem. In addition, we analyze the impact of that recent divestitures in the California electricity market will have on estimated market power. We close with a discussion of the policy implications of the results.
Histopathologic findings of transbronchial biopsy in usual interstitial pneumonia (2010)

The role of transbronchial biopsy in diagnosis of usual interstitial pneumonia (UIP) is controversial. In this study, we retrospectively reviewed transbronchial biopsy specimens according to the similar criteria of previous studies, and evaluated whether diagnostic findings of UIP could be found in transbronchial biopsies. Thirty two patients with usual interstitial pneumonia, confirmed by surgical lung biopsy, were identified. In three cases (9.4%), there were combinations of interstitial fibrosis and fibroblast foci, and these findings were considered consistent with usual interstitial pneumonia. No patchwork fibrosis or honeycomb change was found. Diagnostic findings of usual interstitial pneumonia were not frequently manifested in transbronchial biopsy specimens in our study (3 out of 32 cases, 9.4%), compared with a previous report (9 out of 22 cases, 41%). In conclusion, it cannot be claimed that transbronchial biopsy is more useful in confirming usual interstitial pneumonia than previously recognized. The primary and main role of transbronchial biopsy in diagnosis of usual interstitial pneumonia is thought not to confirm a diagnosis, but to exclude other infiltrative diseases, such as malignancy, sarcoidosis or infections.
Solving the I/O Bandwidth Problem in System on a Chip Testing (2000)

The first part of this paper describes the control of CAS-BUS, a P1500 compatible Test Access Mechanism (TAM). Boundary scan features are used to allow controlling of the TAM and the P1500 wrappers. The final architecture characteristics are its flexibility, scalability and reconfigurability. It also allows trade-off to optimize test time and area overhead. The second part deals with a test pin expansion method in order to solve the bandwidth problem. The solution we propose is based on a new compression/decompression mechanism which avoid TAM performances degradation.
Combinatorics of The Vaccine Design Problem: Definition and An Algorithm (2007)

Abstract. Recently Nickle et al. introduced a new model of genetic diversity that summarizes a large input dataset into a short sequence containing overlapping subsequences from the dataset. This model has direct applications to rational vaccine design. In this paper we formally investigate the combinatorics of the vaccine optimization problem. Here the vaccine is constructed as a sequence S of amino-acids such that as many of the most frequently occurring epitopes found in mutated viruses are subsequences to S. We rigorously present the related design optimization problem, establish its complexity, and present a simple probabilistic algorithm to find an efficient solution. Our vaccine designs show improvement of over 20 % in the coverage score over the previously best designs and produce over 15 % shorter vaccines that achieve equivalent epitope coverage. 1
Vitamin D Binding Protein (Gc-Globulin)* (1989)

UNLIKE other hydrophobic hormone-binding systems in mammalian plasma, the binding protein for vitamin D and its metabolites circulates in remarkably higher titer (5 × 10−6 M) compared to its major circulating ligand 25-hydroxycholecalciferol (25-OHD3) (5 × 10−8 M), and displays a rapid turnover rate (1) (see Table 1). Initially characterized as group-specific component or Gc-globulin, its identity with the plasma vitamin D binding protein (DBP) was discovered in 1975 (2). This hepatic protein has a strong homology with serum albumin (ALB) and α-fetoprotein (AFP) (3, 4). Although many thousands of sera have been tested, deletion or gross alteration of the DBP gene has not been detected, lending support to the notion that such mutations might be lethal. Since analbuminemia and abnormalities of other plasma binding proteins do not appear to cause disease (5–7), DBP activities are presumably vital. In recent years, new observations on the structure, origin, associations, and activities of DBP have been made. It is the purpose of this paper to review these findings and provide an update of recent developments in our understanding of this protein and its functions.
The role of urodynamics in the treatment of lower urinary tract symptoms in women (2005)

In order to use urodynamics as a proper clinical tool, defining subtypes of stress urinary incontinence and standardization of urodynamics in pelvic organ prolapse and bladder outlet obstruction in women is needed.
Homeotic gene Antennapedia mRNA contains 5'-noncoding sequences that confer translational initiation by internal ribosome binding. (1992)

The Antennapedia (Antp) homeotic gene of Drosophila melanogaster has two promoters, P1 and P2. The resulting Antp mRNAs contain 1512-nucleotide (P1) and 1727-nucleotide (P2) 5'-noncoding regions, composed of exons A, B, D, and E (P1) or exons C, D, and E (P2), respectively. Multiple AUG codons are present in exons A, B, and C. We have found that 252-nucleotide exon D, common to mRNAs from both transcription units and devoid of AUG codons, can mediate initiation of translation by internal ribosome binding in cultured cells. Many mRNAs in Drosophila contain long 5'-noncoding regions with apparently unused AUG codons, suggesting that internal ribosome binding may be a common mechanism of translational initiation, and possibly its regulation, in Drosophila.
Furin activates Pseudomonas exotoxin A by specific cleavage in vivo and in vitro. (1994)

We have demonstrated that the native proenzymatic form of Pseudomonas exotoxin A can be cleaved at its specific activation site by furin in intact Chinese hamster ovary cells or in vitro by furin in isolated membrane fractions from these cells. We have compared the activity of furin in cell membrane fractions with that of purified, recombinant human furin. We have verified that RPE.40, a Pseudomonas toxin-resistant mutant cell strain, is mutant in the fur gene, and we have demonstrated that these cells are deficient in cleavage of the toxin. We have also determined that this cleavage of Pseudomonas toxin by furin takes place at the authentic activation site to release the 37-kDa active fragment.
Role of adherence in pathogenesis of Enterococcus faecalis urinary tract infection and endocarditis (1989)

Enterococcus faecalis strains isolated from urinary tract infections (UTIs) and endocarditis were analyzed for their ability to adhere to urinary tract epithelial cells (ECs) and Girardi heart (GH) and human embryonic kidney (HEK) cell cultures. UTI isolates adhered to urinary tract ECs more efficiently than to the cultured cells, at the same time showing the least affinity for GH cells. In contrast, endocarditis isolates adhered to GH cell cultures more readily than to urinary tract ECs. Moreover, although strains isolated from endocarditis adhered to GH cells more efficiently than those derived from UTI, the latter strains adhered to urinary tract cells better than the former. Studies of the ability of GH and HEK cells to internalize E. faecalis showed that for UTI isolates, 9 to 74% of adhered bacteria were internalized, while for endocarditis isolates, the percentage varied from 76 to 82%. All strains were able to associate with human neutrophils; endocarditis strains, however, associated less efficiently than UTI isolates. Growth in serum raised the adherence of all tested strains by at least 1.5- to 3-fold, with the greatest increase being observed in UTI strain adherence to GH cells (8-fold). In contrast, the association of serum-grown cells with polymorphonuclear leukocytes was reduced by two- to fivefold. In both cases, the observed serum-dependent alterations were cancelled by a few subcultures in brain heart infusion broth. These results indicate that adhesive properties are important virulence factors in the pathogenesis of UTI and endocarditis and also suggest that UTI strains showing the highest invasion and adhesive potential invade the kidneys, cause bacteremia, and, after having expressed the serum-dependent surface modification, colonize the heart.
New allele frequency database: http://www.allelefrequencies.net (2003)

A new website (http://www.allelefrequencies.net) has been compiled to execute the frequency of alleles at various polymorphic regions of different populations in the field of histocompatibility and immunogenetics. Data for HLA alleles has been added but this will be extended to include frequency data of polymorphisms in other immunogenetic regions, e.g. cytokines, KIR receptors, MIC.
FEM analysis of predicting electrode-myocardium contact from RF cardiac catheter ablation system impedance (2002)

We used the finite-element method (FEM) to model and analyze the resistance between the catheter tip electrode and the dispersive electrode during radio-frequency cardiac catheter ablation for the prediction of myocardium-electrode contact. We included deformation of the myocardial surface to achieve accurate modeling. For perpendicular catheter contact, we measured the side view of myocardial deformation using X-ray projection imaging. We averaged the deformation contour from nine samples, and then incorporated the contour information into our FEM model. We measured the resistivity of the bovine myocardium using the four-electrode method, and then calculated the resistance change as the catheter penetrated into the myocardium. The FEM result of resistance versus catheter penetration depth matches well with our experimental data.
Chemoselective backbone cyclization of unprotected peptides (1997)

A fully unprotected 15 residue peptide containing an N-terminal Cys residue and a C-terminal thioester moiety is cleanly converted to the corresponding head-to-tail cyclic peptide in aqueous buffers at around neutral pH.
Effect of α,α-Dialkyl Amino Acids on the Protease Resistance of Peptides (2003)

A tryptic [EC 3.4.21.4] digestion assay of 2-aminoisobutyric acid (Aib)-containing peptides was carried out to investigate the effect of alpha,alpha-dialkyl amino acid residues on the protease resistance. The introduction of Aib residues to the P1' positions exhibited a 19-fold higher protease resistance than the peptide with Aib residues introduced to the P2 position or the non-Aib peptide. The peptide having Aib residues introduced to the P1' and P2 positions resulted in complete resistance.
Electrical stimulation: Complementary therapy to improve the performance of grafts in bone defects? (2018)

The limitations of bone reconstruction techniques have stimulated the tissue engineering for the repair of large bone defects using osteoconductive materials and osteoinductive agents. This study evaluated the effects of low intensity electric current on the inorganic bovine graft in calvaria defects. Bone defects were performed with piezoelectric system in the calvaria of Wistar rats divided into four groups (n = 24): (C) without grafting and without electrical stimulation; (E) with grafting; (MC) without grafting and submitted to electrical stimulation; (MC + E) with grafting and submitted to electrical stimulation. Inflammatory, angiogenic and osteogenic events during bone repair at the 10th, 30th, 60th, and 90th days were considered. Several inflammatory markers demonstrated the efficacy of grafting in reducing inflammation, particularly when subjected to electrical stimulation. Angiogenesis and collagen organization were more evident by electrical stimulation application on the grafts. Moreover, the osteogenic cell differentiation process indicated that the application of microcurrent on grafting modulated the homeostasis of bone remodeling. It is concluded that microcurrent favored the performance of grafts in calvarial rat model. Low-intensity electrical current might improve the osteoconductive property of grafting in bone defects. Therefore, electrical current becomes an option as complementary therapy in clinical trials involving bone surgeries and injuries. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 924-932, 2019.
Oxygen uptake and H2O2 production by fermentative Mycoplasma spp. (1991)

Summary Oxygen uptake and H2O2 accumulation during the metabolism of glucose and glycerol by whole cells, and of L-α-glycerophosphate (GP) and NADH by cells lysed with Triton, was determined for the type strains of six fermentative Mycoplasma species. Oxidation of glucose and of NADH by M. mycoides, M. pneumoniae and M. putrefaciens was accompanied by the accumulation of relatively small quantities of H2O2 (&lt;0.05 mol/mol O2), though larger quantities (0.17–0.24 mol/mol O2) were produced by M. dispar. M. fermentans and M. canis were distinguished from the other strains used in that O2 uptake in the presence of glucose could not be demonstrated. However, metabolism of glucose was indicated by a reduction in the pH of the suspending medium and lysed cells oxidised NADH with the production of approximately 1.0 mol H2O2/mol O2 taken up. Glycerol was oxidised by all the strains studied except M. fermentans, and large quantities of H2O2 (0.48–1.07 mol/mol O2) accumulated. Cells of the glycerol-oxidising strains, lysed with Triton, oxidised GP with the production of approximately 1.0 mol H2O2/mol O2 utilised, which indicated the presence of a GP oxidase. The importance of H2O2 production as a factor in the pathogenicity of some mycoplasmas might depend upon the availability of glycerol in vivo.
Polymyxin B octapeptide and polymyxin B heptapeptide are potent outer membrane permeability-increasing agents. (1992)

Polymyxin B octapeptide (PBOP) and polymyxin B heptapeptide (PBHP) were found to be effective permeabilizers of the outer membrane of Escherichia coli and Salmonella typhimurium. PBOP was as effective as polymyxin B nonapeptide (PMBN), the known very potent permeabilizer. As low a PBOP concentration as 1 microgram/ml sensitized E. coli to rifampicin by a factor of 100. Three micrograms of PBOP per ml was sufficient to sensitize this target to all the other tested hydrophobic antibiotics (erythromycin, fusidic acid, clindamycin, and novobiocin) by a factor of 30. Only a slightly higher (3-fold) concentration of PBHP was required for a similar sensitizing effect.
Molecular diagnosis of lymphoid malignancies by gene expression profiling (2002)

Gene expression profiling using DNA microarrays has great potential to improve the understanding, diagnosis, and management of lymphomas, leukemias, and other malignancies. Gene expression profiling studies of diffuse large B-cell lymphoma (DLBCL) have shown that this diagnostic category encompasses at least two molecularly distinct diseases, differing in differentiation stage (cell of origin), oncogenic mechanisms, and clinical outcome. Gene expression profiling revealed that the antiapoptotic NF-kappaB pathway is constitutively active in one DLBCL subgroup, termed activated B cell-like DLBCL, and subsequent studies validated NF-kappaB as a therapeutic target in this type of lymphoma. DNA microarray studies of chronic lymphocytic leukemia (CLL) have led to a gene expression-based predictor that identifies two subtypes of CLL that differ with respect to clinical course and presence of immunoglobulin gene mutations in the CLL cells. These findings underscore the value of gene expression profiling in defining subtypes within the lymphoid malignancies that are molecularly and clinically distinct and argue that this genomic technology should become an integral part of prospective clinical trials.
Control of growth of estrogen-sensitive cells: role for alpha-fetoprotein. (1980)

The role played by alpha-fetoprotein (AFP) during the perinatal period in rats has not yet been ascertained despite earlier suggestions that this plasma protein affected the multiplication, in an "in animal-in culture" system of tumor cells that are stimulated by estrogen (E) for growth. To test this inference developed from our previous work, AFP was purified by reverse affinity chromatography to homogeneity by electrophoretic and immunochemical criteria. Purified AFP was added at different concentrations to horse serum-supplemented medium which by itself is able to allow maximal exponential growth of a rat pituitary tumor cloned cell line C29RAP. These cells carry estrophilins and their growth is stimulated by E in animals but not in culture. At 3 mg/ml in culture media, AFP prevented growth of C29RAP cells; the effect was dose dependent. F4C1, a rat pituitary cloned cell line that carries estrophilins but shows autonomous behavior when injected into male and female Fisher rats, was not affected in cultured by comparable concentrations of AFP in the culture media. The effect of AFP on the growth of E-sensitive cells in culture was not reversed by E administration. We conclude from these experiments that (i) AFP is a specific inhibitor of the cell multiplication of cells that are E-sensitive for growth (as defined in this presentation), (ii) estrophilins seem not to play a significant role in this inhibition, and (iii) E appears not to be a growth-promoting hormone per se.
Ultrasensitive response of a CW dye laser to selective extinction (1972)

The sensitivity of a broad-band dye laser to selective intracavity absorption is proportional to the number of oscillating modes. This result is obtained from a rate equation model, taking into account the spectral homogeneity, but spatial inhomogeneity of the laser saturation. An increase of absorption sensitivity by a factor of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sup> , compared to a single-pass measurement, is observed in an experiment with an iodine vapor absorption cell inside the cavity of a CW dye laser. The fluorescence of an external iodine vapor cell provides a convenient selective absorption monitor.