gebhart/patrepeval huggingface dataset:
Combination of immunohistochemistry and laser ablation ICP mass spectrometry for imaging of cancer biomarkers (2008)

Laser ablation (LA) ICP-MS has been developed as a new tool for imaging of cancer biomarkers in tissue sections. The distribution of two breast cancer-associated proteins, MUC-1 and HER2 was studied based on multiple line rastering of tissue sections and measurement of relevant Au/Ag tagged antibodies bound to the tissue. Comparisons with optical microscopy indicated extremely high sensitivity for the LA technique and sufficiently good resolution to permit fine scale feature mapping at the cellular level. Application to the quantitative assessment of HER2 expression in tissue microarrays was demonstrated.
Calcium Dysregulation and Membrane Disruption as a Ubiquitous Neurotoxic Mechanism of Soluble Amyloid Oligomers*♦ (2005)

Increasing evidence suggests that amyloid peptides associated with a variety of degenerative diseases induce neurotoxicity in their intermediate oligomeric state, rather than as monomers or fibrils. To test this hypothesis and investigate the possible involvement of Ca2+ signaling disruptions in amyloid-induced cytotoxicity, we made homogeneous preparations of disease-related amyloids (Abeta, prion, islet amyloid polypeptide, polyglutamine, and lysozyme) in various aggregation states and tested their actions on fluo-3-loaded SH-SY5Y cells. Application of oligomeric forms of all amyloids tested (0.6-6 microg ml-1) rapidly (approximately 5 s) elevated intracellular Ca2+, whereas equivalent amounts of monomers and fibrils did not. Ca2+ signals evoked by Abeta42 oligomers persisted after depletion of intracellular Ca2+ stores, and small signals remained in Ca2+-free medium, indicating contributions from both extracellular and intracellular Ca2+ sources. The increased membrane permeability to Ca2+ cannot be attributed to activation of endogenous Ca2+ channels, because responses were unaffected by the potent Ca2+-channel blocker cobalt (20 microm). Instead, observations that Abeta42 and other oligomers caused rapid cellular leakage of anionic fluorescent dyes point to a generalized increase in membrane permeability. The resulting unregulated flux of ions and molecules may provide a common mechanism for oligomer-mediated toxicity in many amyloidogenic diseases, with dysregulation of Ca2+ ions playing a crucial role because of their strong trans-membrane concentration gradient and involvement in cell dysfunction and death.
Maximum likelihood image and blur identification: a unifying approach (1990)

A number of different algorithms have recently been proposed to identify the image and blur model parameters from an image that is degraded by blur and noise. This paper gives an overview of the developments in image and blur identification under a unifying maximum likelihood framework. In fact, we show that various recently published image and blur identification algorithms are different implementations of the same maximum likelihood estimator resulting from different modeling assumptions and/or considerations about the computational complexity. The use of the maximum likelihood estimation in image and blur identification is illustrated by numerical examples.
Gluten-Specific T Cells Cross-React between HLA-DQ8 and the HLA-DQ2α/DQ8β Transdimer (2011)

Because susceptibility to celiac disease is associated strongly with HLA-DQ2 (DQA1*05/DQB1*02) and weakly with HLA-DQ8 (DQA1*03/DQB1*03), a subset of patients carries both HLA-DQ2 and HLA-DQ8. As a result, these patients may express two types of mixed HLA-DQ2/8 transdimers (encoded by DQA1*05/DQB1*03 and DQA1*03/DQB1*02) in addition to HLA-DQ2 and HLA-DQ8. Using T cells from a celiac disease patient expressing HLA-DQ8trans (encoded by DQA*0501/DQB*0302), but neither HLA-DQ2 nor HLA-DQ8, we demonstrate that this transdimer is expressed on the cell surface and can present multiple gluten peptides to T cell clones isolated from the duodenum of this patient. Furthermore, T cell clones derived from this patient and HLA-DQ2/8 heterozygous celiac disease patients respond to gluten peptides presented by HLA-DQ8trans, as well as HLA-DQ8, in a similar fashion. Finally, one gluten peptide is recognized better when presented by HLA-DQ8trans, which correlates with preferential binding of this peptide to HLA-DQ8trans. These results implicate HLA-DQ8trans in celiac disease pathogenesis and demonstrate extensive T cell cross-reactivity between HLA-DQ8 and HLA-DQ8trans. Because type 1 diabetes is strongly associated with the presence of HLA-DQ8trans, our findings may bear relevance to this disease as well.
Production of infectious recombinant Moloney murine leukemia virus particles in BHK cells using Semliki Forest virus-derived RNA expression vectors. (1996)

We describe a heterologous, Semliki Forest virus (SFV)-driven packaging system for the production of infectious recombinant Moloney murine leukemia virus particles. The gag-pol and env genes, as well as a recombinant retrovirus genome (LTR-psi (+)-neoR-LTR), were inserted into individual SFV1 expression plasmids. Replication-competent RNAs were transcribed in vitro and introduced into the cytoplasm of BHK-21 cells using electroporation. The expressed Moloney murine leukemia virus structural proteins produced extracellular virus-like particles. In these particles the gag precursor was processed into mature products, indicating that the particles contained an active protease. The protease of the gag-pol fusion protein was also shown to be active in a trans-complementation assay using a large excess of Pr65gag. Moreover, the particles possessed reverse transcriptase (RT) activity as measured in an in vitro assay. Cotransfection of BHK-21 cells by all three SFV1 constructs resulted in the production of transduction-competent particles at 4 x 10(6) colony-forming units (cfu)/ml during a 5-hr incubation period. Altogether, 2.9 x 10(7) transduction-competent particles were obtained from about 4 x 10(6) transfected cells. Thus, this system represents the first RNA-based packaging system for the production of infectious retroviral particles. The facts that no helper virus could be detected in the virus stocks and that particles carrying the amphotropic envelope could be produced with similar efficiency as those that carry the ecotropic envelope make the system very interesting for gene therapy.
Design of ionic liquids: an ecotoxicity (Vibrio fischeri) discrimination approach (2011)

Ionic liquids have attracted a lot of attention as potential replacements for conventional volatile organic solvents, although they may pose environmental risks to aquatic ecosystems that have to be assessed. There is strong interest in developing mathematical models to estimate the ecotoxicity of ionic liquids, minimising the experimental investigations and the consequent consumption of time and resources. This paper presents a new approach for estimating the ecotoxicity of ILs, based on the standardised assay with the bacterium Vibrio fischeri, by means of the application of Partial Least Squares-Discriminant Analysis (PLS-DA). The PLS-DA model developed makes it possible to discriminate ionic liquids, formed by combinations of 30 anions and 64 cations, on the basis of their expected toxicity with respect to conventional solvents that they may replace. The successful results obtained in the validation of the model reveal that this approach can be useful as a screening tool to easily aid, from the early stages of the process, the design of aquatic environmentally friendly ionic liquids. This approach may also be useful for the further development of predictive models based on other aquatic organisms, for which more data are expected to be available in the near future.
The eukaryotic P loop NTPase Nbp35: An essential component of the cytosolic and nuclear iron–sulfur protein assembly machinery (2005)

Soluble P loop NTPases represent a large protein family and are involved in diverse cellular functions. Here, we functionally characterized the first member of the Mrp/Nbp35 subbranch of this family, the essential Nbp35p of Saccharomyces cerevisiae. The protein resides in the cytosol and nucleus and carries an Fe/S cluster at its N terminus. Assembly of the Fe/S cluster requires the mitochondrial Fe/S cluster (ISC)-assembly and -export machineries. Depletion of Nbp35p strongly impairs the activity of the cytosolic Fe/S protein, isopropylmalate isomerase (Leu1p), whereas mitochondrial Fe/S enzymes are unaffected. Moreover, defects in the de novo maturation of various cytosolic and nuclear Fe/S proteins were observed in the absence of Nbp35p, demonstrating the functional involvement of Nbp35p in the biogenesis of extramitochondrial Fe/S proteins. Furthermore, Nbp35p genetically interacts with the closely similar P loop NTPase, Cfd1p, and the hydrogenase-like Nar1p, both of which were recently shown to perform a crucial function in cytosolic and nuclear Fe/S protein biogenesis. Hence, our study suggests that eukaryotic Nbp35 NTPases function in Fe/S protein maturation. The findings provide strong evidence for the existence of a highly conserved and essential machinery dedicated to assembling cytosolic and nuclear Fe/S proteins.
Regulation of methionine synthesis in Escherichia coli: effect of the MetR protein on the expression of the metE and metR genes. (1989)

A plasmid (pRSE562) containing the metE and metR genes of Escherichia coli was used to study the expression of these genes and the role of the MetR protein in regulating metE expression. DNA sequence analysis of the 236-base-pair region separating these genes showed the presence of seven putative met boxes. When this plasmid was used to transform either wild-type E. coli, metE mutant, or metR mutant, MetE enzyme activity increased 5- to 7-fold over wild-type levels. The metR gene was subcloned from pRSE562, and this plasmid, pMRIII, relieved the methionine auxotrophy of a metR mutant after transformation. The metR gene was also cloned into a vector containing the lambda PL promoter, and the MetR protein was overexpressed and purified to near homogeneity. This protein, when added to an in vitro DNA-dependent protein synthesis system in which the MetE and/or MetR proteins were synthesized, caused a large increase in the expression of the metE gene but a decrease in the expression of the metR gene. The in vitro expression of both genes was inhibited by the MetJ protein and S-adenosylmethionine in the presence or absence of MetR protein. These results provide evidence that the product of the metR gene is a trans-activator of the expression of the metE gene and that the expression of the metR gene is under autogenous regulation and is repressed by the MetJ protein.
Current therapy for malignant melanoma. (1989)

The majority of patients with stage I melanoma can be cured with surgery. Extension of tumor to the regional lymph nodes portends a poor prognosis, with an expected 5-year survival rate of no more than 20% to 25%. Adjuvant therapy has not been particularly useful in such patients. Patients with metastatic melanoma generally do poorly and have a median survival of 4 to 6 months. Such patients are treated with systemic therapy unless they have a surgically resectable single site of metastasis, in which case surgical resection offers the best palliation. The chemotherapeutic agent that is most widely used is dacarbazine (DTIC), which has been in use for the past 20 years. When used as a single agent, DTIC has produced response rates of 15% to 20%. These responses largely occur in soft-tissue disease and last an average of 3 to 6 months. Complete remissions occur in fewer than 5% of patients. In addition to DTIC, other drugs with significant activity against metastatic melanoma are the nitrosoureas, the vinca alkaloids, and cisplatin. Combinations of DTIC and nitrosoureas have not resulted in significant improvement in the response rate, which has generally been 20% to 25%. During the past decade, several triple-drug combinations have been tested, with some evidence of an increase in the response rate to 25% to 30%. More recently developed combinations incorporating cisplatin and the vinca alkaloids in conjunction with DTIC have yielded response rates of 30% to 40%. Because most of these reports are pilot studies and have not been tested in controlled trials, the evidence of the superiority of these combined regimens over DTIC alone cannot be considered conclusive. Combination chemotherapy regimens do produce slightly higher complete response rates of approximately 10%, and the duration of responses is somewhat longer (6 to 9 months). During the past 5 years, biologic therapy with interferons and interleukin-2 (IL-2) has shown clinical evidence of activity against metastatic melanoma. The recombinant alpha interferons (alfa-2a and alfa-2b) have been widely used and have induced tumor regressions in 15% to 20% of patients. Because the activity of interferons is not compromised by prior chemotherapy, their use is more popular as second-line therapy, with an expected overall response rate of 15%. Other studies have utilized interferon in untreated patients, where the response rate may be slightly higher.(ABSTRACT TRUNCATED AT 400 WORDS)
The potential role of speech production models in automatic speech recognition (1996)

This paper investigates the issues that are associated with applying speech production models to automatic speech recognition (ASR). Here the applicability of articulatory representations to ASR is considered independently of the role of articulatory representations in speech perception. While the question of whether it is necessary or even possible for human listeners to recover the state of the articulators during the process of perceiving speech is an important one, it is not considered here. Hence, the authors refrain from posing completely new paradigms for ASR which more closely parallel the relationship between speech production and human speech understanding. Instead, work aimed at integrating speech production models into existing ASR formalisms is described.
Protective T Cell Immunity against Malaria Liver Stage after Vaccination with Live Sporozoites under Chloroquine Treatment (2004)

In this study we present the first systematic analysis of the immunity induced by normal Plasmodium yoelii sporozoites in mice. Immunization with sporozoites, which was conducted under chloroquine treatment to minimize the influence of blood stage parasites, induced a strong protection against a subsequent sporozoite and, to a lesser extent, against infected RBC challenges. The protection induced by this immunization protocol proved to be very effective. Induction of this protective immunity depended on the presence of liver stage parasites, as primaquine treatment concurrent with sporozoite immunization abrogated protection. Protection was not found to be mediated by the Abs elicited against pre-erythrocytic and blood stage parasites, as demonstrated by inhibition assays of sporozoite penetration or development in vitro and in vivo assays of sporozoite infectivity or blood stage parasite development. CD4(+) and CD8(+) T cells were, however, responsible for the protection through the induction of IFN-gamma and NO.
Members of the low density lipoprotein receptor familymediate cell entry of a minor-group common cold virus. (1994)

A protein binding to a minor-group human rhinovirus (HRV2) was purified from HeLa cell culture supernatant. The amino acid sequences of tryptic peptides showed identity with the human low density lipoprotein (LDL) receptor (LDLR). LDL and HRV2 mutually competed for binding sites on human fibroblasts. Cells down-regulated for LDLR expression yielded much less HRV2 upon infection than cells with up-regulated LDLR. Virus also bound to the large subunit of the alpha 2-macroglobulin receptor/LDLR-related protein (alpha 2MR/LRP). LDLR-deficient fibroblasts yielded considerably less virus in the presence of receptor-associated protein (RAP), providing evidence that alpha 2MR/LRP also acts as a minor group HRV receptor.
Protein biomarkers in cancer: natural glycoprotein microarray approaches. (2008)

Protein glycosylation is the most versatile and common protein modification and plays important roles in various biological processes and disease progression. In this review, the development of microarray technology for protein glycosylation analysis is described. Three types are discussed: carbohydrate, lectin and natural glycoprotein microarrays. The advantages of microarray technology to study protein glycosylation are high-volume throughput coupled with a highly miniaturized platform. These techniques show great promise for detecting interactions that involve carbohydrates and as a screening tool to detect glycan patterns important for the early diagnosis of disease.
Block Copolymer Lithography (2013)

This Perspective addresses the current state of block copolymer lithography and identifies key challenges and opportunities within the field. Significant strides in experimental and theoretical thin film research have nucleated the transition of block copolymers “from lab to fab”, but outstanding questions remain about the optimal materials, processes, and analytical techniques for first-generation devices and beyond. Particular attention herein is focused on advances and issues related to thermal annealing. Block copolymers are poised to change the traditional lithographic resolution enhancement paradigm from “top-down” to “bottom-up”.
Pathogenic point mutations in a transmembrane domain of the ε subunit increase the Ca2+ permeability of the human endplate ACh receptor (2007)

The epsilon subunit of the human endplate ACh receptor (AChR) is a key determinant of the large fraction of the ACh-evoked current carried by Ca2+ ions (P(f)). Consequently, missense mutations in the epsilon subunit are potential targets for altering the P(f) of human AChR. In this paper we investigate the effects of two pathogenic point mutations in the M2 transmembrane segment AChR epsilon subunit, epsilonT264P and epsilonV259F, that cause slow-channel syndromes (SCS). When expressed in GH4C1 cells, the mutant receptors subunits raise Ca2+ permeability of the receptors approximately 1.5 and approximately 2-fold above that of wild-type, to attain P(f) values of 11.8% (epsilonT264P) and 15.4% (epsilonV259F). The latter value exceeds most P(f) values reported to date for ligand-gated ion channels. Consistent with these findings, the biionic Ca2+ permeability ratio (P(Ca)/P(Cs)) of the mutant AChRs is also increased. Upon repetitive stimulation with ACh, the mutant receptors show an enhanced current run-down compared with wild-type, leading to a strong reduction of their function. We propose that the enhanced Ca2+ permeability of the mutant receptors overrides the protective effect of desensitization and, together with the prolonged opening events of the AChR channel, is an important determinant of the excitotoxic endplate damage in the SCS.
Analysis of crosstalk in WDM-ring networks (1993)

Crosstalk in multiwavelength ring networks that utilize cascaded EDFAs and cascaded Fabry-Perot filters is analyzed. The channel-spacing and filter-bandwidth requirements for a 15-channel ring network are identified. It is found that a Fabry-Perot filter bandwidth of 12 times the signal bit rate is necessary to ensure a power penalty of less than 2.4 dB. Channel spacing of the same value is required to achieve small crosstalk penalties.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Intermediate biomarkers of colon cancer: modulation of expression of ras oncogene by chemopreventive agents during azoxymethane induced colon carcinogenesis (1993)

In our attempts to evaluate the influence of chemopreventive agents on intermediate biomarkers of colon cancer, we have investigated the effect of D,L-alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase and piroxicam, a non-steroidal anti-inflammatory drug (NSAID) on the expression levels of biochemically active p21ras, the protein product of cellular ras protooncogenes during the development of azoxymethane (AOM) induced colon carcinogenesis in male F344 rats in order to explore the plausibility of using p21ras as an intermediate biochemical marker of colon cancer. Groups of male F344 rats were fed the modified AIN-76A diets containing 0 or 150 p.p.m. piroxicam or 4000 p.p.m. DFMO and administered s.c. AOM dissolved in normal saline at a dose of 15 mg/kg body wt/week, once weekly, for 4 weeks. Vehicle control groups received s.c. equal vol of normal saline. Groups of animals were then killed at 0, 4, 16, 24 and 32 weeks after the last injection of AOM or saline and their colonic mucosa and tumors analyzed for biochemically active p21ras levels. AOM treatment significantly increased the expression of biochemically active p21ras. The AOM-induced expression of biochemically active p21ras was significantly suppressed by dietary DFMO and piroxicam. DFMO exerted a more pronounced inhibitory effect on AOM-induced colon tumor development as well as the expression of biochemically active p21ras. These results indicate that the determination of biochemically active p21ras may be effectively used in clinical chemoprevention trials as an intermediate end-point to monitor the colon carcinogenesis.
Generation of Gradients Having Complex Shapes Using Microfluidic Networks (2001)

This paper describes the generation of gradients having complex shapes in solution using microfluidic networks. Flowing multiple streams of fluid each carrying different concentrations of substances laminarly and side-by-side generated step concentration gradients perpendicular to the direction of the flow. Appropriately designed networks of microchannels for controlled diffusive mixing of substances generated a range of shapes for the gradients, including linear, parabolic, and periodic. The lateral dimensions of the gradients ranged from 900 to 2200 μm. This paper also demonstrates the generation of overlapping gradients composed of different species. Since solutions in the microfluidic network exist as steady states and are continuously renewed, the gradients established in the capillaries are spatially and temporally constant and can be maintained easily for periods of hours. Using laminar flow to generate gradients should be useful in both biological and nonbiological research.
The finite-length multi-input multi-output MMSE-DFE (2000)

A new theoretical framework is introduced for analyzing the performance of a finite length minimum-mean-square error decision feedback equalizer (MMSE-DFE) in a multi-input multi-output (MIMO) environment. The framework includes transmit and receive diversity systems as special cases and quantifies the diversity performance improvement as a function of the number of transmit/receive antennas and equalizer taps. Fast and parallelizable algorithms for computing the finite-length MIMO MMSE-DFE are presented for three common multi-user detection scenarios.