gebhart/patrepeval huggingface dataset:
TCR expression of activated T cell clones in the lungs of patients with pulmonary sarcoidosis. (1994)

Sarcoidosis is a systemic granulomatous disease of unknown etiology in which CD4+ T cells seem to be critically involved. In the lungs of patients with pulmonary disease, CD4+ T cells accumulate in large numbers, and a subset of these cells is activated. By using both quantitative PCR and anti-V beta mAbs, we analyzed the TCR repertoire of total and activated bronchoalveolar lavage T cells, the latter subset being defined by the ability to proliferate in short-term culture supplemented with IL-2. Overall, there was little difference when TCR V beta expression of freshly isolated lung and peripheral blood cells was compared in individual patients. Some individuals did demonstrate a modest increase in a few V beta-expressing subsets. However, after 1 to 2 wk of in vitro growth in IL-2-supplemented media, bronchoalveolar lavage cells from most patients, but not from any healthy individuals, demonstrated a selective expansion of particular V beta-expressing subsets. Interestingly, different V beta-bearing subsets were expanded in different patients. Junctional region sequencing indicated that the proliferating T cells in culture were strikingly oligoclonal and were derived from T cell clones already selectively expanded in vivo. These results provide evidence for a disease process that involves recognition of local Ag(s) by specific subsets of CD4+ T cells. Analysis of the Ag specificity of these IL-2-expanded populations is likely to provide insight into the pathogenesis of this disease.
Secreted int-1 protein is associated with the cell surface. (1990)

The murine int-1 proto-oncogene has been implicated in neural development and, when transcriptionally activated by mouse mammary tumor virus, contributes to the genesis of mammary tumors. To understand the function of the int-1 gene product in these processes, we have characterized the biochemical properties of int-1 protein expressed in a neuroendocrine cell line transfected with int-1 cDNA. Here we provide evidence that int-1 protein is secreted and associates with the cell surface. int-1 protein was very efficiently processed and secreted through the constitutive secretory pathway, although no int-1 protein could be immunoprecipitated from the culture medium. Treatment with suramin effectively released mature int-1 proteins into the culture fluid, which suggests that secreted int-1 protein associates with the cell surface or extracellular matrix. We have also shown directly, by radioiodination of intact cells and by surface antibody adsorption, that secreted int-1 proteins can be detected on the cell surface. These data support a model in which int-1 protein is secreted and functions locally in cell-to-cell signaling.
DNA detection based on capacitive AL/sub 2/O/sub 3//AL microelectrodes (2004)

The electrical detection of DNA hybridization still faces the challenge of detecting very low concentrations. In this work we present the possibility of detecting DNA probes by measuring a capacitance change between interdigitated aluminum micro-fingers coated with a thin alumina layer and constructed over an oxidized silicon wafer. DNA Labeling was performed by biotinylated nucleotides and reaction with anti-biotin/gold nanoparticles, increased in size by silver crystal precipitation. The capacitance change ratio observed was at least of two, using 0.2 nM DNA solutions. This detection method appears compatible with microarray technology and paves the way for further use in biological applications.
Phase-locked loops, principles and practice (1996)

This book is a concise guide to the theory and design of phase-locked loop circuits. It is written from an engineering viewpoint, with many illustrations, block diagrams, example circuits and experimental results - many based on the author's personal experience - and use of engineering analytical methods, such as signal flow graphs and Laplace transforms. The author shows how the potential pit-falls in PLL design may be avoided by adopting a rigorous theoretical approach, with almost all results derived from first principles, although mathematics is used for practical relevance rather than academic interest. An important consequence is that the text is substantially self-contained
Validation of the geriatric depression scale-short form among inpatients (1994)

Little is known about the diagnostic validity of the 15-item Geriatric Depression Scale-Short Form (GDS-SF), especially when compared to the original 30-item version (Geriatric Depression Scale-Long Form; GDS-LF). This study compared the GDS-SF and GDS-LF with a sample of depressed, demented, and thought-disordered inpatients. The GDS-SF and GDS-LF were found to be highly correlated (r = .89) and to have similar high sensitivity rates. The specificity rates for both forms were similar, but lower than desirable. Overall, the GDS-SF was found to be an adequate substitute for the GDS-LF.
The august spoken dialogue system (1999)

This paper describes how a telephone-based application can perform a variety of tasks in a completely hands-free mode. The overall architecture of the speech component is multimodal in that each mode is tailored to a specific need of the interface. The various modes are described as well as the underlying core technology. To illustrate the effectiveness of the implementation, we present experimental results in American English, UK English and French on a variety of benchmarks, including live data collected during actual use of the system.
Effects of dietary n-3 fatty acid supplementation versus thromboxane synthetase inhibition on gentamicin-induced nephrotoxicosis in healthy male dogs. (1996)

Increased renal production/excretion of thromboxane is important in the pathogenesis of gentamicin-induced nephrotoxicosis.
Attraction between Like-Charged Macroions by Coulomb Depletion (1998)

A novel mechanism for counterion-mediated attraction between like-charged spherical macroions is proposed, which originates from a depletion zone of counterions between nearly touching macroions that is induced by Coulomb interactions. Using computer simulations of the primitive model, we show that this depletion effect dominates over the electrostatic contribution in the case of strong Coulomb coupling when all the counterions form a quasi-two-dimensional layer on the spherical macroionic surface. Its range is given by the typical spacing of counterions on the macroion surface.
The genetics of Pak (2004)

p21-activated kinases (Paks) are a highly conserved family of enzymes that bind to and are activated by small GTPases of the Cdc42 and Rac families. With the notable exception of plants, nearly all eukaryotes encode one or more Pak genes, indicating an ancient origin and important function for this family of enzymes. Genetic approaches in many different experimental systems, ranging from yeast to mice, are beginning to decipher the different functions of Paks. Although some of these functions are unique to a given organism, certain common themes have emerged, such as the activation of mitogen-activated protein kinase (MAPK) cascades and the regulation of cytoskeletal structure through effects on the actin and tubulin cytoskeletons.
LRP1 Deficiency in Vascular SMC Leads to Pulmonary Arterial Hypertension That Is Reversed by PPARγ Activation (2019)

Here, we identify LRP1 as an integrator of TGFβ1-mediated mechanisms that regulate vascular remodeling in mice and clinical PAH and PPARγ as a therapeutic target that controls canonical TGFβ1 pathways. Hence, pharmacologic PPARγ activation represents a promising new therapy for patients with PAH who lack the vasoprotective LRP1 in vascular SMC.
Tumor fraction in cell-free DNA as a biomarker in prostate cancer (2018)

Wong Family Award in Translational Oncology, Dana Farber Cancer Institute Medical Oncology grant, Gerstner Family Foundation, Janssen Pharmaceuticals Inc., and Koch Institute Support (core) grant P30-CA14051 from the National Cancer Institute (NCI).
From dystrophinopathy to sarcoglycanopathy: Evolution of a concept of muscular dystrophy (1998)

Duchenne and Becker muscular dystrophies are collectively termed dystrophinopathy. Dystrophinopathy and severe childhood autosomal recessive muscular dystrophy (SCARMD) are clinically very similar and had not been distinguished in the early 20th century. SCARMD was first classified separately from dystrophinopathy due to differences in the mode of inheritance. Studies performed several years ago clarified some immunohistochemical and genetic characteristics of SCARMD, but many remained to be clarified. In 1994, the sarcoglycan complex was discovered among dystrophin-associated proteins. Subsequently, on the basis of our immunohistochemical findings which indicated that all components of the sarcoglycan complex are absent in SCARMD muscles, and the previous genetic findings, we proposed that a mutation of any one of the sarcoglycan genes leads to SCARMD. This hypothesis explained and predicted various characteristics of SCARMD at the molecular level, most of which have been verified by subsequent discoveries in our own as well as various other laboratories. SCARMD is now called sarcoglycanopathy, which is caused by a defect of any one of four different sarcoglycan genes, and thus far mutations in sarcoglycan genes have been documented in the SCARMD patients. In this review, the evolution of the concept of sarcoglycanopathy separate from that of dystrophinopathy is explained by comparing studies on these diseases.
Gonadotropin-releasing Hormone Receptor-coupled Gene Network Organization (2001)

An early gene cDNA microarray was developed to study genes that are regulated immediately following gonadotropin-releasing hormone (GnRH) receptor activation. 956 selected candidate genes were printed in triplicate, a t statistic-based regulation algorithm was used for data analysis, and the response to GnRH in a time course from 1 to 6 h was determined. Measurements were highly reproducible within arrays, between arrays, and between experiments. Accuracy and algorithm reliability were established by real-time polymerase chain reaction assays of 60 genes. Gene changes ranging from 1.3- to 31-fold on the microarray were confirmed by real-time polymerase chain reaction. Many of the genes were found to be highly regulated. The regulated genes identified were all elevated at 1 h of treatment and returned nearly or completely to baseline levels of expression by 3 h of treatment. This broad, robust, and transient transcriptional response to constant GnRH exposure includes modulators of signal transduction (e.g. Rgs2 and IkappaB), cytoskeletal proteins (e.g. gamma-actin), and transcription factors (e.g. c-Fos, Egr1, and LRG21). The interplay of the activators, repressors, and feedback inhibitors identified embodies a combinatorial code to direct the activity of specific downstream secondary genes.
cAMP-Dependent Protein Kinase Phosphorylations on Tau in Alzheimer’s Disease (1999)

To elucidate the role cAMP-dependent protein kinase (PKA) phosphorylations on tau play in Alzheimer's disease, we have generated highly specific monoclonal antibodies, CP-3 and PG-5, which recognize the PKA-dependent phosphorylations of ser214 and ser409 in tau respectively. The present study demonstrates by immunohistochemical analysis, CP-3 and PG-5 immunoreactivity with neurofibrillary pathology in both early and advanced Alzheimer's disease, but not in normal brain tissue and demonstrates that cAMP-dependent protein kinase phosphorylations on tau precede or are coincident with the initial appearance of filamentous aggregates of tau. Studies using heat-stable preparations demonstrate that neither site appears to be phosphorylated to any appreciable extent in normal rodent or human brain. Further analysis demonstrates that the beta catalytic subunit of PKA (Cbeta), the beta II regulatory subunit of PKA (RIIbeta), and the 79 kDa A-kinase-anchoring-protein (AKAP79), are tightly associated with the neurofibrillary pathology, positioning cAMP-dependent protein kinase to participate directly in the pathological hyperphosphorylation of tau seen in Alzheimer's disease.
Immunohistochemical staining for glutathione S-transferase predicts response to platinum-based chemotherapy in head and neck cancer. (1996)

The glutathione S-transferases (GSTs) play an important role in the cell's defense against toxic substances. The GSTs are a family of enzymes produced by several genes that interact with distinct but overlapping substrates and that may play a role in resistance of tumor cells to several chemotherapeutic agents. We examined the correlation between expression of GSTs determined by immunohistochemistry and clinical response to platinum-based chemotherapy in 51 patients with head and neck cancer, who received a total of 56 courses of chemotherapy. The overall response rate for the 56 chemotherapy treatment courses was 48%. The overall response rate (complete response + partial response) for patients with low GST scores was 88% (21 of 24), whereas among the patients with high GST scores, the overall response rate was 19% (6 of 32; P = 0.001). Patients with a low GST score were 4.7 times more likely to respond to chemotherapy than patients with high GST scores. GST scores corresponded to response in 84% of cases. Among 23 patients treated with neoadjuvant chemotherapy, the overall response rate for patients with low GST scores was 100% (14 of 14), whereas among the patients with high GST scores, the overall response rate was 44% (4 of 9; P = 0.002). Among 33 patients treated with chemotherapy for relapsed disease, the overall response rate for patients with low GST scores was 70% (7 of 10), whereas among the patients with high GST scores, the overall response rate was 8.6% (2 of 23; P < 0.001). We conclude that GST expression correlates well with response to platinum-based chemotherapy in head and neck cancer.
Kinetic and Thermodynamic Assessments of the Mediator−Template Assembly of Nanoparticles (2005)

The understanding of kinetic and thermodynamic factors governing the assembly of nanoparticles is important for the design and control of functional nanostructures. This paper describes a study of the kinetic and thermodynamic factors governing the mediator-template assembly of gold nanoparticles into spherical assemblies in solutions. The study is based on spectrophotometric measurements of the surface plasmon (SP) resonance optical property. Gold nanoparticle cores ( approximately 5 nm) encapsulated with tetraoctylammonium bromide shells were studied as a model system. The mediator-template assembly involves a thioether-based multidentate ligand (e.g., MeSi(CH2SMe)3) which functions as a mediator, whereas the tetraoctylammonium bromide capping molecules function as template agents. On the basis of the temperature dependence of the SP optical property in the mediator-template assembly process, the kinetic and thermodynamic parameters such as the reaction rate constant and reaction enthalpy have been determined. The results led to two important findings. First, the mediator-template assembly of nanoparticles is an enthalpy-driven process. Second, the enthalpy change (-1.3 kcal/mol) is close to the magnitude of the van der Waals interaction energy for alkyl chains and the condensation energy of hydrocarbons. Implications of the findings to the understanding of the interparticle interactions have also been discussed.
Overview of General and Discriminating Markers of Differential Microglia Phenotypes (2020)

Inflammatory processes and microglia activation accompany most of the pathophysiological diseases in the central nervous system. It is proven that glial pathology precedes and even drives the development of multiple neurodegenerative conditions. A growing number of studies point out the importance of microglia in brain development as well as in physiological functioning. These resident brain immune cells are divergent from the peripherally infiltrated macrophages, but their precise <i>in situ</i> discrimination is surprisingly difficult. Microglial heterogeneity in the brain is especially visible in their morphology and cell density in particular brain structures but also in the expression of cellular markers. This often determines their role in physiology or pathology of brain functioning. The species differences between rodent and human markers add complexity to the whole picture. Furthermore, due to activation, microglia show a broad spectrum of phenotypes ranging from the pro-inflammatory, potentially cytotoxic M1 to the anti-inflammatory, scavenging, and regenerative M2. A precise distinction of specific phenotypes is nowadays essential to study microglial functions and tissue state in such a quickly changing environment. Due to the overwhelming amount of data on multiple sets of markers that is available for such studies, the choice of appropriate markers is a scientific challenge. This review gathers, classifies, and describes known and recently discovered protein markers expressed by microglial cells in their different phenotypes. The presented microglia markers include qualitative and semi-quantitative, general and specific, surface and intracellular proteins, as well as secreted molecules. The information provided here creates a comprehensive and practical guide through the current knowledge and will facilitate the choosing of proper, more specific markers for detailed studies on microglia and neuroinflammatory mechanisms in various physiological as well as pathological conditions. Both basic research and clinical medicine need clearly described and validated molecular markers of microglia phenotype, which are essential in diagnostics, treatment, and prevention of diseases engaging glia activation.
Functional Phe31Ile polymorphism in Aurora A and risk of breast carcinoma (2004)

Aurora-A/BTAK/STK15, involved in regulating centrosomes and chromosome segregation, is overexpressed in human breast carcinoma and other cancers. The Phe31-->Ile polymorphism in Aurora A alters the kinase function, with the Ile31 variant being preferentially amplified and associated with degree of aneuploidy in human tumors. We have previously shown that the Phe31Ile polymorphism is associated with the occurrence and advanced disease status of esophageal cancer. This case-control study examined the contribution of this polymorphism to susceptibility to development and progression of breast cancer. Aurora A genotypes were determined in 520 patients with breast carcinoma, 191 patients with benign breast diseases (BBD) and 520 controls. It was found that the Aurora A Ile/Ile genotype was significantly associated with increased risk of breast carcinoma occurrence [odds ratio (OR) 1.66; 95% confidence interval (95% CI) 1.29-2.12] compared with the Phe/Phe or Phe/Ile genotype. The increased risk for BBD and breast carcinoma related to the Ile/Ile genotype was more pronounced in younger subjects. Moreover, we found that patients carrying the Ile/Ile genotype tended to have ER-carcinomas (OR 2.56; 95% CI 1.24-5.26). No significant association was observed between the polymorphism and metastasis and disease stage of the cancer. These findings suggest that the Phe31Ile polymorphism in Aurora A may be a genetic modifier for developing breast carcinoma.
A novel method to study contraction characteristics of a single cardiac myocyte using carbon fibers (2001)

To facilitate cardiac muscle research, we developed a novel method by which the force and length of a single ventricular myocyte can be recorded with a pair of carbon graphite fibers attached firmly to both ends. One fiber was stiff, whereas the other fiber was compliant to allow the recording of force and shortening during twitch contractions. The image of the compliant carbon fiber was projected onto a pair of photodiodes, and their output was fed to a piezoelectric transducer after variable amplifications to alter the effective compliance of the carbon fiber. Thus contraction of the myocyte was induced under virtually isometric conditions as well as under auxotonic conditions. We obtained a bell-shaped relation between the compliance under an auxotonic load and the work output of the myocyte, which was directly related to myocyte performance in the heart. Because it is easy to attach myocytes to the experimental apparatus, the present method would allow us to study cardiac muscle mechanics at the cellular and molecular levels.
Aberrant DNA methylation and epigenetic inactivation of Eph receptor tyrosine kinases and ephrin ligands in acute lymphoblastic leukemia (2010)

Eph receptors and their ephrin ligands are involved in normal hematopoietic development and tumorigenesis. Using methylated CpG island amplification/DNA promoter microarray, we identified several EPH receptor and EPHRIN genes as potential hypermethylation targets in acute lymphoblastic leukemia (ALL). We subsequently studied the DNA methylation status of the Eph/ephrin family by bisulfite pyrosequencing. Hypermethylation of EPHA2, -A4, -A5, -A6, -A7, -A10, EPHB1, -B2, -B3, -B4, EFNA1, -A3, -A5, and EFNB1 and -B2 genes was detected in leukemia cell lines and primary ALL bone marrow samples. Expression analysis of EPHB4, EFNB2, and EFNA5 genes demonstrated that DNA methylation was associated with gene silencing. We cloned the promoter region of EPHB4 and demonstrated that promoter hypermethylation can result in EPHB4 transcriptional silencing. Restoration of EPHB4 expression by lentiviral transduction resulted in reduced proliferation and apoptotic cell death in Raji cells in which EPHB4 is methylated and silenced. Finally, we demonstrated that phosphorylated Akt is down-regulated in Raji cells transduced with EPHB4. These results suggest that epigenetic silencing by hypermethylation of EPH/EPHRIN family genes contributes to ALL pathogenesis and that EPHB4 can function as a tumor suppressor in ALL.
Experimental studies of wall interactions of adsorbed spin-polarizedXe131nuclei (1990)

We have made a quantitative study of nuclear spin relaxation of $^{131}\mathrm{Xe}$ atoms adsorbed on the surface of glass cells. By using highly asymmetric glass cells we have increased the wall-induced quadrupole splitting of the nuclear-spin sublevels of $^{131}\mathrm{Xe}$ atoms by almost two orders of magnitude over previously reported values. These large surface interactions were used to extract quantitative information about the electric-field gradients experienced by the nuclei of $^{131}\mathrm{Xe}$ atoms adsorbed on the glass surface and about the activation energies for surface adsorption. The experimental results indicate that the electric-field gradients at any surface site are nearly isotropic. The residual nonzero mean value of the fluctuating field gradient has cylindrical symmetry about the normal direction to the surface. The mean-field gradient along the surface normal direction is only 2.3% as large as the rms value. We find that silicone wall coatings, which slow down the relaxation of $^{129}\mathrm{Xe}$ nuclear spins, speed up the relaxation of $^{131}\mathrm{Xe}$ nuclear spins. This may be due to the nuclear quadrupole interactions of $^{131}\mathrm{Xe}$ atoms dissolved in the relatively thick silicone wall coatings. Measurements of the temperature dependence of the coherent wall interaction show that the activation energy (\ensuremath{\approxeq}0.03 eV) for the coherent wall interaction in well-cured, hydrogen-free cells is about three times smaller than the activation energy (\ensuremath{\approxeq}0.10 eV) in hydrided cells.