gebhart/patrepeval huggingface dataset:
Intracellular pH Sensors: Design Principles and Functional Significance (2007)

Changes in intracellular pH regulate many cell behaviors, including proliferation, migration, and transformation. However, our understanding of how physiological changes in pH affect protein conformations and macromolecular assemblies is limited. We present design principles, current modeling predictions, and examples of pH sensors or proteins that have activities or ligand-binding affinities that are regulated by changes in intracellular pH.
Electrical detection of optically induced charge storage in self-assembled InAs quantum dots (1998)

Spectrally resolved photoresistance investigations of charge storage effects in self-assembled InAs quantum dots (QDs) are reported. Resonant optical excitation of the QDs produces a strong increase of the lateral resistance of a spatially separated electron channel (ΔR) which reflects the stored charge density. This photoresponse is persistent for many hours at 145 K and can be controllably reversed electrically. Pronounced oscillations observed in the spectral variation ΔR are shown to reflect the excitation spectrum of the QD ensemble showing resonances that arise from both direct and phonon-assisted absorption processes.
Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (2007)

Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.
Regulation of Integrin αvβ3-mediated Endothelial Cell Migration and Angiogenesis by Integrin α5β1 and Protein Kinase A (2000)

Recent studies indicate that angiogenesis depends, in part, on ligation of integrin alpha(5)beta(1) by fibronectin. Evidence is now provided that integrin alpha(5)beta(1) regulates the function of integrin alpha(v)beta(3) on endothelial cells during their migration in vitro or angiogenesis in vivo. Secretion of fibronectin by endothelial cells leads to the ligation of integrin alpha(5)beta(1), which potentiates alpha(v)beta(3)-mediated migration on vitronectin without influencing alpha(v)beta(3)-mediated cell adhesion. Endothelial cell attachment to vitronectin suppresses protein kinase A (PKA) activity, while addition of soluble anti-alpha(5)beta(1) restores this activity. Moreover, agents that activate intracellular PKA, such as forskolin, dibutyryl cAMP or alpha(5)beta(1) antagonists, suppress endothelial cell migration on vitronectin in vitro or angiogenesis in vivo. In contrast, inhibitors of PKA reverse the anti-migratory or anti-angiogenic effects mediated by alpha(5)beta(1) antagonists. Therefore, alpha(v)beta(3)-mediated endothelial cell migration and angiogenesis can be regulated by PKA activity, which depends on the ligation state of integrin alpha(5)beta(1).
Studies Leading to Potent, Dual Inhibitors of Bcl-2 and Bcl-xL (2007)

Overexpression of the antiapototic proteins Bcl-2 and Bcl-xL provides a common mechanism through which cancer cells gain a survival advantage and become resistant to conventional chemotherapy. Inhibition of these prosurvival proteins is an attractive strategy for cancer therapy. We recently described the discovery of a selective Bcl-xL antagonist that potentiates the antitumor activity of chemotherapy and radiation. Here we describe the use of structure-guided design to exploit a deep hydrophobic binding pocket on the surface of these proteins to develop the first dual, subnanomolar inhibitors of Bcl-xL and Bcl-2. This study culminated in the identification of 2, which exhibited EC50 values of 8 nM and 30 nM in Bcl-2 and Bcl-xL dependent cells, respectively. Compound 2 demonstrated single agent efficacy against human follicular lymphoma cell lines that overexpress Bcl-2, and efficacy in a murine xenograft model of lymphoma when given both as a single agent and in combination with etoposide.
A poly(A) addition site and a downstream termination region are required for efficient cessation of transcription by RNA polymerase II in the mouse beta maj-globin gene. (1987)

Sequence elements within the mouse beta maj-globin transcription unit required for efficient termination of transcription by RNA polymerase II have been delineated. To facilitate nascent-chain analysis of termination, the DNA segment in which transcription ceases was introduced into the adenovirus chromosome within its E1A transcription unit. Two beta-globin DNA elements were required to effect efficient termination: an upstream sequence that includes two poly(A) addition signals and a downstream region previously shown to be where RNA synthesis stops. The role of poly(A) addition in termination was established by introduction of several single base pair substitutions into the AATAAA polyadenylylation motifs. These mutations inhibited both polyadenylylation and termination within the beta-globin DNA segment. Therefore, poly(A) addition appears to be a prerequisite for efficient termination.
Origin of the Superflock of Cichlid Fishes from Lake Victoria, East Africa (2003)

Lake Victoria harbors a unique species-rich flock of more than 500 endemic haplochromine cichlid fishes. The origin, age, and mechanism of diversification of this extraordinary radiation are still debated. Geological evidence suggests that the lake dried out completely about 14,700 years ago. On the basis of phylogenetic analyses of almost 300 DNA sequences of the mitochondrial control region of East African cichlids, we find that the Lake Victoria cichlid flock is derived from the geologically older Lake Kivu. We suggest that the two seeding lineages may have already been lake-adapted when they colonized Lake Victoria. A haplotype analysis further shows that the most recent desiccation of Lake Victoria did not lead to a complete extinction of its endemic cichlid fauna and that the major lineage diversification took place about 100,000 years ago.
Human mesenchymal stem cells support megakaryocyte and pro-platelet formation from CD34+ hematopoietic progenitor cells (2000)

Megakaryocytopoiesis and thrombocytopoiesis result from the interactions between hematopoietic progenitor cells, humoral factors, and marrow stromal cells derived from mesenchymal stem cells (MSCs) or MSCs directly. MSCs are self-renewing marrow cells that provide progenitors for osteoblasts, adipocytes, chondrocytes, myocytes, and marrow stromal cells. MSCs are isolated from bone marrow aspirates and are expanded in adherent cell culture using an optimized media preparation. Culture-expanded human MSCs (hMSCs) express a variety of hematopoietic cytokines and growth factors and maintain long-term culture-initiating cells in long-term marrow culture with CD34(+) hematopoietic progenitor cells. Two lines of evidence suggest that hMSCs function in megakaryocyte development. First, hMSCs express messenger RNA for thrombopoietin, a primary regulator for megakaryocytopoiesis and thrombocytopoiesis. Second, adherent hMSC colonies in primary culture are often associated with hematopoietic cell clusters containing CD41(+) megakaryocytes. The physical association between hMSCs and megakaryocytes in marrow was confirmed by experiments in which hMSCs were copurified by immunoselection using an anti-CD41 antibody. To determine whether hMSCs can support megakaryocyte and platelet formation in vitro, we established a coculture system of hMSCs and CD34(+) cells in serum-free media without exogenous cytokines. These cocultures produced clusters of hematopoietic cells atop adherent MSCs. After 7 days, CD41(+) megakaryocyte clusters and pro-platelet networks were observed with pro-platelets increasing in the next 2 weeks. CD41(+) platelets were found in culture medium and expressed CD62P after thrombin treatment. These results suggest that MSCs residing within the megakaryocytic microenvironment in bone marrow provide key signals to stimulate megakaryocyte and platelet production from CD34(+) hematopoietic cells.
Principles of operation and analysis of switched-capacitor circuits (1983)

The principles involved in switched-capacitor circuit operation are examined with emphasis on physical insight rather than mathematical abstraction, albeit without sacrificing rigor, generality, and accuracy. Detailed time waveforms are extensively used. Input-output difference equations are discussed. After a complete time domain description, it is shown that a frequency-domain description becomes trivial through the use of phasors; z-transforms are avoided. Equivalent systems are derived. Analysis techniques are developed in parallel with the investigation of circuit properties.
Nonvolatile Flash Memory Device Using Ge Nanocrystals Embedded in HfAlO High-&lt;tex&gt;$kappa$&lt;/tex&gt;Tunneling and Control Oxides: Device Fabrication and Electrical Performance (2004)

We fabricated a nonvolatile Flash memory device using Ge nanocrystals (NCs) floating-gate (FG)-embedded in HfAlO high-/spl kappa/ tunneling/control oxides. Process compatibility and memory operation of the device were investigated. Results show that Ge-NC have good thermal stability in the HfAlO matrix as indicated by the negative Gibbs free energy changes for both reactions of GeO/sub 2/+Hf/spl rarr/HfO/sub 2/+Ge and 3GeO/sub 2/+4Al/spl rarr/2Al/sub 2/O/sub 3/+3Ge. This stability implies that the fabricated structure can be compatible with the standard CMOS process with the ability to sustain source-drain activation anneal temperatures. Compared with Si-NC embedded in HfO/sub 2/, Ge-NC embedded in HfAlO can provide more electron traps, thereby enlarging the memory window. It is also shown that this structure can achieve a low programming voltage of 6-7 V for fast programming, a long charge retention time of ten years maintaining a 0.7-V memory window, and good endurance characteristics of up to 10/sup 6/ rewrite cycles. This paper shows that the Ge-NC embedded in HfAlO is a promising candidate for further scaling of FG Flash memory devices.
Fetal Lymphocytes in the Maternal Blood (1972)

Abstract The fluorescence of the human Y chromosome after staining with quinacrine derivatives was used in an attempt to determine the prevalence of XY lymphocytes presumptively emanating from male fetuses in the blood of pregnant women. Seven women who subsequently gave birth to male infants had 0.03%-0.20% lymphocytes with a Y body. In two women pregnant with male fetuses, no Y bodies were detected. Of 12 women who gave birth to girls, eight had no Y bodies. In the remaining four, fluorescent spots were interpreted as Y bodies. One of those women had previously had an abortion. In the remaining three cases, it was found in retrospect that the fluorescent spots emanated from exceptionally brightly fluorescent autosomal regions in the maternal or paternal chromosomes, or both. Phytohemagglutinin-stimulated and unstimulated lymphocytes showed similar frequencies of Y body. Based on determinations of the incidence of Y body-containing lymphocytes in males (35%-66.5%), it was estimated that approximately 0.1%-0.5% of lymphocytes in the blood of most women pregnant with a male fetus are of fetal origin. This figure is remarkably high, since it exceeds in relative terms that of fetal erythrocytes (which mostly appear in the mother’s blood at the time of delivery) by several orders of magnitude. It is suggested that fetal lymphocytes actively cross the feto-maternal barriers. This phenomenon may have a profound influence on the immunologic interactions between fetus and mother. The method described may not turn out to be profitable in the assessment of the fetal sex, since its accuracy may be of the order of only 80%-95%. Moreover, several limitations prevail.
Increased messenger RNA level of the inhibitory G protein alpha subunit Gi alpha-2 in human end-stage heart failure. (1992)

In human heart failure the positive inotropic and cAMP-elevating effects of both beta-adrenoceptor agonists and phosphodiesterase inhibitors are diminished. This has been explained at least in part by an increase in the inhibitory signal-transducing G protein (Gi) and unchanged stimulatory G protein (Gs). In the present study we determined the mRNA expression pattern of the alpha subunits of Gi-1, Gi-2, Gi-3, and Gs in myocardial tissue samples of patients undergoing heart transplantation. Northern blot analysis of total RNA extracted from left ventricles with 32P-labeled cDNAs demonstrated expression of Gi alpha-2, Gi alpha-3, and Gs alpha mRNA. In contrast, Gi alpha-1 mRNA was not detectable. To investigate whether the increased ratio of Gi/Gs might be due to altered gene expression, we compared mRNA levels of Gi alpha-2, Gi alpha-3, and Gs alpha in left ventricular myocardium from failing hearts with idiopathic dilated cardiomyopathy (n = 8) and ischemic cardiomyopathy (n = 6) and from nonfailing hearts from transplant donors (n = 8). Compared with nonfailing control hearts, the Gi alpha-2 mRNA was increased by 75 +/- 26% (p less than 0.05) in idiopathic dilated cardiomyopathy hearts and 90 +/- 26% (p less than 0.05) in ischemic cardiomyopathy hearts. Gi alpha-3 and Gs alpha mRNA levels were similar in the three groups. The results suggest that as in other mammalian species, Gi alpha-2 and Gi alpha-3 mRNA are the predominant Gi alpha mRNA subtypes in human ventricular myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)
Real-time Kinetic Measurements of the Interactions between Lactogenic Hormones and Prolactin-Receptor Extracellular Domains from Several Species Support the Model of Hormone-induced Transient Receptor Dimerization (1996)

Interactions of recombinant soluble prolactin receptors-extracellular domains (PRLR-ECDs) from rabbit, rat, and cow and human growth hormone receptor ECD with immobilized human growth hormone, several prolactins, and bovine placental lactogen were studied utilizing surface plasmon resonance. This method enables real-time kinetic measurements of the interactions and calculations of kinetic constants and of the stoichiometry of interaction, even in cases where only transient interactions occur. In contrast to gel filtration or crystallographic studies, where in most cases the interaction of PRLR-ECDs with various lactogenic hormones indicated formation of 1:1 complexes, our surface plasmon resonance experiments indicated in all cases the transient formation of a 2:1 complex. In most of the interactions the 2:1 complex was very unstable and underwent rapid dissociation to a 1:1 complex. This situation was particularly characteristic of homologous interactions involving hormone and receptor from the same species and was mainly attributed to increased dissociation constants. We suggest that as in the case of growth hormone PRLR activation occurs via hormone-induced transient homodimerization of the receptor, lasting only a few seconds, and that this may be sufficient to initiate the biological signal. Once the signal is initiated, the receptor dimer is no longer required. Its rapid dissociation to a 1:1 complex or to its components may even be advantageous in that it permits activation of additional receptors.
Characterisation of the P53 status, BCL‐2 expression and radiation and platinum drug sensitivity of a panel of human ovarian cancer cell lines (1998)

The P53gene is frequently mutated in late stage ovarian cancer and has been proposed as a determinant of radiation and chemosensitivity. We have therefore determined the p53 functional status, P53sequence, radiation sensitivity and cytotoxicity of cisplatin and the novel platinum analogue, AMD473, in a panel of 6 human ovarian cancer cell lines. Constitutive p53 protein levels were low in A2780, CH1, LK1, LK2 and PA1 but were markedly induced following irradiation. In OV1P, constitutive p53 protein was readily detectable and levels were induced slightly following irradiation. P21WAF1/CIP1 and MDM-2 mRNA were constitutively expressed in all the cell lines and expression was induced markedly following irradiation. There was marked radiation induced G1/S arrest in A2780 but only partial arrests in CH1, LK1, LK2, PA1 and OV1P lines. No mutations were found in A2780, CH1, LK1, LK2 and PA1 cells by single-strand conformational polymorphism (SSCP) analysis but a heterozygous point mutation was found in exon 5 of OV1P. All the cell lines were radiation sensitive and also relatively sensitive to cisplatin; however, OV1P was the most resistant being consistent with its heterozygous P53 status. AMD473 was less potent than cisplatin but a similar pattern of drug sensitivity was observed with the exception of LK2, which was resistant. CH1, LK1, LK2 and PA1 all expressed BCL-2 protein but there was no expression in A2780 and OV1P. Our results suggest an overall association between wild type P53 and radiation and platinum drug sensitivity in these ovarian cancer cell lines. Int. J. Cancer 77:913–918, 1998.© 1998 Wiley-Liss, Inc.
The Concentration-Effect Relationship of the Respiratory Depressant Effects of Alfentanil and Fentanyl (2001)

This double-blinded, randomized study evaluated the potency ratio of alfentanil and fentanyl-induced respiratory depression. The findings support the notion of parallel analgesic and respiratory depressant effects of alfentanil and fentanyl. Therefore equianalgesic concentrations of both drugs will lead to equally pronounced respiratory depression.
Selective two-photon collagen crosslinking in situ measured by Brillouin microscopy (2016)

Two-photon polymerization has enabled precise microfabrication of three-dimensional structures with applications spanning from photonic microdevices, drug delivery systems, and cellular scaffolds. We present two-photon collagen crosslinking (2P-CXL) of intact corneal tissue using riboflavin and femtosecond laser irradiation. Collagen fiber orientations and photobleaching were characterized by second harmonic generation and two-photon fluorescence imaging, respectively. Measurement of local changes in longitudinal mechanical moduli with confocal Brillouin microscopy enabled the visualization of the cross-linked pattern without perturbation of the surrounding non-irradiated regions. 2P-CXL induced stiffening was comparable to that achieved with conventional one-photon CXL. Our results demonstrate the ability to selectively stiffen biological tissue <i>in situ</i> at high resolution with broad implications in ophthalmology, laser surgery, and tissue engineering.
Genomic Analysis of Viral Outbreaks (2016)

Genomic analysis is a powerful tool for understanding viral disease outbreaks. Sequencing of viral samples is now easier and cheaper than ever before and can supplement epidemiological methods by providing nucleotide-level resolution of outbreak-causing pathogens. In this review, we describe methods used to answer crucial questions about outbreaks, such as how they began and how a disease is transmitted. More specifically, we explain current techniques for viral sequencing, phylogenetic analysis, transmission reconstruction, and evolutionary investigation of viral pathogens. By detailing the ways in which genomic data can help us understand viral disease outbreaks, we aim to provide a resource that will facilitate the response to future outbreaks.
Progress in our understanding of the biology of psoriasis. (1999)

This review describes the progress made in our understanding of the basic biology of psoriasis and how newer, safer clinical approaches to control the disease may result from these developments. It reveals how epidermal hyperproliferation can be permanently induced using transgenic mouse models, how the discovery of methods to generate humanized mouse monoclonal antibodies may be used to control the synthesis of autocrine and paracrine growth factors, how programmed cell death (apoptosis) is regulated in the epidermis, and how the abnormal synthesis of superantigens, cytokines, and chemokines can result in immune dysfunction and generate increased angiogenesis, inflammation, and epidermal hyperproliferation.
An Experimental Study on Thrombogenicity of Various Metallic Microcoils With or Without Thrombogenic Coatings (1998)

Untreated tungsten microcoils showed superior clot promoting activity compared with untreated stainless steel and platinum microcoils. Clot promoting activity of microcoils was increased after coating with thrombin, or both gelatin and thrombin compared with untreated microcoils.
Low-intensity focused ultrasound alters the latency and spatial patterns of sensory-evoked cortical responses in vivo (2018)

These findings support the heretofore unconfirmed assumption that FUS-induced sensory modulation reflects, at least in part, altered reactivity in primary sensory cortex at the site of sonication. The findings are significant given the interest in using FUS to target and alter spatial aspects of sensory receptive fields on the cerebral cortex.
Bayesian detection of periodic mRNA time profiles without use of training examples (2006)

In comparison with recently proposed alternative learning-free detectors for periodic gene expression, Bayesian inference allows systematic incorporation of diffuse a priori knowledge about, e.g. the period time. This results in relative performance improvements due to increased robustness against errors in the underlying assumptions. Results from applying the detector to mRNA expression time profiles from S. cerevisiae include several new findings that deserve further experimental studies.
Population dynamics of natural antibodies in normal and autoimmune individuals. (1991)

We have measured the quantities of naturally occurring autoantibodies in the serum of normal, unmanipulated individuals. These changes over time following broad-band complex dynamical patterns that are similar in mouse and man. The patterns more likely reflect the network architecture of the natural antibody repertoire, regulating the activation and decay of individual clones. The temporal changes of both disease-specific and nonspecific autoantibodies are consistently modified in autoimmune individuals.