gebhart/patrepeval huggingface dataset:
Automated endocardial contour detection in short-axis 2-D echocardiograms; methodology and assessment of variability (2003)

To obtain objective and reproducible data on left-ventricular (LV) wall motion from esophageal short-axis echocardiograms, an automated endocardial contour-detection technique has been developed. The method is based on minimum-cost contour detection using a novel iterative approach, which allows complex nonconvex contours to be found with a simple model. Required operator interaction is limited to the manual definition of the center of the LV cavity. To determine the inter- and intraoperator variabilities of this automated approach, an intermediate evaluation has been carried out on the end-systolic and end-diastolic images of 10 patient studies. The method was found to be minimally sensitive to small variations in the manually indicated LV center points. However, the algorithm requires further improvements for specific problematic image regions, such as at the sites of the papillary muscles.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Hypertriglyceridemic HyperapoB: The Unappreciated Atherogenic Dyslipoproteinemia in Type 2 Diabetes Mellitus (2001)

Abnormalities in insulin and glucose metabolism do not seem to entirely account for the high frequency of cardiovascular disease in patients with type 2 diabetes mellitus. An important additional factor may be hypertriglyceridemic hyperapoB, an atherogenic dyslipoproteinemia that is common in these patients. The major features of hypertriglyceridemic hyperapoB are hypertriglyceridemia; low levels of high-density lipoprotein cholesterol; and increased numbers of small, dense low-density lipoprotein (LDL) particles. This article reviews the pathophysiology of this disorder, focusing on the changes in lipoprotein particle number and composition rather than lipoprotein lipid levels. The in vitro and in vivo evidence that small, dense LDL are more atherogenic than normal larger, buoyant LDL is summarized, and the particularly high-risk state conferred by increased numbers of small, dense LDL is delineated. This review demonstrates how abnormalities in the plasma lipoproteins may relate to the effectiveness with which adipose tissue traps and retains fatty acid. The effects of increased fatty acid flux on the hepatic metabolism of lipids and apoB secretion are detailed, and the mechanisms by which fibrates and statins may improve these are described. An understanding of these principles should provide the physician with a more physiologic basis on which to choose appropriate therapy.
Temporal system‐level organization of the switch from glycolytic to gluconeogenic operation in yeast (2013)

The diauxic shift in Saccharomyces cerevisiae is an ideal model to study how eukaryotic cells readjust their metabolism from glycolytic to gluconeogenic operation. In this work, we generated time-resolved physiological data, quantitative metabolome (69 intracellular metabolites) and proteome (72 enzymes) profiles. We found that the diauxic shift is accomplished by three key events that are temporally organized: (i) a reduction in the glycolytic flux and the production of storage compounds before glucose depletion, mediated by downregulation of phosphofructokinase and pyruvate kinase reactions; (ii) upon glucose exhaustion, the reversion of carbon flow through glycolysis and onset of the glyoxylate cycle operation triggered by an increased expression of the enzymes that catalyze the malate synthase and cytosolic citrate synthase reactions; and (iii) in the later stages of the adaptation, the shutting down of the pentose phosphate pathway with a change in NADPH regeneration. Moreover, we identified the transcription factors associated with the observed changes in protein abundances. Taken together, our results represent an important contribution toward a systems-level understanding of how this adaptation is realized.
Induction of cyclooxygenase-2 in rat vascular smooth muscle cells in vitro and in vivo. (1994)

Prostaglandins are synthesized from arachidonic acid by the rate-limiting enzyme cyclooxygenase (prostaglandin G/H synthase). Active cyclooxygenase is encoded by two distinct and independently regulated genes, termed cyclooxygenase-1 (cox1) and cyclooxygenase-2 (cox2). In this investigation, we examined the expression of cox1 and cox2 mRNA in rat aorta following balloon deendothelialization (BDE) in vivo and in rat aortic smooth muscle cells (SMC) after serum stimulation in vitro. Two h after BDE, rat aortic cox2 mRNA levels increased greater than 50-fold relative to the lowest detectable levels on days 2 and 14. No message was detectable in non-BDE control rat aortas. Similar to the results found in vivo, cultured SMC exhibited a greater than 45-fold increase in cox2 mRNA levels after a 2-h exposure to serum. This increase was transient because cox2 levels declined at 4 and 8 h. In contrast, minimal changes in cox1 mRNA levels were observed after BDE or serum treatments. Increased levels of cox2 mRNA and corresponding protein synthesis led to an accumulation of total cyclooxygenase protein, which remained elevated 24 h after serum stimulation. Serum-treated SMC also generated greater amounts of cyclooxygenase-dependent metabolites than quiescent SMC as evidenced by marked increases in prostaglandin E2 content in conditioned media. This increase is associated with a 2.5-3.0-fold increased rate of arachidonic acid conversion to prostaglandin E2. Our data indicate that injury and serum stimulation differentially regulate mRNA and protein expression of two distinct cox genes in vascular SMC in vivo and in vitro. The findings suggest that the prostanoid responses after vascular injury are, in part, mediated by acute increases in cox2 mRNA and cyclooxygenase-2 protein.
Real-time sound source localization and separation for robot audition (2002)

Robot audition in the real world should cope with environment noises and reverberation and motor noises caused by the robot’s own movements. This paper presents the active direction-pass filter (ADPF) to separate sounds originating from the specified direction with a pair of microphones. The ADPF is implemented by hierarchical integration of visual and auditory processing with hypothetical reasoning on interaural phase difference (IPD) and interaural intensity difference (IID) for each subband. In creating hypotheses, the reference data of IPD and IID is calculated by the auditory epipolar geometry on demand. Since the performance of the ADPF depends on the direction, the ADPF controls the direction by motor movement. The human tracking and sound source separation based on the ADPF is implemented on an upper-torso humanoid and runs in real-time with 4 PCs connected over Gigabit ethernet. The signal-to-noise ratio (SNR) of each sound separated by the ADPF from a mixture of two speeches with the same loudness is improved to about 10 dB from 0 dB.
KW‐3902, a selective high affinity antagonist for adenosine A1 receptors (1996)

We demonstrate that 8‐(noradamantan‐3‐yl)‐1,3‐dipropylxanthine (KW‐3902) is a very potent and selective adenosine A 1 receptor antagonist, assessed by radioligand binding and cyclic AMP response in cells. In rat forebrain adenosine A 1 receptors labelled with [ 3 H]‐cyclohexyladenosine (CHA), KW‐3902 had a K i value of 0.19 nM, whereas it showed a K i value of 170 nM in rat striatal A 2A receptors labelled with [ 3 H]‐2‐[ p ‐(2‐carboxyethyl)‐phenethylamino]‐5′‐N‐ethylcarboxamidoadenosine (CGS21680), indicating 890 fold A 1 receptor selectivity versus the A 2A receptor. KW‐3902 at 10 μ m showed no effect on recombinant rat A 3 receptors expressed on CHO cells. Saturation studies with [ 3 H]‐KW‐3902 revealed that it bound with high affinity ( K d = 77 pM) and limited capacity ( B max = 470 fmol mg −1 of protein) to a single class of recognition sites. A high positive correlation was observed between the pharmacological profile of adenosine ligands inhibiting the binding of [ 3 H]‐KW‐3902 and that of [ 3 H]‐CHA. KW‐3902 showed potent A 1 antagonism against the inhibition of forskolin‐induced cyclic AMP accumulation in DDT1 MF‐2 cells by the Arselective agonist, cyclopentyladenosine with a dissociation constant ( K B value) of 0.34 nM. KW‐3902 antagonized 5′‐N‐ethylcarboxamidoadenosine‐elicited cyclic AMP accumulation via A 2B receptors with a K B value of 52 nM. KW‐3902 exhibited marked species‐dependent differences in the binding affinities. The highest affinity was for the rat A 1 receptor ( K i = 0.19 nM) and these values for guinea‐pig and dog A 1 receptors were 1.3 and 10 nM, respectively.
Quantitative imaging of the T cell antitumor response by positron-emission tomography (2003)

We describe a noninvasive, quantitative, and tomographic method to visualize lymphocytes within the whole animal. We used positron-emission tomography (PET) to follow the localization of adoptively transferred immune T lymphocytes. Splenic T cells from animals that had rejected a Moloney murine sarcoma virus/Moloney murine leukemia virus (M-MSV/M-MuLV)-induced tumor were marked with a PET reporter gene, injected into tumor-bearing mice, and imaged in a microPET by using a substrate specific for the reporter. Specific localization of immune T cells to the antigen-positive tumor was detected over time, by sequential imaging of the same animals. Naive T cells did not localize to the tumor site, indicating that preimmunization was required. Autoradiography and immunohistochemistry analysis corroborated the microPET data. The method we have developed can be used to assess the effects of immunomodulatory agents intended to potentiate the immune response to cancer, and can also be useful for the study of other cell-mediated immune responses, including autoimmunity.
Spontaneous currents in Josephson devices (1999)

The unconventional Josephson coupling in a ferromagnetic weak link between d-wave superconductors is studied theoretically. For strong ferromagnetic barrier influence, the unconventional coupling, with ground state phase difference across the link $0&lt;{\ensuremath{\varphi}}_{\mathrm{gs}}&lt;~\ensuremath{\pi},$ is obtained at small crystal misorientation of the superconducting electrodes, in contrast to the case of normal metal barrier, where it appears at large misorientations. In both cases, with decreasing temperature there is an increasing range of misorientations, where ${\ensuremath{\varphi}}_{\mathrm{gs}}$ varies continuously between $0$ and $\ensuremath{\pi}.$ When the weak link is a part of a superconducting ring, this is accompanied by the flow of spontaneous supercurrent, of intensity which depends (for a given misorientation) on the reduced inductance $l=2\ensuremath{\pi}{\mathrm{LI}}_{c}(T)/{\ensuremath{\Phi}}_{0},$ and is nonzero only for l greater than a critical value. For $l\ensuremath{\gg}1,$ another consequence of the unconventional coupling is the anomalous quantization of the magnetic flux.
Targeting senescent cells enhances adipogenesis and metabolic function in old age (2015)

Senescent cells accumulate in fat with aging. We previously found genetic clearance of senescent cells from progeroid INK-ATTAC mice prevents lipodystrophy. Here we show that primary human senescent fat progenitors secrete activin A and directly inhibit adipogenesis in non-senescent progenitors. Blocking activin A partially restored lipid accumulation and expression of key adipogenic markers in differentiating progenitors exposed to senescent cells. Mouse fat tissue activin A increased with aging. Clearing senescent cells from 18-month-old naturally-aged INK-ATTAC mice reduced circulating activin A, blunted fat loss, and enhanced adipogenic transcription factor expression within 3 weeks. JAK inhibitor suppressed senescent cell activin A production and blunted senescent cell-mediated inhibition of adipogenesis. Eight weeks-treatment with ruxolitinib, an FDA-approved JAK1/2 inhibitor, reduced circulating activin A, preserved fat mass, reduced lipotoxicity, and increased insulin sensitivity in 22-month-old mice. Our study indicates targeting senescent cells or their products may alleviate age-related dysfunction of progenitors, adipose tissue, and metabolism.
Control of Glucose Metabolism in Pancreatic β-Cells by Glucokinase, Hexokinase and Phosphofructokinase: Model Study With Cell Lines Derived From β-Cells (1988)

Glucose usage by soluble fractions of cell extracts from two insulin-producing cell lines, RINm5F and HIT, was investigated. Analysis of enzyme activities indicated that glucose phosphorylation and phosphofructokinase are likely to be the rate-limiting steps of glycolysis in both RINm5F and HIT cell extracts. RINm5F extracts, which lack glucokinase, exhibited relatively flat concentration-dependency curves of glucose usage and showed substantial inhibition of hexokinase. HIT cell extracts, which contain glucokinase but lack hexokinase, exhibited sigmoidal concentration-dependency curves of glucose usage, reflecting almost fully expressed glucokinase activity. A reconstituted system prepared from RINm5F and HIT cell extracts exhibited a composite concentration-dependency curve of glucose usage and showed substantial inhibition of hexokinase and almost fully expressed glucokinase. However, conditions that activate phosphofructokinase, such as addition of ammonium sulfate or fructose 2,6-bisphosphate or alkalization, removed the inhibition of hexokinase without noticeably affecting the glucokinase component of usage. Results obtained with a reconstituted system containing RINm5F cell extract and purified glucokinase were consistent with these findings. The data presented here indicate that this reconstituted cell-free system serves as a valid model for the study of aspects of glycolytic control in the islet. This model illustrates the preeminent role of glucokinase in the control of glycolysis, consistent with its glucose-sensor function in the islet. In addition, these studies help to define the contribution of phosphofructokinase to the control of glycolysis and the mechanism whereby changes in phosphofructokinase activity could modulate, via changes in the glucose 6-phosphate concentration, the activity of hexokinase and hence the net glycolytic flux.
The role of keratin proteins and their genes in the growth, structure and properties of hair (1997)

The importance of wool in the textile industry has inspired extensive research into its structure since the 1960s. Over the past several years, however, the hair follicle has increased in significance as a system for studying developmental events and the process of terminal differentiation. The present chapter seeks to integrate the expanding literature and present a broad picture of what we know of the structure and formation of hair at the cellular and molecular level. We describe in detail the hair keratin proteins and their genes, their structure, function and regulation in the hair follicle, and also the major proteins and genes of the inner and outer root sheaths. We discuss hair follicle development with an emphasis on the factors involved and describe some hair genetic diseases and transgenic and gene knockout models because, in some cases, they stimulate natural mutations that are advancing our understanding of cellular interactions in the formation of hair.
Darkroom (2014)

Specialized image signal processors (ISPs) exploit the structure of image processing pipelines to minimize memory bandwidth using the architectural pattern of line-buffering , where all intermediate data between each stage is stored in small on-chip buffers. This provides high energy efficiency, allowing long pipelines with tera-op/sec. image processing in battery-powered devices, but traditionally requires painstaking manual design in hardware. Based on this pattern, we present Darkroom, a language and compiler for image processing. The semantics of the Darkroom language allow it to compile programs directly into line-buffered pipelines, with all intermediate values in local line-buffer storage, eliminating unnecessary communication with off-chip DRAM. We formulate the problem of optimally scheduling line-buffered pipelines to minimize buffering as an integer linear program. Finally, given an optimally scheduled pipeline, Darkroom synthesizes hardware descriptions for ASIC or FPGA, or fast CPU code. We evaluate Darkroom implementations of a range of applications, including a camera pipeline, low-level feature detection algorithms, and deblurring. For many applications, we demonstrate gigapixel/sec. performance in under 0.5mm 2 of ASIC silicon at 250 mW (simulated on a 45nm foundry process), real-time 1080p/60 video processing using a fraction of the resources of a modern FPGA, and tens of megapixels/sec. of throughput on a quad-core x86 processor.
Role of endothelial selectins in wound repair. (1997)

P- and E-selectins are adhesion molecules expressed on activated endothelium and platelets at sites of vascular injury and inflammation. The selectins are important for leukocyte recruitment. Because little is known about the role of selectins in wound healing, we studied cutaneous wound repair of full-thickness excisional skin wounds in mice lacking P-selectin, E-selectin, or both of these selectins. The absence of either selectin alone had no notable effect on healing, and the only deficit observed was a delay in early neutrophil extravasation in the P-selectin-deficient mice. Mice deficient in both P- and E-selectins had markedly reduced recruitment of inflammatory cells and impaired closure of the wounds. Wound sections, studied up to 3 days after wounding, showed significant impairment of neutrophil influx. Macrophage numbers were also reduced in the double mutants at 3 and 7 days after wounding as compared with wild-type mice. Additionally, a wider epithelial gap in the wounds of the P- and E-selectin-double-deficient mice 3 days after wounding indicated delayed keratinocyte migration. These results demonstrate an important combined role for P- and E-selectins in processes leading to wound healing.
Folding of the Thrombin Aptamer into a G-Quadruplex with Sr2+:  Stability, Heat, and Hydration (2001)

It has been shown that the DNA aptamer d(G(2)T(2)G(2)TGTG(2)T(2)G(2)) adopts an intramolecular G-quadruplex structure in the presence of K+. Its affinity for trombin has been associated with the inhibition of thrombin-catalyzed fibrin clot formation. In this work, we used a combination of spectroscopy, calorimetry, density, and ultrasound techniques to determine the spectral characteristics, thermodynamics, and hydration effects for the formation of G-quadruplexes with a variety of monovalent and divalent metal ions. The formation of cation-aptamer complexes is relatively fast and highly reproducible. The comparison of their CD spectra and melting profiles as a function of strand concentration shows that K+, Rb+, NH(4)+, Sr(2+), and Ba(2+) form intramolecular cation-aptamer complexes with transition temperatures above 25 degrees C. However, the cations Li+, Na+, Cs+, Mg(2+), and Ca(2+) form weaker complexes at very low temperatures. This is consistent with the observation that metal ions with ionic radii in the range 1.3-1.5 A fit well within the two G-quartets of the complex, while the other cations cannot. The comparison of thermodynamic unfolding profiles of the Sr(2+)-aptamer and K+ -aptamer complexes shows that the Sr(2+)-aptamer complex is more stable, by approximately 18 degrees C, and unfolds with a lower endothermic heat of 8.3 kcal/mol. This is in excellent agreement with the exothermic heats of -16.8 kcal/mol and -25.7 kcal/mol for the binding of Sr(2+) and K+ to the aptamer, respectively. Furthermore, volume and compressibility parameters of cation binding show hydration effects resulting mainly from two contributions: the dehydration of both cation and guanine atomic groups and water uptake upon the folding of a single-strand into a G- quadruplex structure.
Theory of mind impairment: a distinct trait‐marker for schizophrenia spectrum disorders and bipolar disorder? (2009)

Mentalizing impairment in schizophrenia spectrum disorders and BD might reflect underlying general cognitive deficits and residual symptom expression, rather than representing a specific trait-marker.
Greatly enhanced detection of a volatile ligand at femtomolar levels using bioluminescence resonance energy transfer (BRET) (2011)

Our goal is to develop a general transduction system for G-protein coupled receptors (GPCRs). GPCRs are present in most eukaryote cells and transduce diverse extracellular signals. GPCRs comprise not only the largest class of integral membrane receptors but also the largest class of targets for therapeutic drugs. In all cases studied, binding of ligand to a GPCR leads to a sub-nanometer intramolecular rearrangement. Here, we report the creation of a novel chimaeric BRET-based biosensor by insertion of sequences encoding a bioluminescent donor and a fluorescent acceptor protein into the primary sequence of a GPCR. The BRET(2)-ODR-10 biosensor was expressed in membranes of Saccharomyces cerevisiae. Assays conducted on isolated membranes indicated an EC(50) in the femtomolar range for diacetyl. The response was ligand-specific and was abolished by a single point mutation in the receptor sequence. Novel BRET-GPCR biosensors of this type have potential application in many fields including explosive detection, quality control of food and beverage production, clinical diagnosis and drug discovery.
Patterns of cytokines released by peripheral blood leukocytes of normal donors and cancer patients during interleukin-2 activation in vitro. (1990)

We have examined the responsiveness to in vitro stimulation with high-dose recombinant interleukin-2 (IL-2) of peripheral blood leukocytes (PBLs), collected from normal donors, or from successive daily cytaphereses of cancer patients with a range of advanced malignancies, following 5 days of continuous infusion with IL-2 in vivo. Normal donor PBLs showed a transient release of tumor necrosis factor (TNF) (up to 400 pg/ml) during the first day, while factors including interferon-gamma (IFN-gamma), soluble IL-2 receptor, and soluble CD-8 showed a gradual increase to modest levels (at best) during the 4 day incubation with IL-2. In contrast, the cancer patients' PBLs, after 5 days of IL-2 activation in vivo, responded with one of two patterns of production of cytokines. In pattern I, exposure to the IL-2 resulted in a transient release of TNF during the first 48 h. The level of TNF released showed a progressive increase from PBLs harvested from the first cytapheresis (up to 50 pg of TNF/ml) through the fourth cytapheresis (up to 2,000 pg of TNF/ml). Additionally, pattern I PBLs showed significant levels of production of IFN-gamma, soluble IL-2 receptor, and soluble CD8. In pattern II, the patients' PBLs from each cytapheresis released only low levels of TNF (less than 300 pg/ml) and minimal levels of IFN-gamma, IL-2 receptor, and CD8. A pattern I response is considered to be consistent with an immunostimulatory role for IL-2, which induces a cooperative interaction of lymphocytes and macrophages that is mediated by other cytokines, while pattern II may reflect an immunosuppression in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)