gebhart/patrepeval huggingface dataset:
Intrinsic and coupling-induced elastic nonlinearity of lanthanum-doped lead magnesium niobate–lead titanate electrostrictive ceramic (2000)

The elastic nonlinearity of lanthanum-doped lead magnesium niobate–lead titanate electrostrictive ceramic has been investigated by using ultrasonic second-harmonic generation technique and field-induced strain measurement. A large ultrasonic nonlinearity parameter, β=30, was observed at room temperature, which is more than twice of the values for lead zirconate–lead titanate piezoelectric ceramics. The third-order elastic constant c111 has been calculated from the β value. By introducing an effective nonlinearity parameter βe that includes both the intrinsic and the electromechanical coupling generated elastic nonlinearities, the nonlinearity parameter can be accurately characterized. The strong field dependence of the nonlinearity parameter shows excellent potential for designing field tunable nonlinear devices using this material.
Towards a methanol economy based on homogeneous catalysis: methanol to H2 and CO2 to methanol (2015)

The possibility to implement both the exhaustive dehydrogenation of aqueous methanol to hydrogen and CO2 and the reverse reaction, the hydrogenation of CO2 to methanol and water, may pave the way to a methanol based economy as part of a promising renewable energy system. Recently, homogeneous catalytic systems have been reported which are able to promote either one or the other of the two reactions under mild conditions. Here, we review and discuss these developments.
Dose and Dose Intensity as Determinants of Outcome in the Adjuvant Treatment of Breast Cancer (1998)

Within the conventional dose range for this chemotherapy regimen, a higher dose is associated with better disease-free survival and overall survival.
Increased Susceptibility to Complement Attack due to Down-Regulation of Decay-Accelerating Factor/CD55 in Dysferlin-Deficient Muscular Dystrophy (2005)

Dysferlin is expressed in skeletal and cardiac muscles. However, dysferlin deficiency results in skeletal muscle weakness, but spares the heart. We compared intraindividual mRNA expression profiles of cardiac and skeletal muscle in dysferlin-deficient SJL/J mice and found down-regulation of the complement inhibitor, decay-accelerating factor/CD55, in skeletal muscle only. This finding was confirmed on mRNA and protein levels in two additional dysferlin-deficient mouse strains, A/J mice and Dysf-/- mice, as well as in patients with dysferlin-deficient muscular dystrophy. In vitro, the absence of CD55 led to an increased susceptibility of human myotubes to complement attack. Evidence is provided that decay-accelerating factor/CD55 is regulated via the myostatin-SMAD pathway. In conclusion, a novel mechanism of muscle fiber injury in dysferlin-deficient muscular dystrophy is demonstrated, possibly opening therapeutic avenues in this to date untreatable disorder.
Mechanisms of the systemic inflammatory response (1999)

The purpose of inflammation is to combat various agents that may injure the tissues. Conditions such as CPB can often cause systemic inflammation and dysfunction of major organs. Pulmonary, renal, myocardial and intestinal function may suffer various degrees of impairment during and after cardiac surgery. Although changes in major organs usually remain clinically insignificant, severe organ failure is not uncommon. The process of systemic inflammation proceeds through activation of serum proteins, activation of leucocytes and endothelial cells, secretion of cytokines, leucocyte-endothelial cell interaction, leucocyte extravasation and tissue damage. Several anti-inflammatory strategies have already been used, some of which have given promising results pertaining to further reduction in the rate of the inflammation-related complications in cardiac surgical patients.
DeTail (2012)

Web applications have now become so sophisticated that rendering a typical page may require hundreds of intra-datacenter flows. At the same time, web sites must meet strict page creation deadlines of 200-300 ms to satisfy user demands for interactivity. Long-tailed flow completion times make it challenging for web sites to meet these constraints. They are forced to choose between rendering a subset of the complex page, or delay its rendering, thus missing deadlines and sacrificing either quality or responsiveness. Either option leads to potential financial loss. In this paper, we present a new cross-layer network stack aimed at reducing the long tail of flow completion times. The approach exploits cross-layer information to reduce packet drops, prioritize latency-sensitive flows, and evenly distribute network load, effectively reducing the long tail of flow completion times. We evaluate our approach through NS-3 based simulation and Click-based implementation demonstrating our ability to consistently reduce the tail across a wide range of workloads. We often achieve reductions of over 50% in 99.9 th percentile flow completion times.
Removal of cellular cholesterol by pre-β-HDL involves plasma membrane microsolubilization (1998)

High density lipoprotein (HDL) is able to remove unesterified cholesterol from peripheral cells in the process of reverse cholesterol transport by an aqueous diffusion mechanism as well as by an apolipoprotein (apo)-mediated process. The aqueous diffusion mechanism is understood but the molecular mechanism of lipid-poor pre-beta-HDL-(apo-) mediated cholesterol removal is not known. Measurements of the initial rates of efflux of unesterified cholesterol and phospholipid from human fibroblasts to lipid-free, human apoA-I showed that both lipids are released from the cells during a 10-min incubation with apoA-I. The concentration-dependence of efflux of the lipids is the same (Km = 0.4 and 0.6 microg apoA-I/ml for cholesterol and phospholipid flux, respectively), suggesting a membrane microsolubilization process. A finite pool of about 1% of the plasma membrane cholesterol is accessible for release by solubilization; the limited size of this cholesterol pool is not due to a lack of availability of apoA-I, but rather to the restricted amount of phospholipid that is removed from the plasma membrane. Plasma membrane domains may be involved in membrane microsolubilization, but caveolar cholesterol seems not to be specifically accessed in this process. Membrane microsolubilization is the process by which pre-beta1-HDL removes cell cholesterol in the first step of reverse cholesterol transport. When apoA-I is present in the extracellular space, the relative contributions of cholesterol efflux by membrane microsolubilization and by aqueous diffusion are determined by the degree of lipidation of the apoA-I molecules.
Apoptosis in tumorigenesis and cancer therapy (1997)

Apoptosis is a morphologically and biochemically distinct form of cell death which can be triggered by a variety of extracellular agents during both normal development as well as in adult pathological states. Much progress has recently been made in understanding the molecular pathways which regulate this process as well as new intersections between these. A direct interaction between components of the 'executioner'--the ICE-family of cysteine proteases--and the Bcl-2 family of proteins, which modulate a cell's propensity to undergo apoptosis, has recently been demonstrated. New pathways to cell survival, like the PI3-K/Akt signal transduction pathway, are also providing new clues as to the regulation of cell death by growth factors and extracellular matrix for example. The links which exist between apoptosis and cancer research are several. Genetic alterations in components of the apoptosis pathway occur during tumorigenesis and confer resistance to a variety of physiological (oncogene-induced cell death, loss of adhesion, growth under hypoxia) as well as therapeutic (chemotherapy and radiation) death triggers. Similarly, antineoplastic therapies are thought to induce tumor cell apoptosis, and consequently, common mutations in apoptosis-regulatory genes carry a poor prognosis for the patient. A more detailed understanding of the biochemistry of apoptosis and the ways in which it is disabled in tumors will likely reveal new transformation selective death triggers which stimulate cell death in ways independent of components like p53 and increase the therapeutic window of these drugs in the clinics.
Discovery of a Potent, Cell Penetrant, and Selective p300/CBP-Associated Factor (PCAF)/General Control Nonderepressible 5 (GCN5) Bromodomain Chemical Probe (2016)

p300/CREB binding protein associated factor (PCAF/KAT2B) and general control nonderepressible 5 (GCN5/KAT2A) are multidomain proteins that have been implicated in retroviral infection, inflammation pathways, and cancer development. However, outside of viral replication, little is known about the dependence of these effects on the C-terminal bromodomain. Herein, we report GSK4027 as a chemical probe for the PCAF/GCN5 bromodomain, together with GSK4028 as an enantiomeric negative control. The probe was optimized from a weakly potent, nonselective pyridazinone hit to deliver high potency for the PCAF/GCN5 bromodomain, high solubility, cellular target engagement, and ≥18000-fold selectivity over the BET family, together with ≥70-fold selectivity over the wider bromodomain families.
The design and performance of a CORBA audio/video streaming service (2003)

Recent advances in network bandwidth and processing power of CPUs has led to the emergence of multimedia streaming frameworks, such as NetShow, Realvideo and Vxtreme. These frameworks typically rely on proprietary stream establishment and control mechanisms to access multimedia context. To facilitate the development of standards-based distributed multimedia streaming applications, the OMG has defined a CORBA-based specification that stipulates the key interfaces and semantics needed to control and manage audio/video streams. This paper makes two contributions to the study of CORBA-based distributed multimedia streaming frameworks. First, it describes the design and performance of an implementation of the OMG audio/video (A/V) streaming model based on TAO, which is a real-time CORBA ORB. Second, it describes the design mid performance of a distributed application that uses TAO's A/V streaming framework to establish and control MPEG video streams. Our experience with TAO's A/V streaming framework indicates that CORBA defines a flexible and efficient model for developing standards-based multimedia streaming applications.
Tumor cell sensitization to apoptotic stimuli by selective inhibition of specific Akt/PKB family members (2005)

Recent studies indicate that dysregulation of the Akt/PKB family of serine/threonine kinases is a prominent feature of many human cancers. The Akt/PKB family is composed of three members termed Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma. It is currently not known to what extent there is functional overlap between these family members. We have recently identified small molecule inhibitors of Akt. These compounds have pleckstrin homology domain-dependent, isozyme-specific activity. In this report, we present data showing the relative contribution that inhibition of the different isozymes has on the apoptotic response of tumor cells to a variety of chemotherapies. In multiple cell backgrounds, maximal induction of caspase-3 activity is achieved when both Akt1 and Akt2 are inhibited. This induction is not reversed by overexpression of functionally active Akt3. The level of caspase-3 activation achieved under these conditions is equivalent to that observed with the phosphatidylinositol-3-kinase inhibitor LY294002. We also show that in different tumor cell backgrounds inhibition of mammalian target of rapamycin, a downstream substrate of Akt, is less effective in inducing caspase-3 activity than inhibition of Akt1 and Akt2. This shows that the survival phenotype conferred by Akt can be mediated by signaling pathways independent of mammalian target of rapamycin in some tumor cell backgrounds. Finally, we show that inhibition of both Akt1 and Akt2 selectively sensitizes tumor cells, but not normal cells, to apoptotic stimuli.
Chemerin Regulates Crosstalk Between Adipocytes and Vascular Cells Through Nox (2015)

Adipocytes produce adipokines, including chemerin, a chemoattractant that mediates effects through its ChemR23 receptor. Chemerin has been linked to endothelial dysfunction and vascular injury in pathological conditions, such as obesity, diabetes mellitus, and hypertension. Molecular mechanisms underlying this are elusive. Here we assessed whether chemerin through redox-sensitive signaling influences molecular processes associated with vascular growth, apoptosis, and inflammation. Human microvascular endothelial cells and vascular smooth muscle cells were stimulated with chemerin (50 ng/mL). Chemerin increased generation of reactive oxygen species and phosphorylation of mitogen-activated protein kinases, effects that were inhibited by ML171, GKT137831 (Nox inhibitors), and N-acetylcysteine (reactive oxygen species scavenger). Chemerin increased mRNA expression of proinflammatory mediators in vascular cells and increased monocyte-to-endothelial cell attachment. In human vascular smooth muscle cells, chemerin induced phosphorylation of mitogen-activated protein kinases and stimulated proliferation (increased proliferating cell nuclear antigen expression [proliferation marker] and BrdU incorporation [proliferation assay]). Chemerin decreased phosphatidylinositol 3-kinase/protein kinase B activation and increased TUNEL-positive human vascular smooth muscle cells. In human microvascular endothelial cells, chemerin reduced endothelial nitric oxide synthase activity and nitric oxide production. Adipocyte-conditioned medium from obese/diabetic mice (db/db), which have elevated chemerin levels, increased reactive oxygen species generation in vascular smooth muscle cells, whereas adipocyte-conditioned medium from control mice had no effect. Chemerin actions were blocked by CCX 832, a ChemR23 inhibitor. Our data demonstrate that chemerin, through Nox activation and redox-sensitive mitogen-activated protein kinases signaling, exerts proapoptotic, proinflammatory, and proliferative effects in human vascular cells. These findings elucidate some molecular mechanisms through chemerin, which is increased in obesity, whereby adipocytes may influence vascular function. We identify chemerin as a novel vasoactive adipokine, which may be important in obesity-related vascular injury.
Design and fabrication of PZN-7%PT single crystal high frequency angled needle ultrasound transducers (2008)

A high-frequency angled needle ultrasound transducer with an aperture size of 0.4 x 0.56 mm2 was fabricated using a lead zinc niobate-lead titanate (PZN- 7%PT) single crystal as the active piezoelectric material. The single crystal was bonded to a conductive silver particle matching layer and a conductive epoxy backing material through direct contact curing. A parylene outer matching layer was formed by vapor deposition. Angled needle probe configuration was achieved by dicing at 45 degrees to the single crystal poling direction to satisfy a clinical request for blood flow measurement in the posterior portion of the eye. The electrical impedance magnitude and phase of the transducer were 42 Omega and -63 degrees , respectively. The measured center frequency and the fractional bandwidth at -6 dB were 43 MHz and 45%, respectively. The two-way insertion loss was approximately 17 dB. Wire phantom imaging using fabricated PZN-7%PT single crystal transducers was obtained and spatial resolutions were assessed.
Spray‐dried plasma: A post‐traumatic blood “bridge” for life‐saving resuscitation (2021)

Massive bleeding remains a major source of morbidity and mortality worldwide. Recent studies have shed light on the pathophysiology of traumatic-induced coagulopathy and the central role of endotheliopathy. Transfusion therapy has changed dramatically in the last decade with use of red cells and plasma in a 1:1 ratio. The use of early transfusion increases the likelihood of a favorable outcome. Early intervention-preferably less than 60 min of injury-is a major factor in improved survival. Experience with dried plasma products-lyophilized or freeze-dried-in Europe and South Africa has demonstrated both safety and efficacy. Dry plasma products are not available in the United States but several products are in development. Spray-dried plasma contains clinically meaningful levels of coagulation activity and in vitro data suggest robust ability to generate thrombus. The decentralized, blood-center based manufacturing model of spray-dried plasma offers advantages for availability to meet routine and extraordinary demands.
Detection of breast cancer (1990)

We do not know the cause of breast cancer, nor do we have any way of preventing the disease. All we have is conclusive evidence, based on an 18-year follow-up of the HIP data, that detection of the disease at an earlier than usual stage leads to substantial saving of lives. Our only means for accomplishing this end is through complete breast examination when a woman is apparently well. The examination must include modern mammography with the latest techniques as well as a thorough, competent clinical examination. We must perform periodic mass screening of all women who may be subject to breast cancer--all women older than age 35. Such mass screening procedures will reduce the death rate from the disease by up to 30%. Mass screening is the only means we have to save the lives of many women with breast cancer.
The KA/KS Ratio Test for Assessing the Protein-Coding Potential of Genomic Regions: An Empirical and Simulation Study (2001)

Comparative genomics is a simple, powerful way to increase the accuracy of gene prediction. In this study, we show the utility of a simple test for the identification of protein-coding exons using human/mouse sequence comparisons. The test takes advantage of the fact that in the vast majority of coding regions, synonymous substitutions (K(S)) occur much more frequently than nonsynonymous ones (K(A)) and uses the K(A)/K(S) ratio as the criterion. We show the following: (1) most of the human and mouse exons are sufficiently long and have a suitable degree of sequence divergence for the test to perform reliably; (2) the test is suited for the identification of long exons and single exon genes, which are difficult to predict by current methods; (3) the test has a false-negative rate, lower than most of current gene prediction methods and a false-positive rate lower than all current methods; (4) the test has been automated and can be used in combination with other existing gene-prediction methods.
Methods of analysis and resources available for genetic trait mapping (1999)

Methods of genetic linkage analysis are reviewed and put in context with other mapping techniques. Sources of information are outlined (books, web sites, computer programs). Special consideration is given to statistical problems in canine genetic mapping (heterozygosity, inbreeding, marker maps).
Refined crystal structure of cytoplasmic malate dehydrogenase at 2.5-.ANG. resolution (1989)

The molecular structure of cytoplasmic malate dehydrogenase from pig heart has been refined by alternating rounds of restrained least-squares methods and model readjustment on an interactive graphics system. The resulting structure contains 333 amino acids in each of the two subunits, 2 NAD molecules, 471 solvent molecules, and 2 large noncovalently bound molecules that are assumed to be sulfate ions. The crystallographic study was done on one entire dimer without symmetry restraints. Analysis of the relative position of the two subunits shows that the dimer does not obey exact 2-fold rotational symmetry; instead, the subunits are related by a 173 degrees rotation. The structure results in a R factor of 16.7% for diffraction data between 6.0 and 2.5 A, and the rms deviations from ideal bond lengths and angles are 0.017 A and 2.57 degrees, respectively. The bound coenzyme in addition to hydrophobic interactions makes numerous hydrogen bonds that either are directly between NAD and the enzyme or are with solvent molecules, some of which in turn are hydrogen bonded to the enzyme. The carboxamide group of NAD is hydrogen bonded to the side chain of Asn-130 and via a water molecule to the backbone nitrogens of Leu-157 and Asp-158 and to the carbonyl oxygen of Leu-154. Asn-130 is one of the corner residues in a beta-turn that contains the lone cis peptide bond in cytoplasmic malate dehydrogenase, situated between Asn-130 and Pro-131. The active site histidine, His-186, is hydrogen bonded from nitrogen ND1 to the carboxylate of Asp-158 and from its nitrogen NE2 to the sulfate ion bound in the putative substrate binding site. In addition to interacting with the active site histidine, this sulfate ion is also hydrogen bonded to the guanidinium group of Arg-161, to the carboxamide group of Asn-140, and to the hydroxyl group of Ser-241. It is speculated that the substrate, malate or oxaloacetate, is bound in the sulfate binding site with the substrate 1-carboxyl hydrogen bonded to the guanidinium group of Arg-161.
Myristoyl-CoA:Protein N-Myristoyltransferase, an Essential Enzyme and Potential Drug Target in Kinetoplastid Parasites (2003)

Co-translational modification of eukaryotic proteins by N-myristoylation aids subcellular targeting and protein-protein interactions. The enzyme that catalyzes this process, N-myristoyltransferase (NMT), has been characterized in the kinetoplastid protozoan parasites, Leishmania and Trypanosoma brucei. In Leishmania major, the single copy NMT gene is constitutively expressed in all parasite stages as a 48.5-kDa protein that localizes to both membrane and cytoplasmic fractions. Leishmania NMT myristoylates the target acylated Leishmania protein, HASPA, when both are co-expressed in Escherichia coli. Gene targeting experiments have shown that NMT activity is essential for viability in Leishmania. In addition, overexpression of NMT causes gross changes in parasite morphology, including the subcellular accumulation of lipids, leading to cell death. This phenotype is more extreme than that observed in Saccharomyces cerevisiae, in which overexpression of NMT activity has no obvious effects on growth kinetics or cell morphology. RNA interference assays in T. brucei have confirmed that NMT is also an essential protein in both life cycle stages of this second kinetoplastid species, suggesting that this enzyme may be an appropriate target for the development of anti-parasitic agents.