gebhart/patrepeval huggingface dataset:
Synthetic Triterpenoids Cooperate with Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand to Induce Apoptosis of Breast Cancer Cells (2005)

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) has been shown to induce apoptosis specifically in cancer cells while sparing normal tissues. Unfortunately not all cancer cells respond to TRAIL; therefore, TRAIL sensitizing agents are currently being explored. We have identified synthetic triterpenoids, including 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and its derivative 1-(2-cyano-3,12-dioxooleana-1,9-dien-28-oyl) imidazole (CDDO-Im), which sensitize TRAIL-resistant cancer cells to TRAIL-mediated apoptosis. Here we show that TRAIL-treated T47D and MDA-MB-468 breast cancer cells fail to initiate detectable caspase-8 processing and, consequently, do not initiate TRAIL-mediated apoptosis. Concomitant treatment with CDDO or CDDO-Im reverses the TRAIL-resistant phenotype, promoting robust caspase-8 processing and induction of TRAIL-mediated apoptosis in vitro. The combination of triterpenoids and monoclonal anti-TRAIL receptor-1 (DR4) antibody also induces apoptosis of breast cancer cells in vitro. From a mechanistic standpoint, we show that CDDO and CDDO-Im down-regulate the antiapoptotic protein c-FLIP(L), and up-regulate cell surface TRAIL receptors DR4 and DR5. CDDO and CDDO-Im, when used in combination with TRAIL, have no adverse affect on cultured normal human mammary epithelial cells. Moreover, CDDO-Im and TRAIL are well tolerated in mice and the combination of CDDO-Im and TRAIL reduces tumor burden in vivo in an MDA-MB-468 tumor xenograft model. These data suggest that CDDO and CDDO-Im may be useful for selectively reversing the TRAIL-resistant phenotype in cancer but not normal cells.
The murine growth differentiation factor 15 is not essential for systemic iron homeostasis in phlebotomized mice (2012)

In conditions of increased erythropoiesis, expression of hepcidin, the master regulator of systemic iron homeostasis, is decreased to allow for the release of iron into the blood stream from duodenal enterocytes and macrophages. It has been suggested that hepcidin suppression is controlled by growth differentiation factor 15 (GDF15), a member of the transforming growth factor-β superfamily of cytokines that is secreted from developing erythroblasts. In this study, we analyzed iron-related parameters in mice deficient for GDF15 under steady-state conditions and in response to increased erythropoietic activity induced by blood loss. We demonstrate that GDF15 suppresses the hepatic mRNA expression of some BMP/TGFβ target genes but not of hepcidin, and show that GDF15 is not required to balance iron homeostasis in response to blood loss.
Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with sunitinib or pazopanib in patients (pts) with metastatic renal cell carcinoma (mRCC). (2014)

5010 Background: Antiangiogenic agents sunitinib (S) and pazopanib (P) are SOC for mRCC, but new therapies are needed as pts advance through therapy with limited survival benefit. We report preliminary results of a phase I trial of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, in combination with S or P in pts with mRCC. Methods: mRCC patients (≥1 prior systemic therapy) received nivolumab in combination with S (50 mg, 4 wks on, 2 wks off; arm S) or P (800 mg daily; arm P), until progression/unacceptable toxicity. Starting dose of nivolumab was 2 mg/kg IV Q3W (N2), with planned escalation to 5mg/kg IV Q3W (N5). Based on tolerability, arm S N5 cohort was expanded to treatment-naïve pts. Primary objectives were safety/tolerability and determination of maximum tolerated dose (MTD) for the combinations; secondary objective was antitumor activity (objective response rate [ORR] and duration of response [DOR]). Results: 7 pts were assigned to each of arms S N2 and N5. No dose-limiting toxicities (DLTs) were observed and MTD was not reached thus N5 was expanded with 19 additional pts (total n=33). Arm P enrolled 20 pts at N2; 4 DLTs (elevated ALT/AST [n=3], fatigue [n=1]) were observed, leading to closure of this arm. Grade 3–4 related AEs were observed in 24/33 pts (73%) in arm S and 12/20 pts (60%) in arm P. Most common related grade 3–4 AEs included elevated ALT (18%), hypertension and hyponatremia (15% each) in arm S and elevated ALT/ AST (20% each) and fatigue (15%) in arm P. Hepatotoxicities were manageable using treatment algorithms. Grade 3 pneumonitis occurred in 1 pt (arm S, N5). Grade 3–4 related AEs led to therapy discontinuation in 8/33 pts (24%; 1 N2, 7 N5) in arm S and 4/20 pts (20%) in arm P. ORR was 52% (17/33) in arm S and 45% (9/20) in arm P. Responses occurred by first assessment (6 wks) in 41% (arm S) and 56% (arm P) of responding pts and were durable (range: arm S: 12.1+ to 54 wks; arm P: 12.1 to 69.1+ wks). Stable disease rate was 33% (n=11) in arm S and 35% (n=7) in arm P. PFS rate at 24 wks was 78% for arm S and 55% for arm P. Conclusions: Nivolumab plus S or P showed encouraging antitumor activity and a manageable safety profile in pts with mRCC. Additional follow up will be presented. Clinical trial information: NCT01472081.
Vapour pressures up to their critical temperatures of normal alkanes and 1-alkanols (1989)

Abstract
台镜早生尘(中)——南朝情诗中的宫廷妇女肖像 (1995)

3.环境观照为了更好地理解《玉台新咏》中女性形象的环境背景,我们暂且撇开诗不谈,先看看徐陵的《玉台新咏序》是很有必要的。在序中,他把宫殿闺房作为爱情诗吟咏的典型场所。继之又罗列了历史上有名的华丽宫殿及与之相关的历史人物:
Regulation of Protein Synthesis in Heart Muscle (1971)

Abstract Components of the ribosome cycle, subunits and polysomes, were extracted from heart muscle and analyzed on exponential sucrose gradients. When MgCl2 was added in concentrations above 2 mm, subunits were aggregated and sedimented in the position in which monomeric ribosomes would be expected. Subunit peaks were identified by extraction and analysis of RNA. Perfusion of hearts with buffer containing phenylalanine and glucose decreased polysomes and increased levels of ribosomal subunits. These findings, together with a fall in the rate of protein synthesis, indicated that a block in initiation of peptide chains had developed during perfusion of the heart. When 1 or 5 times normal plasma levels of amino acids were added to the buffer, protein synthesis increased and levels of subunits decreased, indicating that initiation had been facilitated. However, levels of subunits and polysomes were not restored to levels in vivo. Protein synthesis in perfused hearts was inhibited by cycloheximide in association with lower levels of subunits and increased polysomes. These findings indicated that steps involved in elongation of peptide chains had been inhibited. When protein synthesis of hearts perfused with buffer containing glucose and amino acids was stimulated by addition of insulin, levels of subunits decreased and levels of polysomes rose, indicating that insulin had accelerated steps involved in initiation of peptide chains.
Critical video quality for distributed automated video surveillance (2005)

Large-scale distributed video surveillance systems pose new scalability challenges. Due to the large number of video sources in such systems, the amount of bandwidth required to transmit video streams for monitoring often strains the capability of the network. On the other hand, large-scale surveillance systems often rely on computer vision algorithms to automate surveillance tasks. We observe that these surveillance tasks present an opportunity for trade-off between the accuracy of the tasks and the bit rate of the video being sent. This paper shows that there exists a sweet spot, which we term critical video quality that can be used to reduce video bit rate without significantly affecting the accuracy of the surveillance tasks. We demonstrate this point by running extensive experiments on standard face detection and face tracking algorithms. Our experiments show that face detection works equally well even if the quality of compression is significantly reduced, and face tracking still works even if the frame rate is reduced to 6 frames per second. We further develop a prototype video surveillance system to demonstrate this idea. Our evaluation shows that we can achieve up to 29 times reduction in video bit rate when detecting faces and 16 times reduction when tracking faces. This paper also proposes a formal rate-accuracy optimization framework which can be used to determine appropriate encoding parameters in distributed video surveillance systems that are subjected to either bandwidth constraints or accuracy constraints.
NVP-DPP728 (1-[[[2-[(5-Cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)-pyrrolidine), a Slow-Binding Inhibitor of Dipeptidyl Peptidase IV (1999)

Inhibition of dipeptidyl peptidase IV (DPP-IV) has been proposed recently as a therapeutic approach to the treatment of type 2 diabetes. N-Substituted-glycyl-2-cyanopyrrolidide compounds, typified by NVP-DPP728 (1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S )-p yrrolidine), inhibit degradation of glucagon-like peptide-1 (GLP-1) and thereby potentiate insulin release in response to glucose-containing meals. In the present study NVP-DPP728 was found to inhibit human DPP-IV amidolytic activity with a K(i) of 11 nM, a k(on) value of 1.3 x 10(5) M(-)(1) s(-)(1), and a k(off) of 1.3 x 10(-)(3) s(-)(1). Purified bovine kidney DPP-IV bound 1 mol/mol [(14)C]-NVP-DPP728 with high affinity (12 nM K(d)). The dissociation constant, k(off), was 1.0 x 10(-)(3) and 1.6 x 10(-)(3) s(-)(1) in the presence of 0 and 200 microM H-Gly-Pro-AMC, respectively (dissociation t(1/2) approximately 10 min). Through kinetic evaluation of DPP-IV inhibition by the D-antipode, des-cyano, and amide analogues of NVP-DPP728, it was determined that the nitrile functionality at the 2-pyrrolidine position is required, in the L-configuration, for maximal activity (K(i) of 11 nM vs K(i) values of 5.6 to >300 microM for the other analogues tested). Surprisingly, it was found that the D-antipode, despite being approximately 500-fold less potent than NVP-DPP728, displayed identical dissociation kinetics (k(off) of 1.5 x 10(-)(3) s(-)(1)). NVP-DPP728 inhibited DPP-IV in a manner consistent with a two-step inhibition mechanism. Taken together, these data suggest that NVP-DPP728 inhibits DPP-IV through formation of a novel, reversible, nitrile-dependent complex with transition state characteristics.
Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study (2013)

Treatment with epratuzumab 2400 mg cd was well tolerated in patients with moderately to severely active SLE, and associated with improvements in disease activity. Phase III studies are ongoing.
Consensus PCR and Microarray for Diagnosis of the Genus Staphylococcus , Species, and Methicillin Resistance (2001)

We propose the use of DNA microarray for the discrimination of homologous products after a single PCR amplification with consensus primers. The method was applied to Staphylococcus identification. The femA nucleotide sequences, which are phylogenetically conserved among the staphylococci, were first amplified using a consensus primer pair together with the mecA sequence, a molecular marker for methicillin resistance. Products were then identified on a glass array. The microarray contained five selective DNA capture probes for the simultaneous and differential identification of the five most clinically relevant staphylococcal species (S. aureus, S. epidermidis, S. haemolyticus, S. hominis, and S. saprophyticus), while a consensus capture probe could detect all femA sequences, allowing the identification of the genus Staphylococcus. The mecA sequence hybridized to a specific capture probe. The identification was univocal because only a single capture probe had to be present for each sequence to be identified. The hybridization and identification processes were completed in less than 2 h. Current results demonstrate that low-density microarrays are powerful multigenotypic post-PCR analyzers and could compete with conventional bacteria identification.
Lasing characteristics of low threshold microcavity lasers using half-wave spacer layers and lateral index confinement (1995)

Data are presented characterizing threshold and transverse mode behavior of microcavity lasers, which use a half-wavelength cavity spacer layer surrounding a single quantum well active region. Selective conversion of AlAs into AlxOy is used to define lateral device dimensions of 2, 5, and 8 μm. Initial results demonstrate a continuous-wave room-temperature lasing threshold current of 97 μA for a 2 μm device and 220 μA for an 8 μm device. We show that lasing operation is influenced by the AlxOy located only 200 Å from the quantum well.
Lipopolysaccharide Sequestrants:  Structural Correlates of Activity and Toxicity in Novel Acylhomospermines (2005)

Lipopolysaccharides (LPS), otherwise termed "endotoxins", are outer membrane constituents of Gram-negative bacteria. Lipopolysaccharides play a key role in the pathogenesis of "septic shock", a major cause of mortality in the critically ill patient. Therapeutic options aimed at limiting downstream systemic inflammatory processes by targeting lipopolysaccharide do not exist at the present time. We have defined the pharmacophore necessary for small molecules to specifically bind and neutralize LPS and, using animal models of sepsis, have shown that the sequestration of circulatory LPS by small molecules is a therapeutically viable strategy. In this paper, the interactions of a series of acylated homologated spermine compounds with LPS have been characterized. The optimal acyl chain length for effective sequestration of LPS was identified to be C(16) for the monoacyl compounds. The most promising of these compounds, 4e, binds LPS with an ED(50) of 1.37 muM. Nitric oxide production in murine J774A.1 cells, as well as TNF-alpha in human blood, is inhibited in a dose-dependent manner by 4e at concentrations orders of magnitude lower than toxic doses. Administration of 4e to d-galactosamine-sensitized mice challenged with supralethal doses of LPS provided significant protection against lethality. Potent antiendotoxic activity, low toxicity, and ease of synthesis render this class of compounds candidate endotoxin-sequestering agents of potential significant therapeutic value.
Gene Therapy for Aromatic l -Amino Acid Decarboxylase Deficiency (2012)

Aromatic L-amino acid decarboxylase (AADC) is required for the synthesis of the neurotransmitters dopamine and serotonin. Children with defects in the AADC gene show compromised development, particularly in motor function. Drug therapy has only marginal effects on some of the symptoms and does not change early childhood mortality. Here, we performed adeno-associated viral vector-mediated gene transfer of the human AADC gene bilaterally into the putamen of four patients 4 to 6 years of age. All of the patients showed improvements in motor performance: One patient was able to stand 16 months after gene transfer, and the other three patients achieved supported sitting 6 to 15 months after gene transfer. Choreic dyskinesia was observed in all patients, but this resolved after several months. Positron emission tomography revealed increased uptake by the putamen of 6-[(18)F]fluorodopa, a tracer for AADC. Cerebrospinal fluid analysis showed increased dopamine and serotonin levels after gene transfer. Thus, gene therapy targeting primary AADC deficiency is well tolerated and leads to improved motor function.
Discordant effects of anti–VLA-4 treatment before and after onset of relapsing experimental autoimmune encephalomyelitis (2001)

Initial migration of encephalitogenic T cells to the central nervous system (CNS) in relapsing experimental autoimmune encephalomyelitis (R-EAE), an animal model of multiple sclerosis (MS), depends on the interaction of the alpha4 integrin (VLA-4) expressed on activated T cells with VCAM-1 expressed on activated cerebrovascular endothelial cells. Alternate homing mechanisms may be employed by infiltrating inflammatory cells after disease onset. We thus compared the ability of anti-VLA-4 to regulate proteolipid protein (PLP) 139-151-induced R-EAE when administered either before or after disease onset. Preclinical administration of anti-VLA-4 either to naive recipients of primed encephalitogenic T cells or to mice 1 week after peptide priming, i.e., before clinical disease onset, inhibited the onset and severity of clinical disease. In contrast, Ab treatment either at the peak of acute disease or during remission exacerbated disease relapses and increased the accumulation of CD4(+) T cells in the CNS. Most significantly, anti-VLA-4 treatment either before or during ongoing R-EAE enhanced Th1 responses to both the priming peptide and endogenous myelin epitopes released secondary to acute tissue damage. Collectively, these results suggest that treatment with anti-VLA-4 Ab has multiple effects on the immune system and may be problematic in treating established autoimmune diseases such as MS.
A CNN based algorithm for retinal vessel segmentation (2008)

A retinal vessel segmentation method based on cellular neural networks (CNNs) is proposed. The CNN design is characterized by a virtual template expansion obtained through a multi-step operation. It is based on linear, space-invariant 3×3 templates, and can be realized using real-life devices with minor changes. The proposed design is capable to perform vessel segmentation within short computation time. It was tested on a publicly available database of color images of the retina, using receiver operating characteristic (ROC) curves. The simulation results show the good performance, comparable with the best existing methods.
Tolerating faults in a mesh with a row of spare nodes (2003)

The authors present an efficient method for tolerating faults in a two-dimensional mesh architecture. The approach is based on adding spare components (nodes) and extra links (edges) such that the resulting architecture can be reconfigured as a mesh in the presence of faults. The cost of the fault-tolerant mesh architecture is optimized by adding about one row of redundant nodes in addition to a set of k spare nodes (while tolerating up to k node faults) and minimizing the number of links per node. The results are surprisingly efficient and seem to be practical for small values of k. The degree of the fault-tolerant architecture is k+5 for odd k, and k+6 for even k. The results can be generalized to d-dimensional meshes such that the number of spare nodes is less than the length of the shortest axis plus k, and the degree of the fault-tolerant mesh is (d-1)k+d+3 when k is odd and (d-1)k+2d+2 when k is even.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Plasma cardiotrophin-1 following acute myocardial infarction: relationship with left ventricular systolic dysfunction (2001)

The glycoprotein 130 (gp 130) signalling pathway is important in the development of heart failure. Cardiotrophin-1 (CT-1), a cytokine acting via the gp 130 pathway, is involved in the process of ventricular remodelling following acute myocardial infarction (AMI) in animals. The aims of the present study were to examine the profile of plasma CT-1 following AMI in humans, and its relationship with echocardiographic parameters of left ventricular (LV) systolic function. Serial measurements of plasma CT-1 levels were made in 60 patients at 14-48 h, 49-72 h, 73-120 h and 121-192 h following AMI and at a later clinic visit. LV function was assessed using a LV wall motion index (WMI) score on admission (WMI-1) and at the clinic visit (WMI-2). Compared with values in control subjects (29.5+/-3.6 fmol/ml), the plasma CT-1 concentration was elevated in AMI patients at 14-48 h (108.1+/-15.1 fmol/ml), 49-72 h (105.2+/-19.7 fmol/ml), 73-120 h (91.2+/-14.9 fmol/ml) and 121-192 h (118.8+/-22.6 fmol/ml), and at the clinic visit (174.9+/-30.9 fmol/ml) (P<0.0001). Levels were higher following anterior compared with inferior AMI. For patients with anterior AMI, CT-1 levels were higher at the clinic visit than at earlier times. WMI-1 correlated with CT-1 at all times prior to hospital discharge (P<0.05). On best subsets analysis, the strongest correlate with WMI-1 was CT-1 level at 49-72 h (R(2)=20%, P<0.05). In conclusion, plasma levels of CT-1 are elevated soon after AMI in humans and rise further in the subsequent weeks in patients after anterior infarction. CT-1 measured soon after AMI is indicative of LV dysfunction, and this cytokine may have a role in the development of ventricular remodelling and heart failure after AMI.
Algal autoflocculation—verification and proposed mechanism (1984)

Biomass autoflocculation in outdoor algal cultures was found to be associated with increases of culture pH levels, due to CO(2) consumption by the algal photosynthetic activity. Under these alkaline conditions, some medium chemical ions precipitated together with the algal biomass. The chemical substances involved with the process and its dependence on pH value were studied by simulation of autoflocculation in laboratory experiments. Proper concentrations of calcium and orthophosphate ions in the medium are important for autoflocculation and, in order to attain it within the pH range 8.5-9.0, the culture should contain 0.1mM-0.2mM orthophosphate and 1.5mM-2.5mM calcium prior to raising the pH level. Calcium phosphate precipitates are considered as the flocculating agent which reacts with the negatively charged surface of the algae and promotes aggregation and flocculation.
Risk Factors Related to Inflammation and Endothelial Dysfunction in the DCCT/EDIC Cohort and Their Relationship With Nephropathy and Macrovascular Complications (2008)

The best predictor for IMT progression in the DCCT/EDIC cohort was plasma fibrinogen, and the levels of soluble E-selectin discriminate patients with albuminuria better than conventional risk factors.
Diabetes and the stomach. (1984)

Abnormalities in the function of the stomach in patients with long-standing diabetes mellitus, usually insulin-dependent, may provide difficult management problems. There is a reduced frequency of peptic ulcer disease in diabetics. Gastric atrophy, often with parietal cell antibodies, is common and the frequency of pernicious anemia with its expected intrinsic factor antibodies is increased. Gastric analysis results have been conflicting but generally suggest that long-standing diabetics have lower acid levels than normals, possibly secondary to vagal neuropathy. Gastric atony occurring in a small but significant number of patients with longstanding insulin-dependent diabetes, usually with a clinically apparent peripheral neuropathy, has been associated with upper abdominal discomfort, vomiting, and a clinical picture of gastric outlet obstruction. Various degrees of subclinical delays in gastric emptying are probably present in many asymptomatic patients and, indeed, are underemphasized contributors to poor control of blood sugar levels. Studies utilizing radioactive-labeled physiological meals have demonstrated abnormalities in the gastric emptying of solids, in particular, and sometimes liquids in the latter stages of the disease. Metoclopramide, a dopamine antagonist, which stimulates upper gastrointestinal smooth musculature, results in accelerated gastric emptying; clinical trials have shown that it is capable of alleviating symptoms related to diabetic gastroparesis and with its recent approval and release in this country, it promises improved management of this entity. Another agent, domperidone, a selective peripheral dopamine antagonist with no appreciable side effects, is in this country an investigational drug which has shown clinical efficacy in Europe in improving gastric stasis syndromes.