gebhart/patrepeval huggingface dataset:
Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications (2008)

Hypertriglyceridemia is a risk factor for atherosclerotic coronary heart disease. Very high triglyceride (TG) levels (> or =500 mg/dl [5.65 mmol/l]) increase the risk of pancreatitis. One therapeutic option to lower TG levels is omega-3 fatty acids, which are derived from the oil of fish and other seafood. The American Heart Association has acknowledged that fish oils may decrease dysrhythmias, decrease sudden death, decrease the rate of atherosclerosis and slightly lower blood pressure, and has recommended fish consumption or fish oil supplementation as a therapeutic strategy to reduce cardiovascular disease. A prescription omega-3-acid ethyl esters (P-OM3) preparation has been available in many European nations for at least a decade, and was approved by the US FDA in 2004 to reduce very high TG levels (> or =500 mg/dl [5.65 mmol/l]). Mechanistically, most evidence suggests that omega-3 fatty acids reduce the synthesis and secretion of very-low-density lipoprotein (VLDL) particles, and increase TG removal from VLDL and chylomicron particles through the upregulation of enzymes, such as lipoprotein lipase. Omega-3 fatty acids differ mechanistically from other lipid-altering drugs, which helps to explain why therapies such as P-OM3 have complementary mechanisms of action and, thus, complementary lipid benefits when administered with statins. Additional human studies are needed to define more clearly the cellular and molecular basis for the TG-lowering effects of omega-3 fatty acids and their favorable cardiovascular effects, particularly in patients with hypertriglyceridemia.
Insights into Structure-Activity Relationships and CNS Therapeutic Applications of NR2B Selective Antagonists (2010)

Excessive stimulation of NMDA receptors is involved in various CNS pathologies such as Parkinson's disease, acute and chronic pain and cerebral ischaemia. The use of NMDA antagonists as therapeutic agents has been restricted as a result of unwanted side effects including hallucinations and loss of co-ordination. NR2B subtype selective antagonists have previously shown a therapeutic effect without causing the side effects of broad spectrum NMDA antagonists. Considerable research has since been devoted to the development of orally bioavailable, selective NR2B antagonists and their applications in various neurological diseases. The improved therapeutic index of these compounds is expected to be the result of the subtype selectivity and cellular location of the NR2B receptors within the CNS. This review describes recent advances in the development of NR2B antagonists as well as their therapeutic applications.
Directional Loudspeakers Using Sound Beams (2000)

The relative merits of two directional loudspeakers intended for localized sound-field production, each driven by a single, compact transducer, are considered. They are intended for applications in which audio is required by listeners congregated in a small region of an otherwise reverberant or noisy environment, such as multimedia venues involving kiosks, museum displays, theme parks, and game centers. The loudspeakers are end-fire line arrays consisting of 1) a ducted point source employing a single compression driver, in which the point sources are at the open ends of tubes of unequal length connected to a common manifold and 2) a parametric acoustic source produced by an intense beam of ultrasound. The directionality, frequency response, and audio output of the arrays are compared by measurement and simulation.
A Logical Topology and Discrete Capacity Assignment Algorithm for Reconfigurable Networks (1995)

A reconfigurable network is a circuit-switched network where the effective topology and capacities can be dynamically adapted to changes in the traffic requirements or to changes in the structure of the network due to failures. The application of reconfigurable networks considered in this paper is data communications. We formulated the joint topology, capacity and routing problem in a reconfigurable network as a nonlinear, mixed integer programming problem. To solve this problem, we present a partial branch-and-bound algorithm. The reduced gradient method is used to solve the problem with the integrality constraints relaxed. Lagrangian relaxation is applied to obtain lower bounds. In the computational experiments, the algorithm found good solutions in a few minutes of CPU time. In addition, the reduction in the minimal delay due to the reconfiguration capability can be as large as 62%.
Urinary cystatin C is diagnostic of acute kidney injury and sepsis, and predicts mortality in the intensive care unit (2010)

Australian New Zealand Clinical Trials Registry ACTRN012606000032550.
Discovery and Structural Optimization of N5-Substituted 6,7-Dioxo-6,7-dihydropteridines as Potent and Selective Epidermal Growth Factor Receptor (EGFR) Inhibitors against L858R/T790M Resistance Mutation (2016)

EGFR-targeted inhibitors (gefitinib and erlotinib) provided an effective strategy for the treatment of non-small-cell lung cancer. However, the EGFR T790M secondary mutation has become a leading cause of clinically acquired resistance to these agents. Herein, on the basis of the previously reported irreversible EGFR inhibitor (compound 9), we present a structure-based design approach, which is rationalized via analyzing its binding model and comparing the differences of gatekeeper pocket between the T790M mutant and wild-type (WT) EGFR kinases. Guided by these results, a novel 6,7-dioxo-6,7-dihydropteridine scaffold was discovered and hydrophobic modifications at N5-position were conducted to strengthen nonpolar contacts and improve mutant selectivity over EGFR(WT). Finally, the most representative compound 17d was identified. This work demonstrates the power of structure-based strategy in discovering lead compounds and provides molecular insights into the selectivity of EGFR(L858R/T790M) over EGFR(WT), which may play an important role in designing new classes of mutant-selective EGFR inhibitors.
Alcelaphine herpesvirus type 1 has a semaphorin-like gene (1995)

Alcelaphine herpesvirus type 1, a rhadinovirus causing malignant catarrhal fever of ruminants, has an 1959 nucleotide open reading frame with significant homologies to semaphorin genes. While truncated genes of similar structure have been found in poxviruses, this is the first known example of a semaphorin-like gene in a herpesvirus.
Does bacitracin have an absorption-enhancing effect in the intestine? (1995)

We studied the absorption enhancement effects of three types of protease inhibitors, aprotinin, bacitracin and soybean trypsin inhibitor, in the rat intestine. Of these protease inhibitors, bacitracin enhanced the absorption of FD-4 and phenol red from the rat small and large intestine without mucosal toxicity. Thus, it was suggested that bacitracin has not only a protease-inhibitory but also an absorption-enhancing capability.
Apolipoprotein A-I mimetic peptide helix number and helix linker influence potentially anti-atherogenic properties (2008)

We hypothesize that apolipoprotein A-I (apoA-I) mimetic peptides better mimicking the punctuated alpha-helical repeats of full-length apoA-I are more anti-inflammatory and anti-atherogenic. This study compares a monomeric apoA-I mimetic helix to three different tandem helix peptides in vitro: 4F (18 mer), 4F-proline-4F (37 mer, Pro), 4F-alanine-4F (37 mer, Ala), and 4F-KVEPLRA-4F [the human apoA-I 4/5 interhelical sequence (IHS), 43 mer]. All peptides cleared turbid lipid suspensions, with 4F being most effective. In contrast to lipid clearance, tandem peptides were more effective at remodeling mouse HDL. All four peptides displaced apoA-I and apoE from the HDL, leaving a larger particle containing apoA-II and peptide. Peptide-remodeled HDL particles show no deficit in ABCG1 cholesterol efflux despite the loss of the majority of apoA-I. Tandem peptides show greater ability to efflux cholesterol from lipid-loaded murine macrophages, compared with 4F. Although 4F inhibited oxidation of purified mouse LDL, the Ala tandem peptide increased oxidation. We compared several tandem 4F-based peptides with monomeric 4F in assays that correlated with suggested anti-inflammatory/anti-atherogenic pathways. Tandem 4F-based peptides, which better mimic full-length apoA-I, exceed monomeric 4F in HDL remodeling and cholesterol efflux but not LDL oxidation protection. In addition, apoA-I mimetic peptides may increase reverse cholesterol transport through both ABCA1 as well as ABCG1 pathways.
Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors (2013)

The main goal of brain tumor surgery is to maximize tumor resection while preserving brain function. However, existing imaging and surgical techniques do not offer the molecular information needed to delineate tumor boundaries. We have developed a system to rapidly analyze and classify brain tumors based on lipid information acquired by desorption electrospray ionization mass spectrometry (DESI-MS). In this study, a classifier was built to discriminate gliomas and meningiomas based on 36 glioma and 19 meningioma samples. The classifier was tested and results were validated for intraoperative use by analyzing and diagnosing tissue sections from 32 surgical specimens obtained from five research subjects who underwent brain tumor resection. The samples analyzed included oligodendroglioma, astrocytoma, and meningioma tumors of different histological grades and tumor cell concentrations. The molecular diagnosis derived from mass-spectrometry imaging corresponded to histopathology diagnosis with very few exceptions. Our work demonstrates that DESI-MS technology has the potential to identify the histology type of brain tumors. It provides information on glioma grade and, most importantly, may help define tumor margins by measuring the tumor cell concentration in a specimen. Results for stereotactically registered samples were correlated to preoperative MRI through neuronavigation, and visualized over segmented 3D MRI tumor volume reconstruction. Our findings demonstrate the potential of ambient mass spectrometry to guide brain tumor surgery by providing rapid diagnosis, and tumor margin assessment in near-real time.
Abstract CT007: Entrectinib, an oral pan-Trk, ROS1, and ALK inhibitor in TKI-naïve patients with advanced solid tumors harboring gene rearrangements: Updated phase I results (2016)

Abstract Background: Entrectinib is a potent oral inhibitor of the tyrosine kinases TrkA, TrkB, TrkC (encoded by the genes NTRK1, NTRK2, NTRK3, respectively), ROS1, and ALK with IC50 &amp;lt; 2 nM (biochemical kinase assay). It has been evaluated in two Phase 1 studies (STARTRK-1 and ALKA-372-001) in patients with advanced or metastatic solid tumors harboring NTRK1/2/3, ROS1, or ALK molecular alterations, with or without asymptomatic or controlled CNS disease. Previously, we reported 600 mg daily as the Recommended Phase 2 Dose (RP2D) and an objective response rate of 72% in 18 tyrosine kinase inhibitor (TKI)-naïve patients with NTRK1/2/3 (4), ROS1 (8), or ALK (6) rearrangements treated at or above the RP2D (Siena et al, ESMO 2015). Methods: A 3+3 dose escalation was used to assess safety, pharmacokinetics, and identify the RP2D of entrectinib. Here we provide an update on anti-tumor activity (RECIST v1.1) and safety with continued follow-up of the cohort of patients with gene rearrangements. Results: At a median follow-up of 11 months, 11 of the 18 patients remain on study. Objective responses were observed in 3 of 4 (75%) NTRK1/2/3, 6 of 8 (75%; 1 complete response) ROS1 and 4 of 6 (67%) ALK patients, respectively. Responses were observed in NSCLC, colorectal cancer, mammary analog secretory carcinoma, and other solid tumors, as early as cycle 1 and lasting as long as &amp;gt; 2 years. Notably, a 46-year old male patient with SQSTM1-NTRK1-rearranged NSCLC previously treated with 4 lines of chemotherapy and immunotherapy achieved an overall partial response with a complete response in the brain. He remains on study in response at 10 months. The most common (&amp;gt;10%) treatment-related adverse events (AEs) at the RP2D were fatigue/asthenia (47%), dysgeusia (32%), constipation (26%), dizziness (21%), paresthesia (21%), diarrhea (16%), myalgia (16%), and weight gain (16%). Three treatment-related serious AEs were reported (2 occurred above the RP2D); all resolved with dose modifications. Conclusions: Entrectinib continues to display promising anti-tumor activity in TKI-naive patients across different solid tumor types harboring an NTRK1/2/3, ROS1, or ALK gene rearrangement. Similar patients are now being enrolled in STARTRK-2, a global Phase 2 basket study of entrectinib. Citation Format: Alexander Drilon, Filippo G. De Braud, Salvatore Siena, Sai-Hong I. Ou, Manish Patel, Myung-Ju Ahn, Jeeyun Lee, Todd M. Bauer, Anna F. Farago, Stephen V. Liu, Natasha Reddinger, Rupal Patel, David Luo, Edna Chow Maneval, Pratik S. Multani, Robert C. Doebele, Alice T. Shaw. Entrectinib, an oral pan-Trk, ROS1, and ALK inhibitor in TKI-naïve patients with advanced solid tumors harboring gene rearrangements: Updated phase I results. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT007.
Immune Suppression by Placenta Derived Adherent Cells (PDAC) Correlate with Monocyte Chemoattractant Protein-1 and IL-2 Secretion. (2006)

Abstract The placenta is a readily available and ethically non-controversial source of large amounts of therapeutic stem cells. Placenta Derived Adherent Cells (PDACs) are isolated from the placenta by one of several methods including physical disruption of tissue from several different anatomical sites within the placenta that include the amniotic membrane, chorion, placental cotyledons, or any combination thereof. Flow cytometry analysis showed that PDACs isolated from certain sites exhibit defined phenotypes, including for example CD200+ CD105+ CD73+ CD34− CD45− at percentages ≥70% and constitutively secrete IL-6, IL-8, and Monocyte Chemoattractant Protein-1 (MCP-1). PDACs demonstrate in vitro pluripotency in the adipogenic, osteogenic, and chondrogenic lineages. Furthermore, PDACs suppress T cell proliferation in certain Mixed Leukocyte Reaction (MLR) and the autologous EBV regression assays. Because secreted factors can powerfully modify immune responses and influence therapeutic use of cells, we report on the cytokine secretion in certain PDAC MLR and regression assays. Cytokines were measured on a Luminex system in supernatants from 6-day PDAC cultures, PDAC MLRs or PDAC regression assays. MLRs include PDACs, Dendritic Cells (DC)s, and T cells at DC/PDAC/T ratios 1/2/10. EBV regression assays included PDACs, EBV antigen-presenting cells (APC), and T cells at APC/PDAC/T ratios 1/2/10. Levels of IL-6 (11 ng/ml) and IL-8 (16 ng/ml) stayed constant in PDAC solo cultures, PDAC MLRs, and PDAC regression assays. MCP-1 concentration was 2 ng/ml in PDAC solo cultures, and non-suppressive control adherent cell MLRs and regression assays, but increased to 10 ng/ml in suppressed PDAC MLRs and PDAC regression assays. These values are consistent with reported MCP-1 serum levels. Interleukin-2 (IL-2) is both a T cell survival factor and an obligate factor for CD4+CD25+ T regulatory cells. T regulatory cells are not required for PDAC T cell suppression, but IL-2 levels consistently increase when MLR suppression by PDACs occurs. The CD4 MLR supernatants contained 65 pg/ml IL-2, and the CD8 MLR contained 35 pg/ml IL-2. In the 85% and 75% suppressed CD4 and CD8 PDAC MLRs, the IL-2 levels rose 5-fold to 331 pg/ml (CD4) and 2-fold to 67 pg/ml(CD8). These results indicate that IL-2 and MCP-1, traditionally known as stimulators of the immune response, may play a role in PDAC immune suppression. PDACs, which cause the secretion, may thus be useful therapeutic tools in the clinic.
Acceleration of allogeneic antitumor immunity with immune RNA in vitro and T-cell suppression by L1210 tumor bearer spleen cells. (1981)

RNA fractions extracted from the spleens of immunized animals prepared against L1210 leukemia cells can transfer allospecific cell-mediated immunity both in vitro and in vivo. Both preculture of nonsensitized lymphocytes prior to the treatment with immune RNA and additional culture of lymphocytes after 1-hr treatment with immune RNA enhance the growth-inhibitory activity of immune RNA-treated lymphocytes. Preculture for 5 hr and additional culture for 24 hr are sufficient for maximal enhancement of the growth-inhibitory activity. There is no significant difference in inhibition between lymphocytes treated with immune RNA for 1 hr and 24 hr. The growth inhibition by lymphocytes is augmented proportionally to the increase in the dose of immune RNA in vitro but not in vivo. In mice given i.p. injections of immune RNA-treated syngeneic spleen cells (before or after inoculation with L1210 cells), a significant prolongation of the mean survival time [27.0 +/- 5.4 (S.D.) days, 0.05 < p < 0.1] was not achieved when compared with control mice (21.4 +/- 1.6 days). Evidence is presented that suppressor cells in the spleens of L1210-bearing mice are involved in preventing effector cell function in vivo. The present study revealed that 8 X 10(3) and 5 X 10(5) suppressor cells were sufficient to inhibit completely the activity of immune RNA-treated effector cells in vitro and in vivo, respectively. Suppressive activity was abolished by treatment with anti-Thy 1.2 serum and complement and partially abolished with irradiation (1500 R). The suppressor cells belonged to a radiation-sensitive T-cell population. The limited activity of immune RNA in vivo is probably due to the destruction of immune RNA by RNase present in the host plasma and tissues and the acquisition of suppressor cells which inhibits nonadherent peritoneal exudate cell activity in the animal.
Signal processing methods for upper airway and pulmonary dysfunction diagnosis (1990)

Methods and algorithms for the analysis of acoustical pulmonary signals and their application to pulmonary diagnosis are examined. The analysis of breath and adventitious sounds, voice sounds and percussion, and snoring and stridor is considered. It is shown that analysis of the acoustic characteristics of the thorax by sophisticated signal processing methods shows promise for assisting clinical diagnosis. The technique is simple, quantitative, noninvasive, and objective. In some cases, especially in pediatrics, it closes a gap between the simple stethoscope and expensive invasive methods.
DNA helix destabilization by proline and betaine: possible role in the salinity tolerance process (1997)

Evidence is provided for the ability of proline, a salinity induced osmoprotectant, to destabilize the double helix and lower the Tm of DNA in a concentration dependent manner. At the reported salinity-adaptive bio-accumulation of 1 M and above, proline could considerably decrease the Tm and partially counteract the effect of sodium chloride and spermidine on DNA stability. On the contrary, several other amino acids tested did not show any such destabilizing effect on DNA helix. Enhanced susceptibility to S1 nuclease and insensitivity to DNase I in presence of increasing proline concentrations have further suggested a clear destabilization of the double helix. Such an effect is somewhat reminiscent of the interaction between betaine, another salinity induced osmolyte, and DNA resulting in decreased Tm values. These interactions may be significant in view of the abundance of such osmolytes in cells under salinity stress-adapted conditions, with many a bacterial mutant accumulating them exhibiting improved tolerance to salinity.
Thermal denaturation of DNA from bromodeoxyuridine substituted cells (1976)

The thermal denaturation of DNA from cell lines extensively substituted with bromodeoxyuridine has been examined spectrophotometrically over a wide range in ionic strength and by thermal elution from hydroxyapatite columns. BrdU substitution stabliizes DNA at all ionic strengths between 7.5 mM and 1350 mM potassium ion concentration, although a plot of log ionic strength vs Tm deviates from linearity above 150 mM. This nonlinearity is most pronounced with BrdU-substituted DNAs, resulting in a lowered delta Tm between unsubstituted and substituted DNA with increasing ionic strength. DMSO is shown to decrease the Tm of both unsubstituted and BrdU-substituted DNA equally, at a rate of .5 degrees C per 1% DMSO.
Global analysis of the mammalian RNA degradome reveals widespread miRNA-dependent and miRNA-independent endonucleolytic cleavage (2011)

The Ago2 component of the RNA-induced silencing complex (RISC) is an endonuclease that cleaves mRNAs that base pair with high complementarity to RISC-bound microRNAs. Many examples of such direct cleavage have been identified in plants, but not in vertebrates, despite the conservation of catalytic capacity in vertebrate Ago2. We performed parallel analysis of RNA ends (PAREs), a deep sequencing approach that identifies 5'-phosphorylated, polyadenylated RNAs, to detect potential microRNA-directed mRNA cleavages in mouse embryo and adult tissues. We found that numerous mRNAs are potentially targeted for cleavage by endogenous microRNAs, but at very low levels relative to the mRNA abundance, apart from miR-151-5p-guided cleavage of the N4BP1 mRNA. We also find numerous examples of non-miRNA-directed cleavage, including cleavage of a group of mRNAs within a CA-repeat consensus sequence. The PARE analysis also identified many examples of adenylated small non-coding RNAs, including microRNAs, tRNA processing intermediates and various other small RNAs, consistent with adenylation being part of a widespread proof-reading and/or degradation pathway for small RNAs.
Incremental construction of minimal acyclic finite state automata and transducers (1998)

In this paper, we describe a new method for constructing minimal, deterministic, acyclic finite state automata and transducers. Traditional methods consist of two steps. The first one is to construct a trie, the second one --- to perform minimization. Our approach is to construct an automaton in a single step by adding new strings one by one and minimizing the resulting automaton on-the-fly. We present a general algorithm as well as a specialization that relies upon the lexicographical sorting of the input strings.
Observation of Berry's Phase in a Solid-State Qubit (2007)

In quantum information science, the phase of a wave function plays an important role in encoding information. Although most experiments in this field rely on dynamic effects to manipulate this information, an alternative approach is to use geometric phase, which has been argued to have potential fault tolerance. We demonstrated the controlled accumulation of a geometric phase, Berry's phase, in a superconducting qubit; we manipulated the qubit geometrically by means of microwave radiation and observed the accumulated phase in an interference experiment. We found excellent agreement with Berry's predictions and also observed a geometry-dependent contribution to dephasing.