gebhart/patrepeval huggingface dataset:
Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study (2006)

Most adults with acute lymphoblastic leukemia (ALL) who achieve complete remission (CR) will relapse. We examined the outcome of 609 adults with recurring ALL, all of whom were previously treated on the Medical Research Council (MRC) UKALL12/ECOG2993 study, where the overall survival (OS) of newly diagnosed patients is 38% (95% confidence interval [CI]=36%-41%) at 5 years. By contrast, OS at 5 years after relapse was 7% (95% CI=4%-9%). Factors predicting a good outcome after salvage therapy were young age (OS of 12% in patients younger than 20 years vs OS of 3% in patients older than 50 years; 2P<.001) and short duration of first remission (CR1) (OS of 11% in those with a CR1 of more than 2 years versus OS of 5% in those with a CR1 of less than 2 years; 2P<.001). Treatment received in CR1 did not influence outcome after relapse. In a very highly selected subgroup of patients who were able to receive HSCT after relapse, some were long-term survivors. We conclude from a large, unselected series with mature follow-up that most adults with recurring ALL, whatever their prior treatment, cannot be rescued using currently available therapies. Prevention of recurrence is the best strategy for long-term survival in this disease.
Topical Administration of Ibuprofen for Injured Athletes: Considerations, Formulations, and Comparison to Oral Delivery (2017)

Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of drugs commonly used to treat both the acute and chronic injuries sustained by athletes during training and competition. In many parts of the world, NSAIDs can be purchased over-the-counter and used without any physician oversight. However, the chronic nature of overuse injuries requires NSAIDs to be taken orally for an extended period of time. As a result, they can have significant adverse effects on athletes, namely gastrointestinal (GI), renal, and cardiovascular damage. Dyspepsia and upper GI ulceration and bleeding are of great concern in chronic NSAID use, and as such oral NSAIDs are generally contraindicated in those with a history of peptic ulcers or irritable bowel disease. In the setting of chronic overuse soft tissue or joint disease, topically administered NSAIDs offer an alternate route of administration that has the potential to deliver a similar level of pain and anti-inflammatory relief while bypassing the harmful side effects associated with oral intake. Topically applied NSAIDs are able to achieve high concentrations within the targeted site of action while simultaneously keeping plasma concentrations low, offering several advantages over oral administration. One commonly used generic NSAID is ibuprofen (2-(4-isobutylphenyl)propanoic acid). First synthesized in the 1960s, ibuprofen has since become widely available as an over-the-counter pharmaceutical. In this review, we outline new and different techniques that have been used to deliver ibuprofen into diseased tissues, including supersaturations, microemulsions, gels, nanosystems, and microneedles. We also review relevant clinical trials comparing transdermally delivered ibuprofen to placebo and orally administered ibuprofen.
Enantioselective Analysis of Chloroquine and Desethylchloroquine after Oral Administration of Racemic Chloroquine (1986)

An enantioselective high-performance liquid chromatographic method for chloroquine and desethylchloroquine was developed using a chiral alpha 1-acid glycoprotein column. This method was used to determine concentrations of chloroquine and desethylchloroquine enantiomers in plasma and urine from volunteers given single oral doses of racemic chloroquine. The disposition of the enantiomers was different. The renal clearance of the chloroquine enantiomers was indicative of stereoselective renal secretion of the drug, and evidence for stereoselective metabolism also was found.
A compact 2-D full-wave finite-difference frequency-domain method for general guided wave structures (2002)

A compact two-dimensional (2-D) full-wave finite-difference frequency-domain method is proposed for the analysis of dispersion characteristics of a general guided wave structure. Because the longitudinal field components are eliminated in the proposed method, only four transverse field components are involved in the final resulting eigen equation. This feature considerably reduces the required CPU time as compared to the existing approaches by which six field components are comprised. Additionally, unlike other 2-D finite-difference schemes that determine the eigenfrequency for a given propagation constant, the new method finds the propagation constant /spl beta/ for a given k/sub o/ (frequency). The new method has been verified by examining the computed results of a number of typical guided wave structures with the published results. Very good agreement is achieved.
Stem Cell Work Restarted (2007)

SEOUL—South Korea's National Bioethics Committee has decided to allow scientists to resume studies on human embryonic stem cells, removing a ban imposed in March last year after the Woo Suk Hwang scandal. Last week's decision barred transfers of human cells into animal eggs and egg donations solely for research purposes, allowing donations only of unused eggs collected originally for in vitro fertilization. South Korea's National Assembly will review the rules, which include a 3-year research ban for violators, before incorporating them in an expected bioethics bill later this year.
Organ Dysfunction in Patients with Severe Sepsis (2006)

Quantifying organ dysfunction in patients with sepsis can assist in assessing prognosis and determining treatment effectiveness. The simplicity, reliability, and reproducibility of current scores facilitate their widespread use.
Laboratory diagnosis of heparin‐associated thrombocytopenia and comparison of platelet aggregation test, heparin‐induced platelet activation test, and platelet factor 4/heparin enzyme‐linked immunosorbent assay (1994)

The majority of HAT antibodies react with a PF4/heparin complex, but there is strong evidence that other antigens are involved in some patients. The HIPA test and the PF4/heparin ELISA are sensitive for diagnosing HAT, and they complement one another.
Specific Acetylation of Chromosomal Protein HMG-17 by PCAF Alters Its Interaction with Nucleosomes (1999)

Nonhistone chromosomal proteins HMG-14 and HMG-17 are closely related nucleosomal binding proteins that unfold the higher-order chromatin structure, thereby enhancing the transcription and replication potential of chromatin. Here we report that PCAF, a transcription coactivator with intrinsic histone acetyltransferase activity, specifically acetylates HMG-17 but not HMG-14. Using mass spectrum sequence analysis, we identified the lysine at position 2 as the predominant site acetylated by PCAF. Lysine 2 is a prominent acetylation site in vivo, suggesting that this PCAF-mediated acetylation is physiologically relevant. Experiments with HMG-17 deletion mutants and competition studies with various protein fragments indicate that the specific acetylation of HMG-17 is not determined solely by the primary sequence near the acetylation site. By equilibrium dialysis we demonstrated that acetylation reduces the affinity of HMG-17 to nucleosome cores. In addition, we found that the binding of HMG-14 and HMG-17 to nucleosome cores inhibits the PCAF-mediated acetylation of histone H3. Thus, the presence of HMG-14 and HMG-17 affects the ability of PCAF to acetylate chromatin, while the acetylation of HMG-17 reduces its binding affinity to chromatin. Conceivably, in HMG-17-containing chromatin, acetylation of HMG-17 precedes the acetylation of histones.
Mammalian ORMDL Proteins Mediate the Feedback Response in Ceramide Biosynthesis (2012)

Therapeutically manipulating levels of the pro-death lipid, ceramide, requires a molecular understanding of its regulation. The mammalian ORMDL proteins are orthologues of the yeast Orm proteins (Orm1/2), which are regulators of ceramide biosynthesis. In mammalian cells, ceramide is a proapoptotic signaling sphingolipid, but it is also an obligate precursor to essential higher order sphingolipids. Therefore levels of ceramide are expected to be tightly controlled. We tested the three ORMDL isoforms for their role in homeostatically regulating ceramide biosynthesis in mammalian cells. Treatment of cells with a short chain (C6) ceramide or sphingosine resulted in a dramatic inhibition of ceramide biosynthesis. This inhibition was almost completely eliminated by ORMDL knockdown. This establishes that the ORMDL proteins mediate the feedback regulation of ceramide biosynthesis in mammalian cells. The ORMDL proteins are functionally redundant. Knockdown of all three isoforms simultaneously was required to alleviate the sphingolipid-mediated inhibition of ceramide biosynthesis. The lipid sensed by the ORMDL-mediated feedback mechanism is medium or long chain ceramide or a higher order sphingolipid. Treatment of permeabilized cells with C6-ceramide resulted in ORMDL-mediated inhibition of the rate-limiting enzyme in sphingolipid biosynthesis, serine palmitoyltransferase. This indicates that C6-ceramide inhibition requires only membrane-bound elements and does not involve diffusible proteins or small molecules. We also tested the atypical sphingomyelin synthase isoform, SMSr, for its role in the regulation of ceramide biosynthesis. This unusual enzyme has been reported to regulate ceramide levels in the endoplasmic reticulum. We were unable to detect a role for SMSr in regulating ceramide biosynthesis. We suggest that the role of SMSr may be in the regulation of downstream metabolism of ceramide.
Regulation of plasminogen activation by components of the extracellular matrix (1990)

The kinetics of activation of Glu-plasminogen (Glu-Pg) and Lys77-Pg by two-chain recombinant tissue plasminogen activator (t-PA) were determined in the presence of isolated protein components of the extracellular matrix (ECM) and compared to activation in the presence of fibrinogen and fibrinogen fragments and in the absence of added protein. Several ECM protein components were as effective as fibrinogen fragments at stimulating Pg activation. Stimulation of Glu-Pg activation resulted from both a decrease in Km and an increase in Vmax, whereas stimulation of Lys77-Pg was due primarily to increases in Vmax. The most effective stimulators of activation were basement membrane type IV collagen and gelatin which resulted in a 21- and 55-fold increase, respectively, in the kcat/Km of Glu-Pg (relative to a 10-fold increase observed with fibrinogen fragments). Amidolytic activity of t-PA was also enhanced up to 12-fold by ECM proteins. However, plasmin amidolytic activity was unaffected by the presence of added proteins. These data suggest that several ECM-associated proteins can enhanced the activation of Pg in the absence of fibrin.
Ligand for EPH-related Kinase (LERK) 7 Is the Preferred High Affinity Ligand for the HEK Receptor (1997)

HEK is a member of the EPH-like receptor tyrosine kinase family, which appear to have roles in development and oncogenesis. Recently, we purified a soluble HEK ligand which is also a ligand (AL1) for the HEK-related receptor EHK1. Promiscuity appears to be a characteristic feature of interactions between the EPH-like receptors and their ligands, termed ligands for EPH-related kinases (LERKs). This prompted us to analyze the interactions between the HEK exodomain and fusion proteins comprising candidate LERKs and the Fc portion of human IgG1 (Fc) or a FLAGTM-peptide tag by surface plasmon resonance, size exclusion high performance liquid chromatography, sedimentation equilibrium, and transphosphorylation. Our results indicate that AL1/LERK7 is the preferred high-affinity ligand for HEK, forming a stable 1:1 complex with a dissociation constant of 12 nM. As expected the apparent affinities of bivalent fusion proteins of LERKs and the Fc portion of human IgG1 had significantly reduced dissociation rates compared with their monovalent, FLAGTM-tagged derivatives. High-avidity binding of monovalent ligands can be achieved by antibody-mediated cross-linking of monovalent ligands and with LERK7 results in specific phosphorylation of the receptor. By extrapolation, our findings indicate that some of the reported LERK-receptor interactions are a consequence of the use of bivalent ligand or receptor constructs and may be functionally irrelevant.
The MIT spoken lecture processing project (2005)

We will demonstrate the MIT Spoken Lecture Processing Server and an accompanying lecture browser that students can use to quickly locate and browse lecture segments that apply to their query. We will show how lecturers can upload recorded lectures and companion text material to our server for automatic processing. The server automatically generates a time-aligned word transcript of the lecture which can be downloaded for use within a browser. We will also demonstrate a browser we have created which allows students to quickly locate and browse audio segments that are relevant to their query. These tools can provide students with easier access to audio (or audio/visual) lectures, hopefully improving their educational experience.
Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids (2004)

These results indicate that bisdemethoxycurcumin is the most active of the curcuminoids present in turmeric for modulation of MDR-1 gene. Treatment of drug resistant KB-V1 cells with curcumin increased their sensitivity to vinblastine, which was consistent with a decreased MDR-1 gene product, a P-glycoprotein, on the cell plasma membrane. Although many drugs that prevent the P-glycoprotein function have been reported, this report describes the inhibition of MDR-1 expression by a phytochemical. The modulation of MDR-1 expression may be an attractive target for new chemosensitizing agents.
Recombinational Repair of DNA Damage in Escherichia coli and Bacteriophage λ (1999)

Although homologous recombination and DNA repair phenomena in bacteria were initially extensively studied without regard to any relationship between the two, it is now appreciated that DNA repair and homologous recombination are related through DNA replication. In Escherichia coli, two-strand DNA damage, generated mostly during replication on a template DNA containing one-strand damage, is repaired by recombination with a homologous intact duplex, usually the sister chromosome. The two major types of two-strand DNA lesions are channeled into two distinct pathways of recombinational repair: daughter-strand gaps are closed by the RecF pathway, while disintegrated replication forks are reestablished by the RecBCD pathway. The phage lambda recombination system is simpler in that its major reaction is to link two double-stranded DNA ends by using overlapping homologous sequences. The remarkable progress in understanding the mechanisms of recombinational repair in E. coli over the last decade is due to the in vitro characterization of the activities of individual recombination proteins. Putting our knowledge about recombinational repair in the broader context of DNA replication will guide future experimentation.
Glucagon-like peptide-1 induces a cAMP-dependent increase of [Na+]iassociated with insulin secretion in pancreatic β-cells (2003)

Glucagon-like peptide-1 (GLP-1) elevates the intracellular free calcium concentration ([Ca2+]i) and insulin secretion in a Na+-dependent manner. To investigate a possible role of Na ion in the action of GLP-1 on pancreatic islet cells, we measured the glucose-and GLP-1-induced intracellular Na+ concentration ([Na+]i), [Ca2+]i, and insulin secretion in hamster islet cells in various concentrations of Na+. The [Na+]i and [Ca2+]i were monitored in islet cells loaded with sodium-binding benzofuran isophthalate and fura 2, respectively. In the presence of 135 mM Na+ and 8 mM glucose, GLP-1 (10 nM) strongly increased the [Na+]i, [Ca2+]i, and insulin secretion. In the presence of 13.5 mM Na+, both glucose and GLP-1 increased neither the [Na+]i nor the [Ca2+]i. In a Na+-free medium, GLP-1 and glucose did not increase the [Na+]i. SQ-22536, an inhibitor of adenylate cyclase, and H-89, an inhibitor of PKA, incompletely inhibited the response. In the presence of both 8 mM glucose and H-89, 8-pCPT-2'-O-Me-cAMP, a PKA-independent cAMP analog, increased the insulin secretion and the [Na+]i. Therefore, we conclude that GLP-1 increases the cAMP level via activation of adenylate cyclase, which augments the membrane Na+ permeability through PKA-dependent and PKA-independent mechanisms, thereby increasing the [Ca2+]i and promoting insulin secretion from hamster islet cells.
Atom Selective Imaging and Mechanical Atom Manipulation based on Noncontact Atomic Force Microscope Method (2003)

We investigated performances and functions of the noncontact atomic force microscope (NC-AFM) method. As a result, we found that the NC-AFM functions not only as the atomic resolution microscope but also novel atomic tools based on a mechanical method as follows; a three-dimensional mapping tool of atomic force between the tip and sample atoms, a discrimination tool of atomic force mechanisms and atom species of the sample surface, a control tool of atomic force and atom position on the sample surface, and an atom manipulation tool. [DOI: 10.1380/ejssnt.2003.158]
Optimal resolution in Fresnel incoherent correlation holographic fluorescence microscopy (2011)

Fresnel Incoherent Correlation Holography (FINCH) enables holograms and 3D images to be created from incoherent light with just a camera and spatial light modulator (SLM). We previously described its application to microscopic incoherent fluorescence wherein one complex hologram contains all the 3D information in the microscope field, obviating the need for scanning or serial sectioning. We now report experiments which have led to the optimal optical, electro-optic, and computational conditions necessary to produce holograms which yield high quality 3D images from fluorescent microscopic specimens. An important improvement from our previous FINCH configurations capitalizes on the polarization sensitivity of the SLM so that the same SLM pixels which create the spherical wave simulating the microscope tube lens, also pass the plane waves from the infinity corrected microscope objective, so that interference between the two wave types at the camera creates a hologram. This advance dramatically improves the resolution of the FINCH system. Results from imaging a fluorescent USAF pattern and a pollen grain slide reveal resolution which approaches the Rayleigh limit by this simple method for 3D fluorescent microscopic imaging.
Autoradiographic localization of relaxin binding sites in rat brain. (1991)

Relaxin is a member of the insulin family of polypeptide hormones and exerts its best understood actions in the mammalian reproductive system. Using a biologically active 32P-labeled human relaxin, we have previously shown by in vitro autoradiography specific relaxin binding sites in rat uterus, cervix, and brain tissues. Using the same approach, we describe here a detailed localization of human relaxin binding sites in the rat brain. Displaceable relaxin binding sites are distributed in discrete regions of the olfactory system, neocortex, hypothalamus, hippocampus, thalamus, amygdala, midbrain, and medulla of the male and female rat brain. Characterization of the relaxin binding sites in the subfornical organ and neocortex reveals a single class of high-affinity sites (Kd = 1.4 nM) in both regions. The binding of relaxin to two of the circumventricular organs (subfornical organ and organum vasculosum of the lamina terminalis) and the neurosecretory magnocellular hypothalamic nuclei (i.e., paraventricular and supraoptic nuclei) provides the anatomical and biochemical basis for emerging physiological evidence suggesting a central role for relaxin in the control of blood pressure and hormone release. We conclude that specific, high-affinity relaxin binding sites are present in discrete regions of the rat brain and that the distribution of some of these sites may be consistent with a role for relaxin in control of vascular volume and blood pressure.
A Stable Thin‐Film Lithium Electrolyte: Lithium Phosphorus Oxynitride (1997)

The electrochemical and optical properties of lithium phosphorous oxynitride (Lipon) thin films have been studied with an emphasis on the stability window vs. lithium metal and the behavior of the Li/Lipon interface. Impedance measurements made between −26 and 140°C show that Lipon exhibits a single, ‐ion conducting phase with an average conductivity of 2.3 (±0.7) × 10−6 S/cm at 25°C and an average activation energy of . No detectable reaction or degradation was evident at the Li/Lipon interface, and linear sweep voltammetry measurements on three‐electrode cells indicated that Lipon is stable from 0 to about 5.5 V with respect to a /Li reference. The complex refractive index of Lipon was measured by spectroscopic ellipsometry. Optical bandgaps of 3.45 and 3.75 eV were obtained from the ellipsometry data and from optical absorption measurements, respectively.
The semantics of fuzzy logic (1991)

Summarized here are the results of recent research on the conceptual foundations of fuzzy logic. The focus is primarily on the principle characteristics of a model that quantifies resemblance between possible worlds by means of a similarity function that assigns a number between 0 and 1 to every pair of possible worlds. Introduction of such a function permits one to interpret the major constructs and methods of fuzzy logic: conditional and unconditional possibility and necessity distributions and the generalized modus ponens of Zadeh on the basis of related metric relationships between subsets of possible worlds.
BIOLOGICAL ACTIVITY OF THE β NERVE GROWTH FACTOR: THE EFFECTS OF VARIOUS ADDED PROTEINS (1979)

Abstract —The biological activity of β nerve growth factor varies greatly when other proteins are added to the culture medium. We have found that the biological activity can vary by a factor of 7 in a bioassay using 9 day embryonic chick sensory ganglia by adding bovine serum albumin to the culture medium. Adding the α and γ subunits in the form of 7S nerve growth factor has no effect on the biological activity of the β nerve growth factor. On the other hand, cytochrome c has an intermediate effect. Most of the increase in the biological activity seen on the addition of other proteins seems to be due to the ability of the other proteins to keep β nerve growth factor in solution; i.e. to prevent its adsorption to the culture tubes. However, some of the increase may also be due to an interaction that causes an activation of the β nerve growth factor.
Health monitoring of lithium-ion batteries (2013)

An integrated technique for health monitoring of lithium-ion batteries is presented in this paper. Monitoring is performed using an ultrasonic transducer pulser and receiver that are attached to the external surfaces of a lithium-ion cell. The cell being monitored can be representative of other cells that are part of a battery pack consisting of multiple cells connected in series, parallel, or a combination. Real time data from the ultrasonic transducer and receiver are used to non-destructively evaluate the internal condition of vital interfaces inside the cell. These interfaces are located between the anode current collector and anode active material, the cathode current collector and cathode material. The inter-electrode gap inside the battery is also measured. Information about the change in state or degradation at these interfaces can be an input into the prediction of the remaining life of the complete battery pack. Real-time measurements from the ultrasonic transducer can be utilized to update a degradation model on a battery management system.