gebhart/patrepeval huggingface dataset:
A Randomized Comparison of All Transretinoic Acid (ATRA) Followed by Chemotherapy and ATRA Plus Chemotherapy and the Role of Maintenance Therapy in Newly Diagnosed Acute Promyelocytic Leukemia (1999)

All transretinoic acid (ATRA) followed by daunorubicin (DNR)-AraC chemotherapy (CT) has improved the outcome of acute promyelocytic leukemia (APL) by comparison to CT alone. In a randomized trial, (1) we compared 2 induction schedules (ATRA followed by CT [ATRA-->CT] and ATRA plus CT [ATRA+CT, with CT added on day 3 of ATRA treatment]) and (2) we assessed the role of maintenance treatment. Four hundred thirteen patients </=75 years of age and with newly diagnosed APL were included. Induction treatment was stratified on white blood cell (WBC) count and age: patients </=65 years of age and with an initial WBC count of </=5,000/microL (n = 208) were randomized between ATRA-->CT and ATRA+CT (initially randomized patients); patients with a WBC count greater than (high WBC count group, n = 163) and patients 66 to 75 years of age with a WBC count greater than 5,000/microL (elderly group, n = 42) were not initially randomized and received ATRA+CT from day 1 and ATRA -->CT, respectively. All patients achieving CR received 2 additional DNR-AraC courses (only 1 in patients 66 to 75 years of age) and were then randomized for maintenance between no treatment, intermittent ATRA (15 days every 3 months) for 2 years, continuous low-dose CT (6 mercaptopurine + methotrexate) for 2 years, or both, using a 2-by-2 factorial design. Overall, 381 (92%) of the patients achieved complete remission (CR), 31 (7%) suffered an early death, and only 1 patient had leukemic resistance. ATRA syndrome occurred in 64 patients (15%) and was fatal in 5 cases. The CR rate was similar in all induction treatment groups. Event-free survival (EFS) was significantly lower in the high WBC group (P =.0002) and close to significance in the elderly group (P =.086) as compared with initially randomized patients. Relapse at 2 years was estimated at 6% in the ATRA+CT group, versus 16% in the ATRA-->CT group (P =.04, relative risk [RR] =.41). EFS at 2 years was estimated at 84% in the ATRA+CT group, versus 77% in the ATRA-->CT group (P =.1, RR =.62). Two hundred eighty-nine patients were randomized for maintenance. The 2-year relapse rate was 11% in patients randomized to continuous maintenance CT and 27% in patients randomized to no CT (P =.0002) and 13% in patients randomized to intermittent ATRA and 25% in patients randomized to no ATRA (P =.02). An additive effect of continuous maintenance CT and intermittent ATRA was seen, and only 6 of the 74 patients who received both maintenance treatments had relapsed. Overall survival was improved in patients who received maintenance CT (P =.01), and there was a trend for better survival in patients who received maintenance ATRA (P =.22). Our findings strongly suggest that early addition of chemotherapy to ATRA and maintenance therapy combining continuous CT and intermittent ATRA can reduce the incidence of relapse in APL. This effect already translates into significantly better survival for maintenance treatment with continuous CT.
Novel pharmacologic therapies for cystic fibrosis (1999)

The diagnosis of inherited disorders is increasingly more complex. It is no longer sufficient to make a clinical diagnosis. We must determine the precise sequence abnormalities in order to select the appropriate therapeutic approach. Whereas currently approved pharmaceuticals target the symptoms of CF, progress must now be made in repairing the nucleotide abnormality or intervening to assist a defective protein. This will also be true in other disorders. Monogenic inherited diseases affecting widely different gene families, tissues, or enzymatic pathways reveal common themes in their disruption of cellular processes. It is increasingly more likely that progress made with one orphan disease may favorably influence therapeutic development for another, as is currently being recognized for diseases that result from protein folding or trafficking abnormalities.

It has been harder to foresee that drugs developed for one purpose, such as the butyrates for excretion of waste nitrogen, also have profound effects on gene regulation and alternative enzymatic pathways in diseases such as the hemoglobinopathies, cystic fibrosis, adrenoleukodystrophy, and cancer. CF is a complex systemic inherited disorder with a wide variety of severity. The relative abundance of new compounds directed at the Class II trafficking mutation ΔF508 is encouraging and likely to benefit the majority of patients with CF. Because a single mutation can affect both protein function and location, combination therapies may be needed. Multiple approaches will almost certainly be required to control this disease.
Platelet interaction with progenitor cells: Potential implications for regenerative medicine (2007)

Circulating endothelial progenitor cells have been shown to instigate new vessel formation via angiogenesis and neovascularisation and to induce ongoing vascular and tissue repair by domiciliation to sites of vascular or tissue damage. However, the mechanisms that recruit circulating endothelial progenitor cells towards vascular lesions and regulate repair mechanisms of ischemic peripheral organs are poorly described. Domiciliation of endothelial progenitor cells in peripheral tissue is a multi-step cascade including initial adhesion to subendothelial matrix or endothelium, transmigration and invasion of the target tissue. Platelets are the first circulating blood cells that interact with the injured vessel wall. They contain a number of growth factors, chemokines, cytokines and adhesive proteins that are released or surface-expressed upon platelet activation including adhesion. Recent studies suggest that platelet interaction with endothelial progenitor cells influences chemotaxis, adhesion, activation and differentiation of progenitor cells. Release of the chemokine SDF-1 from platelets enhances neovascularization through mobilization of progenitor cells. Adherent platelets recruit bone marrow-derived progenitor cells to arterial thrombi in vitro and in vivo and induce their subsequent differentiation towards an endothelial phenotype. Moreover, platelet accumulation in a co-culture system with CD34(+) progenitor cells results in the differentiation of the latter to macrophages in vitro. Although further studies are needed to elucidate the mechanisms that platelets determine the fate of endothelial progenitor cells into vascular lesions, platelet interaction with progenitor cells seems to play a decisive role in vascular and tissue regeneration.
Analysis of BRAF and N-RAS mutations in metastatic melanoma tissues. (2003)

We examined mutations in BRAF exons 11 and 15 and N-RAS exons 2 and 3, in 77 metastatic melanoma cases and 11 melanoma cell lines. Significant differences in the mutation rates observed at different metastatic sites could not be detected. The most frequent mutation, the V599E amino acid substitution in BRAF exon 15, was observed in 31 of 77 (40%) tissues and 5 of 11 (45%) cell lines. Tandem base-pair substitutions encoding V599R and V599K amino acid changes were observed in two cases. Novel findings with respect to melanoma include a cell line possessing a 2 base-pair substitution in BRAF exon 11 and a case harboring mutations in both BRAF exon 11 and N-RAS exon 3. Our data show that BRAF mutation is common in melanoma metastases, regardless of their site, that mutations include both exons 11 and 15, and suggest that anti-RAS/RAF strategies may be effective in metastatic melanoma patients.
Interferon-γ: an overview of signals, mechanisms and functions (2003)

Abstract Interferon-γ (IFN-γ) coordinates a diverse array of cellular programs through transcriptional regulation of immunologically relevant genes. This article reviews the current understanding of IFN-γ ligand, receptor, ignal transduction, and cellular effects with a focus on macrophage responses and to a lesser extent, responses from other cell types that influence macrophage function during infection. The current model for IFN-γ signal transduction is discussed, as well as signal regulation and factors conferring signal specificity. Cellular effects of IFN-γ are described, including up-regulation of pathogen recognition, antigen processing and presentation, the antiviral state, inhibition of cellular proliferation and effects on apoptosis, activation of microbicidal effector functions, immunomodulation, and leukocyte trafficking. In addition, integration of signaling and response with other cytokines and pathogen-associated molecular patterns, such as tumor necrosis factor-α, interleukin-4, type I IFNs, and lipopolysaccharide are discussed.
Targeted dual-color silica nanoparticles provide univocal identification of micrometastases in preclinical models of colorectal cancer (2012)

The results reported here demonstrate that our rationally designed modular nanosystems have the ability to produce a breakthrough in the detection of micrometastases for subsequent translation to clinics in the immediate future.
Continuous Noninvasive Glucose Monitoring Technology Based on “Occlusion Spectroscopy” (2007)

This study indicates the potential use of OrSense's NBM device as a noninvasive sensor for continuous blood glucose evaluation. The device was safe and well tolerated.
Efficient Identification of Novel Hla-A*0201–Presented Cytotoxic T Lymphocyte Epitopes in the Widely Expressed Tumor Antigen Prame by Proteasome-Mediated Digestion Analysis (2001)

We report the efficient identification of four human histocompatibility leukocyte antigen (HLA)-A(*)0201-presented cytotoxic T lymphocyte (CTL) epitopes in the tumor-associated antigen PRAME using an improved "reverse immunology" strategy. Next to motif-based HLA-A(*)0201 binding prediction and actual binding and stability assays, analysis of in vitro proteasome-mediated digestions of polypeptides encompassing candidate epitopes was incorporated in the epitope prediction procedure. Proteasome cleavage pattern analysis, in particular determination of correct COOH-terminal cleavage of the putative epitope, allows a far more accurate and selective prediction of CTL epitopes. Only 4 of 19 high affinity HLA-A(*)0201 binding peptides (21%) were found to be efficiently generated by the proteasome in vitro. This approach avoids laborious CTL response inductions against high affinity binding peptides that are not processed and limits the number of peptides to be assayed for binding. CTL clones induced against the four identified epitopes (VLDGLDVLL, PRA(100-108); SLYSFPEPEA, PRA(142-151); ALYVDSLFFL, PRA(300-309); and SLLQHLIGL, PRA(425-433)) lysed melanoma, renal cell carcinoma, lung carcinoma, and mammary carcinoma cell lines expressing PRAME and HLA-A(*)0201. This indicates that these epitopes are expressed on cancer cells of diverse histologic origin, making them attractive targets for immunotherapy of cancer.
Osteoblast-Derived Cells Express Functional Glucose-Dependent Insulinotropic Peptide Receptors1 (2000)

Glucose-dependent insulinotropic peptide (GIP) is a 42-amino acid peptide synthesized and secreted from endocrine cells in the small intestine. The role of GIP in coupling nutrient intake and insulin secretion, the incretin effect, is well known. We report that GIP receptor messenger RNA and protein are present in normal bone and osteoblast-like cell lines, and that high affinity receptors for GIP can be demonstrated by [125I]GIP binding studies. When applied to osteoblast-like cells (SaOS2), GIP stimulated increases in cellular cAMP content and intracellular calcium, with both responses being dose dependent. Moreover, administration of GIP results in elevated expression of collagen type I messenger RNA as well as an increase in alkaline phosphatase activity. Both of these effects reflect anabolic actions of presumptive osteoblasts. These results provide the first evidence that GIP receptors are present in bone and osteoblast-like cells and that GIP modulates the function of these cells.
The Influence of Tiered Layers of Surface-Grafted Poly(ethylene glycol) on Receptor−Ligand-Mediated Adhesion between Phospholipid Monolayer-Stabilized Microbubbles and Coated Glass Beads (2000)

The goal of the current study is to measure the strength of specific adhesion between a prototypical phospholipid-stabilized ultrasound contrast agent, the surface of which has been derivatized with a ligand molecule, and a glass bead surface coated with the corresponding receptor. In particular, the role of surface “architecture” (the size and density of surface-grafted molecules) in mediating adhesion is examined. The ligand surface density on bubble shells is varied by changing the mole ratios of shell components [lipid:poly(ethylene glycol) (PEG)ylated surfactant stabilizer:ligand−lipid] during preparation. Two receptor−ligand systems are tested: avidin−biotin and antifluorescein−fluorescein. The central investigative method is a novel application of the micromanipulation technique in which an individual microbubble and a glass bead are captured by separate pipets in an aqueous environment and brought into adhesive contact with each other. Aspiration pressure applied by the bead pipet is incrementally increased until the level of force required to detach the bead from the bubble is exerted. The micromanipulation technique offers the advantage that a single adhesion event can be observed under controlled conditions, and the force required to effect bubble detachment is determined from pressure and system geometry. The strength of adhesion is examined as a function of composition and structure of the lipid shell and the receptor−ligand pair. The success of adhesion between surfaces is dependent on the availability of ligand proximal to the steric barrier of surface PEG. If the ligand is attached to the shell via a PEG spacer longer than that of the PEG stabilizer, then adhesion succeeds; if the ligand is not on an extended spacer, adhesion fails. Adhesion strength increases and plateaus with increasing ligand−lipid concentration. Such phenomena must be considered when engineering a targetable stabilized contrast agent.
Participation of cathepsin L on bone resorption (1993)

The proteinase responsible for bone collagen degradation in osteo-resorption was examined. The bone pit formation induced by parathyroid hormone (PTH) was markedly suppressed by leupeptin, E-64 and cystatin A, while no inhibition was observed by CA-074, a specific inhibitor of cathepsin B. Pig leucocyte cysteine proteinase inhibitor (PLCPI), a specific inhibitor of cathepsin L, and chymostatin, a selective inhibitor of cathepsin L, completely inhibited the pit formation. Cathepsin L activity in osteoclasts was much higher than the other cathepsin activities. Serum calcium in rats placed on a low calcium diet was decreased by treatment of E-64 or cystatin A, but not by CA-074. These findings suggest that cathepsin L is the main proteinase responsible for bone collagen degradation.
STUDIES ON TSUSHIMYCIN. I (1968)

A new antibiotic, tsushimycin, was isolated from cultures of a Streptomyces strain. The antibiotic is an acidic acylpeptide related to the amphomycinglumamycin group of antibiotics. However, fatty acid analysis by means of gas-liquid chromatography revealed that the antibiotic contains isotetradecenoic acid which has not been found in known antibiotics. The constituent fatty acids as well as the amino acid composition were compared with those of the above group of antibiotics.
The synaptic vesicle protein 2C mediates the uptake of botulinum neurotoxin A into phrenic nerves (2006)

Botulinum neurotoxins (BoNTs) inhibit neurotransmitter release by selectively cleaving core components of the vesicular fusion machinery. The synaptic vesicle proteins Synaptotagmin-I and -II act as receptors for BoNT/B and BoNT/G. Here we show that BoNT/A also interacts with a synaptic vesicle protein, the synaptic vesicle glycoprotein 2C (SV2C), but not with the homologous proteins SV2A and SV2B. Binding of BoNT/A occurs at the membrane juxtaposed region preceding transmembrane domain 8. A peptide comprising the intravesicular domain between transmembrane domains 7 and 8 specifically reduces the neurotoxicity of BoNT/A at phrenic nerve preparations demonstrating the physiological relevance of this interaction.
The Impact of Fremanezumab on Migraine-Specific Health-Related Quality of Life in Episodic Migraine (P4.115) (2018)

Understand the impact of fremanezumab vs. placebo on Migraine-Specific Quality of Life (MSQoL) in episodic migraine (EM).
Association of an RNA kissing complex analyzed using 2-aminopurine fluorescence (2001)

The fluorescent probe, 2-aminopurine-2'-O-methyl riboside (2-AP) has been selectively incorporated at adenosine positions in stem-loops (so called R1inv and R2inv), derived from the ColE1 plasmid encoded RNA I and RNA II transcripts, that interact to form stable loop-loop kissing complexes and bind the RNA one modulator (Rom) protein, such that fluorescence-detected stopped-flow and equilibrium methods could be used to study the detailed mechanism of this RNA-RNA interaction. Formation of loop-loop kissing complexes between R1inv and R2inv hairpins, substituted with 2-AP at positions in the complementary loops, results in a 5-10-fold fluorescence emission decrease (F(max) = 370 nm), which provides a sensitive measure for the binding reaction. The 2-AP substituted complexes are found to have equilibrium binding properties (average K(D) = 2.6 +/- 1.7 nM) and affinity for Rom (average K(D) = 60 +/- 24 nM) that are similar to complexes formed with equivalent unlabeled hairpins. Using stopped-flow experiments, it was found that the 2-AP probes experienced at least three different microenvironments during association of the RNA complex, thus suggesting a kinetic intermediate in the kissing pathway. In contrast, dissociation of the complex was found to fit a single exponential decay (average k(off) = 8.9 x 10(-5) s(-1)). Consistent with these observations, a two-step mechanism for RNA loop-loop complex association is proposed in which the complementary loops of R1inv and R2inv first base pair to form the loop-loop helix (average k(1) = 0.13 microM(-1)s(-1)) in the initial encounter reaction, and subsequently isomerize to the final tertiary fold in a second slower step (average k(2) = 0.09 s(-1)), where the helical stacking around the junctions is optimized.
Genome-wide analysis of gene-expression profiles in chronic myeloid leukemia cells using a cDNA microarray (2003)

To characterize molecular mechanisms operating in chronic myeloid leukemia (CML) cells with a view toward development of novel therapeutic targets, we analyzed gene-expression profiles of cancer cells from 27 CML patients using a cDNA microarray representing 23,040 human genes. By comparing expression patterns of CML with those of normal cells, we identified 150 genes that were commonly highly up-regulated in CML cells. In addition to 54 genes (34 of them ESTs) whose functions are currently unknown, the up-regulated elements included genes encoding cell-cycle regulators, transcriptional activators, transcriptional factors, and protein kinases as well as proteins already known to be induced in CML, such as some hemoglobins, haptoglobin (HP1), and matrix metalloproteinase 9 (MMP-9), a protein involved in tissue remodeling and tumor invasion. On the other hand, our protocol selected 106 genes, including 13 of unknown function, as being commonly significantly down-regulated in all phases of CML. The results of semiquantitative RT-PCR experiments with 11 representatives of the up-regulated group supported the reliability of our microarray analysis. These data should provide useful information for finding candidate genes whose products might serve as molecular targets for treatment of CML patients.
Femtosecond photon echo measurements of electronic coherence relaxation between the X(1Σg+) and B(3Π0u+) states of I2 in the presence of He, Ar, N2, O2, C3H8 (2003)

Photon echo and reverse transient grating measurements of the loss of electronic coherence for molecular iodine are presented. Systematic measurements of the coherence decay rate were made as a function of buffer gas. From the dependence of decay rate on numerical density, we calculated experimental cross sections of decoherence. These values range from 135 Å2 for helium to 1170 Å2 for I2. We find Lennard-Jones parameters for the long-range interactions responsible for decoherence which can be modeled by dispersion forces.
TGF-β Induces Surface LAP Expression on Murine CD4 T Cells Independent of Foxp3 Induction (2010)

Unlike human CD4 T cells, surface LAP expression on mouse CD4 T cells is controlled by Foxp3 and TGF-β. Our newly described anti-mouse LAP mAbs will provide a useful tool for the investigation and functional analysis of T cells that express LAP on their surface.
Optimized null-subcarrier selection for CFO estimation in OFDM over frequency-selective fading channels (2002)

We address the problem of frequency synchronization in OFDM-based communications systems in the context of frequency-selective fading channels. Frequency offsets are estimated by inserting null sub-carriers into a single OFDM block. The paper clarifies issues related to acquisition range and identifiability of carrier frequency offset (CFO), and performance of estimators. A deterministic maximum likelihood estimation approach is adopted. We derive necessary and sufficient conditions on the number of null-subcarriers and their placement in order to ensure identifiability. The Cramer-Rao bound (CRB) for the CFO is derived; for a given number of null sub-carriers, the optimal placement which minimizes the CRB is derived. We show that if the number of null sub-carriers is less than half the total number of sub-carriers, performance is optimal when the null sub-carriers are equispaced.
Relationship marketing for industrial markets (1999)

The purpose of this article is to discuss the merits and applicability of relationship marketing in industrial markets. Various definitions of relationship marketing are reviewed, and a literature review of relationship marketing is presented. This forms the basis of a theoretical synthesis for a proposed model to identify ideal situations in which to apply relationship marketing in industrial markets. A conceptual framework is developed from a transaction cost perspective to identify situations in which relationship marketing is appropriate in industrial markets. Relationship marketing is necessary in buyer-seller relationships characterised by goal congruence and high performance ambiguity. Such situations offer the best opportunities for relationship marketing to decrease transaction costs and maximise joint value.
Multicast routing in bus-based computer networks (2003)

The authors address multicast routing of integrated voice, video, and messages in bus-based computer networks, particularly in grids of buses. Graph theoretical formulations of the multicast routing problem are presented and an algorithm is given that produces optimal multicast routes in grids of buses. The performance of this algorithm is compared with that of heuristic algorithms. Finally, the bilevel grid, a hierarchical grid topology, is described, and an algorithm is given that produces optimal multicast routes in such networks.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>