gebhart/patrepeval huggingface dataset:
Therapies Directed Against Epidermal Growth Factor Receptor in Aerodigestive Carcinomas (2007)

EGFR is a promising therapeutic target in ADC. Further translational research is needed to optimize ways of inhibiting EGFR using single-agent or combination regimens and to identify patients who benefit the most from these therapies.
Differential Use of the βL Subunit of the Type I Interferon (IFN) Receptor Determines Signaling Specificity for IFNα2 and IFNβ (1998)

The signaling specificity for cytokines that have common receptor subunits is achieved by the presence of additional cytokine-specific receptor components. In the type I interferon (IFN) family, all 14 subtypes of IFNalpha, IFNbeta, and IFNomega bind to the same alpha and betaL subunits of the type I IFN-R, yet differences in signaling and biological effects exist among them. Our data demonstrate that IFNalpha2 and IFNbeta utilize different regions of the betaL subunit for signaling. Thus, in contrast to other cytokine systems, signal diversity in the type I IFN system can be accomplished within the same receptor complex by utilizing different regions of the same receptor subunits.
AAV8‐mediated expression of glucocerebrosidase ameliorates the storage pathology in the visceral organs of a mouse model of Gaucher disease (2006)

These data demonstrate the effectiveness of AAV-mediated gene therapy at preventing and correcting the biochemical and pathological abnormalities in a Gaucher mouse model, and thus support the continued consideration of this vector as an alternative approach to treating Gaucher disease.
Distributed computing with the CLAN network (2003)

CLAN (collapsed LAN) is a high performance user-level network targeted at the server room. It presents a simple low-level interface to applications: connection-oriented non-coherent shared memory for data transfer, and Tripwire, a user-level programmable content addressable memory (CAM) for synchronisation. This simple interface is implemented using only hardware state machines on the network interface controller (NIC), yet is flexible enough to support many different applications and communications paradigms. We show how CLAN is used to support a number of standard transport protocols and middleware: MPI, VIA, TCP/IP and CORBA. In each case we demonstrate performance that approaches,the underlying network. For TCP/IP we present our initial results using an in-kernel stack, and describe the architecture of our prototype Gigabit Ethernet/CLAN bridge, which demultiplexes Ethernet frames directly to user-level TCP/IP stacks via the CLAN network. For VIA we present a software implementation with better latency than a commercial VIA NIC implemented on ASIC technology.
The Inhibition of Autoreactive T Cell Functions by a Peptide Based on the CDR1 of an Anti-DNA Autoantibody Is via TGF-β-Mediated Suppression of LFA-1 and CD44 Expression and Function (2005)

Systemic lupus erythematosus (SLE), which is characterized by the increased production of autoantibodies and defective T cell responses, can be induced in mice by immunization with a human anti-DNA mAb that expresses a major Id, designated 16/6Id. A peptide based on the sequence of the CDR1 of the 16/6Id (human CDR1 (hCDR1)) ameliorated the clinical manifestations of SLE and down-regulated, ex vivo, the 16/6Id-induced T cell proliferation. In this study, we examined the mechanism responsible for the hCDR1-induced modulation of T cell functions related to the pathogenesis of SLE. We found that injection of hCDR1 into BALB/c mice concomitant with their immunization with 16/6Id resulted in a marked elevation of TGF-beta secretion 10 days later. Addition of TGF-beta suppressed the 16/6Id-stimulated T cell proliferation similarly to hCDR1. In addition, we provide evidence that one possible mechanism underlying the hCDR1- and TGFbeta-induced inhibition of T cell proliferation is by down-regulating the expression, and therefore the functions, of a pair of key cell adhesion receptors, LFA-1 (alphaLbeta2) and CD44, which operate as accessory molecules in mediating APC-T cell interactions. Indeed, T cells of mice treated with hCDR1 showed a TGF-beta-induced suppression of adhesion to the LFA-1 and CD44 ligands, hyaluronic acid and ICAM-1, respectively, induced by stromal cell-derived factor-1alpha and PMA. The latter suppression is through the inhibition of ERK phosphorylation. Thus, the down-regulation of SLE-associated responses by hCDR1 treatment may be due to the effect of the up-regulated TGF-beta on the expression and function of T cell adhesion receptors and, consequently, on T cell stimulation, adhesion, and proliferation.
A human myeloma cell line suitable for the generation of human monoclonal antibodies (2001)

Ever since monoclonal antibodies were produced in 1975 with mouse myeloma cells there has been interest in developing human myeloma cultures for the production of monoclonal antibodies. However, despite multiple attempts, no human myeloma line suitable for hybridoma production has been described. Here we report the derivation of a hypoxanthine-aminopterin-thymidine-sensitive and ouabain-resistant human myeloma cell line (Karpas 707H) that contains unique genetic markers. We show that this line is useful for the generation of stable human hybridomas. It can easily be fused with ouabain-sensitive Epstein-Barr virus-transformed cells as well as with fresh tonsil and blood lymphocytes, giving rise to stable hybrids that continuously secrete very large quantities of human immunoglobulins. The derived hybrids do not lose immunoglobulin secretion over many months of continuous growth. The availability of this cell line should enable the in vitro immortalization of human antibody-producing B cells that are formed in vivo. The monoclonal antibodies produced may have advantages in immunotherapy.
Three-Wave Mixing with Three Incoming Waves: Signal-Idler Coherent Attenuation and Gain Enhancement in a Parametric Amplifier (2013)

We demonstrate the time-reversed process of nondegenerate three-wave parametric amplification from three distinct sources in the fully nonlinear regime using a Josephson amplifier. In the reverse process, coherent attenuation, signal and idler beams destructively interfere in the presence of a pump to generate additional pump photons. This effect is observed through the symmetric phase-dependent amplification and attenuation of the signal and idler beams and, in the depleted pump regime, through the phase-dependent modulation of the amplifier gain, directly probing the enhancement of the pump. Results are found to be in good agreement with theory.
High-power, strained-layer amplifiers and lasers with tapered gain regions (1993)

Laterally tapered gain regions designed to accommodate the diffraction of narrow single-lobe beams that have been used in both optical amplifiers and lasers are described. Amplifier output power of 3.5 W with 3.1 W in a 1.05 times diffraction-limited lobe and laser output power of over 4 W with approximately half the power in a 1.7 times diffraction-limited lobe have been achieved.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Medical treatment of glaucoma (1991)

Recent developments in the medical management of glaucoma are reviewed for the period of October 1989 through September 1990. Topics discussed include: the protection afforded by β-adrenergic antagonists against the progression of glaucomatous damage; new studies demonstrating the efficacy of topically active carbonic anhydrase inhibitors; the efficacy and mechanisms of action of new formulations of topically administered prostaglandins; the vascular actions and consequent potential concerns as well as benefits of β-adrenergic antagonists, of calcium channel blockers, and of α2-adrenergic agonists; and possible new horizons in the medical therapy of glaucoma arising from the study of angiotensin converting enzyme inhibitors and atrial natriuretic peptides. Current Opinion in Ophthalmology 1991, 2:140-150
Synthesis and Quality Control of Thiol Tagged Compound Libraries for Chemical Microarrays (2006)

Abstract A method for the synthesis and quality control of compound collections containing reactive thiol functions was developed. Such libraries form the basis for the construction of chemical microarrays to be used in fragment‐based screening. Amino‐modified polymer membranes fixed into the wells of microtiter plates were used as the solid phase for the nanomole‐scale synthesis of a thiol‐tagged small molecule library using a spatial one‐compound/one‐well strategy. A thiolselective Liquid Chromatography‐Mass Spectroscopy (LC‐MS) protocol of each compound before attachment to the microarray surface was established, allowing an exact determination of compound purity and concentration. The established synthesis and quality control method is an important prerequisite for an accurate read‐out of the array compound–target interaction data, and simplifies the usage of small molecule microarrays for low affinity screening.
Cardiovascular abnormalities in progeria. Case report and review of the literature. (1981)

The cardiovascular findings in cases of progeria are similar in many respects to the changes associated with aging. These changes include prominent atherosclerosis and calcification of the aortic and mitral valves, coronary arteries, and aorta. The coronary artery disease leads to ischemic changes in the myocardium, including well-defined infarcts. In addition, the present case demonstrates narrowing of the small intramural arteries, which may have contributed to myocardial fibrosis.
Fatal cyclophosphamide cardiomyopathy: its clinical course and treatment. (1996)

Acute decompensating cardiomyopathy induced by cyclophosphamide is usually irreversible. To investigate the clinical course and the outcome of therapy, 13 patients (1.7%) with grade III acute cardiomyopathy and hypotension who were treated with ablative transplant regimens between January 1980 and September 1995 were analyzed. Eight of nine patients died of acute fatal restrictive cardiomyopathy with unresponsive hypotension (ARCH), whereas three of four patients who survived the initial episode died of subacute congestive heart failure (SCHF). Acute fatal restrictive cardiomyopathy was characterized with extreme sensitivity to volume overload, myocardial edema and a rapidly fatal course. It was associated with progressive, unresponsive hypotension, reduced left ventricular stroke work index (LVSWI: 29.29 +/- 9.74 g-m/beat/m2) and markedly reduced systemic and pulmonary vascular resistance indices (SVRI: 429.72 +/- 168.84, PVRI: 58.63 +/- 45.08 dyne.sec/cm5.m2). Subacute CHF was identified by myocardial edema, dilated chambers and biventricular pump failure represented by decreases in fractional shortening (FS: 19.5 +/- 4.9%). Of 10 patients who received conventional therapy, nine died and one sustained chronic CHF. One of three patients with ARCH on antioxidant therapy of ascorbic acid and theophylline survived the episode. The data suggests peripheral vascular collapse may also be responsible for fatal ARCH.
The effect of beta-xylosides on heparan sulfate synthesis by SV40-transformed Swiss mouse 3T3 cells. (1979)

The medium and cell surface heparan sulfates isolated from SV40-transformed Swiss mouse 3T3 cells were examined in the presence and absence of 1.0 mM p-nitrophenyl-beta-D-xyloside. Incubation of the SV3T3 cells with this beta-xyloside resulted in: (a) a 4- to 5-fold reduction in the molecular weight distribution of medium heparan sulfate, (b) a 10-fold increase in the total synthesis of medium heparan sulfate, and (c) a small reduction in cell growth. There was little, if any, change in either the total level of synthesis or the molecular weight distribution of cell surface heparan sulfate. The covalent association of the beta-xyloside to the medium heparan sulfate was demonstrated by an analysis of the medium heparan sulfate produced by cells grown in the presence of [35S]sulfate and the fluorogenic beta-xyloside, 4-methylumbelliferyl-beta-D-xyloside. Treatment of the purified radiolabeled and fluorogenic heparan sulfate with either nitrous acid or heparitinase resulted in a decrease in the molecular weight of both radiolabeled and fluorogenic material. The data presented in this paper are discussed with respect to both the structure of heparan sulfate and the putative role of heparan sulfate in cell social behavior.
The pro‐Th2 cytokine IL‐33 directly interacts with invariant NKT and NK cells to induce IFN‐γ production (2009)

IL-33 has recently been identified as a cytokine endowed with pro-Th2 functions, raising the question of its effect on invariant natural killer T cell (iNKT), which are potent IL-4 producers. Here, we report a two-fold increase of iNKT-cell counts in spleen and liver after a 7-day treatment of mice with IL-33, which results from a direct effect, given that purified iNKT cells express the T1/ST2 receptor constitutively and respond to IL-33 by in vitro expansion and functional activation. Conversely to the expected pro-Th2 effect, IL-33 induced a preferential increase in IFN-gamma rather than IL-4 production upon TCR engagement that depended on endogenous IL-12. Moreover, in combination with the pro-inflammatory cytokine IL-12, IL-33 enhanced IFN-gamma production by both iNKT and NK cells. Taken together these data support the conclusion that IL-33 can contribute as a co-stimulatory factor to innate cellular immune responses.
Myotonic dystrophy: candidate small molecule therapeutics (2017)

Myotonic dystrophy type 1 (DM1) is a rare multisystemic neuromuscular disorder caused by expansion of CTG trinucleotide repeats in the noncoding region of the DMPK gene. Mutant DMPK transcripts are toxic and alter gene expression at several levels. Chiefly, the secondary structure formed by CUGs has a strong propensity to capture and retain proteins, like those of the muscleblind-like (MBNL) family. Sequestered MBNL proteins cannot then fulfill their normal functions. Many therapeutic approaches have been explored to reverse these pathological consequences. Here, we review the myriad of small molecules that have been proposed for DM1, including examples obtained from computational rational design, HTS, drug repurposing, and therapeutic gene modulation.
The clinical significance of elevated levels of serum CA 19-9. (2003)

The tumour marker CA19-9 is a sensitive marker for pancreatic, gastric and hepatobiliary malignancies. High CA 19-9 level indicates unresectable lesions and a poor prognosis. The objective of the study was to determine the significance and implications of elevated CA 19-9 levels in the serum. A one-year retrospective review of all patients who had CA19-9 measured in our Medical Centre was undertaken; 69 patients were found to have CA 19-9 level above the cut-off value (37 U/ml). Thirty-six patients had malignant and the remaining 33 had benign lesions. CA 19-9 was found to be elevated in malignancies of pancreas, colorectum, lung, liver and ovary. Benign conditions associated with elevation of CA 19-9 included disease of the hepatobiliary system, pneumonia, pleural effusion, renal failure and SLE. In two individuals, there was no obvious cause for the elevation of this marker. CA 19-9 levels were significantly lower in benign than in malignant conditions. In conclusion, elevated CA 19-9 may be found in patients with benign as well as malignant disease. Therefore, it is important (1) that elevated levels of CA 19-9 are interpreted in the light of the clinical presentation of the patient and (2) to be aware of the benign conditions that can be associated with increased levels of this marker. With these factors in mind, CA 19-9 can be used to assist in the diagnosis of pancreatic cancer and assessment of resection adequacy post-operatively.
The usefulness of p63 as a marker of breast myoepithelial cells. (2004)

The identification of an outer layer of myoepithelial cells is a valuable clue in the differential diagnosis of breast lesions. Myoepithelial cells can usually be appreciated with standard hematoxylin-eosin stains, however in pathology practice one encounters difficult cases, particularly in core biopsy specimens. There are several reported markers for the immunohistochemical detection of myoepithelial cells. Smooth muscle specific proteins, such as smooth muscle actin, smooth muscle myosin heavy chain, calponin and h-caldesmone are utilized to highlight myoepithelium. Smooth muscle actin is the most commonly used and has been established as a specific and sensitive marker. However, sometimes the staining can not be interpreted, since actin stains stromal fibroblasts and vascular smooth muscle cells as well. S100 protein and specific cytokeratins (keratins 5,7,14 and 17) also stain myoepithelial cells, but the staining is not specific and is not optimally sensitive. Maspin and CD10 are relatively new and promising markers. The nuclear protein p63 has attracted much attention in recent reports. p63-positive myoepithelial cells have been shown to surround benign epithelial lesions and form a consistent, although discontinuous, rim around epithelial cells in carcinomas in situ. No staining has been noted in infiltrative carcinomas. p63-immunostaining is nuclear and so it is easily appreciated, even in cytologic preparations. It is also highly specific since neither stromal fibroblasts nor vascular smooth muscle cells are stained. In conclusion, it appears that p63 is a sensitive and specific myoepithelial marker and may be included in immunohistochemical panels aiming at identifying myoepithelial cells in problematic breast lesions.
Coronary restenosis and gene therapy. (1994)

Restenosis continues to limit the efficacy of coronary angioplasty, despite the various mechanical and pharmaceutical interventions that have been employed. The migration, proliferation, and extracellular matrix production by vascular smooth muscle cells are processes integral to restenosis, and sustained local delivery of drugs at high concentration should curtail these vascular responses to balloon angioplasty. Our laboratory and others are exploring the potential of using somatic cell gene therapy to provide such treatment and thereby prevent restenosis. However, conventional methods of gene transfer fail to produce physiologic levels of recombinant protein in vivo. This obstacle might be overcome by using adenoviral vectors to mediate efficient direct gene transfer. Herein we summarize these developments and focus upon our laboratory's progress towards evaluating adenovirus-mediated gene therapy in porcine coronary arteries. Recombinant adenoviruses directing the expression of the beta-galactosidase and luciferase reporter genes were evaluated in cultured coronary vascular smooth muscle cells in vitro and in porcine coronary arteries in vivo. Following percutaneous transluminal gene transfer in vivo, recombinant adenoviruses were shown to produce 70- to 240-fold more reporter protein than that produced by Lipofectin-DNA complexes. Furthermore, the high levels of adenovirus-mediated gene expression were shown to persist for at least 14 days following catheterization. Additional histologic studies will be required to determine the cellular distribution of gene expression and to elucidate potential interactions between adenovirus and the host's immune system, but recombinant adenovirus appears to be a promising vector for evaluating gene therapy against coronary restenosis.
Hu- ets -1 and Hu- ets -2 Genes Are Transposed in Acute Leukemias with (4;11) and (8;21) Translocations (1986)

Human probes identifying the cellular homologs of the v-ets gene, Hu-ets-1 and Hu-ets-2, and two panels of rodent-human cell hybrids were used to study specific translocations occurring in acute leukemias. The human ets-1 gene was found to translocate from chromosome 11 to 4 in the t(4;11)(q21;23), a translocation characteristic of a subtype of leukemia that represents the expansion of a myeloid/lymphoid precursor cell. Similarly, the human ets-2 gene was found to translocate from chromosome 21 to chromosome 8 in the t(8;21)(q22;q22), a nonrandom translocation commonly found in patients with acute myeloid leukemia with morphology M2 (AML-M2). Both translocations are associated with expression different from the expression in normal lymphoid cells of ets genes, raising the possibility that these genes play a role in the pathogenesis of these leukemias.
Low-Dose Nitric Oxide as Targeted Anti-biofilm Adjunctive Therapy to Treat Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis (2017)

Despite aggressive antibiotic therapy, bronchopulmonary colonization by Pseudomonas aeruginosa causes persistent morbidity and mortality in cystic fibrosis (CF). Chronic P. aeruginosa infection in the CF lung is associated with structured, antibiotic-tolerant bacterial aggregates known as biofilms. We have demonstrated the effects of non-bactericidal, low-dose nitric oxide (NO), a signaling molecule that induces biofilm dispersal, as a novel adjunctive therapy for P. aeruginosa biofilm infection in CF in an ex vivo model and a proof-of-concept double-blind clinical trial. Submicromolar NO concentrations alone caused disruption of biofilms within ex vivo CF sputum and a statistically significant decrease in ex vivo biofilm tolerance to tobramycin and tobramycin combined with ceftazidime. In the 12-patient randomized clinical trial, 10 ppm NO inhalation caused significant reduction in P. aeruginosa biofilm aggregates compared with placebo across 7 days of treatment. Our results suggest a benefit of using low-dose NO as adjunctive therapy to enhance the efficacy of antibiotics used to treat acute P. aeruginosa exacerbations in CF. Strategies to induce the disruption of biofilms have the potential to overcome biofilm-associated antibiotic tolerance in CF and other biofilm-related diseases.
Novel Checkpoint 1 Inhibitors (2006)

Cell cycle ckeckpoints are activated in response to DNA damage. Their role consists in blocking the cell cycle to allow time for DNA repair. The activity of the G1 checkpoint is dependent on the p53 protein. In more than 50% of human tumor cells, the p53 gene is mutated. In the p53 mutated cells, the G1 checkpoint is lacking. In these cells, only the G2 checkpoint, although weaker than in healthy cells, provides cancer cells with the opportunity to repair the DNA after damage. Therefore, combining a G2 checkpoint inhibitor with a DNA damaging agent should force, selectively cancer cells, into a premature and lethal mitosis, due to an accumulation of DNA lesions. Among the regulators of the G2 checkpoint, Checkpoint 1 kinase (Chk1) plays a major role. A widespread interest has been recently devoted to the discovery of Chk1 inhibitors as potential useful compounds to enhance the antitumor efficiency of DNA damaging agents. This review article will summarize: (i) the chemical structures of the novel Chk1 inhibitors reported in the recent patents; (ii) their inhibitory activity towards Chk1; (iii) their effects on tumor cells in combination with DNA damaging agents; and (iv) the in vivo results on animal models.
Enhancement of Hexose Entry into Chick Fibroblasts by Starvation: Differential Effect on Galactose and Glucose (1972)

Glucose entry, as measured by 5-min uptake into the acid-soluble fraction, is enhanced 15-30 times by long-term (12-24 hr) hexose starvation of chick fibroblasts. The rate of galactose accumulation in the cells increases only 5 times under the same conditions of starvation. Several carbon and energy sources that were tested for their effect on this "derepression" can be classified as: (i) those resembling glucose in blocking the "stimulation," (ii) those permitting full "derepression"; and (iii) those partially preventing the enhanced entry. Inhibitors of protein synthesis block enhancement under conditions otherwise conducive to it. We conclude that the glucose and galactose carrier systems are not identical, based largely on the asymmetric "repression" observed when glucose and galactose are compared as "repressors."