gebhart/patrepeval huggingface dataset:
Clinical Studies of Histone Deacetylase Inhibitors (2009)

Over the last 5 years, a plethora of histone deacetylase inhibitors (HDACi) have been evaluated in clinical trials. These drugs have in common the ability to hyperacetylate both histone and nonhistone targets, resulting in a variety of effects on cancer cells, their microenvironment, and immune responses. To date, responses with single agent HDACi have been predominantly observed in advanced hematologic malignancies including T-cell lymphoma, Hodgkin lymphoma, and myeloid malignancies. Therefore, in this review we focus upon hematologic malignancies. Generally HDACi are well tolerated with the most common acute toxicities being fatigue, gastrointestinal, and transient cytopenias. Of note, few patients have been treated for prolonged periods of time and little is known about long-term toxicities. The use of the biomarker of histone hyperacetylation has been useful as a guide to target specificity, but generally does not predict for response and the search for more clinically relevant biomarkers must continue.
The human recombinant c-kit receptor ligand, rhSCF, induces mediator release from human cutaneous mast cells and enhances IgE-dependent mediator release from both skin mast cells and peripheral blood basophils (1992)

The gene product of the steel locus of the mouse represents a growth factor for murine mast cells and a ligand for the c-kit proto-oncogene receptor, a member of the tyrosine kinase receptor class of oncogenes (for review, see O. N. Witte. 1990. Cell 63:5). We have studied the effect of the human recombinant c-kit receptor ligand stem cell factor (rhSCF) on the release of inflammatory mediators from human skin mast cells and peripheral blood basophils and compared its activity to that of rhIL-3, rhSCF (1 ng/ml to 1 microgram/ml) activated the release of histamine and PGD2 from mast cells isolated from human skin. Analysis by digital video microscopy indicated that purified human skin mast cells (84 +/- 5% pure) responded to rhSCF (0.1 to 1 microgram/ml) challenge with a rapid, sustained rise in intracellular Ca2+ levels that was accompanied by secretion of histamine. A brief preincubation (10 min) of mast cells with rhSCF (0.1 pg/ml to 1 ng/ml) significantly enhanced (100 +/- 35%) the release of histamine induced by anti-IgE (3 micrograms/ml), but was much less effective on IgE-mediated release of PGD2. In contrast, a short term incubation with rhSCF did not potentiate the secretion of histamine activated by substance P (5 microM). A 24-h incubation of mast cells with rhSCF did not affect the release of mediators induced by anti-IgE (3 micrograms/ml), probably due to receptor desensitization, rhSCF (1 ng/ml to 3 micrograms/ml) neither caused release of histamine or leukotriene C4 (LTC4) release from leukocytes of 14 donors, nor induced a rise in intracellular Ca2+ levels in purified (greater than 70%) basophils. Brief preincubation (10 min) of leukocytes with rhSCF (1 ng/ml to 3 micrograms/ml) caused an enhancement (69 +/- 11%) of anti-IgE-induced release of histamine that was significant at concentrations as low as 3 ng/ml (p less than 0.05), whereas it appeared less effective in potentiating IgE-mediated LTC4 release. In contrast, a prolonged incubation (24 h) with rhSCF (0.1 pg/ml to 100 ng/ml) did not enhance the release of histamine or LTC4 induced by anti-IgE (0.1 microgram/ml), whereas rhIL-3 (3 ng/ml) significantly potentiated the release of both mediators.(ABSTRACT TRUNCATED AT 400 WORDS)
Transsynaptic neuronal loss induced in hippocampal slice cultures by a herpes simplex virus vector expressing the GluR6 subunit of the kainate receptor. (1993)

Patients with severe temporal lobe epilepsy lose neurons within the CA3 and hilar regions of the hippocampus. Loss of CA3 and hilar neurons was also induced by transducing organotypic hippocampal slice cultures with a replication-defective herpes simplex virus (HSV) vector expressing the GluR6 kainate subtype of the glutamate receptor (HSVGluR6). In transduced fibroblasts, HSVGluR6 expressed a M(r) 115,000 protein that reacted with anti-GluR6 serum. After exposure of fibroblast to HSVGluR6, a kainate-dependent toxicity appeared in cells that were previously resistant to kainate. Microapplication of nanoliter amounts of recombinant HSV stocks into organotypic hippocampal slice cultures resulted in localized transduction and gene transfer at the site of microapplication. Microapplication of 100 HSVGluR6 virions into CA3 stratum pyramidale induced a large loss of CA3 pyramidal cells and hilar neurons, despite the small number of transduced neurons. This effect was not seen when 100 virions of HSVGluR6 were microapplied to CA1 stratum pyramidale. Tetrodotoxin or N-methyl-D-aspartate receptor antagonists inhibited the large loss of CA3 and hilar neurons, suggesting that the small cluster of HSVGluR6-transduced cells induced an N-methyl-D-aspartate-dependent transsynaptic loss of non-transduced neurons.
Nuclear Accumulation of NFAT4 Opposed by the JNK Signal Transduction Pathway (1997)

The nuclear factor of activated T cells (NFAT) group of transcription factors is retained in the cytoplasm of quiescent cells. NFAT activation is mediated in part by induced nuclear import. This process requires calcium-dependent dephosphorylation of NFAT caused by the phosphatase calcineurin. The c-Jun amino-terminal kinase (JNK) phosphorylates NFAT4 on two sites. Mutational removal of the JNK phosphorylation sites caused constitutive nuclear localization of NFAT4. In contrast, JNK activation in calcineurin-stimulated cells caused nuclear exclusion of NFAT4. These findings show that the nuclear accumulation of NFAT4 promoted by calcineurin is opposed by the JNK signal transduction pathway.
Electronic assistive devices: their impact on the quality of life of high level quadriplegic persons. (1981)

The impact of electronic assistive devices (ie, the environmental control system or ECS) on the day-to-day living of high-level quadriplegics (C3-C5) was studied. Twenty male quadriplegic persons (7 ECS users and 13 nonusers) were interviewed using the following material: Activity Pattern Indicators (APIs), Bell Adjustment Inventory, Locus of Control, Multiple Affect Adjective Checklist and McClelland's adaptation of the Thematic Apperception Test. It was found that ECS impact was most clearly demonstrated in the API results. The ECS users made greater use of a variety of adaptive devices to function relatively more independently and with minimal assistance. The users participated in more activities and spent considerably more time educating themselves than the nonusers, who more frequently participated in quiet activities and spent more time in passive recreational activities in residence. Since the ECS and other adaptive devices have a positive impact on the lives of users, patients should be exposed to them as early as possible in their rehabilitation programs to promote their acceptance. Additionally, home planning and equipment ordering should be done conjointly before discharge so that patients and their families do not become acclimated to a less safe and less efficient way of functioning. An assessment protocol consisting of both intrapsychic and behavioral measures (similar to the one presented in this article) is recommended as a comprehensive and systematic way of evaluating both the short- and long-term effects of using assistive devices.
Characterization of a p43 human thymocyte antigen. (1986)

Two murine monoclonal antibodies (MoAbs), designated WM-25 and WM-35, have been prepared which react with human thymocyte cell surface membrane antigens. Both antigens were found to be expressed by normal and leukaemic immature human thymocytes. However, comparative examination by tissue section staining, immunoprecipitation, and electrophoresis, as well as competitive binding studies, demonstrated clear differences in the antigens detected by these two MoAbs. Antibody WM-35 identified a 48 kilodalton (kD) protein expressed on epidermal Langerhans cells as well as thymocytes, and appears similar to the previously reported Mabs OKT-6 and NA1-34. In contrast, MoAb WM-25 immunoprecipitated a 43 kD antigen, non-covalently associated with a 12 kD light chain, which was not present on Langerhans cells. Competitive binding and sequential immunoprecipitation studies confirmed that the 48 and 43 kD proteins are antigenically distinct. These results support the concept of at least two forms of thymocyte antigens within Cluster of Differentiation One (CD-1).
Long Term Vagal Stimulation in Patients with Advanced Heart Failure First Experience in Man (2008)

This novel approach to the treatment of patients with HF is feasible, and appears safe and tolerable. The preliminary efficacy results appear promising. These findings suggest the opportunity to proceed with a larger multicentre study.
Early Mechanisms of Renal Injury in Hypercholesterolemic or Hypertriglyceridemic Rats (2000)

Hyperlipidemia in conjunction with uninephrectomy leads to renal injury in rats. It is unknown whether this is due to mesangial cell or podocyte injury and whether the injuries induced by hypercholesterolemia and hypertriglyceridemia share a similar pathogenesis. Therefore, renal effects of hypercholesterolemia were studied in male rats with dietary hypercholesterolemia compared with rats on a regular diet. Renal effects of hypertriglyceridemia were studied in female Nagase analbuminemic rats (NAR). Hypertriglyceridemia was reduced in NAR by ovariectomy. Both models were studied after uninephrectomy or sham operation. Dietary hypercholesterolemia had little effect on plasma triglycerides, whereas ovariectomy in the NAR had no effect on plasma cholesterol. However, an increase in intermediate density lipoprotein cholesterol was common to both models. Dietary hypercholesterolemia and uninephrectomy separately induced a similar increase in proteinuria after 13 wk, which was additive when these interventions were combined. At this stage, only a minimal increase was present in glomerular alpha-smooth muscle actin staining, a marker of mesangial cell activation, or in mesangial matrix expansion. Moreover, platelet-derived growth factor-B chain, a marker of mesangial cell proliferation, was not increased. However, podocyte injury was prominent as evidenced by podocytic de novo expression of desmin and ultrastructural changes. Glomerular macrophage counts were increased by hypercholesterolemia but not by uninephrectomy, and were not related to the level of proteinuria. Hypertriglyceridemia and uninephrectomy in female NAR induced an increase in proteinuria after 24 wk, which was also associated with an increase in podocyte desmin expression without any mesangial activation and proliferation or matrix accumulation. Hypertriglyceridemia, proteinuria, and the increase in desmin staining were largely prevented by ovariectomy. Interstitial myofibroblast activation and tubulointerstitial injury accompanied proteinuria in both models. These findings indicate that both hypercholesterolemia and hypertriglyceridemia aggravate renal injury primarily via podocyte rather than via mesangial cell damage. Such podocyte injury is accompanied by tubulointerstitial cell activation and injury.
Recent Advances in Materials with Room‐Temperature Phosphorescence: Photophysics for Triplet Exciton Stabilization (2017)

Room‐temperature phosphorescence (RTP), which has a much longer emission lifetime than fluorescence, often enables unique material characteristics and fabrication of state‐of‐the‐art optoelectronic devices that cannot be realized using conventional fluorescent materials. The triplet exciton characteristics related to the appearance of efficient RTP also often provide intrinsic intra‐ and inter‐molecular physical information about the materials. This article reviews recently reported aromatic materials that present RTP characteristics. Various aromatic materials with RTP characteristics are classified in terms of their radiative rates and radiationless rates from the lowest triplet excited state (T 1 ) while taking the presence and absence of heavy atoms and charge transfer characteristics at T 1 into consideration. Statistical arrangements based on physical factors of RTP materials indicate that the recent appearance of RTP in various metal‐free aromatic structures is related to a large reduction in quenching caused by strong intermolecular interaction between the aromatics and the surrounding materials; additionally, intrinsic factors of the aromatics including the radiative rate and the nonradiative rate caused by intramolecular vibration are still not well controlled. Intrinsic control of these rates is important for overall control of the RTP yield and lifetime for potential material applications. Finally, recent applications using the RTP characteristics are highlighted.
Enhanced spread in time on-off keying technique for dense Terahertz nanonetworks (2017)

Nanotechnology becomes reality paving the way for many new applications. In nanonetwork system, each nanosized device is equipped with limited capabilities and is dedicated to a basic task but the combination of the numerous devices actions results in high-level functions. In this context, large number of devices concentrated in a limited area must exchange data using wireless links. Spread in Time On-Off Keying (TS-OOK) protocol was proposed as a technique to share the radio channel over the different terahertz nano-devices. TS-OOK is based on a Femtosecond-Long pulse modulation where communication data are sent using a sequence of pulses interleaved by a constant duration randomly selected. In this paper we provide a critical analysis of the TS-OOK approach. We prove that the TS-OOK is not adaptive against the traffic load variation and induces an imbalance between the active nodes. This inequity is due to the dependency of a communication quality on the randomly chosen symbol rate. We propose a dynamic TS-OOK modulation approach, called SRH-TSOOK (Symbol rate Hopping TSOOK), where the duration between two consecutive pulses of the same transmission follows a pseudo-random sequence. We show that this approach performs better than the standard protocol when the number of active nodes increases and guarantees a better distribution of the channel capacity over the active communications. For instance, while the throughput of a communication within a TS-OOK protocol may falls bellow 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sup> frames/s with 300 active nodes, the throughput in the SRH-TSOOK protocol stabilizes around 20 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">7</sup> frames/s for all the active communications. The comparison is made on the basis of probabilistic analysis allowing a numerical and accurate evaluation of the protocols performance.
Redirected Cytotoxic Effector Function (1996)

The aim of this study was to construct a single chain chimeric FcepsilonRIalpha receptor capable of effector function in leukocytes, including cytotoxic lymphocytes. To determine the most effective single chain FcepsilonRIalpha receptor with respect to IgE binding and signaling function, a variety of chimeric gene constructs were transiently transfected into COS-7 cells. The most effective chimera consisted of four parts including: wild-type or mutated extracellular domains (Trp130 --> Ala130, W130A) of FcepsilonRIalpha, membrane proximal and transmembrane regions of FcgammaRIIa, and intracellular CD3zeta (epsilonIIaIIazeta). Scatchard analysis indicated that these FcepsilonRIalpha chimeric receptor bound ligand with an affinity of 0.9 to 2.2 x 10(9) -1. Ligand binding capacity was dramatically reduced with the deletion of 11 membrane proximal amino acids of FcepsilonRIalpha; however, function was restored by substitution with the equivalent region of FcgammaRIIa, suggesting a crucial requirement for a "spacer" segment between the transmembrane and extracellular ligand binding domain. Chimeras that bound IgE effectively also mediated phagocytosis. Chimeric receptors that contained transmembrane zeta were expressed as multimers and consequently did not bind IgE effectively; however, cotransfection of these chimeras with gamma-chain largely reconstituted IgE-mediated phagocytosis. The mouse cytotoxic T lymphocyte cell line, CTLLR8 was stably transfected with epsilonIIaIIazeta, and cloned transfectants were demonstrated to lyse target cells in an anti-FcepsilonRIalpha or IgE antibody-dependent manner. Therefore, functional single chain chimeric FcepsilonRIalpha receptors were expressed in the absence or presence of associated zeta or gamma molecules and were used to redirect killer lymphocytes to target cells.
Broadly Neutralizing Antibodies Elicited by the Hypervariable Neutralizing Determinant of HIV-1 (1990)

The principal neutralizing determinant (PND) of human immunodeficiency virus (HIV)-1 resides within the V3 loop of the envelope protein. Antibodies elicited by peptides of this region were able to neutralize diverse isolates. Serum from one of three animals immunized with the human T cell lymphoma virus (HTLV)-IIIMN PND peptide, RP142, neutralized MN and the sequence-divergent HTLV-IIIB isolate. Serum from one of three animals immunized with a 13-amino acid IIIB PND peptide (RP337) also neutralized both of these isolates. Characterization of these sera revealed that the cross-neutralizing antibodies bound the amino acid sequence GlyProGlyArgAlaPhe (GPGRAF) that is present in both isolates. This sequence is frequently found in the PNDs analyzed in randomly selected HIV-1 isolates. Sera from two rabbits immunized with a peptide containing only the GPGRAF residues neutralized divergent isolates, including IIIB and MN.
Characterization of factor VIII/von Willebrand factor concentrates using a modified method of von Willebrand factor multimer analysis (1998)

In order to provide patients with von Willebrand disease a factor VIII (FVIII)/von Willebrand factor (vWF) concentrate of reproducible quality, an SDS-agarose gel electrophoresis method has been established to determine the content of the high molecular weight multimers (band 11 and higher) of vWF. This method has been used to characterize the content of high molecular weight vWF multimers in Humate P/Haemate P, a commercial FVIII/vWF concentrate. The average content of high molecular weight vWF multimers of 47 batches of Humate P/Haemate P has been determined to be 84.1% of the corresponding bands in normal human plasma. Use of this multimer analysis method for the characterization of five further commercial products revealed clear differences with respect to the high molecular weight vWF multimer content. Furthermore, there is a linear correlation (r2 = 0.73) between the content of high molecular weight vWF multimers and the specific activity of vWF (determined as vWF:RCoF/vWF:Ag). The method described here for analysis of the content of high molecular weight vWF multimers is a reliable and reproducible method to characterize this class of factor concentrates with respect to vWF multimer composition.
Role of MT‐MMPs and MMP‐2 in pancreatic cancer progression (2000)

Activation of matrix metalloproteinase-2 (MMP-2) by the membrane-type matrix metalloproteinases (MT-MMPs) has been associated with tumor progression. In the present study, we examined the role of MMP-2 and its activators MT1-MMP, MT2-MMP and MT3-MMP in pancreatic tumor cell invasion and the development of the desmoplastic reaction characteristic of pancreatic cancer tissues. Northern blot analyses revealed that transcript levels of MT1-MMP and MT2-MMP, but not MT3-MMP, were enhanced in pancreatic cancer tissues (n = 18) compared with both chronic pancreatitis (n = 9) and healthy pancreas (n = 9). A good correlation was found between MT1-MMP and both MMP-2 expression (p < 0.01) and activity in pancreatic cancer tissues. In addition, expression and activation of MMP-2 were strongly associated with the extent of the desmoplastic reaction in pancreatic cancer tissues. Invasion assays showed a good correlation between MMP-2 expression and activity and the invasive potential of pancreatic cancer cell lines. In cell lines with high levels of MMP-2 expression and activity, the MMP inhibitor Batimastat led to significant reduction of the number of invading cells. Our results suggest that MT1-MMP is involved in the progression of pancreatic cancer via activation of MMP-2. MMP-2 itself plays an important role in tumor cell invasion and appears to be associated with the development of the characteristic desmoplastic reaction in pancreatic cancer. Int. J. Cancer 85:14–20, 2000. © 2000 Wiley-Liss, Inc.
Multiply damaged sites in DNA: interactions with Escherichia coli endonucleases III and VIII (1998)

Bursts of free radicals produced by ionization of water in close vicinity to DNA can produce clusters of opposed DNA lesions and these are termed multiply damaged sites (MDS). How MDS are processed by the Escherichia coli DNA glycosylases, endonuclease (endo) III and endo VIII, which recognize oxidized pyrimidines, is the subject of this study. Oligonucleotide substrates were constructed containing a site of pyrimidine damage or an abasic (AP) site in close proximity to a single nucleotide gap, which simulates a free radical-induced single-strand break. The gap was placed in the opposite strand 1, 3 or 6 nt 5' or 3' of the AP site or base lesion. Endos III and VIII were able to cleave an AP site in the MDS, no matter what the position of the opposed strand break, although cleavage at position one 5' or 3' was reduced compared with cleavage at positions three or six 5' or 3'. Neither endo III nor endo VIII was able to remove the base lesion when the gap was positioned 1 nt 5' or 3' in the opposite strand. Cleavage of the modified pyrimidine by endo III increased as the distance increased between the base lesion and the opposed strand break. With endo VIII, however, DNA breakage at the site of the base lesion was equivalent to or less when the gap was positioned 6 nt 3' of the lesion than when the gap was 3 nt 3' of the lesion. Gel mobility shift analysis of the binding of endo VIII to an oligonucleotide containing a reduced AP (rAP) site in close opposition to a single nucleotide gap correlated with cleavage of MDS substrates by endo VIII. If the strand break in the MDS was replaced by an oxidized purine, 7,8-dihydro-8-oxoguanine (8-oxoG), neither endo VIII cleavage nor binding were perturbed. These data show that processing of oxidized pyrimidines by endos III and VIII was strongly influenced by the position and type of lesion in the opposite strand, which could have a significant effect on the biological outcome of the MDS lesion.