gebhart/patrepeval huggingface dataset:
The IL-2 Receptor Promotes Lymphocyte Proliferation and Induction of the c- myc, bcl-2, and bcl-x Genes Through the trans- Activation Domain of Stat5 (2000)

Studies assessing the role of Stat5 in the IL-2 proliferative signal have produced contradictory, and thus inconclusive, results. One factor confounding many of these studies is the ability of IL-2R to deliver redundant mitogenic signals from different cytoplasmic tyrosines on the IL-2R beta-chain (IL-2Rbeta). Therefore, to assess the role of Stat5 in mitogenic signaling independent of any redundant signals, all cytoplasmic tyrosines were deleted from IL-2Rbeta except for Tyr510, the most potent Stat5-activating site. This deletion mutant retained the ability to induce Stat5 activation and proliferation in the T cell line CTLL-2 and the pro-B cell line BA/F3. A set of point mutations at or near Tyr510 that variably compromised Stat5 activation also compromised the proliferative signal and revealed a quantitative correlation between the magnitude of Stat5 activation and proliferation. Proliferative signaling by a receptor mutant with a weak Stat5 activating site could be rescued by overexpression of wt Stat5a or b. Additionally, the ability of this receptor mutant to induce c-myc, bcl-x, and bcl-2 was enhanced by overexpression of wt Stat5. By contrast, overexpression of a version of Stat5a lacking the C-terminal trans-activation domain inhibited the induction of these genes and cell proliferation. Thus, Stat5 is a critical component of the proliferative signal from Tyr510 of the IL-2R and regulates expression of both mitogenic and survival genes through its trans-activation domain.
An alvocidib-containing regimen is highly effective in AML patients through a mechanism dependent on MCL1 expression and function. (2015)

7062 Background: Through multiple Phase I/II studies, alvocidib (flavopiridol) has proven to be highly effective in both frontline and relapsed/refractory AML when sequentially administered before ara-C and mitoxantrone (FLAM). In frontline patients, FLAM resulted in a complete remission (CR) rate of 70% versus 46% CR with ara-C and daunorubicin (7+3). Among patients with secondary (s)AML, FLAM produced 60% CR versus 35% CR with 7+3. The clinical activity of alvocidib in AML strongly correlates with inhibition of cyclin-dependent kinase-9 (CDK9) and disruption of super enhancer mediated transcription. The myeloid leukemia cell 1 (MCL1) gene is critically regulated by CDK9 activity under SE-mediated transcriptional control. Methods: Studies with AML cell lines were conducted to model the sequential treatment of the FLAM regimen. MCL1 expression and apoptosis were monitored in these nonclinical experiments. To further substantiate this mechanism clinically, mitochondrial profiling was conducted on 63 archived FLAM-treated samples. Results: Treatment with alvocidib results in a rapid downregulation of MCL1. In AML cell lines, we observe a two-fold decrease in MCL1 following alvocidib treatment that is associated with increased sensitivity to subsequent treatment with ara-C and mitoxantrone and enhanced apoptosis. Analysis of the BH3 priming states in AML clinical samples revealed NOXA priming was significantly higher in CR bone marrow samples (44.5% primed) compared with samples from non-responders (NR) (5.2% primed) (p = 0.006). NOXA is known to interact most directly with MCL1, suggesting that the AML samples that are most responsive to FLAM treatment may have a high survival dependence on MCL1. Interestingly, combining NOXA priming data with cytogenetic risk factors in pts with sAML, increased the predictive power of the assay as evident by a receiver operating characteristic (ROC) analysis yielding an AUC of 0.92 with p = 0.0002. Importantly, the correlation between NOXA and FLAM response is distinct from priming states predicting response to other ara-C regimens. Conclusions: This work reveals a potential biomarker for identification of patients likely to respond to FLAM.
Renal renin-angiotensin system in diabetes: functional, immunohistochemical, and molecular biological correlations (1993)

Recent evidence indicates a role for the renin-angiotensin system (RAS) in the pathogenesis of glomerular injury in diabetes. To further explore the RAS in diabetes, studies were conducted in nondiabetic control rats and in moderately hyperglycemic diabetic (DM) rats. In DM rats, both acute and chronic therapy with the specific angiotensin II (ANG II) receptor antagonist losartan did not affect glomerular hyperfiltration or hyperperfusion but selectively normalized the glomerular capillary hydraulic pressure and ultrafiltration coefficient. To determine the basis of intrarenal hemodynamic responsiveness to RAS inhibition, we conducted biochemical, molecular biological, and immunohistochemical studies to assess endogenous RAS activity. Values for plasma renin concentration and serum angiotensin-converting enzyme (ACE) activity in DM rats were normal. In contrast, intrarenal renin protein content, and renin and angiotensinogen mRNAs, were increased in DM rats, suggesting disproportionate activation of the intrarenal RAS. Total renal ACE activity was significantly reduced in DM rats, but immunohistochemical studies indicated redistribution of ACE in the diabetic kidney. Proximal tubule ACE activity was reduced, but ACE immunostaining intensity was enhanced in glomeruli and renal vasculature. Together, these observations indicate increased RAS activity in those sites (glomeruli and vasculature) most likely to regulate hemodynamic function, potentially explaining the prominent responses to pharmacological blockade of ANG II formation and/or action.
Manifold exploration (2012)

It is a long-standing problem in unbiased Monte Carlo methods for rendering that certain difficult types of light transport paths, particularly those involving viewing and illumination along paths containing specular or glossy surfaces, cause unusably slow convergence. In this paper we introduce Manifold Exploration, a new way of handling specular paths in rendering. It is based on the idea that sets of paths contributing to the image naturally form manifolds in path space, which can be explored locally by a simple equation-solving iteration. This paper shows how to formulate and solve the required equations using only geometric information that is already generally available in ray tracing systems, and how to use this method in in two different Markov Chain Monte Carlo frameworks to accurately compute illumination from general families of paths. The resulting rendering algorithms handle specular, near-specular, glossy, and diffuse surface interactions as well as isotropic or highly anisotropic volume scattering interactions, all using the same fundamental algorithm. An implementation is demonstrated on a range of challenging scenes and evaluated against previous methods.
Structure-function relationships of curaremimetic neurotoxin loop 2 and of a structurally similar segment of rabies virus glycoprotein in their interaction with the nicotinic acetylcholine receptor (1991)

Peptides corresponding to portions of curaremimetic neurotoxin loop 2 and to a structurally similar segment of rabies virus glycoprotein were synthetically modified in order to gain information on structure-function relationships of neurotoxin loop 2 interactions with the acetylcholine receptor. Binding of synthetic peptides to the acetylcholine receptor of Torpedo electric organ membranes was assessed by measuring their ability to inhibit the binding of 125I-alpha-bungarotoxin to the receptor. The peptides showing the highest affinity for the receptor were a peptide corresponding to the sequence of loop 2 (residues 25-44) of Ophiophagus hannah (king cobra) toxin b (IC50 = 5.7 x 10(-6) M) and the structurally similar segment (residues 173-203) of CVS rabies virus glycoprotein (IC50 = 2.6 x 10(-6) M). These affinities were comparable to those of d-tubocurarine (IC50 = 3.4 x 10(-6) M) and suberyldicholine (IC50 = 2.5 x 10(-6) M). These results demonstrate the importance of loop 2 in the neurotoxin interaction with the receptor. N- and C-terminal deletions of the loop 2 peptides and substitution of residues invariant or highly conserved among neurotoxins were performed in order to determine the role of individual residues in binding. Residues 25-40 are the most crucial in the interaction with the acetylcholine receptor. Modifications involving Lys-27, Trp-29, Phe-33, Arg-37, and Gly-38 reduced affinity of binding. R37D and F33T modifications reduced the affinity of alpha-bungarotoxin residues 28-40 by an order of magnitude. Arg-37 may correspond to the positively charged quaternary ammonium group and Phe-33 to the hydrophobic acetyl methyl group of acetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)
Status and perspectives of Heavy Ion Fusion (1984)

Heavy ion accelerators are the most promising driver candidates for power generation by inertial confinement fusion. Present activities are reviewed and discussed with respect of the perspectives of future developments in the field.
Carbon nanotube field-effect transistor operation at microwave frequencies (2006)

A top-gated carbon nanotube (CNT) field-effect transistor (FET) was fabricated on a quartz substrate. We used a novel measurement approach and demonstrated for the first time frequency-independent performance of a CNT FET for frequencies as high as 23GHz. This observed maximum operating frequency represents a significant breakthrough in the realization of carbon nanotube-based electronics for high frequency applications.
Enrichment of xanthohumol in the brewing process (2005)

Xanthohumol (XN), a component of hops, is lost in significant quantities in the conventional brewing process. In commercial beers less than 0.2 mg XN/L are found. In order to increase the yield of XN in the brewing process, the parameters of XN recovery were studied. During wort boiling, XN is largely isomerised to isoxanthohumol. Further losses are owing to the precipitation and absorption of XN to yeast cells and haze particles and by filtration. The use of XN-enriched hop products combined with a late hop dosage during wort boiling proved to be effective in increasing the XN content in beer. The yield was further raised by a low-pitching rate and the abnegation of beer stabilisation. The use of dark malts had a positive effect on the XN recovery. Investigations of roasted malt extracts revealed several high-molecular substances that are able to form complexes with XN. These complexes proved to be stable in the brewing process. Depending on the addition of roasted malt or special XN-enriched roasted malt extracts, dark beers with more than 10 mg XN/L were achieved. Results obtained led to a brewing technology that produced on an industrial scale pale wheat beer with more than 1 mg XN/L.
The Consequence of Sequence Alteration of an Amphipathic α-Helical Antimicrobial Peptide and Its Diastereomers (2002)

The search for antibiotics with a new mode of action led to numerous studies on antibacterial peptides. Most of the studies were carried out with l-amino acid peptides possessing amphipathic alpha-helix or beta-sheet structures, which are known to be important for biological activities. Here we compared the effect of significantly altering the sequence of an amphipathic alpha-helical peptide (15 amino acids long) and its diastereomer (composed of both l- and d-amino acids) regarding their structure, function, and interaction with model membranes and intact bacteria. Interestingly, the effect of sequence alteration on biological function was similar for the l-amino acid peptides and the diastereomers, despite some differences in their structure in the membrane as revealed by attenuated total reflectance Fourier-transform infrared spectroscopy. However, whereas the all l-amino acid peptides were highly hemolytic, had low solubility, lost their activity in serum, and were fully cleaved by trypsin and proteinase K, the diastereomers were nonhemolytic and maintained full activity in serum. Furthermore, sequence alteration allowed making the diastereomers either fully, partially, or totally protected from degradation by the enzymes. Transmembrane potential depolarization experiments in model membranes and intact bacteria indicate that although the killing mechanism of the diastereomers is via membrane perturbation, it is also dependent on their ability to diffuse into the inner bacterial membrane. These data demonstrate the advantage of the diastereomers over their all l-amino acid counterparts as candidates for developing a repertoire of new target antibiotics with a potential for systemic use.
High frequency (GHz) and low resistance integrated inductors using magnetic materials (2001)

Integrated microinductors using magnetic materials were fabricated with cutoff frequencies over 3 GHz. Magnetic materials are typically not used in high-frequency inductors because their frequency range has been limited to <100 MHz. The high-frequency magnetic film, amorphous CoZrTa, was integrated into standard silicon process technology. Inductors consume large amounts of chip area, but with magnetic materials, the inductors can be made smaller thereby reducing their capacitance and resistance. A novel 3-dimensional structure for reducing the inductor's resistance by an order of magnitude was also developed. Simulations of inductors with magnetics and measurements are presented.
Synergistic interaction between cisplatin and gemcitabine in vitro. (1996)

2',2'-Difluorodeoxycytidine (dFdC; gemcitabine) is a new antineoplastic agent that is active against ovarian carcinoma, non-small-cell lung carcinoma, and head and neck squamous cell carcinoma. cis-diamminedichloroplatinum (CDDP; cisplatin) is used commonly for the treatment of these tumors. Because the two drugs have mechanisms of action that might be complementary, we investigated a possible synergism between dFdC and CDDP on growth inhibition. The combination was tested in the human ovarian carcinoma cell line A2780, its CDDP-resistant variant ADDP and its dFdC-resistant variant AG6000, the human head and neck squamous cell carcinoma cell line UMSCC-22B, and the murine colon carcinoma cell line C26-10. The cells were exposed to dFdC and CDDP as single agents and to combinations in a molar ratio of 1:500 for 1, 4, 24, and 72 h with a total culture time of 72 h. Synergy was evaluated using the multiple drug effect analysis. In A2780 and ADDP cells, simultaneous exposure to the drugs for 24 and 72 h resulted in synergism, but shorter exposure times were antagonistic. No synergism was found in the UMSCC-22B and C26-10 cell lines at prolonged simultaneous exposure. However, a preincubation with CDDP for 4 h followed by a dFdC incubation for 1, 4, 24, and 72 h was synergistic in all cell lines except C26-10 cells. A 4-h preincubation with dFdC followed by an incubation with the combination for 20 and 68 h was synergistic in all cell lines. Initial studies of the mechanism of interaction concentrated on the effect of CDDP on dFdCTP accumulation and DNA strand break formation. In all cell lines, CDDP failed to increase dFdCTP accumulation at 4- or 24-h exposure to dFdC; in two cell lines, CDDP even tended to decrease dFdCTP accumulation. Neither dFdC nor CDDP caused more than 25% double strand break formation, whereas in the combination, CDDP even tended to decrease this type of DNA damage. The synergistic interaction between the two drugs is possibly the result of dFdC incorporation into DNA and/or CDDP-DNA adduct formation, which may be affected by each other.
Fundamentals of bioMEMS and medical microdevices (2006)

Fundamentals of bioMEMS and medical microdevices , Fundamentals of bioMEMS and medical microdevices , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Binding of the terminal mannosyl units of lipoarabinomannan from a virulent strain of Mycobacterium tuberculosis to human macrophages. (1994)

Recent studies from this laboratory have demonstrated that macrophage phagocytosis of virulent strains (Erdman and H37Rv), but not the attenuated H37Ra strain of Mycobacterium tuberculosis, is mediated by phagocyte mannose receptors (MR) in addition to complement receptors (CR1 and the leukocyte integrins CR3 and CR4). Lipoarabinomannan (LAM) is a major surface lipoglycan of M. tuberculosis. LAM from the Erdman strain (Man-LAM) contains mannose oligosaccharides at the terminal portions of the molecule. This study investigated the ability of ManLAM to serve as a microbial ligand in adherence to human monocyte-derived macrophages (MDM). Polystyrene microspheres were coated with known amounts of purified ManLAM, LAM without the terminal mannosyl units from an avirulent mycobacterium (AraLAM), lipomannan (LM), or buffer and incubated with MDM monolayers in the absence of serum. The presence of LAM on microspheres was confirmed by indirect immunofluorescence studies. Microspheres coated with ManLAM demonstrated a more than threefold increase in adherence to MDM when compared with microspheres coated with AraLAM, LM, or buffer and the low levels of adherence of microspheres in the latter three groups were comparable. Compared with control monolayers, selective down-modulation of MDM MR on a mannan substrate abrogated the enhanced adherence of microspheres mediated by ManLAM. Adherence of microspheres coated with AraLAM, LM, or buffer was not influenced by MR modulation. To confirm the importance of the terminal mannosyl units of ManLAM in the enhanced adherence of ManLAM microspheres to MDM, these units were selectively removed by exomannosidase treatment. The structure of LAM products before and after enzyme treatment was confirmed by high performance anion exchange chromatography with pulsed amperometric detection. Removal of the terminal mannosyl units abolished the capacity of ManLAM to mediate enhanced adherence of microspheres to MDM. Finally, preincubation of Erdman M. tuberculosis with CS-40, a mAb directed against LAM, resulted in a consistent inhibition of adherence of the bacteria to MDM (up to 49% inhibition), confirming a role for ManLAM on intact bacteria in adherence to MDM. Thus, we provide evidence for a novel receptor-ligand pathway in phagocytosis of M. tuberculosis that consists of MR on macrophages and mannosyl units at the terminal end of ManLAM, a major microbial surface lipoglycan.
The implementation of an integrated concurrency control and recovery scheme (1982)

This paper describes the implementation level design of an integrated concurrency control and recovery scheme based on the maintenance of multiple versions of data objects in a database. The concurrency control mechanism enhances parallelism by eliminating interference between retrieval and update transactions. The recovery mechanism permits efficient transaction and system recovery by keeping before-images of data objects at the page (block) level. This paper addresses the key technical problems in the implementation of such an integrated scheme. We present an efficient garbage collection algorithm for reclaiming storage space used by old versions of data objects that will no longer be accessed. We also propose an on-line backup algorithm that will permit the backup procedure to run in parallel with regular transactions. This integrated concurrency control and recovery scheme is being implemented in the LDM: the local database manager component of a distributed database management system, now being developed by Computer Corporation of America, that will support the ADAPLEX database application programming language [Chan81a, Smith81].
Pediatric brainstem gangliogliomas show overexpression of neuropeptide prepronociceptin (PNOC) by microarray and immunohistochemistry (2012)

PNOC IHC was often superior to IHC for NeuN, synaptophysin, or neurofilament for highlighting neoplastic neurons.
Use of hypnosis with witnesses of vehicular homicide (1999)

Abstract This is a case study of hypnosis with witnesses of vehicular homicide victims. An investigation was made of three separate vehicular homicide cases which were all hit‐and‐run fatalities. The medical examiners referred the three witnesses for hypnosis as they had difficulty in recalling the description of either the drivers or the vehicles who had committed the offence. Hypnosis was used both for memory refreshment and to relax the witnesses. The technique of hypnotic time regression revealed the description of each of the hit‐and‐run drivers and their respective vehicles. Copyright © 1999 British Society of Experimental and Clinical Hypnosis
3D EM imaging from a single borehole; a numerical feasibility study (1998)

PreviousNext No AccessSEG Technical Program Expanded Abstracts 19983D EM imaging from a single borehole; a numerical feasibility studyAuthors: David L. AlumbaughMichael J. WiltDavid L. AlumbaughSandia National Laboratories, Albuquerque, NM and Michael J. WiltElectroMagnetic Instruments, Inc., Richmond, CAhttps://doi.org/10.1190/1.1820459 SectionsAboutPDF/ePub ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InRedditEmail Permalink: https://doi.org/10.1190/1.1820459FiguresReferencesRelatedDetailsCited byNumerical analysis of near‐borehole and anisotropeic layer effects on the response of multicomponent induction logging toolsMichael J. Tompkins, David L. Alumbaugh, Darrell T. Stanley, and Xinyou Lu28 January 2004 | GEOPHYSICS, Vol. 69, No. 1 SEG Technical Program Expanded Abstracts 1998ISSN (print):1052-3812 ISSN (online):1949-4645Copyright: 1998 Pages: 2092 publication data© 1998 Copyright © 1998 Society of Exploration GeophysicistsPublisher:Society of Exploration Geophysicists HistoryPublished Online: 06 Jan 2005 CITATION INFORMATION David L. Alumbaugh and Michael J. Wilt, (1998), "3D EM imaging from a single borehole; a numerical feasibility study," SEG Technical Program Expanded Abstracts : 448-451. https://doi.org/10.1190/1.1820459 Plain-Language Summary PDF DownloadLoading ...
Rapid techniques for DNA extraction from routinely processed archival tissue for use in PCR. (1994)

Chelex boiling, proteinase K digestion, and proteinase K digestion followed by Chelex boiling produce suitable templates for the PCR from a large variety of paraffin wax embedded tissues. As the simple 20 minute boiling method in 5% Chelex-100 solution requires minimal manipulation and time, it could be useful, especially in the routine processing of large amounts of material.