gebhart/patrepeval huggingface dataset:
Messenger RNA for two type IV collagenases is located in stromal cells in human colon cancer. (1993)

The gene expression of two type IV collagen-degrading enzymes (72-kd and 92-kd type IV collagenases) was investigated in human colon adenocarcinomas by in situ hybridization. In all cases (18 out of 18), messenger RNA for the 72-kd type IV collagenase was present and located in numerous fibroblasts in the stroma surrounding the invasive cancer tissue. In normal-appearing colonic mucosa distant from the cancer tissue, either no expression or only very weak expression of this enzyme was detected. Also the 92-kd type IV collagenase was found in all samples investigated (10 out of 10), exclusively expressed by tissue macrophages. A very strong hybridization signal for messenger RNA for the 92-kd enzyme was found in a subpopulation of tissue macrophages surrounding invading malignant epithelium. In normal-appearing colon tissue, a markedly weaker hybridization signal was observed in macrophages contained in Peyer's patches. No hybridization signals for either of the two type IV collagenases were detected in cancer cells. Together with previous findings on expression of components of the plasminogen activation system, these results indicate that several nonepithelial cell types in the tumor stroma are involved in production of factors involved in extracellular proteolysis during colon cancer invasion.
Quantitative Prediction of Improvement in Cardiac Function after Revascularization with MR Imaging and Modeling: Initial Results (2001)

A simple mathematical model combined with functional information provided by MR imaging was used to predict improvements in global EF resulting from revascularization.
Efficient Storage and Retrieval by Content and Address of Static Files (1974)

We consider a set of static files or inventories, each consisting of the same number of entries, each entry a binary word of the same fixed length selected (with replacement) from the set of all binary sequences of that length, and the entries in each file sorted into lexical order. We also consider several retrieval questions of interest for each such file. One is to find the value of the j th entry, another to find the number of entries of value less than k . When a binary representation of such a file is stored in computer memory and an algorithm or machine which knows only the file parameters (i.e. number of entries, number of possible values per entry) accesses some of the stored bits to answer a retrieval question, the number of bits stored and the number of bits accessed per retrieval question are two cost measures for the storage and retrieval task which have been used by Minsky and Papert. Bits stored depends on the representation chosen: bits accessed also depends on the retrieval question asked and on the algorithm used. We give firm lower bounds to minimax measures of bits stored and bits accessed for each of four retrieval questions, and construct representations and algorithms for a bit-addressable machine which come within factors of two or three of attaining all four bounds at once for files of any size. All four factors approach one for large enough files.
Niagara: A 32-Way Multithreaded Sparc Processor (2005)

The Niagara processor implements a thread-rich architecture designed to provide a high-performance solution for commercial server applications. This is an entirely new implementation of the Sparc V9 architectural specification, which exploits large amounts of on-chip parallelism to provide high throughput. The hardware supports 32 threads with a memory subsystem consisting of an on-board crossbar, level-2 cache, and memory controllers for a highly integrated design that exploits the thread-level parallelism inherent to server applications, while targeting low levels of power consumption.
La autoantigen enhances and corrects aberrant translation of poliovirus RNA in reticulocyte lysate (1993)

Translation initiation on poliovirus RNA occurs by internal binding of ribosomes to a sequence within the 5' untranslated region. We have previously characterized a HeLa cell protein, p52, that binds to a fragment of the poliovirus 5' untranslated region (K. Meerovitch, J. Pelletier, and N. Sonenberg, Genes Dev. 3:1026-1034, 1989). Here we report the purification of the HeLa p52. Protein microsequencing identified p52 as La autoantigen. The La protein is a human antigen that is recognized by antibodies from patients with autoimmune disorders such as systemic lupus erythematosus and Sjögren's syndrome. We show that the La protein stimulates translation of poliovirus RNA, but not brome mosaic virus, tobacco mosaic virus, and alfalfa mosaic virus 4 RNA, translation in a reticulocyte lysate. In addition, La corrects aberrant translation of poliovirus RNA in a reticulocyte lysate. Subcellular immunolocalization showed that La protein is mainly nuclear, but after poliovirus infection, La is redistributed to the cytoplasm. Our results suggest that La protein is involved in poliovirus internal initiation of translation and might function through a similar mechanism in the translation of cellular mRNAs.
Identification of a Somatodendritic Targeting Signal in the Cytoplasmic Domain of the Transferrin Receptor (1997)

Neurons are highly polarized cells that must sort proteins synthesized in the cell body for transport into the axon or the dendrites. Given the amount of time and energy needed to deliver proteins to the distal processes, neurons must have high fidelity mechanisms that ensure proper polarized protein trafficking. Although a variety of proteins are localized either to the somatodendritic domain or to the axon (), the question of whether there are signal-dependent mechanisms that sort proteins to distinct neuronal domains is only beginning to be addressed. To determine sequence requirements for the polarized sorting of transmembrane proteins into dendrites, we expressed mutant transferrin receptors in cultured rat hippocampal neurons, using a defective herpes virus vector. Wild-type human transferrin receptor colocalized with the endogenous protein in dendritic endosomes and was strictly excluded from axons, despite overexpression. Polarized targeting was abolished by deletion of cytoplasmic amino acids 7-10, 11-14, or 19-28, but not 29-42 or 43-58. These deletions also increased the appearance of transferrin receptor on the plasma membrane, implying that endocytosis and dendritic targeting are mediated by overlapping signals and similar molecular mechanisms. In addition, we have characterized a specialized para-Golgi endosome poised to play a critical role in the polarized recycling of transmembrane proteins.
Selective polymorph transformation via solvent-drop grinding (2005)

A method of inducing specific polymorph transformations is exemplified with two single-component systems, whereby a given crystal form undergoes conversion when subjected to solid state grinding in the presence of a minor quantity of a certain solvent.
Fumaric acid esters in the management of severe psoriasis (2007)

The relatively low toxicity and absence of hepatotoxicity makes FAEs a reasonable first-line systemic treatment in selected patients with difficult psoriasis.
Mutations in the B Subunit of Escherichia coli DNA Gyrase That Affect ATP-dependent Reactions (1996)

We have previously reported specific labeling of Escherichia coli DNA gyrase by the ATP affinity analog pyridoxal 5'-diphospho-5'adenosine (PLP-AMP), which resulted in inhibition of ATP-dependent reactions. The analog was found to be covalently bound at Lys103 and Lys110 on the gyrase B subunit (Tamura, J. K., and Gellert, M. (1990) J. Biol. Chem. 265, 21342-21349). In this study, the importance of these two lysine residues is examined by site-directed mutagenesis. Substitutions of Lys 103 result in the loss of ATP-dependent functions. These mutants are unable to supercoil DNA, to hydrolyze ATP, or to bind a nonhydrolysable ATP analog, 5'-adenylyl-beta,gamma-imidodiphosphate (ADPNP). The ATP-independent functions of gyrase, such as relaxation of negatively supercoiled DNA and oxolinic acid-induced cleavage of double-stranded DNA, are unaffected by these mutations, suggesting that the mutant B subunits are assembling correctly with the A subunits. Gyrase with substitutions of Lys110 retains all activities. However, the affinity of ATP is decreased. The DNA supercoiling activity of gyrase A2B2, tetramers reconstituted with varying ratios of inactive mutant and wild-type gyrase B subunits is consistent with a mechanism of DNA supercoiling that requires the interdependent activity of both B subunits in ATP binding and hydrolysis.
Quantum Dot–Peptide–Fullerene Bioconjugates for Visualization of in Vitro and in Vivo Cellular Membrane Potential (2017)

We report the development of a quantum dot (QD)-peptide-fullerene (C<sub>60</sub>) electron transfer (ET)-based nanobioconjugate for the visualization of membrane potential in living cells. The bioconjugate is composed of (1) a central QD electron donor, (2) a membrane-inserting peptidyl linker, and (3) a C<sub>60</sub> electron acceptor. The photoexcited QD donor engages in ET with the C<sub>60</sub> acceptor, resulting in quenching of QD photoluminescence (PL) that tracks positively with the number of C<sub>60</sub> moieties arrayed around the QD. The nature of the QD-capping ligand also modulates the quenching efficiency; a neutral ligand coating facilitates greater QD quenching than a negatively charged carboxylated ligand. Steady-state photophysical characterization confirms an ET-driven process between the donor-acceptor pair. When introduced to cells, the amphiphilic QD-peptide-C<sub>60</sub> bioconjugate labels the plasma membrane by insertion of the peptide-C<sub>60</sub> portion into the hydrophobic bilayer, while the hydrophilic QD sits on the exofacial side of the membrane. Depolarization of cellular membrane potential augments the ET process, which is manifested as further quenching of QD PL. We demonstrate in HeLa cells, PC12 cells, and primary cortical neurons significant QD PL quenching (ΔF/F<sub>0</sub> of 2-20% depending on the QD-C<sub>60</sub> separation distance) in response to membrane depolarization with KCl. Further, we show the ability to use the QD-peptide-C<sub>60</sub> probe in combination with conventional voltage-sensitive dyes (VSDs) for simultaneous two-channel imaging of membrane potential. In in vivo imaging of cortical electrical stimulation, the optical response of the optimal QD-peptide-C<sub>60</sub> configuration exhibits temporal responsivity to electrical stimulation similar to that of VSDs. Notably, however, the QD-peptide-C<sub>60</sub> construct displays 20- to 40-fold greater ΔF/F<sub>0</sub> than VSDs. The tractable nature of the QD-peptide-C<sub>60</sub> system offers the advantages of ease of assembly, large ΔF/F<sub>0</sub>, enhanced photostability, and high throughput without the need for complicated organic synthesis or genetic engineering, respectively, that is required of traditional VSDs and fluorescent protein constructs.
Microarray Technology: A Review of New Strategies to Discover Candidate Vulnerability Genes in Psychiatric Disorders (2003)

Microarrays present a methodology that can identify genes or pathways for new and unique potential drug targets, determine premorbid diagnosis, predict drug responsiveness for individual patients, and, eventually, initiate gene therapy and prevention strategies.
Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance (2007)

Systemic iron balance is regulated by hepcidin, a peptide hormone secreted by the liver. By decreasing cell surface expression of the iron exporter ferroportin, hepcidin decreases iron absorption from the intestine and iron release from reticuloendothelial stores. Hepcidin excess has been implicated in the pathogenesis of anemia of chronic disease, while hepcidin deficiency has a key role in the pathogenesis of the iron overload disorder hemochromatosis. We have recently shown that hemojuvelin is a coreceptor for bone morphogenetic protein (BMP) signaling and that BMP signaling positively regulates hepcidin expression in liver cells in vitro. Here we show that BMP-2 administration increases hepcidin expression and decreases serum iron levels in vivo. We also show that soluble hemojuvelin (HJV.Fc) selectively inhibits BMP induction of hepcidin expression in vitro and that administration of HJV.Fc decreases hepcidin expression, increases ferroportin expression, mobilizes splenic iron stores, and increases serum iron levels in vivo. These data support a role for modulators of the BMP signaling pathway in treating diseases of iron overload and anemia of chronic disease.
Targeting fidelity of adenine and cytosine base editors in mouse embryos (2018)

Base editing directly converts a target base pair into a different base pair in the genome of living cells without introducing double-stranded DNA breaks. While cytosine base editors (CBE) and adenine base editors (ABE) are used to install and correct point mutations in a wide range of organisms, the extent and distribution of off-target edits in mammalian embryos have not been studied in detail. We analyze on-target and proximal off-target editing at 13 loci by a variety of CBEs and ABE in more than 430 alleles generated from mouse zygotic injections using newly generated and published sequencing data. ABE predominantly generates anticipated A•T-to-G•C edits. Among CBEs, SaBE3 and BE4, result in the highest frequencies of anticipated C•G-to-T•A products relative to editing byproducts. Together, these findings highlight the remarkable fidelity of ABE in mouse embryos and identify preferred CBE variants when fidelity in vivo is critical.
An Approach to Rigid Minimum Residual Power Level of Nodes in Multi-Hop Wireless Network (2012)

In multi hop wireless network nodes have finite battery energy to participate active role in network operations. Nodes not only dissipate amount of energy during the transmission of data even in sleep mode also. The energy dissipation of nodes arise network partition and irregular data transmission issue. To resolve that issue a lot of research has been done in which aware about battery energy of nodes during the discovery of route and data transmission. In this paper an approach is presented that specify minimum residual energy level of nodes to prevent data transmission from irregular manner. The proposed approach also offered to sending prioritized data packets and discard Route-Request packets comes from other nodes during regular transmission. The work minimized battery dissipation via discarding route discovery request packets and maximize the period of data transmissions.
Characterisation of the tumour necrosis factor (TNF)-α response elements in the human ICAM-2 promoter (1999)

ICAM-2 is a cell surface adhesion molecule constitutively expressed on the endothelium, involved in leukocyte recruitment into tissues. We recently showed that pro-inflammatory cytokines tumour necrosis factor (TNF)-(alpha) and interleukin (IL)-1(beta) down-regulate ICAM-2 expression at the transcriptional level. Here we investigate the elements in the ICAM-2 promoter required for the TNF-(alpha)-mediated down-regulation. Site directed mutagenesis of the ICAM-2 promoter implicated three consensus sites for Ets transcription factors in basal activity; two of these sites were also involved in the TNF-(alpha)-induced down-regulation. Electrophoretic mobility shift assays (EMSA) performed in human umbilical vein endothelial cells (HUVEC) showed that all three Ets binding sites (EBS) bind nuclear proteins. TNF-(alpha) treatment (10 ng/ml for 24 hours) decreased binding to the double -135/-127EBS, but not to the -44EBS. The Ets family member Erg was found to be constitutively expressed in HUVEC, and TNF-(alpha) down-regulated Erg protein levels. Furthermore, an Erg cDNA transactivated the ICAM-2 promoter when transiently transfected into both HeLa cells and HUVEC. Protein expression of ICAM-2 and Erg was found to be similarly regulated by TNF-(alpha) in an ex vivo artery model. These data suggest that constitutive endothelial genes ICAM-2 and Erg are on the same pathway of cytokine-dependent regulation of gene expression.
Psychosocial Correlates and Impact of Chronic Tension‐type Headaches (2000)

Chronic tension-type headache has a greater impact on individuals' lives than has generally been realized, with affective distress being an important correlate of impairment. If treatment is to remedy impairment in functioning, affective distress, as well as pain, thus needs to be addressed.
Fungal cellulase systems. Comparison of the specificities of the cellobiohydrolases isolated from Penicillium pinophilum and Trichoderma reesei (1989)

Reaction patterns for the hydrolysis of chromophoric glycosides from cello-oligosaccharides and lactose by the cellobiohydrolases (CBH I and CBH II) purified from Trichoderma reesei and Penicillium pinophilum were determined. They coincide with those found for the parent unsubstituted sugars. CBH I enzyme from both organisms attacks these substrates in a random manner. Turnover numbers are, however, low and do not increase appreciably as a function of the degree of polymerization of the substrates. The active-site topology of the CBH I from T. reesei was further probed by equilibrium binding experiments with cellobiose, cellotriose, lactose and some of their derivatives. These point to a single interaction site (ABC), spatially restricted as deduced from the apparent independency of the thermodynamic parameters. It appears that the putative subsite A can accommodate a galactopyranosyl or glucopyranosyl group, and subsite B a glucopyranosyl group, whereas in subsite C either a glucopyranosyl or a chromophoric group can be bound, scission occurring between subsites B and C. The apparent kinetic parameters (turnover numbers) for the hydrolysis of cello-oligosaccharides (and their derivatives) by the CBH II type enzyme increase as a function of chain length, indicative of an extended binding site (A-F). Its architecture allows for specific binding of beta-(1----4)-glucopyranosyl groups in subsites A, B and C. Binding of a chromophore in subsite C produces a non-hydrolysable complex. The thermodynamic interaction parameters of some ligands common to both type of enzyme were compared: these substantiate the conclusions reached above.
Increased Anatomical Specificity of Neuromodulation via Modulated Focused Ultrasound (2014)

Transcranial ultrasound can alter brain function transiently and nondestructively, offering a new tool to study brain function now and inform future therapies. Previous research on neuromodulation implemented pulsed low-frequency (250-700 kHz) ultrasound with spatial peak temporal average intensities (ISPTA) of 0.1-10 W/cm(2). That work used transducers that either insonified relatively large volumes of mouse brain (several mL) with relatively low-frequency ultrasound and produced bilateral motor responses, or relatively small volumes of brain (on the order of 0.06 mL) with relatively high-frequency ultrasound that produced unilateral motor responses. This study seeks to increase anatomical specificity to neuromodulation with modulated focused ultrasound (mFU). Here, 'modulated' means modifying a focused 2-MHz carrier signal dynamically with a 500-kHz signal as in vibro-acoustography, thereby creating a low-frequency but small volume (approximately 0.015 mL) source of neuromodulation. Application of transcranial mFU to lightly anesthetized mice produced various motor movements with high spatial selectivity (on the order of 1 mm) that scaled with the temporal average ultrasound intensity. Alone, mFU and focused ultrasound (FUS) each induced motor activity, including unilateral motions, though anatomical location and type of motion varied. Future work should include larger animal models to determine the relative efficacy of mFU versus FUS. Other studies should determine the biophysical processes through which they act. Also of interest is exploration of the potential research and clinical applications for targeted, transcranial neuromodulation created by modulated focused ultrasound, especially mFU's ability to produce compact sources of ultrasound at the very low frequencies (10-100s of Hertz) that are commensurate with the natural frequencies of the brain.
Circumferential and Posterolateral Fusion for Lumbar Disc Disease (2003)

Clinical outcome of low back fusion is unpredictable. There are various reports discussing the merits and clinical outcome of these two procedures. The patients were selected from a population of patients who had chronic low back pain unresponsive to conservative treatment. Thirty-six instrumented posterolateral fusions and 35 instrumented circumferential fusions with posterior lumbar interbody fusions were done simultaneously. Preoperative radiographic assessment included plain radiographs, magnetic resonance imaging scans, and provocative discography in all the patients. Posterolateral fusion or anterior lumbar interbody fusion was done for internal disc disruption. The Oswestry disability index, subjective scoring, and assessment of fusion were done at a minimum followup of 2 years. On subjective scoring assessment there was a satisfactory outcome of 63.9% (23 patients) in the posterolateral fusion group and 82.8% (29 patients) in the posterior lumbar interbody fusion group. On assessment by the Oswestry index no difference was found in outcome between the two groups. The posterolateral fusion group had a 63.9% satisfactory outcome and the posterior lumbar interbody fusion group had an 80% satisfactory outcome using the Oswestry disability index for postoperative assessment. There was 61.1% improvement in working ability in the posterolateral fusion group and 77.1% improvement in the posterior lumbar interbody fusion group which was not statistically significant. The authors consider instrumented circumferential fusion with posterior lumbar interbody fusion better than instrumented posterolateral fusion for managing chronic disabling low back pain.
Changes in oxidative stress markers and NF-κB activation induced by sprint exercise (2005)

This study was aimed to investigate changes in blood markers of oxidative damage induced by short-term supramaximal anaerobic exercise and to determine whether oxidative stress was associated to activation of the redox-sensitive transcription factor nuclear factor-kappaB (NF-kappaB). Both a single Wingate test (WAnT) test and series of four WAnTs separated by 60 min rest intervals were carried out by eight professional cyclists. Leukocyte 8-OH-2-deoxyguanosine levels were significantly elevated 24 h after both exercise protocols. A significant decrease in blood reduced glutathione (GSH) concentration was observed immediately after and at 15, 60 and 120 min of the single WAnT, followed by a return to basal value after 24 h. This decrease was parallel to a significant increase of the oxidised/reduced glutathione (GSSG/GSH) ratio, to an activation of NF-kappaB and to a significant decrease in the protein level of its inhibitor IkappaB. GSH concentration and the GSSG/GSH ratio changed significantly for the first three of the WAnTs series and normalised thereafter. A significant activation of NF-kappaB and a decrease in the IkappaB protein level were also detected. We conclude that short-term supramaximal anaerobic exercise induces oxidative stress, as evidenced by non cumulative damage to macromolecules and changes in the glutathione status. Our data also indicate that high intensity anaerobic work gives rise to an activation of the transcription factor NF-kappaB accompanied by a degradation of IkappaB.