gebhart/patrepeval huggingface dataset:
Nested polymerase chain reaction for detection of human immunodeficiency virus type 1 DNA in clinical specimens (1992)

A highly sensitive two-step polymerase chain reaction (PCR) method was evaluated for detection of human immunodeficiency virus type 1 (HIV-1) DNA in clinical specimens. The product resulting from the first amplification reaction is used as the template for the second PCR with an internal (nested) primer pair. Even when starting from a single copy of HIV-1 DNA, the double PCR product was readily detected by direct visualization in ethidium bromide-stained agarose gels. Amplification of minute amounts of HIV-1 DNA was successful in a considerable excess of HIV-1 negative DNA than reported previously. All of 85 HIV-1-infected individuals were PCR-positive with at least two of the three sets of primers used, 252 of 255 amplifications allowing unambiguous visualization of a unique DNA fragment of the expected size. The two-step amplification protocol is simple and rapid and fulfills the requirements of sensitivity and specificity for use in a clinical laboratory.
Critical Role of Prostaglandin E2 Overproduction in Impaired Pulmonary Host Response following Bone Marrow Transplantation (2006)

The success of bone marrow transplantation (BMT) as a therapy for malignant and inherited disorders is limited by infectious complications. We previously demonstrated syngeneic BMT mice are more susceptible to Pseudomonas aeruginosa pneumonia due to defects in the ability of donor-derived alveolar macrophages (AMs), but not polymorphonuclear leukocytes (PMNs), to phagocytose bacteria. We now demonstrate that both donor-derived AMs and PMNs display bacterial killing defects post-BMT. PGE2 is a lipid mediator with potent immunosuppressive effects against antimicrobial functions. We hypothesize that enhanced PGE2 production post-BMT impairs host defense. We demonstrate that lung homogenates from BMT mice contain 2.8-fold more PGE2 than control mice, and alveolar epithelial cells (2.7-fold), AMs (125-fold), and PMNs (10-fold) from BMT animals all overproduce PGE2. AMs also produce increased prostacyclin (PGI2) post-BMT. Interestingly, the E prostanoid (EP) receptors EP2 and EP4 are elevated on donor-derived phagocytes post-BMT. Blocking PGE2 synthesis with indomethacin overcame the phagocytic and killing defects of BMT AMs and the killing defects of BMT PMNs in vitro. The effect of indomethacin on AM phagocytosis could be mimicked by an EP2 antagonist, AH-6809, and exogenous addition of PGE2 reversed the beneficial effects of indomethacin in vitro. Importantly, in vivo treatment with indomethacin reduced PGE2 levels in lung homogenates and restored in vivo bacterial clearance from the lung and blood in BMT mice. Genetic reduction of cyclooxygenase-2 in BMT mice also had similar effects. These data clearly demonstrate that overproduction of PGE2 post-BMT is a critical factor determining impaired host defense against pathogens.
Notch2 Signaling Is Required for Potent Antitumor Immunity In Vivo (2010)

CD8(+) T cells play a central role in cancer immunosurveillance, and the efficient induction of CTLs against tumor Ags is required for successful immunotherapy for cancer patients. Notch signaling directly regulates the transcription of effector molecules in CTLs. However, it remains unclear whether Notch signaling in CD8(+) T cells is required for antitumor CTL responses and whether modulation of Notch signaling can augment antitumor CTL responses. In this study, we demonstrate that signaling by Notch2 but not Notch1 in CD8(+) T cells is required for antitumor CTL responses. Notch2(flox/flox) mice crossed with E8I-cre transgenic (N2F/F-E8I) mice, in which the Notch2 gene is absent only in CD8(+) T cells, die earlier than control mice after inoculation with OVA-expressing EG7 thymoma cells. In contrast, Notch1(flox/flox) mice crossed with E8I-cre transgenic mice inoculated with EG7 cells die comparable to control mice, indicating that Notch2 is crucial for exerting antitumor CTL responses. Injection of anti-Notch2 agonistic Ab or delta-like 1-overexpressing dendritic cells augmented the antitumor response in C57BL/6 mice inoculated with EG7 cells. These findings indicate that Notch2 signaling in CD8(+) T cells is required for generating potent antitumor CTLs, thus providing a crucial target for augmenting tumor immune responses.
High-power broad-band AlGaN/GaN HEMT MMICs on SiC substrates (2001)

Broad-band high-power cascode AlGaN/GaN high electron-mobility transistor monolithic-microwave integrated-circuit (MMIC) amplifiers with high gain and power-added efficiency (PAE) have been fabricated on high-thermal conductivity SiC substrates. A cascode gain cell exhibiting 5 W of power at 8 GHz with a small-signal gain of 19 dB was realized. A nonuniform distributed amplifier (NDA) based on this process was designed, fabricated, and tested, yielding a saturated output power of 3-6 W over a dc-8-GHz bandwidth with an associated PAE of 13%-31%. A broad-band amplifier MMIC using cascode cells in conjunction with a lossy-match input matching network showed a useful operating range of dc-8 GHz with an output power of 5-7.5 W and a PAE of 20%-33.% over this range. The third-order intermodulation products of the amplifiers under two-tone excitation were studied and third-order-intercept values of 42 and 43 dBm (computed using two-tone carrier power) for the lossy match and NDA amplifiers were obtained.
Hierarchical Bayesian estimation improves depth accuracy and spatial resolution of diffuse optical tomography (2012)

High-density diffuse optical tomography (HD-DOT) is an emerging technique for visualizing the internal state of biological tissues. The large number of overlapping measurement channels due to the use of high-density probe arrays permits the reconstruction of the internal optical properties, even with a reflectance-only measurement. However, accurate three-dimensional reconstruction is still a challenging problem. First, the exponentially decaying sensitivity causes a systematic depth-localization error. Second, the nature of diffusive light makes the image blurred. In this paper, we propose a three-dimensional reconstruction method that overcomes these two problems by introducing sensitivity-normalized regularization and sparsity into the hierarchical Bayesian method. Phantom experiments were performed to validate the proposed method under three conditions of probe interval: 26 mm, 18.4 mm, and 13 mm. We found that two absorbers with distances shorter than the probe interval could be discriminated under the high-density conditions of 18.4-mm and 13-mm intervals. This discrimination ability was possible even if the depths of the two absorbers were different from each other. These results show the high spatial resolution of the proposed method in both depth and horizontal directions.
Lipophilic 1,1-bisphosphonates are potent squalene synthase inhibitors and orally active cholesterol lowering agents in vivo. (1993)

Squalene synthase catalyzes the reductive dimerization of two molecules of farnesyl diphosphate to form squalene at the final branchpoint of the cholesterol biosynthetic pathway. We report herein that isoprenyl 1,1-bisphosphonates and related analogs are potent inhibitors of rat microsomal squalene synthase (I50 = 0.7-32 nM). In addition, members of this family are potent inhibitors of cholesterol biosynthesis in rats on intravenous and oral dosing, as well as cholesterol lowering agents in rats and hamsters. Significant inhibition of cholesterol biosynthesis in rats by lovastatin occurs with a concomitant inhibition of dolichol and coenzyme-Q9 synthesis. In contrast, bisphosphonate 4 has no effect on dolichol and coenzyme-Q9 biosynthesis in rats under conditions where cholesterol biosynthesis is > 90% inhibited.
Two-axis bend measurement with Bragg gratings in multicore optical fiber (2003)

We describe what is to our knowledge the first use of fiber Bragg gratings written into three separate cores of a multicore fiber for two-axis curvature measurement. The gratings act as independent, but isothermal, fiber strain gauges for which local curvature determines the difference in strain between cores, permitting temperature-independent bend measurement.
Organosilicon chemistry. Part 24. Homogeneous rhodium-catalysed hydrosilation of alkenes and alkynes: the role of oxygen or hydroperoxides (1980)

The hydrosilation of propene, hex-1-ene, and hex-1-yne, catalysed by [RhCl(PPh3)3] has been reinvestigated. When all reagents are carefully purified, the hydrosilation reaction is completely inhibited but can be initiated by the addition of oxygen or t-butyl hydroperoxide. The rate and extent of reaction in the latter case is unaffected by the presence of phenolic radical traps. For optimum reaction, stoicheiometric quantities of hydroperoxide are required. In the hex-1-yne system, variation of the PPh3: Rh ratio gives maximum activity at 1 : 1 and, with this stoicheiometry, the reaction rate is relatively insensitive to purification of the reagents. It is suggested that the role of oxygen or hydroperoxide is to remove triphenylphosphine from the system, by oxidation, generating a highly active catalyst with a low PPh3: Rh ratio. In the ‘clean’ conditions isomerisation of hex-1-ene proceeds rapidly, being catalysed by the silyl complex [RhH(Cl)(SiR3)(PPh3)2].
Microsatellite instability and gene mutations in transforming growth factor‐beta type II receptor are absent in small bowel carcinoid tumors (2004)

The molecular events leading to the formation of carcinoid tumors in the small bowel were different from those resulting in epithelial carcinomas. The usually slow-growing and relatively nonaggressive carcinoid tumors had variable expression of TGFbetaRII but were associated with the retention of mismatch repair protein function and a microsatellite-stable phenotype.
Membrane Interface-Interacting Sequences within the Ectodomain of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein: Putative Role during Viral Fusion (2000)

We have identified a region within the ectodomain of the fusogenic human immunodeficiency virus type 1 (HIV-1) gp41, different from the fusion peptide, that interacts strongly with membranes. This conserved sequence, which immediately precedes the transmembrane anchor, is not highly hydrophobic according to the Kyte-Doolittle hydropathy prediction algorithm, yet it shows a high tendency to partition into the membrane interface, as revealed by the Wimley-White interfacial hydrophobicity scale. We have investigated here the membrane effects induced by NH(2)-DKWASLWNWFNITNWLWYIK-CONH(2) (HIV(c)), the membrane interface-partitioning region at the C terminus of the gp41 ectodomain, in comparison to those caused by NH(2)-AVGIGALFLGFLGAAGSTMGARS-CONH(2) (HIV(n)), the fusion peptide at the N terminus of the subunit. Both HIV(c) and HIV(n) were seen to induce membrane fusion and permeabilization, although lower doses of HIV(c) were required for comparable effects to be detected. Experiments in which equimolar mixtures of HIV(c) and HIV(n) were used indicated that both peptides may act in a cooperative way. Peptide-membrane and peptide-peptide interactions underlying those effects were further confirmed by analyzing the changes in fluorescence of peptide Trp residues. Replacement of the first three Trp residues by Ala, known to render a defective gp41 phenotype unable to mediate both cell-cell fusion and virus entry, also abrogated the HIV(c) ability to induce membrane fusion or form complexes with HIV(n) but not its ability to associate with vesicles. Hydropathy analysis indicated that the presence of two membrane-partitioning stretches separated by a collapsible intervening sequence is a common structural motif among other viral envelope proteins. Moreover, sequences with membrane surface-residing residues preceding the transmembrane anchor appeared to be a common feature in viral fusion proteins of several virus families. According to our experimental results, such a feature might be related to their fusogenic function.
Techniques for Fast Physical Synthesis (2007)

The traditional purpose of physical synthesis is to perform timing closure , i.e., to create a placed design that meets its timing specifications while also satisfying electrical, routability, and signal integrity constraints. In modern design flows, physical synthesis tools hardly ever achieve this goal in their first iteration. The design team must iterate by studying the output of the physical synthesis run, then potentially massage the input, e.g., by changing the floorplan, timing assertions, pin locations, logic structures, etc., in order to hopefully achieve a better solution for the next iteration. The complexity of physical synthesis means that systems can take days to run on designs with multimillions of placeable objects, which severely hurts design productivity. This paper discusses some newer techniques that have been deployed within IBM's physical synthesis tool called PDS that significantly improves throughput. In particular, we focus on some of the biggest contributors to runtime, placement, legalization, buffering, and electric correction, and present techniques that generate significant turnaround time improvements
Förster Resonance Energy Transfer Measurements Are Consistent with a Helical Bundle Model for Lipid-Free Apolipoprotein A-I (2005)

Apolipoprotein (apo) A-I mutants were constructed for FRET studies to distinguish between two possible lipid-free conformers, a globular helix bundle and an elongated helical hairpin. Mutants containing a single Trp at position 50 were prepared by replacing Trps at positions 8, 72, and 108 with Phe (W@50). Two mutants were constructed from W@50 by incorporating Cys at Arg83 (W@50R83C) or Arg173 (W@50R173C) for attachment of the fluorescent probe AEDANS. Secondary structure of the mutants is very similar to wild type (wt) apo A-I, and fluorescence emission indicates that W50 is protected from solvent. Thermal stabilities of the AEDANS-labeled mutants are also similar to wt. These results indicate that no discernible changes occur in structure or stability as a result of mutations or labeling. The FRET data from W@50 to AEDANS are well-represented by a single distance distribution function with a distance of approximately 22 A for W@50R83C and approximately 19 A for W@50R173C. These distances are consistent with theoretical values calculated from a helical bundle model but not from a helical hairpin. A probability distance distribution function yields significantly small half-width values of 5.6 and 3.7 A, respectively, suggesting low conformational dynamics in both mutants. Differential scanning calorimetry (DSC) was performed on wt and a C-terminal deletion mutant, Delta(187-243), to obtain information on domain architecture. Contrary to expectations, both proteins unfold cooperatively. The results are consistent with the presence of a single folded domain within residues 1-186. These results support the presence of a discrete globular bundle conformation for lipid-free apo A-I.
X-ray/Neutron Diffraction and Electrochemical Studies of Lithium De/Re-Intercalation in Li<sub>1</sub><sub>-</sub><i><sub>x</sub></i>Co<sub>1/</sub><sub>3</sub>Ni<sub>1/3</sub>Mn<sub>1/3</sub>O<sub>2</sub> (<i>x</i> = 0 → 1) (2006)

X-ray and neutron diffraction studies were carried out on highly ordered (2−3% Li/Ni exchange) layered Li1-xCo1/3Ni1/3Mn1/3O2 [(1 − x) = 1.0; 0.8, 0.6, 0.45, 0.30, 0.04] prepared by chemical delithiation and relithiation. The studies reveal that the initial R3̄m phase (O3) is maintained up to extraction of 0.70−0.75 Li and exhibits only ∼1% change in volume over the range of composition. Additional extraction of Li results in the appearance of the O1 phase (trigonal; P3̄m1), which displays a strong contraction in the c axis by 5.3% and a volume decrease of 7.2%. Oxygen vacancies were not evident in the completely delithiated material. Re-intercalation of lithium in this phase was relatively irreversible, however, resulting in poorly defined mixtures of the O3 and O1 structures that exhibited a large fraction of stacking faults. In contrast, materials that were not delithiated beyond x = 0.30 resulted in fully reversible reformation of the original crystalline O3 phase on re-intercalation. Electrochemical cycling under different cutoff voltages were in accord with these observations and suggest an optimum upper cutoff voltage of 4.3−4.4 V.
Extracting Information for Automatic Indexing of Multimedia Material. (2002)

This paper discusses our work on information extraction (IE) from multi-lingual, multi-media, multi-genre Language Resources, in a domain where there are many different event types. This work is being carried out in the context of MUMIS, an EU-funded project that aims at the development of basic technology for the creation of a composite index from multiple and multi-lingual sources. Our approach to IE relies on a finite state machinery provided by GATE, a General Architecture for Text Engineering, pipelined with full syntactic analysis and discourse interpretation implemented in Prolog.
Studies on transfer ribonucleic acids and related compounds. IX<sup>(1)</sup>Ribo-oligonucleotide synthesis using a photosensitive o-nitrobenzyl protection at the 2′-hydroxyl group (1974)

o-Nitrobenzyl group was introduced to the 2'-hydroxyl function of uridine via 2',3'-O-(dibutylstannylene) uridine. The benzylated uridine was protected at the 5'-hydroxyl group with monomethoxytrityl chloride and condensed with 2',3'-O-dibenzoyluridine 5'-phosphate or N,N',2',3'-O-tetrabenzoyladenosine 5'-phosphate using dicyclohexylcarbodiimide (DCC). o-Nitrobenzyl ether linkage of the dinucleotides was removed by UV irradiation with wavelength longer than 320 nm. Deprotected UpU and UpA thus obtained were characterized by RNase A digestion.
A Method for Constricting Large Veins for Use in Arterial Vascular Reconstruction (1990)

A satisfactory biologic graft can be created if dilated, but otherwise unusable veins are wrapped with a constrictive mesh tube. The purpose of this study was to determine whether a resorbable constrictive tube creates an appropriately sized vascular graft by induction of neoarterial wall growth. In 8 sheep a 5 cm segment of the carotid artery was resected and the external jugular vein inserted as a tubular graft. The vein was either wrapped with a polydioxanon (PDS) reinforced polyglactin (Vicryl) mesh (n = 4), a Vicryl mesh (n = 4), or a Dacron mesh tube (n = 3) to achieve a diameter reduction to 7 mm. Or the vein was used without reinforcement (n = 3). At angiography after 6 months the unreinforced veins had a diameter of 19 mm (range 15-22). The Vicryl reinforced veins measured 9.4 (8.5-10) mm, but 3 of 4 developed aneurysmatic dilatations at sites of valve sinuses with a mean diameter of 19 (15-21) mm. PDS reinforced veins measured 7.4 mm (7.1-7.9). Two of 4 had minor aneurysms of 13 and 16 mm. The two remaining PDS reinforced grafts were indistinguishable from the native artery. Dacron tubes reduced the vein size reliably to 7.6 (7.5-7.9) mm, but showed narrowing at the proximal anastomoses (PDS 7.2 +/- 0.4, Dacron 6.1 +/- 0.4, p = 0.016). PDS wrapping reduced maximal graft diameter to 10.9 +/- 4 mm as compared to that of the native vein, 18.7 +/- 3.5 (p less than 0.05). Resorbable meshes can reduce the diameter of a venous graft by strengthening the vessel wall.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of the interaction between protein phosphatase 1 glycogen-targeting subunit and glycogen phosphorylase increases glycogen synthesis in primary rat hepatocytes (2008)

In Type 2 diabetes, increased glycogenolysis contributes to the hyperglycaemic state, therefore the inhibition of GP (glycogen phosphorylase), a key glycogenolytic enzyme, is one of the possibilities to lower plasma glucose levels. Following this strategy, a number of GPis (GP inhibitors) have been described. However, certain critical issues are associated with their mode of action, e.g. an impairment of muscle function. The interaction between GP and the liver glycogen targeting subunit (termed G(L)) of PP1 (protein phosphatase 1) has emerged as a new potential anti-diabetic target, as the disruption of this interaction should increase glycogen synthesis, potentially providing an alternative approach to counteract the enhanced glycogenolysis without inhibiting GP activity. We identified an inhibitor of the G(L)-GP interaction (termed G(L)-GPi) and characterized its mechanism of action in comparison with direct GPis. In primary rat hepatocytes, at elevated glucose levels, the G(L)-GPi increased glycogen synthesis similarly to direct GPis. Direct GPis significantly reduced the cellular GP activity, caused a dephosphorylation of the enzyme and decreased the amounts of GP in the glycogen-enriched fraction; the G(L)-GPi did not influence any of these parameters. Both mechanisms increased glycogen accumulation at elevated glucose levels. However, at low glucose levels, only direct GPis led to increased glycogen amounts, whereas the G(L)-GPi allowed the mobilization of glycogen because it did not block the activity of GP. Due to this characteristic, G(L)-GPi in comparison with GPis could offer an advantageous risk/benefit profile circumventing the potential downsides of a complete prevention of glycogen breakdown while retaining glucose-lowering efficacy, suggesting that inhibition of the G(L)-GP interaction may provide an attractive novel approach for rebalancing the disturbed glycogen metabolism in diabetic patients.
The use of 19F spectroscopy and diffusion-weighted MRI to evaluate differences in gene-dependent enzyme prodrug therapies (2004)

To evaluate noninvasive measures of gene expression and tumor response in a gene-dependent enzyme prodrug therapy (GDEPT), a bifunctional fusion gene between Saccharomyces cerevisiae cytosine deaminase (CD) and Haemophilus influenzae uracil phosphoribosyltransferase (UPRT) was constructed. CD deaminates 5-fluorocytosine (5FC) to 5-fluorouracil (5FU), and UPRT subsequently converts 5FU to fluorouridine monophosphate, and both of these reactions can be monitored noninvasively in vitro and in vivo using 19F magnetic resonance spectroscopy (MRS). Following transient transfection the CD-UPRT fusion protein exhibited both UPRT and CD enzymatic activities as documented by 19F MRS. In addition, an increase in CD activity and thermal stability was witnessed for the fusion protein compared to native CD. Stable expression of CD-UPRT in 9L glioma cells increased both 5FC and 5FU sensitivity in vitro compared to CD-expressing and wild-type 9L cells. Noninvasive 19F MRS of both CD and UPRT gene function in vivo demonstrated that in animals bearing CD-expressing tumors there was limited conversion of 5FC to 5FU with no measurable accumulation of cytotoxic fluorinated nucleotides (F-nucs). In contrast, CD-UPRT-expressing tumors had increased CD gene activity with a threefold higher intratumoral accumulation of 5FU and significant generation of F-nucs. Finally, CD-UPRT yielded increased efficacy in an orthotopic animal model of high-grade glioma. More importantly, early changes in cellular water mobility, which are felt to reflect cellular death, as measured by diffusion-weighted MRI, were predictive of both durable response and increased animal survival. These results demonstrate the increased efficacy of the CD-UPRT GDEPT compared to CD alone both biochemically and in a preclinical model and validate both 19F MRS and diffusion-weighted MRI as tools to assess gene function and therapeutic efficacy.