gebhart/patrepeval huggingface dataset:
Use of minimum-adder multiplier blocks in FIR digital filters (1995)

The computational complexity of VLSI digital filters using fixed point binary multiplier coefficients is normally dominated by the number of adders used in the implementation of the multipliers. It has been shown that using multiplier blocks to exploit redundancy across the coefficients results in significant reductions in complexity over methods using canonic signed-digit (CSD) representation, which in turn are less complex than standard binary representation. Three new algorithms for the design of multiplier blocks are described: an efficient modification to an existing algorithm, a new algorithm giving better results, and a hybrid of these two which trades off performance against computation time. Significant savings in filter implementation cost over existing techniques result in all three cases. For a given wordlength, it was found that a threshold set size exists above which the multiplier block is extremely likely to be optimal. In this region, design computation time is substantially reduced.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Homologs of vascular endothelial growth factor are encoded by the poxvirus orf virus (1994)

A gene encoding a polypeptide with homology to mammalian vascular endothelial growth factors (VEGFs) has been discovered in the genome of orf virus (OV), a parapoxvirus that affects sheep and goats and, occasionally, humans. The gene is transcribed abundantly early in infection and is found immediately outside the inverted terminal repeat at the right end of the genome. In the NZ2 strain of OV (OV NZ2), the gene encodes a polypeptide with a molecular size of 14.7 kDa, while in another strain, OV NZ7, there is a variant gene that encodes a polypeptide of 16 kDa. The OV NZ2 and OV NZ7 polypeptides show 22 to 27% and 16 to 23% identity, respectively, to the mammalian VEGFs. The viral polypeptides are only 41.1% identical to each other, and there is little homology between the two genes at the nucleotide level. Another unusual feature of these genes is their G+C content, particularly that of OV NZ7. In a genome that is otherwise 63% G+C, the OV NZ2 gene is 57.2% G+C and the OV NZ7 gene is 39.7% G+C. The OV NZ2 gene, but not the OV NZ7 gene, is homologous to the mammalian VEGF genes at the DNA level, suggesting that the gene has been acquired from a mammalian host and is undergoing genetic drift. The lesions induced in sheep and humans after infection with OV show extensive dermal vascular endothelial proliferation and dilatation, and it is likely that this is a direct effect of the expression of the VEGF-like gene.
Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy (2008)

Carbon nanotubes are promising new materials for molecular delivery in biological systems. The long-term fate of nanotubes intravenously injected into animals in vivo is currently unknown, an issue critical to potential clinical applications of these materials. Here, using the intrinsic Raman spectroscopic signatures of single-walled carbon nanotubes (SWNTs), we measured the blood circulation of intravenously injected SWNTs and detect SWNTs in various organs and tissues of mice ex vivo over a period of three months. Functionalization of SWNTs by branched polyethylene-glycol (PEG) chains was developed, enabling thus far the longest SWNT blood circulation up to 1 day, relatively low uptake in the reticuloendothelial system (RES), and near-complete clearance from the main organs in approximately 2 months. Raman spectroscopy detected SWNT in the intestine, feces, kidney, and bladder of mice, suggesting excretion and clearance of SWNTs from mice via the biliary and renal pathways. No toxic side effect of SWNTs to mice was observed in necropsy, histology, and blood chemistry measurements. These findings pave the way to future biomedical applications of carbon nanotubes.
Abstract 4455: Differential response to AS1411 in a pair of VHL-positive and VHL-negative renal carcinoma cell lines (2010)

Abstract AS1411 is a G-rich phosphodiester oligonucleotide that forms a stable G-quadruplex structure and functions as an aptamer to nucleolin. Preclinical studies have shown that AS1411 exhibits antiproliferative activity against a variety of cancer types, but has little effect on normal cells. In a Phase I clinical trial of AS1411 in 30 patients with advanced solid tumors, there were no serious adverse events associated with AS1411 treatment. Furthermore, there was evidence of clinical benefit, particularly in patients with metastatic renal cell carcinoma (RCC), including durable disease stabilization and objective responses. A phase II trial of AS1411 in metastatic RCC is now underway. Renal cell carcinomas (RCC) are the most common form of kidney cancer and the majority of these (75%) have biallelic inactivation of the von Hippel-Lindau tumor suppressor gene (VHL) by mutation or less commonly by hypermethylation. The VHL gene product, pVHL, has multiple functions including ubiquitination of HIF transcription factors, regulation of endocytosis, and control of microtubule orientation. Here we investigated the effect of AS1411 on two previously established matched RCC cell lines with and without functional VHL: RCC4 cells which harbor a mutation in VHL and do not express functional VHL (VHL-negative), and RCC4/VHL which are stably transfected to express wild type VHL (VHL-positive). Using a variety of techniques (MTT assay, colony forming assay, and cell cycle analysis), we observed a clear difference in response to AS1411 between RCC4 and RCC4/VHL cells, with the VHL-negative line being much more sensitive to growth inhibition following AS1411 treatment. Cell cycle analysis showed that VHL-negative RCC4 cells treated with AS1411 accumulate predominantly in S phase after 72 h (as seen in other AS1411-responsive cell lines), followed by S and G2/M phase of cell cycle after 96 h treatment. In contrast, there was no perturbation of the cell cycle in the VHL-positive RCC4/VHL cells. Further studies are ongoing to determine if this is a general effect, dependent directly on pVHL, or if it is related to specific phenotypic differences between these two cell lines. In any case, the availability of two closely related cell lines with markedly different sensitivities to AS1411 should greatly facilitate our efforts to identify markers that may predict response to AS1411. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4455.
Glucagon-like peptide 1 improved glycemic control in type 1 diabetes (2003)

BACKGROUND: Glucagon-like peptide-1 (GLP-1) and its agonists are under assessment in treatment of type 2 diabetes, by virtue of their antidiabetic actions, which include stimulation of insulin secretion, inhibition of glucagon release, and delay of gastric emptying. We examined the potential of GLP-1 to improve glycemic control in type 1 diabetes with no endogenous insulin secretion. METHODS: Dose-finding studies were carried out to establish mid range doses for delay of gastric emptying indicated by postponement of pancreatic polypeptide responses after meals. The selected dose of 0.63 micrograms/kg GLP-1 was administered before breakfast and lunch in 8-hour studies in hospital to establish the efficacy and safety of GLP-1. In outside-hospital studies, GLP-1 or vehicle was self-administered double-blind before meals with usual insulin for five consecutive days by five males and three females with well-controlled C-peptide-negative type 1 diabetes. Capillary blood glucose values were self-monitored before meals, at 30 and 60 min after breakfast and supper, and at bedtime. Breakfast tests with GLP-1 were conducted on the day before and on the day after 5-day studies. Paired t-tests and ANOVA were used for statistical analysis. RESULTS: In 8-hour studies time-averaged incremental (delta) areas under the curves(AUC) for plasma glucose through 8 hours were decreased by GLP-1 compared to vehicle (3.2 PlusMinus; 0.9, mean PlusMinus; se, vs 5.4 PlusMinus; 0.8 mmol/l, p <.05), and for pancreatic polypeptide, an indicator of gastric emptying, through 30 min after meals (4.0 PlusMinus; 3.1 vs 37 PlusMinus; 9.6 pmol/l, p <.05) with no adverse effects. Incremental glucagon levels through 60 min after meals were depressed by GLP-1 compared to vehicle (-3.7 PlusMinus; 2.5 vs 3.1 PlusMinus; 1.9 ng/l, p <.04). In 5-day studies, AUC for capillary blood glucose levels were lower with GLP-1 than with vehicle (-0.64 PlusMinus; 0.33 vs 0.34 PlusMinus; 0.26 mmol/l, p <.05). No assisted episode of hypoglycaemia or change in insulin dosage occurred. Breakfast tests on the days immediately before and after 5-day trials showed no change in the effects of GLP-1. CONCLUSION: We have demonstrated that subcutaneous GLP-1 can improve glucose control in type 1 diabetes without adverse effects when self-administered before meals with usual insulin during established intensive insulin treatment programs.
Superconducting Y-Ba-Cu-O oxide films by sputtering (1987)

We have prepared superconducting thin films of Y-Ba-Cu-O with Tc onsets above 95 K by both diode and magnetron sputtering. Films with full superconductivity (R=0) at 85 K have been produced by dc magnetron sputtering. The compositions of the films are fairly uniform across an area 50 mm in diameter and through the film thickness. Structural properties of the films were studied by x-ray diffraction. Critical current densities in the range of 3000 to 104 A/cm2 have been measured at 4.2 K.
Ezrin, a plasma membrane–microfilament linker, signals cell survival through the phosphatidylinositol 3-kinase/Akt pathway (1999)

ERM (Ezrin-Radixin-Moesin) proteins function as plasma membrane-actin cytoskeleton linkers and participate in the formation of specialized domains of the plasma membrane. We have investigated ezrin function in tubulogenesis of a kidney-derived epithelial cell line, LLC-PK1. Here we show that cells overproducing a mutant form of ezrin in which Tyr-353 was changed to a phenylalanine (Y353F) undergo apoptosis when assayed for tubulogenesis. While investigating the mechanism responsible for this apoptosis, we found that ezrin interacts with p85, the regulatory subunit of phosphatidylinositol 3-kinase (PI 3-kinase). Two distinct sites of ezrin are involved in this interaction, the amino-terminal domain containing the first 309 aa and the phosphorylated Tyr-353 residue, which binds to the carboxyl-terminal SH2 domain of p85. Cells producing Y353F ezrin are defective in activation of the protein kinase Akt, a downstream target of PI 3-kinase that protects cells against apoptosis. Furthermore, the apoptotic phenotype of these cells is rescued by production of a constitutively activated form of PI 3-kinase. Taken together, these results establish a novel function for ezrin in determining survival of epithelial cells by activating the PI 3-kinase/Akt pathway.
Design principle for a circularly birefringent optical fiber (1988)

A suitable cross section incorporating material anisotropy is shown to give circular birefringence in a slowly spun monomode fiber. It is assumed that the fractional variation Deltan/n of the refractive index satisfies the weak guidance condition Deltan/n << 1 and that the period (or pitch) p of the spun fiber is large enough so that the fundamental modes remain effectively bound. Under these assumptions the magnitude of the circular birefringence can be calculated from solutions of the scalar wave equation and in any case lies between the limits (0, 4pi/p). The value is zero in the absence of material anisotropy. The required material anisotropy could be produced by stress implanted in the core.
Olfactory Receptor Interactions with Other Receptors (2009)

Olfactory receptors expressed in heterologous cells often suffer from retention in the endoplasmic reticulum and poor trafficking to the plasma membrane. Interactions of the olfactory receptor M71 with several subtypes of adrenergic and purinergic receptors can alleviate M71 trafficking deficits in heterologous cells and allow for robust M71 plasma membrane expression. Furthermore, the signaling pathway to which M71 couples upon agonist stimulation can be strongly influenced by the partner receptor's driving M71 trafficking to the plasma membrane. These studies provide evidence that olfactory receptors can interact with other G protein-coupled receptors and that these interactions can promote olfactory receptor surface expression and functionality in heterologous cells.
Novel PPV derivatives emitting light over a broad wavelength range (1997)

Organic films for display applications have usually been developed with the aim of individual emission of red, blue, and green light. Another approach, presented here, is to design organic light‐emitting devices that emit over a broad spectral range, i.e., essentially white light. The preparation of two new polymer (see Figure) films is described, together with the results of absorption, photoluminescence, and electroluminescence measurements. magnified image
High-Pressure Gradients Generated by Closed-Suction Surgical Drainage Systems (2002)

Closed suction drains are capable of generating high pressures that may contribute to some complications associated with their use. Closed suction drainage systems differ with regard to their generation of negative pressure.
The pnk/pnl gene (ORF 86) of Autographa californica nucleopolyhedrovirus is a non-essential, immediate early gene. (1998)

Autographa californica nucleopolyhedrovirus (AcMNPV) ORF 86, located within the HindIII C fragment, potentially encodes a protein which shares sequence similarity with two T4 bacteriophage gene products, RNA ligase and polynucleotide kinase. This AcMNPV gene has been designated pnk/pnl but has yet to be assigned a function in virus replication. It has been classified as an immediate early virus gene, since the promoter was active in uninfected insect cells and mRNA transcripts were detectable from 4 to 48 h post-infection and in the presence of cycloheximide or aphidicolin in virus-infected cells. The extremities of the transcript have been mapped by primer extension and 3' RACE-PCR to positions -18 from the translational start codon and +15 downstream of the stop codon. The function of pnk/pnl was investigated by producing a recombinant virus (Acdel86lacZ) with the coding region replaced with that of lacZ. This virus replicated normally in Spodoptera frugiperda (Sf 21) cells, indicating that pnk/pnl is not essential for propagation in these cells. Virus protein production in Acdel86lacZ-infected Sf 21 cells also appeared to be unaffected, with normal synthesis of the IE-1, GP64, VP39 and polyhedrin proteins. Shut-down of host protein synthesis was not abolished in recombinant infection. When other baculovirus genomes were examined for the presence of pnk/pnl by restriction enzyme digestion and PCR, a deletion was found in AcMNPV 1.2, Galleria mellonella NPV (GmMNPV) and Bombyx mori NPV (BmNPV), suggesting that in many isolates this gene has either never been acquired or has been lost during genome evolution. This is one of the first baculovirus immediate early genes that appears to be nonessential for virus survival.
Cytokine-in-adjuvant steering of the immune response phenotype to HIV-1 vaccine constructs: granulocyte-macrophage colony-stimulating factor and TNF-alpha synergize with IL-12 to enhance induction of cytotoxic T lymphocytes (1997)

To enhance and steer immune responses to synthetic peptide vaccines toward selected functional types and to understand the cooperative action of cytokines in fine-tuning the immune response, we attempted to influence the in vivo cytokine environment by delivering cytokines directly to the microenvironment in which the immune response is initiated. Here we study the effects of IL-2, IL-4, IL-7, IL-1beta, IL-12, IFN-gamma, TNF-alpha, and granulocyte-macrophage CSF (GM-CSF) incorporated with peptide in adjuvant on a variety of responses elicited: CTL, T cell proliferation, cytokine production and message, and Ab isotype. We show GM-CSF to be the single most effective cytokine for enhancing both cellular and humoral immunity to two previously characterized HIV-1 MN vaccine constructs. Novel synergies were also detected. GM-CSF synergized with IL-12 for CTL induction in BALB/c mice concomitant with suppression of Th2 cytokines IL-4 and IL-10. TNF-alpha also synergized with IL-12, but by a different mechanism, inducing IFN-gamma production in BALB/c mice and thus shifting the response to a Th1 phenotype. The results presented here suggest that in addition to IL-2, optimum induction of CD8+ CTL in vivo requires a combination of cytokines, including GM-CSF (probably acting to enhance Ag presentation and CD4+ cell help) and IL-12 (steering the Th response toward Th1 cytokines).
Structure-Based Design of Orally Bioavailable 1H-Pyrrolo[3,2-c]pyridine Inhibitors of Mitotic Kinase Monopolar Spindle 1 (MPS1) (2013)

The protein kinase MPS1 is a crucial component of the spindle assembly checkpoint signal and is aberrantly overexpressed in many human cancers. MPS1 is one of the top 25 genes overexpressed in tumors with chromosomal instability and aneuploidy. PTEN-deficient breast tumor cells are particularly dependent upon MPS1 for their survival, making it a target of significant interest in oncology. We report the discovery and optimization of potent and selective MPS1 inhibitors based on the 1H-pyrrolo[3,2-c]pyridine scaffold, guided by structure-based design and cellular characterization of MPS1 inhibition, leading to 65 (CCT251455). This potent and selective chemical tool stabilizes an inactive conformation of MPS1 with the activation loop ordered in a manner incompatible with ATP and substrate-peptide binding; it displays a favorable oral pharmacokinetic profile, shows dose-dependent inhibition of MPS1 in an HCT116 human tumor xenograft model, and is an attractive tool compound to elucidate further the therapeutic potential of MPS1 inhibition.
IAP family proteins---suppressors of apoptosis (1999)

Apoptosis is a physiological cell suicide program that is critical for the development and maintenance of healthy tissues. Dysregulation of cell death pathways occur in cancer, autoimmune and immunodeficiency diseases, reperfusion injury after ischemic episodes, and in neurodegenerative disorders. Thus, proteins involved in apoptosis regulation are of intense biological interest and many are attractive therapeutic targets. This review discusses the Inhibitor of Apoptosis (IAP) family of proteins. First discovered in baculoviruses, IAPs were shown to be involved in suppressing the host cell death response to viral infection. Interestingly, ectopic expression of some baculoviral IAPs blocks apoptosis in mammalian cells, suggesting conservation of the cell death program among diverse species and commonalities in the mechanism used by the IAPs to inhibit apoptosis. Although the mechanism used by the IAPs to suppress cell death remains debated, several studies have provided insights into the biochemical functions of these intriguing proteins. Moreover, a variety of reports have suggested an important role for the IAPs in some human diseases.
Gentamicin administration in Duchenne patients with premature stop codon. Preliminary results. (2003)

Aim of the study was to investigate whether the administration of gentamicin could restore dystrophin expression in striated muscles of patients with Duchenne muscular dystrophy caused by premature stop codon, as reported in mdx mice. Four Duchenne patients, still ambulant or in wheelchair stage for less than 4 months, selected among those with point mutations resulting in premature stop codons, received two 6-day cycles of gentamicin sulfate, at an interval of 7 weeks, according to the protocol approved by the Ethics Committee of the Second University of Naples. A muscle biopsy was performed after the second cycle of administration; the specimens were analysed by both immuno-histochemistry and Western blotting. Skeletal muscle changes were monitored by dynamic tests and Creatine Kinase values; at the beginning and end of treatment, cardiac and respiratory status was evaluated by electrocardiography, echocardiography, acoustic densitometry and vital capacity. Side-effects such as nephrotoxicity and ototoxicity were also monitored. Three out of four patients, who had the most permissive UGA as stop codon, showed positive results. In one patient, there was a dramatic re-expression of dystrophin by both immuno-histochemistry and Western blot; in two patients, dystrophin positive fibres were seen by the antibody to the rod domain with immuno-histochemistry; the fourth patient, with UAA as stop codon, showed no expression of dystrophin at all. These results suggest that gentamicin is able to recover dystrophin expression in a subset of Duchenne patients with nonsense mutations, raising the possibility of the first pharmacological treatment for muscular dystrophy.
Activation of acetyl-CoA carboxylase. Purification and properties of a Mn2+-dependent phosphatase. (1985)

Acetyl-CoA carboxylase was isolated from rat liver by polyethylene glycol precipitation and avidin affinity chromatography. Sodium dodecyl sulfate electrophoresis of the enzyme gives one protein band (Mr 250,000). Phosphate analysis of the carboxylase showed the presence of 8.3 mol of phosphate/mol of subunit (Mr 250,000). The purified carboxylase has low activity in the absence of citrate (specific activity = 0.3 units/mg). However, addition of 10 mM citrate activates the carboxylase 10-fold, with half-maximal activation observed at 2 mM citrate, well above the physiological citrate level. Using this carboxylase as a substrate, we have isolated from rat liver a protein that activates the enzyme about 10-fold. This protein has been purified to near homogeneity (Mr 90,000). Incubation of this protein with 32P-labeled acetyl-CoA carboxylase results in a time-dependent activation of carboxylase with concomitant release of 32Pi, indicating that this protein is a phosphoprotein phosphatase. Both activation and dephosphorylation are dependent on Mn2+, but not citrate. This phosphatase does not hydrolyze p-nitrophenyl phosphate but does show high affinity for acetyl-CoA carboxylase (Km = 0.2 microM) as compared to its action on phosphorylase a (Km = 5.5 microM) and phosphohistone (Km = 20 microM). Activated acetyl-CoA carboxylase was isolated after dephosphorylation by the phosphatase. Such preparations contain about 5 mol of phosphate/mol of subunit and have specific activities of 2.6-3.0 units/mg in the absence of citrate. These activities are comparable to those of the phosphorylated carboxylase in the presence of 10 mM citrate. Thus, dephosphorylation by the Mn2+-dependent phosphatase renders the carboxylase citrate-independent, as compared to the phosphorylated form, which is citrate-dependent. To our knowledge this is the first report of a preparation of animal acetyl-CoA carboxylase that has substantial catalytic activity independent of citrate.