gebhart/patrepeval huggingface dataset:
Dual Inhibitors of Src and Abl Tyrosine Kinases (2004)

Chronic myelogenous leukemia (CML) is characterized by the expression of Bcr-Abl, a constitutively active form of the Abl tyrosine kinase. Gleevec, a small molecule Abl inhibitor developed by Novartis, is effective in treating early-stage CML patients, however those with advanced disease often acquire resistance to the drug. In many cases, this resistance is associated with mutations in the Abl kinase domain that no longer allow Gleevec to bind to the protein. In contrast to Gleevec, which does not inhibit members of the Src family of kinases (SFKs), several compounds initially identified as Src inhibitors also inhibit Abl. Crystallography showed that while Gleevec binds only to the inactive conformation of the Abl catalytic domain, PD 173955, a dual Src / Abl inhibitor, binds to both the active and inactive conformations. This finding is consistent with the activity of several Src / Abl inhibitors against cell lines harboring certain Gleevec resistant mutated forms of Bcr-Abl. In addition, since SFKs are implicated in Bcr-Abl signaling, these dual Src / Abl inhibitors may prove to be highly effective agents for the treatment of CML, both as first line agents and for those patients who develop Gleevec resistance. This review summarizes the considerable efforts focused on the design of dual inhibitors of Src and Abl kinases.
Desolvation of Ions in Subnanometer Pores and Its Effect on Capacitance and Double‐Layer Theory (2008)

Recasting the double layer: The implicit assumption that electrochemical double layers are governed only by ion/electrode charge separation may be short-sighted and lead to a fundamental misunderstanding of the phenomenological response. This is shown in a study performed on ions confined in nanoporous carbon with pores smaller than the size of an ion surrounded by a solvation shell (see picture; TEA+=tetraethylammonium, AN=acetonitrile). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z704894_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Characterization of degQ and degS, Escherichia coli genes encoding homologs of the DegP protease (1996)

The degQ and degS genes of Escherichia coli encode proteins of 455 and 355 residues, respectively, which are homologs of the DegP protease. The purified DegQ protein has the properties of a serine endoprotease and is processed by the removal of a 27-residue amino-terminal signal sequence. A plasmid expressing degQ rescues the temperature-sensitive phenotype of a strain bearing the degP41 deletion, implying that DegQ, like DegP, functions as a periplasmic protease in vivo. Deletions in the degQ gene cause no obvious growth defect, while those in the degS gene result in a small-colony phenotype. The latter phenotype is rescued by a plasmid expressing the degS gene but not by plasmids expressing the degQ or degP genes. This result and the inability of a plasmid expressing degS to rescue the temperature-sensitive degP41 phenotype indicate that the DegS protein is functionally different from the DegQ and DegP proteins.
Microbial Interactions in the Respiratory Tract (2009)

Upper respiratory tract infections are caused by the synergistic and antagonistic interactions between upper respiratory tract viruses and 3 predominant bacterial pathogens: Streptococcus pneumoniae, nontypeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis, which are members of the commensal flora of the nasopharynx. For many bacterial pathogens, colonization of host mucosal surfaces is a first and necessary step in the infectious process. S. pneumoniae and H. influenzae have intricate interactions in the nasopharynx. The host innate immune response may influence these interactions and therefore influence the composition of the colonizing flora and the invading bacteria. S. pneumoniae, nontypeable H. influenzae, and M. catarrhalis can behave as opportunistic pathogens of the middle ear when conditions are optimal. Chronic otitis media (OM) and recurrent OM include a biofilm component. Each of the 3 predominant pathogens of OM can form a biofilm and have been shown to comprise biofilms present on middle ear mucosa specimens recovered from children with recurrent or chronic OM. Some of these characterized biofilms are of mixed bacterial etiology, suggesting that progress made on single-microbe directed strategies for treatment and/or prevention of OM, although highly encouraging, are likely to be inadequate. A significantly greater understanding about microbial physiology is required as it relates to the involvement of biofilms in OM, to identify points in the natural course of the disease that are perhaps more amenable to treatment strategies, as well as to identify biofilm-relevant antigenic targets that would be helpful in the rational design of vaccines to prevent OM.
Vortex Mask: Making 80nm contacts with a twist! (2002)

An optical vortex has a phase that spirals like a corkscrew. Since any nonzero optical amplitude must have a well-defined phase, the axis of a vortex (where the phase is undefined) is always dark. Printed in negative resist, lowest order vortices would produce contact holes with 0.2<k<sub>1</sub><0.5, roughly 80-200nm diameter, with 248nm exposure and NA=0.63. Arrays of vortices with k<sub>pitch</sub>>0.6 can be produced using a chromeless phase-edge mask composed of rectangles with phases of 0&deg;, 90&deg;, 180&deg; and 270&deg;. EMF and Kirchhoff-approximation simulations reveal that the image quality of the dark spots is excellent, and predict a process window with 15% exposure latitude and 400nm DOF for 80nm diameter spots on pitches &ge;250nm at &sigma;=0.15. EMF simulations predict that the 0-270&deg; phase step will not be excessively dark if the quartz wall is vertical. Chrome spots at the centers can control the diameters which otherwise are set by the parameters of the imaging system and exposure dose. Unwanted vortices can be erased from the image by exposing with a second, more conventional, trim mask. This method would be superior to the other ways of producing sub-wavelength vias, but successful implementation requires the development of appropriate negative-tone resist processes.
Enhanced homology searching through genome reading frame predetermination (2004)

We demonstrate that by searching against a genome fragmented into all possible reading frames, the sensitivity of homology-based searches is enhanced without degrading its selectivity. Using the ETS-domain, bromodomain and acetyl-CoA acetyltransferase gene as queries, we were able to demonstrate that direct protein-protein searches using BLAST2P or FASTA3 against a human genome segmented among all possible reading frames and translated was substantially more sensitive than traditional protein-DNA searches against a raw genomic sequence using an application such as TBLAST2N. Receiver operating characteristic analysis was employed to demonstrate that the algorithms remained selective, while comparisons of the algorithms showed that the protein-protein searches were more sensitive in identifying hits. Therefore, through the overprediction of reading frames by this method and the increased sensitivity of protein-protein based homology search algorithms, a genome can be deeply mined, potentially finding hits overlooked by protein-DNA searches against raw genomic data.
Hand-Eye Calibration Using Dual Quaternions (1999)

To relate measurements made by a sensor mounted on a mechanical link to the robot’s coordinate frame, we must first estimate the transformation between these two frames. Many algorithms have been proposed for this so-called hand-eye calibration, but they do not treat the relative position and orientation in a unified way. In this paper, we introduce the use of dual quaternions, which are the algebraic counterpart of screws. Then we show how a line transformation can be written with the dual-quaternion product. We algebraically prove that if we consider the camera and motor transformations as screws, then only the line coefficients of the screw axes are relevant regarding the hand-eye calibration. The dual-quaternion parameterization facilitates a new simultaneous solution for the hand-eye rotation and translation using the singular value decomposition. Real-world performance is assessed directly in the application of hand-eye information for stereo reconstruction, as well as in the positioning of cameras. Both real and synthetic experiments show the superiority of the approach over two other proposed methods.
Osteopontin‐c is a selective marker of breast cancer (2007)

While the acquisition of invasiveness is a critical step in early stage breast carcinomas (DCIS), no established molecular markers reliably identify tumor progression. The metastasis gene osteopontin is subject to alternative splicing, which yields 3 messages, osteopontin-a, osteopontin-b and osteopontin-c. Osteopontin-c is selectively expressed in invasive, but not in noninvasive, breast tumor cell lines, and it effectively supports anchorage independence. We evaluated osteopontin-c as a biomarker. The RNA message for osteopontin-c was present in 16 of 20 breast cancers (80%), but was undetectable in 22 normal specimens obtained from reduction mammoplasty. In contrast, osteopontin-a RNA was expressed at various levels in all 20 breast cancers, 11 tumor-surrounding tissues and 21 normal samples. The splice variant osteopontin-b was present at barely detectable levels in 18 of 20 cancers and in 6 of 22 normal breasts. By immunohistochemistry, 66 of 69 normal breasts were negative, while 3 showed low level staining. Among the breast cancers, 43 of 56 cores (77%) stained positive for osteopontin-c. When correlated with tumor grade, the staining for osteopontin-c increased from grade 1 to grade 3. In a total of 178 breast specimens analyzed, osteopontin-c was present in 78% of cancers, 36% of surrounding tissues and 0% of normal tissues. Furthermore, osteopontin-c detects a higher fraction of breast cancers than estrogen receptor (ER), progesterone receptor or HER2. In conjunction, osteopontin-c, ER and HER2 reliably predict grade 2-3 breast cancer. Hence, osteopontin-c is a diagnostic and prognostic marker that may have value in a diagnostic panel together with conventional breast cancer markers.
Formation Behavior of Infrared Light Scattering Defects in Silicon during Czochralski Crystal Growth (1995)

The formation behavior of grown‐in defects which are considered to be oxygen precipitates formed during CZ‐Si crystal growth, was investigated by means of infrared light scattering tomography. The following results were obtained. (i) The density of the IR light scattering defects decreases with a reduction in the crystal pulling rate. (ii) The defects are not formed just after solidification, but they grow to a size detectable by LST during cooling to about 1100°C. (iii) The defect density decreases by slow cooling in the temperature range from to 1500 to 1000°C, while their size increases. The formation mechanism of the defects was qualitatively discussed from the point of view of the interaction between oxygen atoms and point defects by a consideration of the free energy change and the critical radii of nuclei for oxygen precipitation. It was suggested that the formation of the defects depends on the vacancy concentration. In the case of a constant vacancy concentration, their density and size are determined by the cooling rate in the temperature range from 1150 to 1000°C.
Sequencing and overexpression of the Escherichia coli aroE gene encoding shikimate dehydrogenase (1988)

The Escherichia coli aroE gene encoding shikimate dehydrogenase was sequenced. The deduced amino acid sequence was confirmed by N-terminal amino acid sequencing and amino acid analysis of the overproduced protein. The complete polypeptide chain has 272 amino acid residues and has a calculated Mr of 29,380. E. coli shikimate dehydrogenase is homologous to the shikimate dehydrogenase domain of the fungal arom multifunctional enzymes and to the catabolic quinate dehydrogenase of Neurospora crassa.
The inflammasome pathway in stable COPD and acute exacerbations (2016)

Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation that bursts during exacerbations of the disease (ECOPD). The NLRP3 inflammasome is a key regulatory molecule of the inflammatory response. Its role in COPD is unclear. We investigated the NLRP3 inflammasome status in: 1) lung tissue samples from 38 patients with stable COPD, 15 smokers with normal spirometry and 14 never-smokers; and 2) sputum and plasma samples from 56 ECOPD patients, of whom 41 could be reassessed at clinical recovery. We observed that: 1) in lung tissue samples of stable COPD patients, NLRP3 and interleukin (IL)-1β mRNA were upregulated, but both caspase-1 and ASC were mostly in inactive form, and 2) during infectious ECOPD, caspase-1, oligomeric ASC and associated cytokines (IL-1β, IL-18) were significantly increased in sputum compared with clinical recovery. The NLRP3 inflammasome is primed, but not activated, in the lungs of clinically stable COPD patients. Inflammasome activation occurs during infectious ECOPD. The results of this study suggest that the inflammasome participates in the inflammatory burst of infectious ECOPD.
Antiobese Effects of Novel Saponins from Edible Seeds of Japanese Horse Chestnut (Aesculus turbinata BLUME) after Treatment with Wood Ashes (2008)

Recently, we have identified novel saponins from edible seeds of Japanese horse chestnut ( Aesculus turbinata BLUME) after processing the natural seeds with wood ashes to remove bitterness. We attempted to determine anti-obesity effects of those saponins from edible seeds as well as natural seeds. The purified individual components of saponins from natural and edible seeds inhibited pancreatic lipase in vitro. The potency was in the order of escins > desacylescins > deacetylescins. Escins Ib and IIb as well as deacetylescins Ib and IIb with the angeloyl moiety were more potent than the corresponding Ia and IIa series with the tigloyl moiety. Moreover, in vivo anti-obesity effects of the saponin fractions were monitored for 8 weeks in mice fed high-fat diets. Saponin fractions from both seeds significantly attenuated the elevation in body weight, the mass of peritoneal adipose tissues, and plasma triacylglycerol, which was accompanied by higher contents of undigested fats in feces without changes in food intake, indicating the effective inhibition of fat digestion in vivo. Taken together, saponin fractions including desacylescins and deacetylescins from edible seeds are potentially useful for the development of nutraceutical foods with anti-obesity effects and more attenuated bitter taste.
NiAl underlayers for CoCrTa magnetic thin films (1994)

CoCrTa films were sputter-deposited on either NiAl or Cr underlayers on glass substrates and their coercivities were compared. The NiAl film was found have the B2 structure with a lattice parameter of /spl sim/0.288 nm. The grain size of a 100 nm NiAl film is /spl sim/15 nm, which is about 50% smaller than a similarly deposited Cr film. As for the CoCrTa/Cr films the CoCrTa/NiAl films show a similar increase of the in-plane coercivity with thickening of the underlayer. X-ray diffraction studies showed that CoCrTa/NiAl films have a stronger (101~0) peak than CoCrTa/Cr films. Substrate heating and biasing during deposition of the NiAl underlayer are less helpful than in the case of Cr underlayer.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Vision-Based Tracking with Dynamic Structure Light (1998)

Livingston, Mark A. (1998). Vision-Based Tracking with Dynamic Structure Light. (Link Foundation Fellowship Final Reports: Modeling, Simulation, and Training Program.) Retrieved from The Scholarship Repository of Florida Institute of Technology website: https://repository.lib.fit.edu/
A meta-analysis of nonsense mutations causing human genetic disease (2008)

Nonsense mutations account for approximately 11% of all described gene lesions causing human inherited disease and approximately 20% of disease-associated single-basepair substitutions affecting gene coding regions. Pathological nonsense mutations resulting in TGA (38.5%), TAG (40.4%), and TAA (21.1%) occur in different proportions to naturally occurring stop codons. Of the 23 different nucleotide substitutions giving rise to nonsense mutations, the most frequent are CGA --> TGA (21%; resulting from methylation-mediated deamination) and CAG --> TAG (19%). The differing nonsense mutation frequencies are largely explicable in terms of variable nucleotide substitution rates such that it is unnecessary to invoke differential translational termination efficiency or differential codon usage. Some genes are characterized by numerous nonsense mutations but relatively few if any missense mutations (e.g., CHM) whereas other genes exhibit many missense mutations but few if any nonsense mutations (e.g., PSEN1). Genes in the latter category have a tendency to encode proteins characterized by multimer formation. Consistent with the operation of a clinical selection bias, genes exhibiting an excess of nonsense mutations are also likely to display an excess of frameshift mutations. Tumor suppressor (TS) genes exhibit a disproportionate number of nonsense mutations while most mutations in oncogenes are missense. A total of 12% of somatic nonsense mutations in TS genes were found to occur recurrently in the hypermutable CpG dinucleotide. In a comparison of somatic and germline mutational spectra for 17 TS genes, approximately 43% of somatic nonsense mutations had counterparts in the germline (rising to 98% for CpG mutations). Finally, the proportion of disease-causing nonsense mutations predicted to elicit nonsense-mediated mRNA decay (NMD) is significantly higher (P=1.56 x 10(-9)) than among nonobserved (potential) nonsense mutations, implying that nonsense mutations that elicit NMD are more likely to come to clinical attention.
The 3′-Terminal Sequence of Escherichia coli 16S Ribosomal RNA: Complementarity to Nonsense Triplets and Ribosome Binding Sites (1974)

With a stepwise degradation and terminal labeling procedure the 3'-terminal sequence of E. coli 16S ribosomal RNA is shown to be Pyd-A-C-C-U-C-C-U-U-A(OH). It is suggested that this region of the RNA is able to interact with mRNA and that the 3'-terminal U-U-A(OH) is involved in the termination of protein synthesis through base-pairing with terminator codons. The sequence A-C-C-U-C-C could recognize a conserved sequence found in the ribosome binding sites of various coliphage mRNAs; it may thus be involved in the formation of the mRNA.30S subunit complex.
Bone Marrow Stromal Cells Create a Permissive Microenvironment for Myeloma Development: A New Stromal Role for Wnt Inhibitor Dkk1 (2012)

The rapid progression of multiple myeloma is dependent upon cellular interactions within the bone marrow microenvironment. In vitro studies suggest that bone marrow stromal cells (BMSC) can promote myeloma growth and survival and osteolytic bone disease. However, it is not possible to recreate all cellular aspects of the bone marrow microenvironment in an in vitro system, and the contributions of BMSCs to myeloma pathogenesis in an intact, immune competent, in vivo system are unknown. To investigate this, we used a murine myeloma model that replicates many features of the human disease. Coinoculation of myeloma cells and a BMSC line, isolated from myeloma-permissive mice, into otherwise nonpermissive mice resulted in myeloma development, associated with tumor growth within bone marrow and osteolytic bone disease. In contrast, inoculation of myeloma cells alone did not result in myeloma. BMSCs inoculated alone induced osteoblast suppression, associated with an increase in serum concentrations of the Wnt signaling inhibitor, Dkk1. Dkk1 was highly expressed in BMSCs and in myeloma-permissive bone marrow. Knockdown of Dkk1 expression in BMSCs decreased their ability to promote myeloma and the associated bone disease in mice. Collectively, our results show novel roles of BMSCs and BMSC-derived Dkk1 in the pathogenesis of multiple myeloma in vivo.
Box-like filter response and expansion of FSR by a vertically triple coupled microring resonator filter (2002)

The Lorentzian-shape filter response of a microring resonator filter is not suitable for practical use in wavelength division multiplexing (WDM) systems because of the lack of passband flatness, high crosstalk, and the large wing in the rejection band. Therefore, the tailoring of filter response shape is required to improve the performance. The series coupled microring resonator is one of the solutions. We designed and fabricated vertically triple coupled microring resonator add/drop filters with a stacked configuration. A box-like filter response with a flat passband was successfully obtained, and the free spectral range (FSR) was expanded to 25.8 nm owing to the Vernier effect.
Bioactive Diterpenoids Isolated fromSalvia mellifera (1996)

Eight diterpenoids were isolated from the roots of Salvia mellifera Greene. Their structures were elucidated by comparison to their physical and spectroscopy data with those reported in the literature or that of authentic samples as: abieta-8,11,13-triene, ferruginol, 15-deoxi-fuerstione, taxodione, isotanishinone III, rolyeanone, 7αsl-hydroxi-rolyleanone and demethylsalvicanol. Demethylsalvican-11-12-dione was obtained by oxidation with Ag2O from demethylsalvicanol. Compounds ferruginol, taxodione, isotanshinone III, and 7αsl-hydroxi-royleanone showed cytotoxic activity against both HeLa and Hep-2 cells in culture. Royleanone and demethylsalvican-11-12-dione were active on Hep-2 and HeLa cells respectively. Antimicrobial activity against some Gram (+) bacteria was observed for the diterpenoids ferruginol, taxodione, 7α-hydroxi-royleanone and demethylsalvican-11-12-dione. None of them was active on Gram (−) bacteria or Candida albicans.
High-performance GaAs switch IC's fabricated using MESFET's with two kinds of pinch-off voltages and a symmetrical pattern configuration (1994)

GaAs MESFET switch IC's operating at low control voltages of 0/-3 V and +3/0 V have been developed for use in Personal Handy Phones using the 1.9 GHz band. The switch IC's have excellent RF characteristics, and have no need for external circuit installation. The unique points of these IC's are the use of GaAs MESFET's with two kinds of pinch-off voltages and a symmetrical source and drain pattern configuration with respect to the gate. The 0/-3 V IC had low insertion loss of 0.55 dB and 0.65 dB, and high isolation of 31 dB and 24 dB at receiving and transmitting operations, respectively. The +3/0 V IC also had excellent characteristics such as insertion loss of 0.73 dB and 0.95 dB, and isolation of 27 dB and 23 dB, respectively. Both IC's had an output power at 1 dB gain compression point of 25.4 dBm and 3rd order intercept point of more than 46 dBm.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>