gebhart/patrepeval huggingface dataset:
Nomogram for predicting overall survival (OS) in patients (pts) treated with liposomal irinotecan (nal-IRI) ± 5-fluorouracil/leucovorin (5-FU/LV) in metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy in NAPOLI-1. (2018)

459 Background: Results from NAPOLI-1 (NCT01494506), a phase 3 study in pts with mPDAC previously treated with gemcitabine-based therapy, demonstrated an improvement in OS (primary endpoint), progression-free survival, and objective response rate with nal-IRI+5-FU/LV vs 5-FU/LV. The MPACT study reported a nomogram to predict OS using baseline pt variables in previously untreated mPDAC. We conducted an exploratory post hoc analysis of NAPOLI-1 variables to develop a nomogram to predict OS in the post-gemcitabine setting. Methods: In NAPOLI-1, pts were randomized to receive nal-IRI 80 mg/m2 q2w + 5-FU/LV, nal-IRI 100 mg/m2 q3w, or 5-FU/LV. Univariate and multivariate analyses determined factors significantly predictive of OS. A multivariable Cox model was created using these factors to develop a nomogram that assigned points equal to the weighted sum of relative significance of each variable. Predictive accuracy of the nomogram as measured by the concordance index (c-index) was evaluated by internal bootstrap validation. Results: Data from the 417-pt univariate analysis and 399-pt multivariate analysis (18 pts excluded for missing baseline data) were used. Eight of 21 variables were retained in the multivariate analysis (p &lt; 0.01 except BMI [p=0.08]). Conclusions: In NAPOLI-1, predictors of OS were nal-IRI+5-FU/LV treatment, KPS, NLR, albumin level, baseline CA19-9, stage 4 at diagnosis, BMI, and presence of liver metastasis. The nomogram, which will distinguish between risk groups and may aid in clinical decision making, will be presented in the poster. Clinical trial information: NCT01494506. [Table: see text]
Identification of Ligand-binding Site III on the Immunoglobulin-like Domain of the Granulocyte Colony-stimulating Factor Receptor (2001)

The granulocyte colony-stimulating factor receptor (G-CSF-R) forms a tetrameric complex with G-CSF containing two ligand and two receptor molecules. The N-terminal Ig-like domain of the G-CSF-R is required for receptor dimerization, but it is not known whether it binds G-CSF or interacts elsewhere in the complex. Alanine scanning mutagenesis was used to show that residues in the Ig-like domain of the G-CSF-R (Phe(75), Gln(87), and Gln(91)) interact with G-CSF. This binding site for G-CSF overlapped with the binding site of a neutralizing anti-G-CSF-R antibody. A model of the Ig-like domain showed that the binding site is very similar to the viral interleukin-6 binding site (site III) on the Ig-like domain of gp130, a related receptor. To further characterize the G-CSF-R complex, exposed and inaccessible regions of monomeric and dimeric ligand-receptor complexes were mapped with monoclonal antibodies. The results showed that the E helix of G-CSF was inaccessible in the dimeric but exposed in the monomeric complex, suggesting that this region binds to the Ig-like domain of the G-CSF-R. In addition, the N terminus of G-CSF was exposed to antibody binding in both complexes. These data establish that the dimerization interface of the complete receptor complex is different from that in the x-ray structure of a partial complex. A model of the tetrameric G-CSF.G-CSF-R complex was prepared, based on the viral interleukin-6.gp130 complex, which explains these and previously published data.
Replacement of the Proximal Humerus with a Ceramic Prosthesis (1980)

Insertion of a multicomponent ceramic prosthesis with extracortical fixation to the conically reamed shaft of the humerus was performed in 7 patients after resection of 4 malignant and 3 benign tumors of the proximal humerus. The length of the replacement ranged from 9 to 18 cm. Fixation was secure in all but one patient, who sustained a fracture through the proximal humerus. Subluxation occurred in 3 patients but posed no difficulty, except in one patient who required revision for a dislocation. Functionally, little active motion is achieved, but the implant provides a spacer to permit efficient use of the hand and elbow. No patient has had local recurrence of the tumor. One patient died one year postoperatively from an unrelated second primary cancer. Although the preliminary results are encouraging, further investigations are necessary on the mechanical aspects of the cone fixation principle and of the techniques of shoulder muscle reconstruction to improve the function of the prosthetic joint.
Dissecting the Marrow Microenvironment (1999)

Cloned human stromal cell lines representing functionally distinct cellular components of the marrow microenvironment were generated to serve as tools for identifying gene products that regulate hematopoiesis. Oligonucleotide arrays, or "gene chips" were used to provide a comprehensive comparison of gene expression among the cell lines. One line, designated HS-5, was found to secrete large amounts of cytokines, and conditioned media from this line was found to support the ex vivo expansion of both immature and mature progenitors. In contrast, a second line, designated HS-27a, does not secrete known cytokines but does support cobblestone area formation by CD34+/38lo cells. HS-27a, but not HS-5, was also found to express hJagged1, a ligand for Notch1, which may function to influence cell fate decisions of hematopoietic precursors. Both cell lines are currently being used to identify other gene products that regulate hematopoiesis and to generate reagents that will allow more formal evaluation of the putative role of hJagged1 in hematopoietic cell fate decisions.
E1a transactivation of the human HSP70 promoter is mediated through the basal transcriptional complex. (1989)

We have examined the promoter sequence requirements for E1a transactivation of the human HSP70 gene by using a transient cotransfection assay. A 5' deletion study has defined a basal transcription unit extending to -74 relative to the transcription initiation site which was fully E1a responsive. Further deletion, abolishing a CCAAT element at -67, drastically reduced basal and E1a-induced expression. A linker-scanner analysis has identified four functional elements within the basal transcription unit which may interact with CTF, SP1, TFIID, and an ATF/AP1-like factor. Sequences between -100 and -188 can partially compensate for mutations in these elements. No mutation specifically abolished E1a inducibility. Any reduction in absolute E1a-induced levels was accompanied by a corresponding reduction in absolute basal levels, thereby maintaining a constant relative fold induction. We conclude that E1a transactivation of the human HSP70 promoter does not require any single basal transcription element. We also examined an HSP70 promoter fragment, containing the CCAAT element at -67 and the purine-rich element at -54, out of its normal context by fusing it upstream of a transcriptionally inactive herpes simplex virus thymidine kinase deletion construct containing only the TATA box. The resulting chimeric promoter was fully E1a responsive. Mutagenesis of this promoter fusion demonstrated that the CCAAT element was essential for detectable basal and E1a-induced expression. Mutations in the purine-rich element resulted in an approximately 10-fold elevation in basal levels and rendered the promoter nonresponsive to E1a.
The Velocity of Sound through Tissues and the Acoustic Impedance of Tissues (1950)

The velocity of sound through various animal organ tissues and through living human tissues is measured, using an ultrasonic pulse method, at 1.25 and 2.5 Mc. The effect of anisotropy (fiber direction) on velocity is determined with beef muscle. Values obtained with the beam traversing the tissue perpendicularly to the long axis of the muscle bundles do not differ significantly from those found with the energy directed parallel with the muscle fibers. Velocity through living human tissues, consisting mostly of muscle, is measured by transmitting the ultrasound through various thicknesses of the arm, leg, and thigh. Specific gravities of the tissues are measured. The characteristic acoustic impedances (ρc values), calculated from the density and velocity data, vary between 1.5×105 and 1.7×105 g/cm2/sec. The imaginary component of tissue impedance is calculated and found to be negligible at the frequencies at which these measurements are made.
Treatment of Medulloblastoma with Hedgehog Pathway Inhibitor GDC-0449 (2009)

Medulloblastoma is the most common malignant brain tumor in children. Aberrant activation of the hedgehog signaling pathway is strongly implicated in the development of some cases of medulloblastoma. A 26-year-old man with metastatic medulloblastoma that was refractory to multiple therapies was treated with a novel hedgehog pathway inhibitor, GDC-0449; treatment resulted in rapid (although transient) regression of the tumor and reduction of symptoms. Molecular analyses of tumor specimens obtained before treatment suggested that there was activation of the hedgehog pathway, with loss of heterozygosity and somatic mutation of the gene encoding patched homologue 1 (PTCH1), a key negative regulator of hedgehog signaling.
Liner conformality in ionized magnetron sputter metal deposition processes (1996)

The conformality of thin metal films (liners) formed on high-aspect-ratio trench structures in ionized magnetron sputter deposition processes is studied numerically and experimentally. The numerical simulator (SHADE) used to predict the surface topography is based on the shock-tracking method for surface evolution. The simulation results are in good agreement with experimentally observed thin-film topography. It is shown that combination of direct deposition and trench-bottom resputtering results in good conformality of step coverages and the amount of the resputtering needed for the good conformality is almost independent of trench aspect ratios.
Structure, polymorphism and novel repeated DNA elements revealed by a complete sequence of the human .alpha.-fetoprotein gene (1987)

The human alpha-fetoprotein gene spans 19,489 base pairs from the putative "Cap" site to the polyadenylation site. It is composed of 15 exons separated by 14 introns, which are symmetrically placed within the three domains of alpha-fetoprotein. In the 5' region, a putative TATAAA box is at position -21, and a variant sequence, CCAAC, of the common CAT box is at -65. Enhancer core sequences GTGGTTTAAAG are found in introns 3 and 4, and several copies of glucocorticoid response sequences AGATACAGTA are found on the template strand of the gene. There are six polymorphic sites within 4690 base pairs of contiguous DNA derived from two allelic alpha-fetoprotein genes. This amounts to a measured polymorphic frequency of 0.13%, or 6.4 X 10(-4)/site, which is about 5-10 times lower than values estimated from studies on polymorphic restriction sites in other regions of the human genome. There are four types of repetitive sequence elements in the introns and flanking regions of the human alpha-fetoprotein gene. At least one of these is apparently a novel structure (designated Xba) and is found as a pair of direct repeats, with one copy in intron 7 and the other in intron 8. It is conceivable that within the last 2 million years the copy in intron 8 gave rise to the repeat in intron 7. Their present location on both sides of exon 8 gives these sequences a potential for disrupting the functional integrity of the gene in the event of an unequal crossover between them. There are three Alu elements, one of which is in intron 4; the others are located in the 3' flanking region. A solitary Kpn repeat is found in intron 3. The Xba and Kpn repeats were only detected by complete sequencing of the introns. Neither X, Xba, nor Kpn elements are present in the related human albumin gene, whereas Alu's are present in different positions. From phylogenetic evidence, it appears that Alu elements were inserted into the alpha-fetoprotein gene at some time postdating the mammalian radiation 85 million years ago.
Cf-252 physics and dosimetry (1986)

At the request of an ad hoc committee on the dosimetry of californium-252 medical neutron sources, the author in 1971-1972 conducted a review of the dosimetry data then available and prepared a status report which was subsequently published. The committee was convened by the Cf-252 Biomedical Advisory Panel of the U.S. Atomic Energy Commission's Div. of Biology and Medicine. The report suggested possible explanations for disagreements among existing data and recommended interim ''best values'' for use in clinical dose calculations. Since its publication, a number of further Cf-252 dosimetry studies have appeared in the literature. Although generally confirming the data recommended earlier, some of these studies have contributed specific insights which permit more accurate clinical application of dosimetry results.
Polarization separation/combination based on self-imaging (2001)

An integrated optical device for the separation/combination of orthogonal polarizations is described. The device relies on simultaneous symmetric and antisymmetric 131 off-center self-imaging. Calculations show that 90% throughput and 0.1% crosstalk can often be attained, with device length less than or comparable to other integrated optical polar- ization separation devices. The device is passive, requires only a single mask, and is not restricted to a specific fabrication method or material system. Devices can even be made in isotropic material systems with a deep etch. Simulation results are presented for the lithium niobate and glass waveguide material systems. © 2001 Society of Photo-Optical Instrumen- tation Engineers. (DOI: 10.1117/1.1402623)
Interrelationships between digestive proteolytic activities and production and quantitation of toxins in pseudomembranous colitis induced by Clostridium difficile in gnotobiotic mice (1989)

Clostridium difficile pathogenicity is related to in vivo production of toxins, and it is of great interest to detect toxins produced in biological samples. Several reports have shown that proteases in stools interfere with immunological methods for quantitation of toxin A. The purpose of this work was to estimate the relationship between the proteases and the C. difficile toxins produced in a gnotobiotic mouse model of pseudomembranous cecitis. Cecal proteolytic activities hydrolyzed toxin A, and immunoglobulin G bound to the microtiter plate used in immunoassays. This interference could be blocked by the addition of trypsin inhibitor to the samples. The ability of soluble toxin A to bind to bound antibodies in an enzyme-linked immunosorbent assay was not affected by the proteases, but the biological activity was reduced 100-fold. The cytotoxicity of toxin B was not modified by proteolytic activity treatment. Mice inoculated with a low toxin A-producing strain of C. difficile did not died, and no modulation of proteolytic activities occurred. After inoculation with the lethal VPI strain of C. difficile, toxins A and B reached maximum levels in the ceca at 12 h postinfection. At this time, the proteolytic activities did not decrease from the levels seen at zero time. Mice died within 2 days. At this time (about 32 postinfection), proteolytic activities were sharply decreased in the lower parts of the digestive tracts. The findings that serum inhibited the proteases and that there was a 100-fold increase in serum-derived mouse immunoglobulins in the lumen as the C. difficile infection progressed suggest that the decrease in protease activity in the lower digestive tract may be related to the exudation of serum from the inflammation process.
Group-based interface for content-based image retrieval (2002)

In Content-based Image Retrieval (CBIR) systems, the Query-by-Example (QBE) approach is commonly used. However, because of inevitable "semantic gaps" between visual features and the user's concepts, trial-and-error query is essential for successful retrieval. Unfortunately, traditional user interfaces are not suitable for trying different combinations of query examples. This is because in these systems, query specification and result display are done on the same workspace. Once the user removes an image from the query examples, the image may disappear from the user interface. In addition, it is difficult to combine the result of different queries.
Synthesis and Structural Features of Arduengo Carbene Complexes of Group 4 Metallocene Cations (2002)

Treatment of [Cp2TiCH3(thf)+] (5, with [BPh4-] anion) with 1,3-diisopropylimidazol-2-ylidene (4) at ambient temperature resulted in a rapid displacement of the thf ligand by the stable heterocyclic carbene to yield the Arduengo carbene methyltitanocene cation complex 6a (>90% isolated). The X-ray crystal structure analysis of 6a showed that the heteroatom-stabilized carbene ligand [d(Ti−C(carbene) = 2.289(2) Å, d(Ti−CH3) = 2.178(3) Å] was bonded to titanium in an orientation where the imidazol-2-ylidene ring lies in the major σ-ligand plane of the bent metallocene moiety. A DFT calculation of 6a and a series of related model compounds has revealed that the Arduengo carbene serves as a pure σ-donor ligand to the titanocene moiety. The observed favored “in-plane” orientation of the ligand is steric in origin. Consequently, complex 6a attains an analogous Cs-symmetric structure in solution, featuring symmetry-equivalent Cp rings and a pair of diastereotopic isopropyl substituents as well as chemically differentiated imidazol-2-ylidene C4HC5H groups. The reaction of the ion pair [(Cp2ZrCH3)+(CH3B(C6F5)3-] (7) with 4 gave the analogous Arduengo carbene zirconocene cation complex 6b (>95% isolated, with [CH3B(C6F5)3-] anion).
On The Possibility of Combining Radiotherapy and Photodynamic Therapy (2014)

The scintillation yield of rare-earth doped LaF3 nanoparticles (NPs) was experimentally measured. Taken together with evidence of FRET between NPs and covalently bound photosensitizer molecules, this suggests a route to combine radiation and photodynamic therapy.
Glycothermal synthesis of metal oxides (2004)

The author has been exploring the synthesis of inorganic materials in organic solvents at temperatures (200–300 °C) higher than their boiling points (solvothermal reaction), and has developed various reaction methods for the synthesis of ultrafine particles of metal oxides. In this paper, the reactions of aluminium compounds (aluminium hydroxide (Al(OH)3; gibbsite), aluminium alkoxides, and aluminium salts) in various organic solvents (alcohols, glycols, aminoalcohols, and inert organic solvents) are first reviewed, and reaction mechanisms and effects of the starting materials and solvents on the products are discussed. Then, the specificity of the use of glycols, especially 1,4-butanediol (glycothermal reaction), is clarified, and glycothermal synthesis of crystalline mixed oxides such as yttrium aluminium garnet is described. Finally, the use of the solvothermally prepared products as the catalyst materials is described.
Low-Dose Radioactive Endovascular Stents Prevent Smooth Muscle Cell Proliferation and Neointimal Hyperplasia in Rabbits (1995)

The results of this study clearly indicate that low-dose radioactive endovascular stents potently inhibit SMC proliferation and neointimal hyperplasia in rabbits.
Acoustics and Thrust of Quiet Separate-Flow High-Bypass-Ratio Nozzles (2003)

TheNASAGlennResearchCenterrecentlycompletedanexperimentalstudytoreducethejetnoisefrommodern turbofan engines. The study concentrated on exhaust nozzle designs for high-bypass-ratio engines. These designs modie ed the core and fan nozzles individually and simultaneously. In comparison with chevrons, tabs appeared to be an inefe cient method for reducing jet noise. Data trends show that interaction between fan e ow and the core cowl could strongly impact noise and cruise performance irrespective of the mixing device installed. The study demonstrates that modie cations of the core nozzle are generally more advantageous than of the fan nozzle. Even greater advantage in noise reduction and associated cruise thrust penalties is demonstrated through simultaneous modie cation of both nozzles. Thebestnozzledesign had a 0.06% cruisethrustlossand, corrected fortakeoff thrust loss, a 2.7-EPNdB reduction for the effective perceived noise level metric. This design simultaneously employed chevrons on the core and fan nozzles. Last, e ve nozzle cone gurations with cruise thrust loss of less than 0.5% and noise reductions of over 2.5 EPNdB are identie ed as candidates for full-scale engine and e ight demonstrations.
The protein splicing domain of the homing endonuclease PI-sceI is responsible for specific DNA binding (1998)

The homing endonuclease PI- Sce I consists of a protein splicing domain (I) and an endonucleolytic domain (II). To characterize the two domains with respect to their contribution to DNA recognition we cloned, purified and characterized the isolated domains. Both domains have no detectable endonucleolytic activity. Domain I binds specifically to the PI- Sce I recognition sequence, whereas domain II displays only weak non-specific DNA binding. In the specific complex with domain I the DNA is bent to a similar extent as observed with the initial complex formed between PI- Sce I and DNA. Our results indicate that protein splicing domain I is also involved in recognition of the DNA substrate.
TIME COURSE OF PULMONARY RESPONSE OF RATS TO INHALATION OF CRYSTALLINE SILICA: NF-kappa B ACTIVATION, INFLAMMATION, CYTOKINE PRODUCTION, AND DAMAGE (2002)

In vitro studies suggest that silica-induced lung disease may be linked to processes regulated by nuclear factor-kappa B (NF-kappa B) activation, but this has not been examined in vivo. Rats were exposed to a silica aerosol of 15 mg/m(3) (6 h/day, 5 days/wk) for 116 days, and bronchoalveolar lavage (BAL) was conducted at various times during the exposure. Silica-induced pulmonary inflammation and damage were determined by measuring BAL cell differentials and first BAL fluid lactate dehydrogenase (LDH) activity and serum albumin concentrations, respectively. NF-kappa B activation and production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) by BAL cells were also measured. The results demonstrate that NF-kappa B activation occurred after 5 days exposure, and continued to increase thereafter. BAL cell production of IL-1 and TNF-alpha had increased incrementally by 10 and 30 days of exposure, respectively. This elevation continued through 79 days of exposure before further increasing at 116 days of exposure. Pulmonary inflammation and damage in silica-exposed rats were also significantly elevated at 5 days of exposure, further increased at a slow rate through 41 days of exposure, and dramatically increased thereafter. Taken together, the results indicate that the initial molecular response of NF-kappa B activation in BAL cells occurs in response to low levels of silica deposition in the lung and increases more rapidly versus exposure duration than silica-induced pulmonary inflammation, cellular damage, and cytokine production by BAL cells. This suggests that NF-kappa B activation in BAL cells may play an important role in the initiation and progression of silica-induced pulmonary inflammation, cellular damage, and fibrosis.