gebhart/patrepeval huggingface dataset:
Risk factors for brain metastases in patients with a metastatic relapse of breast cancer (2004)

837 Background: Brain metastases are a more and more frequent, difficult clinical problem in advanced breast cancer (BC) patients (pts). We searched for risk factors of brain metastasis (BM) among pts diagnosed with a metastatic relapse of BC. Methods: A total of 557 premenopausal BC pts receiving systematic adjuvant chemotherapy were accrued at Institut Gustave-Roussy in a randomized trial of ovarian suppression [Arriagada et al, ASCO 03]. After a median follow-up of 9.5 years, 215 developed a first metastasis at a site other than brain alone. Of these 215 metastatic patients, 31 developed BM. The risk of BM in these 215 patients was analyzed as a function of patient, tumor and treatment characteristics by Cox models. Risk factors identified in the multivariate analysis were re-evaluated in a confirmatory series of 199 patients with metastatic relapse registered at Institut Gustave-Roussy in two randomized adjuvant chemotherapy trials (691 postmenopausal node-positive pts [Arriagada et al, Ann Oncol 2002] and 247 premenopausal node-negative pts [Arriagada et al, submitted]). Of these 199 pts, 19 developed BM. Results: In the first series, risk factors for BM in univariate analyses were lung metastasis as first site (yes/no): 2-year incidence rates of BM 24% vs 7% (p<0.001), negative hormone receptor (HR- vs HR+): 2-year BM rates 34% vs 5% (p<0.001) and short interval between BC and metastatic relapse (≤ vs >24 months): 18% vs 6% (p<0.008). In the multivariate analysis, only lung metastases remained prognostic (RR 5.3, 95% confidence interval (95%CI): 2.6–11, p<0.001). This was confirmed in the second series where the 2-year rates of BM were respectively 44% [95% CI: 26%–64%] and 3% [95%CI: 1–7%] in pts with or without lung metastases (RR 10 [95%CI: 3.8–27], p< 0.0001). Conclusions: This study shows that lung metastasis is a strong risk factor for the occurrence of brain metastases among BC patients. The occurrence of brain and lung metastases could be due to a common, albeit unknown, biological determinant. We suggest that prophylaxis of brain metastases may be evaluated in BC patients with lung metastases. No significant financial relationships to disclose.
Von Willebrand factor abnormalities in IgA nephropathy (1997)

This study, by showing the presence of a pre-peak and of large vWF multimers in IgAN patients, suggests an altered postsecretory handling of the vWF in IgAN and possibly a different role of the vWF in IgAN in respect to PGN.
Laser Doppler measurement of retinal blood velocity: validity of the single scattering model (1985)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text Charles E. Riva, Juan E. Grunwald, and Benno L. Petrig, "Laser Doppler measurement of retinal blood velocity: validity of the single scattering model," Appl. Opt. 24, 605-607 (1985) Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
P16-56 LB. Novel tetramer technology for the detection of high affinity CD8 T cells (2009)

Background Defining the quality of HIV T cell responses is a major hurdle in the development of T cell based vaccines. A key determinant of viral control is the affinity of the T Cell Receptor (TCR) for the HLA/epitope complex. We report for the first time in HIV the development of Class I HLA tetramers, which allow detection of CD8 with high TCR affinity that may prove to be invaluable in assessing the quality of T cell immunity. Methods HLA Class I molecules A*0201 and B*0702 were mutated at positions D227K and T228A to nullify CD8 binding and refolded with HIV epitopes: SLYNTVATL (A*0201), ILKEPVHGV (A*0201) and GPGHKARVL (B*0702). BIACORE confirmed abolition of CD8 binding and HLA molecule conformation. Mutated HLA monomers were termed CD8null. Peripheral blood mononuclear cells from HLA-matched acute patients in the SPARTAC trial (n = 30) were stained with A*0201 or B*0702 CD8 wild-type and CD8null tetramers. Real-time Image Flow Cytometry, directly examined the CD8null and CD8 wild-type tetramer/TCR interaction on an individual cell level. Results HLA Class I A*0201 and B*0702 CD8 null monomers had undetectable CD8 binding. Wild-type monomers had comparable CD8 binding capacity for A*0201 and B*0702 (KD = 5.9 × 10-4 and 6.0 × 10-4 M, respectively). Both CD8wild-type and CD8null monomers are bound by the anti-HLA w6/32 antibody with equal affinity (KD = 4.2 × 10-10 M). Ex vivo imaging showed slower internalisation of CD8null, compared to CD8wild-typetetramers, indicating prolonged HLA/TCR interaction. HIV patients stained with CD8null and CD8wild-type had distinct high affinity CD8 populations for A*0201 SLYNTVATL and ILKEPVHGV (p < 0.05) but not for B*0702 GPGHKARVL. Conclusion CD8null tetramers represent a novel technology that allow the direct ex vivo detection and characterisation of high affinity CD8 T responses. This represents a crucial new tool for assessing the quality of T cell responses to vaccination.
Effects of triarimol, tridermorph and triparanol on sterol biosynthesis in carrot, tobacco and soybean suspension cultures (1984)

Abstract The effects of triarimol, tridemorph and triparanol on sterol biosynthesis in carrot, tobacco and soybean suspension cultures were studied. The 3 plant species normally contain campesterol, stigmasterol and sitosterol as major sterols. Triarimol inhibited demethylation at C 14 and the second alkylation of the side chain in all 3 species. The primary effects of tridemorph were the inhibition of the opening of the 9β,19‐cyclopropane ring and the second alkylation of the side chain. Triparanol treatments resulted in the accumulation of 14α‐methyl sterols, and the inhibition of second alkylation in the side chain in carrot and tobacco cultures. Cyclopropyl sterols also accumulated in carrot and tobacco cultures treated with triparanol. Triparanol did not alter the sterol composition of soybean cultures except for decreasing concentrations of campesterol and stigmasterol and increasing amounts of sitosterol.
THE ABILITY OF VARIOUS INSULINS AND INSULIN FRAGMENTS TO INHIBIT THE ANGIOTENSIN I CONVERTING ENZYME (1974)

A variety of insulins and insulin fragments were shown to be active as inhibitors of angiotensin I converting enzyme from guinea pig plasma when tested in vitro. Angiotensin I was used as substrate and the consumption rate of angiotensin I as well as the generation rate of angiotensin II were measured by means of specific radioimmunoassays for angiotensin I and II. The B‐chain of insulin from different species possessed about the same inhibitory capacity as the whole insulin molecule. In an attempt to locate the active part of the sequence of the B‐chain, the five peptides which resulted from tryptic digestion of the duck insulin B‐chain were studied. They were, however, all active as inhibitors and on molar basis equal to or slightly more potent than the B‐chain and insulin. This demonstrates the unspecific nature of converting enzyme. Its affinity for insulin and its peptide fragments were, however, two to four orders of magnitude lower than it was for the most potent inhibitor described so far, the synthetic nonapeptide SQ 20.881. This difference was confirmed in in vivo experiments.
Induction Therapy with Fludarabine, ara-C and G-CSF Results in Improved Event Free Survival in Core Binding Factor Leukemia. (2006)

Abstract Previously (Blood2001;98:3575–3583) we reported that pts with inv (16) or t(8;21) (CBF) seemed to benefit from receiving fludarabine + ara-C (FA) rather than idarubicin + ara-C (IA), although other groups did not. Ara-C doses were 2g/m2 daily X 4–5 with FA and 1.5g/m2 daily X 2–4 by continuous infusion with IA. Because this observation was based on only 14 CBF pts given FA we proceeded, from 2000-present, to give all CBF pts FA either with (2000–2002; 22 pts) or without G-CSF (2003-present; 45 pts) on the days when FA was administered. Idarubicin(12 mg/m2 daily X 3) was given only if pts presented with WBC > 50,000, forcing start of treatment before cytogenetic results were known; once CR was achieved and CBF status was known, pts received 6 courses of post-remission therapy with FA (or FA +GCSF, FLAG) as described above. Median age was 41.5 years (range 16–83), 61 were male, 16 patients had antecedent hematologic disorder (AHD), 96 patients had ECOG performance status (PS) ≤ 1. One hundred and six patients (93%) achieved complete remission (CR). Events were defined as death, failure or relapse. Median time to event was 91 weeks and estimated EFS at 10 years was approximately 40%. Event-free survival (EFS) was compared in the 67 pts treated with FA or FLAG with EFS in 47 pts treated with IA +/− GCSF (IA/IAG). Because IA/IAG was given to CBF pts from 1991–2000 and FA or FLAG from 2000-present, we compared covariate-adjusted EFS in 436 pts with cytogenetics other than CBF according to whether they received IA before or after 2000 to estimate “period-effect”.EFS was superior in the earlier period, and this difference, seeming to inherently favor IA/IAG rather than FA or FLAG, was accounted for in the comparisons of these treatments in the CBF group. Preliminary analyses suggested that EFS in CBF pts was similar between IA and IAG (these groups were considered together for subsequent analyses) and longer with FLAG than with FA or IA/IAG (p= 0.06). After adjustments for covariates (age, WBC,platelets, marrow blasts etc) we compared EFS with FA, FLAG ,and IA/IAG, using both standard (Cox regression) and Bayesian approaches. The Bayesian model indicated that the posterior probability that FLAG was superior to IA/IAG was 0.98, and that, among pts given FA, the posterior probability that FLAG was superior to FA was 0.91. The Cox model indicated that the risk of an event with FLAG relative to IA/IAG was 0.84 (p = 0.07). A possible explanation for the seeming superiority of FLAG is the ability of G to increase accumulation of fludarabine-triphosphate in blasts during therapy (Clin Cancer Res1995; 1:169–178). Figure Figure Figure Figure
Processing of asparagine‐linked oligosaccharides is an early biochemical marker of the enterocytic differentiation of HT‐29 cells (1989)

The inability of HT-29 cells to undergo an enterocytic differentiation when grown in a glucose-containing (Glc+) medium has been recently correlated to an overall impairment of N-glycan processing. These results were obtained using confluent HT-29 cells in which the differentiation characteristics are fully expressed under differentiation permissive conditions (glucose-deprived medium, Glc-). Whether these changes of N-glycan processing appear progressively during the cell growth or are already present from the beginning of the culture was investigated in this work by comparing the actual status of N-glycan processing in both exponentially growing Glc+ and Glc- HT-29 cells. Under these conditions, HT-29 cells do not express any characteristics of enterocytic differentiation, even when grown in differentiation permissive conditions. We show here that the conversion of high-mannose to complex glycoproteins is, however, severely reduced in HT-29 cells grown in differentiation non-permissive conditions (HT-29 Glc+) whatever the phase of growth studied. In contrast, HT-29 cells grown in differentiation permissive conditions (HT-29 Glc-) display a normal pattern of N-glycan processing in both the exponential and the stationary phase of growth. We also show that both growing and confluent HT-29 Glc+ cells accumulate Man GlcNAc2 species, thus suggesting that there is an important regulatory point at this level. We therefore conclude that the N-glycan processing may be used as an early biochemical probe for the enterocytic differentiation of HT-29 cells. Whether these early changes result from an early metabolic regulation or are the consequence of a genetic control remains to be studied.
Molecular genetic analysis of neural stem cells after space flight and simulated microgravity on earth (2021)

Understanding how stem cells adapt to space flight conditions is fundamental for human space missions and extraterrestrial settlement. We analyzed gene expression in boundary cap neural crest stem cells (BCs), which are attractive for regenerative medicine by their ability to promote proliferation and survival of cocultured and co-implanted cells. BCs were launched to space (space exposed cells) (SEC), onboard sounding rocket MASER 14 as free-floating neurospheres or in a bioprinted scaffold. For comparison, BCs were placed in a random positioning machine (RPM) to simulate microgravity on earth (RPM cells) or were cultured under control conditions in the laboratory. Using next-generation RNA sequencing and data post-processing, we discovered that SEC upregulated genes related to proliferation and survival, whereas RPM cells upregulated genes associated with differentiation and inflammation. Thus, (i) space flight provides unique conditions with distinctly different effects on the properties of BC compared to earth controls, and (ii) the space flight exposure induces postflight properties that reinforce the utility of BC for regenerative medicine and tissue engineering.
A New Method for the Stereoselective Synthesis of α-Substituted Serine Amino Acid Analogues (2003)

[reaction: see text]. A new method was developed for the stereoselective synthesis of alpha-substituted serine amino acids. The strategy utilizes a common enantiomerically enriched intermediate obtained through an enzymatic desymmetrization. A variety of amino acids were synthesized in good ee's through nucleophilic acetylide addition reactions and palladium-catalyzed Sonogashira couplings.
Long-range dispersal moved Francisella tularensis into Western Europe from the East (2016)

For many infections transmitting to humans from reservoirs in nature, disease dispersal patterns over space and time are largely unknown. Here, a reversed genomics approach helped us understand disease dispersal and yielded insight into evolution and biological properties of <i>Francisella tularensis</i>, the bacterium causing tularemia. We whole-genome sequenced 67 strains and characterized by single-nucleotide polymorphism assays 138 strains, collected from individuals infected 1947-2012 across Western Europe. We used the data for phylogenetic, population genetic and geographical network analyses. All strains (<i>n</i>=205) belonged to a monophyletic population of recent ancestry not found outside Western Europe. Most strains (<i>n</i>=195) throughout the study area were assigned to a star-like phylogenetic pattern indicating that colonization of Western Europe occurred via clonal expansion. In the East of the study area, strains were more diverse, consistent with a founder population spreading from east to west. The relationship of genetic and geographic distance within the <i>F. tularensis</i> population was complex and indicated multiple long-distance dispersal events. Mutation rate estimates based on year of isolation indicated null rates; in outbreak hotspots only, there was a rate of 0.4 mutations/genome/year. Patterns of nucleotide substitution showed marked AT mutational bias suggestive of genetic drift. These results demonstrate that tularemia has moved from east to west in Europe and that <i>F. tularensis</i> has a biology characterized by long-range geographical dispersal events and mostly slow, but variable, replication rates. The results indicate that mutation-driven evolution, a resting survival phase, genetic drift and long-distance geographical dispersal events have interacted to generate genetic diversity within this species.
RHEOLOGICAL AND PHYSICOCHEMICAL PROPERTIES OF DERIVATIZED WHEY PROTEIN CONCENTRATE POWDERS (2002)

ABSTRACT The gelling ability of whey proteins provides important textural and water holding properties in many foods. However, because many products cannot be heated to the temperature needed for thermal gelation of whey proteins, cold-set gelation of whey proteins could be very advantageous to the food industry. A derivatization procedure for the production of a cold gelling whey protein isolate (WPI) consisting of protein hydration, pH adjustment, thermal gelation, freeze drying, and milling was applied to three commercial whey protein concentrates (WPC). The resulting derivatized WPC powders were reconstituted in water and evaluated through a range of rheological and physical property studies. The effects of temperature, concentration, and shear on viscosity as well as water holding capacity and intrinsic viscosity were assessed. Although the composition of the starting materials influenced the functionality of the final derivatized powders, all samples exhibited a dramatic increase in thickening and water holding ability. All samples were able to form cold-set weak gel structures suitable for contributing viscosity and texture to a wide range of food systems.
GM 58/8: a monoclonal antibody that identifies a new lineage‐specific determinant expressed by myeloid progenitors (CFU‐GM) and their progeny (1984)

A cytotoxic (IgM) monoclonal antibody (McAb) raised against human erythroleukaemia cell line HEL appears specific for the myelomonocytic lineage. Indirect immunofluorescence and fluorescence-activated cell sorter analyses of peripheral blood and bone marrow cells showed that this McAb (designated GM 58/8) reacts exclusively with more than 90% of the granulocytes, monocytes and myeloid precursors. The positive (fluorescent) fraction sorted from McAb-treated bone marrow buffy coat cells showed a marked enrichment of myeloid precursors, while nonmyeloid cells were recovered in the negative fraction. GM 58/8 specifically inhibited the growth of 90-100% of the committed myelomonocytic progenitors (CFU-GM) in five complement-mediated cytotoxicity experiments. GM 58/8 had virtually no effect on the erythroid progenitor (BFU-E and CFU-E) growth. Cell sorting experiments using this McAb resulted in recovery of 84% of CFU-GM among the fluorescent fractions. Comparisons with other anti-myelomonocytic McAbs reported so far suggest that GM 58/8 has more restricted reactivity and shows more efficient CFU-GM cytotoxicity. Patterns of reactivity with normal cells and established lines indicate that the antigenic determinant identified by GM 58/8 is different from that recognized by previously described anti-myelomonocytic McAbs. McAb GM 58/8 could be used to isolate or remove pure populations of progenitors and/or more differentiated cells of the myelomonocytic lineage for in vitro studies. This study also provides evidence that the HEL cell line, derived originally from an erythroleukaemia patient, expresses an antigenic determinant shared by the normal cells of myelomonocytic lineage.
Synthesis of tetrahedral mixed-metal clusters of the iron triad. Preparation and characterization of H/sub 2/FeRu/sub 2/Os(CO)/sub 13/ and H/sub 2/FeRuOs/sub 2/(CO)/sub 13/ (1977)

Transition metal cluster complexes have become a very important class of compounds, principally because of their potential in catalysis. Clusters have been shown to behave as catalysts in their own right and they hold considerable promise for serving as models for catalytic surfaces. Clusters comprised of two or more different transition metals in the cluster framework are particularly interesting in this regard because of possible bimetallic effects. Further, mixed-metal clusters have non-equivalent bonding sites. As such they are ideally suited for modeling studies which employ variable temperature NMR to follow the movements of substrates over their surfaces. One of the problems which has hampered studies of mixed-metal clusters is their relative lack of availability. Only a very few isostructural series have been achieved, and general synthetic methods for mixed-metal clusters are lacking. Carbonylmetalates have been widely used as synthetic reagents in cluster chemistry and several of the reported reactions appear to be adaptable to design. This is particularly true of the reactions of Knight and Mays who prepared a series of Group 7 - Group 8 tetrameric mixed-metal clusters through the addition of a carbonylmetalate to a closed M/sub 3/(CO)/sub 12/ trimer.
Communicating Science to the Public through a University-Museum Partnership (2005)

An innovative National Science Foundation-supported program at the University of Wisconsin–Madison called Internships in Public Science Education (IPSE) enables graduate and undergraduate interns to communicate science concepts to pre-college and museum audiences through a university–museum collaboration. Interns work with researchers from the UW Materials Research Science and Engineering Center (MRSEC), science museum personnel from Discovery World in Milwaukee, Wisconsin, and local K–12 educators to expand their knowledge of advanced materials and nanotechnology while developing exciting grade-appropriate activities for classroom and museum settings. Activities range from answering the question, “What is the nanoscale?” to investigating the societal implications of nanotechnology and the structure–property relationships of carbon allotropes. These activities use cutting-edge examples to explain basic science concepts. The programâ€™s impact on various stakeholders has been assessed and is discussed. The program serves as a model for other colleges and universities interested in communicating cutting-edge research to the public.
Activity Measurement of Gallium in Ga&ndash;Bi and Ga&ndash;Sb&ndash;Bi Alloys by EMF Method Using Zirconia as Solid Electrolyte (1993)

EMF of galvanic cells with zirconia solid electrolytes was measured to determine the activity of gallium in liquid Ga–Bi and Ga–Sb–Bi alloys in the temperature range 1050–1150 K in the entire composition range. Ga, Ga2O3 and Fe, FexO mixtures were used as reference electrodes. The activity of gallium in Ga–Bi alloys shows a moderately positive deviation from ideality at 1073 K. The isoactivity curves at 1073 K are obtained in the ternary system, and the shape of the curves are simple and show a very small deviation from the straight lines which connect the starting points in the Ga–Sb system and the ending points in the Ga–Bi system.
Isolation of the yeast INO1 gene: located on an autonomously replicating plasmid, the gene is fully regulated. (1984)

The Saccharomyces cerevisiae gene, INO1 , encoding the highly regulated enzyme, myo-inositol-1-phosphate synthase [1L-myo-inositol-1-phosphate lyase (isomerizing), EC 5.5.1.4], was isolated by genetic complementation. The cloned sequence was shown to complement two independent IN01 alleles ( ino1 -5 and ino1 -13). One of these mutants ( ino1 -5) fails to make any material that is crossreactive with antibody to the wild-type inositol-1-phosphate synthase. The cloned DNA restored not only inositol prototrophy to this mutant but also its ability to make material crossreactive with anti-inositol-1-phosphate synthase antibody. The sequence on an integrative plasmid was also shown to recombine with the INO1 locus, thereby confirming its genetic identity. The DNA was subcloned and used for Southern blot analysis, revealing that the cloned DNA (5.4 kilobases long) represents a unique sequence in the yeast genome. Inositol-1-phosphate synthase was fully regulated when its gene was located extrachromosomally on the autonomously replicating plasmid. In cells ( ino1 -) containing the cloned INO1 gene on a high-copy-number plasmid, the enzyme was fully repressible. Furthermore, the gene product was not expressed when the plasmid was transferred into a strain containing an ino4 mutation, which also prevents expression of chromosomal copies of INO1 . These results establish that the intact structural gene and associated regulatory components have been isolated and that positioning of the gene in its normal chromosomal location is not required for full regulation of inositol-1-phosphate synthase.