gebhart/patrepeval huggingface dataset:
The genetic defect in two well-studied cases of Bernard-Soulier syndrome: a point mutation in the fifth leucine-rich repeat of platelet glycoprotein Ib alpha (1995)

Bernard-Soulier syndrome (B-Ss) is a rare congenital bleeding disorder caused by abnormal giant platelets, thrombocytopenia, and defective glycoprotein (GP) Ib-V-IX, the adhesion receptor for von Willebrand factor (vWF). This report describes the molecular defect in two related individuals with well-established B-Ss whose platelets exhibit decreased GPIb-IX and normal GPV on their surfaces. The GPIb-V-IX genes of the two patients were analyzed by Southern blotting, hetero-duplex analysis, and polymerase chain reaction (PCR) amplification/sequencing. A point mutation was found in codon 129 of the GPIb alpha gene that results in the substitution of proline for leucine in the first position of the fifth leucine-rich glycoprotein repeat of the mature gene product. The mutation (CTC: leucine, wild-type to CCC: proline, mutant) eliminates a Sac I restriction site, facilitating analysis of the mutation in the propositi (both homozygotes), unaffected family members (8 heterozygotes and 8 wild-type), and 58 normal controls (116 wild-type alleles). The status of the genomes was confirmed by the sequencing of platelet cDNA. The mutation does not affect transcription of the Ib-IX genes, as estimated by PCR and Northern blot analysis, but it does inhibit surface expression of the receptor as assessed by transient transfection of mutant and wild-type GPIb alpha genes into mouse Ib beta-IX L cells. Many of the cells (43%) transfected with the normal gene express surface GPIb alpha, whereas untransfected cells and those transfected with the mutant gene lack surface GPIb alpha entirely. Patient platelets were tested both for vWF binding in the presence of ristocetin and for surface GPIb-IX expression. In these instances, despite their inability to agglutinate with ristocetin and vWF, patient platelets exhibit about 40% of normal vWF binding and 40% of normal Ib-IX surface antigens. The results suggest that the described mutation (GPIb alpha: Leu129 -> Pro) affects the conformation of the GPIb-V-IX receptor, alters its availability on platelet surfaces, and causes the observed Bernard-Soulier phenotype.
Syk kinase inhibitors in allergic diseases (2009)

Recent advances in the understanding of allergic mechanisms have highlighted the role of immunoglobulin E (IgE) signaling in the mast cell. One of the most important kinases in the IgE signaling pathway is spleen tyrosine kinase (Syk) which has a critical function early in the signaling cascade following binding of allergen to receptor bound IgE on the mast cell. A number of Syk inhibitors have now been developed which have been shown to effectively inhibit IgE-driven mast cell degranulation and release of inflammatory cytokines in vitro and inhibit allergic responses in a variety of in vivo models. In humans, allergen-driven symptoms were reduced in allergic rhinitic patients exposed to tree pollen in an outdoor environment following intranasal dosing of the Syk inhibitor R-112. Syk therefore represents a promising target for therapeutic intervention in allergic diseases.
Expression and function of CYR61, an angiogenic factor, in breast cancer cell lines and tumor biopsies. (2000)

We have previously shown that expression of heregulin (HRG) is closely correlated with breast cancer progression. We have subsequently isolated Cyr61, a ligand for the alpha(v)beta3 integrin that is differentially expressed in HRG-positive cells, and have shown that it is expressed in all of the invasive and metastatic breast cancer cell lines tested. Preliminary evaluation of Cyr61 expression in breast tumor biopsies revealed expression of Cyr61 in about 30% of invasive breast carcinomas. Significantly, we demonstrated that Cyr61 is a downstream effector of HRG action, because a Cyr61-neutralizing antibody abolished the ability of HRG-expressing cells to migrate in vitro. Furthermore, we have shown that HRG-expressing cells denote higher levels of alpha(v)beta3 expression, and we have established that Cyr61 action is mediated, at least in part, through its receptor alpha(v)beta3, because a functional blocking antibody of the alpha(v)beta3 blocked the Matrigel outgrowth of HRG-expressing cells. These results strongly suggest that Cyr61 is necessary for HRG-mediated chemomigration and that Cyr61 plays a functional role in breast cancer progression, possibly through its interactions with the alpha(v)beta3 receptor.
Transition Metal Binding in DNA Solutions (1962)

Paramagnetic ions in water shorten the spin-lattice relaxation time T1 of the water protons. The effectiveness with which the relaxation takes place depends not only on the ion concentration, but also on the environment of the paramagnetic ion. In some cases where the paramagnetic ion is bound to a large molecule such as DNA, it shortens the proton relaxation time to a greater extent than when it is in solution. By measuring T1 by a pulsed nuclear magnetic resonance method, we have studied the binding of transition metal ions to DNA. We have obtained estimates for the number of available binding sites as well as information on the type of site which the various ions are bound to.
Fourier Transform Spectrometry with a Near Infrared Supercontinuum Source (2009)

Near-infrared Fourier transform absorption spectrometry with a supercontinuum (SC) source is demonstrated for trace methane detection. The SC source allows for long distance propagation while exhibiting amplitude noise ten times greater than comparable incandescent sources.
Digestion and metabolism in the ruminant. (1975)

Death from liver haemorrhage decreased in association with the introduction of haemostatic resuscitation while the incidence, severity and surgical management of liver trauma was comparable.
Palenque: an interactive multimedia digital video interactive prototype for children (1988)

The Palenque interactive multimedia digital video interactive prototype is based on themes, locations, and characters from The Second Voyage of the Mimi television show, which is being produced at Bank Street College. In the TV show, a cast of scientists and children explore the Yucatan's ancient Maya ruins and are introduced to the science of archeology. The Palenque prototype incorporates this theme to the extent that the user's experience is based on a virtual travel exploration of an ancient Maya site, Palenque, and on the perusal of a multimedia Palenque Museum database. One of our goals was to create a visually interesting database environment in which information in many formats could be browsed through spatially and thematically by children. In addition, we experimented with icon and window-based interface conventions that would make navigation around the video environment motivating and comprehensible for young users.
Applications of Nanowire Arrays in Nanomedicine (2009)

nanowire, nanomedicine
Disruptions of the Futures Market: A Comment on Dealing with Market Manipulation (1991)

In his article, "The Manipulation of Commodity Futures Prices-The Unprosecutable Crime," Jerry Markham examines the history of futures market manipulation as a regulatory problem and sets forth a number of suggestions to improve the policing of this unwanted activity. He rightly observes that market "corners" and "squeezes" have occurred throughout the long and colorful history of the commodity futures markets, whether in the form of raw and defiant exercises in financial power, or as a less spectacular form of market opportunism. He also notes correctly that the seventy-year effort by the federal government to eliminate these market manipulations has been more or less unsuccessful.
Therapy of hepatitis C: Interferon alfa-2a trials (1997)

Interferon alfa-2a resembles other recombinant alpha interferons in structure and pharmacology. Studies delineating its efficacy suggest that after 6 to 12 months of therapy, sustained biochemical responses occur in 4% to 49% of patients, providing adequate doses (> or = 3 million units three times weekly) are used. Overall, a dose-response curve is evident in regard to biochemical responses, decrease in histological scores for inflammation, and virological responses (percent negative serum hepatitis C virus [HCV] RNA) after treatment. Differences in response rates between studies probably reflect patient selection and particularly the percent of patients with established cirrhosis, because these patients respond less well than those with earlier histological stages of disease. A variety of regimens of interferon alfa-2a have been used, including use of higher doses, longer periods of treatment, induction using higher doses initially, and intermittent pulse therapy. Both longer periods of therapy and induction dosing show strong but not significant trends toward improvement in response rates, which reach significance when the two strategies are combined. Outcome is not significantly improved by escalating doses during therapy when inadequate responses are seen, or by pulse therapy. The side effect profile of interferon alfa-2a is similar to that of other interferons. Long-term follow-up studies have demonstrated that 90% of patients with a sustained biochemical response at 6 months after therapy maintain the response, and 95% remain negative for HCV RNA in serum. Challenges for the future include better delineation of the advantages of induction dosing, the optimal duration of therapy, and further understanding of the frequent discordance between HCV RNA data and aminotransferase levels. This latter finding suggests that use of both parameters is necessary to evaluate fully responses to therapy.
Self-Assembled M 24 L 48 Polyhedra and Their Sharp Structural Switch upon Subtle Ligand Variation (2010)

Self-assembly is a powerful technique for the bottom-up construction of discrete, well-defined nanoscale structures. Large multicomponent systems (with more than 50 components) offer mechanistic insights into biological assembly but present daunting synthetic challenges. Here we report the self-assembly of giant M24L48 coordination spheres from 24 palladium ions (M) and 48 curved bridging ligands (L). The structure of this multicomponent system is highly sensitive to the geometry of the bent ligands. Even a slight change in the ligand bend angle critically switches the final structure observed across the entire ensemble of building blocks between M24L48 and M12L24 coordination spheres. The amplification of this small initial difference into an incommensurable difference in the resultant structures is a key mark of emergent behavior.
Intravenous iron alone resolves anemia in patients with functional iron deficiency and lymphoid malignancies undergoing chemotherapy (2014)

This randomized trial evaluated ferric carboxymaltose without erythropoiesis-stimulating agents (ESA) for correction of anemia in cancer patients with functional iron deficiency. Patients on treatment for indolent lymphoid malignancies, who had anemia [hemoglobin (Hb) 8.5-10.5 g/dL] and functional iron deficiency [transferrin saturation (TSAT) ≤ 20%, ferritin >30 ng/mL (women) or >40 ng/mL (men)], were randomized to ferric carboxymaltose (1,000 mg iron) or control. Primary end point was the mean change in Hb from baseline to weeks 4, 6 and 8 without transfusions or ESA. Difficulties with patient recruitment led to premature termination of the study. Seventeen patients (8 ferric carboxymaltose and 9 control) were included in the analysis. In the ferric carboxymaltose arm, mean Hb increase was significantly higher versus control at week 8 (p = 0.021). All ferric carboxymaltose-treated patients achieved an Hb increase >1 g/dL (control 6/9; p = 0.087), and mean TSAT was >20% from week 2 onwards. No treatment-related adverse events were reported. In conclusion, ferric carboxymaltose without ESA effectively increased Hb and iron status in this small patient population.
GC- and E-box Motifs as Regulatory Elements in the Proximal Promoter Region of the Neuronal Nicotinic Receptor α7 Subunit Gene (1998)

The alpha7 subunit is a component of alpha-bungarotoxin-sensitive nicotinic acetylcholine receptors expressed in bovine adrenomedullary chromaffin cells. The proximal promoter of the gene coding for this subunit contains several GC-boxes and one E-box. Deletion analysis and transient transfections showed that a 120-base pair region (-77 to +43) including all of these elements gave rise to approximately 70 and 95% of the maximal transcriptional activity observed in chromaffin and SHSY-5Y neuroblastoma cells, respectively. Site-directed mutagenesis of the different elements indicated that both GC and E motifs contribute to the activity of the alpha7 gene in a very prominent way. Using electrophoretic mobility shift assays, the upstream stimulatory factor (USF) was shown to be a component of the complexes that interacted with the E-box when nuclear extracts from chromaffin and SHSY-5Y cells were used. Binding of the early growth response gene transcription factor (Egr-1) to three different GC-boxes was also demonstrated by shift assays and DNase I footprint analysis. Likewise, alpha7 promoter activity increased by up to 5-fold when alpha7 constructs and an Egr-1 expression vector were cotransfected into chromaffin cell cultures. Mutagenesis of individual GC-boxes had little effect on Egr-1 activation. By contrast, pairwise suppression of GC-boxes abolished activation, especially when the most promoter-proximal of the Egr-1 sites was removed. Taken together, these studies indicate that the alpha7 gene is likely to be a target for multiple signaling pathways, in which various regulatory elements are involved.
Construction and Behavior of Circularly Permuted and Telocentric Chromosomes in Saccharomyces cerevisiae (1986)

We developed techniques that allow us to construct novel variants of Saccharomyces cerevisiae chromosomes. These modified chromosomes have precisely determined structures. A metacentric derivative of chromosome III which lacks the telomere-associated X and Y' elements, which are found at the telomeres of most yeast chromosomes, behaves normally in both mitosis and meiosis. We made a circularly permuted telocentric version of yeast chromosome III whose closest telomere was 33 kilobases from the centromere. This telocentric chromosome was lost at a frequency of 1.6 X 10(-5) per cell compared with a frequency of 4.0 X 10(-6) for the natural metacentric version of chromosome III. An extremely telocentric chromosome whose closet telomere was only 3.5 kilobases from the centromere was lost at a frequency of 6.0 X 10(-5). The mitotic stability of telocentric chromosomes shows that the very high frequency of nondisjunction observed for short linear artificial chromosomes is not due to inadequate centromere-telomere separation.
Use of Trialkyl Ammonium Phosphate (TAAP) Buffers in Reverse Phase HPLC for High Resolution and High Recovery of Peptides and Proteins (1978)

Abstract A new buffer system compatible with reverse phase high pressure liquid chromatography (RP -HPLC) column packings and giving high recoveries and high resolution for peptides and proteins is described. The TEAP buffer (triethylammonium phosphate), one of several TAAP buffers (trialkylammonium phosphate) compatible with RP-HPLC, gives high resolution and high recovery for closely related peptides or proteins as well as day to day reproducibility. It is UV transparent to less than 200 nm, extremely versatile, and could probably be used for several other classes of compounds (phosphatidyl cholines and sphingomyelin, for example). Furthermore, this system is compatible with in vitro and in vivo biological systems after removal of the organic solvent. We have applied our system to the purification of radioactive peptides, i.e. the separation and total recovery of tritiated luteinizing hormone releasing factor (LRF) from closely related radioactive impurities. Peptides and proteins as different as LRF, somatostatin, insulin and cytochrome C are easily separated and recovered. Application to peptide mapping is also described. The influence of flow rate, temperature and column packings on resolution is discussed and illustrated. Linearity between load and integrated response is demonstrated over four order of magnitude while retention time for a particular component remains constant. A flow rate of 1–1.5 ml/min and ambient or lower temperatures gives optimal resolution. Furthermore, it was found that the higher the hydrophobicities of the support was, the higher the resolution, but also possible the higher the chances for peptide or protein loss.
FloorNet: A Unified Framework for Floorplan Reconstruction from 3D Scans (2018)

The ultimate goal of this indoor mapping research is to automatically reconstruct a floorplan simply by walking through a house with a smartphone in a pocket. This paper tackles this problem by proposing FloorNet, a novel deep neural architecture. The challenge lies in the processing of RGBD streams spanning a large 3D space. FloorNet effectively processes the data through three neural network branches: 1) PointNet with 3D points, exploiting the 3D information; 2) CNN with a 2D point density image in a top-down view, enhancing the local spatial reasoning; and 3) CNN with RGB images, utilizing the full image information. FloorNet exchanges intermediate features across the branches to exploit the best of all the architectures. We have created a benchmark for floorplan reconstruction by acquiring RGBD video streams for 155 residential houses or apartments with Google Tango phones and annotating complete floorplan information. Our qualitative and quantitative evaluations demonstrate that the fusion of three branches effectively improves the reconstruction quality. We hope that the paper together with the benchmark will be an important step towards solving a challenging vector-graphics reconstruction problem. Code and data are available at https://github.com/art-programmer/FloorNet.
pdb-care (PDB CArbohydrate REsidue check): a program to support annotation of complex carbohydrate structures in PDB files (2004)

Frequent use of pdb-care will help to improve the quality of carbohydrate data contained in the PDB. Automatic assignment of carbohydrate structures contained in PDB entries will enable the cross-linking of glycobiology resources with genomic and proteomic data collections.
Preliminary investigation of the effects of surface treatments on biological response to shape memory NiTi stents (1999)

Nickel-titanium (NiTi) offers many advantages for the fabrication of coronary stents: shape memory, superelasticity, and radiopacity. However, many authors highlighted the selective dissolution of Ni from the alloy during the corrosion process that could lead to potential toxicity. The improvement of the NiTi stent's corrosion resistance by different surface treatments (electropolishing, heat treatment, and nitric acid passivation) was reported in a previous article. In the present study a comparative biocompatibility evaluation of such stents was performed through in vitro and in vivo assays. A cell proliferation test was completed to evaluate the cytotoxicity of surface treated NiTi using human fibroblasts. Then a stent implantation was performed in rabbit paramuscular muscle to study the inflammatory response generated by the same implants. Cell proliferation tests generally indicated an in vitro biocompatibility of our samples similar to the control group. An in vivo implantation study demonstrated the gradual overall reduction with time of the fibrocellular capsule thickness surrounding the implants. After a 12-week implantation period, the fibrous capsules surrounding the different implants tended toward the same value of 0.07 mm, which suggested that all surface treatments produced a similar biological response. This low value of the fibrocellular capsule indicated that our NiTi surface treated implants were relatively inert.
Cyclooxygenase-1-dependent Prostaglandin Synthesis Modulates Tumor Necrosis Factor-α Secretion in Lipopolysaccharide-challenged Murine Resident Peritoneal Macrophages (2004)

Comprehensive studies of prostaglandin (PG) synthesis in murine resident peritoneal macrophages (RPM) responding to bacterial lipopolysaccharide (LPS) revealed that the primary PGs produced by RPM were prostacyclin and PGE(2). Detectable increases in net PG formation occurred within the first hour, and maximal PG formation had occurred by 6-10 h after LPS addition. Free arachidonic acid levels rose and peaked at 1-2 h after LPS addition and then returned to baseline. Cyclooxygenase-2 (COX-2) and microsomal PGE synthase levels markedly increased upon exposure of RPM to LPS, with the most rapid increases in protein expression occurring 2-6 h after addition of the stimulus. RPM constitutively expressed high levels of COX-1. Studies using isoform-selective inhibitors and RPM from mice bearing targeted deletions of ptgs-1 and ptgs-2 demonstrated that COX-1 contributes significantly to PG synthesis in RPM, especially during the initial 1-2 h after LPS addition. Selective inhibition of either COX isoform resulted in increased secretion of tumor necrosis factor-alpha (TNF-alpha); however, this effect was much greater with the COX-1 than with the COX-2 inhibitor. These results demonstrate autocrine regulation of TNF-alpha secretion by endogenous PGs synthesized primarily by COX-1 in RPM and suggest that COX-1 may play a significant role in the regulation of the early response to endotoxemia.
Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. (1989)

The generation of invasiveness in transformed cells represents an essential step of tumor progression. We show here, first, that nontransformed Madin-Darby canine kidney (MDCK) epithelial cells acquire invasive properties when intercellular adhesion is specifically inhibited by the addition of antibodies against the cell adhesion molecule uvomorulin; the separated cells then invade collagen gels and embryonal heart tissue. Second, MDCK cells transformed with Harvey and Moloney sarcoma viruses are constitutively invasive, and they were found not to express uvomorulin at their cell surface. These data suggest that the loss of adhesive function of uvomorulin (which is identical to E-cadherin and homologous to L-CAM) is a critical step in the promotion of epithelial cells to a more malignant, i.e., invasive, phenotype. Similar modulation of intercellular adhesion might also occur during invasion of carcinoma cells in vivo.
A Novel Potent Nicotinamide Phosphoribosyltransferase Inhibitor Synthesized via Click Chemistry (2009)

The inhibition of NAD synthesis or salvage pathways has been proposed as a novel target for antitumoral drugs. Two molecules with this mechanism of action are at present undergoing clinical trials. In searching for similar novel molecules, we exploited copper-catalyzed [3 + 2] cycloaddition between azides and alkynes (click chemistry) to synthesize 185 novel analogues. The most promising compound displays an IC(50) for cytotoxicity in vitro of 3.8 +/- 0.3 nM and an IC(50) for NAD depletion of 3.0 +/- 0.4 nM. Herein, we strengthen previous data suggesting that this class of compounds induces autophagic cell death. In addition to characterizing this compound and providing a rationale via molecular docking, we reinforce the excellent potential of click chemistry for rapidly generating structure-activity relationships and for drug screening.
Primary Allogeneic T-Cell Responses against Mantle Cell Lymphoma Antigen-Presenting Cells for Adoptive Immunotherapy after Stem Cell Transplantation (2005)

These results show the feasibility to generate primary allogeneic T-cell responses against MCL-APC, and may provide new immunotherapeutic tools to further exploit the graft-versus-lymphoma effect following allogeneic stem cell transplantation in patients with MCL.