gebhart/patrepeval huggingface dataset:
Bone marrow transplantation from related donors other than HLA-identical siblings: effect of T cell depletion. (1991)

Results of 470 bone marrow transplants from related donors other than genotypically HLA-identical siblings (alternative related donors) were analysed to identify factors associated with transplant outcome and to determine whether T cell depletion improved results. As compared to 3648 transplant from HLA-identical siblings, alternative related donor transplants were associated with increased graft failure, increased acute graft-versus-host disease (GVHD), and lower disease-free survival. The likelihood of adverse outcome correlated with increasing donor-recipient HLA-disparity. In multivariate analysis of alternative related donor transplants, donor age greater than or equal to 30 years, (relative risk [RR] 1.7, p less than 0.006), intermediate and advanced leukemia (RR 1.5 and 1.6, p less than 0.01 and p less than 0.003), infection pretransplant (RR 1.7, p less than 0.005) and 2- and 3-locus donor-recipient HLA-disparity (RR 1.3, p less than 0.04) were associated with increased risks of treatment failure. The 2-year probability of leukemia-free survival after alternative related donor transplants (n = 43) with none of these adverse prognostic features was 44% (95% confidence interval 28-59%) compared to 56% (95% confidence interval 52-59%) for similar patients receiving HLA-identical sibling transplants (n = 868, univariate p less than 0.03). T cell depletion increased graft failure and decreased acute GVHD after alternative related donor transplants but did not improve leukemia-free survival.
VEGFR-1 (FLT-1) activation modulates acute lymphoblastic leukemia localization and survival within the bone marrow, determining the onset of extramedullary disease (2005)

The presence of persistent circulating leukemia cells, or engrafted into extramedullary tissues, is a bad prognostic factor for patients with acute leukemia. However, little is known about the mechanisms that regulate the exit of leukemia cells from the bone marrow (BM) microenvironment. We reveal that vascular endothelial growth factor receptor 1 (FLT-1) modulates acute leukemia distribution within the BM, along VEGF and PlGF gradients, regulating leukemia survival and exit into the peripheral circulation. FLT-1 activation on acute lymphoblastic leukemia (ALL) cells results in cell migration and proliferation in vitro, whereas in vivo FLT-1-overexpressing cells accumulate in the BM epiphysis of nonobese diabetic-severe combined immunodeficient (NOD-SCID) recipients and are detected in circulation 2 weeks after inoculation. In turn, FLT-1 neutralization affects leukemia localization (now in the BM diaphysis), increases leukemia apoptosis, and impedes the exit of ALL cells, prolonging the survival of inoculated mice. We demonstrate further that FLT-1-induced cell migration involves actin polymerization and lipid raft formation. Taken together, we show that FLT-1 regulates the BM localization of ALL cells, determining their survival and exit into the circulation and ultimately the survival of inoculated recipients. FLT-1 targeting on subsets of acute leukemias may delay the onset of extramedullary disease, which may be advantageous in combinatorial therapeutic settings.
Pressure Losses in Globe and Gate Valves during Two-Phase Oil/Water Emulsion Flow (1998)

The loss coefficients for fully-open and half-open globe and gate valves were determined experimentally during turbulent flow of two-phase oil/water mixtures. The oil concentration was varied from 0 to 97.3 vol %. The emulsions were of oil-in-water type up to an oil concentration of 64 vol %. Above 64 vol % oil, the emulsions were water-in-oil type. An in-line conductance cell was used to monitor the inversion point and the type of emulsion. The loss coefficients for the globe and gate valves during turbulent flow of emulsions are found to be comparable to the values reported for single-phase turbulent flow. The concentration and type of emulsions (oil-in-water or water-in-oil) flowing through the valves have negligible effect on the loss coefficients.
Nucleotide Sequences from a Rabbit Alpha Globin Gene Inserted in a Chimeric Plasmid (1977)

Rabbit alpha globin gene copies have been made, using reverse transcriptase and DNA polymerase I, and cloned in bacterial plasmids. Plasmid pHb72 has been shown to contain the alpha gene sequence by restriction enzyme analysis and nucleotide sequencing studies, and therefore has been approved for propagation under P2 plus EK1 conditions by the National REcombinant DNA Committee.
Alkaline hydrolysis of monomethyl esters of maleic and fumaric acids (1983)

The kinetics of alkaline hydrolysis of maleic and fumaric acids monomethyl esters were studied as function of the temperature, ionic strength, and relative permittivity of the reaction medium. Electrostatic and nonelectrostatic contributions of the interaction energies of reacting species were calculated from the measured data and compared with the experimental activation energy values. The dependence of the rate constant on the temperature brings an evidence for the mutual compensation of the electrostatic and nonelectrostatic effects.
Decarboxylation of gamma-carboxyglutamic acid residues in human prothrombin. Stoichiometry of calcium binding to gamma-carboxyglutamic acid in prothrombin. (1982)

The abbreviations used are: Gla, y-carboxyglutamic acid; 0.5-Gla I1 variant, fully decarboxylated prothrombin; 3-Gla 11 variant, Partially decarboxylated prothrombin; 10-Gla 11 110 "C variant, Prothrombin protected by Ca2+ from thermal decarboxylation; 10-Gla I1 variant, normal native prothrombin; IIa,
Poly (DL- Lactide-co-glycol ide)/Noreth isterone Microcapsules: An Injectable Biodegradable Contraceptive (1983)

Microcapsules made from a biocompatible, biodegradable polymeric excipient, poly(DL-lactide-co-glycolide) (DL-PLGA) that contained 22 weight percent (wt %) norethisterone (NET), were prepared by a solvent-evaporation microencapsulation process. The effects of changing both the lactide-to-glycolide ratio of the DL-PLGA and the size of the microcapsules on the rate of NET release and the rate of excipient biodegradation were determined in vivo. NET release rates were determined in baboons after injecting the microcapsule formulations intramuscularly. Serum samples obtained at various times following treatment were analyzed for NET, progesterone, and estrogen by radioimmunoassay (RIA). Biodegradation kinetics were determined by injecting NET microcapsules made from radiolabeled DL-PLGA intramuscularly into the hind legs of rats. Residual radioactivity at the injection site was determined at various times after treatment by combustion analysis of the muscle tissue. Changing the ratio of the comonomers to include more glycolide (DL-lactide:glycolide-96:4, 92:8, 87:13, 74:26) increased the rate of NET release and accelerated the biodegradation of the copolymer excipient. Decreasing the size of the microcapsules increased the rate of NET release. On the basis of these studies a NET microcapsule formulation has been identified for clinical testing which releases NET for 3 months and biodegrades completely within 6 months.
Precise and high-throughput femtopulse laser mask repair of large defects (2006)

As mask complexity has increased and design rules continued to shrink, the manufacturing cost per mask has steadily increased as well. Studies also show that defects are the number one issue for mask yield. Smaller defects are typically addressed through process development, or through photomask repair. The occurrence of large defects often may only be further reduced through use of expensive clean room improvements, like SMIF handling systems. The impact of each large defect therefore increases while the feasibility in their repair decreases as they can span a large number of adjoining densely packed patterns. The presence of sub-resolution features such as scatter bars and the increasing use of embedded phase-shifting masks also complicates the timely repair of such defects. Existing mask repair techniques such as nanomachining, electron beam, or focused ion beam are challenged to produce high yield repairs on such large defects within a reasonable timeframe. Often very complex repairs may in fact take longer than a rewrite of the mask! Deep UV (DUV) femtosecond pulse laser mask repair provides a unique solution to this defect repair need. Methods and results are discussed for the process optimization for the removal of large (5&#956;m) area repair on both Cr and MoSi absorber films on quartz. Additionally, high repair throughput results are shown for unknown contamination removal, and reproduction of &#8805;1 &#956;m complex unconnected patterns in a single repair run lasting a matter of minutes. Closed-loop CD feedback in-situ with the iterative repair process for such structures can readily result in an edge placement control within ±15 nm. Prior iterative CD closed-loop repairs on specific structures have reliably yielded results within ±10 nm, as confirmed by AIMS CD error, even after aggressive mask wet clean. The nanometer scale dimensional resolution and repeatability of such repairs is shown with the use of sub-pixel resolution automated pattern reconstruction using integrated high-NA DUV microscope imaging.
Mutation detection using Surveyor™ nuclease (2004)

We have developed a simple and flexible mutation detection technology for the discovery and mapping of both known and unknown mutations. This technology is based on a new mismatch-specific DNA endonuclease from celery, Surveyor nuclease, which is a member of the CEL nuclease family of plant DNA endonucleases. Surveyor nuclease cleaves with high specificity at the 3' side of any mismatch site in both DNA strands, including all base substitutions and insertion/deletions up to at least 12 nucleotides. Surveyor nuclease technology involves four steps: (i) PCR to amplify target DNA from both mutant and wild-type reference DNA; (ii) hybridization to form heteroduplexes between mutant and wild-type reference DNA; (iii) treatment of annealed DNA with Surveyor nuclease to cleave heteroduplexes; and (iv) analysis of digested DNA products using the detection/separation platform of choice. The technology is highly sensitive, detecting rare mutants present at as low as 1 in 32 copies. Unlabeled Surveyor nuclease digestion products can be analyzed using conventional gel electrophoresis or high-performance liquid chromatography (HPLC), while end labeled digestion products are suitable for analysis by automated gel or capillary electrophoresis. The entire protocol can be performed in less than a day and is suitable for automated and high-throughput procedures.
Identification of nuclear proteins that specifically interact with adeno-associated virus type 2 inverted terminal repeat hairpin DNA (1989)

A palindromic hairpin duplex containing the inverted terminal repeat sequence of adeno-associated virus type 2 (AAV) DNA was used as a substrate in gel retardation assays to detect putative proteins that specifically interact with the AAV hairpin DNA structures. Nuclear proteins were detected in extracts prepared from human KB cells coinfected with AAV and adenovirus type 2 that interacted with the hairpin duplex but not in nuclear extracts prepared from uninfected, AAV-infected, or adenovirus type 2-infected KB cells. The binding was specific for the hairpin duplex, since no binding occurred with a double-stranded DNA duplex with the identical nucleotide sequence. Furthermore, in competition experiments, the binding could be reduced with increasing concentrations of the hairpin duplex but not with the double-stranded duplex DNA with the identical nucleotide sequence. S1 nuclease assays revealed that the binding was sensitive to digestion with the enzyme, whereas the protein-bound hairpin duplex was resistant to digestion with S1 nuclease. The nucleotide sequence involved in the protein binding was localized within the inverted terminal repeat of the AAV genome by methylation interference assays. These nuclear proteins may be likely candidates for the pivotal enzyme nickase required for replication or resolution (or both) of single-stranded palindromic hairpin termini of the AAV genome.
Preclinical and Clinical Studies on the Use of Platinum Complexes for Breast Cancer Treatment (2007)

As platinum compounds display high antitumoral efficacy against several breast cancer cell lines in-vitro they may be an interesting option for future clinical therapy of this disease. On the preclinical stage hormonally active and tissue selective platinum anticancer drugs have been investigated. Clinical trials on established platinum drugs (mainly cisplatin and carboplatin) showed that they can be efficient cytostatics for breast cancer therapy, if patients are carefully selected and suitable combination regimens (e.g. including taxanes) are administered. This review covers the latest findings about new platinum complexes in preclinical studies on the use against breast cancer as well as the outcome of the most relevant clinical trials.
Instantaneous Spatial Light Interference Microscopy (iSLIM) (2010)

We developed Instantaneous Spatial Light Interference Microscopy (iSLIM) as white light-based quantitative phase imaging method, which provides single-shot, speckle-free imaging at different colors (RGB) simultaneously. It is implemented as add-on module to phase contrast microscope.
Serotonergic function, two-mode models of self-regulation, and vulnerability to depression: What depression has in common with impulsive aggression. (2008)

Evidence from diverse literatures supports the viewpoint that two modes of self-regulation exist, a lower-order system that responds quickly to associative cues of the moment and a higher-order system that responds more reflectively and planfully; that low serotonergic function is linked to relative dominance of the lower-order system; that how dominance of the lower-order system is manifested depends on additional variables; and that low serotonergic function therefore can promote behavioral patterns as divergent as impulsive aggression and lethargic depression. Literatures reviewed include work on two-mode models; studies of brain function supporting the biological plausibility of the two-mode view and the involvement of serotonergic pathways in functions pertaining to it; and studies relating low serotonergic function to impulsiveness, aggression (including extreme violence), aspects of personality, and depression vulnerability. Substantial differences between depression and other phenomena reviewed are interpreted by proposing that depression reflects both low serotonergic function and low reward sensitivity. The article closes with brief consideration of the idea that low serotonergic function relates to even more diverse phenomena, whose natures depend in part on sensitivities of other systems.
Detecting malicious inclusions in secure hardware: Challenges and solutions (2008)

This paper addresses a new threat to the security of integrated circuits (ICs) used in safety critical, security and military systems. The migration of IC fabrication to low-cost foundries has made ICs vulnerable to malicious alterations, that could, under specific conditions, result in functional changes and/or catastrophic failure of the system in which they are embedded. We refer to such malicious alternations and inclusions as Hardware Trojans. The modification(s) introduced by the Trojan depends on the application, with some designed to disable the system or degrade signal integrity, while others are designed to defeat hardware security and encryption to leak plain text information. This paper explores the wide range of malicious alternations of ICs that are possible and proposes a general framework for their classification. The taxonomy is essential for properly evaluating the effectiveness of methods designed to detect Trojans. The latter portion of the paper explores several Trojan detection strategies and the classes of Trojans each is most likely to detect.
E2F integrates cell cycle progression with DNA repair, replication, and G 2 /M checkpoints (2002)

The E2F transcription factor family is known to play a key role in the timely expression of genes required for cell cycle progression and proliferation, but only a few E2F target genes have been identified. We explored the possibility that E2F regulators play a broader role by identifying additional genes bound by E2F in living human cells. A protocol was developed to identify genomic binding sites for DNA-binding factors in mammalian cells that combines immunoprecipitation of cross-linked protein-DNA complexes with DNA microarray analysis. Among approximately 1200 genes expressed during cell cycle entry, we found that the promoters of 127 were bound by the E2F4 transcription factor in primary fibroblasts. A subset of these targets was also bound by E2F1. Most previously identified target genes known to have roles in DNA replication and cell cycle control and represented on the microarray were confirmed by this analysis. We also identified a remarkable cadre of genes with no previous connection to E2F regulation, including genes that encode components of the DNA damage checkpoint and repair pathways, as well as factors involved in chromatin assembly/condensation, chromosome segregation, and the mitotic spindle checkpoint. Our data indicate that E2F directly links cell cycle progression with the coordinate regulation of genes essential for both the synthesis of DNA as well as its surveillance.
Just-in-time information retrieval agents (2000)

A just-in-time information retrieval agent (JITIR agent) is software that proactively retrieves and presents information based on a person's local context in an easily accessible yet nonintrusive manner. This paper describes three implemented JITIR agents: the Remembrance Agent, Margin Notes, and Jimminy. Theory and design lessons learned from these implementations are presented, drawing from behavioral psychology, information retrieval, and interface design. They are followed by evaluations and experimental results. The key lesson is that users of JITIR agents are not merely more efficient at retrieving information, but actually retrieve and use more information than they would with traditional search engines.
Expression of a multidrug resistance-adenosine deaminase fusion gene (1989)

A novel fusion gene has been created in which the expression of a dominant selectable marker, the human multidrug resistance gene, is directly linked to the expression of human adenosine deaminase cDNA. The chimeric gene was inserted between the long terminal repeats of a Harvey murine sarcoma virus expression vector and used to transfect drug-sensitive human KB carcinoma cells. Transfectants were selected in increasing concentrations of colchicine and found to contain multiple copies of the intact fusion gene, which is stably and efficiently expressed. A membrane-associated 210-kDa human P-glycoprotein-adenosine deaminase fusion protein is synthesized which retains function of the multidrug transporter and also exhibits adenosine deaminase activity. The data indicate that the human multidrug resistance gene may be used as a dominant selectable marker to introduce other genes in the form of gene fusions into cultured cells.
The Emerging Importance of IgG Fab Glycosylation in Immunity (2016)

Human IgG is the most abundant glycoprotein in serum and is crucial for protective immunity. In addition to conserved IgG Fc glycans, ∼15-25% of serum IgG contains glycans within the variable domains. These so-called "Fab glycans" are primarily highly processed complex-type biantennary N-glycans linked to N-glycosylation sites that emerge during somatic hypermutation. Specific patterns of Fab glycosylation are concurrent with physiological and pathological conditions, such as pregnancy and rheumatoid arthritis. With respect to function, Fab glycosylation can significantly affect stability, half-life, and binding characteristics of Abs and BCRs. Moreover, Fab glycans are associated with the anti-inflammatory activity of IVIgs. Consequently, IgG Fab glycosylation appears to be an important, yet poorly understood, process that modulates immunity.
Identification and purification of cytolytic antibodies directed against O-acetylated sialic acid in childhood acute lymphoblastic leukemia (2000)

Sialic acids typically present as terminal sugars of oligo-saccharides are reported to be modified by O-acetylation at the C-9 position on lymphoblasts of childhood acute lymphoblastic leukemia (ALL) patients (Sinha et al., 1999a, Leukaemia, 13, 119-125). We now report high titers of IgG antibodies directed against O-acetylated derivatives of sialic acids (O-AcSA) in serum of ALL patients. These antibodies were purified using bovine submaxillary mucin (BSM) and the IgG distribution was confined to IgG(1)and IgG(2)subclasses; their binding was totally abolished with de-O-acetylation confirming their specificity towards O-AcSA determinants. Flow cytometry demonstrated binding of these antibody fractions to peripheral blood mononuclear cells (PBMC) of both T- and B-ALL patients having increased cell surface 9-O-AcSA determinants. Western blotting of membranes derived from PBMC of ALL patients confirmed binding of the antibody to O-acetylated sialoglycoconjugates corresponding to 144, 135, 120, 90, and 36 kDa whereas binding to PBMC from normal individuals corresponded to 144 and 36 kDa. Specificity of the antibody fraction towards 9-O-AcSA was substantiated by hemagglutination and hemagglutination-inhibition assays. The antibody purified from ALL serum selectively mediates complement dependent cytolysis of lymphoblasts expressing O-AcSAs and thereby possibly confers passive protection. The enhanced anti O-AcSA antibody levels allowed for development of a serodiagnostic assay (BSM-ELISA) specific for ALL. Minimal crossreactivity was observed with other hematological disorders like acute myeloid leukemia (n = 16), chronic myeloid leukemia (n = 6), chronic lymphocytic leukemia (n = 7) and non-Hodgkin's lymphoma (n = 3) as well as normal healthy individuals (n = 28). The BSM-ELISA therefore provides a simple, noninvasive alternative diagnostic approach for ALL and merits clinical consideration.
Distribution, functional impact, and origin mechanisms of copy number variation in the barley genome (2013)

We present the first catalog of CNVs in a diploid Triticeae species, which opens the door for future genome diversity research in a tribe that comprises the economically important cereal species wheat, barley, and rye. Our findings constitute a valuable resource for the identification of CNV affecting genes of agronomic importance. We also identify potential mechanisms that can generate variation in copy number in plant genomes.