gebhart/patrepeval huggingface dataset:
Deferred effects of preweaning diet on atherosclerosis in adolescent baboons. (1988)

We examined the effects of breast and formula feeding during infancy on the serum lipoproteins and on atherosclerosis in young adult baboons. Baboons were breast-fed (n = 13) or formula-fed (n = 32) until weaning at 16 weeks of age and thereafter they were fed a diet containing 1.7 mg cholesterol/kcal and 40% of calories as lard until 5 years of age. At 12 weeks of age, breast-fed baboons had higher serum high density lipoprotein cholesterol concentration (HDL-C, 68 vs. 51 mg/dl), lower serum triglyceride concentration (37 vs. 68 mg/dl), and lower very low density plus low density lipoprotein cholesterol (VLDL + LDL-C) to HDL-C ratio (0.65 vs. 0.98) than formula-fed infants. From weaning to 92 weeks of age, breast-fed baboons had a lower serum triglyceride concentration (23 vs. 38 mg/dl) than formula-fed baboons. After weaning, the VLDL + LDL-C/HDL-C ratio increased from 0.65 to 1.0 in breast-fed baboons, but decreased from 0.98 to 0.72 in formula-fed baboons. From 92 to 246 weeks of age, the VLDL + LDL-C/HDL-C ratio was consistently higher in breast-fed baboons compared to formula-fed baboons. At 5 years of age, baboons breast-fed as infants had a greater percentage of intimal surface area involved with atherosclerosis in the abdominal aorta, the iliac-femoral artery, the aortic arch, the brachial artery, and the carotid artery, than did those formula-fed as infants. The greater prevalence of lesions in breast-fed baboons was explained mainly by the higher VLDL + LDL-C/HDL-C ratio.
Vitamin K-dependent carboxylation. Evidence that at least two microsomal dehydrogenases reduce vitamin K1 to support carboxylation. (1982)

It has been shown that NAD(P)H dehydrogenase (EC 1.6.99.2) reduces vitamin K1 and can support the [vitamin K1 + NADH]-dependent carboxylation reaction in rat liver microsomes (Wallin, R., Gebhardt, O., and Prydz, H. (1978) Biochem. J. 169, 95-101). Antibodies were raised in rabbits against the purified enzyme from liver cytosol and used to study the importance of NAD(P)H dehydrogenase in the vitamin K-dependent carboxylation reaction. The antibodies neutralized the warfarin-sensitive NAD(P)H dehydrogenase activity in Triton X-100-solubilized microsomes; however, they neutralized only 45% of the total [vitamin K1 + NADH]-dependent carboxylation activity. Chromatography on protein A-sepharose showed that the remaining carboxylase activity was not the result of soluble antigen-antibody complexes. The data presented support the conclusion that the microsomal preparation also contains a non-warfarin-sensitive dehydrogenase(s) that, in addition to NAD(P)H dehydrogenase, can reduce vitamin K1 to support the carboxylation reaction.
A Case of Compound Mutations in the <b><i>MYBPC3</i></b> Gene Associated with Biventricular Hypertrophy and Neonatal Death (2012)

Hypertrophic cardiomyopathy (HCM) is a familial, genetically determined, primary cardiomyopathy caused by mutations in genes coding for proteins of the sarcomere, or, less frequently, genes involved in storage diseases. In pediatric settings, pure HCM has an estimated incidence of 4.7 per million children. The disease is often sub-clinical and goes unrecognized mainly because most patients with HCM have only mild symptoms, if any. However, sudden cardiac death, the most dramatic clinical occurrence and the primary concern for patients and physicians alike, may be the first manifestation of the disease. We describe a case of compound heterozygosity in the MYBPC3 gene (p.Glu258Lys and IVS25-1G>A) associated with biventricular hypertrophy, atrial enlargement and subsequent neonatal death 33 days postpartum. Other studies have reported compound and/or double heterozygosis in the same or different sarcomeric genes during childhood and adulthood, and neonatal presentations have also been described. Our observations show that the combination of a missense (p.Glu258Lys) and a splice-site mutation (IVS25-1G>A) profoundly affects the clinical course. In families in which parental mutations are known, preimplantation (where ethically and legally feasible) or prenatal genetic screening should be adopted because: (1) neonatal HCM in genetic heterozygosity is potentially lethal and (2) heart disease is the most common developmental malformation and the leading cause of neonatal mortality and morbidity.
On indoor position location with wireless LANs (2003)

Location aware services are becoming attractive with the deployment of next generation wireless networks and broadband multimedia wireless networks especially in indoor and campus areas. To provide location aware services, obtaining the position of a user accurately is important. While it is possible to deploy additional infrastructure for this purpose, using existing communications infrastructure is preferred for cost reasons. Because of technical restrictions, location fingerprinting schemes are the most promising. In this paper we present a systematic study of the performance tradeoff and deployment issues. In this paper we present some experimental results towards such a systematic study and discuss some issues related to the indoor positioning problem.
Disk Micelles from Nonionic Coil−Coil Diblock Copolymers (2006)

The micellization of an almost symmetric diblock copolymer, 1,2-polybutadiene-b-poly(hexafluoropropylene oxide), with block molecular weights of 6000 and 5700, respectively, was examined in the polybutadiene-selective solvent bis(2-ethylhexyl) phthalate. Cryogenic transmission electron microscopy indicated that the copolymer self-assembled into thin disk micelles, with radii from 20 to 150 nm. Small-angle X-ray scattering measurements were effectively modeled by the form factor for a thin disk and gave a core thickness of approximately 10 nm. Dynamic light scattering measurements gave a distribution of hydrodynamic radii that was fully consistent with the dimensions inferred from microscopy and X-ray scattering. The unprecedented adoption of the flat disk morphology by a nonionic, coil−coil diblock copolymer is attributed to the extremely strong interfacial tension between the fluoropolymer core and the solvated hydrocarbon corona, as anticipated by superstrong segregation theory.
Increased erbB-2 gene copies and expression in multiple stages of breast cancer. (1990)

In order to examine the role of the erbB-2 oncogene in human breast cancer, gene amplification and expression were examined in multiple stages of tumor progression. Gene amplification ranging from 2-fold to 32-fold was found in 30 (29%) of 130 cases analyzed. Expression of the receptor-like gene product was determined by a combination of Western immunoblotting and immunohistochemistry. In each case of gene amplification, there was high level overexpression (+ + +) of the protein product. In an additional 29 of 111 cases in which expression was studied (26%), there was moderate level overexpression (+ +) of erbB-2 in the absence of gene amplification. Amplification and overexpression of the erbB-2 gene were found in early clinical stages of breast cancer as well as in more advanced cases. In 23 patients, gene number and level of gene expression were equivalent in the primary tumor site compared with single or multiple metastatic sites in regional lymph nodes. Using a combination of immunohistochemistry and in situ cytohybridization, high (+ + +) and moderate (+ +) level overexpression were homogeneously present in all malignant epithelial cells within histological sections of both primary and metastatic tumor. The intraductal component of carcinoma was identified in sections from 16 invasive primary tumors. erbB-2 gene expression in the intraductal lesions was equivalent to or exceeded expression in the infiltrating components of these tumors. Because erbB-2 alterations are (a) present in all clinical stages, (b) maintained during metastatic spread, (c) homogeneously present throughout tumor sections, and (d) present in the in situ as well as infiltrating component, we conclude that these alterations are selected for early and may be important in the initiation of certain mammary cancer.
Eph/Ephrin Profiling in Human Breast Cancer Reveals Significant Associations between Expression Level and Clinical Outcome (2011)

Pre-clinical studies provide compelling evidence that Eph family receptor tyrosine kinases (RTKs) and ligands promote cancer growth, neovascularization, invasion, and metastasis. Tumor suppressive roles have also been reported for the receptors, however, creating a potential barrier for clinical application. Determining how these observations relate to clinical outcome is a crucial step for translating the biological and mechanistic data into new molecularly targeted therapies. We investigated eph and ephrin expression in human breast cancer relative to endpoints of overall and/or recurrence-free survival in large microarray datasets. We also investigated protein expression in commercial human breast tissue microarrays (TMA) and Stage I prognostic TMAs linked to recurrence outcome data. We found significant correlations between ephA2, ephA4, ephA7, ephB4, and ephB6 and overall and/or recurrence-free survival in large microarray datasets. Protein expression in TMAs supported these trends. While observed no correlation between ephrin ligand expression and clinical outcome in microarray datasets, ephrin-A1 and EphA2 protein co-expression was significantly associated with recurrence in Stage I prognostic breast cancer TMAs. Our data suggest that several Eph family members are clinically relevant and tractable targets for intervention in human breast cancer. Moreover, profiling Eph receptor expression patterns in the context of relevant ligands and in the context of stage may be valuable in terms of diagnostics and treatment.
Nonlinear effects of transition broadening (1991)

Nonlinear broadening of closely spaced transitions has been studied using micromagnetics simulations. Results show a large increase in the width of a transition due to the demagnetizing field effect of earlier transitions. Based on this observation, a simple recording channel model is developed to investigate the effects of nonlinear transition broadening on detection performance. This analysis shows that the conventional peak detector is much less sensitive to the detrimental effects of nonlinearity than the more advanced partial response maximum likelihood (PRML) scheme, mainly due to the extra transition spacing provided by the minimum run-length-limited constraint. This result suggests that in order to preserve the improved signal detection capability of advanced signal processing schemes like PRML, reduction of nonlinearity is essential in the media design.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The JAK2 V617F Tyrosine Kinase Mutation in Myelofibrosis with Myeloid Metaplasia: Clinical Correlates and Prognostic Relevance in 157 Patients. (2005)

Abstract Background: The occurrence of an activating JAK2 mutation (JAK2 V617F) has been reported in a variable proportion of patients with bcr/abl-negative myeloproliferative disorders including myelofibrosis with myeloid metaplasia (MMM). In the current study, we report mutational frequencies in each of the 3 MMM variants as well as examine the prognostic relevance of the mutation in a large group of patients from a single institution. Methods: Mutation analysis for JAK2 V617F was performed in DNA derived from peripheral blood mononuclear cells (PBMC) from all study patients (n=157). Concomitant analysis was also performed in DNA derived from purified granulocytes (n=57), CD34-positive cells (n=25), and T cells (n=19). Genomic DNA was amplified by PCR and fluorescent dye chemistry sequencing was performed using the same primers used for amplification. Results: The study cohort included 157 consecutive patients with MMM including 117 with agnogenic (AMM), 22 with post polycythemic (PPMM), and 18 with post thrombocythemic (PTMM) myeloid metaplasia. The overall detection rate for JAK2 V617F in PBMC was 51% (homozygous in 5.7%) and was significantly (p=0.0002) higher in PPMM (91%; homozygous in 18%) compared to either AMM (45.3%; homozygous in 2.6%) or PTMM (38.9%; homozygous in 11.1%). In AMM (n=117), the presence of JAK2 V617F was significantly associated with an older age at diagnosis (p=0.03), and a history of both thrombosis (p=0.01) and pruritus (p=0.005). No other statistical associations were evident and the presence of the mutation did not predict leukemic transformation. Furthermore, multivariate analysis for overall survival of patients with AMM identified only age and the Dupriez prognostic score as independent prognostic factors; JAK2 V617F had no prognostic significance. Finally, the mutation was not found in T cells and its detection rate in either granulocytes or CD34-positive cells was similar to that in PBMC. Conclusion: JAK2 V617F is a myeloid lineage-specific event, its incidence in MMM is significantly higher with an antecedent history of polycythemia vera, and its presence in AMM does not affect prognosis but is associated with PV-characteristic clinical features.
Elements of Artificial Neural Networks (1996)

Elements of Artificial Neural Networks provides a clearly organized general introduction, focusing on a broad range of algorithms, for students and others who want to use neural networks rather than simply study them. The authors, who have been developing and team teaching the material in a one-semester course over the past six years, describe most of the basic neural network models (with several detailed solved examples) and discuss the rationale and advantages of the models, as well as their limitations. The approach is practical and open-minded and requires very little mathematical or technical background. Written from a computer science and statistics point of view, the text stresses links to contiguous fields and can easily serve as a first course for students in economics and management. The opening chapter sets the stage, presenting the basic concepts in a clear and objective way and tackling important—yet rarely addressed—questions related to the use of neural networks in practical situations. Subsequent chapters on supervised learning (single layer and multilayer networks), unsupervised learning, and associative models are structured around classes of problems to which networks can be applied. Applications are discussed along with the algorithms. A separate chapter takes up optimization methods. The most frequently used algorithms, such as backpropagation, are introduced early on, right after perceptrons, so that these can form the basis for initiating course projects. Algorithms published as late as 1995 are also included. All of the algorithms are presented using block-structured pseudo-code, and exercises are provided throughout. Software implementing many commonly used neural network algorithms is available at the book's website. Transparency masters, including abbreviated text and figures for the entire book, are available for instructors using the text. Bradford Books imprint
Expression of Hemolytically Active Human Complement Component Clr Proenzyme in Insect Cells Using a Baculovirus Vector (1989)

The gene of human C1r has been expressed in a baculovirus-insect-cell system via the pAc373 transplacement vector. The full-length cDNA copy was inserted into the pAc373 vector downstream from the strong polyhedrin promoter of the baculovirus, Autographa californica nuclear polyhedrosis virus (AcNPV). Spodoptera frugiperda cells were cotransfected with the resultant plasmid, pAcC1r, and the wild-type AcNPV DNA. Recombinant viruses, which drove the expression of C1r protein, were selected by plaque morphology and ELISA. Insect cells infected with the recombinant virus produced and secreted human C1r protein, at a level of 1-2 mg/l of medium. The expressed C1r was isolated from the medium by chromatofocusing. On reducing gels only a single Coomassie-staining band was observed, and this band migrated at 80-83 kD characteristic of the unactivated C1r proenzyme. Its identification as C1r was immunologically confirmed on Western blots. C1 reconstituted from purified C1r expressed in insect cells together with human C1q and C1s proved biologically active in a hemolytic assay. Thus, the baculovirus-insect-cell system is capable of expressing and secreting a sophisticated, multifunctional human complement subcomponent in its biologically activatable form.
Prevention of dyskinesia by an NMDA receptor antagonist in MPTP monkeys: Effect on adenosine A2Areceptors (2006)

Adenosine A(2A) receptors (A(2A)R) have received increasing attention for the treatment of L-DOPA-induced dyskinesias in Parkinson disease. In the present study, A(2A)R messenger RNA (mRNA) and receptor-specific binding in the brain of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys were studied after treatment with L-DOPA and a selective NR1A/2B NMDA receptor antagonist, CI-1041. Four MPTP monkeys received L-DOPA/benserazide and all developed dyskinesias, whereas among the four MPTP monkeys who additionally received CI-1041, only one developed mild dyskinesias. Four normal monkeys and four MPTP-treated monkeys were also studied. All MPTP monkeys had similar striatal dopamine (DA) denervation. A(2A)R mRNA levels, measured by in situ hybridization, were increased in the rostral lateral caudate and putamen of saline-treated MPTP monkeys as well as in the caudal lateral and medial putamen when compared with those of controls. A(2A)R mRNA levels remained elevated in the rostral caudate and putamen of L-DOPA-treated MPTP monkeys when compared with those of controls. A(2A)R mRNA levels of L-DOPA + CI-1041-treated monkeys were at control levels and decreased in the lateral rostral caudate and caudal putamen when compared with those of L-DOPA-treated and saline-treated MPTP monkeys respectively. No change was measured in the caudal medial putamen and caudate nucleus. A(2A)Rs labeled by autoradiography with [(3)H]SCH-58261 had lower level in the L-DOPA + CI-1041-treated MPTP monkeys compared with saline- or L-DOPA-treated MPTP and control monkeys in the rostral lateral and medial caudate and the putamen. No effect of lesion or L-DOPA treatment was measured on [(3)H]SCH-58261-specific binding. These findings suggest that blockade of NMDA receptors could prevent the development of dyskinesias by altering A(2A)Rs.
Structure of a dermatan sulfate hexasaccharide that binds to heparin cofactor II with high affinity. (1990)

Dermatan sulfate increases the rate of inhibition of thrombin by heparin cofactor II (HCII) approximately 1000-fold by providing a catalytic template to which both the inhibitor and the protease bind. Dermatan sulfate is a linear polymer of D-glucuronic acid (GlcA) or L-iduronic acid (IdoA) alternating with N-acetyl-D-galactosamine (GalNAc) residues. Heterogeneity in dermatan sulfate results from varying degrees of O-sulfation and from the presence of the two types of uronic acid residues. To characterize the HCII-binding site in dermatan sulfate, we isolated the smallest fragment of dermatan sulfate that bound to HCII with high affinity. Dermatan sulfate was partially N-deacetylated by hydrazinolysis, cleaved with nitrous acid at pH 4, and reduced with [3H]NaBH4. The resulting fragments, containing an even number of monosaccharide units with the reducing terminal GalNAc converted to [3H]2,5-anhydro-D-talitol (ATalR), were size-fractionated and then chromatographed on an HCII-Sepharose column. The smallest HCII-binding fragments were hexasaccharides, of which approximately 6% bound. Based on ion-exchange chromatography, the bound material appeared to comprise a heterogeneous mixture of molecules possessing four, five, or six sulfate groups per hexasaccharide. Subsequently, hexasaccharides with the highest affinity for HCII were isolated by overloading the HCII-Sepharose column. The high-affinity hexasaccharides were fractionated by strong anion-exchange chromatography, and one major peak representing approximately 2% of the starting hexasaccharides was isolated. The high-affinity hexasaccharide was cleaved to disaccharides that were analyzed by anion-exchange chromatography, paper electrophoresis, and paper chromatography. A single disulfated disaccharide, IdoA(2-SO4)----ATalR(4-SO4) was observed, indicating that the hexasaccharide has the following structure: IdoA(2-SO4)----GalNAc(4-SO4)----IdoA(2-SO4)---- GalNAc(4-SO4)----IdoA(2-SO4)----ATalR(4-SO4). Since IdoA(2-SO4)----GalNAc(4-SO4) comprises only approximately 5% of the disaccharides present in intact dermatan sulfate, clustering of these disaccharides must occur during biosynthesis to form the high-affinity binding site for HCII.
THE IFNγ RECEPTOR:A Paradigm for Cytokine Receptor Signaling (1997)

During the last several years, the mechanism of IFN gamma-dependent signal transduction has been the focus of intense investigation. This research has recently culminated in the elucidation of a comprehensive molecular understanding of the events that underlie IFN gamma-induced cellular responses. The structure and function of the IFN gamma receptor have been defined. The mechanism of IFN gamma signal transduction has been largely elucidated, and the physiologic relevance of this process validated. Most recently, the molecular events that link receptor ligation to signal transduction have been established. Together these insights have produced a model of IFN gamma signaling that is nearly complete and that serves as a paradigm for signaling by other members of the cytokine receptor superfamily.
Mapping the Arabidopsis genome. (1991)

We are engaged in a project to assemble a complete physical map of the Arabidopsis thaliana (L.) Heynh. genome. The first stage of this project involved the analysis of approximately 20,000 random cosmid clones representing an 8- to 10-fold sampling redundancy. Using computer matching programs, these clones have been assembled into some 750 contigs, encompassing 90-95% of the Arabidopsis genome. We are currently attempting to bridge the gaps by selecting the missing clones by hybridization. As a complement to this project we have constructed an RFLP map which currently contains 175 markers. The RFLP map provides contact points between the physical map and classical genetic map. Our main objective for undertaking this project is to simplify the cloning of genes where only the locus and not the product of the gene is known. In other words, the combined RFLP/physical map serves as a general cloning tool by simplifying the movement from the genetic locus to the cloned gene.