gebhart/patrepeval huggingface dataset:
Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis (2003)

Oxidation products of low-density lipoproteins have been suggested to promote inflammation during atherogenesis, and reticulocyte-type 15-lipoxygenase has been implicated to mediate this oxidation. In addition, the 5-lipoxygenase cascade leads to formation of leukotrienes, which exhibit strong proinflammatory activities in cardiovascular tissues. Here, we studied both lipoxygenase pathways in human atherosclerosis. The 5-lipoxygenase pathway was abundantly expressed in arterial walls of patients afflicted with various lesion stages of atherosclerosis of the aorta and of coronary and carotid arteries. 5-lipoxygenase localized to macrophages, dendritic cells, foam cells, mast cells, and neutrophilic granulocytes, and the number of 5-lipoxygenase expressing cells markedly increased in advanced lesions. By contrast, reticulocyte-type 15-lipoxygenase was expressed at levels that were several orders of magnitude lower than 5-lipoxygenase in both normal and diseased arteries, and its expression could not be related to lesion pathology. Our data support a model of atherogenesis in which 5-lipoxygenase cascade-dependent inflammatory circuits consisting of several leukocyte lineages and arterial wall cells evolve within the blood vessel wall during critical stages of lesion development. They raise the possibility that antileukotriene drugs may be an effective treatment regimen in late-stage disease.
Treatment of ovarian cancer ascites by intra-peritoneal injection of diphtheria toxin A chain-H19 vector: a case report (2010)

On the basis of this preliminary experience, we are currently conducting an extensive Phase I study on a larger number of patients in order to assess the safety and preliminary efficacy of this novel patient-oriented treatment approach.
Synthesis of 7-Substituted Indolo[3,2-b]quinoline Derivatives (1992)

Indolo [3,2-b] quinoline derivatives [7b-j] having the substituent, such as a nitro, amino, methyl, halogen, methoxy, or hydroxy group were prepared by three methods
Vascular permeability factor expression influences tumor angiogenesis in human melanoma lines xenografted to nude mice. (1995)

We studied the expression of the angiogenic factor vascular permeability factor) (VPF, also called vascular endothelial growth factor), in human melanoma cells in vitro and in vivo. Melanoma lines that develop tumors with a low metastatic potential in nude mice were found to have low expression levels of VPF in vitro, and the VPF expression levels in melanoma lines that yield highly metastatic xenografts were high. However, in vivo the correlation between VPF mRNA levels and the frequency of metastasis was lost; in all xenografts equally high levels of VPF mRNA were found, independent of the parental cell line. Hence, in vivo VPF gene expression was upregulated in the low expressing lines. The external factor responsible for this induction may be hypoxia, given that we found that low oxygen tension caused a (reversible) increase in the VPF mRNA levels in otherwise low expressing melanoma lines in vitro. A melanoma line with an inducible VPF expression was engineered into a line with a constitutive VPF expression. In the xenografts from this line a change in the vascular architecture was seen, indicating that the pattern or the level of VPF expression is important for tumor angiogenesis in melanoma xenografts.
Coarse-grained, foldable, physical model of the polypeptide chain (2013)

Although nonflexible, scaled molecular models like Pauling-Corey's and its descendants have made significant contributions in structural biology research and pedagogy, recent technical advances in 3D printing and electronics make it possible to go one step further in designing physical models of biomacromolecules: to make them conformationally dynamic. We report here the design, construction, and validation of a flexible, scaled, physical model of the polypeptide chain, which accurately reproduces the bond rotational degrees of freedom in the peptide backbone. The coarse-grained backbone model consists of repeating amide and α-carbon units, connected by mechanical bonds (corresponding to ϕ and ψ) that include realistic barriers to rotation that closely approximate those found at the molecular scale. Longer-range hydrogen-bonding interactions are also incorporated, allowing the chain to readily fold into stable secondary structures. The model is easily constructed with readily obtainable parts and promises to be a tremendous educational aid to the intuitive understanding of chain folding as the basis for macromolecular structure. Furthermore, this physical model can serve as the basis for linking tangible biomacromolecular models directly to the vast array of existing computational tools to provide an enhanced and interactive human-computer interface.
Plant lipid biochemistry, structure and utilization : the proceedings of the Ninth International Symposium on Plant Lipids, held at Wye College, Kent, July 1990 (1990)

Lipid structure and analysis, physical properties of membrane lipids, role of lipids in membranes, fatty acid synthesis, acylthioesterases and acyltransferases, triacylglycerol formation, polar lipid synthesis and transolcation, catabolism of lipids, sterols and terpenoids, modulation of membrane lipid turnover, effect of light and temperature, herbicides and pathological changes in plant lipids, molecular biology and biotechnology.
Ultrastructural surface changes associated with dextran synthesis by Leuconostoc mesenteroides (1977)

When Leuconostoc mesenteroides NCDO 1875 was grown in MRS broth and fixed for electron microscopy in the presence of ruthenium red, the cell wall appeared as a triple-layered structure similar to other, gram-positive bacteria. When such logarithmic-phase cultures were exposed to sucrose, the appearance and growth of a uniform layer of electron-dense material was evident on the surface of the cell wall. After 2 h in the presence of sucrose, the formation of this surface coat (110 to 130 nm thick) was complete. For 85 to 90% of the cells, continued exposure to sucrose did not produce any further change in their appearance, but the rest of the population began to accumulate insoluble capsular dextran at the surface of their coat material. Within 18 h, these cells had produced a large capsule (maximum diameter, 6 micrometer) composed mainly of an extensive reticulum of fine filaments. Periodate-reactive carbohydrate was localized cytochemically in the capsular dextran and in the surface coat of all cells. It is suggested that the surface coat of sucrose-grown cells represents a cell-bound dextran-dextransucrase complex and that the acapsulate cells produce the relatively soluble S dextran reported by previous workers.
Human homologue of the rat chondroitin sulfate proteoglycan, NG2, detected by monoclonal antibody 7.1, identifies childhood acute lymphoblastic leukemias with t(4;11)(q21;q23) or t(11;19)(q23;p13) and MLL gene rearrangements (1996)

Monoclonal antibody 7.1, which recognizes the chondroitin sulfate proteoglycan molecule NG2, was used to screen prospectively blast cells from 104 consecutive children at initial presentation with acute lymphoblastic leukemia (ALL). Reactivity with this antibody was found in 9 cases (8.6%), of whom 5 had a t(4;11)(q21;q23) and 4 had a t(11;19)(p13;q23). None of the NG2- cases had either translocation. Southern blot analysis disclosed MLL gene rearrangement in only the 9 cases with 7.1 reactivity plus the t(4;11)(q21;q23) or t(11;19)(q23;p13) translocation. MLL gene rearrangements were not detected in 89 patient leukemic samples that did not express NG2, including 7 patients with del(11)(q23) or inv(11)(p13q23). As expected from the association with t(4;11) and t(11;19), NG2+ cases were significantly more likely to be infants, to have hyperleukocytosis and central nervous system involvement, to be CD10-, and to express myeloid-associated antigens CD15 and CD65. Despite short follow-up duration, 3 of the NG2+ cases have relapsed while the other 101 patients remain in remission. Thus, blast cell surface expression of NG2 is useful for identifying patients with ALL having t(4;11) or t(11;19) translocations that are associated with poor prognosis, especially in the infant age group.
An open clinical trial of risperidone monotherapy in young children with autistic disorder. (1997)

Autistic disorder (AD) may be associated with dysfunctional behaviors which significantly interfere with a child's functioning. Risperidone has been described as having salutary effects as an adjunctive pharmacotherapy in adult and pediatric patients with AD. The purpose of this 8-week, open-label study was to examine the effectiveness and tolerability of risperidone monotherapy in young patients with AD. Doses of risperidone were to be started at 0.25 mg qhs and were titrated to maximize clinical efficacy. Six patients (ages 5 to 9 years) were enrolled in this protocol, and all completed it. After 8 weeks of treatment, with a mean risperidone dose of 1.1 mg, improvement in symptomatology was demonstrated by reduced scores on both the Children's Psychiatric Rating Scale (p < .005) and the Clinical Global Impressions Scale (p < .001). The most common side effect were weight gain and sedation. This study provides preliminary evidence that risperidone monotherapy may be safe and effective in ameliorating dysfunctional behaviors in children with AD.
Human monocyte-mediated cytotoxicity: the use of Ig-bearing hybridomas as target cells to detect trigger molecules on the monocyte cell surface. (1987)

We recently reported the preparation and characterization of a monoclonal antibody, 32.2, specific for the high-affinity Fc receptor (FcR) for IgG on human monocytes. We have utilized the hybridoma cell line producing this antibody as a target for monocyte-mediated cytotoxicity. The hybridoma was selected for stable sublines that expressed high quantities of surface 32.2 immunoglobulin (Ig) through flow cytometry. Monocyte-mediated cytotoxicity, with these sublines used as targets, was evaluated with the use of a 51Cr-release assay. It was found that monocytes could efficiently lyse the hybridoma cells (HC 32.2) bearing surface Ig directed to the high-affinity FcR. Consistent with the specificity of the 32.2 antibody for an epitope on the high-affinity receptor outside of the ligand binding site, human IgG did not block monocyte killing of HC 32.2. In contrast, monocytes could not mediate lysis of hybridoma cells bearing high levels of antibody directed to other monocyte cell surface molecules, in particular, class I MHC molecules, the C3bi receptor, and the My 23 antigen. The effect of IFN-gamma on the ability of monocytes to mediate lysis of the 32.2 Ig-bearing hybridomas was also assessed. Monocytes cultured in the absence of IFN-gamma could lyse the hybridoma line expressing high levels of 32.2 Ig as efficiently as monocytes cultured in the presence of IFN-gamma. However, untreated monocytes were less able than IFN-gamma-treated monocytes to kill HC 32.2 expressing lower levels of Ig. Thus, IFN-gamma may enhance the efficiency of monocyte-mediated antibody-dependent killing under conditions where limited antibody is available on the target. These studies demonstrate that the high-affinity FcR on monocytes can act as a cytotoxic trigger molecule for killing of tumor cell targets and that this trigger does not require specific binding to the Fc binding epitope. These results further encourage possible clinical application of the 32.2 monoclonal antibody in tumor therapy.
Thermodynamic Parameters for an Expanded Nearest-Neighbor Model for Formation of RNA Duplexes with Watson−Crick Base Pairs (1998)

Improved thermodynamic parameters for prediction of RNA duplex formation are derived from optical melting studies of 90 oligoribonucleotide duplexes containing only Watson−Crick base pairs. To test end or base composition effects, new sets of duplexes are included that have identical nearest neighbors, but different base compositions and therefore different ends. Duplexes with terminal GC pairs are more stable than duplexes with the same nearest neighbors but terminal AU pairs. Penalizing terminal AU base pairs by 0.45 kcal/mol relative to terminal GC base pairs significantly improves predictions of ΔG°37 from a nearest-neighbor model. A physical model is suggested in which the differential treatment of AU and GC ends accounts for the dependence of the total number of Watson−Crick hydrogen bonds on the base composition of a duplex. On average, the new parameters predict ΔG°37, ΔH°, ΔS°, and T M within 3.2%, 6.0%, 6.8%, and 1.3 °C, respectively. These predictions are within the limit of the model, based on experimental results for duplexes predicted to have identical thermodynamic parameters.
Engineering of aromatic amino acid metabolism in Saccharomyces cerevisiae (2006)

Saccharomyces cerevisiae is a popular industrial microorganism. It has since long been used in bread, beer and wine making. More recently it is also being applied for heterologous protein production and as a target organism for metabolic engineering. The work presented in this thesis describes how S. cerevisiae may be used as a metabolic-engineering platform to produce aromatic compounds such as phenylalanine or its catabolites, phenylethanol and phenylacetate. In this thesis two research lines were followed: The first research line focused on the molecular identity and substrate specificity of 2-oxo-acid decarboxylase in S. cerevisiae whereas the second line of research investigated the elimination of feedback inhibition steps in the phenylalanine biosynthetic pathway in S. cerevisiae. The impact of feedback inhibition on the aromatic biosynthesis pathway was quantified by analyzing intra- and extracellular concentrations of relevant aromatic compounds in glucose-limited chemostat cultures of wild-type and engineered strains.
Broad neutralization by a combination of antibodies recognizing the CD4 binding site and a new conformational epitope on the HIV-1 envelope protein (2012)

Two to three years after infection, a fraction of HIV-1-infected individuals develop serologic activity that neutralizes most viral isolates. Broadly neutralizing antibodies that recognize the HIV-1 envelope protein have been isolated from these patients by single-cell sorting and by neutralization screens. Here, we report a new method for anti-HIV-1 antibody isolation based on capturing single B cells that recognize the HIV-1 envelope protein expressed on the surface of transfected cells. Although far less efficient than soluble protein baits, the cell-based capture method identified antibodies that bind to a new broadly neutralizing epitope in the vicinity of the V3 loop and the CD4-induced site (CD4i). The new epitope is expressed on the cell surface form of the HIV-1 spike, but not on soluble forms of the same envelope protein. Moreover, the new antibodies complement the neutralization spectrum of potent broadly neutralizing anti-CD4 binding site (CD4bs) antibodies obtained from the same individual. Thus, combinations of potent broadly neutralizing antibodies with complementary activity can account for the breadth and potency of naturally arising anti-HIV-1 serologic activity. Therefore, vaccines aimed at eliciting anti-HIV-1 serologic breadth and potency should not be limited to single epitopes.
Budget impact analysis of ustekinumab in the management of moderate to severe psoriasis in Greece (2012)

The inclusion of ustekinumab in the treatment of moderate to severe psoriasis in Greece is anticipated to have short- and long-term health and economic benefits, both on an annual and per-patient basis.
Activation In Vitro of Mouse Macrophages by Syngeneic, Allogeneic, or Xenogeneic Lymphocyte Supernatants2 (1975)

Macrophages from normal C57BL/6 mice, those with a subcutaneous B16 melanoma, and mice immunized against the tumor were examined for in vitro cytotoxicity to B16 tumor cells. Macrophages were treated by incubation with supernatants from B16 cells grown either in unmixed cultures or in cultures containing syngeneic, normal, or sensitized allogeneic (A mouse), or xenogeneic (rat) lymphocytes. The various treated and untreated macrophages were then cultured for 5 days with viable B16 cells prelabeled with 125I-5-iodo-2'-deoxyuridine; the cultures were terminated, and the extent of destruction of the B16 target cells was determined from the amounts of radioactivity remaining in adherent tumor cells. Of the untreated macrophages, only those from immunized mice were cytotoxic to the tumor cells; macrophages from normal and tumor-bearing mice became cytotoxic by incubation with supernatants from cultures containing lymphocytes from immunized syngeneic mice, sensitized allogeneic mice, or sensitized rats; and macrophages incubated with supernatants from cultures containing normal nonsensitized allogeneic or xenogeneic lymphocytes showed no cytotoxicity. Thes results suggested that macrophages from tumor-bearing animals are potentially cytotoxic to their syngeneic tumors and can be activated by mediators released from sensitized syngeneic, allogeneic, and/or xenogeneic lymphocytes in vitro.
Effect of Bilateral Atrial Appendectomy on Postprandial Sodium Excretion in Conscious Monkeys (1994)

We have shown that bilateral atrial appendectomy attenuates the increase in atrial natriuretic factor and sodium excretion that occurs after acute blood volume expansion. These findings suggest that the atrial appendages influence renal sodium excretion. The purpose of the present study was to determine whether atrial appendectomy alters the increase in sodium excretion that occurs postprandially. One to two weeks after surgery, conscious monkeys (Macaca fascicularis) were given a meal through a nasogastric tube. The meal consisted of water (20 ml/kg), sodium (2.5 mmol/kg), carbohydrate (2.65 g/kg), protein (0.68 g/kg), and fat (0.89 g/kg). Postprandial changes in renal function were monitored for 210 min after the meal was started. In the sham animals, urine flow increased from 0.23 +/- 0.04 to 0.55 +/- 0.05 ml/min, sodium excretion increased from 28.6 +/- 7.8 to 84.4 +/- 12.3 mumol/min and fractional sodium excretion increased from 1.35 +/- 0.38% to 3.06 +/- 0.43%. Bilateral atrial appendectomy (ATX) significantly attenuated the renal responses to the meal. Urine flow in the ATX animals increased from 0.19 +/- 0.03 to 0.30 +/- 0.02 ml/min, sodium excretion increased from 26.5 +/- 5.8 to 45.8 +/- 15.2 mumol/min, and fractional sodium excretion increased from 0.99 +/- 0.02% to 1.53 +/- 0.34%. Postprandial changes in renal and systemic hemodynamics were also monitored and were similar in both groups. Plasma levels of atrial natriuretic factor were also similar in both groups and did not increase postprandially. These findings demonstrate that bilateral atrial appendectomy attenuates postprandial-induced increases in sodium excretion by mechanisms that do not involve an increase in atrial natriuretic factor.
Introducing a new cache design into vector computers (1993)

Introduces an innovative cache design for vector computers, called prime-mapped cache. By utilizing the special properties of a Mersenne prime, the new design does not increase the critical path length of a processor, nor does it increase the cache access time as compared to existing cache organizations. The prime-mapped cache minimizes cache miss ratio caused by line interferences that have been shown to be critical for numerical applications by previous investigators. With negligibly additional hardware cost, significant performance gains are obtained by adding the proposed cache memory to an existing vector computer. The performance of the design is studied analytically, using a generic vector computation model. The analytical model is validated through extensive simulation experiments. A performance analysis for various vector access patterns shows that the prime-mapped cache performs significantly better than conventional cache organizations in the vector processing environment. The performance gain will increase with the increase of the speed gap between processors and memories.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Activity of aclidinium bromide, a new long‐acting muscarinic antagonist: a phase I study (2010)

Aclidinium produced statistically significant and sustained bronchodilation over 24 h, suggesting long-acting efficacy and providing a rationale for future studies in patients with COPD.
Evaluation of MYBPC3 trans -Splicing and Gene Replacement as Therapeutic Options in Human iPSC-Derived Cardiomyocytes (2017)

Gene therapy is a promising option for severe forms of genetic diseases. We previously provided evidence for the feasibility of trans-splicing, exon skipping, and gene replacement in a mouse model of hypertrophic cardiomyopathy (HCM) carrying a mutation in MYBPC3, encoding cardiac myosin-binding protein C (cMyBP-C). Here we used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from an HCM patient carrying a heterozygous c.1358-1359insC MYBPC3 mutation and from a healthy donor. HCM hiPSC-CMs exhibited ∼50% lower MYBPC3 mRNA and cMyBP-C protein levels than control, no truncated cMyBP-C, larger cell size, and altered gene expression, thus reproducing human HCM features. We evaluated RNA trans-splicing and gene replacement after transducing hiPSC-CMs with adeno-associated virus. trans-splicing with 5' or 3' pre-trans-splicing molecules represented ∼1% of total MYBPC3 transcripts in healthy hiPSC-CMs. In contrast, gene replacement with the full-length MYBPC3 cDNA resulted in ∼2.5-fold higher MYBPC3 mRNA levels in HCM and control hiPSC-CMs. This restored the cMyBP-C level to 81% of the control level, suppressed hypertrophy, and partially restored gene expression to control level in HCM cells. This study provides evidence for (1) the feasibility of trans-splicing, although with low efficiency, and (2) efficient gene replacement in hiPSC-CMs with a MYBPC3 mutation.
Soft Tissue Augmentation Using Silk Gels: An In Vitro and In Vivo Study (2009)

The results indicate that silk-gel material was able to create a lasting three-dimensional soft tissue augmentation and is a promising biomaterial for periodontal and maxillofacial therapies, either as a scaffold for cells or alone as a biomaterial.