gebhart/patrepeval huggingface dataset:
8 Antibiotics and the RNA World: A Role for Low-molecular-weight Effectors in Biochemical Evolution? (1993)

There is much more to molecular and cell biology than DNA, RNA, and proteins! A very large number of secondary metabolites produced by microbes and plants have been identified; these natural products include some of the most potent inhibitors of cellular metabolic reactions. The best-known inhibitors are antibiotics, used in the therapy of infectious disease, which have a number of cellular targets. Not surprisingly, antibiotics may interact with different macromolecules to inhibit cellular processes. The protein synthesis inhibitors have been studied for many years, beginning with the pioneering work of the laboratory of E.F. Gale in Cambridge on the inhibition of bacterial cells, which could be interpreted as translation inhibition. The development of cell-free polypeptide synthesis in the early 1960s permitted the testing of many putative protein synthesis inhibitors. Probably the first conclusive experiments to focus on cellular targets for translation inhibitors were those of Erdos and Ullmann (1959) with streptomycin. Subsequently, the use of fractionated cell-free extracts with separated ribosomal subunits allowed the identification of many antibiotics as specific inhibitors of ribosome function. Within a few years, the mechanism of action of most inhibitors of translation had been worked out in general terms, although not in any great detail at the chemical level. An important concept, first elaborated by Vazquez (1964), was the species specificity of the interaction between inhibitors of protein synthesis and their targets (for an excellent review, see Cundliffe 1981). The narrow range of activity of many of these compounds is well known and is critical...
Enzymatic degradation of polar lipids in Vigna unguiculata leaves and influence of drought stress (1998)

14 C‐labelled polar lipids (monogalactosyl‐diacylglycerol [MGDG], digalactosyl‐diacylglycerol [DGDG], phosphatidylcholine [PC] and phosphatidylglycerol [PG]), purified from Vigna unguiculata leaves, were used as substrates to study the lipolytic activities of Vigna unguiculata leaf extracts. Analysis of the radioactive degradation products revealed the presence of at least three enzyme activities contributing to the hydrolysis of the four main leaf membrane lipids: Lipolytic acyl hydrolase (LAH) activities responsible for the deacylation of galactolipids and phospholipids, phospholipase D (PLD, EC 3.1.4.4) activity which gives rise to phosphatidic acid, and as suggested by the presence of diacylglycerols in minor quantities after phospholipid hydrolysis, phosphatidate phosphohydrolase (PAP, EC 3.1.3.4) and/or phospholipase C (PLC, EC 3.1.4.3.) activity. Under the conditions described in the present paper, the presence of phospholipase A (PLA 1 , EC 3.1.1.3 and PLA 2 , EC 3.1.1.4) activities remains hypothetical, due to the absence of lysophospholipids. LAH and PLD were partially soluble and partially associated with the membranes. When Vigna unguiculata plants were submitted to drought, the enzymatic degradation of galactolipids and phospholipids increased. The stimulation of lipolytic activities was greater in the drought‐sensitive cultivar of Vigna unguiculata (cv. 1183) than in the drought‐tolerant (cv. EPACE‐1) one. In cv. 1183, MGDG‐ and DGDG‐LAH activities in the membrane fractions were dramatically stimulated at a rather moderate water deficit (−0.75 MPa). A sharp increase in membrane phospholipolytic activities was also observed at mild drought stress (−1.2 MPa). In contrast, in cv. EPACE‐1, the stimulation of lipolytic activities was less drastic and occurred at lower leaf water potentials (below −1.2 MPa for galactolipases, and below −1.4 MPa for phospholipases). Our results confirm the presence in leaves of higher plants of a very active LAH acting on galactolipids, whereas PLD is the main enzyme responsible for the degradation of phospholipids, particularly when plants are submitted to drought stress. The differences in stimulation of lipolytic activities between the two Vigna cultivars was in accordance with the different levels of membrane lipid degradation shown previously and could explain their different capacity to sustain drought.
Strains of CHO-K1 cells resistant to Pseudomonas exotoxin A and cross-resistant to diphtheria toxin and viruses (1983)

We have investigated two phenotypically distinct types of mutants of CHO-K1 cells that are resistant to Pseudomonas exotoxin A due to a defect in the delivery of active toxin to the target site in the cell, elongation factor 2. Both types contain normal levels of toxin-sensitive elongation factor-2. Hybridization studies have shown that these cells fall into two distinct complementation groups. One group, designated DPVr, is resistant to Pseudomonas toxin, diphtheria toxin, and four enveloped RNA viruses. This group is also hypersensitive to ricin. The resistance of this group is apparently related to a defect in a mechanism for the acidification of endocytic vesicles. The other group, designated PVr, is resistant to Pseudomonas toxin and to three enveloped RNA viruses. The resistance of this group appears to be related to a defect in a cellular mechanism required for the maturation of Sindbis virus that is likewise required for the entry of active Pseudomonas toxin.
Potential neuroleptic agents. 3. Chemistry and antidopaminergic properties of substituted 6-methoxysalicylamides (1985)

A series of substituted 6-methoxysalicylamides were synthesized from their corresponding 2,6-dimethoxybenzamides by demethylation of one methoxy group with boron tribromide. Substituted 6-methoxysalicylamides having a lipophilic aromatic substituent in the 3-position para with respect to the methoxy group, e.g. a bromo or an iodo atom or an ethyl or a propyl group, and having an (S)-N-(1-alkyl-2-pyrrolidinyl)methyl moiety as the side chain were found to be potent blockers of [3H]spiperone binding in vitro and potent inhibitors of the apomorphine syndrome in the rat. Similar to remoxipride but in contrast to haloperidol, some of the substituted salicylamides show a 10-20-fold separation between the dose that inhibits hyperactivity and that which inhibits stereotypy. It was concluded that, besides the requirement of a lipophilic substituent in the position para to the methoxy group for antidopamine activity in vivo, the formation of a coplanar six-membered pseudoring involving the amide moiety and the methoxy group is a structural requirement for activity in vitro.
Bonding of Amalgam Filling to Tooth Cavity with Adhesive Resin (1986)

The effects of some adhesives on the bonding of amalgam filling to tooth substance were studied. The bonding agents were 4-META resin with adhesive ability derived from the acid anhydride functional group and PANAVIA EX, a composite type adhesive. The sealing and the bonding effects were measured using the dye penetration and shear tests. Both of the adhesive materials had an excellent ability to seal the leakage between the amalgam and the tooth substance.
Neuromorphic vision chip fabricated using three-dimensional integration technology (2002)

Information processing in the human brain is based on advanced parallel processing with a large number of memories and interconnections. To achieve such highly advanced parallel processing, the human brain has modules with layered structures, that is, three-dimensional structures as basic processing units. The human retina and visual cortex also have layered structures with various kinds of cells. The three-dimensional (3D) integration technology reported here achieves an image processing and pattern recognition system with parts of functions of the retina and visual cortex using silicon.
High-content siRNA screening (2007)

Very recent developments in instrumentation and image analysis have made microscopy applicable to high-throughput screening (HTS). For 'High-Content Screening' modern automated microscopy systems provide a throughput of up to 100,000 (confocal) images, with amazingly high resolution, of cells fluorescently stained using multiple colours that are imaged simultaneously during the screen. Image analysis tools provide multi-parametric pattern extraction and quantification on-the-fly. Big pharmaceutical companies have presented image-based screens of more than 100,000 compounds, while academia has published data on large RNA interference screens for functional genomics. Numerous whole-genome sequencing projects have been completed and published. Gene annotation is still in flux. Nevertheless, about 23,000 human genes have been reliably annotated. Additionally, gene expression array technologies and proteomics have added further data on molecules present in cells and tissues. The major challenge of the present and future is to unravel the detailed function of all these gene products and their interaction. One way to gain insight, is to design oligonucleotides that induce lack-of-function phenotypes by specifically inhibiting protein production.
Decline in skeletal muscle mitochondrial function with aging in humans (2005)

Cumulative mtDNA damage occurs in aging animals, and mtDNA mutations are reported to accelerate aging in mice. We determined whether aging results in increased DNA oxidative damage and reduced mtDNA abundance and mitochondrial function in skeletal muscle of human subjects. Studies performed in 146 healthy men and women aged 18-89 yr demonstrated that mtDNA and mRNA abundance and mitochondrial ATP production all declined with advancing age. Abundance of mtDNA was positively related to mitochondrial ATP production rate, which in turn, was closely associated with aerobic capacity and glucose tolerance. The content of several mitochondrial proteins was reduced in older muscles, whereas the level of the oxidative DNA lesion, 8-oxo-deoxyguanosine, was increased, supporting the oxidative damage theory of aging. These results demonstrate that age-related muscle mitochondrial dysfunction is related to reduced mtDNA and muscle functional changes that are common in the elderly.
Detection of the PAX8-PPARγ Fusion Oncogene in Both Follicular Thyroid Carcinomas and Adenomas (2003)

Chromosomal translocations encoding fusion oncoproteins are common in hematological malignancies, sarcomas, and papillary thyroid carcinomas. A recent study of follicular thyroid carcinomas reported a novel chromosomal translocation, t(2;3)(q13;p25), that fused the thyroid-specific transcription factor PAX8 with a nuclear receptor, peroxisome proliferator-activated receptor gamma (PPAR gamma). Herein we report the detection of this putative oncoprotein in 6 of 17 (35%) follicular thyroid carcinomas as well as in 6 of 11 (55%) follicular thyroid adenomas. Concordant expression of protein was found in 91% of those tumors in which PAX8-PPAR gamma mRNA was detected by RT-PCR, whereas a further 20% of follicular tumors were positive for PPAR gamma immunohistochemistry alone. Our findings suggest that the PAX8-PPAR gamma fusion protein promotes differentiated follicular thyroid neoplasia, although it is not sufficient per se for carcinogenesis.
Abstract 1483: MT-3724, an engineered toxin body targeting CD20 for non-Hodgkin's lymphoma (2016)

Abstract Molecular Templates has developed engineered toxin bodies (ETBs), potent recombinant immunotoxins that combine the specificity of an antibody fragment with the powerful direct cytotoxicity of the Shiga-like toxin A subunit to specifically destroy target expressing cells. The use of other immunotoxins and antibody-drug conjugates is limited to targets with tumor-specific cell surface expression that efficiently internalize. The ETB scaffold has been designed to overcome this limitation and promote forced internalization of ETBs, a property that expands the potential targets to receptors with poor internalization kinetics. An additional benefit to ETBs is the mechanism of action (MOA) which is unique to that of other oncology treatments. CD20, a receptor that does not undergo rapid internalization, is a well characterized target for agents used to treat non-Hodgkin's lymphoma (NHL). Thus, successful CD20-targeted clinical strategies include monoclonal antibodies (mAbs) and radiolabeled mAbs that act on the cell surface. Molecular Templates’ lead compound, MT-3724, is a CD20-targeted ETB that has been engineered to force the rapid internalization of the immunotoxin after binding to CD20. MT-3724 has potent direct cell kill activity on CD20 positive lymphoma cells and is the first immunotoxin to CD20 to enter the clinic. The on-going phase I study being conducted at Memorial Sloan-Kettering Cancer Center, MD Anderson Cancer Center, and New York University Langone Medical Center has shown promising safety and efficacy in highly refractory NHL patients. Once MT-3724 is delivered to appropriate cells, the Shiga toxin A subunit inhibits protein synthesis and promotes apoptosis of tumor cells. The difference in MOA allows for activity in the refractory setting, where resistance to other treatments has emerged, and may also allow for combination therapy. Pre-clinical studies with immunomodulatory drugs (IMiDs), PI3K and Bcl-2 inhibitors that are used in treatment of NHL have shown promising results when combined with MT-3724. MT-3724 is a promising novel agent in the treatment of NHL and other CD20 positive hematological malignancies. Data around the internalization kinetics, enzymatic activity, and combination with other agents will be presented. Citation Format: Garrett L. Robinson, Sangeetha Rajagopalan, Brigitte Brieschke, Jennifer Erdman, Jane Neill, Rodney E. Flores-Lefranc, Julia Foree, William Null, Jensing Liu, Jack P. Higgins, Erin K. Willert. MT-3724, an engineered toxin body targeting CD20 for non-Hodgkin's lymphoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1483.
De Novo Formation of Adipose Tissue by Controlled Release of Basic Fibroblast Growth Factor (2000)

De novo adipogenesis at the implanted site of a basement membrane extract (Matrigel) was induced through controlled release of basic fibroblast growth factor (bFGF). bFGF was incorporated into biodegradable gelatin microspheres for its controlled release. When the mixture of Matrigel and bFGF-incorporated gelatin microspheres was implanted subcutaneously into the back of mice, a clearly visible fat pad was formed at the implanted site 6 weeks later. Histologic examination revealed that the de novo formation of adipose tissue accompanied with angiogenesis was observed in the implanted Matrigel at bFGF doses of 0.01, 0.1, and 1 microg/site, the lower and higher doses being less effective. The de novo formation induced by the bFGF-incorporated microspheres was significantly higher than that induced by free bFGF of the same dose. The mRNA of a lipogenesis marker protein, glycerophosphate dehydrogenase, was detected in the formed adipose tissues, biochemically indicating de novo adipogenesis. Free bFGF, the bFGF-incorporated gelatin microspheres, or Marigel alone and bFGF-free gelatin microspheres with or without Matrigel did not induce formation of adipose tissue. This de novo adipogenesis by mixture of Matrigel and the bFGF-incorporated gelatin microspheres will provide a new idea for tissue engineering of adipose tissue.
New Monoclonal Antibodies to Mesothelin Useful for Immunohistochemistry, Fluorescence-Activated Cell Sorting, Western Blotting, and ELISA (2005)

Our two newly established MAbs, MN and MB, have different and useful properties compared with current antibodies used for the detection of mesothelin by immunohistochemistry, fluorescence-activated cell sorting, ELISA, and Western blotting.
Computational Intelligence for Movement Sciences (2006)

Recent years have seen many new developments in computational intelligence (CI) techniques and, consequently, this has led to an exponential increase in the number of applications in a variety of areas, including: engineering, finance, social and biomedical. In particular, CI techniques are increasingly being used in biomedical and human movement areas because of the complexity of the biological systems, as well as the limitations of the existing quantitative techniques in modelling. Computational Intelligence for Movement Sciences: Neural Networks and Other Emerging Techniques contains information regarding state-of-the-art research outcomes and cutting-edge technology from leading scientists and researchers working on various aspects of the human movement. Readers of this book will gain an insight into this field, as well as access to pertinent information, which they will be able to use for continuing research in this area.
Local Expression of Bovine Decorin by Cell-Mediated Gene Transfer Reduces Neointimal Formation After Balloon Injury in Rats (2000)

Decorin is an extracellular matrix (ECM) proteoglycan that may modify vascular smooth muscle cell (SMC) function by altering the response to growth factors and the accumulation of ECM proteins during vascular injury. To investigate these possibilities in vivo, decorin was overexpressed at the site of arterial injury by cell-mediated gene transfer. Fischer rat SMCs were transduced in vitro with a retroviral construct that contained the bovine decorin gene and were subsequently seeded into injured rat carotid arteries. A species-specific antibody to bovine decorin and polymerase chain reaction primers were used to detect bovine decorin and distinguish it from endogenous rat decorin. Immunohistochemical and Northern analyses of rat carotid arteries revealed only low levels of rat decorin expression up to 8 weeks after balloon injury. However, after cell-mediated transfer of bovine decorin, strong expression of bovine decorin was verified by immunohistochemistry and reverse transcriptase-polymerase chain reaction. Four weeks after injury, the intimal area in vessels seeded with bovine decorin-overexpressing SMCs was significantly reduced by 35+/-4% (mean+/-SEM, n=9; P<0.01). Decorin overexpression also induced a higher intimal nuclear density and decreased volume of ECM. Specifically, immunostaining for versican and fibronectin was markedly reduced. In contrast, immunostaining for collagen type I was increased, and electron microscopy confirmed that collagen accumulation was altered. Bromodeoxyuridine labeling indicated that intimal SMC proliferation was not affected by the expression of bovine decorin. In summary, we demonstrate that gene transfer of the ECM proteoglycan, decorin, into the injured arterial wall reduces intimal ECM volume and alters the composition of the ECM.
Evaluierung von alginatverkapselten Endostatin sezernierenden Stammzellen zur Behandlung des Glioblastoms (2005)

Despite aggressive
 therapy consisting of surgery, post-operative radiation and chemotherapy, the
 prognosis for glioblastoma patients is extremely poor with a
 median survival of 12-14 months. During this time, diffuse-infiltration
 allows the tumour to recur, thereby necessitating repeated excision.
 In this present study, an
 ex-vivo-gene therapy of glioblastoma multiforme using alginate
 encapsulated human mesenchymal stem cells which release endostatin was
 developed and evaluated. This therapeutic protein is a potent angiogenesis
 inhibitor, a factor indispensable in tumour growth. It is intended to place
 the microcapsules post surgically in the resection area in order to inhibit
 the renewed recruitment of blood vessels. The advantages of the intracraniell
 implantation are to bypass the blood-brain-barrier and to achieve high
 concentrations of endostatin. Alginate, which is used for
 encapsulation, is proven to be non-immunogenic. It can therefore
 remain without problem in the brain tissue. Important
 advantages of endostatin are the lack of drug resistance and
 the very low mutation rate of endothelial cells. This is
 because they are homogenous and genetically stable. In contrast, tumour
 cells, as a result of constant changes in their genome, present a rapidely
 moving target while treating them with chemotherapeutic agents. In order to examine the
 efficiency of the angiogenesis inhibitor, syngene glioma cells and endostatin
 secreting CellBeads® were implanted intracranially in
 immunocompetent BDIX-rats. The control group received only glioma cells. The
 results showed that endostatin greatly reduced tumour growth and the
 median survival time was prolonged by almost 100 %.
 Further studies need to
 establish, how long the CellBeads® remain intact thereby retaining
 their ability to encapsulate endostatin producing cells.
Common Skin Disorders and Their Topical Treatment (2002)

I. INTRODUCTION Dermatologists have the advantage over other clinicians in that their patients present with diseases that are usually visible and accessible. This means that the majority of skin diseases may be treated topically with treatment delivered directly to the desired site of action, thereby avoiding, or at least we hope attenuating, the potential for systemic side effects. Systemic treatment may be needed if the skin disease is severe, recalcitrant, or fails to respond to topical therapy. The aim of this chapter is to provide a brief synopsis of common skin disorders and their current topical treatment for nonspecialists. A glossary of common dermatological terms has been included at the end of this chapter (see Sec. XII).
A Kringle-Specific Monoclonal Antibody (1994)

Kringle domains are found in several plasma proteins of blood coagulation and fibrinolysis. A murine monoclonal antibody, designated alpha HII-5, was produced against a synthetic peptide representing residues 216-231 of human prothrombin kringle 2. The sequence of the hexadecapeptide (Glu-Asn-Phe-Cys-Arg-Asn-Pro-Asp-Gly-Asp-Glu-Glu-Gly-Val-Gly-Cys) is conserved in several kringle-containing proteins, represents a predicted region of high local hydrophilicity in prothrombin kringle 2, and contains the anionic (Asp-223 and Asp-225) residues that contribute to lysine binding by plasminogen kringle 4. In a solution-phase immunoassay, antibody alpha HII-5 bound prothrombin and the kringle 5 light chain fragment of plasminogen (miniplasminogen), but not plasminogen or plasmin. In contrast, using a solid-phase assay with antigen immobilized onto a surface (polystyrene microtiter plates, glass, or nitrocellulose) antibody alpha HII-5 specifically bound prothrombin, plasminogen, recombinant tissue plasminogen activator (tPA), and the apo(a) subunit of lipoprotein(a). By immunoblotting analysis antibody alpha HII-5 bound determinants on prothrombin fragment 2 and plasminogen kringle 5. These observations suggest that a subset of kringle domains on plasma proteins, including prothrombin kringle 2 and plasminogen kringle 5, contains a homologous antigenic determinant in the region of the kringle lysine-binding site. In contrast to prothrombin kringle 2, the homologous peptide site on plasminogen is not available for antibody binding except when plasminogen is adsorbed to a nonphysiological surface, or when kringles 1-4 are removed.
Parallel mining of association rules (1996)

We consider the problem of mining association rules on a shared nothing multiprocessor. We present three algorithms that explore a spectrum of trade-offs between computation, communication, memory usage, synchronization, and the use of problem specific information. The best algorithm exhibits near perfect scaleup behavior, yet requires only minimal overhead compared to the current best serial algorithm.