gebhart/patrepeval huggingface dataset:
The Structure of Neuritic Plaques in the Cerebral Cortex of Aged Rats (1981)

Discrete patches of spongiform degeneration have been found in the cerebral cortex of three rats, 28 and 30 months of age. Many of these patches have in their midst a central nonvacuolated region containing a star-shaped homogeneous core. Using Congo red stain, there is evidence for the presence of amyloid in this core. In the electron microscope, this central region is seen to be composed of degenerating and abnormal neuronal processes, reactive neuroglia, and extracellular filamentous material with the fine structural characteristics of amyloid. Microglial cells are uniquely modified to accommodate bundles of these extracellular filaments, which are often contained in furrows that deeply invaginate the surfaces of these cells. On the basis of its three main constituents, the central region is considered to be a form of neuritic plaque. The large complex clearings in the vacuolar region of each lesion appear to be formed by the coalescence of smaller vacuoles in the surrounding neuropil.
Renagel®: reducing serum phosphorus in haemodialysis patients (2000)

Approximately half of all dialysis patients experience persistent hyperphosphataemia, which causes significant problems. Renagel is a calcium-free, aluminium-free phosphate binder which reduces serum phosphorus in haemodialysis patients by reducing absorption of dietary phosphorus. This article reviews the management of hyperphosphataemia and presents some Renagel clinical trial data.
Inhibition of the Reverse Transcriptase Activity and Replication of Human Immunodeficiency Virus Type 1 by AS 101 In Vitro (1992)

In a search for compounds active against human immunodeficiency virus type 1 (HIV-1), it was found that the novel low-molecular weight immunoenhancer ammonium trichloro(dioxyethylene-O,O'-) tellurate (AS101) suppresses production of HIV-1 in vitro. Treatment of HIV-1-infected peripheral blood mononuclear cells (PBMC) with increasing concentrations of AS101 resulted in substantial inhibition of virus production as measured by both reverse transcriptase (RT) activity and antigen presence in supernatants of treated cells. AS101 had no effect on PBMC viability, growth, or morphology up to a concentration of 15 microM for 14 days. To elucidate a possible mechanism for the inhibition of AS101, we have analyzed the effect of the drug on the catalytic functions associated with HIV RT, namely the RDDP, DDDP, and RNase H activities. RDDP and DDDP activities were impaired by the drug with calculated IC50 value of about 4 microM. On the other hand, the RNase H activity was less sensitive to AS101, with an apparent IC50 value of about 30 microM. The anti-HIV-1 activity of AS101 as reflected by inhibition of the different catalytic functions associated with viral RT, in the absence of drug-related toxicity to lymphocytes, together with its immunomodulating activity strongly argues in favor of its evaluation, as a therapeutic agent for patients with HIV infection.
Aromatic Plants from Western Cuba. V: Composition of the Leaf Oils ofBaccharis halimifoliaL. andEugenia foetida(Sw.) Willd (2006)

Abstract The chemical composition of the leaf oils of Baccharis halimifolia L. and Eugenia foetida (Sw.) Willd. were studied by GC and GC/MS. Sixty-four compounds of the oil of B. halimifolia were identifed of which β-pinene (11.9%) was the major constituent. In the oil of E. foetida, 75 compounds were identifed of which caryophyllene oxide (14.8%) was the major component.
Polyclonal antibody directed against human RANTES ameliorates disease in the Lewis rat adjuvant-induced arthritis model. (1998)

Adjuvant-induced arthritis (AIA) is one of many animal models of rheumatoid arthritis, a disease characterized by a T-lymphocyte and macrophage cellular infiltrate. We have characterized the development of this disease model with respect to chemokine expression. Increased levels of two chemokines, RANTES, a T-lymphocyte and monocyte chemo-attractant, and KC a chemoattractant for neutrophils, were found in whole blood and in the joint. Surprisingly, levels of MIP-1alpha, another T-lymphocyte and monocyte chemoattractant, were unchanged throughout the course of the disease in whole blood and only slightly elevated in the joint. RANTES expression plays an important role in the disease since a polyclonal antibody to RANTES greatly ameliorated symptoms in animals induced for AIA and was found to be as efficacious as treatment with indomethacin, a non-steroidal anti inflammatory. Polyclonal antibodies to either MIP-1alpha or KC were ineffective. This is the first report to show the importance of RANTES in the development of AIA.
Fluidic self-assembly for the integration of GaAs light-emitting diodes on Si substrates (1994)

The integration of GaAs optoelectronic devices on Si VLSI is important for many high-bandwidth communication applications. In this paper we describe a novel technique for the quasi-monolithic integration of GaAs light-emitting diodes on Si substrates that utilizes fluid transport and shape differentiation for placement and orientation. GaAs light-emitting diodes fabricated into trapezoidal blocks are suspended in a carrier fluid and deposited over holes etched in Si for integration. Top-side ring contact and bottom electrical contact are fabricated on the blocks prior to integration.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Dietary nonprotein calories and cerebral infarction size in rats. (1992)

It may be possible to develop a diet for patients with neurological injuries using noncarbohydrate calorie sources, such as 1,3-butanediol, triacetin, or tributyrin, that would supply systemic caloric and protein requirements without the adverse effect of conventional diets.
Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia (2012)

The identification of new genetic lesions in chronic lymphocytic leukemia (CLL) prompts a comprehensive and dynamic prognostic algorithm including gene mutations and chromosomal abnormalities and their changes during clonal evolution. By integrating mutational and cytogenetic analysis in 1274 CLL samples and using both a training-validation and a time-dependent design, 4 CLL subgroups were hierarchically classified: (1) high-risk, harboring TP53 and/or BIRC3 abnormalities (10-year survival: 29%); (2) intermediate-risk, harboring NOTCH1 and/or SF3B1 mutations and/or del11q22-q23 (10-year survival: 37%); (3) low-risk, harboring +12 or a normal genetics (10-year survival: 57%); and (4) very low-risk, harboring del13q14 only, whose 10-year survival (69.3%) did not significantly differ from a matched general population. This integrated mutational and cytogenetic model independently predicted survival, improved CLL prognostication accuracy compared with FISH karyotype (P < .0001), and was externally validated in an independent CLL cohort. Clonal evolution from lower to higher risk implicated the emergence of NOTCH1, SF3B1, and BIRC3 abnormalities in addition to TP53 and 11q22-q23 lesions. By taking into account clonal evolution through time-dependent analysis, the genetic model maintained its prognostic relevance at any time from diagnosis. These findings may have relevant implications for the design of clinical trials aimed at assessing the use of mutational profiling to inform therapeutic decisions.
Peptides that mimic the carboxy‐terminal domain of SNAP‐25 block acetylcholine release at an Aplysia synapse (1999)

Botulinum neurotoxin serotypes A and E (BoNT/A and BoNT/E) block neurotransmitter release, presumably by cleaving SNAP-25, a protein involved in docking of synaptic vesicles with the presynaptic plasma membrane. Three excitation-secretion uncoupling peptides (ESUPs), which mimic the carboxy-terminal domain of SNAP-25 and span or adjoin the cleavage sites for BoNT/A and BoNT/E, also inhibit transmitter release from permeabilized bovine chromaffin cells. In this study, these peptides were tested for effects on acetylcholine (ACh) release at an identified cholinergic synapse in isolated buccal ganglia of Aplysia californica. The presynaptic neuron was stimulated electrically to elicit action potentials. The postsynaptic neuron was voltage-clamped, and evoked inhibitory postsynaptic currents (IPSCs) were recorded. The ESUPs were pressure-injected into the presynaptic neuron, and their effects on the amplitude of the IPSCs were studied. Acetylcholine release from presynaptic cells, as measured by IPSC amplitudes, was gradually inhibited by the ESUPs. All three peptides caused ca. 40% reduction in IPSC amplitude in 2 h. Random-sequence peptides of the same amino acid composition had no effect. Injection of BoNT/E, in contrast, caused ca. 50% reduction in IPSC amplitude in 30 min and almost complete inhibition in 2 h. These results are the first demonstration that ESUPs block neuronal cholinergic synaptic transmission. They are consistent with the concept that ESUPs compete with the intact SNAP-25 for binding with other fusion proteins, thus inhibiting stimulus-evoked exocytosis of neurotransmitter.
Activation of multiple cancer-associated genes at the ERBB2 amplicon in breast cancer (2006)

During the past decade the role of the ERBB2 (neu/HER2) oncogene as an important predictor of patient outcome and response to various therapies in breast cancer has been clearly established. This association of ERBB2 aberrations with more aggressive disease and poor clinical outcome, together with the high prevalence of such alterations in breast cancer, has also made ERBB2 an attractive target for therapy. A specific antibody-based therapy, Herceptin, directed against the extracellular domain of the ERBB2 receptor tyrosine kinase, was recently developed and several clinical trials have shown the therapeutic efficacy of this drug against ERBB2-positive breast cancer. However, a relatively large fraction of patients does not benefit from Herceptin treatment, indicating that other factors beyond ERBB2 itself must influence therapy response in ERBB2-positive tumors. It is well known that amplification of the 17q12-q21 region is the most common mechanism for ERBB2 activation in breast cancer and that it leads to simultaneous activation of several other genes. These co-amplified and co-activated genes may have an impact on disease progression and the clinical behavior of ERBB2-positive tumors and thus represent important targets of research. In this paper we discuss the current knowledge on the structure of the ERBB2 amplicon, the genes involved, and their possible contribution to breast cancer pathogenesis.
Puzzling Out the Pains in the Gut (2007)

Newly identified mutations and immune cells are clearing up the mysteries of inflammatory bowel diseases and suggesting novel drug targets. (Read more.)
Electrophoretic deposition of textured YBa2Cu3O7−x films on silver substrates (1989)

We have deposited 10–20-μm-thick YBa2Cu3O7−x films by an electrophoretic process on silver substrates in a magnetic field of 8 T. X-ray diffraction patterns of these 2.4-cm-diameter samples show a high degree of c-axis texturing perpendicular to the surface. Their microwave surface resistance Rs was measured at 21.5 GHz in the temperature range from 4.2 to 300 K. It was found to drop sharply at 92.4 K to reach 18±3 mΩ at 77 K and less than 3 mΩ at 4.2 K. These first results exceed the values obtained from bulk samples and untextured thick films, and are lower than Rs of pure copper at the same frequency and temperature. The electrophoretic deposition technique is applicable to large substrates of nonplanar geometry and is therefore suitable for applications of high-Tc superconductors in the field of microwave technology.
Measurement of Dicumarol-Sensitive NADPH:(Menadione–Cytochrome c) Oxidoreductase Activity Results in an Artifactual Assay of DT-Diaphorase in Cell Sonicates (1997)

Purified DT-diaphorase can be assayed as either dicumarol-inhibitable NAD(P)H:menadione oxidoreductase or dicumarol-inhibitable NAD(P)H:dichlorophenolindophenol reductase. Both of these methods have been utilized to assay DT-diaphorase activity in tissue and cell homogenates. When DT-diaphorase activity was measured as dicumarol-inhibitable NADPH:dichlorophenolindophenol reductase in sonicates of two cell lines previously shown to not have any measurable activity of this enzyme, no enzymatic activity was detected. However, when the water-soluble bisulfite addition product of menadione was used as the electron acceptor, an artifactual activity for DT-diaphorase was detected in these cell lines. When another cell line was assayed utilizing menadione bisulfite, an apparent activity of about three times that found with dichlorophenolindophenol was measured, and thus, may overestimate DT-diaphorase activity in cells having activity. When menadione was used in place of menadione bisulfite, an artifactual DT-diaphorase activity was also detected, but was about one-half that obtained with menadione bisulfite. Polarographic determinations of the midpoint potentials for menadione and menadione bisulfite indicated that the latter compound was easier to reduce and may account for the greater apparent DT-diaphorase activity measured with this compound.
ADAMs in cancer cell proliferation and progression (2007)

A disintegrin and metalloproteinases (ADAMs) are a new gene family of proteins with sequence similarity to the reprolysin family of snake venomases that share the metalloproteinase domain with matrix metalloproteinases (MMPs). They are structurally classified into two groups: the membrane-anchored ADAM and ADAM with thrombospondin motifs (ADAMTS). These molecules are involved in various biological events such as cell adhesion, cell fusion, cell migration, membrane protein shedding and proteolysis. Studies on the biochemical characteristics and biological functions of ADAMs are in progress, and accumulated lines of evidence have shown that some ADAMs are expressed in malignant tumors and participate in the pathology of cancers. The activities of ADAMs are regulated by gene expression, intracytoplasmic and pericellular regulation, activation of the zymogens and inhibition of activities by inhibitors. Many ADAM species, including ADAM8, ADAM9, ADAM10, ADAM12, ADAM15, ADAM17, ADAM19, ADAM28, ADAMTS1, ADAMTS4 and ADAMTS5, are expressed in human malignant tumors. Many of them are involved in the regulation of growth factor activities and integrin functions, leading to promotion of cell growth and invasion, although the precise mechanisms of these are not clear at the present time. In this article, we review recent information about ADAM family members and their implications for cancer cell proliferation and progression.
Aprotinin and aprotinin analogues expressed in yeast. (1990)

Synthetic genes encoding aprotinin and aprotinin analogues were constructed and fused in frame to the S. cerevisiae mating factor alpha 1 signal-leader (1-85) sequence. Expression in yeast resulted in secretion into the culture medium of a moderate yield of correctly processed aprotinin (1-58) together with two N-terminally extended forms. Des-Arg1, Pro2-aprotinin was expressed in a higher yield. In this case only the correct N-terminal amino acid sequence was found. Substitution of Ser42 for Arg42 in the potential internal KEX2 processing site improved the secretion yield. The aprotinins are characterized by an inhibition profile similar to that of native aprotinin. Des-Arg1, Pro2-[Arg15, Ser42] aprotinin has a strongly increased plasma kallikrein inhibition profile.
Fluorescence in situ hybridization with Alu and L1 polymerase chain reaction probes for rapid characterization of human chromosomes in hybrid cell lines. (1990)

Human-rodent hybrid cell lines have been analyzed with regard to their human DNA content by using various DNA probe sets, derived from the hybrids, for in situ hybridization to normal human metaphase chromosome spreads. Total genomic hybrid DNA was compared with probe sets of hybrid DNA that were highly enriched in human sequences. The latter probes were obtained by amplification through the polymerase chain reaction (PCR) using oligonucleotide primers directed to human specific subsequences of the interspersed repetitive sequences Alu and L1. Previously unidentified chromosomal material within hybrid lines was characterized with speed and precision. It is demonstrated that the complete human complement of hybrid lines can be rapidly assessed by comparing the data obtained with the Alu-PCR products with the results from the L1-PCR products or from the genomic hybrid DNA. This approach using interspersed repetitive sequence-PCR products is simple and fast and also provides an alternative way of generating complex DNA probe sets for the specific delineation of entire chromosomes or subchromosomal regions by in situ hybridization.
Amyloid in skin and brain: What′s the link? (2010)

For too long, amyloids have been under general suspicion to merely cause diseases. In recent years, we have learned that these interesting proteins may also fulfill important biological tasks. Moreover, recent publications show emerging evidence for a so-called brain-skin axis. This viewpoint paper aims to address the question what is known about the link between brain and skin based on the literature available for two diseases caused by amyloid formation: Alzheimer's disease (AD) and cutaneous amyloidoses. In addition, we acquaint the reader with a different perspective on the role of amyloid in skin and brain.
Secondary ion mass spectrometry sensitivity factors versus ionization potential and electron affinity for many elements in HgCdTe and CdTe using oxygen and cesium ion beams (1988)

We implanted ions of 45 elements into HgCdTe, and into CdTe in some cases, at a variety of energies and fluences, and successfully measured the resulting depth distributions for 43 of them using oxygen and cesium primary ion beams and positive and negative secondary ion mass spectrometry (SIMS), respectively. Relative sensitivity factors for SIMS were determined for these elements in HgCdTe and CdTe using the known implantation fluences. The SIMS relative sensitivity factor is proportional to the inverse of the relative ion yield. We have plotted the results from oxygen SIMS and positive ions versus ionization potential (I), and from cesium SIMS and negative ions versus electron affinity (A) of the implanted elements. These data can be used to test models and theories about the dependence of positive and negative ion yield on I and A. Many of the data from oxygen SIMS for elements with ionization potential between 5 and 10 eV are consistent with the model of positive ion yield dependence on exp(−I), but some elements differ reproducibly and consistently from that model. Elements with ionization potential less than 5 eV and greater than 10 eV follow different dependencies. The data from Cs SIMS tend to fit the model of negative ion yield proportional to exp(+A), but no consistent single curve can be drawn through the data. The data for CdTe agree with those for HgCdTe within experimental error.
X‐Ray Diffraction (2012)

X-ray diffraction is an analytical technique that reveals the crystallographic structure of materials, especially thin films. In this chapter, we introduce X-rays and X-ray diffraction, and we present the general set up for the collection of X-ray diffraction data. Because X-ray diffraction yields the atomic structure of a material, it is also called characteristic X-ray. We present the X-ray tube and the synchrotron radiator as the two general types of X-ray source. We introduce small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS), which belong to a family of X-ray scattering techniques used in the characterization of materials. X-ray scattering is a universal tool for exploring the structure of matter. We present the use of X-ray scattering to characterize protein composite films. SAXS and WAXS are used to determine the orientation and molecular spacing of thin films.
ATP-DEPENDENT TRANSPORT SYSTEMS IN BACTERIA AND HUMANS: Relevance to Cystic Fibrosis and Multidrug Resistance (1993)

The prokaryotic permeases are members of a superfamily of membrane transporters called traffic ATPases, which includes the medically important eukaryotic multidrug resistance (MDR) protein and cystic fibrosis transmembrane regulator (CFTR). Members of this superfamily have extensive sequence and structural similarity, in particular in an ATP-binding motif, and are believed to use ATP to energize translocation of substrates across biological membranes. The prokaryotic histidine permease is well-characterized and serves as a convenient model system. In this review, we highlight some of the biochemical and molecular biological approaches used to study the functional and architectural organization of this permease and relate the results of these approaches to what is known about other traffic ATPases. We have identified specific regions that we believe critical for the function of the histidine permease and propose that the corresponding regions in the eukaryotic traffic ATPases are also important for their function. In light of the fact that CFTR (and possibly the MDR protein) is an ion channel, we compare the properties of channels and transporters; in addition, we discuss the possibility that other members of the traffic ATPases may also have channel-like activity.
Cartilage development and degeneration: a Wnt Wnt situation (2012)

The Wnt signaling pathway plays a crucial role in the development and homeostasis of a variety of adult tissues and, as such, is emerging as an important therapeutic target for numerous diseases. Factors involved in the Wnt pathway are expressed throughout limb development and chondrogenesis and have been shown to be critical in joint homeostasis and endochondral ossification. Therefore, in this review, we discuss Wnt regulation of chondrogenic differentiation, hypertrophy and cartilage function. Moreover, we detail the role of the Wnt signaling pathway in cartilage degeneration and its potential to act as a target for therapy in osteoarthritis.
A novel suicide inhibitor strategy for antiparasitic drug development (1991)

DL-alpha-Difluoromethylornithine (DFMO), a suicide inhibitor of eukaryotic ornithine decarboxylase (ODC), has therapeutic activities against African trypanosomiasis. The Ki value of DFMO for ODC of Trypanosoma brucei is somewhat higher than that for mouse ODC. The therapeutic efficacy of DFMO cannot therefore be attributed to a preferential inhibition of the parasite enzyme. The T. brucei gene encoding ODC was cloned and sequenced, and the derived amino acid sequence has 61.5% homology with that of mouse ODC, except that the C-terminal 36 amino acids of the mouse enzyme are missing from the parasite enzyme. The cloned T. brucei and mouse ODC genes were expressed in ODC-deficient Chinese hamster ovary cells (CHO) where the T. brucei enzyme was stable, but mouse ODC was unstable. Thus, the observed difference in intracellular stability is a property of the ODC protein itself, rather than of the cellular environment in which it is expressed. A chimeric ODC composed of the amino terminus of trypanosome ODC and the C-terminus of mouse ODC also was rapidly degraded in CHO cells, suggesting that peptide sequences in the mouse ODC carboxy-terminus determine its stability. The relatively slow turnover of the parasite enzyme constitutes the basis of selective antitrypanosomal action of DFMO. By this same token, many other proteins known to perform crucial functions in bacteria, fungi, protozoa, helminths, etc., also may have shorter half-lives in the mammalian hosts than in parasites. Suicide inhibitors of these proteins may have desirable characteristics as good chemotherapeutic agents. This new approach could provide an additional strategy for controlling infectious diseases.