gebhart/patrepeval huggingface dataset:
Small Misfolded Tau Species Are Internalized via Bulk Endocytosis and Anterogradely and Retrogradely Transported in Neurons (2012)

The accumulation of Tau into aggregates is associated with key pathological events in frontotemporal lobe degeneration (FTD-Tau) and Alzheimer disease (AD). Recent data have shown that misfolded Tau can be internalized by cells in vitro (Frost, B., Jacks, R. L., and Diamond, M. I. (2009) J. Biol. Chem. 284, 12845-12852) and propagate pathology in vivo (Clavaguera, F., Bolmont, T., Crowther, R. A., Abramowski, D., Frank, S., Probst, A., Fraser, G., Stalder, A. K., Beibel, M., Staufenbiel, M., Jucker, M., Goedert, M., and Tolnay, M. (2009) Nat. Cell Biol. 11, 909-913; Lasagna-Reeves, C. A., Castillo-Carranza, D. L., Sengupta, U., Guerrero-Munoz, M. J., Kiritoshi, T., Neugebauer, V., Jackson, G. R., and Kayed, R. (2012) Sci. Rep. 2, 700). Here we show that recombinant Tau misfolds into low molecular weight (LMW) aggregates prior to assembly into fibrils, and both extracellular LMW Tau aggregates and short fibrils, but not monomers, long fibrils, nor long filaments purified from brain extract are taken up by neurons. Remarkably, misfolded Tau can be internalized at the somatodendritic compartment, or the axon terminals and it can be transported anterogradely, retrogradely, and can enhance tauopathy in vivo. The internalized Tau aggregates co-localize with dextran, a bulk-endocytosis marker, and with the endolysosomal compartments. Our findings demonstrate that exogenous Tau can be taken up by cells, uptake depends on both the conformation and size of the Tau aggregates and once inside cells, Tau can be transported. These data provide support for observations that tauopathy can spread trans-synaptically in vivo, via cell-to-cell transfer.
Cholesterol Reduction Yields Clinical Benefit (1998)

Adding the results from the statin trials confirmed our original conclusion that lowering cholesterol is clinically beneficial. The relationships (slope) between cholesterol lowering and reduction in CHD and total mortality risk became stronger, and the standard error of the estimated slopes decreased by about half. Use of statins does not increase non-CHD mortality risk. The effect of the statins on CHD and total mortality risk can be explained by their lipid-lowering ability and appears to be directly proportional to the degree to which they lower lipids.
Tumor necrosis factor-?: A potentially neurodestructive cytokine produced by glia in the human glaucomatous optic nerve head (2000)

Tumor necrosis factor-alpha (TNF-alpha) mediates a range of cellular responses, which have potentially detrimental consequences that affect multiple cell types. To determine whether TNF-alpha contributes to glaucomatous optic neuropathy, we have studied the expression of this cytokine and its receptor, tumor necrosis factor receptor-1 (TNF- R1), in human glaucomatous optic nerve heads from patients with different stages of disease using double labeling fluorescence immunohistochemistry. We have also investigated the ability of this cytokine to induce nitric oxide synthase (NOS-2) in cultured human optic nerve astrocytes by immunocytochemistry and immunoblot. Normal tissue showed constitutive expression of TNF-R1 in the vasculature of the optic nerve heads but no positive labeling for TNF-alpha. In the glaucomatous optic nerve heads, the expression of both TNF-alpha and TNF-R1 were apparently upregulated, primarily in glial fibrillary acidic protein (GFAP)-positive astrocytes, and appeared to parallel the progression of optic nerve degeneration. In eyes with severe glaucomatous damage, some HLA-DR positive microglia also contained TNF-alpha and TNF-R1. In the most severely damaged optic nerve heads, the axons of the retinal ganglion cells contained TNF-R1 and, therefore, are direct targets for neurodegeneration caused by TNF-alpha. In vitro astrocytes constitutively express TNF-R1 and TNF-alpha stimulation induces expression of NOS-2. We hypothesize that TNF-alpha contributes to the progression of optic nerve degeneration in glaucoma by both a direct effect on the axons of the retinal ganglion cells and by inducing NOS-2 in astrocytes.
<title>Automated layout of mask assist-features for realizing 0.5 k<formula><inf><roman>1</roman></inf></formula> ASIC lithography</title> (1995)

The virtues of mask-plane assist features for improving imaging performance of generic ASIC layouts in the 0.5k<SUB>1</SUB> realm has been previously proclaimed. In this report we provide experimental verification and introduce a methodology to automatically deploy these features on ASIC layouts.
The blending of narrative and argument in the generic texture of newspaper editorials (2000)

This paper is a study in textural mode analysis (TMA). It examines the generic discourse texture of a set of editorials from the London Times and Guardian , on the topic of the British General Election of May 1997. It describes how the texture of the set can be accounted for in terms of just three representational textural modes – narrative, description and argument – and shows how argument predominates in the editorial genre. Toulmin's influential rhetorical model of argumentation, consisting of grounds, claims and warrants, is used and related to the realisation of argument mode through a number of functions, namely hypotheses, predictions, evaluations and assertions. The last of these frequently perform an ideological role in editorial discourse, via unmodalized assertions. The extremely common blending of textural modes by means of linear and layered blending is brought out, particularly through a ‘case study’of one of the editorials.
Viscosity and Electrical Resistivity of Molten Alkali Borates (1953)

The viscosity and electrical resistance of members of the systems Li 2 O–B 2 O 3 , Na 2 O–B 2 O 3 , and K 2 O–B 2 O 3 have been measured in the approximate temperature range 600° to 1000°C. The log viscosity isotherms in the range 700° to 800°C. showed a minimum in the low‐alkali region followed by a maximum as the alkali concentration was increased. This behavior could be explained by postulating an equilibrium between two antithetical effects caused by the addition of alkali oxide to B 2 O 3 . The log electrical resistance isotherms decreased rapidly with increased alkali content up to about five equivalents of alkali ions per liter and decreased less rapidly in a linear fashion with further increase in alkali ion concentration. The equivalent conductance increased with alkali concentration, indicating behavior rather typical of liquids of low dielectric constant. The rate of increase of equivalent conductance was greater in the concentration region where the viscosity was increasing than where the viscosity was decreasing, thus illustrating that viscosity is not a controlling factor in electrical conduction. A plot of log R vs. log gave straight lines whose slopes decreased with alkali content. The hypothesis that electrical resistance and viscosity of each glass were both related to the concentration of weak bonds in that glass was advanced to account for the constancy of the relation between the temperature coefficients of the two properties.
Physiological Changes and Clinical Implications of Syndromic Craniosynostosis (2016)

Syndromic craniosynostosis has severe cranial stenosis and deformity, combined with hypoplastic maxillary bone and other developmental skeletal lesions. Among these various lesions, upper air way obstruction by hypoplastic maxillary bone could be the first life-threatening condition after birth. Aggressive cranial vault expansion for severely deformed cranial vaults due to multiple synostoses is necessary even in infancy, to normalize the intracranial pressure. Fronto-orbital advancement (FOA) is recommended for patients with hypoplastic anterior part of cranium induced by bicoronal and/or metopic synostoses, and posterior cranial vault expansion is recommended for those with flattening of the posterior part of the cranium by lambdoid synostosis. Although sufficient spontaneous reshaping of the cranium can be expected by expansive cranioplasty, keeping the cranial bone flap expanded sufficiently is often difficult when the initial expansion is performed during infancy. So far distraction osteogenesis (DO) is the only method to make it possible and to provide low rates of re-expansion of the cranial vault. DO is quite beneficial for both FOA and posterior cranial vault expansion, compared with the conventional methods. Associated hydrocephalus and chronic tonsillar herniation due to lambdoid synostosis can be surgically treatable. Abnormal venous drainages from the intracranial space and air way obstruction should be always considered at any surgical procedures. Neurosurgeons have to know well about the managements not only of the deformed cranial vault and the associated brain lesions but also of other multiple skeletal lesions associated with syndromic craniosynostosis, to improve treatment outcome.
Instability of the faecal microbiota in diarrhoea-predominant irritable bowel syndrome (2013)

The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder with a largely unknown aetiology and a wide range of symptoms. Most cross-sectional studies carried out so far suggest subtle alterations in the structure of the intestinal microbiota that are barely reproduced, partly because of the high inter-subject variation in the community composition and disorder-specific features. We performed a longitudinal study to explore the within-subject variation in the faecal microbiota in two patients with IBS classified into the diarrhoea subtype and the healthy spouse of one of them. Faecal communities were monitored over 6-8 weeks and analysed through metagenomic and metatranscriptomic approaches. We found a higher temporal instability in the fraction of active microbiota related to the IBS condition and fluctuating symptoms. Strong and quick shifts in the distribution of the active microbiota and changes in the global pattern of gene expression were detected in association with acute diarrhoea, whereas microbial composition and encoded functions were more stable. The specific alterations in the microbiota were barely reproduced within and between patients. Further research is needed to assess whether these changes are a consequence of the abnormal gut function in acute diarrhoeic episodes and the potential usefulness of tackling them.
The choice of prodrugs for gene directed enzyme prodrug therapy of cancer. (1995)

Prodrugs are chemicals that are pharmacodynamically and toxicologically inert but which can be converted to highly active species. In cancer chemotherapy, enzyme activated prodrugs have been effective against certain animal tumours. However, in the clinic it has been found that human tumours containing appropriately high levels of the activating enzymes were rare and not associated with any particular type of tumour. Gene directed enzyme prodrug therapy (GDEPT) attempts to overcome this problem by killing tumour cells by the activation of a prodrug after the gene encoding for an activating enzyme has been targeted to the malignant cell. Here we summarise the various enzyme/prodrug systems that have been proposed for cancer therapy and comment on their suitability for GDEPT. This is because systems developed for other applications such as antibody directed enzyme prodrug therapy (ADEPT) may not be suitable for GDEPT. What is required are nontoxic prodrugs that can be converted intracellularly to highly cytotoxic metabolites that are not cell cycle specific in their mechanism of action. The active drugs released should also be readily diffusible and exert a bystander effect. Alkylating agents best meet these criteria. An example of a suitable enzyme/prodrug system may be a bacterial nitroreductase that can convert a relatively nontoxic monofunctional alkylating agent to a difunctional alkylating agent that is some ten thousand times more cytotoxic.
Anhydrolide Macrolides. 2. Synthesis and Antibacterial Activity of 2,3-Anhydro-6-O-methyl 11,12-Carbazate Erythromycin A Analogues (1998)

A series of 3-descladinosyl-2,3-anhydro-6-O-methylerythromycin A 11,12-cyclic carbazate analogues was prepared and evaluated for antibacterial activity. These 2,3-anhydro macrolides were found to be potent antibacterial agents in vitro against macrolide-susceptible organisms including Staphylococcus aureus 6538P, Streptococcus pyogenes EES61, and Streptococcus pneumoniae ATCC6303. These compounds were also very active against some organisms that show macrolide resistance (S. aureus A5177, S. pyogenes PIU2584, and S. pneumoniae 5649). The compounds generally showed poor activity against organisms with constitutive MLS resistance. Selected compounds were evaluated in vivo in mouse protection studies. Although most of the compounds tested in vivo showed poor efficacy, two compounds, 38 and 57, were more active than clarithromycin against S. pneumoniae ATCC6303.
Contribution of the diethyl phosphonate group to a first approach of calcium-inhibiting activity: study of a series of various substituted 2-phenylbenzothiazoles. (1990)

Eighteen substituted 2-phenyl benzothiazoles, nine of which are new, are described. Pharmacological investigation of these Fostedil analogues did not demonstrate the same calcium inhibitory properties shown by Fostedil. The enhancement induced by the diethyl phosphonate group is confirmed.
A 0.8V 1.52MHz MSVC Relaxation Oscillator with Inverted Mirror Feedback Reference for UHF RFID (2006)

A 0.8V nano-power relaxation oscillator for EPC standard UHF RFID transponder is presented. A low-voltage inverted mirror feedback V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">GS</sub> /R reference is proposed to provide correlated current and voltage references for the oscillator. As a result, the oscillator frequency is solely determined by the resistor in the reference and the timing capacitor to meet the frequency tolerance specification. Meanwhile, to minimize the power consumption, a minimum-supply-voltage-constraint (MSVC) design criterion is proposed to minimize the required supply voltage. The inverted mirror feedback technique reduces the headroom requirement of the traditional V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">GS </sub> /R to meet the MSVC. Measurement results show that the entire oscillator requires a minimum supply voltage of 0.8V in the prototype chip fabricated in CMOS 0.13mum technologies. The measured oscillation frequency is 1.52MHz with 400nA total current consumption. The chip area is 13400mum <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup>
Increased capsaicin receptor TRPV1-expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain (2008)

Increased TRPV1 nerve fibres are observed in IBS, together with a low-grade inflammatory response. The increased TRPV1 nerve fibres may contribute to visceral hypersensitivity and pain in IBS, and provide a novel therapeutic target.
Mutational analysis of a yeast transcriptional terminator. (1989)

We have isolated and mutagenized a DNA fragment from Saccharomyces cerevisiae that specifies mRNA 3' end formation for the convergently transcribed CYC1 and UTR1 genes. An in vivo plasmid supercoiling assay previously showed that this fragment is a transcriptional terminator, and "run-on" assays shown here are consistent with this interpretation. The poly(A) sites in the mRNAs formed by the fragment are the same whether the fragment resides at the native location or at a heterologous location. No single linker substitution abolishes the fragment's activity, whereas certain large, nonoverlapping deletions have strong, deleterious effects. Therefore, the yeast terminator behaves more like rho-dependent bacterial terminators than terminators of higher eukaryotes. That a number of deletions or substitutions have different effects in the two orientations suggests that the fragment contains the sequences of two, unidirectional terminator elements.
Cloning of an isoform of mouse TGF‐β type II receptor gene (1994)

A variant of transforming growth factor-beta type II receptor (TGF-beta RII) cDNA was isolated from a mouse brain cDNA library. The predicted receptor is identical to previously reported mouse TGF-beta RII except that the isoform has an insertion sequence of 25 amino acids in the predicted ligand-binding domain. By the use of reverse transcription-polymerase chain reaction (RT-PCR), transcripts for both isoforms were detected in all tissues and developing embryos examined. The isoform transiently expressed in COS cells showed a similar ligand-binding specificity to authentic TGF-beta RII. These results suggest that the mouse TGF-beta RII gene generates multiple isoforms, possibly by alternative splicing, as reported for activin type IIB receptor; and an isoform which has the extra sequence in the ligand-binding domain is also involved in the TGF-beta signal transduction.
Purification, crystallization and preliminary X-ray crystallographic studies on acetolactate decarboxylase (2003)

Acetolactate decarboxylase has the unique ability to decarboxylate both enantiomers of acetolactate to give a single enantiomer of the decarboxylation product, (R)-acetoin. A gene coding for alpha-acetolactate decarboxylase from Bacillus brevis (ATCC 11031) was cloned and overexpressed in B. subtilis. The enzyme was purified in two steps to homogeneity prior to crystallization. Three different diffraction-quality crystal forms were obtained by the hanging-drop vapour-diffusion method using a number of screening conditions. The best crystal form is suitable for structural studies and was grown from solutions containing 20% PEG 2000 MME, 10 mM cadmium chloride and 0.1 M Tris-HCl pH 7.0. They grew to a maximum dimension of approximately 0.4 mm and belong to the trigonal space group P3(1,2)21, with unit-cell parameters a = 47.0, c = 198.9 A. A complete data set was collected to 2 A from a single native crystal using synchrotron radiation.
Thermal Analysis of Hybrid Circuits with Mounted Components (1988)

In this contribution a linear thermal model for hybrid circuits is presented. Both the heat dissipated in screen printed resistors and in mounted components such as transistors and integrated circuits is taken into account.
Plasma and platelet excitatory amino acids in psychiatric disorders (1993)

Plasma and platelet levels of excitatory amino acids were measured in 38 psychiatric out-patients and in 19 comparison subjects; the patients had DSM-III-R diagnoses of organic mental disorders (N = 3), mood disorders (N = 15), schizophrenia (N = 13), and anxiety disorders (N = 7). The glutamate plasma levels were significantly higher in the patients with mood disorders than in the comparison group.
Glycerol Metabolism in Yeasts (1968)

The utilization of glycerol by Candida utilis has been studied. It has been found that this yeast has a permeability for glycerol and other three carbon compounds much greater than that of baker's yeast. This permeability allows the entrance of glycerol in Candida cells rapidly enough to permit its efficient utilization even at low concentrations. The inducibility of glycerol kinase has been established. An increase in the concentration of the mitochondrial L‐α‐glycerophosphate oxidase when the yeast is grown on glycerol has also been observed. A model is presented for the substrate specificity pattern of glycerol kinase of C. mycoderma . It postulates the involvement of three hydroxyl groups in the spatial distribution corresponding to the formation of L‐α‐glycerophosphate from glycerol. This requirement can be met by aldo‐and ketotrioses in their respective hydrated forms. The pathway of glycerol formation in S. cerevisiae has also been studied. Evidence is shown of the existence of a NADH dependent enzymatic activity reducing triose phosphate to α‐glycerophosphate which can roughly account for the glycerol production. A low ionic strength seems to be required for the activity of this enzyme. The α‐glycerophosphatase is specific for the L from, the efficiency of α‐glycerophosphatase on D‐α‐glycerophosphate being 1/30 of that on L‐α‐glycerophosphate. The concentration of the α‐glycerophosphatase in yeasts is higher when grown on hexoses than when grown on non‐sugar carbon sources.
Ex‐Chiral‐Pool Synthesis of β‐Hydroxyphosphonate Nucleoside Analogues (2006)

Abstract A new series of mononucleotide analogues bearing a nonhydrolysable P–C bond instead of the P–O phosphate linkage is presented. We intend to set up an approach that allows the synthesis of β‐hydroxyphosphonate nucleoside analogues as a single diastereoisomer. In this respect, the key “sugar‐phosphonate” intermediate was obtained through an Arbusov reaction from an iodosugar derivative in which the stereochemistry of the β‐hydroxy group is determined by the choice of the starting material and remains in the resulting nucleotide analogues. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)
Epitopes on proteinase-3 recognized by antibodies from patients with Wegener's granulomatosis. (1994)

The 228 amino acid primary sequence of proteinase-3 (PR3) was studied for antigenic epitopes, which react with IgG Ab in sera of patients with Wegener's granulomatosis, by synthesizing overlapping 7 mers of PR3 linear sequence on pins. Main regions of linear sequence reactivity included GHEAQPH (at residues 4-10), QPHSRPY (8-14), TQEPTQQ (65-71), ATVQLPQ (108-114), QLPQQDQ (111-117), PVPHGTQ (118-124), RVGAHDP (132-138), FCRPHNI (154-160), PRRKAGI (165-171), FGDSGGP (173-179), and IDSFVIW (189-195). All of these regions were surface accessible and seemed to be on the outside of the molecule. By substituting a glycine or an alanine for each residue within each reactive epitope, we identified the arginine at 12, valine at 119, proline at 120, histidine at 121, arginine at 132, alanine at 135, histidine at 136, and glycine at 178 as major immunodominant single residues that contribute to antigenic determinants. Visualization of these reactive regions on a three-dimensional computer-generated carbon PR3 trace diagram showed that one aspect of the molecule on the inferolateral surface comprised most of the antigenic regions. Two peptides, ATVQLPQ and RVGAHDP, when preincubated with Wegener's granulomatosis sera, produced almost complete inhibition of Wegener's granulomatosis IgG Abs either binding to PR3 on the ELISA plate or by reacting with polymorphonuclear leukocyte azurophilic granules in immunofluorescence assays for cANCA. FGDSGGP (at residues 173-179), one epitope that was recognized by Wegener's patient sera Abs, included part of the active catalytic triad for PR3. Rabbit Abs against the PR3 peptides ATVQLPQ or RVGAHDP showed a cANCA cytoplasmic granular pattern of immunofluorescence staining when they were incubated with polymorphonuclear leukocytes. These findings indicate that it is possible to identify various antigenic sites on PR3 by using overlapping 7 mers of portions of the solvent, accessible linear sequence.