gebhart/patrepeval huggingface dataset:
Non-clinical evaluation of JR-051 as a biosimilar to agalsidase beta for the treatment of Fabry disease (2018)

Fabry disease (FD) is an X-linked lysosomal storage disease. It is caused by deficiency of the enzyme α-galactosidase A (α-Gal A), which leads to excessive deposition of neutral glycosphingolipids, especially globotriaosylceramide (GL-3), in cells throughout the body. Progressive accumulation of GL-3 causes life-threatening complications in several tissues and organs, including the vasculature, heart, and kidney. Currently available enzyme replacement therapy for FD employs recombinant α-Gal A in two formulations, namely agalsidase alfa and agalsidase beta. Here, we evaluated JR-051 as a biosimilar to agalsidase beta in a non-clinical study. JR-051 was shown to have identical primary and similar higher-order structures to agalsidase beta. Mannose-6-phosphate content was higher in JR-051 than in agalsidase beta, which probably accounts for a slightly better uptake into fibroblasts in vitro. In spite of these differences in in vitro biological features, pharmacokinetic profiles of the two compounds in mice, rats, and monkeys were similar. The ability to reduce GL-3 accumulation in the kidney, heart, skin, liver, spleen, and plasma of Gla-knockout mice, a model of FD, was not different between JR-051 and agalsidase beta. Furthermore, we identified no safety concerns regarding JR-051 in a 13-week evaluation using cynomolgus monkeys. These findings indicate that JR-051 is similar to agalsidase beta in terms of physicochemical and biological properties.
Salicylic Acid Induction–Deficient Mutants of Arabidopsis Express <i>PR-2</i> and <i>PR-5</i> and Accumulate High Levels of Camalexin after Pathogen Inoculation (1999)

In Arabidopsis, systemic acquired resistance against pathogens has been associated with the accumulation of salicylic acid (SA) and the expression of the pathogenesis-related proteins PR-1, PR-2, and PR-5. We report here the isolation of two nonallelic mutants impaired in the pathway leading to SA biosynthesis. These SA induction-deficient (sid) mutants do not accumulate SA after pathogen inoculation and are more susceptible to both virulent and avirulent forms of Pseudomonas syringae and Peronospora parasitica. However, sid mutants are not as susceptible to these pathogens as are transgenic plants expressing the nahG gene encoding an SA hydroxylase that degrades SA to catechol. In contrast to NahG plants, only the expression of PR-1 is strongly reduced in sid mutants, whereas PR-2 and PR-5 are still expressed after pathogen attack. Furthermore, the accumulation of the phytoalexin camalexin is normal. These results indicate that SA-independent compensation pathways that do not operate in NahG plants are active in sid mutants. One of the mutants is allelic to eds5 (for enhanced disease susceptibility), whereas the other mutant has not been described previously.
Development of the Pancreas and Related Structures (2018)

The pancreas functions as both an exocrine secretory organ and an endocrine organ. The cell types responsible for these distinct functions are derived from a common pancreas progenitor cell. The signals, both inductive and permissive, that direct the differentiation of the pancreas progenitors towards these distinct cell fates are conserved across multiple species. The development of the pancreas occurs in concert with the development of other endoderm-derived organs in the region of the foregut, and inappropriate temporal or spatial cues result in aberrant development. As such, the tightly regulated activity of signal transduction pathways and transcription factors that confer permissive and inductive signals is central to appropriate development of the organ. The expression and/or function of the critical factors that regulate pancreas development are altered in pancreatic diseases, including diabetes and pancreatic cancer. Therefore, a clear understanding of normal pancreas development will illuminate disease pathogenesis.
Extraction of oat gum from oat bran: effects of process on yield, molecular weight distribution, viscosity and (1 leads to 3) (1 leads to 4)-beta-D-glucan content of the gum. (1996)

Different processing technologies were examined for their efficiency in production of large amounts of good quality oat gum rich in (1→3)(1→4)-β-D-glucan. Untreated and enzyme-deactivated oat bran concentrate were extracted with aqueous sodium carbonate at pH 10 and 40°C. Oat gums were subsequently isolated either by dialysis, ultrafiltration, or alcoholic precipitation on small, medium, and pilot plant scales. It was possible to produce oat gums with a β-glucan content of 60-65% with all three methodologies. The viscosity of solutions of the gums and the molecular weights differed, depending on the production process. Using dialysis, the production of highly viscous gums was possible, whereas ultrafiltration and alcoholic precipitation yielded gums with lower solution viscosity. Enzyme-deactivated oat bran concentrate gave an oat gum with an increased β-glucan content and solution viscosity, but in lower yield. To produce large amounts of oat gum, alcoholic precipitation would be the process of choice, but ultrafiltration and dialysis are useful alternatives.
Nanoparticles for Neutron Capture Therapy of Cancer (2003)

Abstract The sections in this article are Introduction Principle of Neutron Capture Therapy of Cancer Boron Neutron Capture Therapy Boron Compounds Delivery of Boron Using Nanoparticles Approaches to Gd NCT Typical Research on Gd NCT Delivery of Gadolinium using Lipid Emulsion ( G d ‐ nano LE ) Preparation of Gd ‐ nano LE Biodistribution of Gadolinium after Intraperitoneal Administration of Gd ‐ nano LE Biodistribution of Gadolinium after Intravenous Administration of Gd ‐ nano LE Delivery of Gadolinium using Chitosan Nanoparticles ( Gd ‐ nano CPs ) Preparation of Gd ‐ nano CPs Gd ‐ DTPA Release Property of Gd ‐ nano CPs Gd ‐ DTPA Retention in Tumor Tissue after Intratumoral Injection In vivo Growth Suppression of Experimental Melanoma Solid Tumor Bioadhesion and Uptake of Gd ‐ nano CP in Three Different Cell Lines Conclusions
Oxidation of the alarmin high-mobility group box 1 protein (HMGB1) during apoptosis (2009)

The architectural chromosomal protein high-mobility group box 1 protein (HMGB1) acts as an alarmin when released from cells. It is involved in the pathogenesis of inflammatory and autoimmune diseases. HMGB1 can undergo post-translational modifications including oxidation. However, the mechanisms and functional relevance of HMGB1 oxidation are not yet understood. Increased concentrations of reactive oxygen species (ROS) have been reported during apoptosis and necrosis. Hence, we investigated the oxidative status of HMGB1 in dead cells. Immunoblot analyses under reducing and non-reducing conditions revealed that HMGB1 is oxidized in dead cells. Moreover, tagging of oxidized cysteine residues by a maleimide moiety linked to polyethylene glycol showed that HMGB1 passively released from primary and secondary necrotic cells was predominantly oxidized. Also HMGB1 in plasma of patients with systemic lupus was reversibly oxidized. In conclusion, HMGB1 undergoes reversible oxidative modifications at cysteine residues during cell death, which may modulate its biological properties.
Prospect of utilizing surface-enhanced Raman spectroscopy for bio- and biomedical sensing (1990)

This paper will evaluate the potential applications of SERS for bio- and biomedical sensing. The emphasis willbe on technologies which will allow the development ofcost effective SERS instrumentation. Potential techniques which can be adapted to fiber optic based sensing will also be discussed.
Penetration and binding of radiolabeled anti-carcinoembryonic antigen monoclonal antibodies and their antigen binding fragments in human colon multicellular tumor spheroids. (1987)

The binding and penetration of two 125I-labeled anti-carcinoembryonic antigen (CEA) monoclonal antibodies (MAb) and their F(ab')2 and Fab fragments were measured in multicellular spheroids of poorly (HT29) and moderately well differentiated (Co112) human colon adenocarcinomas which express different amounts of CEA. Spheroids cultured in vitro model tumor microenvironments where poor vascular supply may modulate antigen expression and accessibility. The two MAb studied, 202 and 35, were shown previously to react with different CEA epitopes and to have high affinities of 1.2 and 5.8 X 10(9) M-1, respectively. MAb 202 has also been shown to cross-react with antigens present on human granulocytes and normal epithelial cells from human lung and pancreas. Specific binding of intact MAb and fragments of both antibodies was demonstrated for both types of human colon carcinoma spheroids compared to mouse colon carcinoma (CL26) and mammary tumor (EMT6/Ro) spheroids. Total binding of MAb and fragments was greater (1.5- to 2.5-fold) after 4 h compared to 1 h of exposure; the amount of binding compared to control IgG1 was 5- to 30-fold greater after 1-h incubation and 15 to 200 times greater after 4 h. This binding was stable as demonstrated by short and long wash experiments at 37 degrees and 4 degrees C. The binding of F(ab')2 and Fab fragments of the anti-CEA MAb 35 to spheroids of human colon Co112 was almost 2-fold greater than that of the intact MAb. However, for MAb 202, the binding of intact MAb and F(ab')2 was greater than that of Fab fragments. In addition the binding of both intact and F(ab')2 fragments of MAb 202 was greater than that obtained with MAb 35. Specific binding of both antibodies to HT29 spheroids, which express less CEA, was decreased for MAb and fragments of both 202 and 35. Autoradiography and immunoperoxidase experiments were performed to determine the penetration of MAb and fragments after incubation with intact spheroids. Comparisons were made with labeled MAb directly applied to frozen sections of spheroids. F(ab')2 and Fab fragments of both antibodies were bound at the surface of intact spheroids and penetrated to eight to ten cells, but the intact MAb were localized mainly at the spheroid surface and the outer one to three cell layers. There was much less binding at the surfaces of HT29 compared to Co112 spheroids. An enzyme immunoassay using MAb 35 and 202 demonstrated that Co112 spheroids produced about 8-fold more CEA/mg of cell protein than did monolayer cultures.(ABSTRACT TRUNCATED AT 400 WORDS)
Platinum diffusion into silicon from PtSi (1983)

We have observed platinum diffusion into the silicon underlying a PtSi film. Silicon substrates covered with platinum films were annealed at temperatures from 300 to 800 °C to form the silicide. Backscattering spectrometry spectra show no degradation of the silicide in the samples treated below 700 °C. Deep level transient spectroscopy (DLTS) was used to measure diffused platinum electron traps. Electron trap concentrations in samples treated below 700 °C are below the DLTS detection limit of 5×1011/cm3. Trap concentration profiles for the samples annealed at higher temperatures were obtained. These profiles cannot in general be explained by simple diffusion from an infinite source of platinum at the surface.
Pathological view of sudden cardiac death. (1981)

The common cause of sudden cardiac death is ischaemic heart disease. Such patients may have an occlusive recent thrombosis in a major coronary artery but the largest group has no recent occlusion. Comparison of such patients without occlusion with non-cardiac death control hearts suggests that an area of stenosis of 85 per cent is the best discriminating level. Most subjects who die of ischaemic heart disease suddenly have this degree of stenosis in two or three major arteries. Non-ischaemic sudden cardiac death occurs in hypertrophic obstructive cardiomyopathy and in severe left ventricular hypertrophy particularly from aortic valve stenosis. When the heart is macroscopically normal, review of previous electrocardiograms is the most helpful guide and may disclose conditions such as a long QT interval or pre-excitation. When no such data are available examination of the conduction system histologically may be helpful but is often non-specific. Use of the term "cardiomyopathy" by pathologists to cover all non-ischaemic sudden cardiac death is clinically misleading.
Poly(ether sulfone) of Isosorbide, Isomannide and Isoidide (2008)

Three polyether sulfones were prepared by polycondensation of 4,4'-difluorodiphenyl-sulfone and 1,6-dianhydrosorbitol (isosorbide), 1,6-dianhydromannitol (isomannide) or 1,6-dianhydroiditol (isoidide) in dimethyl sulfoxide (DMSO). Depending on the optimization of the reaction conditions, moderate to high molecular weights were obtained. Cyclic polyethers were the predominant reaction products in the MALDI-TOF mass spectra indicating that the chain growth was mainly limited by cyclization under optimized reaction conditions. The differential scanning calorimetry (DSC) measurements revealed an amorphous character with glass transition temperatures in the range of 213—253°C.
Proton Density Mapping and Receiver Bias Correction for Absolute Quantification with MR Fingerprinting (2017)

MR Fingerprinting (MRF) can simultaneously map multiple parameters and can be used to compute estimates of tissue fractions. However, MRF-derived M maps contain information about both proton density (PD) and the receiver sensitivity profile (RP). Here we estimate relative PD and RP from MRF M and T maps. Relative PD and tissue fractions are combined for absolute quantity mapping of CSF, gray matter, and white matter as a fraction of the voxel equilibrium magnetization.
Simultaneous RNA purification and size selection using on-chip isotachophoresis with an ionic spacer (2019)

We present an on-chip method for the extraction of RNA within a specific size range from low-abundance samples. We use isotachophoresis (ITP) with an ionic spacer and a sieving matrix to enable size-selection with a high yield of RNA in the target size range. The spacer zone separates two concentrated ITP peaks, the first containing unwanted single nucleotides and the second focusing RNA of the target size range (2-35 nt). Our ITP method excludes >90% of single nucleotides and >65% of longer RNAs (>35 nt). Compared to size selection using gel electrophoresis, ITP-based size-selection yields a 2.2-fold increase in the amount of extracted RNAs within the target size range. We also demonstrate compatibility of the ITP-based size-selection with downstream next generation sequencing. On-chip ITP-prepared samples reveal higher reproducibility of transcript-specific measurements compared to samples size-selected by gel electrophoresis. Our method offers an attractive alternative to conventional sample preparation for sequencing with shorter assay time, higher extraction efficiency and reproducibility. Potential applications of ITP-based size-selection include sequencing-based analyses of small RNAs from low-abundance samples such as rare cell types, samples from fluorescence activated cell sorting (FACS), or limited clinical samples.
Association of the PD‐1.3A allele of the <i>PDCD1</i> gene in patients with rheumatoid arthritis negative for rheumatoid factor and the shared epitope (2004)

Patients negative for both RF and the SE alleles showed association with the same allele that we previously identified as being involved in susceptibility to SLE. These results provide the first evidence of the involvement of the human PDCD1 gene in arthritis.
Interframe Coding for 4-MHz Color Television Signals (1975)

An interframe coding system is described which is capable of transmitting a 4-MHz National Television System Commission (NTSC) color television signal. 6.3 Mbit/s transmission gives acceptable picture quality for video telephone or conference TV use. The NTSC color television signal is converted into a timedivision multiplex (TDM) signal which is composed of time-compressed chrominance and luminance signal in sequence. This signal is encoded using a frame-difference coder of the kind that has been used for black-and-white television signals. A field-repeating technique is introduced into the coder, to prevent a buffer memory from overflowing and to improve picture quality. Statistical investigations show that the presence of the timecompressed chrominance signal gives less than 10 percent increase in the amount of information generated by picture movements; this increase scarcely affects the picture quality.
A 170 Volt Tantalum Hybrid™ Capacitor - Engineering Considerations (1997)

The electrical performance of Hybrid capacitors (US Patent 5,369,547) using high capacitance density electrochemical capacitor cathodes, electrolytic capacitor anodes and dielectric, and compatible electrolytes is strongly influenced by the nature of the electrolyte employed and the physical characteristics of the electrodes. Management of overall capacitor performance usually involves optimizing one set of material properties against another. This work describes our efforts in producing a tantalum Hybrid capacitor with a 170 V working voltage.
Synthesis of hyperbranched aliphatic polyethers via cationic ring-opening polymerization of 3-ethyl-3-(hydroxymethyl)oxetane (1999)

Thermally initiated cationic ring-opening polymerization of 3-ethyl-3-(hydroxymethyl)oxetane was carried out using benzyltetramethylenesulfonium hexafluoroantimonate as initiator. The resulting hydroxy-functional polyether was thoroughly analyzed by 1H and 13C NMR spectroscopy and found to have a hyperbranched architecture with a degree of branching of 0.4. The polyether was successfully employed as a multifunctional initiator for ε-caprolactone. Molecular weight measurements on the polyether showed a narrow molecular weight distribution analyzed by SEC and MALDI-TOF (1.3 and 1.4, respectively).
Clathrin-mediated endocytosis in AP-2–depleted cells (2003)

We have used RNA interference to knock down the AP-2 mu2 subunit and clathrin heavy chain to undetectable levels in HeLaM cells. Clathrin-coated pits associated with the plasma membrane were still present in the AP-2-depleted cells, but they were 12-fold less abundant than in control cells. No clathrin-coated pits or vesicles could be detected in the clathrin-depleted cells, and post-Golgi membrane compartments were swollen. Receptor-mediated endocytosis of transferrin was severely inhibited in both clathrin- and AP-2-depleted cells. Endocytosis of EGF, and of an LDL receptor chimera, were also inhibited in the clathrin-depleted cells; however, both were internalized as efficiently in the AP-2-depleted cells as in control cells. These results indicate that AP-2 is not essential for clathrin-coated vesicle formation at the plasma membrane, but that it is one of several endocytic adaptors required for the uptake of certain cargo proteins including the transferrin receptor. Uptake of the EGF and LDL receptors may be facilitated by alternative adaptors.
Sur les ensembles de distances des ensembles de points d'un espace euclidien. By Sophie Piccard Pp. 212. 7.50 Swiss francs. 1940. Memoires de I'Universite de Neuchâtel, tome XIII. (Gauthier-Villars) (1940)

Sur les ensembles de distances des ensembles de points d'un espace euclidien. By Sophie Piccard Pp. 212. 7.50 Swiss francs. 1940. Memoires de I'Universite de Neuchâtel, tome XIII. (Gauthier-Villars) - Volume 24 Issue 261
Specific eradication of HIV-1 from infected cultured cells (2010)

A correlation between increase in the integration of Human Immunodeficiency virus-1 (HIV-1) cDNA and cell death was previously established. Here we show that combination of peptides that stimulate integration together with the protease inhibitor Ro 31-8959 caused apoptotic cell death of HIV infected cells with total extermination of the virus. This combination did not have any effect on non-infected cells. Thus it appears that cell death is promoted only in the infected cells. It is our view that the results described in this work suggest a novel approach to specifically promote death of HIV-1 infected cells and thus may eventually be developed into a new and general anti-viral therapy.
Expressing implicit semantic relations without supervision (2006)

We present an unsupervised learning algorithm that mines large text corpora for patterns that express implicit semantic relations. For a given input word pair X:Y with some unspecified semantic relations, the corresponding output list of patterns (P1,..., Pm) is ranked according to how well each pattern Pi expresses the relations between X and Y. For example, given X = ostrich and Y = bird, the two highest ranking output patterns are "X is the largest Y" and "Y such as the X". The output patterns are intended to be useful for finding further pairs with the same relations, to support the construction of lexicons, ontologies, and semantic networks. The patterns are sorted by pertinence, where the pertinence of a pattern Pi for a word pair X:Y is the expected relational similarity between the given pair and typical pairs for Pi. The algorithm is empirically evaluated on two tasks, solving multiple-choice SAT word analogy questions and classifying semantic relations in noun-modifier pairs. On both tasks, the algorithm achieves state-of-the-art results, performing significantly better than several alternative pattern ranking algorithms, based on tf-idf.
Comparative Prognostic Utility of Indexes of Microvascular Function Alone or in Combination in Patients With an Acute ST-Segment–Elevation Myocardial Infarction (2016)

URL: https//www.clinicaltrials.gov. Unique identifier: NCT02072850.
Human and Mouse CD8+CD25+FOXP3+ Regulatory T Cells at Steady State and during Interleukin-2 Therapy (2015)

In addition to CD4(+) regulatory T cells (Tregs), CD8(+) suppressor T cells are emerging as an important subset of regulatory T cells. Diverse populations of CD8(+) T cells with suppressive activities have been described. Among them, a small population of CD8(+)CD25(+)FOXP3(+) T cells is found both in mice and humans. In contrast to thymic-derived CD4(+)CD25(+)FOXP3(+) Tregs, their origin and their role in the pathophysiology of autoimmune diseases (AIDs) are less understood. We report here the number, phenotype, and function of CD8(+) Tregs cells in mice and humans, at the steady state and in response to low-dose interleukin-2 (IL-2). CD8(+) Tregs represent approximately 0.4 and 0.1% of peripheral blood T cells in healthy humans and mice, respectively. In mice, their frequencies are quite similar in lymph nodes (LNs) and the spleen, but two to threefold higher in Peyer patches and mesenteric LNs. CD8(+) Tregs express low levels of CD127. CD8(+) Tregs express more activation or proliferation markers such as CTLA-4, ICOS, and Ki-67 than other CD8(+) T cells. In vitro, they suppress effector T cell proliferation as well as or even better than CD4(+) Tregs. Owing to constitutive expression of CD25, CD8(+) Tregs are 20- to 40-fold more sensitive to in vitro IL-2 stimulation than CD8(+) effector T cells, but 2-4 times less than CD4(+) Tregs. Nevertheless, low-dose IL-2 dramatically expands and activates CD8(+) Tregs even more than CD4(+) Tregs, in mice and humans. Further studies are warranted to fully appreciate the clinical relevance of CD8(+) Tregs in AIDs and the efficacy of IL-2 treatment.