gebhart/patrepeval huggingface dataset:
Estimation of Tissue Hypothyroidism by a New Clinical Score: Evaluation of Patients with Various Grades of Hypothyroidism and Controls1 (1997)

The classical signs and symptoms of hypothyroidism were reevaluated in the light of the modern laboratory tests for thyroid function. We analyzed 332 female subjects: 50 overt hypothyroid patients, 93 with subclinical hypothyroidism (SCH), 67 hypothyroid patients treated with T4, and 189 euthyroid subjects. The clinical score was defined as the sum of the 2 best discriminating signs and symptoms. Beside TSH and thyroid hormones, we measured parameters known to reflect tissue manifestations of hypothyroidism, such as ankle reflex relaxation time and total cholesterol. Classical signs of hypothyroidism were present only in patients with severe overt hypothyroidism with low T3, but were rare or absent in patients with normal T3 but low free T4 or in patients with SCH (normal thyroid hormones but elevated basal TSH; mean scores, 7.8 +/- 2.7 vs. 4.4 +/- 2.2 vs. 3.4 +/- 2.0; P < 0.001). Assessment of euthyroid subjects and T4-treated patients revealed very similar results (mean score, 1.6 +/- 1.6 vs. 2.1 +/- 1.5). In overt hypothyroid patients, the new score showed an excellent correlation with ankle reflex relaxation time and total cholesterol (r = 0.76 and r = 0.60; P < 0.0001), but no correlation with TSH (r = 0.01). The correlation with free T4 was r = -0.52 (P < 0.0004), and that with T3 was r = -0.56 (P < 0.0001). In SCH, the best correlation was found between the new score and free T4 (r = -0.41; P < 0.0001) and TSH (r = 0.35; P < 0.0005). Evaluation of symptoms and signs of hypothyroidism with the new score in addition to thyroid function testing is very useful for the individual assessment of thyroid failure and the monitoring of treatment.
Hierarchical modeling of flow in naturally fractured formations with multiple length scales (2001)

This paper describes hierarchical approach to modeling flow in a naturally fractured formation. Our model is based on calculating the effective permeability of a fractured formation, as a function of grid block size, and using the results in a conventional finite difference flow simulator. On the basis of their length ( lf ) relative to the finite difference grid size ( l g ), fractures are classified as belonging to one of three groups: (1) short fractures ( l f ≪ l g ), (2) medium‐length fractures ( l f ∼ l g ), and (3) long fractures ( l f ≫ l g ). The effects of the fractures belonging to each class are computed in a hierarchical manner. The permeability contribution from short fractures is derived in an analytical expression and used as an enhanced matrix permeability for the next‐scale (medium‐length) calculation. The effective matrix permeability associated with medium‐length fractures is numerically solved using a boundary element method. The long fractures are modeled explicitly as major fluid conduits. As numerical examples, tracer transport in fractured formations was illustrated. The numerical results clearly indicated that effective tensor permeability well represented directional, enhanced permeability in fractured formations. The fluid‐conduit formulation captured the efficient fluid transport by long fractures.
Over 40 Years of Fosmidomycin Drug Research: A Comprehensive Review and Future Opportunities (2022)

To address the continued rise of multi-drug-resistant microorganisms, the development of novel drugs with new modes of action is urgently required. While humans biosynthesize the essential isoprenoid precursors isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) via the established mevalonate pathway, pathogenic protozoa and certain pathogenic eubacteria use the less well-known methylerythritol phosphate pathway for this purpose. Important pathogens using the MEP pathway are, for example, <i>Plasmodium falciparum</i>, <i>Mycobacterium tuberculosis</i>, <i>Pseudomonas aeruginosa</i> and <i>Escherichia coli</i>. The enzymes of that pathway are targets for antiinfective drugs that are exempt from target-related toxicity. 2<i>C</i>-Methyl-D-erythritol 4-phosphate (MEP), the second enzyme of the non-mevalonate pathway, has been established as the molecular target of fosmidomycin, an antibiotic that has so far failed to be approved as an anti-infective drug. This review describes the development and anti-infective properties of a wide range of fosmidomycin derivatives synthesized over the last four decades. Here we discuss the DXR inhibitor pharmacophore, which comprises a metal-binding group, a phosphate or phosphonate moiety and a connecting linker. Furthermore, non-fosmidomycin-based DXRi, bisubstrate inhibitors and several prodrug concepts are described. A comprehensive structure-activity relationship (SAR) of nearly all inhibitor types is presented and some novel opportunities for further drug development of DXR inhibitors are discussed.
High extinction ratio optical modulator using active intensity trimmers (2005)

We demonstrated high extinction ratio optical intensity switching by an integrated Mach-Zehnder LiNbO3 modulator, where each arm has a small Mach-Zehnder interferometer for compensation of amplitude mismatching in the arms. The extinction ratio was 50 dB. (2 pages)
Reactivity of Hydroxyl Radical in Nonaqueous Phases: Addition Reactions (2018)

The effect of ring substitution on the kinetics of reaction of arenes, heterocycles, and alkenes with hydroxyl radical is investigated in terms of reactivity and selectivity, using laser flash photolysis (LFP) in acetonitrile solution. The LFP data indicate that charge-transfer contributions in the transition state play an important role in dictating reactivity, and there is a correlation between the experimental and calculated ionization potentials of the arenes and alkenes and their respective reactivities. The reactivity observed for arenes in acetonitrile exhibits a much greater sensitivity toward substitution on the ring than in water, and therefore aqueous data cannot be used to predict reactivity in nonaqueous environments. Nonaqueous solution data may be predictable from gas phase data, and vice versa.
Detection of Yield Point Behavior by Acoustic Emission in thin Films (2015)

Fabrication of domain-boundary based thin-film devices needs to control the yield point of a strained/cooled ferroelastics. We show that such control is possible by acoustic emission measurements using an integrated detector system. Through molecular dynamics simulations, we find that in thin films, the potential energy reduction during the yield event can reach to 4 meV/atom, and generate strain of 0.005 at the surface which lead to detectable acoustic emission signals.
Flexible operation of parallel grid-connecting converters under unbalanced grid voltage (2017)

According to the European grid code, grid-connecting converters should always be connected to the grid under grid voltage unbalance. However, grid voltage unbalance severely affects the stable operation of the converters and leads to the various power issues, such as active power oscillation, DC-link voltage ripple, and overloading. Moreover, under grid voltage unbalance, the active power delivery ability is decreased due to the converter's current rating limitation. In this paper, a thorough study on the current limitation of the grid-connecting converter under grid voltage unbalance is conducted. In addition, based on the principle that total output active power should be oscillation free, a coordinated control strategy is proposed for the parallel grid-connecting converters. The case study has been conducted to demonstrate the effectiveness of this proposed control strategy.
DENDRITIC CELL-DERIVED EXOSOMES CONTAINING MILK FAT GLOBULE EPIDERMAL GROWTH FACTOR-FACTOR VIII ATTENUATE PROINFLAMMATORY RESPONSES IN SEPSIS (2006)

In sepsis, several cell types (e.g., lymphocytes) undergo apoptosis and have the potential to harm the host if not cleared by professional phagocytes. Apoptotic cells display "eat me" signals such as phosphatidylserine that can be readily recognized by phagocytes. For full engulfment of these cells, binding to integrin alpha(v)beta(3), mediated by the bridging protein, milk fat globule epidermal growth factor-factor VIII (MFG-E8), is necessary. We hypothesized that, in sepsis, phagocytosis of apoptotic cells is impaired due to decreased MFG-E8 expression and that adoptive transfer of exosomes containing MFG-E8 is beneficial. Sepsis was induced in rats by cecal ligation and puncture (CLP) and MFG-E8 expression assessed by Western blot 20 h later. Dendritic cells were generated from bone marrow cells, and secreted exosomes were collected and injected into CLP animals. Plasma cytokines (enzyme-linked immunosorbent assay) and thymocyte apoptosis (TC-Ao, annexin V) were assessed. The ability of peritoneal macrophages from septic animals to engulf apoptotic cells was determined in an ex vivo phagocytosis assay. A 10-day survival study was conducted. Cecal ligation and puncture reduced MFG-E8 protein levels in the spleen and liver by 48% and 70%, respectively, and increased TC-Ao by 1.6-fold. Injection of MFG-E8-containing exosomes, however, led to a 33% reduced detection of TC-Ao, without directly inhibiting apoptosis. In fact, peritoneal macrophages from exosome-treated rats displayed a 2.8-fold increased ability to phagocytose apoptotic thymocytes. Inhibition of MFG-E8 before injection of exosomes completely abrogated the enhanced phagocytosis. Treatment with bone marrow dendritic cell-derived exosomes also reduced plasma tumor necrosis factor alpha and interleukin (IL)-6 levels and improved survival from 44% to 81%. We conclude that, by providing the indispensable factor MFG-E8 for complete engulfment of apoptotic cells, these exosomes lead to an attenuation of the systemic inflammatory response and overall beneficial effect in sepsis.
Taxol transport by human intestinal epithelial Caco-2 cells. (1998)

Taxol (paclitaxel) belongs to a new class of antimicrotubule anticancer drugs with clinical activity against common solid tumors and acute leukemias. Preclinical studies have suggested that taxol is not absorbed after oral doses. However, whether the observed low oral bioavailability is the result of poor absorption or extensive presystemic hepatic metabolism is not clear. For this reason, we studied the transepithelial flux of taxol, using the human colonic cell line Caco-2 as a model. The cells were grown to confluency on permeable polycarbonate membrane inserts, to permit flux experiments after loading of [3H]taxol on either the apical or basolateral side. The flux of taxol across the Caco-2 cell layer was linear with time for up to 3 hr. The flux from the basolateral to the apical side was 4-10 times greater than that from the apical to the basolateral side. Whereas the absorptive transport appeared linearly related to the taxol concentration (0.5-20 microM), the efflux was saturable. The apparent KM of the active efflux component was 16.5 microM. Verapamil (50 microM) significantly decreased the active transport component. These data support the conclusion that rapid passive diffusion of taxol through the intestinal epithelium is partially counteracted by the action of an outwardly directed efflux pump, presumably P-glycoprotein. However, the relatively high apparent permeability coefficient for the apical to basolateral taxol transport (4.4 +/- 0.4 x 10(-6) cm/s; N = 17) suggests that the drug may still be effectively absorbed in the intestinal tract.
Disability Rating Scales in Multiple Sclerosis (1984)

The International Federation of Multiple Sclerosis Societies has been attempting to define a Minimal Data Set for multiple sclerosis following the tripartite scheme of the World Health Organization, with one rating scheme for neurologic signs, one for physical disabilities, and one for the societal impact of the disease. Current recommendations are the Disability Status Scale or the Expanded DSS plus Functional Systems for the first, Incapacity Status Scale of 16 items for the second, and Environmental Status Scale of 7 items for the third. All are graded in an ordinal (rank) scale from 0 (normal) with larger numbers for greater involvement. ISS scores range from 0-4 and ESS from 0-5 for each item. The only part of this scheme useful for measurement in clinical trials is the (E)DSS + FS. The DSS ranges from 0-10; EDSS subdivides each DSS grade 1-9 into two. FS are pyramidal, cerebellar, brain stem, sensory, bowel and bladder, visual, cerebral, or other; all save the last are graded 0-5 or 0-6. The DSS correlates well with both frequency and severity of involvement in all FS, which in turn represent a coded standard neurologic examination.
LinkedIn's Audience Engagements API: A Privacy Preserving Data Analytics System at Scale (2020)

We present a privacy system that leverages differential privacy to protect LinkedIn members' data while also providing audience engagement insights to enable marketing analytics related applications. We detail the differentially private algorithms and other privacy safeguards used to provide results that can be used with existing real-time data analytics platforms, specifically with the open sourced Pinot system. Our privacy system provides user-level privacy guarantees. As part of our privacy system, we include a budget management service that enforces a strict differential privacy budget on the returned results to the analyst. This budget management service brings together the latest research in differential privacy into a product to maintain utility given a fixed differential privacy budget.
Quantitative Binding Site Model Generation: Compass Applied to Multiple Chemotypes Targeting the 5-HT1A Receptor (1995)

We present enhancements to the Compass algorithm that automatically deduce interchemotype relationships and generate predictive quantitative models of receptor binding based solely on structure-activity data. We applied the technique to a series of compounds assayed for 5-HT1A binding. A model was constructed from 20 compounds of two chemotypes and used to predict the affinities and bioactive conformation of 35 new compounds, most of which had new underlying scaffolds and/or functional groups. The model's mean error of prediction was 0.5 log units (essentially the assay resolution), even on quite divergent series. The predictions are supported by an interpretable hypothesis for the binding determinants of the receptor and the geometric relationships of the chemotypes.
Synthesis and Properties of Metal Chelates of the Group IV Element with the Ligand of Schiff Base (1987)

芳香族2, 2′-ジヒドロキシ型Schiff塩基を配位子とするチタン, ジルコニウムおよびケイ素キレートの合成およびこれらのキレートの耐熱・耐光性と樹脂着色剤としての性質を検討した。ケイ素キレートは400℃以上の熱分解点を有し, 特に配位子がベンゼン-ベンゼン骨格から成るキレートの熱分解点は500℃以上であり, チタンやジルコニウムキレートに比べ極めて高い熱安定性を有している。一方, ポリスチレン系樹脂に対する着色テストの結果から, キレートの着色力や諸堅ろう度を評価した。キレートは金属によりチタンで褐色から赤色, ジルコニウムで黄色から橙色, ケイ素で黄色から赤色系の透明な色調を示した。配位子の置換基が電子吸引基より置換基が無いがメチル基の場合にキレートの熱安定性が高く, チタンやケイ素およびジルコニウムキレートで4.5～5級の値を有するものが認められた。キレートの耐ブリード性におよぼす金属や配位子の影響は認められず, いずれも2～3級の値を示した。これに対し, キレートの耐光性には金属により顕著な差が認められ, ジルコニウム, ケイ素, チタンの順に安定性が高く, 特にチタンキレートはいずれも7～8級のきわめて高い値を示した。
3T3 fibroblasts induce cloned interleukin 3-dependent mouse mast cells to resemble connective tissue mast cells in granular constituency. (1988)

As assessed by ultrastructure, histochemical staining, and T-cell dependency, in vitro-differentiated inter-leukin 3-dependent mouse mast cells are comparable to the mast cells that reside in the gastrointestinal mucosa but not in the skin or the serosal cavity of the mouse. We now demonstrate that when cloned interleukin 3-dependent mast cells are cocultured with mouse skin-derived 3T3 fibroblasts in the presence of WEHI-3 conditioned medium for 28 days, the mast cells acquire the ability to stain with safranin, increase their histamine content approximately equal to 50-fold and their carboxypeptidase A content approximately equal to 100-fold, and augment approximately equal to 45-fold their biosynthesis of proteoglycans bearing 35S-labeled heparin relative to 35S-labeled chondroitin sulfate glycosaminoglycans. Thus, fibroblasts induce interleukin 3-dependent mouse mast cells to change phenotype from mucosal-like to connective tissue-like, indicating that the biochemical and functional characteristics of this mast cell type are strongly influenced by the connective tissue microenvironment.
Groupware that learns (2002)

The authors developed a groupware toolkit, called Michele, which supports asynchronous group work in distributed open environments. It is based on a multi-agent model of communication and allows a user to customize the interface by a specially designed language called MDL (multi-agent description language). The authors incorporate a learning mechanism in Michele. With the mechanism, Michele learns interactions between the user and the system, and stores learned knowledge in each user's environment. A document generation macro function has been added to MDL. With this macro function, cooperative work can be viewed as a set of document-driven procedures. Michele makes a decision tree for each query to the user when making new documents within the document generation macro function. The authors describe Michele and its agent description language MDL. They describe how to introduce a learning mechanism within Michele and explain the details of its implementation. An evaluation of the learning mechanism with a real example is described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Effect of Gamma Irradiation on Immune Activity and Physicochemical Properties of Myagropsis myagroides Water Extract (2011)

This study examined the effect of gamma irradiation (3-20 kGy) on the immune activity and physicochemical properties of Myagropsis myagroides (MM) water extracts. MM powder and water extracts were subjected to gamma irradiation at 3, 7, and 20 kGy. The effects of gamma-irradiated MM water extracts on splenocyte proliferation and cytokine IFN-<TEX>${\gamma}$</TEX> and IL-2 secretion were evaluated. The gamma-irradiated MM water extracts resulted in decreased splenocyte proliferation without cytotoxicity. The IFN-<TEX>${\gamma}$</TEX> and IL-2 secretion increased by gamma-irradiated MM water extracts with increasing irradiation dose. For MM powder, the yield and total phenolic compounds (TPC) of water extracts were increased slightly after gamma irradiation. In MM water extracts, the TPC was higher at a dose of 20 kGy, while gamma irradiation decreased the viscosity, pH, and color of the MM extracts. In conclusion, gamma irradiation improved the immunomodulatory activity of MM water extracts, overcoming its potential weakness when applied in the food industry.
The major receptor for c-reactive protein on leukocytes FcyII (1999)

C-reactive protein (CRP) is an acute phase serum protein that shares several functions with\nimmunoglobulin (Ig)G including complement activation and binding to receptors on monocytes\nand neutrophils. The identity of the receptor for CRP has been the target of extensive research.\nWe previously determined that CRP binds to the high affinity receptor for IgG, Fc\ngRI\n(CD64). However, this interaction could not account for the majority of binding of CRP to\nneutrophils or monocytic cells. We now determine that CRP also interacts with Fc\ngRIIa\n(CD32), the low affinity receptor for IgG on monocytes and neutrophils. COS-7 cells were\ntransfected with a construct containing the human Fc\ngRIIA cDNA. CRP binding and the\npresence of CD32 were detected by mAb and analyzed by two-color flow cytometry. Cells expressing\nCD32 bound CRP in a dose-dependent and saturable manner consistent with receptor\nbinding. CRP bound to transfectants and K-562 cells with similar kinetics, and in both\ncases binding was completely inhibited by aggregated IgG. On monocytic cell lines, treatment\nwith Bt2cAMP increased Fc\ngRII expression and enhanced CRP binding. CRP also specifically\nprecipitated Fc\ngRI and Fc\ngRII from the monocytic cell line, THP-1. It is suggested that the\nmajor receptor for CRP on phagocytic cells is Fc\ngRII.
Emergence of MD type infectious hematopoietic necrosis virus in Washington State coastal steelhead trout (2013)

Infectious hematopoietic necrosis virus (IHNV) occurs in North America as 3 major phylogenetic groups designated U, M, and L. In coastal Washington State, IHNV has historically consisted of U genogroup viruses found predominantly in sockeye salmon Oncorhynchus nerka. M genogroup IHNV, which has host-specific virulence for rainbow and steelhead trout O. mykiss, was detected only once in coastal Washington prior to 2007, in an epidemic among juvenile steelhead trout in 1997. Beginning in 2007 and continuing through 2011, there were 8 IHNV epidemics in juvenile steelhead trout, involving 7 different fish culture facilities in 4 separate watersheds. During the same time period, IHNV was also detected in asymptomatic adult steelhead trout from 6 coastal watersheds. Genetic typing of 283 recent virus isolates from coastal Washington revealed that the great majority were in the M genogroup of IHNV and that there were 2 distinct waves of viral emergence between the years 2007 and 2011. IHNV type mG110M was dominant in coastal steelhead trout during 2007 to 2009, and type mG139M was dominant between 2010 and 2011. Phylogenetic analysis of viral isolates indicated that all coastal M genogroup viruses detected in 1997 and 2007 to 2011 were part of the MD subgroup and that several novel genetic variants related to the dominant types arose in the coastal sites. Comparison of spatial and temporal incidence of coastal MD viruses with that of the rest of the Pacific Northwest indicated that the likely source of the emergent viruses was Columbia River Basin steelhead trout.
Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPARdelta (1999)

We have demonstrated previously that cyclo-oxygenase-2 (COX2), the rate-limiting enzyme in the biosynthesis of prostaglandins (PGs), is essential for blastocyst implantation and decidualization. However, the candidate PG(s) that participates in these processes and the mechanism of its action remain undefined. Using COX2-deficient mice and multiple approaches, we demonstrate herein that COX2-derived prostacyclin (PGI2) is the primary PG that is essential for implantation and decidualization. Several lines of evidence suggest that the effects of PGI2 are mediated by its activation of the nuclear hormone receptor PPARdelta, demonstrating the first reported biologic function of this receptor signaling pathway.
Induced alignment of a reactive mesogen-based polymer electrolyte for dye-sensitised solar cells (2017)

Controlling the morphology of liquid crystal-directed polymer templates at the micrometer scale using external alignment layers and electric fields.
Lethal Invasive Cestodiasis in Immunosuppressed Patients (2003)

Using both traditional methods and broad-range 18S ribosomal DNA (rDNA) polymerase chain reaction, we examined 2 cases of lethal cestodiasis, in which the disease agent had been poorly identified or misidentified. In one case, involving a patient with AIDS, we identified the human dwarf tapeworm, Hymenolepis nana, as a cause of aberrant metastatic larval disease. In the second case with similar pathologic abnormalities, involving a patient with Hodgkin disease, we identified a larval cestode with a previously uncharacterized 18S rDNA sequence. A prior report of this case nearly 30 years ago, based on tissue examination, had suggested that the parasite was a sparganum.