gebhart/patrepeval huggingface dataset:
Evidence for glucuronide (small molecule) sorting by human hepatic endoplasmic reticulum (1995)

The entry of substrates into, and the export of glururonides from, the lumen of hepatic endoplasmic reticulum (ER) in vitro (sealed microsomes) has been measured using radioactivity-labelled materials and a rapid filtration assay. Analysis of liver microsomes from a jaundiced patient showed the accumulation of bilirubin glucuronides within the lumen of the ER. Further analysis of these hepatic microsomes revealed that newly synthesized 1-naphthol glucuronide could exit from the microsomes whereas bilirubin glucuronide was accumulated within the microsomes. These results suggest the existence of mechanisms for the sorting of small molecules, destined for export through bile canalicular or basolateral plasma membranes, by ER. Furthermore, these sorting processes may be regulated by specific transporters within the ER.
Synthesis of functionalized macroinimer by N,N‐diethyldithiocarbamate‐mediated living free‐radical polymerization (2004)

We presented a one-pot approach to functionalized macroinimer via living free-radical polymerization. The living free-radical copolymerization of the mixture of (N,N-diethyldithiocarbamyl)methyl styrene (DTCS), maleic anhydride (MA), and styrene (100:10 equiv mixture of styrene and MA) was studied in tetrahydrofuran under UV irradiation. The formation of alternating sequences was initially fast with preferential consumption of styrene and MA. Further polymerization involved growth of a homopolystyrene block.
Deletion of chromosome band 13q14 as detected by fluorescence in situ hybridization is a prognostic factor in patients with multiple myeloma who are receiving allogeneic dose-reduced stem cell transplantation (2004)

We investigated in a retrospective multicenter study the impact of chromosome arm 13q deletion (13q-) as detected by fluorescence in situ hybridization (FISH) on outcome after dose-reduced allografting in patients with multiple myeloma. In 68 of 140 patients, data on chromosome 13q status were available. Most patients included had advanced myeloma. At 2 years, patients with 13q deletion (n = 31) had a shorter event-free (18% vs 42%; P =.05) and overall survival (18% vs 67%; P =.03) than patients without 13q- (n = 37). Patients with 13q- experienced a higher relapse rate (77% vs 44%; P <.001) but a similar incidence of transplantation-related mortality at one year (24% vs 18%). In a multivariate analysis, 13q- remained a significant risk factor for a higher relapse rate (hazard ratio [HR], 3.28; 95% confidence interval [CI], 1.31-8.24; P =.01) and a shorter event-free survival (HR, 1.94; 95% CI, 1.03-3.67; P =.04). Concerning overall survival, 2 or more cycles of prior high-dose chemotherapy were associated with a significantly higher probability of death (HR, 2.48; 95% CI, 1.19-5.17; P =.02), while patients with deletion 13q had a nearly 2 times higher risk of death (HR, 1.94; 95% CI, 0.95-3.98; P =.07) after dose-reduced allogeneic stem cell transplantation.
Developmental Regulation of Lymphocyte-Specific Protein 1 (LSP1) Expression in Thymus During Human T-Cell Maturation (1998)

The lymphocyte specific protein 1 (LSP1) phosphoprotein is an F-actin binding molecule restricted to cells of hematopoietic origin in mice and humans. LSP1 is localized to the internal surface of the plasma membrane, the cytoplasm, and NP-40-insoluble actin filaments and is thought to mediate cytoskeleton-driven responses in activated leukocytes that involve receptor capping, cell-cell interactions and cell motility. Here, we generated two monoclonal antibodies (MAbs), 5E3 and 14G8, that are specific for human LSP1 to define the expression of LSP1 throughout human T-cell development. Both MAbs reacted with a 52-kDa protein in BW5147 cells transfected with human LSP1 cDNA in pcDNA3, but not in cells transfected with cDNA in an antisense orientation, indicating the specificity of 5E3 and 14G8 for human LSP1. In developing T cells, LSP1 was expressed on human fetal liver CD7+ NK and T-cell precursors, the CD7+, CD3-, CD4-, CD8- human stem cell line DU-528, and on CD4-, CD8- double-negative (DN) thymocytes. Immunohistochemistry and three-color flow cytometry analysis of fetal or postnatal thymocytes revealed that LSP1 was increasingly expressed during intrathymic human T-cell maturation. While immature CD4+CD8+ double-positive (DP) thymocytes expressed low to undetectable levels of LSP1, mature CD4+CD8- and CD4-CD8+ single-positive (SP) thymocytes expressed high levels of LSP1. Thus, LSP1 is developmentally regulated during T-cell maturation within the human thymus and may play a functional role in the motility of DN and SP thymocytes.
Molecular basis of factor xiii deficiency H.Mikkola (1996)

Factor XIII deficiency is a rare autosomal recessive bleeding disorder that is characterized by defective crosslinking of fibrin and poor resistance to fibrinolysis. We have characterized seven mutations in FXIII A-subunit gene: Four missense mutations (Met242-&gt;Thr. Arg252-&gt;Ile, Arg326-&gt;Gln and Leu498-&gt;Pro) and three nonsense mutations (Arg661-&gt;Stop, delT Phe8 and a splicing defect T-&gt;C at position +6 in intron C) The expression of FXIII Asubunit was studied in vivo on mRNA and protein level. The structural effects of the mutations were predicted from the three dimensional model of crystallized FXIII A-subunit. (Mikkola et al. Blood 1994, 84:517-525, Mikkola et al. Blood 1996,87:141-151) The missense mutations were further studied by in vitro expression in COS cells. All of them interfere with the enzymatic activity and render the protein susceptible for intracellular degradation. There is considerable phenotypic variation within FXIII deficient patients but little is known about the phenotype-genotype correlation. One of the Finnish patients has an untypically mild phenotype as she has had two succesful pregnancies without FXIII substitutions. She is a compound heterozygote for Arg661-&gt;Stop mutation and the splicing mutation (T-&gt;C at position +6 of intron C). Analysis of the patients FXIII A-subunit mRNA, antigen and activity in platelets and fibrin cross-linking pattern in plasma suggest partial readthrough of the splicing mutation resulting in a small amount of active enzyme and thus a milder phenotype.
Host cell signalling inhibitors against helicobacter pylori (2009)

More than 50% of the world population is infected by Helicobacter pylori nowdays. Although in most cases it doesn't causes any symptoms it's a significant risk factor in the development of gastric ulcer or gastric carcinoma. Elimination of the bacteria can be attained by the combination of at least three drugs and it may also causes several side effects. It's beyond doubt that a new drug showing good efficacy without side effects is needed. Kinase inhibitors have proved their usefulness in the treatment of cancer inhibiting cell proliferation via inhibition of intracellular signaling system. Moreover host cell kinases can be involved in viral or bacterial infections, this way human kinases may be the targets of the treatment. In our research we are investigating kinase inhibitors and developing novel compounds for host cell inhibition. The point of our strategy (called chemistry driven drug development) is to identify active compounds in cellular assay and identify cellular targets afterwards. Initially, we are using the Nested Chemical Library™ (NCL) technology for hit finding and lead optimization. Core of the NCL is Chemical Validation Library (CVL) which can be used for hit finding in the preliminary screen. 313 compounds of CVL were tested and focused libraries were prepared around the validated hit molecules of the first screen. After three optimization cycle lead compounds were identified. From one of the best lead compounds we have prepared a special derivative containing a linker which can be used to attach to an affinity column for target fishing in chemistry driven drug development. Target fishing is an efficient proteomic method in seeking cellular drug targets based on affinity chromatography, 2D electrophoresis and MS-MS protein identification.
Improving neuronal adhesion on chip using a phagocytosis-like event (2007)

Efficient integration of neuronal cells and electronic devices could result in hybrid bi-directional communication systems that would enable us to interact at fundamental levels with biological structures and gain insight in the mechanisms governing their functions. Such systems require a very tight coupling between the neuronal cell membrane and the surface of an electronic chip. In this paper we report an approach where the combination of specialized surface chemistry and the manipulation of biological processes, like a phagocytosis-like process, might improve this coupling. As a model, we used coated micro- and nano-sized beads and induced phagocytosis-like events by adding them to cultured cells. The development of the surface chemistry and the results obtained with beads functionalized with a laminin derived peptide are presented.
28.1: Optically Compensated IPS‐LCD for TV Applications (2005)

Abstract A light leakage and a color shift along diagonal viewing angle directions in the black representation were dramatically reduced for IPS‐LCDs using a newly developed biaxial film and pixel structure. We have studied the optical compensation method suitable for a newly developed panel with the higher white transmission (IPS‐Pro). This new film technology has been successfully applied for the 32‐inch IPS‐LCD with performances of significantly wide viewing angle performance in all images and contrast ratio over 900:1.
The Missense Mutation Arg593 → Cys Is Related to Antibody Formation in a Patient With Mild Hemophilia A (1997)

The development of inhibitory antibodies to factor VIII in patients affected by a mild form of hemophilia A (factor VIII > 0.05 IU/mL) is considered a rare event. In this study, we evaluated the relationship between genotype and anti-factor VIII antibody formation in a patient with mild hemophilia A. Mutation analysis showed that a missense mutation in the factor VIII gene leading to replacement of Arg593 by Cys in the A2 domain of factor VIII was associated with hemophilia A in this patient. The anti-factor VIII antibodies present in the patient's plasma were characterized using metabolically labeled factor VIII fragments expressed in insect cells. The anti-factor VIII antibodies, composed of subclasses IgG2 and IgG4, reacted with both the fragment corresponding to the factor VIII heavy chain and the A2 domain. The Arg593 --> Cys substitution was introduced into the cDNA encoding the A2 domain of factor VIII and the resulting construct was expressed in insect cells. Strikingly, the metabolically labeled A2 domain carrying the Arg593 --> Cys mutation was not recognized by the anti-factor VIII antibodies present in the plasma of the patient. These data indicate that the anti-factor VIII antibodies are exclusively directed against exogenous factor VIII. This strongly suggests that the Arg593 --> Cys substitution results in recognition of wild-type factor VIII as nonself and is thereby related to the formation of anti-factor VIII antibodies after factor VIII replacement therapy in this particular patient.
Reaktionen an Indolderivaten XXXVII. Stereoselektive Synthese polycyclischer Cyclopropanderivate in der Indolochinolizin‐Reihe (1979)

Abstract Es wird über eine in guten Ausbeuten verlaufende stereoselektive Synthese des pentacyclischen Cyclopropanlactams 8 berichtet.
Associations between age, respiratory comorbidities, and dysphagia in infants with down syndrome (2019)

We confirmed that dysphagia is common in infants with DS and comorbidities and provided preliminary evidence that swallow study findings may be more likely to change in children tested under 6 months of age. Providers should consider that results for instrumental swallow studies may change, particularly if the test was completed on a young infant.
Proof of concept for continuous enantioselective liquid–liquid extraction in capillary microreactors using 1-octanol as a sustainable solvent (2017)

Separation of racemates in microreactors using liquid–liquid extraction with 1-octanol as the solvent is successfully demonstrated.
Chloro- and Trifluoromethyl-Substituted Flanking-Ring m-Terphenyl Isocyanides: η6-Arene Binding to Zero-Valent Molybdenum Centers and Comparison to Alkyl-Substituted Derivatives (2013)

Presented herein are synthetic and structural studies exploring the propensity of m-terphenyl isocyanide ligands to provide flanking-ring η(6)-arene interactions to zerovalent molybdenum centers. The alkyl-substituted m-terphenyl isocyanides CNAr(Mes2) and CNAr(Dipp2) (Ar(Mes2) = 2,6-(2,4,6-Me3C6H2)2C6H3; Ar(Dipp2) = 2,6-(2,6-(i-Pr)2C6H3)2C6H3) react with Mo(η(6)-napthalene)2 in a 3:1 ratio to form tris-isocyanide η(6)-arene Mo complexes, in which a flanking mesityl or 2,6-diisopropylphenyl group, respectively, of one isocyanide ligand is bound to the zerovalent molybdenum center. Thermal stability and reactivity studies show that these flanking ring η(6)-arene interactions are particularly robust. To weaken or prevent formation of a flanking-ring η(6)-arene interaction, and to potentially provide access to the coordinatively unsaturated [Mo(CNAr(R))3] fragment, the new halo-substituted m-terphenyl isocyanides CNAr(Clips2) and CNAr(DArF2) (Ar(Clips) = 2,6-(2,6-Cl2C6H3)2(4-t-Bu)C6H2; Ar(DArF2) = 2,6-(3,5-(CF3)2C6H3)2C6H3) have been prepared. Relative to their alkyl-substituted counterparts, synthetic and structural studies demonstrate that the flanking aryl rings of CNAr(Clips2) and CNAr(DArF2) display a lower tendency toward η(6)-binding. In the case of CNAr(DArF2), it is shown that an η(6)-bound 3,5-bis(trifluoromethyl)phenyl group can be displaced from a zerovalent molybdenum center by three molecules of acetonitrile. This observation suggests that the CNAr(DArF2) ligand effectively masks low-valent metal centers in a fashion that provides access to low-coordinate isocyano targets such as [Mo(CNAr(R))3]. A series of Mo(CO)3(CNAr(R))3 complexes were also prepared to compare the relative π-acidities of CNAr(Mes2), CNAr(Clips2), and CNAr(DArF2). It is found that CNAr(DArF2) shows increased π-acidity relative to CNAr(Mes2) and CNAr(Clips2), despite the fact that its electron-withdrawing CF3 groups are fairly distal to the terminal isocyano unit.
Phase Separation of Binary Blends in Polymer Nanoparticles (2007)

Polymer blends in nanoparticles have been studied by transmission electron microscopy (TEM) and photoluminescence (PL) spectroscopy. The TEM studies show that blend particles formed from two immiscible polymers by the miniemulsion process exhibit biphasic morphologies. The fact that no core-shell type but Janus-like structures were found indicates that the surface free energies between both polymers and the solution-water interface (including the surfactant molecules) are similar; therefore, the blend morphology and composition of the individual phases are mainly determined by the interaction between the two polymer components. Both the TEM studies and the PL experiments provide strong evidence that phase separation in these particles strictly follows the Flory-Huggins theory. This highlights the applicability of the nanoparticle approach to fabricate blend systems with well-controllable properties and to study structure-property relationships under well-defined conditions.
The Development of the Rotational Friction Welding Process for the Welding of γ-TiAl-Casting Alloy Ti-47Al-3.5(Mn+Cr+Nb)-0.8(B+Si) to Ti6Al4V (2014)

Abstract This article reports on the development of the rotational friction welding process for the welding of γ-TiAl- casting alloy Ti-47Al-3.5(Mn+Cr+Nb)-0.8(B+Si) to Ti6Al4V base metal and on the characterisation of the mechanical and microstructural properties of dissimilar metal friction welding. Pre- and post welding heat treatment is necessary in order to reduce the occurrence of bonding defects. The mechanical behaviour of friction welded joints under tensile loading at room temperature is primarily determined by the properties of the inter-metallic γTiAl- casting alloy base metal and not by the bonding zone itself. At the relevant service temperature of 700 °C, failure by fracture does not take place on the Ti6Al4V side of the dissimilar metal friction welded joint due to the super-plastic deformation of this alloy.
TROPiCS-03: A phase 2 basket study of sacituzumab govitecan (SG) in patients (pts) with metastatic solid tumors—Early analysis in pts with advanced/metastatic endometrial cancer (EC). (2023)

5610 Background: Pts with advanced/metastatic EC who progressed on or after platinum (PT)-based and anti–PD-(L)1 therapies have a poor prognosis with limited treatment options. SG is a Trop-2–directed antibody-drug conjugate. In the open-label, phase 1/2 IMMU-132-01 basket study, SG monotherapy resulted in a 22% objective response rate (ORR) with a manageable safety profile in 18 pts with metastatic EC who had relapsed after or were refractory to ≥1 prior standard therapeutic regimen (Bardia et al. Ann Oncol. 2021). Here, we report early data in pts with advanced/ metastatic disease from the EC cohort of the TROPiCS-03 Ph2 study. Methods: TROPiCS-03 (NCT03964727) is a multicohort, open-label, Ph 2 basket study in pts with metastatic solid tumors. Adult pts in the EC cohort progressed after prior PT-based chemotherapy and anti–PD-(L)1 directed therapy [requirement for PD-(L)1 progression added in amendment], had ECOG PS 0-1 and creatinine clearance ≥30 mL/min. Pts received 10 mg/kg of SG on D1 and D8 of a 21-D cycle. The primary endpoint was ORR by investigator’s assessment per RECIST 1.1. Secondary endpoints included duration of response (DOR), clinical benefit rate (CBR), and progression-free survival (PFS) per investigator’s assessment, overall survival, and safety. The safety population included pts who received ≥1 dose of SG; the efficacy population included pts receiving ≥1 dose of SG and had ≥13 weeks of follow-up. Results: As of data extraction on October 11, 2022, 28 pts received ≥1 dose of SG. Median study follow-up was 5.3 mo (range, 0.4-13.1); median age 69 y (range, 44-83), 57% ECOG PS 1,14% microsatellite instability high. Pts received a median of 3 prior therapies (range, 1-6); 100% received prior PT-based chemotherapy, 61% prior immunotherapy, 54% prior targeted agents, and 11% prior hormonal therapy. In 20 pts with ≥13 weeks of follow-up, ORR was 25% (95% CI, 8.7-49.1). Regarding best overall response, all responses were partial response (PR). In addition, stable disease (SD) was 40% and progressive disease was 15%; CBR (confirmed complete response + PR + SD ≥ 6 mo) was 35% (95% CI, 15.4-59.2). Median PFS was 5.6 mo (95% CI, 2.3 mo-not reached [NR]) and median DOR was NR (95% CI, 2.76 mo-NR; n = 5). Treatment was ongoing for 50% of pts. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 64% of pts; most common grade ≥3 TRAEs were neutropenia (25%), febrile neutropenia (14%), and diarrhea (14%). Discontinuation rate due to TRAEs was 7%. While on treatment, two deaths occurred due to causes unrelated to SG. Conclusions: Preliminary findings showed encouraging efficacy of SG with a manageable toxicity profile in a pretreated population with advanced/metastatic EC. Safety signals were consistent with the known SG safety profile. This early analysis will be updated with the full dataset. Clinical trial information: NCT03964727 .
Novel In-Service OSNR Monitoring Method for Reconfigurable Coherent Networks (2018)

A novel in-service OSNR monitoring technique is experimentally validated on tightly filtered polarization-multiplexed signals for a range of network operating conditions and reconfigurations. The results demonstrate sufficient accuracy and robustness for measurements in practical networks.
Validation of the FAM19A4 / mir124-2 DNA methylation test for both lavage- and brush-based self-samples to detect cervical (pre)cancer in HPV-positive women (2016)

FAM19A4/mir124-2 methylation analysis performs equally well in HPV-positive lavage- and brush self-samples to identify women with CIN3+. In combination with HPV16/18 genotyping, significantly higher CIN3+ sensitivities are obtained, at decreased specificity.
O4–03–04: Safety assessments and biomarker changes following a monoclonal Aβ antibody given to subjects with Alzheimer's disease (2006)

Immune therapies have been suggested as treatments for Alzheimer's disease (AD). A humanized monoclonal antibody directed at the central domain of Aβ was investigated for safety and biomarker changes. Subjects with AD were given a single intravenous infusion over approximately 30 minutes. Cohorts 1–4 were given doses of 0.5 mg/kg, 1.5 mg/kg, 4.0 mg/kg and 10 mg/kg respectively or placebo. Magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) samples were obtained at baseline and 21 days after treatment. The Alzheimer's Disease Assessment Scale – cognition (ADAS–cog) was administered at baseline and 3 and 21 days after dosing. Multiple plasma samples were taken for pharmacokinetic and Aβ analyses. The mean age for antibody–treated subjects was 69.0 ± 8.5 years (N=4 for each dose group) and 70.3 ± 5.5 years for placebo–treated subjects (N=3). Mean baseline Mini–Mental Status Exam (MMSE) scores were 19.7 ± 3.3 and 19.3 ± 2.5 for antibody– and placebo–treated subjects respectively. Adverse events were similar among the cohorts except that 2 of 4 subjects receiving 10 mg/kg reported mild shaking and dizziness lasting less than 2 hours after the infusions. Routine safety laboratory values, CSF cell counts and protein, and MRI scans were unremarkable. ADAS–cog scores showed no consistent changes. Plasma Aβ1–40 concentrations at baseline were 226 +40 pg/mL, 249 ± 85 pg/mL, 135 ± 31 pg/mL, and 163 ± 83 pg/mL for subjects receiving antibody in Cohorts 1–4 respectively. These values increased to maximum values of 32,900 ± 9150 pg/mL, 52,675 ± 8882 pg/mL, 85,600 ± 26,533 pg/mL, and 81,700 ± 5370 pg/mL respectively (p< 0.0001). CSF Aβ1–40 concentrations, expressed as a percent of baseline value, were 89% (60–107%); 120% (72–196%); 132% (159–170%) and 178% (87–237%) [mean (range)] after treatment for Cohorts 1–4 respectively (p=0.11 for linearity with dose). The terminal half–life of the antibody was approximately 3–4 weeks. Single doses of this humanized antibody were well tolerated up to 4 mg/kg. No change in cognitive function, but a marked increase in plasma Aβ was demonstrated.
Improvements to Phenomenologically Modeled Behavior of Shape Memory Alloys (2009)

This paper presents improvements to phenomenological modeled behavior of Shape Memory Alloys (SMAs). The specific type of SMA analyzed is the two-way SMA wire that contracts upon heating and extends upon cooling due to an internal phase transformation. To optimally design controllers for SMAs, the proposed model accounts for varying conditions such as input supply voltages and wire diameters and at the same time exhibits attractive numerical features such as differentiability and numerical stability. The paper also analyzes some of the shortcomings of the conventional nonlinear model. For example, the conventional model is not fully able to describe the initial contraction behavior due to an artificial dead zone. The proposed improvements include a new method of approximating the phase transformation behavior, incorporating a dynamic internal resistance, and implementing a heat transfer model that accounts for changing diameter and latent heat. Nonlinear system identification is performed to show the effectiveness of the improved model.
20306 Simulation of Removal Rate Dependency on Polishing Pressure in ECMP (2010)

As the first stage of predicting the step height reduction of Cu wiring pattern in dissolution-type electro-chemical mechanical polishing (ECMP), the removal rate dependency on the polishing pressure was simulated. Simulation results showed lower removal rate than experimental value, but the difference was almost within the range of the experimental error. Therefore, the simulation method is thought applicable to simulate the step height reduction of wiring pattern.