gebhart/patrepeval huggingface dataset:
Nonlysosomal, pre-Golgi degradation of unassembled asialoglycoprotein receptor subunits: a TLCK- and TPCK-sensitive cleavage within the ER. (1991)

The human asialoglycoprotein receptor subunit H2a is cotranslationally inserted into the ER membrane. When expressed together with subunit H1 in mouse fibroblasts part forms a hetero-oligomer that is transported to the cell surface, but when expressed alone it is all rapidly degraded. Degradation is insensitive to lysosomotropic agents and the undegraded precursor is last detected in the ER region of the cell. Small amounts of an intermediate 35-kD degradation product can be detected (Amara, J. F., G. Lederkremer, and H. F. Lodish. 1989. J. Cell Biol. 109:3315). We show here that the oligosaccharides on both precursor H2a and the 35-kD fragment are Man6-9GlcNAc2, structures typically found in pre-Golgi compartments. Subcellular fractionation shows that the intermediate degradation product does not cofractionate with the lysosomal enzyme beta-galactosidase, but is found in a part of the ER that contains ribosomes. Thus the intermediate degradation product is localized in the ER, indicating that the initial degradation event does take place in the ER. All degradation of H2a, including the initial endoproteolytic cleavage generating the 35-kD intermediate, is blocked by the protease inhibitors N-tosyl-L-lysine chloromethyl ketone and N-tosyl-L-phenylalanine chloromethyl ketone. These drugs do not inhibit ER-to-Golgi transport of H1. Depleting the cells of ATP or inhibiting protein synthesis allows the initial endoproteolytic cleavage to occur, but blocks further degradation of the 35-kD intermediate; thus we can convert all cellular H2 into the 35-kD intermediate. Approximately 50% of H2b, a splicing variant differing from H2a by a five amino acid deletion, can be transported to the cell surface, and the rest appears to be degraded by the same pathway as H2a, both when expressed alone in fibroblasts and together with H1 in HepG2 cells. Addition of N-tosyl-L-lysine chloromethyl ketone or N-tosyl-L-phenylalanine chloromethyl ketone blocks degradation of the approximately 50% that is not transported, but does not affect the fraction of H2b that moves to the Golgi region. Thus, a protein destined for degradation will not be transported to the Golgi region if degradation is inhibited.
Multiple myeloma treated with high dose intravenous melphalan (1987)

High dose melphalan (HDM, 140 mg/m2 i.v.) has been evaluated in 58 patients under 63 years with multiple myeloma. Among previously untreated patients 11/41 (27%) entered a complete remission (CR: no measurable myeloma protein and a normal bone marrow) and 21 (51%) entered a partial remission (more than 50% reduction in myeloma protein and improvement in all other features). Median duration of remission is 19 months. Two patients who had responded to previous conventional treatment entered CR after HDM. Among 15 patients who had failed on previous chemotherapy the response rate was 66% including two CRs. However, in this group all patients have relapsed within 1 year. Profound myelosuppression, moderate nausea, vomiting, mucositis and diarrhoea with reversible alopecia occurred in all patients. There were 10 deaths within 2 months of treatment mainly due to sepsis and haemorrhage. In a subsequent study, high dose methyl prednisolone (1 g/m2 daily for 5 d) has been added to HDM. Response rates are similar with 6/22 (27%) CR, 13/22 (59%) PR and 2/22 NR but there was only one early death, reflecting improvements in medical management. The high CR rate is an encouraging feature of this approach which is now to be the basis of a prospective trial sponsored by the Medical Research Council in which HDM, with and without steroids, is compared to the best available conventional therapy (the MRC VI Myelomatosis trial).
Editor's Page (2001)

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTEditor's PageDietmar SeyferthCite this: Organometallics 2001, 20, 24, 4977Publication Date (Web):November 19, 2001Publication History Published online19 November 2001Published inissue 1 November 2001https://pubs.acs.org/doi/10.1021/om010906thttps://doi.org/10.1021/om010906teditorialACS PublicationsCopyright © 2001 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views391Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (34 KB) Get e-AlertscloseSUBJECTS:Alloys,Anions,Molecules,Physical and chemical processes,Silicones Get e-Alerts
Thermostable alanine dehydrogenase from thermophilic <i>Bacillus sphaericus</i> DSM 462 (1990)

Alanine dehydrogenase (L-alanine: NAD+ oxidoreductase, deaminating) was simply purified to homogeneity from a thermophile, Bacillus sphaericus DSM 462, by ammonium sulfate fractionation, red-Sepharose 4B chromatography and preparative slab gel electrophoresis. The enzyme had a molecular mass of about 230 kDa and consisted of six subunits with an identical molecular mass of 38 kDa. The enzyme was much more thermostable than that from a mesophile, B. sphaericus, and retained its full activity upon heating at 75 degrees C for at least 60 min and with incubation in pH 5.5-9.5 at 75 degrees C for 10 min. The enzyme can be stored without loss of its activity in a frozen state (-20 degrees C, at pH 7.2) for over 5 months. The optimum pH for the L-alanine deamination and pyruvate amination were around 10.5 and 8.2, respectively. The enzyme exclusively catalyzed the oxidative deamination of L-alanine in the presence of NAD+, but showed low amino acceptor specificity; hydroxypyruvate, oxaloacetate, 2-oxobutyrate and 3-fluoropyruvate are also aminated as well as pyruvate in the presence of NADH and ammonia. Initial velocity and product inhibition studies showed that the reductive amination proceeded through a sequential mechanism containing partially random binding. NADH binds first to the enzyme, and then pyruvate and ammonia bind in a random fashion. The products are sequentially released from the enzyme in the order L-alanine then NAD+. A dead-end inhibition by the formation of an abortive ternary complex which consists of the enzyme, NAD+ and pyruvate was included in the reaction. A possible role of the dead-end inhibition is to prevent the enzyme from functioning in the L-alanine synthesis. The Michaelis constants for the substrates were as follows: NADH, 0.10 mM; pyruvate, 0.50 mM; ammonia, 38.0 mM; L-alanine, 10.5 mM and NAD+, 0.26 mM.
Suppl. Figure 9 from Integrated Genomic and Immunophenotypic Classification of Pancreatic Cancer Reveals Three Distinct Subtypes with Prognostic/Predictive Significance (2023)

&lt;p&gt;RHAMM&lt;/p&gt;
Decomposition in Reliability Analysis of Fault-Tolerant Systems (1983)

Two important problems which arise in modeling fault-tolerant systems with ultra-high reliability requirements are discussed. 1) Any analytic model of such a system has a large number of states, making the solution computationally intractable. This leads to the need for decomposition techniques. 2) The common assumption of exponential holding times in the states is intolerable while modeling such systems. Approaches to solving this problem are reviewed. A major notion described in the attempt to deal with reliability models with a large number of states is that of behavioral decomposition followed by aggregation. Models of the fault-handling processes are either semi-Markov or simulative in nature, thus removing the usual restrictions of exponential holding times within the coverage model. The aggregate fault-occurrence model is a non-homogeneous Markov chain, thus allowing the times to failure to possess Weibull-like distributions. There are several potential sources of error in this approach to reliability modeling. The decomposition/aggregation process involves the error in estimating the transition parameters. The numerical integration involves discretization and round-off errors. Analysis of these errors and questions of sensitivity of the output (R(t)) to the inputs (failure rates and recovery model parameters) and to the initial system state acquire extreme importance when dealing with ultra-high reliability requirements.
Calorimetric study of field-induced ferroelectric transition in Pb(Mg&lt;inf&gt;1/3&lt;/inf&gt;Nb&lt;inf&gt;2/3&lt;/inf&gt;)O&lt;inf&gt;3&lt;/inf&gt; relaxor ferroelectrics (2012)

The electric field induced ferroelectric transition was studied by heat capacity measurements in relaxor Pb(Mg <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/3</sub> Nb <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2/3</sub> )O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> (PMN) single crystal oriented in [110] direction. The modified relaxation measurements allow us to study the thermal response of sample at glassy to ferroelectric transition at isothermal condition. The thermal response of sample show a temperature anomaly at field induced transition as a consequence of the released latent heat.
Targeting prohibitins induces apoptosis in acute myeloid leukemia cells (2016)

Fluorizoline is a new synthetic molecule that induces apoptosis by selectively targeting prohibitins (PHBs). In this study, the pro-apoptotic effect of fluorizoline was assessed in two cell lines and 21 primary samples from patients with debut of acute myeloid leukemia (AML). Fluorizoline induced apoptosis in AML cells at concentrations in the low micromolar range. All primary samples were sensitive to fluorizoline irrespectively of patients' clinical or genetic features. In addition, fluorizoline inhibited the clonogenic capacity and induced differentiation of AML cells. Fluorizoline increased the mRNA and protein levels of the pro-apoptotic BCL-2 family member NOXA both in cell lines and primary samples analyzed. These results suggest that targeting PHBs could be a new therapeutic strategy for AML.
Spontaneous Formation of an Air‐Stable Radical upon the Direct Fusion of Diphenylmethane to a Triarylporphyrin (2016)

The direct fusion of a diphenylmethane segment to a Ni(II) 5,10,15-triarylporphyrin with three linkages furnished an air- and moisture-stable neutral radical through unexpected and spontaneous oxidation. This radical was demetalated by treatment with H2 SO4 and CF3 CO2 H to provide the corresponding free-base radical. These porphyrin radicals are very stable owing to spin delocalization and have been fully characterized through UV/Vis/NIR absorption spectroscopy, X-ray crystallographic analysis, magnetic susceptibility measurements, electrochemical studies, laser-based ultrafast spectroscopic studies, and theoretical calculations. They were chemically oxidized and reduced to the corresponding cation and anion but did not react with hydrogen-atom donors.
Intranasal Delivery of Lipid Nanoparticles: A Ground-breaking Approachfor Brain Targeting (2023)

Abstract: In the present scenario, various novel delivery systems are available for drug delivery to systemic circulation. So, to accomplish a greater therapeutic effect, the nature of the drug delivery is very important. This delivery is one of the innovative approaches where the drug is targeted to the brain through the nasal cavity. As we know, the human brain is the most crucial part of the body that controls various functions of our system. So, safely reaching the targeted site of the brain is necessary to achieve brain specificity. This delivery system helps us to tackle the problems that may arise in the other delivery system and helps the drug reach the brain without any difficulties. The major obstacles we faced during this delivery were the blood-brain barrier (BBB) and the brain-cerebrospinal fluid barrier. So, if we target the drug to the brain, then we have to overcome these challenges, and before that, we must have a clear understanding of the targeted site and the mechanism behind the drug targeting. Advancements in science and technology have helped discover many recent strategies and formulations available for intranasal delivery. The development of lipid nanoparticles is one of the primitive approaches for targeting any type of drug(hydrophilic/lipophilic) in the brain. So, the aim of this review mainly focused on the mechanism of intranasal delivery, the devices used, and some recent strategies like the development of lipid nanoparticles, surface-modified lipid nanocarriers, and noseto-brain patches. This review article also includes a few FDA-approved formulations for nose-to-brain delivery and their regulatory aspects related to clinical trials and future perspectives.
Efficient double electrochemiluminescence quenching based label-free highly sensitive detection of haptoglobin on a novel nanocomposite modified carbon nanofibers interface (2019)

ECL behaviour is highly dependent on electrode surface, materials and dimensions. Therefore, in this work ECL intensity of [Ru(bpy)3]2+/TPrA system was studied with the bare carbon nanofiber screen-printed electrode (CNFs-SPE) and the novel AuNPs/CdTe-QDs/SWCNTs/Chitosan nanocomposite modified CNFs-SPE (CdTe/AuNPs/SWCNTs/Chitosan/CNFs-SPE). ECL intensity was enhanced about 1.0 time with the AuNPs/CdTe-QDs/SWCNTs/Chitosan/CNFs-SPE interface in comparison to the bare CNFs-SPE. Additionally, AuNPs/CdTe-QDs/SWCNTs/Chitosan/CNFs-SPE interface produced ~ 200% increase both in electronic conductivity and in effective surface area in comparison to the bare CNFs-SPE. AuNPs/CdTe-QDs/SWCNTs/Chitosan/CNFs-SPE interface with a combined advantage of high effective surface area, electronic conductivity and ECL intensity was for the first time used to develop an efficient double ECL quenching based immunosensor for the highly sensitive and selective label-free detection of haptoglobin (Hp). Under optimum conditions, the constructed Hp-immunosensor displayed a wide: 100 fg mL−1 to 10 ng mL−1 linear detection range, with a low limit of detection 100 fg mL−1. The calibration plot provides a negative linear relationship between log[c] of Hp and ECL intensity with a coefficient of correlation 0.99. Moreover, this novel biocompatible nanocomposite interface could be used for the ECL based detection of other biomarkers and biomolecules. Keywords: Electrochemiluminescence, Nanotechnology, Biosensor, Diagnostic device, Label-free immunosensor, Haptoglobin
Supplementary Figure 1 from Ectopic Expression of Vascular Cell Adhesion Molecule-1 as a New Mechanism for Tumor Immune Evasion (2023)

Supplementary Figure 1 from Ectopic Expression of Vascular Cell Adhesion Molecule-1 as a New Mechanism for Tumor Immune Evasion
Dual targeting of MCL1 and NOXA as effective strategy for treatment of mantle cell lymphoma (2017)

Imbalances in the composition of BCL2 family proteins contribute to tumourigenesis and therapy resistance of mantle cell lymphoma (MCL), making these proteins attractive therapy targets. We studied the efficiency of dual targeting the NOXA/MCL1 axis by combining fatty acid synthase inhibitors (NOXA stabilization) with the CDK inhibitor Dinaciclib (MCL1 reduction). This combination synergistically induced apoptosis in cell lines and primary MCL cells and led to almost complete inhibition of tumour progression in a mouse model. Apoptosis was NOXA-dependent and correlated with the NOXA/MCL1 ratio, highlighting the importance of the NOXA/MCL1 balance for effective cell death induction in MCL.
Abstract 13572: Ambulatory Recordings of Cardiac Acoustic Biomarkers Demonstrate Early Recovery of Diastolic Function (2017)

Introduction: Ambulatory management of heart failure (HF) is challenging. Cardiac acoustic biomarkers (CABs) can be recorded in ambulatory settings using a noninvasive accelerometer on the chest ke...
Supplementary figure 1 from Tadalafil Reduces Myeloid-Derived Suppressor Cells and Regulatory T Cells and Promotes Tumor Immunity in Patients with Head and Neck Squamous Cell Carcinoma (2023)

&lt;p&gt;Supplementary figure 1. Gating strategy for MDSCs enumeration in the blood&lt;/p&gt;
Regulation of urokinase receptor expression by phosphoglycerate kinase is independent of its catalytic activity (2005)

Posttranscriptional regulation of urokinase-type plasminogen activator receptor (uPAR) mRNA involves the interaction of a uPAR mRNA coding region sequence with phosphoglycerate kinase (PGK), a 50-kDa uPAR mRNA binding protein. PGK catalyzes a reversible transfer of a phosphoryl group from 1,3-biphosphoglycerate to ADP in the glycolytic pathway. Our previous studies showed that overexpression of PGK in uPAR-overproducing H157 lung carcinoma cells results in decreased cytoplasmic uPAR mRNA and cell surface uPAR protein expression through destabilization of the mRNA. In order to determine the role of PGK enzymatic activity on uPAR mRNA stability we mutated PGK by changing amino acid P204H and amino acid D219A. The mutant proteins were expressed in Epicurian coli BL21 cells, and the purified proteins were analyzed for PGK activity. We found that mutation of amino acid P204H and D219A reduced PGK activity by 99 and 83%, respectively. By gel mobility shift and Northwestern assay, we found that the mutant proteins were able to bind to uPAR mRNA as effectively as wild-type PGK. Overexpression of mutant, inactive PGK in H157 cells reduced cell surface uPAR protein as well as uPAR mRNA expression. Run-on transcription analysis indicated that overexpression of mutant PGKs fails to alter the rate of synthesis of uPAR mRNA, whereas transcription chase experiments demonstrated that both mutants and wild-type PGK reduce the stability of the uPAR mRNA transcripts to a similar extent. Overexpression of mutant PGK also inhibited the rate of DNA synthesis and the invasion-migration ratio. These results demonstrate that uPAR mRNA binding activity as well as PGK-mediated regulation of uPAR mRNA are independent of PGK enzymatic activity.
Geometrical Contact Zone Analysis of the Skive Hobbing Process (2016)

In this paper, an innovative approach for contact zone analysis of skive hobbing is presented. This process is characterised by varying tool engagements and very small chip thicknesses. The paper describes the process-modelling and the analysis of the workpiece-tool contact. For efficient modelling, a novel dexel-based method for the description of a gear segment with discretized stock allowance is presented. Characteristic for the method is an analytical description of the target workpiece contour which allows to describe points of the surface by Cartesian coordinates on the winding off. On this workpiece contour, dexel are modelled in surface-orthogonal direction. The initial lengths of these dexel describe the stock allowance. By cutting these dexel with a tool, a time-and position-dependent prediction of material removal values, like width of undeformed chip, undeformed chip thickness or cutting directions can be obtained. Selected results are presented and interpreted.
Schur-based decomposition for reachability analysis of linear time-invariant systems (2009)

We present a method for complexity reduction in reachability analysis and controller synthesis via a Schur-based decomposition for LTI systems. The decomposition yields either decoupled or weakly-coupled subsystems, each of lower dimension than the original system. Reachable sets, computed for each subsystem, are back-projected and intersected to yield an overapproximation of the actual reachable set. Evaluating our method for a variety of examples (3D, 4D, and 8D), we show that significant reduction in the computational costs can be achieved. This technique has considerable potential utility for use in conjunction with computationally intensive reachability tools.
The Effect of Finishing Diet on Consumer Perception of Enhanced and Non-Enhanced Honduran Beef (2018)

The effects of experimental finishing diets and enhancement were tested to determine if they could improve Honduran beef palatability. Fifteen enhanced (ENH) and non-enhanced (NE) paired loins from 7 different finishing diets (n = 210 loins) were fed to Honduran consumers (n = 288). Diets consisted of a grass-finished control (CON) or diets with the inclusion of distiller’s dry grain (DDG), palm kernel meal (PKM), PKM replication (PKMR), sorghum (SORG), soybean meal and corn (SBMC), or sugarcane (SC). An interaction (P &lt; 0.01) occurred between diet and enhancement to influence scores for all palatability traits, willingness to pay (WTP), and acceptability of traits. Consumers found enhanced samples were more tender (P &lt; 0.05) than NE counterparts, excluding ENH- and NE-CON (P &gt; 0.05). Without enhancement, CON was rated more tender (P &lt; 0.05) than all other treatments, except PKMR. All ENH samples were juicier (P &lt; 0.05) and had a flavor that was liked more (P &lt; 0.05) than NE counterparts. Diet alone resulted in similar (P &gt; 0.05) juiciness scores between CON, DDG, PKM, and PKMR; however, CON was rated juicier (P &lt; 0.05) than all other treatments. Among NE samples, flavor liking scores were not different (P &gt; 0.05) between CON, DDG, PKM, PKMR, and SBMC, and CON was liked more (P &lt; 0.05) than SORG and SC. All enhanced steaks, except CON, had greater overall liking scores and WTP values (P &lt; 0.05) than NE counterparts. Diet alone resulted in similar (P &gt; 0.05) overall liking and WTP values between CON, DDG, PKM, PKMR, and SBMC, while SORG and SC were liked less overall (P &lt; 0.05) than CON, which reduced (P &lt; 0.05) WTP values. Experimental diets in conjunction with enhancement were able to improve the consumers’ perception of palatability traits, acceptability, and WTP.
Fabrication and Replication of Polymer Integrated Optical Devices Using Electron-Beam Lithography and Soft Lithography (2004)

Polymeric integrated optical devices, including microring resonator optical filters and Mach−Zehnder interferometer modulators, fabricated by electron-beam lithography and soft lithography are considered in this article. Microring resonator optical filters made of SU-8 (MicroChem, Newton, MA), directly patterned by electron-beam lithography, demonstrate that SU-8 is a good candidate for high-precision, easily fabricated, and good-optical-quality passive integrated optical devices. Due to the electron-beam lithography process, the coupling between the straight waveguide and the microring resonator is precisely controlled, and the critical coupling condition can be achieved. Additionally, films containing several devices patterned by electron-beam lithography are peeled from the silicon substrate, yielding ultrathin all-polymer flexible free-standing microring resonator optical filters exhibiting up to −27 dB filtering extinction. Using a PDMS stamp, molded from these electron-beam-patterned microring resonator optical filters, identical replicas are fabricated by the soft lithography molding technique. Soft lithography is also applied to active polymer materials. A short 2-mm active-section prototype Mach−Zehnder interferometer modulator is made by the replica molding process, using CLD-1/APC electrooptic polymer as the core material. A reasonable intensity-modulation effect is observed by applying voltage to one arm of the interferometer.