gebhart/patrepeval huggingface dataset:
Cross-Species Investigations Reveal Role, Mechanism and Predictive Power of Paracrine, Secondary Senescence in B-Cell Lymphoma Therapy (2012)

Abstract Abstract 3715 Apoptosis and cellular senescence operate as anti-tumor safeguard mechanisms. Unlike apoptotic cells, senescent cells remain viable, and, hence, may crosstalk to other cells in their vicinity over extended periods of time. In fact, cells that entered oncogene-induced senescence or anticancer therapy-induced senescence (TIS) present with a senescence-associated secretory phenotype (SASP), a massive production of secretable factors, which reportedly reinforces senescence through an intracellular mechanism. Utilizing the Eμ-myc transgenic mouse lymphoma model, we provide evidence for an outcome-relevant paracrine, DNA damage-independent secondary senescence program (SecS) in vitro and in vivo. Apoptosis-blocked (bcl2-infected) lymphoma cells from different genetic backgrounds were treated with the DNA-damaging anticancer agent adriamycin in vitro or the alkylating agent cyclophosphamide upon lymphoma formation in mice in vivo. TIS and SecS was detected based on senescence-associated b-galactosidase activity (SA-b-gal), Ki67 staining and BrdU incorporation. The secretome of senescent cells was analyzed by proteomics, gene expression and protein arrays. Overall and progression free survival in mice and patients was assessed by Kaplan-Meier analysis. Transcriptome and secretome analyses followed by functional studies found extracellular matrix proteins, especially small leucine-rich proteoglycans (SLRP), but not NF-kB-dependent cytokines and chemokines, to induce SecS in proliferating lymphoma cells in a paracrine fashion, and linked a “high secretor” status to stronger SecS induction. Dissecting senescence-mediating pathways in recipient cells by biochemical, genetic and pharmacological means unveiled an essential role for the LDL receptor-related protein 1 (LRP1), a receptor for SLRP and other SASP components, through the cell-cycle inhibitor p21CIP1 in SecS. Accordingly, mice harboring TIS-capable but genetically SecS-defective lymphomas (e.g. lacking LRP1 or p21CIP1 expression) experienced inferior long-term outcome to therapy. Not only the recipient cell-based LRP1 status but also the genetically and biologically distinct donor cell-based secretor gene signature stratified outcome in mice. Strikingly, humanized versions of both classifiers were predictive in a large cohort of diffuse large B-cell lymphoma (DLBCL) patients, where they identified – although composed of different gene sets – largely overlapping patient subgroups with superior prognosis, again suggesting SecS as the critical underlying treatment effector principle. Our study highlights the predictive power of senescence for treatment outcome in DLBCL, and provides functional examples (which will be discussed at the meeting) for SASP-related non-genotoxic pro-senescent therapies. Disclosures: No relevant conflicts of interest to declare.
The Puzzles and Resolvent in the Development of Traditional Chinese Medicine (2003)

Ever since the 1950's,scholars have made a great deal of experimental and clinical researches to find ways to combine TCM with the modern medicine and to modernize TCM. But,most of the works were not so successful.The sticking point is that usually we just make copy of the research methods of modern medicine in our studies,but have not find a specific way to modernize TCM.In this paper we discussed the key difference between TCM and the modern medicine,the kernel of the basic theory of TCM,the combination of TCM with the modern medicine,the type of scholars in dire need of the modernization of TCM,the linguistic conversion,the connotation of the modernization of TCM and the modernization of Chinese herbs.Thus we get the conclusion that to develop TCM,we must find our own way.
In situ determination of kinetic parameters for biofilms: Isolation and characterization of oligotrophic biofilms (1986)

This article develops and utilizes an in situ technique to estimate the Monod half-maximum rate concentration, K(s) and the maximum specific utilization rate constant, k, for biofilms. The technique employs a curve-matching method with kinetic results from several short-term experiments with completely mixed biofilm reactors. Use of the in situ method eliminates the two drawbacks of using conventional suspended-growth measurements to characterize biofilm: possible alteration of cell physiology and a major investment to run the suspended-growth tests. Results with five cultures of biofilm-forming oligotrophs demonstrated the in situ technique and supported the hypothesis that K(s) values were lower for the biofilm oligotrophs than for typical copiotrophs.
A single oral dose of Silodosin and Diclofenac sodium is effective in reducing pain after ureteric stent removal: a prospective, randomized, double blind placebo-controlled study (2016)

A prospective double-blinded placebo controlled randomized study was conducted in our institute to compare the efficacy of oral Silodosin, an alpha 1 selective antagonist and Diclofenac in relieving pain after stent removal. All patients with unilateral stent placement following renal and ureteric stone endoscopic surgery were randomized into four groups: group A (Placebo), group B (Diclofenac), group C (Silodosin) and group D (combination of Diclofenac and Silodosin). Visual analogue score (VAS score) and other relevant parameters were assessed during OPD visit. Patients were handed over randomized drug envelope and asked to take the medications one hour before the stent removal. Patients were contacted 24 h after stent removal and relevant parameters were recorded. The mean VAS scores were significantly decreased in Diclofenac (2.9), Silodosin (3.08) and combination group (2.85) when compared to placebo (4.20) (p < 0.001). However there was no statistically significant difference in VAS scores between the treatment groups, i.e., group B, C and D (p > 0.5). Analgesics requirement and severe pain rates were not significantly reduced (p = 0.07, 0.35) in the three treatment groups when compared to placebo. Thus Silodosin and Diclofenac, both are effective in preventing pain after stent removal.
Heterozygous and homozygous variants in STX1A cause a neurodevelopmental disorder with or without epilepsy (2022)

The neuronal SNARE complex drives synaptic vesicle exocytosis. Therefore, one of its core proteins syntaxin 1A (STX1A) has long been suspected to play a role in neurodevelopmental disorders. We assembled eight individuals harboring ultra rare variants in STX1A who present with a spectrum of intellectual disability, autism and epilepsy. Causative variants comprise a homozygous splice variant, three de novo missense variants and two inframe deletions of a single amino acid. We observed a phenotype mainly driven by epilepsy in the individuals with missense variants in contrast to intellectual disability and autistic behavior in individuals with single amino acid deletions and the splicing variant. In silico modeling of missense variants and single amino acid deletions show different impaired protein-protein interactions. We hypothesize the two phenotypic courses of affected individuals to be dependent on two different pathogenic mechanisms: (1) a weakened inhibitory STX1A-STXBP1 interaction due to missense variants results in an STX1A-related developmental epileptic encephalopathy and (2) a hampered SNARE complex formation due to inframe deletions causes an STX1A-related intellectual disability and autism phenotype. Our description of a STX1A-related neurodevelopmental disorder with or without epilepsy thus expands the group of rare diseases called SNAREopathies.
New method for connection of test bus to a line interface circuit (1986)

An arrangement for the connection of the inward test bus to subscriber line interface circuits in an electronic telephone exchange is proposed. The described solution uses significantly fewer relays or high-voltage switches than previous solutions.
Abstract 367: Pcsk6 Is a Key Protease Modulating Smooth Muscle Cell Activation in Vascular Remodeling and Plaque Vulnerability (2015)

Proprotein convertases (PCSKs) are conserved among species and involved in processing of MMPs and growth factors, but poorly characterised in atherosclerosis. Previously we demonstrated upregulation of PCSK6 in a large cohort of plaques from symptomatic vs. asymptomatic patients. This protease localized to smooth muscle cells (SMCs) and showed a positive correlation to markers of inflammation, extracellular matrix remodeling and cytokines in plaques. Here we aimed at elucidating its role in vascular development and disease. In zebrafish embryos PCSK6 localized to heart and vasculature and its ablation caused defective peripheral vascular patterning with cerebral and myocardial hemorrhage. Increased expression of PCSK6 in vascular pathologies was validated by microarrays from carotid plaques vs. undiseased arteries (n=32 patients, p&lt;0.0001), abdominal (AAA, n=14, p&lt;0.0001) and thoracic aortic aneurysms (TAA, n=244, p=0.012). By immunohistochemistry, PCSK6 localized mainly to SMCs in the fibrous cap and neo-vessels in plaques, AAA and TAA tissues. Investigation of mouse carotid ligation, rat artery balloon injury and human restenosis tissues with pronounced intimal hyperplasia confirmed induction of PCSK6 in proliferating SMCs. By microarrays following progression of rat carotid injury, PCSK6 was downregulated in early phases defined by inflammatory pathways, while upregulated in later phases with SMCs activation and localized in SMCs. Expression of PCSK6 in this model was positively correlated to PDGFB and IGF1 (Spearman r&gt;0.7, p&lt;0.0001). PCSK6 overexpression in SMCs in vitro increased their migration in a wound-healing assay, especially upon PDGFBB stimulation. By eQTL analyses several polymorphisms in the PCSK6 gene were found to influence its expression in plaques and aneurysm tissue. Among these, rs6598465 showed association with maximum progression of arterial intima-media thickness in high-risk coronary artery disease subjects (n=3400, p=0.037). We identified a functional link between elevated expression of PCSK6 and vascular remodeling characterized by SMC activation. The present study establishes PCSK6 as one of the key modulators of pathological processes in relation to plaque vulnerability.
Prevention of total thyroidectomy in noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) based on combined interpretation of ultrasonographic and cytopathologic results (2017)

Combining the US and cytopathological results could sensitively reduce total thyroidectomy in cases of NIFTP.
Developing a Nuclear Grade of Alloy 617 for Gen IV Nuclear Energy Systems (2010)

Alloy 617, an attractive material not particularly developed for nuclear use, is now being considered as a leading candidate alloy by several countries for applications in the Gen IV Nuclear Energy Systems. An extensive review of its existing data suggests that it would be beneficial to refine the alloy s specification to a nuclear grade for the intended Gen IV systems. In this paper, rationale for developing a nuclear grade of the alloy is first discussed through an analysis on existing data from various countries. Then initial experiments for refining the alloy specification are described. Preliminary results have suggested the feasibility of the refinement approach, as well as the possibility for achieving a desirable nuclear grade. Based on the results, further research activities are recommended.
Preparation of high solids content poly(n-butyl acrylate) latexes through miniemulsion polymerization (1997)

An approach to prepare high solids content latexes (> 50 wt %) is presented. The approach is based on a two-stage polymerization where in the first stage low-to-medium solids content seed latexes with a broad particle-size distribution (PSD) were prepared by semicontinuous miniemulsion polymerization. In the second polymerization stage, the solids contents of the latexes prepared in the previous step were increased to 60–70 wt % using relatively low emulsifier concentrations. The approach was used successfully to prepare fluid- and coagulum-free poly(n-butyl acrylate) latexes up to solids contents of 61 wt % using an emulsifier (sodium lauryl sulfate) concentration of 0.5 wt % based on a monomer. Nonfluid (pastelike) latexes having solids contents higher than 61 wt % were also prepared using this method. As a result, some guidelines related to the required particle-size distribution to produce fluid latexes of higher solids contents are also presented. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 64: 1797–1809, 1997
Structure Based Prediction of Protein Folding Intermediates (1994)

The complete unfolding of a protein involves the disruption of non-covalent intramolecular interactions within the protein and the subsequent hydration of the backbone and amino acid side-chains. The magnitude of the thermodynamic parameters associated with this process is known accurately for a growing number of globular proteins for which high-resolution structures are also available. The existence of this database of structural and thermodynamic information has facilitated the development of statistical procedures aimed at quantifying the relationships existing between protein structure and the thermodynamic parameters of folding/unfolding. Under some conditions proteins do not unfold completely, giving rise to states (commonly known as molten globules) in which the molecule retains some secondary structure and remains in a compact configuration after denaturation. This phenomenon is reflected in the thermodynamics of the process. Depending on the nature of the residual structure that exists after denaturation, the observed enthalpy, entropy and heat capacity changes will deviate in a particular and predictable way from the values expected for complete unfolding. For several proteins, these deviations have been shown to exhibit similar characteristics, suggesting that their equilibrium folding intermediates exhibit some common structural features. Employing empirically derived structure-energetic relationships, it is possible to identify in the native structure of the protein those regions with the higher probability of being structured in equilibrium partly folded states. In this work, a thermodynamic search algorithm aimed at identifying the structural determinants of the molten globule state has been applied to six globular proteins; alpha-lactalbumin, barnase, IIIGlc, interleukin-1 beta, phage T4 lysozyme and phage 434 repressor. Remarkably, the structural features of the predicted equilibrium intermediates coincide to a large extent with the known structural features of the corresponding intermediates determined by NMR hydrogen-exchange experiments.
Prolonged‐release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects (2007)

Melatonin, secreted nocturnally by the pineal gland, is an endogenous sleep regulator. Impaired melatonin production and complaints on poor quality of sleep are common among the elderly. Non-restorative sleep (perceived poor quality of sleep) and subsequently poor daytime functioning are increasingly recognized as a leading syndrome in the diagnostic and therapeutic process of insomnia complaints. The effects of 3-weeks prolonged-release melatonin 2 mg (PR-melatonin) versus placebo treatment were assessed in a multi-center randomized placebo-controlled study in 170 primary insomnia outpatients aged > or =55 years. Improvements in quality of sleep (QOS) the night before and morning alertness (BFW) were assessed using the Leeds Sleep Evaluation Questionnaire and changes in sleep quality (QON) reported on five categorical unit scales. Rebound insomnia and withdrawal effects following discontinuation were also evaluated. PR-melatonin significantly improved QOS (-22.5 versus -16.5 mm, P = 0.047), QON (0.89 versus 0.46 units; P = 0.003) and BFW (-15.7 versus -6.8 mm; P = 0.002) compared with placebo. The improvements in QOS and BFW were strongly correlated (Rval = 0.77, P < 0.001) suggesting a beneficial treatment effect on the restorative value of sleep. These results were confirmed in a subgroup of patients with a greater symptom severity. There was no evidence of rebound insomnia or withdrawal effects following treatment discontinuation. The incidence of adverse events was low and most side-effects were judged to be of minor severity. PR-melatonin is the first drug shown to significantly improve quality of sleep and morning alertness in primary insomnia patients aged 55 years and older-suggesting more restorative sleep, and without withdrawal symptoms upon discontinuation.
Bone Marrow Edema and Joint Overuse in Athletes: a Mini-Review (2020)

Bone marrow edema (BME) on MRI is defined as an area of
low signal intensity on Tl-weighted MR images and associated...
Behavior of Inorganic Nanoparticles in Silver Polymer Electrolytes and Their Effects on Silver Ion Activity for Facilitated Olefin Transport (2009)

TiO2 and Al2O3 nanoparticles having different chemical properties were introduced into a poly(2-ethyl-2-oxazoline) (POZ) membrane to make inactive AgNO3 chemically more active in olefin complexation, resulting in facilitated olefin transport. The interaction schemes were particularly emphasized to understand the activation of AgNO3 for facilitated olefin transport. The separation performances were similar in both cases, consistent with similar changes in the binding energy of silver ions and the relative concentrations of the added ionic species. However, the bond strength of C═O in POZ increased with TiO2 whereas it decreased with Al2O3, as confirmed by FT-IR spectroscopy. This difference was explained in terms of the difference in the zeta potential: TiO2 and Al2O3 displayed zeta potentials of −18 and +6.5 mV at pH 4, respectively. On the basis of these, the following interaction scheme was proposed: the TiO2 nanoparticles predominantly interact with silver cations, whereas the Al2O3 nanoparticles preferentially interact with NO3−. As a result, both nanoparticles help to loosen the bond strength between Ag+ and NO3−, resulting in the activation of the silver cations in olefin complexation; consequently, olefin transport is facilitated, which results in improved separation performance in the separation of propylene/propane mixtures.
PanCGH: a genotype-calling algorithm for pangenome CGH data (2009)

We have developed the algorithm PanCGH that incorporates orthology information about genes to predict the presence or absence of orthologous genes in a query organism using CGH arrays that target the genomes of sequenced representatives of a group of microorganisms. PanCGH was tested and applied in the analysis of genetic diversity among 39 Lactococcus lactis strains from three different subspecies (lactis.cremoris, hordniae) and isolated from two different niches (dairy and plant). Clustering of these strains using the presence/absence data of gene orthologs revealed a clear separation between different subspecies and reflected the niche of the strains.
Efficient and Copper-Free Pd(OAc)2/DABCO-Catalyzed Sonogashira Cross-Coupling Reaction (2005)

An efficient and copper-free palladium-catalyzed Sonogashira cross-coupling reaction protocol is presented. In the presence of 3 mol% of Pd(OAc)2 and 6 mol% of DABCO, cross-coupling of various aryl halides (iodides and bromides) with terminal alkynes afforded the corresponding alkynes in moderate to excellent­ yields. Moreover, high TONs (turnover numbers, up to 720 000 for the reaction of 1-iodo-4-nitrobenzene with phenylacetylene) for the Sonogashira cross-coupling reaction were observed.
Impact of Driving Cycles on Greenhouse Gas Emissions and Fuel Economy for SI Car Real World Driving (2008)

&lt;div class="htmlview paragraph"&gt;The transport sector is one of the major contributors to greenhouse gas emissions. This study investigated three greenhouse gases emitted from road transport: CO&lt;sub&gt;2&lt;/sub&gt;, N&lt;sub&gt;2&lt;/sub&gt;O and CH&lt;sub&gt;4&lt;/sub&gt; emissions as a function of engine warm up and driving cycles. Five different urban driving cycles were developed and used including free flow driving and congested driving. An in-vehicle FTIR (Fourier Transform Inferred) emission measurement system was installed on a EURO2 emission compliant SI (Spark Ignition) car for emissions measurement at a rate of 0.5 HZ under real world urban driving conditions. This emission measurement system was calibrated on a standard CVS (Constant Volume Sampling) measurement system and showed excellent agreement on CO&lt;sub&gt;2&lt;/sub&gt; measurement with CVS results. The N&lt;sub&gt;2&lt;/sub&gt;O and CH&lt;sub&gt;4&lt;/sub&gt; measurement was calibrated using calibration gas in lab. A MAX710 real time in-vehicle fuel consumption measurement system was installed in the test vehicle and real time fuel consumption was then obtained. The temperatures across the TWC (Three Way Catalyst) and engine out exhaust gas lambda were measured. The GHG (greenhouse gas) mass emissions and consequent GWP (Global Warming Potential) for different urban diving conditions were analyzed and presented. The results provided a better understanding of traffic related greenhouse gas emission profile in urban area and will contribute to the control of climate change.&lt;/div&gt;
Erratum: Developmental phytotoxicity of metal oxide nanoparticles to Arabidopsis thaliana (2010)

On page 669, Reference [14] in the manuscript discusses the effects of nTiO2 on the growth of spinach (Spinacia oleracea). We cited the reference as reporting promotion of spinach growth with the addition of nTiO2 at 2.5 to 40 g/kg of soil. It was incorrectly stated and should be replaced with “addition of nTiO2 at .25 to 4.0% in solution.” The seeds were soaked in nTiO2 solution then planted. Page 673, “and caused complete germination failure at 4,000 mg/L compared to 4,000 mg/L for micron-sized…” should read “and caused complete germination failure at 400 mg/L compared to 4,000 mg/L for micron-sized…”
Q&A. How Do You Program Innovative Thinking into Company Culture? (2013)

Q. How do you program innovative thinking into company culture?A. When someone in a business context mentions “innovation”, we tend to think about someone like Steve Jobs, Henry Ford, or perhaps Thomas Edison. We often associate innovation with an individual and their force of personality, entrepreneurial spirit, and dogged determination to bend the world to their way.