gebhart/patrepeval huggingface dataset:
Role of Cleaning-in-Place in the Purification of mAb Supernatants Using Continuous Cation Exchange Chromatography (2009)

Abstract Monoclonal antibodies (mAbs) are among the most important therapeutic proteins for the treatment of cancer. They also find wide application in the field of diagnostics. The market for mAbs was US$ 5.4 billion in 2002 and is expected to triple by 2010 (1). MAbs are mainly produced in cell culture and purified by chromatography. Apart from the mAb, the downstream processing is confronted with a multitude of impurities from the upstream process. Some of these impurities bind strongly to the chromatographic stationary phase and can only be removed by separate cleaning solutions. Depending on the type of media used, e.g. affinity or ion exchange, differing cleaning regimes may have to be applied. In addition, sanitization is required to prevent microbial contamination. Both steps are closely tied to the mAb production step and need to be repeated in regular intervals. In this work, the impact of irreversible impurity adsorption on the separation performance is investigated experimentally; first for a batch column and then for a continuous chromatographic process. At first, the retention time of a model substance is established as a suitable measure to describe the degree of irreversible adsorption. The impact of the presence and the absence of cleaning-in-place (CIP) on the retention time of the model substance is demonstrated. Since the issue of column cleaning is particularly important if processes are operated in continuous mode, in the second part of this work the introduction of a CIP step in the continuous multicolumn countercurrent solvent gradient purification (MCSGP) process is investigated. The process purifies a mAb from a cell culture supernatant that also contains irreversibly adsorbing impurities—or impurities that desorb in a later cycle of the process as a contamination. Following the same approach as for the batch experiments, the MCSGP process is operated in the presence and the absence of CIP in order to track prospective changes of the process performance caused by changes in the product retention time. Instead of the model substance, a cell culture supernatant, providing a real case impurity profile in an industrial application is used for the process. Although an impact of the product retention time change on the process yield is not observed it is shown that CIP is required for a stable long-term operation in terms of purity and system pressure drop. With the introduction of a CIP step the process was successfully operated for 9000 min (6 days) without interruption.
Sphingolipid Depletion Increases Formation of the Scrapie Prion Protein in Neuroblastoma Cells Infected with Prions (1999)

Sphingolipid-rich rafts play an essential role in the posttranslational (Borchelt, D. R., Scott, M., Taraboulos, A., Stahl, N., and Prusiner, S. B. (1990) J. Cell Biol. 110, 743-752)) formation of the scrapie prion protein PrP(Sc) from its normal conformer PrP(C) (Taraboulos, A., Scott, M., Semenov, A., Avrahami, D., Laszlo, L., Prusiner, S. B., and Avraham, D. (1995) J. Cell Biol. 129, 121-132). We investigated the importance of sphingolipids in the metabolism of the PrP isoforms in scrapie-infected ScN2a cells. The ceramide synthase inhibitor fumonisin B(1) (FB(1)) reduced both sphingomyelin (SM) and ganglioside GM1 in cells by up to 50%, whereas PrP(Sc) increased by 3-4-fold. Whereas FB(1) profoundly altered the cell lipid composition, the raft residents PrP(C), PrP(Sc), caveolin 1, and GM1 remained insoluble in Triton X-100. Metabolic radiolabeling demonstrated that PrP(C) production was either unchanged or slightly reduced in FB(1)-treated cells, whereas PrP(Sc) formation was augmented by 3-4-fold. To identify the sphingolipid species the decrease of which correlates with increased PrP(Sc), we used two other reagents. When cells were incubated with sphingomyelinase for 3 days, SM levels decreased, GM1 was unaltered, and PrP(Sc) increased by 3-4-fold. In contrast, the glycosphingolipid inhibitor PDMP reduced PrP(Sc) while increasing SM. Thus, PrP(Sc) seems to correlate inversely with SM levels. The effects of SM depletion contrasted with those previously obtained with the cholesterol inhibitor lovastatin, which reduced PrP(Sc) and removed it from detergent-insoluble complexes.
Long-Lasting, Patient-Controlled, Procedure-Free Contraception: A Review of Annovera with a Pharmacist Perspective (2020)

Annovera (segesterone acetate and ethinyl estradiol vaginal system) is a US Food and Drug Administration FDA-approved long-lasting, reversible contraceptive that is fully administered by the user and does not require a procedure for insertion or removal. The vaginal system is in the shape of a ring and contains low doses of a novel progestin, egesterone acetate, and ethinyl estradiol. It is made of silicone and is fully pliable and flexible. The vaginal system is reusable for 13 cycles, using a 21 days in/7 days out regimen, providing women with the ability to control their fertility. Particularly now during the COVID-19 pandemic when access to contraception has been further reduced, patients may benefit from a method that is both long-lasting and patient-controlled.
Supplemental Figure S5 from A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor–Resistant Lung Tumors (2023)

&lt;p&gt;Efficacy of JNJ-61186372 in H292-HGF Xenograft Tumors&lt;/p&gt;
Evaluation of Five Methods for Total DNA Extraction from Western Corn Rootworm Beetles (2010)

These evaluations provide a guide for choosing methods of DNA extraction from western corn rootworm beetles based on expected DNA yield and quality, extraction time, cost, and waste control. The extraction conditions for this mid-size insect were optimized. The DNA extracted by the five methods was suitable for further molecular applications such as PCR and sequencing by synthesis.
Eigenvalue Based Sensing and SNR Estimation for Cognitive Radio in\n Presence of Noise Correlation (2012)

Herein, we present a detailed analysis of an eigenvalue based sensing\ntechnique in the presence of correlated noise in the context of a Cognitive\nRadio (CR). We use a Standard Condition Number (SCN) based decision statistic\nbased on asymptotic Random Matrix Theory (RMT) for decision process. Firstly,\nthe effect of noise correlation on eigenvalue based Spectrum Sensing (SS) is\nstudied analytically under both the noise only and the signal plus noise\nhypotheses. Secondly, new bounds for the SCN are proposed for achieving\nimproved sensing in correlated noise scenarios. Thirdly, the performance of\nFractional Sampling (FS) based SS is studied and a method for determining the\noperating point for the FS rate in terms of sensing performance and complexity\nis suggested. Finally, an SNR estimation technique based on the maximum\neigenvalue of the received signal's covariance matrix is proposed. It is shown\nthat proposed SCN-based threshold improves sensing performance in the presence\nof correlated noise and SNRs upto 0 dB can be reliably estimated without the\nknowledge of noise variance.\n
Word level confidence measurement using semantic features (2003)

This paper proposes two principled methods to incorporate semantic information into word level confidence measurement. The first technique uses tag and arc probabilities obtained from a statistical classer and parser tree. The second technique uses a maximum entropy based semantic structured language model to use semantic structure of a sentence to assign semantic probabilities to each word. Semantic features provide significant improvements over a posterior probability based confidence measure when used together in an air travel reservation task.
A11yBoard: Using Multimodal Input and Output to Make Digital Artboards Accessible to Blind Users (2022)

We present A11yBoard, an interactive multimodal system that makes interpreting and authoring digital artboards, such as presentation slides or vector drawings, accessible to blind and low-vision (BLV) users. A11yBoard combines a web-based application with a mobile touch screen device such as a smartphone or tablet. The artboard is mirrored from the PC onto the touch screen, enabling spatial exploration of the artboard via touch and gesture. In addition, speech recognition and non-speech audio are used for input and output, respectively. Finally, keyboard input is used with a custom search-driven command line interface to access various commands and properties. These modalities combine into a rich, accessible system in which artboard contents, such as shapes, lines, text boxes, and images, can be interpreted, generated, and manipulated with ease. With A11yBoard, BLV users can not only consume accessible content, but create their own as well.
Identification and Characterization of a B-Raf Kinase Alpha Helix Critical for the Activity of MEK Kinase in MAPK Signaling (2020)

Abstract In the MAPK pathway, an oncogenic V600E mutation in B-Raf kinase causes the enzyme to be constitutively active, leading to aberrantly high phosphorylation levels of its downstream effectors, MEK and ERK kinases. The V600E mutation in B-Raf accounts for more than half of all melanomas and ∼3% of all cancers and many drugs target the ATP-binding site of the enzyme for its inhibition. Since B-Raf can develop resistance against these drugs and such drugs can induce paradoxical activation, drugs that target allosteric sites are needed. To identify other potential drug targets, we generated and kinetically characterized an active form of B-Raf V600E expressed using a bacterial expression system. In doing so, we identified an alpha helix on B-Raf, found at the B-Raf-MEK interface, that is critical for their interaction and the oncogenic activity of B-Raf V600E . We performed binding experiments between B-Raf mutants and MEK using pull downs and biolayer interferometry, and assessed phosphorylation levels of MEK in vitro and in cells as well as its downstream target ERK to show that mutating certain residues on this alpha helix is detrimental to binding and downstream activity. Our results suggest that this B-Raf alpha helix binding site on MEK could be a site to target for drug development to treat B-Raf V600E -induced melanomas.
On the Approximation Relationship between Optimizing Ratio of Submodular (RS) and Difference of Submodular (DS) Functions (2021)

We demonstrate that from an algorithm guaranteeing an approximation factor for the ratio of submodular (RS) optimization problem, we can build another algorithm having a different kind of approximation guarantee -- weaker than the classical one -- for the difference of submodular (DS) optimization problem, and vice versa. We also illustrate the link between these two problems by analyzing a \textsc{Greedy} algorithm which approximately maximizes objective functions of the form $Ψ(f,g)$, where $f,g$ are two non-negative, monotone, submodular functions and $Ψ$ is a {quasiconvex} 2-variables function, which is non decreasing with respect to the first variable. For the choice $Ψ(f,g)\triangleq f/g$, we recover RS, and for the choice $Ψ(f,g)\triangleq f-g$, we recover DS. To the best of our knowledge, this greedy approach is new for DS optimization. For RS optimization, it reduces to the standard \textsc{GreedRatio} algorithm that has already been analyzed previously. However, our analysis is novel for this case.
A Functional Polymorphism in RGS6 Modulates the Risk of Bladder Cancer (2004)

RGS proteins negatively regulate heterotrimeric G protein signaling. Recent reports have shown that RGS proteins modulate neuronal, cardiovascular, and lymphocytic activity, yet their role in carcinogenesis has not been explored. In an epidemiologic study of 477 bladder cancer patients and 446 matched controls, three noncoding single-nucleotide polymorphisms (SNPs) in RGS2 and RGS6 were each associated with a statistically significant reduction in bladder cancer risk. The risk of bladder cancer was reduced by 74% in those individuals with the variant genotype at all three SNPs (odds ratio, 0.26; 95% confidence interval, 0.09-0.71). When the SNPs were analyzed separately, the RGS6-rs2074647 (C-->T) polymorphism conferred the greatest overall reduction in risk of bladder cancer (odds ratio, 0.66; 95% confidence interval, 0.46-0.95). These reductions in risk were more pronounced in ever smokers, suggesting a gene-environment interaction. In transfection assays, the RGS6-rs2074647 (C-->T) polymorphism increased the activity of a luciferase-RGS fusion protein by 2.9-fold, suggesting that this SNP is functionally significant. Finally, we demonstrate that RGS2 transcripts and several splice variants of RGS6 are expressed in bladder cancer cells. These data provide the first evidence that RGS proteins may be important modulators of cancer risk and validate RGS6 as a target for further study.
Correction: Corrigendum: Crystal structures of highly simplified BPTIs provide insights into hydration-driven increase of unfolding enthalpy (2017)

Scientific Reports 7: Article number: 41205; published online: 07 March 2017; updated: 09 May 2017 This Article contains errors in the Data Availability section, “The coordinates and structure factors of BPTI-21A, BPTI-22Ab, BPTI-23A and BPTI-24A variants are deposited in the Protein Data Bank underthe PDB entry codes 4YPK, 4YPP, 4YR4 and 4YR5, respectively and we previously reported the structures of BPTI-19A (3AUB) and BPTI-20A (3CI7)”.
Bio-orthogonal triazolinedione (TAD) crosslinked protein nanocapsules affect protein adsorption and cell interaction (2020)

Albumin-based protein nanocarriers obtained by TAD click chemistry have been widely exploited as drug delivery systems, since they show excellent degradability, low toxicity, but at the same time provide high loading capacity and relevant uptake into cells.
Abstract 14086: Do Outcomes Differ Between STEMI and NSTEMI Cardiogenic Shock? (2022)

Background: Acute myocardial infarction relatedcardiogenic shock (AMI-CS) is a multifactorial syndrome with high morbidity andmortality. Contemporary, real-world data comparing outcomes among patients withST-elevation myocardial infarction related CS (STEMI-CS) versus non-STEMI(NSTEMI-CS) is lacking. Methods: Using data from 17 sites from the CardiogenicShock Working Group (CSWG) registry, we compared the clinical characteristics,hemodynamic, and metabolic profiles between STEMI-CS and NSTEMI-CS patients. Between 2016 to 2020, data from 1110 adultpatient hospital admissions with the diagnosis of AMI-CS were collected. Patientswith available data within 24 hours of admission were stratified according to baselineand maximum SCAI Stage. We performed comparison between STEMI vs NSTEMI groupusing one-way Anova analysis. Results: Among 1,110 patients with AMI-CS, 731(65.8%) had STEMI-CS and 379 (34.2%) had NSTEMI-CS. Most patients were male andwhite. Compared with NSTEMI-CS patients, STEMI-CS patients were younger (63.8±12.3 vs 69.2 ± 12.3, p&lt;0.001). Overall unadjusted in-hospital mortality was41%. Mortality was similar among STEMI-CS and NSTEMI-CS patients (43% vs 39%,p=0.23). Patients with out-of-hospital (OHCA) or in-hospital cardiac arrest (IHCA)had higher in-hospital mortality (55% vs 39%, p =0.002; 62%% vs 33%, p&lt;0.001, respectively) (Fig 1A).Shock severity defined by SCAI Stage within 24 hours of admission (baseline)and throughout hospitalization (maximum) directly correlated with in-hospitalmortality in both STEMI- and NSTEMI-CS (Fig 1B). Conclusion: We report one of the largest contemporary analysesspecifically comparing outcomes with STEMI-CS and NSTEMI-CS. Cardiac arrest is an important determinant ofmortality and SCAI Stages are directly associated with poor outcomes in bothcohorts.
Estren (4-Estren-3α,17β-diol) Is a Prohormone that Regulates Both Androgenic and Estrogenic Transcriptional Effects through the Androgen Receptor (2004)

Alternative mechanisms of steroid action, through both traditional nuclear receptors and indirect pathways of gene activation, are emerging. Recent studies suggest that the synthetic steroid, 4-estrene-3alpha,17beta-diol (estren), has nongenotropic as well as sex-nonspecific osteogenic effects in ovariectomized and orchidectomized mice. We found limited estrogen receptor-dependent effects by estren on gene expression in primary osteoblast cultures and showed that it binds poorly to estrogen and androgen receptors in vitro. However, estren potently regulated direct and indirect androgen receptor-dependent effects on gene expression by osteoblasts. Consistent with this, osteoblasts produced the potent androgen 19-nortestosterone from estren by way of a 3alpha-hydroxysteroid dehydrogenase-like activity. Moreover, recombinant 3alpha-hydroxysteroid dehydrogenase (AKR1C9) and osteoblast-derived cell lysate each effectively converted estren to 19-nortestosterone in vitro, and mRNA encoding this enzyme occurs in osteoblasts. In addition to its androgenic activity, estren potently stimulated androgen receptor-dependent effects on gene expression through conventional estrogen-sensitive transcriptional elements in osteoblasts. Therefore, through local metabolism, estren indirectly activates the androgen receptor to regulate both androgen- and estrogen-like transcriptional responses by bone-forming cells.
Design and characterization of radiation tolerant CMOS image sensor for space applications (2011)

In this paper, we address the issues of designing a CMOS image sensor for space applications. The performance of a 4T pinned photodiode pixel under irradiation is shown and an example of a CMOS image sensor designed for sun tracking is given. It has been shown that the radiation tolerance level of the pixel is improved by using more advanced pixel architecture and more advanced fabrication process. Special measures are required in the sensor design to increases the sensor immunity on single event upset and latch-up.
Does Cord Blood Contain Enough Progenitor Cells for Transplantation? (1994)

We analyzed 125 blood samples obtained from umbilical cord immediately after delivery of full-term neonates. Between 0.1 and 10.4% (mean 1.13%, SD 1.34) of the density-separated glycophorin A (GPA)-negative mononuclear cells (MNC) expressed CD34 as analyzed by flow cytometry. These hematopoietic progenitor cells did not coexpress CD19, and the majority were negative for CD45RA. The number of MNC determined per ml cord blood ranged from 1 x 10(5) to 200 x 10(5) (mean 20.2 x 10(5), SD 24.7). Regression analysis revealed that a mean of 56% (n = 26, R = 0.8) and 120% (n = 35, R = 0.94) of the analyzed CD34+ MNC gave rise to day 14 colonies in the clonogenic assay when cultured without or with stem cell factor (SCF). The number and the exact phenotype of progenitor cells required for successful transplantation are not known. If the transplantation of 5 x 10(5) CD34% cells/kg body weight is required for engraftment and one-third of the progenitor cells are lost to cell processing, and if 180 ml blood can be collected from a single umbilical cord (and placenta), our data suggest that 90% of the collections do not contain enough precursors to transplant a 25 kg recipient. To meet these conditions, an average of 1439 ml cord blood would be necessary for transplantation.
GROWTH AND SOME MACRONUTRIENTS UPTAKE BY CASTOR BEAN IRRADIATED WITH GAMMA RAY AND IRRIGATED WITH WASTEWATER UNDER SANDY SOIL CONDITION (2015)

A field experiment was carried out at Experimental Farm of Soil and Water Research Department, Nuclear Research Centre, Atomic Energy Authority, Inshas Egypt, to follow up the effects of different doses of gamma ray on castor bean (Ricinus communis L.) grown on a sandy soil and irrigated with either fresh water or wastewater from El-Gabal El Asfar. Irradiation resulted in higher values of both fresh and dry weight of castor bean. This effect seemed more obvious by increasing the dose of gamma ray up to 50 Gy beyond which a gradual decrease occurred. Nitrogen, phosphorus and potassium contents in castor bean under the effect of gamma irradiation were arranged in the following descending order; 50Gy > 100Gy > 150Gy > 200Gy > 0 > 250Gy> 300 Gy. Nitrogen, phosphorus, potassium and oil contents in castor bean plants irrigated with wastewater were higher than the corresponding ones in plants irrigated with fresh water.
Blending to Make Nonhealable Polymers Healable: Nanophase Separation Observed by CP/MAS 13C NMR Analysis (2022)

Abstract Can commodity polymers are made to be healable just by blending with self‐healable polymers? Here we report the first study on the fundamental aspect of this practically challenging issue. Poly(ether thiourea) (PTUEG 3 ; T g =27 °C) reported in 2018 is extraordinary in that it is mechanically robust but can self‐heal even at 12 °C. In contrast, poly(octamethylene thiourea) (PTUC 8 ; T g =50 °C), an analogue of PTUEG 3 , cannot heal below 92 °C. We found that their polymer blend self‐healed in a temperature range above 32 °C even when its PTUEG 3 content was only 20 mol %. Unlike PTUEG 3 alone, this polymer blend, upon exposure to high humidity, barely plasticized, keeping its excellent mechanical properties due to the non‐hygroscopic nature of the PTUC 8 component. CP/MAS 13 C NMR analysis revealed that the polymer blend was nanophase‐separated, which possibly accounts for why such a small amount of PTUEG 3 provided the polymer blend with humidity‐tolerant self‐healable properties.
The Pain Divide: a cross-sectional analysis of chronic pain prevalence, pain intensity and opioid utilisation in England (2018)

There are geographical differences in chronic pain prevalence, pain intensity and opioid utilisation across England-with evidence of a 'pain divide'. Given the public health concerns associated with the long-term use of opioid analgesics-and their questionable activity in the management of chronic pain-more guidance is needed to support prescribers in the management of chronic pain, so the initiation of opioids can be avoided.
A scheduling model for reduced CPU energy (2002)

The energy usage of computer systems is becoming an important consideration, especially for battery-operated systems. Various methods for reducing energy consumption have been investigated, both at the circuit level and at the operating systems level. In this paper, we propose a simple model of job scheduling aimed at capturing some key aspects of energy minimization. In this model, each job is to be executed between its arrival time and deadline by a single processor with variable speed, under the assumption that energy usage per unit time, P, is a convex function, of the processor speed s. We give an off-line algorithm that computes, for any set of jobs, a minimum-energy schedule. We then consider some on-line algorithms and their competitive performance for the power function P(s)=s/sup p/ where p/spl ges/2. It is shown that one natural heuristic, called the Average Rate heuristic, uses at most a constant times the minimum energy required. The analysis involves bounding the largest eigenvalue in matrices of a special type.
Drehen mit Niobcarbid-basierten Werkzeugen (2018)

Niobcarbid (NbC) stellt aufgrund vorteilhafter Eigenschaften, wie zum Beispiel eine geringe Diffusionsneigung, in der Zerspannung eine vielversprechende Alternative zu konventionellen Schneidstoffen wie Wolframcarbid (WC) dar. Als Substitution der Hartstoff-Phase WC im Hartmetall wird NbC in der trockenen Drehbearbeitung von eisen-basierten Werkstoffen untersucht. Diesbezuglich wurden zwei NbC-Substrate mit WC hinsichtlich ihres Werkzeugverschleises quantitativ verglichen. Im Gegensatz zu WC-Werkzeugen wird das Potential von NbC bei zunehmender Schnittgeschwindigkeit vc durch eine steigende Prozessstabilitat deutlich.