gebhart/patrepeval huggingface dataset:
Chinese hamster ovary K1 host cell enables stable cell line development for antibody molecules which are difficult to express in DUXB11‐derived dihydrofolate reductase deficient host cell (2013)

Therapeutic monoclonal antibodies (mAb) are often produced in Chinese hamster ovary (CHO) cells. Three commonly used CHO host cells for generating stable cell lines to produce therapeutic proteins are dihydrofolate reductase (DHFR) positive CHOK1, DHFR-deficient DG44, and DUXB11-based DHFR deficient CHO. Current Genentech commercial full-length antibody products have all been produced in the DUXB11-derived DHFR-deficient CHO host. However, it has been challenging to develop stable cell lines producing an appreciable amount of antibody proteins in the DUXB11-derived DHFR-deficient CHO host for some antibody molecules and the CHOK1 host has been explored as an alternative approach. In this work, stable cell lines were developed for three antibody molecules in both DUXB11-based and CHOK1 hosts. Results have shown that the best CHOK1 clones produce about 1 g/l for an antibody mAb1 and about 4 g/l for an antibody mAb2 in 14-day fed batch cultures in shake flasks. In contrast, the DUXB11-based host produced ∼0.1 g/l for both antibodies in the same 14-day fed batch shake flask production experiments. For an antibody mAb3, both CHOK1 and DUXB11 host cells can generate stable cell lines with the best clone in each host producing ∼2.5 g/l. Additionally, studies have shown that the CHOK1 host cell has a larger endoplasmic reticulum and higher mitochondrial mass.
Midterm Results of the Treatment of Cartilage Defects in the Knee Using Alginate Beads Containing Human Mature Allogenic Chondrocytes (2011)

This investigation provided useful information on the efficacy of the implantation of alginate beads containing human mature allogenic chondrocytes for the treatment of cartilage lesions in the knee. The midterm clinical outcome of the presented technique was satisfactory. However, these results were not confirmed by the MRI findings.
Automated Dynamic Mechanism Design (2021)

We study Bayesian automated mechanism design in unstructured dynamic environments, where a principal repeatedly interacts with an agent, and takes actions based on the strategic agent's report of the current state of the world. Both the principal and the agent can have arbitrary and potentially different valuations for the actions taken, possibly also depending on the actual state of the world. Moreover, at any time, the state of the world may evolve arbitrarily depending on the action taken by the principal. The goal is to compute an optimal mechanism which maximizes the principal's utility in the face of the self-interested strategic agent. We give an efficient algorithm for computing optimal mechanisms, with or without payments, under different individual-rationality constraints, when the time horizon is constant. Our algorithm is based on a sophisticated linear program formulation, which can be customized in various ways to accommodate richer constraints. For environments with large time horizons, we show that the principal's optimal utility is hard to approximate within a certain constant factor, complementing our algorithmic result. We further consider a special case of the problem where the agent is myopic, and give a refined efficient algorithm whose time complexity scales linearly in the time horizon. Moreover, we show that memoryless mechanisms do not provide a good solution for our problem, in terms of both optimality and computational tractability. These results paint a relatively complete picture for automated dynamic mechanism design in unstructured environments. Finally, we present experimental results where our algorithms are applied to synthetic dynamic environments with different characteristics, which not only serve as a proof of concept for our algorithms, but also exhibit intriguing phenomena in dynamic mechanism design.
MELK is not necessary for the proliferation of basal-like breast cancer cells (2017)

Thorough preclinical target validation is essential for the success of drug discovery efforts. In this study, we combined chemical and genetic perturbants, including the development of a novel selective maternal embryonic leucine zipper kinase (MELK) inhibitor HTH-01-091, CRISPR/Cas9-mediated MELK knockout, a novel chemical-induced protein degradation strategy, RNA interference and CRISPR interference to validate MELK as a therapeutic target in basal-like breast cancers (BBC). In common culture conditions, we found that small molecule inhibition, genetic deletion, or acute depletion of MELK did not significantly affect cellular growth. This discrepancy to previous findings illuminated selectivity issues of the widely used MELK inhibitor OTSSP167, and potential off-target effects of MELK-targeting short hairpins. The different genetic and chemical tools developed here allow for the identification and validation of any causal roles MELK may play in cancer biology, which will be required to guide future MELK drug discovery efforts. Furthermore, our study provides a general framework for preclinical target validation.
Epithelial Phenotypes in the Developing Human Prostate (2007)

An intermediate population has been identified among prostate glands called transiently amplifying (TA) cells, which are characterized by coexpression of basal and luminal cytokeratins (CKs), high proliferation, and lack of p27 expression. These cells are rare in the normal adult prostate and increase in pretumoral conditions, but their importance in the developing gland remains unknown. We analyzed fetal prostates for the expression of CKs (5/6, 18, 19) and factors involved in proliferation and apoptosis: p63, Ki67, p27, epidermal growth factor (EGFR), Bcl2, androgen receptor (AR). Immunostaining was performed on a tissue microarray, including 40 prostates from fetuses aged 13-42 weeks and normal prostate tissue from 10 adults. In both solid buds and the basal compartment of canalized glands, cells expressed p63, CK5/6, CK19, CK18, BCL2, EGFR and were p27 negative. Luminal cells of fetal canalized glands continue to express CK19, EGFR, and BCL2, without p27 expression. In contrast, adult epithelial luminal cells showed diffuse AR and p27 expression, without CK19, BCL2, and EGFR staining. Proliferation was high and diffuse in fetal glands and rare and restricted to basal cells in adult glands. These results indicate that most fetal epithelial prostatic cells exhibit the phenotype of TA cells, suggesting their regulatory function in prostate development.
In situ visualization of Li/Ag <sub>2</sub> VP <sub>2</sub> O <sub>8</sub> batteries revealing rate-dependent discharge mechanism (2015)

The functional capacity of a battery is observed to decrease, often quite dramatically, as discharge rate demands increase. These capacity losses have been attributed to limited ion access and low electrical conductivity, resulting in incomplete electrode use. A strategy to improve electronic conductivity is the design of bimetallic materials that generate a silver matrix in situ during cathode reduction. Ex situ x-ray absorption spectroscopy coupled with in situ energy-dispersive x-ray diffraction measurements on intact lithium/silver vanadium diphosphate (Li/Ag2VP2O8) electrochemical cells demonstrate that the metal center preferentially reduced and its location in the bimetallic cathode are rate-dependent, affecting cell impedance. This work illustrates that spatial imaging as a function of discharge rate can provide needed insights toward improving realizable capacity of bimetallic cathode systems.
Chemical and Electrochemical Li-Insertion into the Li<sub>4</sub>Ti<sub>5</sub>O<sub>12</sub> Spinel (2004)

Lithium has been inserted into the spinel Li4Ti5O12 by both chemical and electrochemical methods. The cation distribution in the lithiated phases has been analyzed by 6,7Li NMR, Raman spectroscopy, and X-ray diffraction, and the distribution in the chemically inserted compound has been analyzed additionally by neutron diffraction. A refinement of structural parameters has been carried out by applying the Rietveld method to the neutron diffraction pattern. It is shown that the two insertion methods are based on different mechanisms. Chemically inserted lithium ions are trapped in the (48f) sites of the spinel structure from which they cannot be extracted by electrochemical means. In contrast to the electrochemical Li-insertion, which is accompanied by a spinel to rocksalt phase transition, no such structural change is found for chemical insertion. The consequences of the two different mechanisms for the reversibility of the insertion process are discussed.
KEYNOTE-052: Phase 2 study of pembrolizumab (MK-3475) as first-line therapy for patients (pts) with unresectable or metastatic urothelial cancer ineligible for cisplatin-based therapy. (2015)

TPS4572 Background: Standard first-line therapy for advanced urothelial cancer is cisplatin-based chemotherapy. Pts who are ineligible for cisplatin therapy, mainly due to renal dysfunction and/or poor performance status, have limited treatment options. The programmed death receptor 1 (PD-1) pathway is used by tumors to suppress immune control. Pembrolizumab is a highly selective, IgG4 anti-PD-1 humanized monoclonal antibody designed to block the interaction between PD-1 and its ligands PD-L1 and PD-L2. In the phase 1 KEYNOTE-012 trial, pembrolizumab 10 mg/kg once every 2 weeks (Q2W) demonstrated an ORR of 24% (RECIST v1.1, central review) in 33 pts with PD-L1–positive advanced urothelial cancer, 76% of whom received ≥ 1 prior therapy. Methods: KEYNOTE-052 (ClinicalTrials.gov, NCT02335424) is an international, open-label, phase 2 trial of pembrolizumab 200 mg Q3W as first-line therapy for adults with unresectable or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra who are ineligible to receive cisplatin. Pts are considered cisplatin ineligible if they have ≥ 1 of the following: ECOG PS 2, creatinine clearance (calculated or measured) < 60 but ≥ 30 mL/min, grade ≥ 2 (CTCAE v4) audiometric hearing loss or peripheral neuropathy, or NYHA class III heart failure. All pts must provide a recently obtained biopsy sample for PD-L1 evaluation at a central laboratory. Pembrolizumab will be given for up to 24 mo or until disease progression, unacceptable toxicity, or investigator decision; treatment may be discontinued following complete response. Select pts may continue pembrolizumab beyond initial evidence of radiographic progression. Response will be evaluated per RECIST v1.1 by independent central review at 9 wk and every 6 wk thereafter. Survival follow-up will occur every 3 mo. Primary end point is ORR in pts with PD-L1–dependent tumors. Secondary end points include ORR in all pts, PFS, OS, duration of response, and the association between PD-L1 positivity and ORR. Up to 350 pts will be enrolled. KEYNOTE-052 is currently enrolling pts. Clinical trial information: NCT02335424.
Clumping Factor B, a Fibrinogen-binding MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules) Adhesin of Staphylococcus aureus, Also Binds to the Tail Region of Type I Cytokeratin 10 (2004)

The primary habitat of Staphylococcus aureus in humans is the moist squamous epithelium of the anterior nares. We showed previously that S. aureus adheres to desquamated epithelial cells and that clumping factor B (ClfB), a surface-located MSCRAMM (microbial surface components recognizing adhesive matrix molecules) known for its ability to bind to the alpha-chain of fibrinogen, is partly responsible (O'Brien, L. M., Walsh, E. J., Massey, R. C., Peacock, S. J., and Foster, T. J. (2002) Cell. Microbiol. 4, 759-770). We identified cytokeratin 10 (K10) as the ligand recognized by ClfB. Here we have shown that purified recombinant human and murine K10 immobilized on a plastic surface supports adherence of S. aureus in a ClfB-dependent manner. Furthermore, the recombinant A domain of ClfB (rClfB 45-542) bound to immobilized K10 dose-dependently and saturably. Subdomains of human and murine K10 were expressed and purified. The N-terminal head domain (residues 1-145) did not support the binding of rClfB or adherence of S. aureus ClfB+. In contrast, the C-terminal tail domains (human rHK10 452-593, mouse rMK10 454-570) promoted avid binding and adherence. Isothermal titration microcalorimetry and intrinsic tryptophan fluorescence experiments gave dissociation constants for rClfB 45-542 binding to rMK10 454-570 of 1.4 and 1.7 microM, respectively. The tail region of K10 is composed largely of quasi-repeats of Tyr-(Gly/Ser)n. A synthetic peptide corresponding to a typical glycine loop (YGGGSSGGGSSGGY; Y-Y loop peptide) inhibited the adherence of S. aureus ClfB+ to immobilized MK10 to a level of 80%, whereas control peptides had no effect. The KD of rClfB 45-542 for the Y-Y loop peptide was 5.3 microm by intrinsic tryptophan fluorescence. Thus ClfB binds to the glycine loop region of the tail domain of keratin 10 where there are probably multiple binding sites. Binding is discussed in the context of the dock-lock-latch model for MSCRAMM-ligand interactions. We provide an explanation for the molecular basis for S. aureus adherence to the squamous epithelium and suggest that nasal colonization might be prevented by reagents that inhibit this interaction.
Molecular Markers Linked to Genes Important for Hard Winter Wheat Production and Marketing in the U.S. Great Plains (2014)

Biotic stresses including diseases [leaf, stem and stripe rusts], arthropods [greenbug (GB), Hessian fly (Hf), Russian wheat aphid (RWA), and wheat curl mite (WCM)] and their transmitted viral diseases significantly affect grain yield and end-use quality of hard winter wheat (Triticum aestivum L.) in the U.S. Great Plains. Many genes or quantitative trait loci (QTL) have been identified for seedling or adult plant resistance to these stresses. Molecular markers for these genes or QTL have been identified using mapping or cloning. This study summarizes the markers associated with various effective genes including genes or QTL conferring resistances to arthropods, such as GB (7), RWA (4), Hf (9), and WCM (4) and diseases including leaf, stem and stripe rusts (26) and Wheat streak mosaic virus (WSMV) (2); genes or QTL for end-use quality traits such as high (3) and low (13) molecular weight glutenin subunits, gliadin (3), polyphenol oxidase (2), granule-bound starch synthase (3), puroindoline (2), and pre-harvesting sprouting (1); genes on wheat-rye (Secale cereale L.) chromosomal translocations of 1AL.1RS and 1BL.1RS; and genes controlling plant height (12), photoperiod sensitivity (1), and vernalization (2). A subset of the markers was validated using a set of diverse wheat lines developed by breeding programs in the Great Plains. These analyses showed that most markers are diagnostic in only limited genetic backgrounds. However, some markers developed from the gene sequences or alien fragments are highly diagnostic across various backgrounds, such as those marking or linked to Rht-B1, Rht-D1, Ppd-D1, Glu-D1, Glu-A1, and 1AL.1RS. Knowledge of both genotype and phenotype of advanced breeding lines could help Page 2 of 63 Crop Science Accepted paper, posted 02/21/2014. doi:10.2135/cropsci2013.08.0564
ChemInform Abstract: EXTREMELY FACILE REACTION BETWEEN THE ULTIMATE CARCINOGEN BENZO(A)PYRENE‐7,8‐DIOL 9,10‐EPOXIDE AND ELLAGIC ACID (1983)

Abstract Die extrem schnelle Reaktion zwischen der Titelsäure (I) und dem Benzopyrendiolepoxid (II) in wäßriger Lösung in Abhängigkeit vom pH‐Wert, der Konzentration und dem Lösungsmittelgemisch wird spektrophotometrisch untersucht; kinetische Daten werden ermittelt und diskutiert.
Dimensions (2003)

An important class of networked systems is emerging that involve very large numbers of small, low-power, wireless devices. These systems offer the ability to sense the environment densely, offering unprecedented opportunities for many scientific disciplines to observe the physical world. In this paper, we argue that a data handling architecture for these devices should incorporate their extreme resource constraints - energy, storage and processing - and spatio-temporal interpretation of the physical world in the design, cost model, and metrics of evaluation. We describe DIMENSIONS, a system that provides a unified view of data handling in sensor networks, incorporating long-term storage, multi-resolution data access and spatio-temporal pattern mining.
Adeno-Associated Viral Vectors Show Serotype Specific Transduction of Equine Joint Tissue Explants and Cultured Monolayers (2014)

Adeno-associated virus (AAV) receptors range from heparan sulfate proteoglycan to sialic acid moieties present on cell surfaces. Abundance of the glycan profiles is greatly influenced by animal species, cell type, and culture conditions. The objective of this study was to determine whether AAV serotypes' transduction efficiencies specifically in the equine monolayer culture model are an accurate representation of transduction efficiencies in tissue explants, a model more closely related to in vivo transduction. It was found that AAV 2 and 2.5 transduced cells more efficiently in explants than in monolayers. Through experiments involving assessing enzyme degradation of cell surface proteoglycans, this change could not be attributed to differences in the extra cellular matrix (ECM), but a similar change in AAV 5 transduction efficiency could be readily explained by differences in cell surface sialylated glycan. Unexpectedly it was found that in a small but diverse sample of horses evidence for serum neutralizing antibodies was only found to AAV 5. This suggests a unique relationship between this capsid and the equine host or an unresolved relationship between similar bovine AAV and the AAV 5 capsid immune response.
RESEARCH OF TECHNOLOGY FOR CREATING HIGH-TEMPERATURE TEXTURED MATERIALS FOR MANUFACTURING MULTILAYER PIEZO TRANSDUCER ELEMENTS (2023)

Background. The most important stimulus for the study of piezoceramic materials is the increasing requirements for extending the operating temperature range, improving the measurement characteristics, and the stability to destabilizing factors of the devices created on their basis. However, along with a search for new promising materials and refinement of manufacturing technology to solve the above problems, the development of high-temperature textured materials for manufacturing multilayer piezoelectric transducer elements is becoming increasingly necessary. Materials and methods. Research methods were chosen based on the possibility of obtaining the most complete information about the change in the structure and properties of the material after sintering and polarization of products. When carrying out research, X-ray structural, radiographic, metallographic and electron-microscopic analyses were used. The measurements of mechanical and electrical strength, fracture resistance, dielectric permittivity, piezoelectric and segmented elastic characteristics of the products were carried out in the course of the work. Results. The technology of multilayer piezo packages production has been developed, the results of the technology of solid solution system piezoceramics production have been obtained, the structure, dielectric and piezoelectric properties of ceramics in the temperature range 20÷600 ℃ have been studied. Experimental samples of multilayer piezoelements were made.
A Versatile Solution Route to Efficient Cu<sub>2</sub>ZnSn(S,Se)<sub>4</sub> Thin-Film Solar Cells (2015)

A simple solution-based approach for the deposition of Cu2ZnSn(S,Se)4 using an amine–thiol mixture is presented. The versatility of this solvent mixture in dissolving different cation sources and chalcogens opens the door for a variety of metal chalcogenide molecular precursor designs. The process involves incorporating the metal sources and chalcogens into an amine–thiol solvent mixture at room temperature, spin coating a precursor film, and heat-treating precursor films in both an inert gas and selenium atmosphere. With this solution approach, high-quality kesterite CZTS and CZTSSe thin films were formed after low-temperature annealing and selenization. Solar cells were fabricated based on these CZTSSe thin films, resulting in a total area power conversion efficiency of 7.86% for a cell area of 0.47 cm2 under standard AM 1.5 illumination.
Tactile Frequency-Specific High-Gamma Activities in Human Primary and Secondary Somatosensory Cortices (2017)

Humans can easily detect vibrotactile stimuli up to several hundred hertz, but underlying large-scale neuronal processing mechanisms in the cortex are largely unknown. Here, we investigated the macroscopic neural correlates of various vibrotactile stimuli including artificial and naturalistic ones in human primary and secondary somatosensory cortices (S1 and S2, respectively) using electrocorticography (ECoG). We found that tactile frequency-specific high-gamma (HG, 50-140 Hz) activities are seen in both S1 and S2 with different temporal dynamics during vibration (>100 Hz). Stimulus-evoked S1 HG power, which exhibited short-delayed peaks (50-100 ms), was attenuated more quickly in vibration than in flutter (<50 Hz), and their attenuation patterns were frequency-specific within vibration range. In contrast, S2 HG power, which was activated much later than that of S1 (150-250 ms), strikingly increased with increasing stimulus frequencies in vibration range, and their changes were much greater than those in S1. Furthermore, these S1-S2 HG patterns were preserved in naturalistic stimuli such as coarse/fine textures. Our results provide persuasive evidence that S2 is critically involved in neural processing for high-frequency vibrotaction. Therefore, we propose that S1-S2 neuronal co-operation is crucial for full-range, complex vibrotactile perception in human.
Three-dimensional imaging of a thoracic duct cyst before thoracoscopic surgery (2013)

Figure 1: (A) Three-dimensional magnetic resonance image (MRI) of the thoracic duct and mediastinal cyst. MRI visualized the thoracic duct, revealing the continuity of the duct with the cystic mass in the mediastinum. The arrows indicate the thoracic duct. The square arrow indicates the cystic mass in the mediastinum. The arrowhead indicates the descending aorta. (B) Combined multidetector-row CT (MDCT) and MRI showed that the cystic mass was located between the descending aorta, left bronchus and oesophagus and visualized the course of the thoracic duct well. T: trachea; E: oesophagus. (C) Intraoperative thoracoscopic view of the mediastinal cyst. The arrow indicates the cystic mass in the mediastinum, and the double arrows indicate the thoracic duct. L: right lung; V: vertebra. (D) The resected thoracic duct cyst.
Freedom from Deadlock of Safe Locking Policies (1982)

The usual method for preserving the consistency of a database when accessed (read and updated) concurrently by several transactions, is by locking the transactions according to some locking policy; a locking policy that guarantees the preservation of consistency of the database is called safe. Furthermore, if no deadlocks can arise the policy is called deadlock-free. In this paper we are concerned with the freedom from deadlock of safe locking policies. We show that a simple extension of the DAG policy of [Y] is the most general safe and deadlock-free policy for a pair of transactions. We prove however, that it is NP-complete to test whether a set of transactions is not deadlock-free even for the simplest kind of transactions, those that are two-phase locked [E]. We show that for the natural class of safe locking policies, the L-policies, studied in [Y], freedom from deadlock is determined only by the order in which entities are accessed by the transactions and not by the way in which safety is ensured. As a consequence of this fact we develop simple conditions that guarantee the freedom from deadlock of a safe L-policy.