gebhart/patrepeval huggingface dataset:
Reproducibility of the external surface position in left‐breast DIBH radiotherapy with spirometer‐based monitoring (2014)

Deep inspiration breath hold (DIBH) in left-sided breast cancer radiotherapy treatments allows for a reduction in cardiac and pulmonary doses without compromising target coverage. The selection of the most appropriate technology for DIBH monitoring is a crucial issue. We evaluated the stability and reproducibility of DIBHs controlled by a spirometric device, by assessing the variability of the external surface position within a single DIBH (intra-DIBH) and between DIBHs performed in the same treatment session (intrafraction) or in different sessions (interfraction). The study included seven left-breast cancer patients treated with spirometer-based DIBH radiotherapy. Infrared optical tracking was used to record the 3D coordinates of seven to eleven passive markers placed on the patient's thoraco-abdominal surface during 29-43 DIBHs performed in six to eight treatment sessions. The obtained results showed displacements of the external surface between different sessions up to 6.3mm along a single direction, even at constant inspired volumes. The median value of the interfraction variability in the position of breast passive markers was 2.9 mm (range 1.9-4.8 mm) in the latero-lateral direction, 3.6 mm (range 2.2-4.6mm) in the antero-posterior direction, and 4.3mm (range 2.8-6.2 mm) in the cranio-caudal direction. There were no significant dose distribution variations for target and organs at risk with respect to the treatment plan, confirming the adequacy of the applied clinical margins (15 mm) to compensate for the measured setup uncertainties. This study demonstrates that spirometer-based control does not guarantee a stable and reproducible position of the external surface in left-breast DIBH radiotherapy, suggesting the need for more robust DIBH monitoring techniques when reduced margins and setup uncertainties are required for improving normal tissue sparing and decreasing cardiac and pulmonary toxicity.
Defining Hierarchies of Unrestricted Somatic Stem Cells and Mesenchymal Stem Cells in Cord Blood (2011)

Multipotent cells termed unrestricted somatic stem cells (USSC) were recently described with the potential to differentiate into mesodermal cells, cardiomyocytes under specialized circumstances, ectodermal neural cells, and endodermal hepatic cells. More recently, it has become clear that USSCs are heterogeneous with regard to their differentiation potential, and distinct functional differences in differentiation potential suggests USSCs are at different developmental stages. Expression of particular genes and differentiation toward the adipogenic lineage can discriminate USSCs from other related cell types such as CB-derived mesenchymal stromal cells. Current work regarding the characterization and differentiation of USSC and their distinct differentiation potential in comparison to other cell populations may enable us to distinguish several distinct multipotent progenitor cell populations.
E1 Enzymes as Therapeutic Targets in Cancer (2020)

Post-translational modifications of cellular substrates with ubiquitin and ubiquitin-like proteins (UBLs), including ubiquitin, SUMOs, and neural precursor cell-expressed developmentally downregulated protein 8, play a central role in regulating many aspects of cell biology. The UBL conjugation cascade is initiated by a family of ATP-dependent enzymes termed E1 activating enzymes and executed by the downstream E2-conjugating enzymes and E3 ligases. Despite their druggability and their key position at the apex of the cascade, pharmacologic modulation of E1s with potent and selective drugs has remained elusive until 2009. Among the eight E1 enzymes identified so far, those initiating ubiquitylation (UBA1), SUMOylation (SAE), and neddylation (NAE) are the most characterized and are implicated in various aspects of cancer biology. To date, over 40 inhibitors have been reported to target UBA1, SAE, and NAE, including the NAE inhibitor pevonedistat, evaluated in more than 30 clinical trials. In this Review, we discuss E1 enzymes, the rationale for their therapeutic targeting in cancer, and their different inhibitors, with emphasis on the pharmacologic properties of adenosine sulfamates and their unique mechanism of action, termed substrate-assisted inhibition. Moreover, we highlight other less-characterized E1s-UBA6, UBA7, UBA4, UBA5, and autophagy-related protein 7-and the opportunities for targeting these enzymes in cancer. SIGNIFICANCE STATEMENT: The clinical successes of proteasome inhibitors in cancer therapy and the emerging resistance to these agents have prompted the exploration of other signaling nodes in the ubiquitin-proteasome system including E1 enzymes. Therefore, it is crucial to understand the biology of different E1 enzymes, their roles in cancer, and how to translate this knowledge into novel therapeutic strategies with potential implications in cancer treatment.
Oxide Formation, Morphology, and Nanohardness of Laser‐Patterned Steel Surfaces (2015)

A large variety of tribological research studies dealt with the effect of laser induced surface textures and the respective parameters such as depth, feature diameter, and area density on the tribological efficiency. However, only few studies have examined chemical and microstructural changes induced by the laser‐patterning process, which can have a significant impact on the tribological properties. The aim of this study is to analyze the surface chemistry of laser‐induced line‐like patterns with a structural wavelength of 18 mm on steel surfaces (AISI 304), i.e., oxide scale thickness and morphology, prior to and after laser processing. X‐ray photoelectron spectroscopy combined with an Argon ion sputtering facility was used to measure depth profiles of the iron‐ and chromium oxide layer. A subsequent analysis performed by atom probe tomography demonstrated that the laser interference patterning leads to an increased iron‐ and chromium oxide layer by a factor of 8 compared to the polished unpatterned reference surface and to a change in the oxide morphology from a solid solution in the reference to a layered structure in the laser‐patterned state. Nanoindentation experiments revealed that the nano‐hardness in the laser‐intensity maximum position is two times larger than in the reference position. Finally, hardness calculations assuming a bilayer model correlate the observed nano‐hardness with the measured surface chemistry.
Sphingosine-1-phosphate receptors regulate individual cell behaviours underlying the directed migration of prechordal plate progenitor cells during zebrafish gastrulation (2008)

During vertebrate gastrulation, cells forming the prechordal plate undergo directed migration as a cohesive cluster. Recent studies revealed that E-cadherin-mediated coherence between these cells plays an important role in effective anterior migration, and that platelet-derived growth factor (Pdgf) appears to act as a guidance cue in this process. However, the mechanisms underlying this process at the individual cell level remain poorly understood. We have identified miles apart (mil) as a suppressor of defective anterior migration of the prospective prechordal plate in silberblick (slb)/wnt11 mutant embryos, in which E-cadherin-mediated coherence of cell movement is reduced. mil encodes Edg5, a sphingosine-1-phosphate (S1P) receptor belonging to a family of five G-protein-coupled receptors (S1PRs). S1P is a lipid signalling molecule that has been implicated in regulating cytoskeletal rearrangements, cell motility and cell adhesion in a variety of cell types. We examined the roles of Mil in anterior migration of prechordal plate progenitor cells and found that, in slb embryos injected with mil-MO, cells migrate with increased motility but decreased directionality, without restoring the coherence of cell migration. This indicates that prechordal plate progenitor cells can migrate effectively as individuals, as well as in a coherent cluster of cells. Moreover, we demonstrate that Mil regulates cell motility and polarisation through Pdgf and its intracellular effecter PI3K, but modulates cell coherence independently of the Pdgf/PI3K pathway, thus co-ordinating cell motility and coherence. These results suggest that the net migration of prechordal plate progenitors is determined by different parameters, including motility, persistence and coherence.
A programmable 80ns 1Mb CMOS EPROM (1985)

CONTINUING DEMANDS for high-speed, low-power and high-density EPROMs are being created by the evolution of high performance computer systems. This paper will describe an asynchronous 1Mb CMOS EPROM with both word and byte operation modes.
Building blocks toward a more effective public sector (1998)

The basic building blocks for effective state capacity are the same for many low-income developing countries as they were historically for developed and more recently for the East Asian economies: strong central capacity for strategic policy formulation and coordination; merit-based recruitment, long term career rewards, adequate pay for professional civil service, and well-functioning systems of financial accountability. Recent reforms in some Organization of Economic Cooperation and Development countries contain some important elements that can improve performance in developing countries including a greater emphasis on results, enhanced transparency, and greater contestability in service delivery and policy advice. At the same time, many other components of these reforms will impose unrealistic demands on state capacity and are in any event no substitute for the basic foundations for effectiveness. In developing countries with weak state capacity, the challenge is to restore or create a professional and accountable bureaucracy and substitute institutionalized feedback and accountability for patrimonial patronage. The principal conclusion is that effective public-sector capacity has been built upon the basic foundations of a professional, meritocratic, well-paid bureaucracy with internal coherence and institutionalized links to external stakeholders for feedback and accountability.
In Vitro Formation of Assimilatory Reduced Nicotinamide Adenine Dinucleotide Phosphate: Nitrate Reductase from a Neurospora Mutant and a Component of Molybdenum-Enzymes (1971)

An active Neurospora-like assimilatory NADPH-nitrate reductase (EC 1.6.6.2), which can be formed in vitro by incubation of extracts of nitrate-induced Neurospora crassa mutant nit-1 with extracts of (a) certain other nonallelic nitrate reductase mutants, (b) uninduced wild type, or (c) xanthine oxidizing and liver aldehyde-oxidase systems was also formed by combination of the nit-1 extract with other acid-treated enzymes known to contain molybdenum. These molybdenum enzymes included (a) nitrogenase, or its molybdenum-iron protein, from Clostridium, Azotobacter, and soybeannodule bacteroids, (b) bovine liver sulfite oxidase, (c) respiratory formate-nitrate reductase from Escherichia coli, (d) NADH-nitrate reductase from foxtail grass (Setaria faberii), and (e) FADH(2)- and reduced methyl viologennitrate reductase preparations from certain Neurospora mutants. Several molybdenum-amino-acid complexes, as possible catalytic models of nitrogenase, were inactive (as were some previously tested 20 nonmolybdenum enzymes) in place of the acid-treated molybdenum-containing enzymes. The results imply the existence of a molybdenum-containing component shared by the known molybdenum-enzymes.
Energy dissipation in a thin polymer film by electron beam scattering (1974)

Monte Carlo calculations have been performed to determine the spatial distribution of energy dissipated in a 4000-Å-thick film of polymethyl methacrylate (PMMA), due to an incident electron beam. The calculations were performed for 5-, 10-, and 20-keV electrons on a silicon substrate and also for 20-keV electrons on copper and gold substrates. The effect of varying the beam diameter from 250 to 3000 Å was evaluated. A detailed comparison is made between the Monte Carlo results and analytic models used to predict the energy dissipated. The plural scattering model is found to be in good agreement with the Monte Carlo calculations, whereas discrepancies are found with the multiple scattering model. The large-angle backscattering model is found to have several important limitations. Energy dissipation is calculated for the exposure of dots, isolated lines, and arrays of closely spaced lines—geometries that are of significance in electron beam lithography.
The riminophenazine agents clofazimine and B669 inhibit the proliferation of cancer cell lines in vitro by phospholipase A2-mediated oxidative and nonoxidative mechanisms. (1993)

Clofazimine, a riminophenazine antimicrobial agent, and its analogue B669 were investigated for their effects on FaDu cells, a human squamous carcinoma cell line. These agents, at concentrations within the therapeutic range (0.25-2 micrograms/ml), caused a dose-dependent tumor cell cytotoxicosis which was greatly enhanced in the presence of human neutrophils. The neutrophil-mediated increment in tumoricidal activity, but not the direct antitumor effects of the drugs per se, was inhibited by catalase. The effects of these drugs on three more cell carcinoma lines as well as on two primary cultures and a noncarcinoma cell line were also investigated and compared with the activity of the standard antitumor chemotherapeutic agents bleomycin, cisplatin, and methotrexate. All seven cultures were sensitive to clofazimine and B669 compared to six that were sensitive to cisplatin, three that were sensitive to bleomycin, and one that was sensitive to methotrexate. The treatment of FaDu cells with clofazimine and B669 was associated with enhanced activity of phospholipase A2, as evidenced by increased release of radiolabeled arachidonate and lysophosphatidylcholine from membrane phospholipids. Inhibitors of arachidonic acid metabolism, protein kinase C inhibitors, as well as water and lipid soluble antioxidants failed to protect the cells against the cytotoxic activity of clofazimine and B669. However, alpha-tocopherol, a lysophospholipid-complexing agent, completely blocked the antiproliferative effects of the riminophenazines and also protected the cells against the direct cytotoxic effect of lysophosphatidylcholine, while the lysophospholipid-neutralizing enzyme lysophospholipase protected against the riminophenazines. These observations demonstrate that the tumoricidal properties of clofazimine and B669 are probably due to increases in the lysophospholipid content of cell membranes.
Androgen Receptor is a Determinant of Melanoma targeted drug resistance (2022)

Abstract Melanoma provides a primary benchmark for targeted drug therapy. Most melanomas with BRAF V600 mutations regress in response to BRAF/MEK inhibitors (BRAFi/MEKi). However, nearly all relapse within the first two years, and there is a connection between pathways involved in BRAFi/MEKi-resistance and poor response to immune checkpoint therapy. We recently showed that androgen receptor (AR) activity is required for melanoma cell proliferation and tumorigenesis. Here we find that AR expression is markedly increased in BRAFi resistant melanoma cells as well as in sensitive cells soon after BRAFi exposure. Increased AR expression is by itself sufficient to render melanoma cells BRAFi-resistant, eliciting transcriptional changes of BRAFi resistant subpopulations and elevated EGFR and SERPINE1 expression of likely clinical significance. Inhibition of AR expression and activity blunts changes in gene expression and suppresses proliferation and tumorigenesis of BRAFi-resistant melanoma cells, enhances MHC I expression and CD8+ T cells infiltration. Our findings point to targeting AR as a possible co-adjuvant approach for the prevention and management of the disease.
Nitric oxide synthesised from L-arginine mediates endothelium dependent dilatation in human veins in vivo (1989)

Endothelium derived relaxing factor (EDRF) has been identified as nitric oxide, synthesised from the amino acid L-arginine, a process which is inhibited by the L-arginine analogue NG-monomethyl L-arginine (L-NMMA). We have studied the effect of local infusions of L-NMMA on venous reactivity in healthy volunteers. Studies were performed using the veins on the back of the hand. The diameter of a single dorsal hand vein was measured in healthy subjects who had taken 600 mg of aspirin 30 min before the experiment. Changes in diameter were recorded during local infusions of noradrenaline, bradykinin, acetylcholine, glyceryl trinitrate, L- and D-arginine and its NG-monomethyl derivatives. L-NMMA (100 nmol.min-1) stereospecifically inhibited vasodilatation induced by acetylcholine and bradykinin (p less than 0.02) but not that induced by the endothelium independent vasodilator glyceryl trinitrate. L-NMMA (100 nmol.min-1) potentiated the venoconstrictor effect of a high dose of acetylcholine (100 nmol.min-1) without affecting the action of noradrenaline and without having a direct venoconstrictor effect in doses up to 10 mumol.min-1. These results show that the venous effects of certain vasodilators in man are mediated through the release of nitric oxide (EDRF) synthesised from L-arginine. They also highlight differences in basal and stimulated production of nitric oxide between arteries and veins.
Mechanochemical Treatment of Precursors of Carbon-Nanoshell-Containing Catalysts for the Oxygen Reduction Reaction (2016)

In an attempt to obtain carbon catalysts with higher activity for the oxygen reduction reaction (ORR), a mechanochemical (M)-treatment was applied to a heat-treated precursor of carbon-nanoshell-containing catalysts at 500°C, where the nanoshell was a catalytically formed, shell-structured carbon material with diameter of 20–30 nm and walls that consisted of hexagonal carbon layers. The precursor was a mixture of cobalt phthalocyanine and a phenol-formaldehyde resin. The carbonized precursor that was mechanochemically treated after the heat-treatment at 500°C showed higher ORR activity, with ORR current density that was five times that of the carbonized untreated precursor. Characterizations of the precursors and the carbons concluded that the enhanced ORR catalytic activity was due to the formation of carbon nanoshells with disordered hexagonal carbon layers located on their surface, and these nanoshells had a higher N/C surface atomic ratio than those of the carbonized untreated precursors. The application of M-treatment to a 500°C-heat-treated precursor was thus revealed to be useful for improving the ORR activity of carbon nanoshells.
Electrically-driven plasmonic sources and sensors (Conference Presentation) (2019)

Electrically-driven nanoscale light sources are imperative in the design on nanophotonic circuits and applications. We will discuss the direct excitation of waveguided modes of a metamaterial slab consisting of array of plasmonic nanoparticles using electron tunnelling effects. The large flux of hot electrons makes the tunnel junctions highly reactive, providing opportunities for designing hydrogen and oxygen sensors. Tunnel-junction based nanoscale light sources provide numerous opportunities for free space and integrated optics applications.
Feasibility of Using Low-Cost Motion Capture for Automated Screening of Shoulder Motion Limitation after Breast Cancer Surgery (2015)

Low-cost, automated motion analysis may be acceptable to screen for moderate to severe motion impairments in active shoulder motion. Automatic detection of motion limitation may allow quick screening to be performed in an oncologist's office and trigger timely referrals for rehabilitation.
Shoe-integrated sensor system for wireless gait analysis and real-time feedback (2002)

We are developing a sensor system for use in clinical gait analysis. This research involves the development of an on-shoe device that can be used for continuous and real-time monitoring of gait. This paper presents the design of an instrumented insole and a removable instrumented shoe attachment. Transmission of the data is in real-time and wireless, providing information about the three-dimensional motion, position, and pressure distribution of the foot. Using pattern recognition and numerical analysis of the calibrated sensor outputs, algorithms will be developed to analyze the data in real-time. Results will be validated by comparison to results from a commercial optical gait analysis system at the Massachusetts General Hospital (MGH) Biomoti on Lab.
Long-Term Survival After Liver Transplantation in 4,000 Consecutive Patients at a Single Center (2000)

Significantly improved patient and graft survival has been observed over time, and graft loss from acute or chronic rejection has emerged as a rarity. Age-related and disease-related causes of graft loss represent the greatest threat to long-term survival.
Alternating electron and proton transfer steps in photosynthetic water oxidation (2012)

Water oxidation by cyanobacteria, algae, and plants is pivotal in oxygenic photosynthesis, the process that powers life on Earth, and is the paradigm for engineering solar fuel-production systems. Each complete reaction cycle of photosynthetic water oxidation requires the removal of four electrons and four protons from the catalytic site, a manganese-calcium complex and its protein environment in photosystem II. In time-resolved photothermal beam deflection experiments, we monitored apparent volume changes of the photosystem II protein associated with charge creation by light-induced electron transfer (contraction) and charge-compensating proton relocation (expansion). Two previously invisible proton removal steps were detected, thereby filling two gaps in the basic reaction-cycle model of photosynthetic water oxidation. In the S(2) → S(3) transition of the classical S-state cycle, an intermediate is formed by deprotonation clearly before electron transfer to the oxidant (Y Z OX). The rate-determining elementary step (τ, approximately 30 µs at 20 °C) in the long-distance proton relocation toward the protein-water interface is characterized by a high activation energy (E(a) = 0.46 ± 0.05 eV) and strong H/D kinetic isotope effect (approximately 6). The characteristics of a proton transfer step during the S(0) → S(1) transition are similar (τ, approximately 100 µs; E(a) = 0.34 ± 0.08 eV; kinetic isotope effect, approximately 3); however, the proton removal from the Mn complex proceeds after electron transfer to . By discovery of the transient formation of two further intermediate states in the reaction cycle of photosynthetic water oxidation, a temporal sequence of strictly alternating removal of electrons and protons from the catalytic site is established.