gebhart/patrepeval huggingface dataset:
Conclusion (2013)

Abstract The Conclusion assesses our contribution to worklife balance research: how the capabilities framework and conceptual tools we applied adds new perspectives for theorizing agency in worklife balance and for analysing its multi-dimensional aspects. It also considers how our institutional models and applications extend the conceptual borders in the capabilities approach. The chapter highlights key points from our research that reveal the agency and capabilities gap in worklife balance and engages with the with cross-currents in the debates on gender inequalities and worklife life balance, specifically the blueprints for change. These are viewed critically through the lens of capabilities. The chapter ends with a discussion of the global financial crises and the widening gap in capabilities and agency for worklife balance across European societies and the deepening inequalities between the global South and North reflected in the global care chain.
Evaluation of drugs for elimination of leukemic cells from the bone marrow of patients with acute leukemia (1988)

Relatively nonmyelotoxic drugs and drug combinations were investigated for their ability to eliminate malignant cells from human bone marrow. In vitro 90% inhibitory concentration (IC90) doses were established on granulocyte macrophage colony-forming units (GM-CFU) in culture of bone marrow by using the GM-CFU assay for the following drugs: 4- hydroperoxycyclophosphamide (4-HC), Adriamycin, L-asparaginase, bleomycin, hydrocortisone, VP-16, spirogermanium, Taxol, and vincristine. The leukemic cell kill efficiency of these drugs at IC90 doses was compared with that of 4-HC on acute lymphoid leukemia (ALL) cell lines by using the limiting-dilution assay. Under these conditions, no single drug was superior to 4-HC. To increase the in vitro effect in leukemic cell kill, combinations of vincristine with hydrocortisone, Adriamycin, VP-16, and 4-HC were investigated. Vincristine at 1 to 5 micrograms/mL increased the marrow cytotoxicity of hydrocortisone, Adriamycin, and VP-16, but it was protective (subadditive) with 4-HC. Vincristine and 4-HC in combination was additive to supraadditive on ALL cell lines, increased the leukemic cell kill by one to two logs above 4-HC alone at IC90 doses (P less than .05), and was not affected by the addition of excess marrow cells. The recommended doses for chemopurging in clinical studies are vincristine, 1 to 5 micrograms/mL, plus 4-HC, 5 micrograms/mL.
From Combinatorial Chemistry to Cancer-Targeting Peptides (2007)

Several monoclonal antibodies that target cell surface receptors have gained approval by the U.S. Food and Drug Administration and are widely used in the treatment of some cancers. These include but are not limited to the anti-CD20 antibody Rituximab, used in lymphoma treatment, as well as anti-HER-2 antibody for breast cancer therapy. The efficacy of this cancer immunotherapy modality is, however, limited by the large size of the antibody (160 kd) and its relatively nonspecific binding to the reticuloendothelial system. This latter property is particularly problematic if the antibody is used as a vehicle to deliver radionuclides, cytotoxic drugs, or toxins to the tumor site. Peptides, peptidomimetic, or small molecules are thus attractive as alternative cell surface targeting agents for cancer imaging and therapy. Cancer cell surface targeting peptides can be derived from known native peptide hormones such as somatostatin and bombesin, or they can be identified through screening combinatorial peptide libraries against unknown cell surface receptor targets. Phage-display peptide library and one-bead one-compound (OBOC) combinatorial library methods have been successfully used to discover peptides that target cancer cells or tumor blood vessel endothelial cells. The phage-display peptide library method, because of its biological nature, can only display l-amino acid peptides. In contrast, the OBOC combinatorial library method allows for bead-surface display of peptides that contain l-amino acids, d-amino acids, unnatural amino acids, or other organic moieties. We have successfully used the OBOC method to discover and optimize ligands against unique cell surface receptors of prostate cancer, T- and B-cell lymphoma, as well as ovarian and lung cancers, and we have used some of these peptides to image xenografts in nude mice with high specificity. Here, we (i) review the literature on the use of phage-display and OBOC combinatorial library methods to discover cancer and tumor blood vessel targeting ligands, and (ii) report on the use of an ovarian cancer targeting ligand, OA02, as an in vivo PET imaging probe in a xenograft model in nude mice.
The acute splanchnic and peripheral tissue metabolic response to endotoxin in humans. (1990)

The in vivo alterations in organ-specific substrate processing and endogenous mediator production induced by endotoxin were investigated in healthy volunteers. An endotoxin bolus (20 U/kg) produced increased energy expenditure, hyperglycemia, hypoaminoacidemia, and an increase in circulating free fatty acids. These changes included increased peripheral lactate and free fatty acid output, along with increased peripheral uptake of glucose. Coordinately, there were increased splanchnic uptake of oxygen, lactate, amino acids, and free fatty acids, and increased splanchnic glucose output. There were no changes in circulating glucagon, or insulin and transient changes in epinephrine and cortisol were insufficient to explain the metabolic changes. Plasma cachectin levels peaked 90 min after the endotoxin infusion, and hepatic venous (HV) cachectin levels (peak 250 +/- 50 pg/ml) were consistently higher than arterial levels (peak 130 +/- 30 pg/ml, P less than 0.05 vs. HV). No interleukin 1 alpha or 1 beta was detected in the circulation. Circulating interleukin 6, measured by B.9 hybridoma proliferation, peaked 2 h after the endotoxin challenge (arterial, 16 +/- 2 U/ml; HV, 21 +/- 3 U/ml). The net cachectin efflux (approximately 7 micrograms) from the splanchnic organs demonstrates that these tissues are a major site for production of this cytokine. Hence, splanchnic tissues are likely influenced in a paracrine fashion by regional cachectin production and may also serve as a significant source for systemic appearance of this cytokine.
1-Hydroxy-3-(methylpentylamino)-propylidene-1,1-bisphosphonic acid as a potent inhibitor of squalene synthase. (1996)

Squalene synthase, the first committed enzyme for sterol synthesis, converts farnesyl pyrophosphate to squalene with presqualene pyrophosphate as an intermediate. It was discovered that BM 21.0955 (1-hydroxy-3-(methylpentylamino)-propylidene-1,1-bisphosphon ic acid), in development for the treatment of bone disorders, inhibited rat liver microsomal squalene synthase (K(i) = nmol/l). BM 21.0955 also inhibited sterol biosynthesis from mevalonate (IC50 = 42 nmol/l), and cholesterol biosynthesis in J774 cells (IC50 = mumol/l). Structural modifications on this molecule to make it more lipophilic may result in a new class of cholesterol-lowering agents.
Self-consistent Electrode Model for Magnetoplasmadynamic Thrusters (2004)

Accurate sheath modeling is of considerable interest to the effective design of ionized flow in several aerospace applications including space propulsion thrusters and high-speed air vehicles. In particular, an electrode sheath (fall) voltage model is necessary to predict the power requirement, which in turn is used to measure the total efficiency for on-board propulsion thrusters. Plasma wall interaction is thus crucial for improving the high power thruster efficiency. In this paper, a finite element discretized two-dimensional self-consistent formulation of plasma–sheath dynamics, using multi-fluid equations for partially ionized plasma, is presented. The formulation is applied to a simplistic electrode model. Computed potential distributions on three locations along the electrode are plotted. The details of the number densities of electrons, ions and neutrals along with ion, electron and neutral dynamics, sheath potential and electron temperature profiles gives insight into the wall potential loss mechanism.
Automated protein crystal structure determination using elves (2004)

Efficient determination of protein crystal structures requires automated x-ray data analysis. Here, we describe the expert system ELVES and its use to determine automatically the structure of a 12-kDa protein. Multiwavelength anomalous diffraction analysis of a selenomethionyl derivative was used to image the Asn-16-Ala variant of the GCN4 leucine zipper. In contrast to the parallel, dimeric coiled coil formed by the WT sequence, the mutant unexpectedly formed an antiparallel trimer. This structural switch reveals how avoidance of core cavities at a single site can select the native fold of a protein. All structure calculations, including indexing, data processing, locating heavy atoms, phasing by multiwavelength anomalous diffraction, model building, and refinement, were completed without human intervention. The results demonstrate the feasibility of automated methods for determining high-resolution, x-ray crystal structures of proteins.
Janus-faced role of endothelial NO synthase in vascular disease: uncoupling of oxygen reduction from NO synthesis and its pharmacological reversal (2006)

Endothelial NO synthase (eNOS) is the predominant enzyme responsible for vascular NO synthesis. A functional eNOS transfers electrons from NADPH to its heme center, where L-arginine is oxidized to L-citrulline and NO. Common conditions predisposing to atherosclerosis, such as hypertension, hypercholesterolemia, diabetes mellitus and smoking, are associated with enhanced production of reactive oxygen species (ROS) and reduced amounts of bioactive NO in the vessel wall. NADPH oxidases represent major sources of ROS in cardiovascular pathophysiology. NADPH oxidase-derived superoxide avidly interacts with eNOS-derived NO to form peroxynitrite (ONOO(-)), which oxidizes the essential NOS cofactor (6R-)5,6,7,8-tetrahydrobiopterin (BH(4)). As a consequence, oxygen reduction uncouples from NO synthesis, thereby rendering NOS to a superoxide-producing pro-atherosclerotic enzyme. Supplementation with BH(4) corrects eNOS dysfunction in several animal models and in patients. Administration of high local doses of the antioxidant L-ascorbic acid (vitamin C) improves endothelial function, whereas large-scale clinical trials do not support a strong role for oral vitamin C and/or E in reducing cardiovascular disease. Statins, angiotensin-converting enzyme inhibitors and AT1 receptor blockers have the potential of reducing vascular oxidative stress. Finally, novel approaches are being tested to block pathways leading to oxidative stress (e.g. protein kinase C) or to upregulate antioxidant enzymes.
Identification of human transferrin-binding sites within meningococcal transferrin-binding protein B (1997)

Transferrin-binding protein B (TbpB) from Neisseria meningitidis binds human transferrin (hTf) at the surface of the bacterial cell as part of the iron uptake process. To identify hTf binding sites within the meningococcal TbpB, defined regions of the molecule were produced in Escherichia coli by a translational fusion expression system and the ability of the recombinant proteins (rTbpB) to bind peroxidase-conjugated hTf was characterized by Western blot and dot blot assays. Both the N-terminal domain (amino acids [aa] 2 to 351) and the C-terminal domain (aa 352 to 691) were able to bind hTf, and by a peptide spot synthesis approach, two and five hTf binding sites were identified in the N- and C-terminal domains, respectively. The hTf binding activity of three rTbpB deletion variants constructed within the central region (aa 346 to 543) highlighted the importance of a specific peptide (aa 377 to 394) in the ligand interaction. Taken together, the results indicated that the N- and C-terminal domains bound hTf approximately 10 and 1000 times less, respectively, than the full-length rTbpB (aa 2 to 691), while the central region (aa 346 to 543) had a binding avidity in the same order of magnitude as the C-terminal domain. In contrast with the hTf binding in the N-terminal domain, which was mediated by conformational epitopes, linear determinants seemed to be involved in the hTf binding in the C-terminal domain. The host specificity for transferrin appeared to be mediated by the N-terminal domain of the meningococcal rTbpB rather than the C-terminal domain, since we report that murine Tf binds to the C-terminal domain. Antisera raised to both N- and C-terminal domains were bactericidal for the parent strain, indicating that both domains are accessible at the bacterial surface. We have thus identified hTf binding sites within each domain of the TbpB from N. meningitidis and propose that the N- and C-terminal domains together contribute to the efficient binding of TbpB to hTf with their respective affinities and specificities for determinants of their ligand.
Ethacrynic acid and piriprost as enhancers of cytotoxicity in drug resistant and sensitive cell lines. (1988)

Ethacrynic acid and piriprost (6,9-deepoxy-6,9-(phenylimino)-delta 6,8-prostaglandin I1) have been shown to potentiate the cytotoxic activity of chlorambucil in rat and human tumor cell lines. Walker 256 rat breast carcinoma cells (WS), with acquired resistance to nitrogen mustards (WR), and two human colon carcinoma cell lines, HT 29 and BE, were sensitized to chlorambucil when either ethacrynic acid or piriprost was administered at the same time as the alkylating agent. Both as single agents and in combination with chlorambucil, there was inhibition of glutathione S-transferase activity as measured with 1-chloro-2,4-dinitrobenzene as a substrate. A depletion in intracellular glutathione was also evident following ethacrynic acid alone or in combination with chlorambucil. Thus, diuretic plant phenols or prostaglandin analogues may have potential therapeutic utility in combination with alkylating agents.
Deep Layer Aggregation (2017)

Visual recognition requires rich representations that span levels from low to high, scales from small to large, and resolutions from fine to coarse. Even with the depth of features in a convolutional network, a layer in isolation is not enough: compounding and aggregating these representations improves inference of what and where. Architectural efforts are exploring many dimensions for network backbones, designing deeper or wider architectures, but how to best aggregate layers and blocks across a network deserves further attention. Although skip connections have been incorporated to combine layers, these connections have been "shallow" themselves, and only fuse by simple, one-step operations. We augment standard architectures with deeper aggregation to better fuse information across layers. Our deep layer aggregation structures iteratively and hierarchically merge the feature hierarchy to make networks with better accuracy and fewer parameters. Experiments across architectures and tasks show that deep layer aggregation improves recognition and resolution compared to existing branching and merging schemes. The code is at https://github.com/ucbdrive/dla.
Impact of Booster Breaks and Computer Prompts on Physical Activity and Sedentary Behavior Among Desk-Based Workers: A Cluster-Randomized Controlled Trial (2016)

Findings varied among the 3 study groups; however, results indicate the potential for consistent attendees of the Booster Break intervention to achieve significant, positive changes related to physical activity, sedentary behavior, and body mass index.
Your phone or mine? (2012)

Determining who is interacting with a multi-user interactive touch display is challenging. We describe a technique for associating multi-touch interactions to individual users and their accelerometer-equipped mobile devices. Real-time device accelerometer data and depth camera-based body tracking are compared to associate each phone with a particular user, while body tracking and touch contacts positions are compared to associate a touch contact with a specific user. It is then possible to associate touch contacts with devices, allowing for more seamless device-display multi-user interactions. We detail the technique and present a user study to validate and demonstrate a content exchange application using this approach.
A human homeobox gene, HB24, inhibits development of CD4+ T cells and impairs thymic involution in transgenic mice. (1993)

The HB24 gene encodes a diverged human homeodomain-containing protein known to be expressed in hematopoietic progenitors and activated lymphocytes. We have generated transgenic mice that express HB24 under the control of the T cell receptor beta chain promoter/enhancer. Analysis of T cells and thymocytes from the transgenic mice revealed a marked increase in activated cells as assessed by cell size profiles and interleukin-2 receptor expression. Within the thymus these changes were most pronounced in the CD4+CD8- subset. Strikingly, the normal development of CD4+ T cells in the transgenic mice was impaired. Single positive CD4 cells were reduced 35% in the thymus, and CD4+ T cells were reduced 90% in the spleen and lymph nodes compared to the controls. Similar findings were found both in young mice (6 weeks old) and in more elderly mice (1 y old). However, the thymuses of the elderly mice failed to undergo normal involution. Sera from HB24 transgenic mice had levels of IgG1 10-100-fold lower than sera from matched controls, most likely as a consequence of the decrease in CD4+ T cells. These transgenic mice provide a useful model for studying the role of HB24 in lymphocyte activation as well as for understanding the effects of abnormal T cell activation on thymic and T cell development.
Computationally designed high specificity inhibitors delineate the roles of BCL2 family proteins in cancer (2016)

Many cancers overexpress one or more of the six human pro-survival BCL2 family proteins to evade apoptosis. To determine which BCL2 protein or proteins block apoptosis in different cancers, we computationally designed three-helix bundle protein inhibitors specific for each BCL2 pro-survival protein. Following in vitro optimization, each inhibitor binds its target with high picomolar to low nanomolar affinity and at least 300-fold specificity. Expression of the designed inhibitors in human cancer cell lines revealed unique dependencies on BCL2 proteins for survival which could not be inferred from other BCL2 profiling methods. Our results show that designed inhibitors can be generated for each member of a closely-knit protein family to probe the importance of specific protein-protein interactions in complex biological processes.
Effect of Water Stress on Cortical Cell Division Rates within the Apical Meristem of Primary Roots of Maize (1997)

We characterized the effect of water stress on cell division rates within the meristem of the primary root of maize (Zea mays L.) seedlings. As usual in growth kinematics, cell number density is found by counting the number of cells per small unit length of the root; growth velocity is the rate of displacement of a cellular particle found at a given distance from the apex; and the cell flux, representing the rate at which cells are moving past a spatial point, is defined as the product of velocity and cell number density. The local cell division rate is estimated by summing the derivative of cell density with respect to time, and the derivative of the cell flux with respect to distance. Relatively long (2-h) intervals were required for time-lapse photography to resolve growth velocity within the meristem. Water stress caused meristematic cells to be longer and reduced the rates of cell division, per unit length of tissue and per cell, throughout most of the meristem. Peak cell division rate was 8.2 cells mm-1 h-1 (0.10 cells cell-1 h-1) at 0.8 mm from the apex for cells under water stress, compared with 13 cells mm-1 h-1 (0.14 cells cell-1 h-1) at 1.0 mm for controls.
Copper interconnect technology for the 32 nm node and beyond (2009)

Copper interconnects have gained wide acceptance in the microelectronics industry due to improved resistivity and reliability compared to Al interconnects. However, there are many challenges with implementation of Cu interconnects at the 32 nm node and beyond, including increased resistivity, integration with porous low-k materials, and reliability. In addition, for RF and mixed signal technology, integration of passive devices is required. In this paper, each of these topics is addressed.
Fabrication of a 50 nm half-pitch wire grid polarizer using nanoimprint lithography (2005)

We report the fabrication of a 50 nm half-pitch wire grid polarizer with high performance using nanoimprint lithography. The device is a form of aluminium gratings on a glass substrate whose size of 5.5 cm × 5.5 cm is compatible with a microdisplay panel. A stamp with a pitch of 100 nm was fabricated on a silicon substrate using laser interference lithography and sidewall patterning. The imprint and the aluminium etching processes are optimized to realize uniform aluminium gratings with aspect ratio of 4. The polarization extinction ratio of the fabricated device is over 2000, with transmission of 85% at a wavelength of 450 nm, which is the highest value ever reported. This work demonstrates that nanoimprint lithography is a unique cost-effective solution for nanopatterning requirements in consumer electronics components.
Circular YAC vectors containing short mammalian origin sequences are maintained under selection as HeLa episomes (2000)

pYACneo, a 15.8-kb plasmid, contains a bacterial origin, G418-resistance gene, and yeast ARS, CEN, and TEL elements. Three mammalian origins have been cloned into this circular vector: 343, a 448-bp chromosomal origin from a transcribed region of human chromosome 6q; X24, a 4.3-kb element containing the hamster DHFR origin of bidirectional replication (oribeta), and S3, a 1.1-kb human anti-cruciform purified autonomously replicating sequence. The resulting constructs have been transfected into HeLa cells, and G418-resistant subcultures were isolated. The frequency of G418-resistant transformation was 1.7-8.7 times higher with origin-containing YACneo than with vector alone. After >45 generations under G418 selection, the presence of episomal versus integrated constructs was assessed by fluctuation assay and by PCR of supercoiled, circular, and linear genomic cellular DNAs separated on ethidium bromide-cesium chloride gradients. In stable G418-resistant subcultures transfected with vector alone or with linearized constructs, as well as in some subcultures transfected with circular origin-containing constructs, resistance was conferred by integration into the host genome. However, several examples were found of G418-resistant transfectants maintaining the Y.343 and the YAC.S3 circular constructs in a strictly episomal state after long-term culture in selective medium, with 80-90% stability per cell division. The episomes were found to replicate semiconservatively in a bromodeoxyuridine pulse-labeling assay for </=130 cell generations after transfection. Furthermore, after </=172 cell generations rescued episomal DNA could be isolated intact and unrearranged, and could be used to retransform bacteria. These versatile constructs, containing mammalian origins, have the capacity for further modification with human telomere or large putative centromere elements, in an effort to move towards construction of a human artificial chromosome.