gebhart/patrepeval huggingface dataset:
A tetravalent bispecific TandAb (CD19/CD3), AFM11, efficiently recruits T cells for the potent lysis of CD19<sup>+</sup>tumor cells (2015)

To harness the potent tumor-killing capacity of T cells for the treatment of CD19(+) malignancies, we constructed AFM11, a humanized tetravalent bispecific CD19/CD3 tandem diabody (TandAb) consisting solely of Fv domains. The molecule exhibits good manufacturability and stability properties. AFM11 has 2 binding sites for CD3 and 2 for CD19, an antigen that is expressed from early B cell development through differentiation into plasma cells, and is an attractive alternative to CD20 as a target for the development of therapeutic antibodies to treat B cell malignancies. Comparison of the binding and cytotoxicity of AFM11 with those of a tandem scFv bispecific T cell engager (BiTE) molecule targeting the same antigens revealed that AFM11 elicited more potent in vitro B cell lysis. Though possessing high affinity to CD3, the TandAb mediates serial-killing of CD19(+) cells with little dependence of potency or efficacy upon effector:target ratio, unlike the BiTE. The advantage of the TandAb over the BiTE was most pronounced at lower effector:target ratios. AFM11 mediated strictly target-dependent T cell activation evidenced by CD25 and CD69 induction, proliferation, and cytokine release, notwithstanding bivalent CD3 engagement. In a NOD/scid xenograft model, AFM11 induced dose-dependent growth inhibition of Raji tumors in vivo, and radiolabeled TandAb exhibited excellent localization to tumor but not to normal tissue. After intravenous administration in mice, half-life ranged from 18.4 to 22.9 h. In a human ex vivo B-cell chronic lymphocytic leukemia study, AFM11 exhibited substantial cytotoxic activity in an autologous setting. Thus, AFM11 may represent a promising therapeutic for treatment of CD19(+) malignancies with an advantageous safety risk profile and anticipated dosing regimen.
Xylose anaerobic conversion by open-mixed cultures (2008)

Xylose is, after glucose, the dominant sugar in agricultural wastes. In anaerobic environments, carbohydrates are converted into volatile fatty acids and alcohols. These can be used as building blocks in biotechnological or chemical processes, e.g., to produce bioplastics. In this study, xylose fermentation by mixed microbial cultures was investigated and compared with glucose under the same conditions. The product spectrum obtained with both substrates was comparable. It was observed that, in the case of xylose, a higher fraction of the carbon was converted into catabolic products (butyrate, acetate, and ethanol) and the biomass yield was approximately 20% lower than on glucose, 0.16 versus 0.21 Cmol X/Cmol S. This lower yield is likely related to the need of an extra ATP during xylose uptake. When submitted to a pulse of glucose, the population cultivated on xylose could instantaneously convert the glucose. No substrate preference was observed when glucose and xylose were fed simultaneously to the continuously operated bioreactor.
Endothall thioanhydride: structural aspects of unusually high mouse toxicity and specific binding site in liver (1990)

The thioanhydride of the herbicide endothall is highly toxic to mice on intraperitoneal (ip) administration, with an LD50 of 0.31 mg/kg compared to 4.0 and 14 mg/kg for the corresponding anhydride and dicarboxylic acid, respectively. This unusually high toxicity of the thioanhydride relative to the anhydride and dicarboxylic acid is observed also for the 5,6-dehydro analogue and less so for the 2-methyl and 5-endo-(cyanomethyl) analogues but not for five related series of 7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acids, anhydrides, and thioanhydrides with various 2-, 3-, 5- and 6-substituents. Synthesis of [exo,exo-5,6-3H]endothall thioanhydride ([3H]ETA) allowed radioligand binding studies with mouse liver cytosol, which was found to have a high-affinity binding site (apparent dissociation constant 32 nM, maximum number of binding sites 2.8 pmol/mg of protein, greater than 95% specific binding). The potency of 18 endothall analogues as dicarboxylic acids and anhydrides for inhibiting [3H]ETA binding in vitro is a very good predictor of their mouse toxicity (r = 0.95, n = 16; two related compounds are of low activity in both assays) in a similar manner to earlier studies with [3H]-2,3-dimethylendothall anhydride (cantharidin) (r = 0.83, n = 15). This correlation does not extend to most of the thioanhydrides, particularly the 2,3-dimethyl and 2,3-trimethylene compounds, which are the most stable to hydrolytic cleavage. The [3H]ETA binding site of liver cytosol is inhibited 75-80% by LD50 doses of 2,3-dimethylendothall anhydride and thioanhydride but only 24% by an LD50 dose of endothall thioanhydride, with assays 30 min after ip treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
<i>Proteus mirabilis</i> urease. Partial purification and inhibition by boric acid and boronic acids (1988)

Urease was purified 800-fold and partially characterized from Proteus mirabilis, the predominant microorganism associated with urinary stones. Boric acid is a rapid reversible competitive inhibitor of urease. The pH-dependence of inhibition exhibited pKa values of 6.25 and 9.3, where the latter value is probably due to the inherent pKa of boric acid. Three boronic acids also were shown to inhibit urease competitively.
Expanding the catalog of <i>cas</i> genes with metagenomes (2013)

The CRISPR (clusters of regularly interspaced short palindromic repeats)-Cas adaptive immune system is an important defense system in bacteria, providing targeted defense against invasions of foreign nucleic acids. CRISPR-Cas systems consist of CRISPR loci and cas (CRISPR-associated) genes: sequence segments of invaders are incorporated into host genomes at CRISPR loci to generate specificity, while adjacent cas genes encode proteins that mediate the defense process. We pursued an integrated approach to identifying putative cas genes from genomes and metagenomes, combining similarity searches with genomic neighborhood analysis. Application of our approach to bacterial genomes and human microbiome datasets allowed us to significantly expand the collection of cas genes: the sequence space of the Cas9 family, the key player in the recently engineered RNA-guided platforms for genome editing in eukaryotes, is expanded by at least two-fold with metagenomic datasets. We found genes in cas loci encoding other functions, for example, toxins and antitoxins, confirming the recently discovered potential of coupling between adaptive immunity and the dormancy/suicide systems. We further identified 24 novel Cas families; one novel family contains 20 proteins, all identified from the human microbiome datasets, illustrating the importance of metagenomics projects in expanding the diversity of cas genes.
Scheduling and Visualization (2004)

Abstract : This report summarizes research performed towards the development of architectures and tools for mixed-initiative scheduling. CMU's approach is rooted in incremental constraint-based search procedures and draws on interactive visual interfaces to integrate user and system decision-making. The report first describes a successful application of CMU's approach to the problem of allocating aircraft and aircrews to airlift and tanker missions at the Air Mobility Command (AMC). The developed system, called the AMC Barrel Allocator, has been taken over by AMC and is now part of the operational air mobility planning system in AMC's Tanker/Airlift Control Center. CMU next considered progress made in the area of configurable scheduling systems. Specifically provided is an overview of the OZONE scheduling ontology, which was designed to provide a conceptual mapping from high-level domain analysis to construction of an executable scheduling model and support rapid application construction. The report also described CMU's work in 2D and 3D visualization of resource capacity constraints, aimed at early identification of mismatches between resource demand and supply. CMU illustrates its use in analyzing port throughput capacity in the context of strategic deployment planning. A technology integration experiment involving a second air campaign scheduling application of the incremental scheduling approach in a visionary, effects-based planning demonstration is then described. The report summarizes the results obtained in the development of core procedures for generating temporally flexible schedules which provide some measure of robustness in a dynamic execution environment.
Sandboxing Applications (2001)

Permission is granted for noncommercial reproduction of the work for educational or research purposes.
Hydrophobic clustering in nonnative states of a protein: Interpretation of chemical shifts in NMR spectra of denatured states of lysozyme (1991)

Chemical shifts of resonances of specific protons in the 1H NMR spectrum of thermally denatured hen lysozyme have been determined by exchange correlation with assigned native state resonances in 2D NOESY spectra obtained under conditions where the two states are interconverting. There are subtle but widespread deviations of the measured shifts from the values which would be anticipated for a random coil; in the case of side chain protons these are virtually all net upfield shifts and it is shown that this may be the averaged effect of interactions with aromatic rings in a partially collapsed denatured state. In a very few cases, notably that of two sequential tryptophan residues, it is possible to interpret these effects in terms of specific, local interresidue interactions. Generally, however, there is no correlation with either native state shift perturbations or with sequence proximity to aromatic groups. Diminution of most of the residual shift perturbations on reduction of the disulfide cross-links confirms that they are not simply effects of residues adjacent in the sequence. Similar effects of chemical denaturants, with the disulfides intact, demonstrate that the shift perturbations reflect an enhanced tendency to side chain clustering in the thermally denatured state. The temperature dependences of the shift perturbations suggest that this clustering is noncooperative and is driven by small, favorable enthalpy changes. While the extent of conformational averaging is clearly much greater than that observed for a homologous protein, alpha-lactalbumin, in its partially folded "molten globule" state, the results clearly show that thermally denatured lysozyme differs substantially from a random coil, principally in that it is partially hydrophobically collapsed.
The Valuation of Health Care Intangible Assets (1997)

Health care entities (and especially medical practices) are valued for a number of reasons: sale transaction pricing and structuring, merger formation and dissolution, taxation and regulatory compliance, and litigation support and dispute resolution. The identification and quantification of the entity's intangible assets are often the most important aspects of the valuation. This article illustrates the generally accepted methods for valuing health care-related intangible assets.
On the fringing-field effect in liquid-crystal beam-steering devices (2004)

A detailed simulation of the fringing-field effect in liquid-crystal (LC)-based blazed-grating structures has been carried out. These studies are aimed at clarifying the relationship between the width of the fringing-field-broadened phase profile of the blazed grating and the LC cell thickness. This fringing-field broadening of the blazed grating's phase profile is shown to affect mostly the 2pi phase-step zone (fly-back zone) of the blazed grating. The results of the simulations carried out on the blazed-grating structure indicate two main effects of the fringing field: (1) reduction in the attainable diffraction efficiency and (2) limitation of the maximum deflection angle of the device. Both effects are shown to be directly linked to the broadening of the fly-back zone, which is shown to be proportional to the LC cell thickness.
Functionalisation of 1,2,3‐triazole <i>via</i> lithiation of 1‐[2‐(trimethylsilyl)ethoxy]methyl‐1<i>H</i>‐1,2,3‐triazole (1992)

Abstract The preparation of a number of 5‐substituted 1‐[2‐(trimethylsilyl)ethoxy]methyl‐1 H ‐1,2,3‐triazoles via reaction of 1‐[2‐(trimethylsilyl)ethoxy]methyl‐1 H ‐1,2,3‐triazole with n ‐butyllithium followed by addition of various electrophiles is reported. Removal of the protecting group by action of diluted aqueous hydrochloric acid or by tetrabutylammonium fluoride in tetrahydrofuran leads to the appropriate 4‐substituted 1 H ‐1,2,3‐triazoles.
MEM relay for reconfigurable RF circuits (2001)

We describe a microelectromechanical (MEM) relay technology for high-performance reconfigurable RF circuits. This microrelay, fabricated using surface micromachining, is a metal contact relay with electrical isolation between signal and drive lines. This relay provides excellent switching performance over a broad frequency band (insertion loss of 0.1 dB and isolation of 30 dB at 40 GHz), versatility in switch circuit configurations (microstrip and coplanar, shunt and series), and the capability for monolithic integration with high-frequency electronics. In addition, this MEM relay technology has demonstrated yields and lifetimes that are promising for RF circuit implementation.
AAV2/8-humanFOXP3 gene therapy shows robust anti-atherosclerosis efficacy in LDLR-KO mice on high cholesterol diet (2015)

Inflammation is a key etiologic component in atherogenesis. Previously we demonstrated that adeno-associated virus (AAV) 2/8 gene delivery of Netrin1 inhibited atherosclerosis in the low density lipoprotein receptor knockout mice on high-cholesterol diet (LDLR-KO/HCD). One important finding from this study was that FOXP3 was strongly up-regulated in these Netrin1-treated animals, as FOXP3 is an anti-inflammatory gene, being the master transcription factor of regulatory T cells. These results suggested that the FOXP3 gene might potentially be used, itself, as an agent to limit atherosclerosis. To test this hypothesis AAV2/8 (AAV)/hFOXP3 or AAV/Neo (control) gene therapy virus were tail vein injected into the LDLR-KO/HCD animal model. It was found that hFOXP3 gene delivery was associated with significantly lower HCD-induced atherogenesis, as measured by larger aortic lumen cross sectional area, thinner aortic wall thickness, and lower aortic systolic blood velocity compared with Neo gene-HCD-treated controls. Moreover these measurements taken from the hFOXP3/HCD-treated animals very closely matched those measurements taken from the normal diet (ND) control animals. These data strongly suggest that AAV/hFOXP3 delivery gave a robust anti-atherosclerosis therapeutic effect and further suggest that FOXP3 be examined more stringently as a therapeutic gene for clinical use.
The Ribble Valley: A Methodological Study in Landscape Development (2008)

Using modern geographic information systems, it is possible to reconstruct landscapes, not only throughout human history, but also back to the time of the last glaciation. A multi-disciplinary project by Oxford Archaeology North and the University of Liverpool, funded by the Aggregates Levy Sustainability Fund (ALSF), implemented by English Heritage, reconstructed the landscapes of the Ribble Valley and Kirkham Moraine in Lancashire, and provided an opportunity for an assessment of different methodological approaches. Many diverse datasets were used in the project, including geological and palaeoecological data, LiDAR, cartographic sources, aerial photography and data from the County's Historic Environment Record. Statistical techniques were then used on the data to highlight patterns in human occupation of the landscape. This resulted in a detailed chronological history, showing the effect of human interaction on fluvial development, and highlighting areas of potential where further archaeology may be discovered. Some methodological techniques such as LiDAR proved very useful for detailed visualisation of landscape and the identification of archaeological sites, whereas statistical analysis was useful in some cases but not in others, demonstrating that qualitative analysis can never be entirely replaced.
Neurogenin3: A master regulator of pancreatic islet differentiation and regeneration (2009)

The basic helix-loop-helix transcription factor neurogenin-3 (Ngn3, Neurog3) is critical for the development of the endocrine cells of the islets. Either disrupted or forced expression of Ngn3 early in mouse pancreas development abrogates the formation of islets. The successive waves of Ngn3 expression that occur during the primary and secondary transitions of endocrine cell development temporally determine the four distinct endocrine cell lineages, α, β, PP, and δ cells that express glucagon, insulin, pancreatic polypeptide, and somatostatin, respectively. During islet regeneration after injury of the adult mouse pancreas, such as by duct ligation or streptozotocin, Ngn3 is activated in duct-associated stem/progenitor cells that transform into alpha and/or beta cells (Xu et al, Collombat et al). The important role of Ngn3 as a master regulator of endocrine pancreas development directs attention to finding therapeutic approaches to enhance Ngn3 expression in diabetes as a means to increase beta cell mass and functions.
Scanning tunneling spectroscopy of InAs nanocrystal quantum dots (2000)

Scanning tunneling spectroscopy is used to investigate single InAs nanocrystals, 20--70 \AA{} in diameter, in a highly asymmetric double barrier tunnel junction configuration. The $I\ensuremath{-}V$ characteristics reflect contributions of both single-electron charging and the atomiclike level structure of the quantum dots. The spectra are simulated and well described within the framework of the ``orthodox model'' for single-electron tunneling. The peaks in the tunneling spectra display a systematic broadening with the reduction of dot diameter, from 40 to 150 meV over the studied quantum dot size range. This is assigned to a decreased electron dwell time on the dot, due to reduction of the barrier height, induced by the blueshift of the quantum-confined levels. The distribution of peak spacings within charging multiplets in the tunneling spectra is found to be Gaussian, resembling observations on metallic quantum dots.
Joint Secure Beamforming Design at the Source and the Relay for an Amplify-and-Forward MIMO Untrusted Relay System (2011)

An amplify-and-forward (AF) multiple-input multiple-output (MIMO) relay network composed of a source, a relay, and a destination is considered, where transmit beamforming is employed both at the source and at the relay. The relay is a user who is willing to help the communication from the source to the destination. In our paper, however, the relay is untrusted in the sense that it may make a passive security attack; that is, it may decode messages of the source. We consider two ways to transmit confidential information of the source to the destination: noncooperative secure beamforming and cooperative secure beamforming. In the noncooperative scheme, the relay is simply treated as an eavesdropper, and does not participate in communication. In the cooperative scheme, the relay is asked to relay signals from the source to the destination. In this paper, the source and relay beamforming is jointly designed to maximize the secrecy rate in the cooperative scheme. The conditions under which the cooperative scheme achieves a higher secrecy rate than the noncooperative scheme are derived in the low and high signal-to-noise ratio (SNR) regimes of the source-relay and relay-destination links. The performance of the secure beamforming schemes is compared through extensive numerical simulations.
Directed Differentiation of Human Embryonic Stem Cells to Dendritic Cells (2007)

Embryonic stem cells represent a pluripotent population of cells capable of self-renewal, large-scale expansion, and differentiation in various cell lineages including cells of hematopoietic lineage. In this chapter, we describe a three-step cell culture method for directed differentiation of human embryonic stem cells (hESCs) to dendritic cells (DCs) that includes (1) hESC differentiation into hematopoietic progenitors by coculture with OP9 stromal cells, (2) expansion of myeloid DC precursors in suspension bulk cultures with granulocyte monocyte-colony stimulating factor (GM-CSF), and (3) differentiation of myeloid precursors to DCs in the serum-free medium with GM-CSF and interleukin-4 (IL-4). The method employs cell culture conditions selecting an almost pure population of myeloid DC precursors and does not require isolation of hematopoietic progenitors. With this method, hESCs can be differentiated to functional DCs within 30 days at an efficiency of at least four DCs per single undifferentiated hESC. Directed differentiation of DCs from hESCs could be useful for studying cellular and molecular mechanisms of DC development and potentially for the generation of antigen-presenting cells for cellular immunotherapy.
Transient Potential Modification of Large Spacecraft Due to Electron Emissions (1997)

Covers advancements in spacecraft and tactical and strategic missile systems, including subsystem design and application, mission design and analysis, materials and structures, developments in space sciences, space processing and manufacturing, space operations, and applications of space technologies to other fields.
HARP chip: a 600 Mflops application-specific LSI for astrophysical N-body simulations (1994)

Describes an application-specific LSI, the HARP (Hermite AcceleratoR Pipe) chip, which will he used in GRAPE-4, a massively-parallel special-purpose computer for astrophysical N-body simulations. The HARP chip calculates the gravitational interaction between particles. It consists of 15 floating point arithmetic units and one unit for function evaluation. The HARP chip performs about 20 floating point operations per clock cycle and works at 30 MHz in the worst case. Therefore, the performance of the HARP chip exceeds 600 Mflops. It is made using 1.0 /spl mu/m CMOS cell-based ASIC (LSI Logic, LCB007). The die size is 14.6 mm/spl times/14.6 mm and the total Rate count is 95,000. The power consumption is 5W at operating voltage of 5 V. The authors have examined successful operations of the sample chip up to 50 MHz. GRAPE-4 will consist of about 2000 HARP chips using multi-chip modules. The peak speed of GRAPE-4 will exceed 1 Tflops even in the worst case, and will reach around 1.8 Tflops in the typical case.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Faster R-CNN: Towards Real-Time Object Detection with Region Proposal\n Networks (2015)

State-of-the-art object detection networks depend on region proposal\nalgorithms to hypothesize object locations. Advances like SPPnet and Fast R-CNN\nhave reduced the running time of these detection networks, exposing region\nproposal computation as a bottleneck. In this work, we introduce a Region\nProposal Network (RPN) that shares full-image convolutional features with the\ndetection network, thus enabling nearly cost-free region proposals. An RPN is a\nfully convolutional network that simultaneously predicts object bounds and\nobjectness scores at each position. The RPN is trained end-to-end to generate\nhigh-quality region proposals, which are used by Fast R-CNN for detection. We\nfurther merge RPN and Fast R-CNN into a single network by sharing their\nconvolutional features---using the recently popular terminology of neural\nnetworks with 'attention' mechanisms, the RPN component tells the unified\nnetwork where to look. For the very deep VGG-16 model, our detection system has\na frame rate of 5fps (including all steps) on a GPU, while achieving\nstate-of-the-art object detection accuracy on PASCAL VOC 2007, 2012, and MS\nCOCO datasets with only 300 proposals per image. In ILSVRC and COCO 2015\ncompetitions, Faster R-CNN and RPN are the foundations of the 1st-place winning\nentries in several tracks. Code has been made publicly available.\n