gebhart/patrepeval huggingface dataset:
Isolation of TGF-β-neutralizing single-domain antibodies of predetermined epitope specificity using next-generation DNA sequencing (2016)

The epitope specificity of therapeutic antibodies is often critical to their efficacy and mode of action. Here, we report the isolation of single-domain antibodies (sdAbs) against a pre-specified epitope of TGF-β3: namely, the site of interaction between the cytokine and its cell-surface type II receptor. By panning a phage-displayed immune llama VhH library against TGF-β3 using competitive elution with soluble dimeric type II receptor ectodomain in tandem with next-generation DNA sequencing, we identified several sdAbs that competed with the receptor for TGF-β3 binding and neutralized TGF-β3 in in vitro cellular assays. In contrast, all other sdAbs identified using conventional panning approaches (i.e., without regard to epitope specificity) did not target the site of receptor:cytokine interaction. We expect this strategy to be generally applicable for identifying epitope-specific sdAbs when binding reagents directed against the epitope of interest are available. The sdAbs identified here are of potential interest as cancer immunotherapeutics.
Deep supervised learning for hyperspectral data classification through convolutional neural networks (2015)

Spectral observations along the spectrum in many narrow spectral bands through hyperspectral imaging provides valuable information towards material and object recognition, which can be consider as a classification task. Most of the existing studies and research efforts are following the conventional pattern recognition paradigm, which is based on the construction of complex handcrafted features. However, it is rarely known which features are important for the problem at hand. In contrast to these approaches, we propose a deep learning based classification method that hierarchically constructs high-level features in an automated way. Our method exploits a Convolutional Neural Network to encode pixels' spectral and spatial information and a Multi-Layer Perceptron to conduct the classification task. Experimental results and quantitative validation on widely used datasets showcasing the potential of the developed approach for accurate hyperspectral data classification.
Use of normal C57BL/6 mice with established Mycobacterium avium infections as an alternative model for evaluation of antibiotic activity (1995)

Several murine models have been used to evaluate the activities of antimicrobial agents against Mycobacterium avium infection. The main model used is the beige mouse model, but beige mice are expensive and not easily available. Thus, we developed a model of infection in wild C57BL/6 mice. The drugs that exhibited some activity in a previous model of early infection were evaluated in a new model of established infection. Sparfloxacin (50 mg/kg of body weight), ethambutol (50 mg/kg), minocycline (25 mg/kg), and the inhibitor of the cortisol receptors RU-40555 (100 mg/kg) were compared with clarithromycin (50 mg/kg). Treatments were started 5 weeks after the inoculation and were continued for 21 days. Sparfloxacin and RU-40555, which exhibited a moderate activity in the model of early infection, were not effective in this model of established infection. Clarithromycin and combinations with clarithromycin kept their activities against M. avium infection, both in the spleen and in lungs. The present model of established infection of normal C57BL/6 mice is more relevant than the model of early infection for a stringent evaluation of drugs.
Patterning challenges in advanced device architectures: FinFETs to nanowires (2016)

Si FinFET scaling is getting more difficult due to extremely narrow fin width control and power dissipation. Nanowire FETs and high mobility channel are attractive options for CMOS scaling. Nanowire FETs can maintain good electrostatics with relaxed nanowire diameter. High mobility channel can provide good performance at low power operation. However their fin patterning is challenging due to fins consisted of different materials or fragile high mobility material. Controlled etch and strip are necessary for good fin cd and profile control. Fin height increase is a general trend of scaled FinFETs and nanowire FETs, which makes patterning difficult not only in fin, but also in gate, spacer and replacement metal gate. It is important that gate and spacer etch have high selectivity to fins and good cd and profile control even with high aspect ratio of fin and gate. Work function metal gate patterning in scaled replacement metal gate module needs controlled isotropic etch without damaging gate dielectric. SF6 based etch provides sharp N-P boundary and improved gate reliability.
Using antibody directed phototherapy to target oesophageal adenocarcinoma with heterogeneous HER2 expression (2018)

Early oesophageal adenocarcinoma (OA) and pre-neoplastic dysplasia may be treated with endoscopic resection and ablative techniques such as photodynamic therapy (PDT). Though effective, discrete areas of disease may be missed leading to recurrence. PDT further suffers from the side effects of off-target photosensitivity. A tumour specific and light targeted therapeutic agent with optimised pharmacokinetics could be used to destroy residual cancerous cells left behind after resection. A small molecule antibody-photosensitizer conjugate was developed targeting human epidermal growth factor receptor 2 (HER2). This was tested in an <i>in vivo</i> mouse model of human OA using a xenograft flank model with clinically relevant low level HER2 expression and heterogeneity. <i>In vitro</i> we demonstrate selective binding of the conjugate to tumour versus normal tissue. Light dependent cytotoxicity of the phototherapy agent <i>in vitro</i> was observed. In an <i>in vivo</i> OA mouse xenograft model the phototherapy agent had desirable pharmacokinetic properties for tumour uptake and blood clearance time. PDT treatment caused tumour growth arrest in all the tumours despite the tumours having a clinically defined low/negative HER2 expression level. This new phototherapy agent shows therapeutic potential for treatment of both HER2 positive and borderline/negative OA.
Encapsulation of Pt(<scp>iv</scp>) prodrugs within a Pt(<scp>ii</scp>) cage for drug delivery (2014)

This report presents a novel strategy that facilitates delivery of multiple, specific payloads of Pt(IV) prodrugs using a well-defined supramolecular system. This delivery system comprises a hexanuclear Pt(II) cage that can host four Pt(IV) prodrug guest molecules. Relying on host-guest interactions between adamantyl units tethered to the Pt(IV) molecules and the cage, four prodrugs could be encapsulated within one cage. This host-guest complex, exhibiting a diameter of about 3 nm, has been characterized by detailed NMR spectroscopic measurements. Owing to the high positive charge, this nanostructure exhibits high cellular uptake. Upon entering cells and reacting with biological reductants such as ascorbic acid, the host-guest complex releases cisplatin, which leads to cell cycle arrest and apoptosis. The fully assembled complex displays cytotoxicity comparable to that of cisplatin against a panel of human cancer cells lines, whereas the cage or the Pt(IV) guest alone exhibit lower cytotoxicity. These findings indicate the potential of utilising well-defined supramolecular constructs for the delivery of prodrug molecules.
Fast Neutron Spectroscopy Using${\rm Cs}_{2}{\rm LiYCl}_{6}{:}{\rm Ce}$ (CLYC) Scintillator (2012)

The response of Cs <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> LiYCl <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sub> :Ce (CLYC) scintillator material to fast neutrons has been measured using a Van de Graaff accelerator. Beams of monoenergetic neutrons in the energy range 0.359 MeV to 4.703 MeV were used to irradiate a 9 mm × 9.5 mm × 12 mm CLYC crystal. Following pulse-shape discrimination to separate neutron and gamma-ray events, peaks are observed in the neutron spectrum and assigned to fast-neutron events in the scintillator. One of the peaks is interpreted as being due to the <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">35</sup> Cl(n, p) <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">35</sup> S reaction, and it is shown that the proton energy released in this reaction varies linearly with the energy of the incoming neutron. The linearity of the response may enable CLYC to be used for fast-neutron spectroscopy with well defined spectral peaks. The response of CLYC to thermal neutrons and gamma rays is well known, and the material has potential for simultaneous thermal-neutron detection, fast-neutron spectroscopy, and gamma-ray spectroscopy.
Optical coherence tomography and Raman spectroscopy of the <b><i>ex‐vivo</i></b> retina (2009)

Imaging the structure and correlating it with the biochemical content of the retina holds promise for fundamental research and for clinical applications. Optical coherence tomography (OCT) is commonly used to image the 3D structure of the retina and while the added functionality of biochemical analysis afforded by Raman scattering could provide critical molecular signatures for clinicians and researchers, there are many technical challenges to combine these imaging modalities. We describe an OCT microscope for ex-vivo imaging combined with Raman spectroscopy capable of collecting morphological and molecular information about a sample simultaneously. We present our first results and discuss the challenges to further development of this dual-mode instrument and limitations for future in-vivo retinal imaging.
Strategic Use of Information Technology in International Business (1993)

Information Technology’s (IT) link to the strategy of the firm has been explored in Information System literature, but the application of IT to the strategy of the international firm has received limited attention. This paper addresses the topic by exploring the use of IT in conjunction with a popular framework, the Integration- Responsiveness (IR) framework, of international business strategy. The framework’s three subgroups; global integration, multifocal, and local responsiveness are discussed. Specific applications of IT are then examined with reference to the dimensions that have been used to operationalize the IR framework. They are complex innovation, marketing differentiation, breadth, and conservative cost control. The paper concludes with implications for practice and research.Request access from your librarian to read this article's full text.
A Detailed Protocol for Bacterial Artificial Chromosome Recombineering to Study Essential Genes in Stem Cells (2008)

Bacterial artificial chromosome (BAC) recombineering is a novel technique for DNA manipulation. It starts from an original chromosomal gene locus that is modified to introduce a transgene under the expression control of the original gene locus. In most cases a cell type specific promoter is chosen and the transgene is placed in a way that the exon containing the start codon is replaced. Alternatively, BACs such as the Rosa26 BAC are chosen because of their known open chromatin and ubiquitous promoter activity that allows a broad expression profile of the transgene in the whole body. Thus, transgenes can be overexpressed within their natural transcriptional regulatory circuit. BAC transgenes have a high tendency to maintain their appropriate chromatin status because the endogenous locus was expressed in different cell types. Here, we give a detailed protocol based on the original idea to choose a BAC approach until the injection of the modified BAC DNA that leads to the generation of novel transgenic mouse lines. As an example for a BAC mouse model suitable for the analysis of stem cell or hematopoietic stem cell functions, we chose modification of the locus for the transcription factor Stat3. Stat3 variants replace the wild-type Stat3 gene to study their function in particular in the earliest cell types of the body.
Stimulus response coupling : the role of intracellular calcium-binding proteins (1990)

The Role of Intracellular Calcium-Binding Proteins in Stimulus-Response Coupling. Chelex 100 Competitive Calcium Binding Assay as a Tool for Identifying Calcium Binding Proteins. Centrin: A Calcium-Binding Protein Associated with Centrosomes. The Contractile System in Non-Muscle Cells: Involvement of Actin and Actin-Binding Proteins. Calcium Vector Protein and Sarcoplasmic Calcium Binding Proteins from Invertebrate Muscle. Calcium-Binding Proteins in Squid Nervous Tissue. Vitamin D-Dependent Calcium-Binding Protein (Calbindin-D28K) in the Central Nervous System: Distribution and Functional Considerations. Sorcin, A Calcium-Binding Protein Overproduced in Many Multidrug-Resistant Cells. The Calcyclin Gene. The L1 Leukocyte Protein. S100 Related Proteins. Genetic Analysis of Calcium-Binding Proteins in Yeast. Torpedo Calelectrin and Related Mammalian Annexins. Calcium-Dependent Membrane-Binding Proteins as Potential Mediators of Stimulus-Secretion Coupling. Intestinal Ca2+/Lipid-Binding Proteins. Calpactins. Lipocortin-II Tetramer: A Calcium-Dependent Regulator of Actin Filament Bundling. Annexins and the Search for Function: An Immunological First Step. Ca2+-Dependent Phospholipid Binding 39 kDa Protein of Neutrophils with Special References to Stimulation Coupled Lipid-Protein Interaction. Calcium-Dependent Membrane Binding Proteins of the Mammary Gland. Lipocortins in Peripheral Blood Mononuclear Cells. Isolation and Characterization of 67 kDa Calcimedin. Lymphocyte Calcium-Binding Proteins. 546 pp., 6 1/4 x 9 1/4, hardcover, 1990, ISBN 0-8493-8805-6.
Impacts of decision support systems on cognition and performance for intelligence-gathering path planning (2023)

Decision Support Systems (DSS) are tools designed to help operators make effective choices in workplace environments where discernment and critical thinking are required for effective performance. Path planning in military operations and general logistics both require individuals to make complex and time-sensitive decisions. However, these decisions can be complex and involve the synthesis of numerous tradeoffs for various paths with dynamically changing conditions. Intelligence collection can vary in difficulty, specifically in terms of the disparity between locations of interest and timing restrictions for when and how information can be collected. Furthermore, plans may need to be changed adaptively mid-operation, as new collection requirements appear, increasing task difficulty. We tested participants in a path planning decision-making exercise with scenarios of varying difficulty in a series of two experiments. In the first experiment, each map displayed two paths simultaneously, relating to two possible routes for the two available trucks. Participants selected the optimal path plan, representing the best solution across multiple routes. In the second experiment, each map displayed a single path, and participants selected the best two paths sequentially. In the first experiment, utilizing the DSS was predictive of adoption of more heuristic decision strategies, and that strategic approach yielded more optimal route selection. In the second experiment, there was a direct effect of the DSS on increased decision performance and a decrease in perceived task workload.
Rochalimaea henselae infection. A new zoonosis with the domestic cat as reservoir (1994)

We have documented that the domestic cat serves as a major persistent reservoir for R henselae, with prolonged, asymptomatic bacteremia from which humans, especially the immunocompromised, may acquire potentially serious infections. Antibiotic treatment of infected cats and control of flea infestation are potential strategies for decreasing human exposure to R henselae.
Real-time Object Segmentation based on GPU (2006)

In this paper we present a new novel GPU-based algorithm for real time object segmentation by employing several techniques which make use of framebuffer, swizzle operator, stencil buffer and the other factors on GPU. Frame buffer is used for the fast processing of image on GPU without going back and forth to the CPU, swizzle operator for the efficient and fast execution of vector operations for object segmentation, and stencil buffer for the fast computation of the masked area for the detected object, thus speeding up the whole algorithm sharply. Moreover, the computation of the histograms and bounding boxes make our algorithm very simple and fast by using 'gather' operation uniquely supported by GPU. Our experimental results have shown that our algorithm is much faster than CPU based one
Laser-produced plasma light source for extreme ultraviolet lithography (2002)

Pulsed Nd:YAG lasers have been developed to achieve high peak power and high pulse repetition rate. These systems are being used as drivers for laser-produced plasmas which efficiently convert the 1064-nm laser output to extreme ultraviolet (EUV) light at 13.5 nm for future microlithography systems. The requirements for laser-produced plasma EUV light sources and their integration in lithography tools for high-volume manufacturing are reviewed to establish the key design issues for high-power lasers and plasma targets. Xenon has been identified as a leading target material to realize the goals of intense EUV emission and clean operation. Recent progress in high-power diode-pumped Nd:YAG lasers and xenon targets for EUV generation is reviewed, showing that laser-produced plasma sources meet the needs for current EUV lithography development tools. Future directions to meet EUV source requirements for high-volume manufacturing tools are discussed.
Transforming loops to recursion for multi-level memory hierarchies (2000)

Recently, there have been several experimental and theoretical results showing significant performance benefits of recursive algorithms on both multi-level memory hierarchies and on shared-memory systems. In particular, such algorithms have the data reuse characteristics of a blocked algorithm that is simultaneously blocked at many different levels. Most existing applications, however, are written using ordinary loops. We present a new compiler transformation that can be used to convert loop nests into recursive form automatically. We show that the algorithm is fast and effective, handling loop nests with arbitrary nesting and control flow. The transformation achieves substantial performance improvements for several linear algebra codes even on a current system with a two level cache hierarchy. As a side-effect of this work, we also develop an improved algorithm for transitive dependence analysis (a powerful technique used in the recursion transformation and other loop transformations)that is much faster than the best previously known algorithm in practice.
Assessment of Antiangiogenic Effect Using <sup>99m</sup> Tc-EC-Endostatin (2002)

The results indicate that it is feasible to use 99mTc-EC-endostatin to assess efficiency of anti-angiogenesis therapy.
Novel browning formulation for fresh-cut apples (2003)

Fresh-cut apples are subject to enzymatic browning, especially in residual core tissue, and must be treated with a browning inhibitor to prevent shelf-life limiting discoloration. This product does not receive a kill step and so may contain viable microorganisms including human pathogens such as Listeria monocytogenes. Preliminary studies indicated that L. innocua could survive in a neutral browning inhibitor solution but not when the solution was acidified. Our objective was to develop an acidic browning inhibitor formulation for fresh-cut apples that was effective in preventing core tissue discoloration. Granny Smith and Fuji apples were cored and cut into wedges, treated with acidic or neutral pH browning inhibitor dips, or with an acidic dip containing sodium hexametaphosphate. Samples were packaged in pouches to produce a modified atmosphere and observed during storage at 4 and 10°C for onset of core tissue browning. A pH 2.9 dip containing 2% ascorbic acid, 1% citric acid and 1% sodium hexametaphosphate was able to suppress core tissue browning in Granny Smith apples for at least 3 weeks at 4°C while comparable neutral and acidic formulations without hexametaphosphate failed within 1 week. Similar results were obtained with Fuji apples when the ascorbic acid concentration was increased to 3%. Tissue breakdown, a result of some phosphate-treatments, was observed only at 10°C, coincident with onset of core tissue browning. These results demonstrate that core tissue browning in fresh-cut apples can be controlled effectively with a browning inhibitor formulation unlikely to support long-term listerial survival or growth.
DNA-PKcs plays a dominant role in the regulation of H2AX phosphorylation in response to DNA damage and cell cycle progression (2010)

DNA-PKcs plays a dominant role in regulating the phosphorylation of H2AX in response to both DNA damage and cell cycle progression. It can directly phosphorylate H2AX independent of ATM and indirectly modulate the phosphorylation level of gamma H2AX via the Akt/GSK3 beta signal pathway.
Software engineering and the academy (2004)

With software engineering (S. E.) now beginning to emerge as a distinct discipline, through initiatives such as the SWEBOK [1], the growth of undergraduate programmes in the U.S. [2] and collaborative efforts to offer programmes with breadth and depth [3], the challenges for the academy in balancing rigour and relevance can only become more intense. For some reason the contrast between the academic and the professional perspectives within the software engineering community is quite marked.
Cysteine-Tailed Class I-Binding Peptides Bind to CpG Adjuvant and Enhance Primary CTL Responses (2005)

Immunostimulatory CpG motifs in synthetic oligonucleotides can be effective adjuvants for the priming of CTLs. We first observed that a single male-specific peptide (KCSRNRQYL) (HY2) was more efficient than another male-specific peptide (WMHHNMDLI) (HY1) at priming IFN-gamma-secreting CTLs in vivo when combined with lipid A and CpG and that it also visibly precipitated CpG. The addition of the six N-terminal residues (KCSRNR) from HY2 to HY1 yielded a peptide, KCSRNR-HY1, that both precipitated CpG and primed increased numbers of HY1-specific CTLs. We refer to this type of peptide as a primotope that includes a class I binding peptide tailed with amino acids that increase priming. Ala residues were substituted for the Arg/Lys residues (ACSANA-HY1), and these substitutions did not reduce in vivo priming potential. However, the substitution of Ala for Cys (KASRNR-HY1) resulted in the complete loss of priming, demonstrating the importance of Cys for in vivo priming when mixed with CpG. This result suggested that increased priming was based in disulfide bonding between Cys residues and internal phosphorothioate groups of synthetic CpG. The addition of Cys-bearing primotopes to radiolabeled CpG with a single thioate group resulted in the appearance of a new band that was inhibited by 1) Cys > Ala substitution and 2) reduction and alkylation of CpG. These results reveal a novel mechanism for complexing class I binding peptides and CpG adjuvant for development of new peptide-adjuvant combinations for vaccines for cancer and infectious diseases.