gebhart/patrepeval huggingface dataset:
A phage display approach for rapid antibody humanization: Designed combinatorial V gene libraries (1998)

The development of a new strategy for antibody humanization is described. This strategy incorporates key recognition sequences from the parental rodent antibody into a phage display-based selection strategy. The original sequences of the third complementarity-determining regions (CDRs) of heavy and light chains, HCDR3 and LCDR3, were maintained and all other sequences were replaced by human sequences selected from phage-displayed antibody libraries. This approach was applied to the humanization of mouse mAb LM609 that is directed to human integrin alphav beta3 and has potential applicability in cancer therapy as an antiangiogenic agent. We demonstrate this approach (i) provides a rapid route for antibody humanization constraining the content of original mouse sequences in the final antibodies to the most hypervariable of the CDRs; (ii) generates several humanized versions with different sequences at the same time; (iii) results in affinities as high as or higher than the affinity of the original antibody; and (iv) retains the antigen and epitope specificity of the original antibody. The production of multiple humanized variants may present advantages in the selection of antibodies that are more readily expressed on a large scale and could be important in therapeutic regimens that call for long-term treatment with antibodies in which antiidiotypic responses might be avoided by administration of alternative antibodies.
Design of an efficient power distribution network for the UltraSPARC-I microprocessor (2002)

The design, implementation, and verification of the power distribution network for the 5.2 million transistor UltraSPARC-I microprocessor is described. A novel simulation method allows rapid identification of exact layout locations with potential electromigration or excessive voltage drop problems. Hierarchical verification capabilities of this approach are utilized to design an efficient and robust distribution of V/sub dd/ and V/sub ss/ across a large die, in the face of stringent IR drop and floorplanning constraints. A comprehensive methodology for power distribution and management, along with seamless integration of the power distribution into existing CAD tools throughout the design cycle results in correct-by-construction power networks for cell libraries and functional blocks, area efficient power interconnections and reduced time-to-market due to correction of all reliability failures in the power networks prior to mask generation.
TWIST Family of Basic Helix-Loop-Helix Transcription Factors Mediate Human Mesenchymal Stem Cell Growth and Commitment (2009)

The TWIST family of basic helix-loop-helix transcription factors, Twist-1 and Dermo-1 are known mediators of mesodermal tissue development and contribute to correct patterning of the skeleton. In this study, we demonstrate that freshly purified human bone marrow-derived mesenchymal stromal/stem cells (MSC) express high levels of Twist-1 and Dermo-1 which are downregulated following ex vivo expansion. Enforced expression of Twist-1 or Dermo-1 in human MSC cultures increased expression of the MSC marker, STRO-1, and the early osteogenic transcription factors, Runx2 and Msx2. Conversely, overexpression of Twist-1 and Dermo-1 was associated with a decrease in the gene expression of osteoblast-associated markers, bone morphogenic protein-2, bone sialoprotein, osteopontin, alkaline phosphatase and osteocalcin. High expressing Twist-1 or Dermo-1 MSC lines exhibited an enhanced proliferative potential of approximately 2.5-fold compared with control MSC populations that were associated with elevated levels of Id-1 and Id-2 gene expression. Functional studies demonstrated that high expressing Twist-1 and Dermo-1 MSC displayed a decreased capacity for osteo/chondrogenic differentiation and an enhanced capacity to undergo adipogenesis. These findings implicate the TWIST gene family members as potential mediators of MSC self-renewal and lineage commitment in postnatal skeletal tissues by exerting their effects on genes involved in the early stages of bone development.
The non-catalytic cellulose-binding domain of a novel cellulase from Pseudomonas fluorescens subsp. cellulosa is important for the efficient hydrolysis of Avicel (1995)

A genomic library of Pseudomonas fluorescens subsp. cellulosa DNA, constructed in lambda ZAPII, was screened for carboxymethyl-cellulase activity. The pseudomonad insert from a recombinant phage which displayed elevated cellulase activity in comparison with other cellulase-positive clones present in the library, was excised into pBluescript SK- to generate the plasmid pC48. The nucleotide sequence of the cellulase gene, designated celE, revealed a single open reading frame of 1710 bp that encoded a polypeptide, defined as endoglucanase E (CelE), of M(r) 59663. The deduced primary structure of CelE revealed an N-terminal signal peptide followed by a 300-amino-acid sequence that exhibited significant identity with the catalytic domains of cellulases belonging to glycosyl hydrolase Family 5. Adjacent to the catalytic domain was a 40-residue region that exhibited strong sequence identity to non-catalytic domains located in two other endoglucanases and a xylanase from P. fluorescens. The C-terminal 100 residues of CelE were similar to Type-I cellulose-binding domains (CBDs). The three domains of the cellulase were joined by linker sequences rich in serine residues. Analysis of the biochemical properties of full-length and truncated derivatives of CelE confirmed that the enzyme comprised an N-terminal catalytic domain and a C-terminal CBD. Analysis of purified CelE revealed that the enzyme had an M(r) of 56000 and an experimentally determined N-terminal sequence identical to residues 40-54 of the deduced primary structure of full-length CelE. The enzyme exhibited an endo mode of action in hydrolysing a range of cellulosic substrates including Avicel and acid-swollen cellulose, but did not attack xylan or any other hemicelluloses. A truncated form of the enzyme, which lacked the C-terminal CBD, displayed the same activity as full-length CelE against soluble cellulose and acid-swollen cellulose, but exhibited substantially lower activity than the full-length cellulase against Avicel. The significance of these data in relation to the role of the CBD is discussed.
Severity of E. coli mastitis is mainly determined by cow factors (2003)

Intramammary infections of dairy cows with Gram-positive bacteria such as Staphylococcus aureus (major cause of mastitis) have received a lot of attention because of their major economic impact on the dairy farm through production losses induced by an increase in somatic cell count. Management strategies, including greater awareness for efficient milking and hygienic measures, have limited the spread of Gram-positive bacteria and resulted in a significant decrease of proportion of S. aureus isolates and subclinical mastitis worldwide. Other organisms such as coliform subspecies and Streptococcus uberis, both environmental bacteria that cause clinical mastitis, have received less attention. Escherichia coli causes inflammation of the mammary gland in dairy cows around parturition and during early lactation with striking local and sometimes severe systemic clinical symptoms. This disease affects many high producing cows in dairy herds and may cause several cases of death per year in the most severe cases. It is well known that bacterial, cow and environmental factors are interdependent and influence mastitis susceptibility. Many studies, executed during the last decade, indicate that the severity of E. coli mastitis is mainly determined by cow factors rather than by E. coli pathogenicity. During E. coli mastitis, the host defense status is a cardinal factor determining the outcome of the disease. Today, we know that the neutrophil is a key factor in the cows' defense against intramammary infection with E. coli. Effective elimination of the pathogen by neutrophils is important for the resolution of infection and the outcome of E. coli mastitis. This review is a compilation of some major findings over the last 15 years concerning mainly host factors that modulate and influence neutrophil function and the mammary inflammatory reaction. The individual chapters address: virulence factors of E. coli strains, how neutrophils kill E. coli, connection between endotoxins, tumor necrosis factor-alpha and nitric oxide, severity classification of E. coli mastitis, lifespan of neutrophils, host factors that influence severity, tissue damage and production loss.
Quantum key distribution with hacking countermeasures and long term field trial (2017)

Quantum key distribution's (QKD's) central and unique claim is information theoretic security. However there is an increasing understanding that the security of a QKD system relies not only on theoretical security proofs, but also on how closely the physical system matches the theoretical models and prevents attacks due to discrepancies. These side channel or hacking attacks exploit physical devices which do not necessarily behave precisely as the theory expects. As such there is a need for QKD systems to be demonstrated to provide security both in the theoretical and physical implementation. We report here a QKD system designed with this goal in mind, providing a more resilient target against possible hacking attacks including Trojan horse, detector blinding, phase randomisation and photon number splitting attacks. The QKD system was installed into a 45 km link of a metropolitan telecom network for a 2.5 month period, during which time the system operated continuously and distributed 1.33 Tbits of secure key data with a stable secure key rate over 200 kbit/s. In addition security is demonstrated against coherent attacks that are more general than the collective class of attacks usually considered.
Environmental regulation of Salmonella pathogenicity island 2 gene expression (1999)

The enteric pathogen Salmonella typhimurium co-ordinates the expression of virulence determinants in response to environmental cues from the host organism. S. typhimurium possesses Salmonella pathogenicity island 2 (SPI2), a large virulence locus encoding a type III secretion system for virulence determinants required for systemic infections and accumulation inside host cells. We have generated transcriptional fusions to SPI2 genes to analyse expression and used antibodies against recombinant SPI2 proteins to monitor levels of SPI2 proteins under various conditions. Here, we demonstrate that SPI2 gene expression is induced by Mg2+ deprivation and phosphate starvation. These conditions are likely to represent the environmental cues encountered by S. typhimurium inside the phagosome of infected host cells. The induction of SPI2 gene expression is modulated by the global regulatory system PhoPQ and is dependent on SsrAB, a two-component regulatory system encoded by SPI2.
Expansion of Active Site Area and Improvement of Kinetic Reversibility in Electrochemical Pseudocapacitor Electrode (2001)

Chemical mixing of carbon and amorphous hydrous manganese oxide particles as an active material for electrochemical pseudocapacitor was proposed to increase the efficiency of added carbon as a conducting agent to expand the active site area on the surface of particle. Instead of physically mixing the conducting carbon and active material using a mortar or ballmilling, added carbon was mixed during synthesis reaction of the active material. The chemical mixing proposed in this study was effective for increasing specific capacitance and improving electrochemical properties as an electrochemical pseudocapacitor to show closer ideal capacitor behavior in high power mode compared with physically mixed electrode. © 2001 The Electrochemical Society. All rights reserved.
Method of Creating a Nanopore-Terminated Probe for Single-Molecule Enantiomer Discrimination (2008)

Nanopores are increasingly utilized as tools for single-molecule detection in biotechnology. Many nanopores are fabricated through procedures that require special materials, expensive facilities and experienced operators, which limit their usefulness on a wider scale. We have developed a simple method of fabricating a robust, low-noise nanopore by externally penetrating a nanocavity enclosed in the terminal of a capillary pipet. The nanocavity was shown to have a pore size on the scale of a single molecule, verified by translocation of molecules of known sizes, including double-stranded DNA (2 nm), gold nanoparticles (10 nm), and ring-shaped cyclodextrin (1.5 nm). The small pore size allows entrapment of a single cyclodextrin molecule. The glass nanopore with a trapped cyclodextrin proves useful in single-molecule discrimination of chiral enantiomers.
Design and performance of a multi-pinhole collimation device for small animal imaging with clinical SPECT and SPECT–CT scanners (2008)

A multi-pinhole collimation device is developed that uses the gamma camera detectors of a clinical SPECT or SPECT-CT scanner to produce high-resolution SPECT images. The device consists of a rotating cylindrical collimator having 22 tungsten pinholes with 0.9 mm diameter apertures and an animal bed inside the collimator that moves linearly to provide helical or ordered-subsets axial sampling. CT images also may be acquired on a SPECT-CT scanner for purposes of image co-registration and SPECT attenuation correction. The device is placed on the patient table of the scanner without attaching to the detectors or scanner gantry. The system geometry is calibrated in-place from point source data and is then used during image reconstruction. The SPECT imaging performance of the device is evaluated with test phantom scans. Spatial resolution from reconstructed point source images is measured to be 0.6 mm full width at half maximum or better. Micro-Derenzo phantom images demonstrate the ability to resolve 0.7 mm diameter rod patterns. The axial slabs of a Micro-Defrise phantom are visualized well. Collimator efficiency exceeds 0.05% at the center of the field of view, and images of a uniform phantom show acceptable uniformity and minimal artifact. The overall simplicity and relatively good imaging performance of the device make it an interesting low-cost alternative to dedicated small animal scanners.
New trend in neuroscience: Low-power laser effect on peripheral and central nervous system (basic science, preclinical and clinical studies) (1992)

The present review summarizes findings in our continuing study of the use of low-power laser irradiation (LPLI) in the treatment of severely injured peripheral (PNS) and central nervous systems (CNS). The radiation method was proposed by Rochkind and has been modified over the last 13 years. LPLI in specific wavelengths and energy density maintains the electrophysiological activity of severely injured peripheral nerve in rats, preventing scar formation (at injury site) as well as degenerative changes in the corresponding motor neurons of the spinal cord, thus accelerating regeneration of the injured nerve. Laser irradiation applied to the spinal cord of dogs following severe spinal cord injury and implantation of a segment of the peripheral nerve into the injured area diminished glial scar formation, induced axonal sprouting in the injured area and restoration of locomotor function. The use of laser irradiation in mammalian CNS transplantation shows that laser therapy prevents extensive glial scar formation (a limiting factor in CNS regeneration) between a neural transplant and the host brain or spinal cord. Abundant capillaries developed in the laser-irradiated transplants, and was of crucial importance in their survival. Intraoperative clinical use of laser therapy following surgical treatment of the tethered spinal cord (resulting from myelomeningocele, lipomyelomeningocele, thickened filum terminale or fibrous scar) increases functional activity of the irradiated spinal cord. In a previous experimental work, we showed that direct laser treatment on nerve tissue promotes restoration of the electrophysiological activity of the severely injured peripheral nerve, prevents degenerative changes in neurons of the spinal cord and induces proliferation of astrocytes and oligodendrocytes. This suggested a higher metabolism in neurons and improved ability for myelin production under the influence of laser treatment. The tethering of the spinal cord causes mechanical damage to neuronal cell membranes leading to metabolic disturbances in the neurons. For this reason, we believe that using LPLI may improve neuronal metabolism, prevent neuronal degeneration and promote improved spinal cord function and repair. The possible mechanism of LPLI is investigated. Using electron paramagnetic resonance in cell culture models, we found that at low radiation doses, singlet oxygen is produced by energy transfer from porphyrin (not cytochrome as commonly assumed) which is known to be present in the cell. At low concentration, singlet oxygen can modulate biochemical processes taking place in the cell and trigger accelerated cell division. On the other hand, at high concentration, singlet oxygen damages the cell.(ABSTRACT TRUNCATED AT 400 WORDS)
Exploiting Covalency to Enhance Metal–Oxide and Oxide–Oxide Adhesion at Heterogeneous Interfaces (2003)

We employ first‐principles density functional calculations to explore atomic‐level interactions and predict the ideal work of adhesion at the SiO 2 /nickel and ZrO 2 /SiO 2 interfaces. We find that chemical bonding at the interface serves to strengthen significantly interfaces formed with SiO 2 , which exhibits significant covalent bonding character, relative to those formed using more ionic oxides, such as Al 2 O 3 , in place of SiO 2 . The improved strength of these interfaces due to local bonding interactions may hold materials design implications for practical applications that require optimal adhesion between metal‐ceramic layered structures, including thermal barrier coatings.
Describing binding time in software design patterns (2016)

Binding time is an important, yet underestimated viewpoint in software architecture and design. It defines the latest time during the software life cycle when something flexible becomes decided and fixed. This heavily impacts the flexibility of a software design and the resulting application. A terminology for describe binding time is established and an analysis is carried out in form of side-by-side comparisons for patterns and mechanisms from the creational, structural, and behavioral domains. These terminology and synoptic comparisons with the binding time considerations can aid software architects and developers in selecting patterns and taking correct architectural decisions for their binding time requirements.
Mitochondrial protein import: precursor oxidation in a ternary complex with disulfide carrier and sulfhydryl oxidase (2008)

The biogenesis of mitochondrial intermembrane space proteins depends on specific machinery that transfers disulfide bonds to precursor proteins. The machinery shares features with protein relays for disulfide bond formation in the bacterial periplasm and endoplasmic reticulum. A disulfide-generating enzyme/sulfhydryl oxidase oxidizes a disulfide carrier protein, which in turn transfers a disulfide to the substrate protein. Current views suggest that the disulfide carrier alternates between binding to the oxidase and the substrate. We have analyzed the cooperation of the disulfide relay components during import of precursors into mitochondria and identified a ternary complex of all three components. The ternary complex represents a transient and intermediate step in the oxidation of intermembrane space precursors, where the oxidase Erv1 promotes disulfide transfer to the precursor while both oxidase and precursor are associated with the disulfide carrier Mia40.
Lisinopril-Lactose Incompatibility (1998)

A chemical interaction between lisinopril and lactose was demonstrated and quantified in dilute mixtures in the solid state.
Increased CCL18 expression in patients with cutaneous T‐cell lymphoma: association with disease severity and prognosis (2012)

CCL18 mRNA is up-regulated in CTCL lesional skin, and serum CCL18 levels are significantly increased and correlated with the severity of CTCL. These results suggest that CCL18 may be associated with the development of CTCL.
Improved Performances of Li[Ni0.65Co0.08Mn0.27]O2Cathode Material with Full Concentration Gradient for Li-Ion Batteries (2014)

Full concentration gradient (FCG) cathode material having nickel-rich core Li[Ni0.89Co0.01Mn0.10]O-2 and nickel-deficient outer layer Li[Ni0.61Co0.09Mn0.30]O-2 was synthesized via co-precipitation method. A smoothly varying concentration gradients for Ni, Co, and Mn extended from the core to the surface within a single cathode particle with an average composition of Li[Ni0.65Co0.08Mn0.27]O-2. Electrochemical and thermal properties of the FCG cathode were evaluated and compared to the conventional cathode (CC) material, Li[Ni0.65Co0.08Mn0.27]O-2 without the concentration gradient. The BET surface area measurement demonstrated the presence of densely agglomerated primary particles in the FCG cathode. Owing to the unique spatial distribution of the cations and particle morphology, the FCG cathode delivered higher discharge capacity, superior cycle stability and excellent thermal stability compared to the CC Li[Ni0.65Co0.08Mn0.27]O-2. (C) The Author(s) 2014. Published by ECS.
Risk of weight gain for specific antipsychotic drugs: a meta-analysis (2018)

People with schizophrenia are at considerably higher risk of cardiometabolic morbidity than the general population. Second-generation antipsychotic drugs contribute to that risk partly through their weight gain effects, exacerbating an already high burden of disease. While standard 'as-randomized' analyses of clinical trials provide valuable information, they ignore adherence patterns across treatment arms, confounding estimates of realized treatment exposure on outcome. We assess the effect of specific second-generation antipsychotics on weight gain, defined as at least a 7% increase in weight from randomization, using a Bayesian hierarchical model network meta-analysis with individual patient level data. Our data consisted of 14 randomized clinical trials contributing 5923 subjects (mean age = 39 [SD = 12]) assessing various combinations of olanzapine (n = 533), paliperidone (n = 3482), risperidone (n = 540), and placebo (n = 1368). The median time from randomization to dropout or trial completion was 6 weeks (range: 0-60 weeks). The unadjusted probability of weight gain in the placebo group was 4.8% across trials. For each 10 g chlorpromazine equivalent dose increase in olanzapine, the odds of weight gain increased by 5 (95% credible interval: 1.4, 5.3); the effect of risperidone (odds ratio = 1.6 [0.25, 9.1]) was estimated with considerable uncertainty but no different from paliperidone (odds ratio = 1.3 [1.2, 1.5]).
Design and Characterization of High Efficiency Nanoantenna Couplers With Plasmonic Integrated Circuit (2016)

Four types of nanoantennas have been designed and characterized at 1.55 μm wavelength: Dipole antenna, Yagi-Uda antenna, dipole antenna array and bowtie antenna. The spectra, coupling efficiency, and far field radiation patterns are also investigated. We also quantitatively characterized the relationship between the couple-in efficiency and the spot size of the incident light. For the three dipole-type antennas, the couple-in and couple-out efficiencies have been measured experimentally. A plasmonic integrated circuit has also been designed and fabricated with these four types of nanoantennas. Direct and efficient optical coupling from an optical fiber into the plasmonic integrated circuit is demonstrated as well, and the couple-out efficiencies for these four nanoantennas are.