gebhart/patrepeval huggingface dataset:
Improvement of a Recombinant Anti-Monkey Anti-CD3 Diphtheria Toxin Based Immunotoxin by Yeast Display Affinity Maturation of the scFv (2007)

Recently, a bivalent recombinant anti-human CD3 diphtheria toxin (DT) based immunotoxin derived from the scFv of UCHT1 antibody has been made that shows enhanced bioactivity and is free from the side effects of Fc receptor interaction. In this case, the diminution of CD3 binding due to the placement of the scFv domain at the C-terminus of the truncated DT in single scFv immunotoxins was compensated by adding an additional scFv domain. However, this strategy was less successful for constructing an anti-rhesus recombinant immunotoxin derived from the scFv of FN18 antibody due to poor binding of the anti-rhesus bivalent immunotoxin. We report here that, by increasing the FN18 scFv affinity through random mutagenesis and selection with a dye-labeled monkey CD3epsilongamma recombinant heterodimer, we greatly improved the bioactivity of FN18 derived immunotoxin. The best mutant, C207, contained nine mutations, two of which were located in CDRs that changed the charge from negative to positive. Binding affinity of the C207 scFv to the monkey T cell line HSC-F increased 9.8-fold. The potency of the C207 bivalent immunotoxin assayed by inhibition of protein synthesis increased by 238-fold.
Spectral response of a gigahertz-range nanomechanical oscillator (2005)

We report the measurement and simulation of the transverse displacement spectrum of a multi-element nanomechanical oscillator at previously inaccessible frequencies of up to 3GHz. The detected displacement signal is enhanced in the high-frequency range by the presence of high-order resonance modes generated by coherent motion of individual elements. The spectrum reveals a rich structure with groups of peaks forming quasibands. The spectral structure is qualitatively analogous to atomic emission spectra.
Layered Decoding of Non-Layered LDPC Codes (2006)

The principle of "layered decoding" is extended to those codes not especially conceived for this practice, as to benefit of the increased convergence speed. Two different strategies are considered to solve the problem and the related architectures presented: one more straightforward, and based on the use for the soft output of the last value originated in a layer; the other based on the computation of the variation (or delta) of the soft output metrics to allow concurrent updates. Then, as in architecture-first approach, the performance is assessed for several widths of the layer, which remarks the robustness of the delta-mechanism to high parallelisation factors. As in the exact layered decoding, the average boost of two times in the convergence speed is shown
Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages (2021)

A quarter of all seasonal influenza cases are caused by type B influenza virus (IBV) that also dominates periodically. Here, we investigated a recombinant adenovirus vaccine carrying a synthetic HA2 representing the consensus sequence of all IBV hemagglutinins. The vaccine fully protected mice from lethal challenges by IBV of both genetic lineages, demonstrating its breadth of protection. The protection was not mediated by neutralizing antibodies but robust antibody-dependent cellular cytotoxicity and cell-mediated immune responses. Complete protection of the animals required the entire codon-optimized HA2 sequence that elicited a balanced immune response, whereas truncated vaccines without either the fusion peptide or the transmembrane domain reduced the efficacy of protection. Finally, the vaccines did not demonstrate any sign of disease exacerbation following lung pathology and morbidity monitoring. Collectively, these data suggest that it could be worth further exploring this prototype universal vaccine because of its considerable efficacy, safety, and breadth of protection.
Development of a universal medical X‐ray imaging phantom prototype (2016)

Diagnostic X-ray imaging depends on the maintenance of image quality that allows for proper diagnosis of medical conditions. Maintenance of image quality requires quality assurance programs on the various X-ray modalities, which consist of pro-jection radiography (including mobile X-ray units), fluoroscopy, mammography, and computed tomography (CT) scanning. Currently a variety of modality-specific phantoms are used to perform quality assurance (QA) tests. These phantoms are not only expensive, but suitably trained personnel are needed to successfully use them and interpret the results. The question arose as to whether a single universal phantom could be designed and applied to all of the X-ray imaging modalities. A universal phantom would reduce initial procurement cost, possibly reduce the time spent on QA procedures and simplify training of staff on the single device. The aim of the study was to design and manufacture a prototype of a universal phantom, suitable for image quality assurance in general X-rays, fluoroscopy, mammography, and CT scanning. The universal phantom should be easy to use and would enable automatic data analysis, pass/fail reporting, and corrective action recommendation. In addition, a universal phantom would especially be of value in low-income countries where finances and human resources are limited. The design process included a thorough investigation of commercially available phantoms. Image quality parameters necessary for image quality assurance in the different X-ray imaging modalities were determined. Based on information obtained from the above-mentioned investigations, a prototype of a universal phantom was developed, keeping ease of use and reduced cost in mind. A variety of possible phantom housing and insert materials were investigated, considering physical properties, machinability, and cost. A three-dimensional computer model of the first phantom prototype was used to manufacture the prototype housing and inserts. Some of the inserts were 3D-printed, others were machined from different materials. The different components were assembled to form the first prototype of the universal X-ray imaging phantom. The resulting prototype of the universal phantom conformed to the aims of a single phantom for multiple imag-ing modalities, which would be easy to use and manufacture at a reduced cost. A PCT International Patent Application No. PCT/IB2016/051165 has been filed for this technology.
Oppositely Biased Multibit Cells for Toggle Magnetic Random Access Memory (2007)

A new type of multibit cell for toggle type MRAM is presented. The dual-bit cell stack consists of two conventional toggle MRAM cells connected in series. These cells have the same cell geometry, anisotropy, and pinned directions but have opposite magnetic bias along the anisotropy axis directions. These oppositely biasing fields shift the write field switching window of the two cells in opposite directions along the anisotropy axis and enable the dual-bit cells to be selectively toggled. The calculated write switching current margins for the multibit cell with respect to the design and material parameters are included. The write current margin is found to be similar to the single biased low write current MRAM case. This oppositely bias scheme can be combined with the earlier multibit cell of distinct anisotropy axes approach to further enhance the density of the MRAM. This new scheme doubles the multicell bit capacity and reduces the power consumption without adding the photo-patterning steps
Subtractive Hybridization Identifies a Novel Predicted Protein Mediating Epithelial Cell Invasion by Virulent Serotype III Group B <i>Streptococcus agalactiae</i> (2003)

Group B Streptococcus agalactiae bacteria (group B streptococci [GBS]) are the most common cause of serious bacterial infection in newborn infants. The majority of serotype III-related cases of neonatal disease are caused by a genetically related subgroup of bacteria, restriction fragment digest pattern (RDP) type III-3, suggesting that these strains possess unique genes contributing to virulence. We used genomic subtractive hybridization to identify regions of genomic DNA unique to virulent RDP type III-3 GBS strains. Within one of these III-3-specific regions is a 1,506-bp open reading frame, spb1 (surface protein of group B streptococcus 1). A mutant type III GBS strain lacking Spb1 was constructed in virulent RDP type III-3 strain 874391, and the interactions of the wild-type and spb1 isogenic mutant with a variety of epithelial cells important to GBS colonization and infection were compared. While adherence of the spb1 isogenic mutant to A549 respiratory, C2Bbe1 colonic, and HeLa cervical epithelial cells was slightly lower than that of the 874391 strain, invasion of the Spb1(-) mutant was significantly reduced with these cell lines compared to what was seen with 874391. The defect in epithelial invasion was corrected by supplying spb1 in trans. These observations suggest that Spb1 contributes to the pathogenesis of neonatal GBS infection by mediating internalization of virulent serotype III GBS and confirm that understanding of the population structure of bacteria may lead to insights into the pathogenesis of human infections.
Abstract 15261: Substrate Modification by Focal Exosome Injection as a Novel Strategy to Prevent Ventricular Tachyarrhythmias: Proof of Concept in a Porcine Model of Chronic Myocardial Infarction (2016)

Introduction: Myocardial infarction (MI) survivors are at increased risk of ventricular arrhythmias (VA) and sudden death. Current therapies for VA include ablation to “destroy” re-entry circuits. Isolated late potentials (ILP), which arise from viable myocardial bundles within scar, are targets for ablation in patients with recurrent VA. Cardiosphere-derived cell exosomes (CDC EXO ) have been shown to reduce scar and improve ventricular function, due to their regenerative, anti-fibrotic and anti-inflammatory properties. Here we sought to determine if substrate modification with CDC EXO could reduce ILP and the incidence of scar-related VA in a pre-clinical model. Methods: A balloon catheter was inflated in the LAD for 90 minutes, then reperfused for 8 weeks in 10 minipigs. MRI, programmed electrical stimulation (PES), and electroanatomic mapping (EAM; Rhythmia, Boston Scientific) were performed to evaluate arrhythmia inducibility and define sites of ILP. At 6-9 such sites, human CDC EXO (7.5mg/2ml, n=5) or vehicle only (2ml, n=5) was injected using a NOGA MYOSTAR catheter (Biosense Webster). Two weeks later, EAM and PES were repeated with continuous 12 lead ECG recordings. Final infarct size (scar mass divided by total LV mass) was quantified by MRI. Results: In CDC EXO -injected pigs vs. controls, infarct size was reduced (-3.4±1.2% vs. 0.6±0.9%, p=0.025) and ejection fraction improved (2.6±2.2% vs. -5.8±2.1% p=0.02). The CDC EXO group exhibited fewer ILP (CDC EXO baseline 18.6±5.9; 2 weeks 3.6±2.9 p EXO -injected pigs (-23.4±5.8 ms vs. 9.4±6.2 ms P=0.007). VA was induced in 5 of 5 CDC EXO animals at baseline, but only 1 of 5 remained inducible 2 weeks later. All control animals had inducible VA during the 2 week follow up (p=0.04 vs CDC EXO ). Conclusions: CDC EXO delivered by endocardial catheter injection can diminish ILP associated with slow conduction, and decrease the inducibility of VA. Substrate modification was evidenced by decreased infarct size and reduced ILP in CDC EXO but not in control animals. Exosome injection may represent a viable nondestructive alternative to conventional VA ablation.
Virotherapy Using Myxoma Virus Prevents Lethal Graft-versus-Host Disease following Xeno-Transplantation with Primary Human Hematopoietic Stem Cells (2012)

Graft-versus-host disease (GVHD) is a potentially lethal clinical complication arising from the transfer of alloreactive T lymphocytes into immunocompromised recipients. Despite conventional methods of T cell depletion, GVHD remains a major challenge in allogeneic hematopoietic cell transplant. Here, we demonstrate a novel method of preventing GVHD by ex vivo treatment of primary human hematopoietic cell sources with myxoma virus, a rabbit specific poxvirus currently under development for oncolytic virotherapy. This pretreatment dramatically increases post-transplant survival of immunocompromised mice injected with primary human bone marrow or peripheral blood cells and prevents the expansion of human CD3(+) lymphocytes in major recipient organs. Similar viral treatment also prevents human-human mixed alloreactive T lymphocyte reactions in vitro. Our data suggest that ex vivo virotherapy with myxoma virus can be a simple and effective method for preventing GVHD following infusion of hematopoietic products containing alloreactive T lymphocytes such as: allogeneic hematopoietic stem and progenitor cells, donor leukocyte infusions and blood transfusions.
Classifying images on the web automatically (2002)

The <i>Journal of Electronic Imaging</i> (JEI), copublished bimonthly with the Society for Imaging Science and Technology, publishes peer-reviewed papers that cover research and applications in all areas of electronic imaging science and technology.
Immune cell function testing: an adjunct to therapeutic drug monitoring in transplant patient management (2003)

Each year, 55 000 organ transplants are performed worldwide. Cumulatively, the number of living organ recipients is now estimated to be over 300 000. Most of these transplant recipients will remain on immunosuppressive drugs for the remainder of their lives to prevent rejection episodes. Controlled doses of these drugs are required to prevent over-medication, which may leave the patient susceptible to opportunistic infection and drug toxicity effects, or under-dosing, which may lead to shortened graft survival because of rejection episodes. This paper describes the result of a multicenter study conducted at the Universities of Pittsburgh, Alabama and Maryland to evaluate an in vitro assay (CylexTM Immune Cell Function Assay) for the measurement of global immune response in transplant patients receiving immunosuppressive therapy. The assay uses a whole blood sample to maintain the presence of the drug during incubation. Following overnight incubation of blood with phytohemagglutinin (PHA), CD4 cells are selected using paramagnetic particles coated with a monoclonal antibody to the CD4 epitope. The CD4-positive cells are targeted as major immunosuppressive drugs are designed to specifically inhibit T-cell activation which has been implicated in rejection. The data generated at these three sites were submitted in support of an Food and Drug Association (FDA) application for the use of this assay in the detection of cell-mediated immunity in an immunosuppressed population. The assay was cleared by the FDA on April 2, 2002. This cross-sectional study was designed to establish ranges for reactivity of this bioassay in the assessment of functional immunity for an individual solid organ recipient at any point in time.
Possible Therapeutic Vaccine Strategy against Human Immunodeficiency Virus Escape from Reverse Transcriptase Inhibitors Studied in HLA-A2 Transgenic Mice (2006)

Mutation of human immunodeficiency virus (HIV) leading to escape from anti-HIV drugs is the greatest challenge to the treatment of HIV infection. High-grade resistance to the nucleoside reverse transcriptase (RT) inhibitor lamivudine (also known as 3TC) is associated with a substitution of valine for methionine at position 184 of RT. This amino acid residue is contained within the HLA-A2-restricted epitope VIYQYMDDL (RT-WT). Here, we sought to determine whether a peptide vaccine could be developed using an epitope enhancement strategy that could induce a cytotoxic T-lymphocyte (CTL) response specific for an epitope containing the drug resistance mutation M184V to exert an opposing selective pressure. RT-WT-specific CTLs developed from HLA-A2 transgenic mice did not recognize the M184V mutation of RT-WT (RT-M184V). However, RT-M184V exhibited higher binding affinity for HLA-A2 than RT-WT. Also, both anchor-enhanced RT-WT (RT-2L9V) and RT-2L9V-M184V-specific CTLs recognized RT-M184V and displayed cross-reactivity to RT-WT. Nevertheless, the CTL repertoire elicited by the epitope-enhanced RT-2L9V-M184V appeared more selective for the RT inhibitor-induced M184V mutation. Peptide vaccines based on such strategies may be worth testing for their ability to exert selective pressure against drug-resistant strains and thus delay or prevent the development of HIV with the M184V resistance mutation.
[1-(L-2-Hydroxy-3-mercaptopropanoic acid)] analogs of arginine-vasopressin, [8-D-arginine]vasopressin, and [4-valine,8-D-arginine]vasopressin (1977)

[1-(L-2-Hdroxy-3-mercaptopropanic acid)]arginine-vasopressin (hydroxy-AVP), [1-(L-2-hydroxy-3-mercaptopropanoic acid),8-D-arginine]vasopressin (hydroxy-DAVP), and [1-(L-2-hydroxy-3-mercaptopropanoic acid),4-valine,8-D-arginine]vasopressin (hydroxy-VDAVP) were synthesized by a combination of the solid-phase and solution methods of peptide synthesis. Protected octapeptides synthesized by the solid-phase method were further acylated by 1 + 8 couplings in solution to furnish the key intermediates. Hydroxy-AVP has antidiuretic potency of 470 units/mg and activity in the rat vasopressor assay of 550 units/mg, representing a small enhancement of activity over that of arginine-vasopressin (AVP) in each case. Hydroxy-DAVP and hydroxy-VDAVP have essentially the same high antidiuretic activity (900 units/mg) and very low vasopressor potencies (0.9 and less than 0.02 units/mg, respectively). Hydroxy-AVP, hydroxy-DAVP, and hydroxy-VDAVP thus have antidiuretic-pressor selectivity (A/P) of 1, 1000, and greater than 45 000, respectively. These data are compared with those of other vasopressin analogues. Hydroxy-VDAVP is a highly specific antidiuretic peptids and may be useful in pharmacological studies of antidiuresis.
New Generation of Selective Androgen Receptor Degraders: Our Initial Design, Synthesis, and Biological Evaluation of New Compounds with Enzalutamide-Resistant Prostate Cancer Activity (2018)

In our effort to find small-molecule treatments of advanced prostate cancers (PCs), a novel series of indolyl and indolinyl propanamides (series II and III) were discovered as selective androgen receptor degraders (SARDs). Initial studies of androgen receptor (AR) antagonist (1) and agonist (2) propanamides yielded a tertiary aniline (3) with novel SARD activity but poor metabolic stability. Cyclization to II and III produced submicromolar AR antagonism and protein degradation selective to AR and AR splice variant (AR SV). II and III maintained potency against enzalutamide-resistant (Enz-R) mutant ARs and PC cells and were efficacious in Enz-R xenografts, suggesting their potential to treat advanced PCs. Design, synthesis, and biological activity of novel SARDs that could potentially be used for the treatment of a wide spectrum of PCs including castration-resistant, Enz-R, and/or AR SV-dependent advanced PCs that are often untreatable with known hormone therapies are discussed.
A hybrid ion exchange-nanofiltration (HIX-NF) process for energy efficient desalination of brackish/seawater (2009)

This study reports a new hybrid ion exchange-nanofiltration (HIX-NF) process for desalination of sea and brackish water that can attain significant energy economy over the conventional membrane-based pressure driven processes. In this hybrid process, an ion exchange step converts monovalent chloride ions of saline water to divalent sulfate ions and the resulting solution, having a reduced osmotic pressure than the feed, is desalinated using a nanofiltration (NF) membrane. The sulfate rich reject stream from the NF process is used to regenerate the anion exchanger. Results validate that NF membranes can desalinate sodium sulfate solution at a much lower transmembrane pressure compared to RO membranes as well as yield a higher permeate flux. The sulfate-chloride selectivity of the anion exchangers plays important role in sustainability of the process. Laboratory studies have revealed that a single type of anion exchanger cannot sustain the process for saline water with different salt concentrations. However, anion exchangers with different sizes of amine functional groups (e.g. quaternary-, tertiary-, secondary- and primary amine) hold the promise that the process can be tailored to achieve sustainability. Laboratory studies have validated the basic premise of the hybrid process including greater than two times less energy requirement than RO process for the same feed water and same permeate recovery condition.
Species-Specific Sequences at the omp2 Locus of Brucella Type Strains (1996)

A DNA sequence analysis of the omp2 locus of Brucella type strains revealed nucleotide differences that can be used for species identification. We developed specific probes which were used to verify the observed differences among the type strains following PCR amplification of portions of the omp2 locus.
MD-Logic Artificial Pancreas System (2010)

OBJECTIVE Current state-of-the-art artificial pancreas systems are either based on traditional linear control theory or rely on mathematical models of glucose-insulin dynamics. Blood glucose control using these methods is limited due to the complexity of the biological system. The aim of this study was to describe the principles and clinical performance of the novel MD-Logic Artificial Pancreas (MDLAP) System. RESEARCH DESIGN AND METHODS The MDLAP applies fuzzy logic theory to imitate lines of reasoning of diabetes caregivers. It uses a combination of control-to-range and control-to-target strategies to automatically regulate individual glucose levels. Feasibility clinical studies were conducted in seven adults with type 1 diabetes (aged 19–30 years, mean diabetes duration 10 ± 4 years, mean A1C 6.6 ± 0.7%). All underwent 14 full, closed-loop control sessions of 8 h (fasting and meal challenge conditions) and 24 h. RESULTS The mean peak postprandial (overall sessions) glucose level was 224 ± 22 mg/dl. Postprandial glucose levels returned to &lt;180 mg/dl within 2.6 ± 0.6 h and remained stable in the normal range for at least 1 h. During 24-h closed-loop control, 73% of the sensor values ranged between 70 and 180 mg/dl, 27% were &gt;180 mg/dl, and none were &lt;70 mg/dl. There were no events of symptomatic hypoglycemia during any of the trials. CONCLUSIONS The MDLAP system is a promising tool for individualized glucose control in patients with type 1 diabetes. It is designed to minimize high glucose peaks while preventing hypoglycemia. Further studies are planned in the broad population under daily-life conditions.