gebhart/patrepeval huggingface dataset:
Abstract 3632: BiTE® antibody constructs for the treatment of SCLC (2017)

Abstract Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor with a poor prognosis and limited therapeutic options. Most patients present with extensive stage disease, where recent advances in immunotherapies, including bi-specific T cell engager (BiTE®) antibody constructs, represent a promising new therapeutic approach. BiTE® molecules have demonstrated durable complete responses in the clinic in hematological malignancies. Similar to hematological malignancies, SCLC is also a widely-disseminated malignancy that shows very high response rate to first line therapies with high rates of disease recurrence, features which may support efficacy of the BiTE® modality. Next generation sequencing (NGS) identified Delta-like Ligand 3 (DLL3) as a highly specific tumor associated antigen for SCLC, with consistent expression in tumors and very low expression in normal tissues. Tumor expression of DLL3 protein was confirmed by IHC, with 30 of 35 SCLC tumors staining positive for DLL3. DLL3 BiTE® antibody constructs showed low pM potency in vitro and also demonstrated significant inhibition of tumor growth in vivo in an orthotopic model of SCLC. A half-life extended (HLE) BiTE® targeting DLL3 demonstrated antibody-like pharmacokinetic properties in single-dose studies in non-human primates (NHP), with a half-life of 11 days. This is predicted to support every other week dosing in humans. The combination of high potency and excellent PK properties suggests that HLE BiTE® molecules may provide a useful tool for targeting residual disease in SCLC patients whose tumors express DLL3. Citation Format: Michael J. Giffin, Ed K. Lobenhofer, Keegan Cooke, Tobias Raum, Jennitte Stevens, Pedro J. Beltran, Angela Coxon, Paul E. Hughes. BiTE® antibody constructs for the treatment of SCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3632. doi:10.1158/1538-7445.AM2017-3632
Novel Furin Inhibitors with Potent Anti‐infectious Activity (2015)

New peptidomimetic furin inhibitors with unnatural amino acid residues in the P3 position were synthesized. The most potent compound 4-guanidinomethyl-phenylacteyl-Arg-Tle-Arg-4-amidinobenzylamide (MI-1148) inhibits furin with a Ki value of 5.5 pM. The derivatives also strongly inhibit PC1/3, whereas PC2 is less affected. Selected inhibitors were tested in cell culture for antibacterial and antiviral activity against infectious agents known to be dependent on furin activity. A significant protective effect against anthrax and diphtheria toxin was observed in the presence of the furin inhibitors. Furthermore, the spread of the highly pathogenic H5N1 and H7N1 avian influenza viruses and propagation of canine distemper virus was strongly inhibited. Inhibitor MI-1148 was crystallized in complex with human furin. Its N-terminal guanidinomethyl group in the para position of the P5 phenyl ring occupies the same position as that found previously for a structurally related inhibitor containing this substitution in the meta position, thereby maintaining all of the important P5 interactions. Our results confirm that the inhibition of furin is a promising strategy for a short-term treatment of acute infectious diseases.
Inotropic support and peritoneal dialysis adequacy in neonates after cardiac surgery (2007)

We describe the impact of cardiovascular pharmacologic support on peritoneal dialysis adequacy in 20 neonates who required postoperative renal replacement therapy following cardiopulmonary bypass exposure. Peritoneal dialysis was administered for 2.5 (2) days. Peritoneal dialysis creatinine clearance was 3.4 (2.1) ml/min/1.73 m(2) and ultrafiltration rate was 9.75 (10) ml/h. Residual creatinine clearance was 31 (26) ml/min/1.73 m(2). Peritoneal dialysis creatinine clearance appeared to be a function of dialysate flow up to 100 ml/h. No correlation was present between inotropes and vasopressors infusion and peritoneal dialysis creatinine clearance/ultrafiltration rate. LDH clearance was 0.59 (0.85) ml/min/1.73 m(2) and it did not appear to have a correlation with dialysate flow. Patients in-hospital mortality was 20%, significantly higher than overall neonatal population admitted to our ICU (4.8%, P=0.02). Peritoneal dialysis in neonates allows optimal ultrafiltration rate and adequate small solute clearance, irrespective of hemodynamic status or vasopressor support.
Autocrine growth stimulation by secreted Kaposi fibroblast growth factor but not by endogenous basic fibroblast growth factor. (1990)

We studied the different potentials of a secreted and a nonsecreted member of the fibroblast growth factor (FGF) family to induce autocrine growth stimulation in human adrenal cortex carcinoma cells (SW-13). These epithelial cells express basic FGF (bFGF) cell surface receptors, and picomolar concentrations of bFGF suffice to induce anchorage-independent growth. The requirement for exogenously added bFGF contrasts with the intracellular storage of biologically active bFGF in SW-13 cells greater than 10,000-fold in excess of the concentration needed to stimulate anchorage independent growth. To study whether the expression of a secreted FGF would alter the growth phenotype of these cells, we transfected them with an expression vector coding for the Kaposi-fgf (K-fgf) oncogene. In contrast to controls, K-fgf-transfected cells secrete significant amounts of biologically active K-fgf protein into the growth media, show up to 50-fold increased colony formation in soft agar, and grow into rapidly progressing, highly vascularized tumors in athymic nude mice. A reversible inhibition of the autocrine growth stimulation in vitro is brought about by the polyanionic compound suramin. We conclude that FGF has to be released from SW-13 cells to function fully as a growth stimulator in vitro and in vivo.
Frequency domain discriminant analysis of the electroencephalogram (1997)

Abstract A frequency domain generalization of the classical quadratic discriminant function was applied to the problem of classifying alpha‐band multichannel electroencephalogram recordings in three task conditions. The data consisted of 41‐channel recordings obtained in eyes closed, verbal, and spatial task conditions. Classifier performance was measured by deriving a decision rule from a training sample of 42 recordings and then applying the obtained rule to a test sample of 46 recordings The proportion of correct classification was 93 in the training sample and 85 in the test sample. The classifier performed better when based on the complete cross‐spectral matrix than when restricted to power spectrum variables Classification based on a subset of 16 leads reduced the overall proportion of correct classification to 79 in the training sample and to 70 in the test sample.
Conformational restriction of the Tyr53 side‐chain in the decapeptide HEL[52‐61]: effects on binding to MHC‐II I‐Ak molecule and TCR recognition (2000)

A series of conformationally restricted analogs of the hen egg lysozyme (HEL) decapeptide 52-61 in which the conformationally flexible Tyr53 residue was replaced by several more constrained tyrosine and phenylalanine analogs was prepared. Among these tyrosine and phenylalanine analogs were 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (Htc), 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), 4-amino- 1,2,4,5-tetrahydro-8-hydroxy-2-benzazepine-3-one (Hba), 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-one (Aba), 2-amino-6-hydroxytetralin-2-carboxylic acid (Hat) and 2-amino-5-hydroxyindan-2-carboxylic acid (Hai) in which the rotations around Calpha-Cbeta and Cbeta-Cgamma were restricted because of cyclization of the side-chain to the backbone. Synthesis of Pht-Hba-Gly-OH using a modification of the Flynn and de Laszlo procedure is described. Analogs of beta-methyltyrosine (beta-MeTyr) in which the side-chains were biased to particular side-chain torsional angles because of substitution at the beta-hydrogens were also prepared. These analogs of HEL[52-61] peptide were tested for their ability to bind to the major histocompatibility complex class II I-Ak molecule and to be recognized in this context by two T-cell hybridomas, specific for the parent peptide HEL[52-61]. The data showed that the conformation and also the configuration of the Tyr53 residue influenced both the binding of the peptide to I-Ak and the recognition of the peptide/I-Ak complex by a T-cell receptor.
208. Physicochemical and Biological Characterization of Cyclodextrin-Based Polycation (CDP)/siRNA Composites Designed for Systemic Delivery (2005)

The feasibility of systemic nucleic acid delivery hinges on the ability to simultaneously incorporate numerous properties into the overall delivery system. For example, the delivery vehicle must have the following characteristics: (i) be small enough to travel through blood capillaries and enter tissues, but not be too small such that it is excreted rapidly through the kidneys; (ii) provide stability against degradation, yet willingly release its cargo once it arrives at the proper site; and (iii) avoid nonspecific interactions (i.e., avoid opsonization by immune system components) while still providing specific targeting to a given cell or molecule. We are developing a cyclodextrin-based polycation (CDP) that achieves a favorable balance in all of these design criteria. Here, we show the physicochemical characterization of the colloidal, composite particles formed with CDP and siRNAs through dynamic light scattering (DLS), multi-angle laser light scattering (MALLS), and gel mobility shift assays to quantitate the size and composition. Upon providing steric stabilization of the particles by surface PEGylation, we determine the average number of polyethylene glycol (PEG) molecules on each particle by isothermal titration calorimetry (ITC) and the average number of targeting ligands per particle using fluorescently labeled transferrin (Tf). Biological characterization of the particles reveals that they provide nuclease resistance to nucleic acids, do not aggregate in the presence of serum, and do not cause any observable hemolysis or aggregation of erythrocytes. Complement activation by polycations is often cited as a major concern for their in vivo application. We show that, at the concentrations required for in vivo delivery of siRNA, the complement activation is negligible for the PEGylated particles. This extensive physicochemical and biological characterization of the composite particles demonstrates their suitability for in vivo delivery of siRNA and provides a baseline for rational optimization of these particles as required for specific therapeutic applications.
Technologies for cooling of large distributed and deployable loads (2007)

In future space applications, widely distributed sensors, as well as, large deployable structures, such as mirrors and sunshades, will require active thermal control. However, thermal integration by conductive coupling with regenerative cryocoolers is not feasible for such distributed loads, as it requires massive copper straps and provides only limited means of thermal control. To address these issues, we are developing a continuous-flow rectified cooling loop (RCL) for use with pulse tube refrigerators. The RCL consists of a rectifier, integrated into the cold heat exchanger of the pulse tube refrigerator, and a flow loop with a MEMS-based, micro-scale, control valve. The RCL allows simple mechanical integration and has the benefit of load temperature regulation using the actively controlled valve to regulate the gas flow. The MEMS valve may also serve as the basis for a system of distributed Joule-Thomson (JT) coolers. In this paper, we summarize the work that has been done to date by Atlas Scientific, in collaboration with the University of Wisconsin Cryogenic Engineering Group (UWCEG) and the University of Michigan Solid State Electronics Lab (UMSSEL), in developing the RCL and the MEMS-based micro-scale control valve.
MR-Guided Unfocused Ultrasound Disruption of the Rat Blood-Brain Barrier (2011)

Therapeutic ultrasound with microbubbles can temporarily disrupt the blood‐brain barrier (BBB) for drug delivery. Contrast‐enhanced MRI (CE‐MRI) can visualize gadolinium passage into the brain, indicating BBB opening. Previous studies used focused ultrasound, which is appropriate for the targeted delivery of drugs. The purpose of this study was to investigate unfocused ultrasound for BBB opening across the whole brain.
Fin bending due to stress and its simulation (2013)

Modern CMOS and memory devices feature fins, which are high aspect ratio elements. While narrow and tall fins enhance electrical characteristics, they are mechanically weak structures. Unexpected failure mechanisms, such as fin bending and even cracking can arise in such devices. This paper discusses such mechanisms and offers a methodology to simulate them.
A low-profile broadband phased array antenna (2004)

A fundamentally different approach to broadband array design is introduced and validated with measured data. This design approach relies on mutual coupling to increase array bandwidth as opposed to the conventional approach of attempting to minimize coupling between array elements designed in isolation. The design leverages from multi-layer FSS design, resulting in a broadband, low profile, highly efficient, conformal array.
<title>Wireless inspection of structures aided by robots</title> (2001)

The inspection of structures by humans is often hampered by safety and accessibility concerns. One method of reducing human inspection activities is to use remotely located sensors, such as strain gages and accelerometers. Running cables to power the sensors and transmit data can be expensive and inconvenient. This paper describes a development effort in which a robot is used to power and interrogate remotely placed sensors. The sensors are powered by a noncontact inductive system, which eliminates the need for batteries or interconnecting lead wires. The data are sent by a wireless connection back to a central data logger and processor. The power demands of telemetering data are decreased by close proximity of robot. The system utilizes existing microminiature, multichannel, wireless programmable Addressable Sensing Modules (ASM's) to sample data from a wide variety of sensors. Demonstration style robots are built and tested with ASMs in simple tabletop design, and a more robust task specific I-beam crawler robot for structural application.
Music rhythm characterization with application to workout-mix generation (2010)

In this paper, we present approaches to musical rhythm pattern extraction, rhythm-based music retrieval, and rhythm-synchronized music mixing. A probabilistic model is used to jointly estimate tempo and time signature as a basis for beat tracking and measure detection. A representative rhythm pattern is then extracted through clustering to characterize the rhythm of a song. Based on this, a probabilistic approach is used for retrieving songs with similar rhythmic patterns. These are then mixed rhythm-synchronously with transitions maintaining continuity and regularity of beats. We apply the presented methods into workout-mix generation, which aims at automatically selecting rhythmically similar music given a seed song and a user-defined tempo profile. Our probabilistic approaches achieve accuracies similar to best published results, but avoid manually tuned parameters and “fudge factors”.
Nonlinear model reduction for simulation and control of rapid thermal processing (1997)

A methodology (based on the proper orthogonal decomposition and approximate inertial manifolds) is proposed for obtaining low order dynamic models of rapid thermal processing (RTP) systems. These nonlinear models are designed to retain the physical understanding of the RTP system dynamics and their dependence on critical parameters, making them an attractive choice for use in developing more advanced and intelligent controllers.
Nicotinamide Riboside and Dihydronicotinic Acid Riboside Synergistically Increase Intracellular NAD+ by Generating Dihydronicotinamide Riboside (2022)

Through evolution, eukaryote organisms have developed the ability to use different molecules as independent precursors to generate nicotinamide adenine dinucleotide (NAD<sup>+</sup>), an essential molecule for life. However, whether these different precursors act in an additive or complementary manner is not truly well understood. Here, we have evaluated how combinations of different NAD<sup>+</sup> precursors influence intracellular NAD<sup>+</sup> levels. We identified dihydronicotinic acid riboside (NARH) as a new NAD<sup>+</sup> precursor in hepatic cells. Second, we demonstrate how NARH, but not any other NAD<sup>+</sup> precursor, can act synergistically with nicotinamide riboside (NR) to increase NAD<sup>+</sup> levels in cultured cells and in mice. Finally, we demonstrate that the large increase in NAD<sup>+</sup> prompted by the combination of these two precursors is due to their chemical interaction and conversion to dihydronicotinamide riboside (NRH). Altogether, this work demonstrates for the first time that NARH can act as a NAD<sup>+</sup> precursor in mammalian cells and how different NAD<sup>+</sup> precursors can interact and influence each other when co-administered.
Specifying Weight Priors in Bayesian Deep Neural Networks with Empirical\n Bayes (2019)

Stochastic variational inference for Bayesian deep neural network (DNN)\nrequires specifying priors and approximate posterior distributions over neural\nnetwork weights. Specifying meaningful weight priors is a challenging problem,\nparticularly for scaling variational inference to deeper architectures\ninvolving high dimensional weight space. We propose MOdel Priors with Empirical\nBayes using DNN (MOPED) method to choose informed weight priors in Bayesian\nneural networks. We formulate a two-stage hierarchical modeling, first find the\nmaximum likelihood estimates of weights with DNN, and then set the weight\npriors using empirical Bayes approach to infer the posterior with variational\ninference. We empirically evaluate the proposed approach on real-world tasks\nincluding image classification, video activity recognition and audio\nclassification with varying complex neural network architectures. We also\nevaluate our proposed approach on diabetic retinopathy diagnosis task and\nbenchmark with the state-of-the-art Bayesian deep learning techniques. We\ndemonstrate MOPED method enables scalable variational inference and provides\nreliable uncertainty quantification.\n
Metabolic Syndrome and Associated Diseases: From the Bench to the Clinic (2017)

Metabolic Syndrome and Associated Diseases: From the Bench to the Clinic, a Society of Toxicology Contemporary Concepts in Toxicology (CCT) workshop was held on March 11, 2017. The meeting was convened to raise awareness of metabolic syndrome and its associated diseases and serve as a melting pot with scientists of multiple disciplines (eg, toxicologists, clinicians, regulators) so as to spur research and understanding of this condition. The criteria for metabolic syndrome include obesity, dyslipidemia (low high-density lipoprotein and/or elevated triglycerides), elevated blood pressure, and alterations in glucose metabolism. It can lead to a greater potential of type 2 diabetes, lipid disorders, cardiovascular disease, hepatic steatosis, and other circulatory disorders. Although there are no approved drugs specifically for this syndrome, many drugs target diseases associated with this syndrome thus potentially increasing the likelihood of drug-drug interactions. There is currently significant research focusing on understanding the key pathways that control metabolism, which would be likely targets of risk factors (eg, exposure to xenobiotics, genetics) and lifestyle factors (eg, microbiome, nutrition, and exercise) that contribute to metabolic syndrome. Understanding these pathways could also lead to the development of pharmaceutical interventions. As individuals with metabolic syndrome have signs similar to that of toxic responses (eg, oxidative stress and inflammation) and organ dysfunction, these alterations should be taken into account in drug development. With the increasing frequency of metabolic syndrome in the general population, the idea of a "normal" individual may need to be redefined. This paper reports on the substance and outcomes of this workshop.
Paxillin Mediates Sensing of Physical Cues and Regulates Directional Cell Motility by Controlling Lamellipodia Positioning (2011)

Physical interactions between cells and the extracellular matrix (ECM) guide directional migration by spatially controlling where cells form focal adhesions (FAs), which in turn regulate the extension of motile processes. Here we show that physical control of directional migration requires the FA scaffold protein paxillin. Using single-cell sized ECM islands to constrain cell shape, we found that fibroblasts cultured on square islands preferentially activated Rac and extended lamellipodia from corner, rather than side regions after 30 min stimulation with PDGF, but that cells lacking paxillin failed to restrict Rac activity to corners and formed small lamellipodia along their entire peripheries. This spatial preference was preceded by non-spatially constrained formation of both dorsal and lateral membrane ruffles from 5-10 min. Expression of paxillin N-terminal (paxN) or C-terminal (paxC) truncation mutants produced opposite, but complementary, effects on lamellipodia formation. Surprisingly, pax-/- and paxN cells also formed more circular dorsal ruffles (CDRs) than pax+ cells, while paxC cells formed fewer CDRs and extended larger lamellipodia even in the absence of PDGF. In a two-dimensional (2D) wound assay, pax-/- cells migrated at similar speeds to controls but lost directional persistence. Directional motility was rescued by expressing full-length paxillin or the N-terminus alone, but paxN cells migrated more slowly. In contrast, pax-/- and paxN cells exhibited increased migration in a three-dimensional (3D) invasion assay, with paxN cells invading Matrigel even in the absence of PDGF. These studies indicate that paxillin integrates physical and chemical motility signals by spatially constraining where cells will form motile processes, and thereby regulates directional migration both in 2D and 3D. These findings also suggest that CDRs may correspond to invasive protrusions that drive cell migration through 3D extracellular matrices.
SDF-1alpha concentration dependent modulation of RhoA and Rac1 modifies breast cancer and stromal cells interaction (2015)

We conclude that SDF-1α concentration modulates migration and adhesion of breast cancer cells, by controlling expression and activation of RhoGTPases.
A general preconditioning scheme for difference measures in deformable registration (2011)

We present a preconditioning scheme for improving the efficiency of optimization of arbitrary difference measures in deformable registration problems. This is of particular interest for high-dimensional registration problems with statistical difference measures such as MI, and the demons method, since in these cases the range of applicable optimization methods is limited. The proposed scheme is simple and computationally efficient: It performs an approximate normalization of the point-wise vectors of the difference gradient to unit length. The major contribution of this work is a theoretical analysis which demonstrates the improvement of the condition by our approach, which is furthermore shown to be an approximation to the optimal case for the analyzed model. Our scheme improves the convergence speed while adding only negligible computational cost, thus resulting in shorter effective runtimes. The theoretical findings are confirmed by experiments on 3D brain data.