gebhart/patrepeval huggingface dataset:
NEXT-GENERATION RECOMBINANT IMMUNOTOXINS FOR GLIOBLASTOMAS AND MELANOMAS TREATMENT (2014)

BACKGROUND: Glioblastoma (GBM) remains uniformly lethal despite the progress of conventional therapies, which lack specificity and thus result in high toxicity to normal cells. Immunotargeting therapy such as recombinant immunotoxin (RIT) is an alternative and a Phase I clinical trial of MR1-1-PE38KDEL is undergoing at Duke University Medical Center. To avoid the production of neutralizing antibodies against toxin portion and to allow for repeat treatment cycles, a less immunogenic form of PE, LR-LO10, has been generated by silencing the human B cell epitopes on PE38 and removing the immunodominant T cell epitopes. We have previously developed an affinity-matured glycoprotein NMB (GPNMB)-specific RIT, F6V-PE38, which exhibits significant in vitro and anti-tumor activity against GBM and melanomas. Here we report a newly engineered F6V-LR-LO10 RIT for efficient, targeted therapy of GBM and other GPNMB-expressing cancer patients with normal immunity. METHODS: We have constructed an RIT, F6V-LR-LO10, by fusing a fully human F6V scFv, as VH-(G4S)3-VL, with a truncated form of Pseudomonas exotoxin A, LR-LO10. F6V-LR-LO10 was expressed in E. coli BL21 (DE3), and the inclusion bodies were reduced, refolded, and purified by ion exchange chromatography and gel filtration. The antigen binding of F6V-LR-LO10 was assessed by surface plasmon resonance and flow cytometric analysis. The cytotoxicity was measured by protein inhibition assay on GPNMB-expressing GBM and melanoma cells. The in vivo animal toxicity was tested in nude mice and anti-tumor activity will be assessed in human xenograft mouse models. RESULTS: The F6V-LR-LO10 protein was purified as a monomer of 51 kDa to 95% homogeneity. The F6V-LR-LO10 bound to GPNMB-coated chips with high affinity at KD = 1.1e-8 M. The F6V-LR-LO10 also bound to native GPNMB protein via flow cytometric analysis on GPNMB positive cell lines. We tested the in vitro activity of F6V-LR-LO10 on various glioma and melanoma xenograft cells and demonstrated cell-killing activity. The IC50 of F6V-LR-LO10 on GBM D392 cells was 1.5 ng/mL; the IC50 was 10 ng/mL and 15 ng/mL on melanoma DM443 and DM440 cells, respectively, and that was comparable to the IC50 of F6V-PE38, while negative control RIT did not kill those cells. The animal toxicity (MTD) was greatly reduced by >17 fold for F6V-LR-LO10 than F6V-PE38. CONCLUSIONS: Our experiments showed that a new fully human anti-GPNMB RIT, F6V-LR-LO10, is highly active with higher therapeutic index and is predicted to have low immunogenicity in humans. This next-generation RIT is suitable for further clinical development in therapy of GBM, melanoma, and other GPNMB-expressing malignancies. SECONDARY CATEGORY: Preclinical Experimental Therapeutics.
ChemInform Abstract: Unusually Long Lifetimes of the Singlet Nitrenes Derived from 4‐Azido‐ 2,3,5,6‐tetrafluorobenzamides. (1994)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Induction of SerumHaemophilus influenzaeType B Capsular Antibodies in Adult Volunteers Fed Cross-ReactingEscherichia coli075:K100:H5 (1975)

Serum Haemophilus influenzae Type b (HITB) anticapsular antibodies were induced in adult volunteers by feeding of either of two strains of a cross-reacting Escherichia coli 075:K100:H5. In all the fed volunteers colonization for a finite period lasting up to eight weeks occurred, without adventitious reactions. Nine of 14 normal volunteers and one of two volunteers previously immunized with the Type 6 H. influenzae polysaccharide responded with a greater than twofold increase in serum Type 6 H. influenzae antibodies. These antibodies induced by Esch. coli were specific for the capsular polysaccharide and had bactericidal activity. The safety of this procedure, the comparable results in laboratory animals and the identification of other cross-reacting strains of Esch. coli with meningococcal and pneumococcal capsular polysaccharides suggest that colonization with these nonpathogenic organisms at birth may provide a general method of preventive immunization to diseases caused by encapsulated bacteria. (N Engl J Med 292:1093–1096, 1975)
Anti-müllerian hormone and testosterone serum levels are inversely during normal and precocious pubertal development. (1993)

Anti-Müllerian hormone (AMH), also called Müllerian inhibiting substance or factor, is produced by Sertoli cells from fetal life until puberty. In the present study, AMH, testosterone (T), LH, and FSH were measured by immunochemical methods in the serum of 50 boys with normal or delayed pubertal development, 4 patients with suspected androgen insensitivity, and 11 patients with either central (CPP) or gonadotropin-independent (GIPP) precocious puberty to investigate the hormonal regulatory mechanisms of AMH secretion at puberty. An inverse relationship between AMH and T levels was demonstrated. In boys with normal or delayed puberty with T concentrations below 6.7 nmol/L, AMH values were elevated (mean +/- SEM, 22.4 +/- 3.1 micrograms/L) and widely dispersed. In subjects with T levels over 6.7 nmol/L, AMH levels were uniformly low (3.4 +/- 0.5 micrograms/L), except in patients with suspected androgen insensitivity. No significant relationship was found between AMH and gonadotropin levels. Similar results were obtained in patients with either CPP or GIPP. Longitudinal studies were performed on four boys with CPP and two with GIPP before and after treatment. At the time of diagnosis, the T concentration was high, and AMH levels were usually low in CPP and GIPP patients alike. When appropriate treatment was initiated, the T concentration was normalized within 2-4 weeks, but restoration of prepubertal AMH levels required several months. Mature Sertoli cells were observed in testicular biopsies performed in three patients with untreated GIPP. Our results suggest that gonadotropins are not directly implicated in repression of AMH synthesis at puberty, but, rather, that the decrease in AMH production is the consequence of an androgen-mediated, long term, reversible chain of events leading to morphological and functional maturation of the Sertoli cells. Thus, the fall in serum AMH levels appears to be an excellent marker of Sertoli cell pubertal development.
Novel wide-band transition between Finite Ground Coplanar Waveguide (FGCPW) and balanced stripline (2009)

A novel wideband transition for connecting the Finite Ground Coplanar Waveguide (FGCPW) to the balanced stripline is proposed. The transition is partly tapered, multilayered and consists of two via interconnects. Its frequency of operation ranges from DC to 65 GHz. Simulation and experimental results, showing good agreement, are presented and discussed. This transition can find its use in a variety of MMIC applications, such as RF systems-on-chip. To our knowledge, this is the first FGCPW to balanced stripline transition described in the literature.
Sensitivity analysis of linear CROW gyroscopes and comparison to a single-resonator gyroscope (2014)

This study presents numerical simulations of the maximum sensitivity to absolute rotation of a number of coupled resonator optical waveguide (CROW) gyroscopes consisting of a linear array of coupled ring resonators. It examines in particular the impact on the maximum sensitivity of the number of rings, of the relative spatial orientation of the rings (folded and unfolded), of various sequences of coupling ratios between the rings and various sequences of ring dimensions, and of the number of input/output waveguides (one or two) used to inject and collect the light. In all configurations the sensitivity is maximized by proper selection of the coupling ratio(s) and phase bias, and compared to the maximum sensitivity of a resonant waveguide optical gyroscope (RWOG) utilizing a single ring-resonator waveguide with the same radius and loss as each ring in the CROW. Simulations show that although some configurations are more sensitive than others, in spite of numerous claims to the contrary made in the literature, in all configurations the maximum sensitivity is independent of the number of rings, and does not exceed the maximum sensitivity of an RWOG. There are no sensitivity benefits to utilizing any of these linear CROWs for absolute rotation sensing. For equal total footprint, an RWOG is &radic;N times more sensitive, and it is easier to fabricate and stabilize.
Rethinking Log Odds: Linear Probability Modelling and Expert Advice in Interpretable Machine Learning (2022)

We introduce a family of interpretable machine learning models, with two broad additions: Linearised Additive Models (LAMs) which replace the ubiquitous logistic link function in General Additive Models (GAMs); and SubscaleHedge, an expert advice algorithm for combining base models trained on subsets of features called subscales. LAMs can augment any additive binary classification model equipped with a sigmoid link function. Moreover, they afford direct global and local attributions of additive components to the model output in probability space. We argue that LAMs and SubscaleHedge improve the interpretability of their base algorithms. Using rigorous null-hypothesis significance testing on a broad suite of financial modelling data, we show that our algorithms do not suffer from large performance penalties in terms of ROC-AUC and calibration.
Haptic interface control-design issues and experiments with a planar device (2002)

Describes the haptic rendering of a virtual environment by drawing upon concepts developed in the area of teleoperation. A four-channel teleoperation architecture is shown to be an effective means of coordinating the control of a 3-DOF haptic interface with the simulation of a virtual dynamic environment.
Optimal power flow emulation of interchange brokerage systems using linear programming (1992)

The authors propose an interchange brokerage system based on an optimal power flow (OPF) solution using linear programming (LP). Interchange brokering schedules power imports and exports between interconnected electric utilities to maximize profits for all participating parties and enhances the security of power systems. The data required for interchange brokerage systems are the amount of power available for trading and the system incremental cost. An LP software package called STORM was used to solve the active and reactive OPF subproblems and the interchange brokerage systems. The steps required for the implementation and problems involved in loss minimization are considered. The development of LP theory for OPF and interchange brokerage systems and its limitations are discussed. The experimental results are included.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Flow Visualization in Artificial Porous Media From Microfluidic PMMA Devices (2011)

Microfluidic polymethylmethacrylate (PMMA) devices for study of particle transport in artificial porous media were designed and microfabricated using hot embossing with a brass mold insert containing a microchannel network with eight layers. After thermal bonding to enclose the microchannel network, a process protocol was applied to successfully remove bubbles in the PMMA device. Characterization protocols were developed for study of fluorescent particle tracking, accumulation, and retention in these microfluidic chip artificial porous media. Particle accumulation and retention was observed throughout the microfluidic network domain and predominantly at the inlet section of the PMMA device due to entrance effects. Particle Image Velocimetry of the PMMA device allowed for generating velocity profiles in the chip microchannel networks.
Microarray profiling reveals the integrated stress response is activated by halofuginone in mammary epithelial cells (2011)

Our findings suggest activation of the ISR may be a common mechanism underlying HF biological effects.
Dithiothreitol Enhances Listeria monocytogenes Mediated Cell Cytotoxicity (2000)

The hybridoma Ped-2E9 based cytotoxicity assay was developed to distinguish virulent from avirulent Listeria species in 6 hr. The cytotoxicity effect on Ped-2E9 was reported to be primarily due the cytolytic action of listeriolysin O (LLO), produced by L. monocytogenes. In this study, the effect of a reducing agent, dithiothreitol (DTT, 0-2 mM) that is known to activate LLO was investigated to make the Ped-2E9 based cytotoxicity assay an even more sensitive and rapid. Also, we examined the effect of fetal bovine serum (FBS, 0-50%), a common ingredient of tissue culture media on cytotoxicity. A DTT concentration of 0.5 mM gave an optimum cytotoxicity effect, which could be measured by both alkaline phosphatase (AP) and lactate dehydrogenase (LDH) assays in just 1.5-2 hr. FBS, at levels between 10 to 50%, significantly inhibited Listeria-mediated cytotoxicity. Concentrated culture filtrates from L. monocytogenes or LLO producing recombinant L. innocua (prfA+ hlyA+) strain also caused cytotoxicity effects, which were observed by scanning electron microscopy or a cytotoxicity assay in 2-3 hr. Interestingly, addition of DTT to culture filtrates produced 100% cell cytotoxicity in just 15 min. This indicated that LLO activity, which is responsible for Ped-2E9 cytotoxicity, was augmented several folds with the addition of a reducing agent. Examination of Listeria isolates belonging to different serogroups from clinical sources or naturally contaminated meat products with DTT gave cytotoxicity results in 2 hr, which were comparable to the 5-hr assay analyzed concurrently without DTT. These results indicated that DTT, which activated the LLO, could be used in the cytotoxicity assay to enhance Listeria-mediated Ped-2E9 cell cytotoxicity. This knowledge will greatly assist us to develop a user-friendly rapid assay to screen cytopathogenic properties of Listeria species.
Deciphering the Role of Extracellular Vesicles Derived from ZIKV-Infected hcMEC/D3 Cells on the Blood–Brain Barrier System (2021)

To date, no vaccines or antivirals are available against Zika virus (ZIKV). In addition, the mechanisms underlying ZIKV-associated pathogenesis of the central nervous system (CNS) are largely unexplored. Getting more insight into the cellular pathways that ZIKV recruits to facilitate infection of susceptible cells will be crucial for establishing an effective treatment strategy. In general, cells secrete a number of vesicles, known as extracellular vesicles (EVs), in response to viral infections. These EVs serve as intercellular communicators. Here, we investigated the role of EVs derived from ZIKV-infected human brain microvascular endothelial cells on the blood-brain barrier (BBB) system. We demonstrated that ZIKV-infected EVs (IEVs) can incorporate viral components, including ZIKV RNA, NS1, and E-protein, and further transfer them to several types of CNS cells. Using label-free impedance-based biosensing, we observed that ZIKV and IEVs can temporally disturb the monolayer integrity of BBB-mimicking cells, possibly by inducing structural rearrangements of the adherent protein VE-cadherin (immunofluorescence staining). Finally, differences in the lipidomic profile between EVs and their parental cells possibly suggest a preferential sorting mechanism of specific lipid species into the vesicles. To conclude, these data suggest that IEVs could be postulated as vehicles (Trojan horse) for ZIKV transmission via the BBB.
A method of plaiting hair (2012)

We propose a new method to solve a neglected problem that is to weave a hair into braids. On specifying a braid type, our method plaits hair into braids.
Lightweight Mechanical Metamaterials with Tunable Negative Thermal Expansion (2016)

Ice floating on water is a great manifestation of negative thermal expansion (NTE) in nature. The limited examples of natural materials possessing NTE have stimulated research on engineered structures. Previous studies on NTE structures were mostly focused on theoretical design with limited experimental demonstration in two-dimensional planar geometries. In this work, aided with multimaterial projection microstereolithography, we experimentally fabricate lightweight multimaterial lattices that exhibit significant negative thermal expansion in three directions and over a temperature range of 170 degrees. Such NTE is induced by the structural interaction of material components with distinct thermal expansion coefficients. The NTE can be tuned over a large range by varying the thermal expansion coefficient difference between constituent beams and geometrical arrangements. Our experimental results match qualitatively with a simple scaling law and quantitatively with computational models.
Adoptive cell therapy of triple negative breast cancer with redirected cytokine-induced killer cells (2020)

ACT, Adoptive Cell Transfer; ADCC, Antibody-Dependent Cell-mediated Cytotoxicity; ADP, Adenosine diphosphate; BLI, Bioluminescence Imaging; CAR, Chimeric Antigen Receptor; CIK, Cytokine Induced Killer cells; CTX, Cetuximab; DMEM, Dulbecco's Modified Eagle Medium; EGFR, Human Epidermal Growth Factor 1; ER, Estrogen; FBS, Fetal Bovine Serum; FFPE, Formalin-Fixed Paraffin-Embedded; GMP, Good Manufacturing Practices; GVHD, Graft Versus Host Disease; HER2, Human Epidermal Growth Factor 2; HRP, Horseradish Peroxidase; IFN-γ, Interferon-γ; IHC, Immunohistochemistry; IL-2, Interleukin-2; ISO, Irrelevant antibody; i.t., intratumoral; i.v., intravenous, mAbs, Monoclonal Antibodies; mIHC, Multiplex Fluorescence Immunohistochemistry; MHC, Major Histocompatibility Complex; NK, Natural Killer; NKG2D, Natural-Killer group 2 member D; NSG, NOD/SCID common γ chain knockout; PARP, Poly ADP-ribose polymerase; PBMCs, Peripheral Blood Mononuclear Cells; PBS, Phosphate-buffered saline; PDX, Patient-derived xenograft; PR, Progesterone; rhIFN-γ, Recombinant Human Interferon-γ; RPMI, Roswell Park Memorial Institute; STR, Short tandem Repeat; TCR, T Cell Receptor; TNBC, Triple Negative Breast Cancer; TSA, Tyramide Signal Amplification.
A new analytical method for the quantification of three Lignans in Coffee by HPLC-MS/MS Triple Quadrupole. (2018)

Lignans, compounds with two phenylpropanoid units, are present in high number of foodstuffs and beverages including coffee[1,2]. Our aim was to develop a new analytical method to quantify three lignans, i.e., secoisolariciresinol (SECO), lariciresinol (LARI) and matairesinol (MAT) in espresso (EC) and ground coffee by using HPLC-MS/MS Triple Quadrupole. Hence, different extraction methods including acid hydrolysis and enzymatic digestion have been evaluated. Subsequently, the most performing process was validated and applied to various coffee samples. Both SECO (from 27.9 to 52.0 μg l-1 in EC; from 84.4 to 257.8 μg Kg-1 in ground coffee) and LARI (from 5.3 to 27.8 μg l-1 in EC; from 26.1 to 86.2 μg Kg-1 in ground coffee) have been found in all coffee samples. Regular consumption of coffee can contribute to dietary lignan intakes. &#13;\n&#13;\nReferences&#13;\n1.\t“Plant and mammalian lignans: a review of source, intake, metabolism, intestinal bacteria and health”. J. M. Landete. (2012) Food Research International, 46, 410-424.&#13;\n2.\t“Chromatographic analysis of lignans”. S. M. Willför, A. I. Smeds, B. R. Holmbom. (2006) Journal of Chromatography A, 1112, 64-77.
Poly(ethylene glycol)-Modified Phospholipids Prevent Aggregation during Covalent Conjugation of Proteins to Liposomes (1995)

Liposome aggregation is a major problem associated with the covalent attachment of proteins to liposomes. This report describes a procedure for coupling proteins to liposomes that results in little or no change in liposome size. This is achieved by incorporating appropriate levels of poly(ethylene glycol)-modified lipids into the liposomes. The studies employed thiolated avidin-D coupled to liposomes containing the thio-reactive lipid N-(4-(p-maleimidophenyl)butyryl)dipalmitoyl phosphatidylethanolamine (1 mol % of total lipid) and various amounts of MePEG-S-POPE (monomethoxypoly(ethylene glycol) linked to phosphatidylethanolamine via a succinate linkage). The influence of PEG chain length and density was also assessed. The presence of PEG on the surface of liposomes is shown to provide an effective method of inhibiting aggregation and the corresponding increase in liposome size during the covalent coupling of avidin-D. A balance between the size of the PEG used and the amount of PEG-lipid incorporated into the liposome had to be achieved in order to maintain efficient coupling. Optimal coupling efficiencies in combination with minimal aggregation effects were achieved using 2 mol % MePEG2000-S-POPE (PEG of 2000 MW) or 0.8 mol % MePEG5000-S-POPE (PEG of 5000 MW). At these levels, the presence of PEG did not affect the biotin binding activity of the covalently attached avidin. The ability of the resulting liposomes to specifically target to biotinylated cells is demonstrated.
Development of a New Correlation for Bubble Point Pressure in Oil Reservoirs Using Artificial IntelligenceTechnique (2017)

Abstract Accurate determination of the bubble point pressure is extremely important for several applications in oil industry. In reservoir engineering applications the bubble point pressure is an essential input for the reservoir simulation and reservoir management strategies. Also, in production engineering the bubble point pressure determines the type of the inflow performance relationship that describes the reservoir production performance. Accurate estimation and prediction of the bubble point pressure will eliminate the risk of producing in two phase region. Current correlations can be used to determine the bubble point pressure with high errors and this will lead to poor reservoir management. Artificial intelligent tools used in the previous studies did not disclose the models they developed and they stated the models as black box. The objective of this research is to develop a new empirical correlation for bubble point pressure (BPP) prediction using artificial intelligent techniques (AI) such as; artificial neural network (ANN), adaptive neuro-fuzzy inference system (ANFIS), and supper vector machine (SVM). For the first time we changed the ANN model to a white box by extracting the weights and the biases from AI models and form a new mathematical equation for BPP prediction. The results obtained showed that the ANN model yielded the highest correlation coefficient (0.988) and lowest average absolute error percent (7.5%) for BPP prediction as a function of the gas specific gravity, the solution gas oil ratio, the oil gravity, and the reservoir temperature as compared with ANFIS and SVM. The developed mathematical equation from the ANN model outperformed the previous AI models and the empirical correlations for BPP prediction. It can be used to predict the BPP with a high accuracy (the average absolute error (3.9%) and the coefficient of determination (R2) of 0.98)