gebhart/patrepeval huggingface dataset:
Abstract 4524: Non-genetic generation of IgG-like immune cell-redirecting antibodies lacking effector function (2020)

Abstract Since the early approval of catumaxomab and blinatumomab, T cell-redirecting antibodies have emerged as a promising biologics in cancer treatment. New technologies are overcoming the limitations of the 1st generation T-cell redirecting bispecifics, especially extending half-life to allow intermittent dosing, reducing immunogenicity and improving the safety profile. Today, T cell-engagers are generated as a wide variety of molecular architectures, typically IgG-type. However, nearly without exception, these bispecifics are generated by genetic fusion of a cancer-binding and an anti-CD3 antibody, which inevitably requires genetic reengineering of an existing targeting antibody and/or extensive optimization of antibody format. We have shown earlier that the native glycan of a monoclonal antibody provides a privileged site for controlled attachment of small-molecule cytotoxic drugs.1 The resulting antibody-drug conjugates (ADCs) were found to display significantly improved therapeutic index versus conventional technologies, while improving manufacturability. This proprietary technology, known as GlycoConnect™, has been adapted by various ADC developers, and entered clinical phase early 2019. Here we present the adaption of GlycoConnect™ technology for the generation of immune cell-redirecting antibodies, without requiring prior protein reengineering. Instead, a two-stage chemoenzymatic process is applied that allows the conversion of any IgG isotype into a T cell-engager by selective attachment of anti-CD3 scFv to the antibody glycan. Studies are presented to precisely control conjugation stoichiometry, providing molecular architectures with defined 2:1 or 2:2 ratio (target-binding:CD3-binding), as well as functional studies to corroborate the biological activity of these GlycoConnect™ bispecifics. Finally, early results will be presented regarding extension of the concept to bispecifics designed to redirect natural killer (NK) cells, or to engage T-cells by activation of costimulatory molecules, such as CD137 (4-1BB). 1 van Geel et al. Chemoenzymatic Conjugation of Toxic Payloads to the Globally Conserved NGlycan of Native mAbs Provides Homogeneous and Highly Efficacious Antibody−Drug Conjugates. Bioconj. Chem. 2015, 26, 2233-2242. Citation Format: Floris L. van Delft, Remon van Geel. Non-genetic generation of IgG-like immune cell-redirecting antibodies lacking effector function [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4524.
On the Correctness of Orphan Management Algorithms (1989)

orphans, transactions, atomic transactions, databases, distributed computing, distributed databases, serializability,
Inositol polyphosphate-mediated iron transport in Pseudomonas aeruginosa (1999)

It has previously been shown that myo-inositol hexakisphosphate (myo-InsP6) mediates iron transport into Pseudomonas aeruginosa and overcomes iron-dependent growth inhibition. In this study, the iron transport properties of myo-inositol trisphosphate and tetrakisphosphate regio-isomers were studied. Pseudomonas aeruginosa accumulated iron (III) at similar rates whether complexed with myo-Ins(1,2,3)P3 or myo-InsP6. Iron accumulation from other compounds, notably D/L myo-Ins(1,2,4,5)P4 and another inositol trisphosphate regio-isomer, D-myo-Ins(1,4,5)P3, was dramatically increased. Iron transport profiles from myo-InsP6 into mutants lacking the outer membrane porins oprF, oprD and oprP were similar to the wild-type, indicating that these porins are not involved in the transport process. The rates of reduction of iron (III) to iron (II) complexed to any of the compounds by a Ps. aeruginosa cell lysate were similar, suggesting that a reductive mechanism is not the rate-determining step.
Antenne Solénoïde segmentée pour applications RFID UHF champ proche (2015)

International audience
Graph theoretical analysis of tau burden and the functional connectome in Alzheimers disease (2019)

The accumulation of intraneuronal “tau-tangles” is a hallmark of Alzheimer's Disease (AD). The similarity of the distribution of AD-pathology with the anatomy of brain networks has raised questions on the pathways and mechanisms of pathology across the brain. Our objective is to address this question using a graph theoretical analysis approach of the functional connectome and in-vivo measures of tau burden.
Inhibition of 3β-hydroxysteroid dehydrogenase by abiraterone as a rationale for dose escalation in castration-resistant prostate cancer. (2012)

209 Background: Treatment with abiraterone acetate (abi) increases the survival of men with castration-resistant prostate cancer (CRPC). Resistance to abi invariably occurs, probably due in part to up-regulation of steroidogenic enzymes and/or other mechanisms that sustain the synthesis of dihydrotestosterone (DHT), which raises the possibility of reversing resistance by concomitant inhibition of other required steroidogenic enzymes. The 1000 mg daily abi dose was selected for the phase III trials despite the absence of dose-limiting toxicities at higher doses. Based on the 3β-hydroxyl, Δ 5 -structure, we hypothesized that abi also inhibits 3β-hydroxysteroid dehydrogenase/isomerase (3βHSD), which is absolutely required for the intratumoral synthesis of DHT in CRPC, regardless of origins or routes of synthesis. Methods: We tested if abi inhibits recombinant 3βHSD2 activity in vitro or endogenous 3βHSD activity in LNCaP and LAPC4 cells, including conversion of [ 3 H]-dehydroepiandrosterone (DHEA) to androstenedione (AD), androgen receptor (AR) nuclear translocation, expression of AR-responsive genes, and LAPC4 xenograft growth in orchiectomized mice supplemented with DHEA. Results: Abi has a mixed inhibition pattern of 3βHSD2 in vitro, blocks the conversion from DHEA to AD and DHT with an IC 50 of &lt; 1 µM in CRPC cell lines, inhibits AR nuclear translocation and expression of TMPRSS2, and decreases CRPC xenograft growth in DHEA-supplemented mice. Conclusions: Abi blocks 3βHSD enzymatic activity, synthesis of AD and DHT, inhibits the AR-response, and suppresses growth of CRPC cells at concentrations that are clinically achievable. Variable abi inhibition of 3βHSD might account in part for the heterogeneous clinical response to abi. More importantly, 3βHSD inhibition with abi might be clinically harnessed to reverse resistance to CYP17A1 inhibition at the standard dose by dose-escalation, or simply by administration with food to increase drug exposure.
Stress reconfigurable tunable magnetoelectric resonators as magnetic sensors (2013)

We report a magnetoelastic effect in doubly clamped ferromagnetic magnetostrictive Metglas resonators with electrically and magnetically reconfigurable frequency response. The field-induced resonance frequency shift is due to magnetostrictive strain, which is shown to have a strong dependence on uniaxial stress. Here, we demonstrate that this magnetic field induced behavior can be used as the basis for a simple, tunable, magnetoelectric magnetic field sensor. The effect of tension on the field dependent magnetostrictive constant and the sensor sensitivity is examined, and the equivalent magnetic noise floor of such a sensor is estimated.
Imaging single nanoparticles using laser terahertz emission nanoscopy (2017)

By utilizing plasmonic coupling to an AFM probe, we demonstrate Laser Terahertz Emission Nanoscopy (LTEN) with ~20 nm resolution. We demonstrate the resolution by imaging a single gold nanorod on an InAs substrate.
AI/Machine Learning in Medical Imaging (2021)

Artificial intelligence (AI), or machine intelligence, can be broadly viewed as the use of computers, instead of humans, to learn from data input to a computer, and then, based on that learning, to problem-solve specific tasks. In medical imaging, the image data serve as the inputs to the AI system. While AI has been investigated over decades for the interpretation of medical images, it has only been in the recent decade that it has been greatly embraced by academia, industry, and the public. AI applications are being demonstrated in multiple areas of medical imaging including the clinical tasks of disease detection, diagnosis, prognosis, and therapeutic patient management, with algorithms of segmentation, computer-extraction of characteristics of abnormal and normal structures, radiomics, and deep learning. The potential practice-changing advances in AI have also yielded discussions on ethics and its effect on healthcare costs and workforce. A major concern in using AI is that some systems present as “black boxes” that, while yielding a correct prediction of a medical condition, lack the corresponding explanation on why the AI-reported decision was made. Overall, many are now viewing AI as ultimately a new “tool” in healthcare that will eventually enable the clinician to be more effective and efficient, as opposed to being replaced.
Biochemical and cellular markers differentiate recovered, in‐line filtered plasma, and plasma obtained by apheresis methods (2021)

Our results show that biochemical and cellular surrogate markers are valuable discriminators of plasma types.
Simultaneous acquisition of multiple images with higher dynamic range (2014)

Computational photography has redefined the possibilities of conventional photography. New effects can be obtained by mixing modified hardware with software. In this paper we present the basis of a theoretical framework for a computational camera. By using coded apertures, the framework is able to multiplex images of a scene and simultaneously acquire them. As an application, we show a system to capture images with different exposure values, a feature that is often useful in high dynamic range imaging. This framework is not limited to the acquisition of images with varying exposure values. It is also adaptable to different types of filters, e.g.: color filters. The advantages of this system are the low cost of implementation and ease of adaption to different conditions. However, the need and difficulty of the decoding process can add extra image artifacts.
P004 PN-943, an oral α4β7 integrin antagonist, inhibits MAdCAM1-mediated proliferation and cytokine release from CD4+ T cells independent of trafficking (2020)

Abstract Background PN-943, an oral gastrointestinal (GI) -restricted peptide antagonist of α4β7 integrin, is being developed for the treatment of inflammatory bowel disease (IBD). Blockade of α4β7 binding to mucosal addressin cell adhesion molecule-1 (MAdCAM1) is thought to treat IBD by preventing extravascular migration of blood T cells into the inflamed GI mucosa. Recent evidence suggests the involvement of other mechanisms. Saturation of circulating T-cell α4β7 by vedolizumab is not sufficient for optimal efficacy; and PTG-100, a PN-943 analogue, showed evidence of clinical and histological remission in ulcerative colitis patients at sub-saturating blood receptor occupancy (%RO). Here, we assessed the potential of a local GI-acting function of α4β7 by evaluating the ability of PN-943 to inhibit MAdCAM1-mediated CD4+ T-cell proliferation and cytokine production. Methods Primary CD4+ T cells were labelled fluorescently and incubated with plate-bound anti-CD3 alone or together with MAdCAM1 with or without inhibitors for three days. Phenotype, distribution of T-helper (Th) subsets and %RO analyses were conducted by flow cytometry. Supernatant cytokine levels were quantified by multiplex assays. Results MAdCAM1 combined with anti-CD3 markedly enhanced proliferation of CD4+ T cells compared with anti-CD3 alone (n = 7, 12–64%). Immune phenotyping revealed that proliferation occurred in both CD45RO- naïve and CD45RO+ memory T cells and was restricted to the β7+ population with successive cycles of proliferation showing increased β7 expression. Amongst the proliferated memory T cells, the percentage of the IFNγ-producing Th1 subset was higher than IL-17A-producing Th17 and IL-4-producing Th2 subsets. Multiplex profiling identified several cytokines, including but not limited to IL-6, IL-13, GM-CSF, and TNFα, whose release were promoted by MAdCAM1. PN-943 abolished MAdCAM1-mediated stimulation (n = 4, IC50 4.6 nM). The inhibitory effects were associated with lowered β7 expression indicative of internalisation by PN-943. Blockade was not observed with an inactive analogue indicating dependency on PN-943 binding to α4β7. Consistent with the requirement for a locally acting drug, 30 mg/kg oral dosing in mice demonstrated high exposure (n = 6, 39 nM) and occupancy of T-cell α4β7 (n = 6, 92%) in the GI compared within the blood. Conclusion The α4β7-MAdCAM1 interaction promoted β7+CD4+ T-cell proliferation and cytokine release, which may contribute to chronic inflammatory responses occurring in the diseased gut of IBD patients independent of T-cell trafficking. PN-943 inhibition of MAdCAM1-mediated signalling through α4β7 supports the potential therapeutic advantages for an oral GI-restricted approach, whereby PN-943 is delivered locally and directly blocks α4β7 function in the GI.
Allelic variation in the vacA gene of Helicobacter pylori isolated from Chinese patients (2001)

OBJECTIVE : To characterize the vacA alleles present in Chinese Helicobacter pylori strains and to compare the allelic variation in the vacA gene of Chinese strains with that of Western strains. METHODS : Twenty‐two single colonies of H. pylori isolated from five biopsy specimens with different gastric disorders were characterized for the expression of VacA protein and for evaluating the cytotoxic activity in HeLa cells. Five representative strains were selected and the vacA gene was amplified by PCR and subjected to automatic DNA sequencing using a primer walking strategy. RESULTS : Four strains expressed the VacA protein. Only one of the five strains induced vacuole degeneration in HeLa cells. All five vacA genes coded for identical signal peptides of the sla allele and had similar sequences encoding a 37 kDa subunit and outer membrane exporter. One of the five strains expressed a VacA protein with a middle region of the m1 allele and the others of the m2 allele. The four m2 allele strains had little vacuolating activity in HeLa cells. Phylogenetic analysis indicated that the homology of the Chinese vacA genes was 97.6–99.2% compared with 91.3–92.0% in the Western strains. CONCLUSIONS : There are allelic variations in the vacA gene between Chinese and Western H. pylori . Chinese H. pylori strains form a phylogenetically independent cluster separated from Western isolates. The m2 ‐type strains seem to be more prevalent in China. Cytotoxicity in HeLa cells appear to associate with the middle region but not the signal sequence.
Polyelectrolyte (2016)

In the past, aggregation and self-assembly have been associated principally with micellar and colloidal systems of molecules; however, with the advent of supramolecular chemistry, molecular self-assembly has been opened to a much wider understanding that has facilitated access to a variety of different shapes and sizes, along with the construction of new and fascinating molecular topologies. This document aims at defining more than 150 terms related to aggregation and self-assembly in the particular case of macromolecules. The list is restricted to the most commonly encountered terms.
Nomogram for predicted probability of cervical cancer and its precursor lesions using miRNA in cervical mucus, HPV genotype and age (2022)

Cervical cancer is the fourth most common cancer in women worldwide. Although cytology or HPV testing is available for screening, these techniques have their drawbacks and optimal screening methods are still being developed. Here, we sought to determine whether aberrant expression of miRNAs in cervical mucus could be an ancillary test for cervical neoplasms. The presence of miRNAs in 583 and 126 patients (validation and external cohorts) was determined by real-time RT-PCR. Performance of a combination with five miRNAs (miR-126-3p, -451a -144-3p, -20b-5p and -155-5p) was estimated by ROC curve analysis. Predicted probability (PP) was estimated by nomograms comprising -ΔCt values of the miRNAs, HPV genotype and age. A combination of five miRNAs showed a maximum AUC of 0.956 (95% CI: 0.933-0.980) for discriminating cancer. Low PP scores were associated with good prognosis over the 2-year observation period (p < 0.05). Accuracy for identifying cancer and cervical intraepithelial neoplasia (CIN) 3 + by nomogram was 0.983 and 0.966, respectively. PP was constant with different storage conditions of materials. We conclude that nomograms using miRNAs in mucus, HPV genotype and age could be useful as ancillary screening tests for cervical neoplasia.
Organic field-effect transistor-based flexible sensors (2020)

Flexible electronic devices have attracted a great deal of attention in recent years due to their flexibility, reduced complexity and lightweight. Such devices can conformably attach themselves to any bendable surface and can possess diverse transduction mechanisms. Consequently, with continued emphasis on innovation and development, major technological breakthroughs have been achieved in this area. This review focuses on the advancements of using organic field-effect transistors (OFETs) in flexible electronic applications in the past 10 years. In addition, to the above mentioned features, OFETs have multiple advantages such as low-cost, readout integration, large-area coverage, and power efficiency, which yield synergy. To begin with, we have introduced organic semiconductors (OSCs), followed by their applications in various device configurations and their mechanisms. Later, the use of OFETs in flexible sensor applications is detailed with multiple examples. Special attention is paid to discussing the effects induced on physical parameters of OFETs with respect to variations in external stimuli. The final section provides an outlook on the mechanical aspects of OSCs, activation and revival processes of sensory layers, small area analysis, and pattern recognition techniques for electronic devices.
Near Term Improvements to WAAS Availability (2013)

Since 2003, when it was first declared operational, the Wide Area Augmentation System (WAAS) has been increasing its availability through successive software updates (for example, new monitoring algorithms) and hardware updates (expanded reference receiver network). Today, WAAS provides vertical guidance to more than 3000 runways in the United States. With the current GPS constellation, WAAS has very high availability, and is even robust to some degradation in the constellation. However, even with the current GPS constellation, WAAS availability can be affected by the loss of a single satellite. In addition, there is growing interest in using WAAS for more demanding operations, such as Autoland. For these reasons, it is worthwhile investigating possible improvements in the ground monitors (which would not require avionics updates). In this paper, we propose and evaluate changes in three areas of the monitoring algorithms: signal deformation monitoring, code noise and multipath characterization, and clock and ephemeris monitoring. We show that even without reducing the ionospheric delay error bounds, which are the biggest contributor to the Protection Levels, it is possible to significantly increase WAAS performance.
Antitumour activity of new semi-synthetic anthracyclines containing fluorotalopyranose. (1988)

The authors have synthesized 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl) adriamycinone (FT-ADM) which exhibited strong antitumour activity and weak toxicity. These characteristics of FT-ADM are partly due to the presence of a 2'-fluoro atom which strengthens the glycoside bond. FT-ADM, however, is sparingly soluble in water because of lack of the 3'-amino group of adriamycin. To increase the solubility of FT-ADM, a hydrophilic group was added at the 14-OH group. Then, the 14-hemisuccinate, 14-hemiglutarate, 14-hemiadipiate, 14-hemipimelate and 14-hemisuberate derivatives of FT-ADM were synthesized. Among them, the 14-hemipimelate derivative (FAD-104) was selected for further development because of its potent antitumour activity and weak toxicity. When drugs were injected intraperitoneally every day from day 1 to 9, FAD-104 showed an apparently stronger antitumour effect against mouse L-1210 leukaemia than adriamycin with lower toxicities. FAD-104 was also more effective than adriamycin on L-1210 using other administration schedules. A characteristic feature is that FAD-104 is effective over a very broad range, which will be advantageous for safe clinical use. FAD-104 also showed marked antitumour effect against L-1210 when it was injected intravenously either once on day 1 or three times on days 1, 5 and 9. Thus, FAD-104 may be a more potent antitumour anthracycline than adriamycin.
Androgen receptor modulation in benign human prostatic tissue and prostatic adenocarcinoma during neoadjuvant endocrine combination therapy (1996)

Modulation of androgen receptor (AR) expression during neoadjuvant endocrine therapy in human prostates of patients with localized prostate cancer was investigated by immunohistochemistry. In 8 of 15 untreated prostatectomy specimens, the majority of prostatic glandular cells displayed nuclear immunostaining for AR, whereas only 1 of 26 pretreated cases displayed a similar glandular AR expression. Expression of AR in the prostatic stromal compartment of nontreated cases proved to be quite heterogeneous, since 4 of the 15 (27%) examined specimens did not show stromal AR expression. After preoperative neoadjuvant therapy, this value was 68%, although this difference did not reach statistical significance. Prostatectomy specimens of the treated patients contained carcinomas with a higher Gleason score than those of untreated patients. AR expression in carcinomas of treated patients was diminished (P=0.05), which may be attributed to their relatively lower differentiation grade. The data strongly suggest that neoadjuvant hormone therapy reduces AR expression by nonneoplastic prostatic glandular cells and carcinoma cells by a selective, but incomplete, elimination of AR-positive cells. © 1996 Wiley-Liss, Inc.
Photonic-crystal based functional devices -- ultra-high-Q nanocavities (2006)

Here, we demonstrate that a formation of a photonic double-heterostructure is the key solution. A nanocavity with an extremely high-Q factor of 600,000, which is more than one to two orders of magnitude higher than any previously reported, has been realized
Three-Dimensional Nanocrystal Superlattices Grown in Nanoliter Microfluidic Plugs (2011)

We studied the self-assembly of inorganic nanocrystals (NCs) confined inside nanoliter droplets (plugs) into long-range ordered superlattices. We showed that a capillary microfluidic platform can be used for the optimization of growth conditions for NC superlattices and can provide insights into the kinetics of the NC assembly process. The utility of our approach was demonstrated by growing large (up to 200 μm) three-dimensional (3D) superlattices of various NCs, including Au, PbS, CdSe, and CoFe(2)O(4). We also showed that it is possible to grow 3D binary nanoparticle superlattices in the microfluidic plugs.
ChemInform Abstract: N‐p‐Toluenesulfonylpyrroles from 1,3‐Dienes. (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.