gebhart/patrepeval huggingface dataset:
Secure Session Layer Services (2017)

Each I2NSF agent and I2NSF client needs to provide application level
support for management traffic during periods of DDoS and network
security attacks to deal with congestion (burst and/or continuous),
high error rates and packet loss due to the attacks, and the inability
to utilize a transport protocol (E.g. TCP) due to a specific protocol
attack. This application level support needs to be able to select the
key management system and provide of data (in order to fit
in reduced effective MTUs), compression of data (in order to fit into
reduced bandwidth), small security envelope )in order to maximize room
for management payload), and fragmentation and reassembly at the
application layer for those protocols which do not support
fragmentation/reassembly (E.g. UDP or SMS). These Secure Session Layer
services may only be deployed on a the few management ports which need
to be protected during DDoS attacks or network security attacks, and
turned on/off based on need. The application and the network
instrumentation need to cooperate to determine if this service needs
to be turned on or off. This draft specifies a security session layer
services(SSLs) which provide these features in terms of APIs (North-
Bound and South-bound), and the component features (interface to key
management systems, data compression, chunking of data, secure session
envelope (SSE) to send data, and fragmentation and reassembly, and
ability to detect existence of attack).
Development of Large Size CPU Package Structure Using Embedded Thin Film Capacitor Package Substrate (2017)

This paper reports on a large-size CPU package for UNIX servers which employs embedded thin film capacitor layers. The substrate of this package has two thin film capacitor layers in the surface of the core layer, which has a capacitance of 25 uF in total. In order to adopt this package substrate, we confirmed the effect of the thin film capacitor layers on the package assembly process. We actually measured mechanical characteristics and the coefficient of thermal expansion (CTE), and confirmed that we can use it like conventional package substrates. This package has passed the preprocessing and subsequent environmental test on JEDEC Level 4, and we think that a high-quality package has been developed this time. Fujitsu adopted a low melting point solder BGA from a previous-generation package. Its composition is Sn-57Bi-1.0Ag. However, this solder has an issue with deformation after a low-temperature reflow profile for the solder ball attachment process on the package. In this work, we were able to find the cause of this phenomenon, and by changing the Ag content from 1.0% to 0.4%, we achieved a complete low-temperature assembly process. In addition, BGA connection reliability was confirmed.
Detection of biomarkers using recombinant antibodies coupled to nanostructured platforms (2012)

The utility of biomarker detection in tomorrow's personalized health care field will mean early and accurate diagnosis of many types of human physiological conditions and diseases. In the search for biomarkers, recombinant affinity reagents can be generated to candidate proteins or post-translational modifications that differ qualitatively or quantitatively between normal and diseased tissues. The use of display technologies, such as phagedisplay, allows for manageable selection and optimization of affinity reagents for use in biomarker detection. Here we review the use of recombinant antibody fragments, such as scFvs and Fabs, which can be affinity-selected from phagedisplay libraries, to bind with both high specificity and affinity to biomarkers of cancer, such as Human Epidermal growth factor Receptor 2 (HER2) and Carcinoembryonic antigen (CEA). We discuss how these recombinant antibodies can be fabricated into nanostructures, such as carbon nanotubes, nanowires, and quantum dots, for the purpose of enhancing detection of biomarkers at low concentrations (pg/mL) within complex mixtures such as serum or tissue extracts. Other sensing technologies, which take advantage of 'Surface Enhanced Raman Scattering' (gold nanoshells), frequency changes in piezoelectric crystals (quartz crystal microbalance), or electrical current generation and sensing during electrochemical reactions (electrochemical detection), can effectively provide multiplexed platforms for detection of cancer and injury biomarkers. Such devices may soon replace the traditional time consuming ELISAs and Western blots, and deliver rapid, point-of-care diagnostics to market.
First-in-Class Chemical Probes against Poly(ADP-ribose) Glycohydrolase (PARG) Inhibit DNA Repair with Differential Pharmacology to Olaparib (2016)

The enzyme poly(ADP-ribose) glycohydrolase (PARG) performs a critical role in the repair of DNA single strand breaks (SSBs). However, a detailed understanding of its mechanism of action has been hampered by a lack of credible, cell-active chemical probes. Herein, we demonstrate inhibition of PARG with a small molecule, leading to poly(ADP-ribose) (PAR) chain persistence in intact cells. Moreover, we describe two advanced, and chemically distinct, cell-active tool compounds with convincing on-target pharmacology and selectivity. Using one of these tool compounds, we demonstrate pharmacology consistent with PARG inhibition. Further, while the roles of PARG and poly(ADP-ribose) polymerase (PARP) are closely intertwined, we demonstrate that the pharmacology of a PARG inhibitor differs from that observed with the more thoroughly studied PARP inhibitor olaparib. We believe that these tools will facilitate a wider understanding of this important component of DNA repair and may enable the development of novel therapeutic agents exploiting the critical dependence of tumors on the DNA damage response (DDR).
Method for measurig Glossiness of Spherical Specimens Employing The Operation Resembling Human Visual Function (1991)

Although we reported some methods for measuring the glossiness of spherical specimens, they had such a problem that the glossiness-errors were easily caused by the deviation of the specimen from normal holding position. In order to reduce the glossiness-errors, the following technique was attempted in this paper. The intensity-distribution of the light reflected from the specimen is measured by the CCD line-sensor and the acquired distribution data are filtered with a spacial weighting function resembling the human visual function, using a personal-computer. From the computed results, a new glossiness was defined for spherical spesimen. As the results, comparing to 30% errors in the old glossiness, we could reduce the errors to less then 12% in the new glossiness for about 1mm deviation of the specimen with a 8mm diameter.
The role of cytoplasmic polyadenylation element sequence on mRNA abundance during porcine embryogenesis and parthenogenetic development (2010)

Development of a porcine germinal vesicle oocyte (GVO) to a 4-cell stage embryo occurs during a transcriptionally silent period when the oocyte/embryo relies on maternally derived mRNA to encode proteins required for development. Regulation of translation and degradation of maternal mRNA is thought to be partially dependent on cytoplasmic polyadenylation elements (CPEs) within the 3' untranslated region of the mRNA. The goal of this study was to determine how CPE sites affect the abundance of mRNA during embryogenesis and parthenogenetic development, and how cordycepin, a 3'-deooxyadenosine (3'-dA) that inhibits poly-(A) tail formation, affects polyadenylation and transcript abundance. Expressed sequence tags (ESTs) from oocytes and 4-cell stage embryos were scanned for the presence of five consensus CPEs. Nineteen different transcripts containing one to three CPEs were selected, and transcript abundance was determined in GVO, metaphase II, 2-cell, and 4-cell stage embryos via real-time PCR while the length of the poly-(A) tail was determined by using a poly-(A) tail PCR (PAT) assays. Real-time PCR was performed on three biological and two technical replicates for each stage. There was no direct correlation between poly-(A) tail length, transcript abundance, and the CPE. In addition, the abundance of some messages was different if the embryo was the result of parthenogenetic activation. Cordycepin prevented polyadenylation of transcripts that normally undergo noticeable polyadenylation. Thus, CPEs may not be the only factors that regulate message stability, and parthenogenetic activation does not result in changes in transcript abundance that mimic in vitro fertilization.
Investigation of photoexcitations of conjugated polymer/fullerene composites embedded in conventional polymers (1998)

A promising approach to improve the processability of semiconducting polymers is their incorporation into host matrices formed by conventional polymers such as polyethylene (PE) or polystyrene (PS). We have characterized the linear optical properties of several guest–host systems by absorption and luminescence measurements and probed the excited states by photoinduced absorption measurements (PIA) and light induced electron spin resonance (LESR). The interesting photophysics of conjugated polymer/fullerene donor–acceptor system, showing an ultrafast photoinduced electron transfer and a metastable charge separation in the pristine state, has been investigated in such composites where the photoactive components are further embedded into a conventional polymer matrix. The composition of the blend and the relative concentration of the components are found to strongly influence the photoinduced interaction between the conjugated polymer and the fullerenes (C60 and functionalized fullerenes). Photoinduced electron transfer between a soluble polyphenylenevinylene (PPV) derivative and C60 is observed in a system with PS as host when the concentration of the both electroactive components is 33%. In diluted composites with PS as matrix we find strong luminescence quenching of the PPV derivative but no electron transfer upon adding C60. Dominant photoexcitations in these PS systems are triplet states as follows from intensity dependencies and lifetime measurements. In diluted systems with PE as matrix neither charge transfer nor luminescence quenching has been observed.
How T cells spot tumour cells (2017)

Immunotherapy can reawaken T cells to destroy tumour cells. Modelling of tumour and T-cell interactions suggests why certain tumour cells are targeted and improves predictions of immunotherapy outcome.
Development of an HTRF Assay for the Detection and Characterization of Inhibitors of Catechol-O-Methyltransferase (2015)

Catechol-O-methyltransferase (COMT) plays an important role in the deactivation of catecholamine neurotransmitters and hormones. Inhibitors of COMT, such as tolcapone and entacapone, are used clinically in the treatment of Parkinson's disease. Discovery of novel inhibitors has been hampered by a lack of suitable assays for high-throughput screening (HTS). Although assays using esculetin have been developed, these are affected by fluorescence, a common property of catechol-type compounds. We have therefore evaluated a new homogenous time-resolved fluorescence (HTRF)-based assay from CisBio (Codolet, France), which measures the production of S-adenosyl-L-homocysteine (SAH). The assay has been run in both HTS and medium-throughput screening (MTS) modes. The assay was established using membranes expressing human membrane-bound COMT and was optimized for protein and time to give an acceptable signal window, good potency for tolcapone, and a high degree of translation between data in fluorescence ratio and data in terms of [SAH] produced. pIC50 values for the hits from the HTS mode were determined in the MTS mode. The assay also proved suitable for kinetic studies such as Km,app determination.
Vascular Targeting of Nanocarriers: Perplexing Aspects of the Seemingly Straightforward Paradigm (2014)

Targeted nanomedicine holds promise to find clinical use in many medical areas. Endothelial cells that line the luminal surface of blood vessels represent a key target for treatment of inflammation, ischemia, thrombosis, stroke, and other neurological, cardiovascular, pulmonary, and oncological conditions. In other cases, the endothelium is a barrier for tissue penetration or a victim of adverse effects. Several endothelial surface markers including peptidases (e.g., ACE, APP, and APN) and adhesion molecules (e.g., ICAM-1 and PECAM) have been identified as key targets. Binding of nanocarriers to these molecules enables drug targeting and subsequent penetration into or across the endothelium, offering therapeutic effects that are unattainable by their nontargeted counterparts. We analyze diverse aspects of endothelial nanomedicine including (i) circulation and targeting of carriers with diverse geometries, (ii) multivalent interactions of carrier with endothelium, (iii) anchoring to multiple determinants, (iv) accessibility of binding sites and cellular response to their engagement, (v) role of cell phenotype and microenvironment in targeting, (vi) optimization of targeting by lowering carrier avidity, (vii) endocytosis of multivalent carriers via molecules not implicated in internalization of their ligands, and (viii) modulation of cellular uptake and trafficking by selection of specific epitopes on the target determinant, carrier geometry, and hydrodynamic factors. Refinement of these aspects and improving our understanding of vascular biology and pathology is likely to enable the clinical translation of vascular endothelial targeting of nanocarriers.
Selective cellular delivery of self-assembled quantum dot-peptide bioconjugates (2007)

We demonstrate the selective delivery of self-assembled luminescent semiconductor quantum dot (QD)-peptide bioconjugates into several eukaryotic cell lines. A 23-mer hetero-bifunctional peptide bearing a positively-charged oligoarginine domain and a terminal polyhistidine tract was synthesized and used to mediate the cellular internalization of the QD-bioconjugates. The polyhistidine tract allows the peptide to self-assemble onto the QD surface via metal-ion coordination while the oligoarginine domain mediates the specific uptake of the QD-bioconjugates via electrostatic interactions with cell surface receptors. In both HEK 293T/17 and COS-1 cells, this peptide-mediated delivery is concentration-dependent in terms of both the QD concentration and the peptide:QD ratio. Intracellularly, the QD signal is punctate in appearance and some, but not all, of the QDs are located within recycling endosomes as evidenced by their colocalization with transferrin. In both cell lines, the QD-bioconjugates elicit minimal cytotoxicity within the timeframe required for adequate cellular uptake. The specificity of this delivery strategy is demonstrated by performing a multicolor QD labeling, wherein the presence or absence of the peptide on the QD surface controls cellular uptake.
ChemInform Abstract: Macrocycles by Ring‐Closing‐Metathesis. Part 11. Syntheses of (R)‐(+)‐Lasiodiplodin, Zeranol and Truncated Salicylihalamides. (1999)

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.
Lensless imaging strategies for micro-particles and bacterial colonies counting (2019)

International audience
Percutaneous biliary drainage: clinical trial of analgesia with interpleural block. (1997)

Interpleural block was effective in decreasing pain and opioid requirements during and after percutaneous biliary drainage and did not compromise the cardiopulmonary status of the patient. However, the rate of pneumothorax was higher than previously reported.
AB195. 194. Clinicopathological features and management of metaplastic breast cancer: a single institution experience (2018)

Background: Metaplastic breast carcinoma (MBC) is a rare heterogenous histopathological subtype of primary breast carcinoma arising from both epithelial and mesenchymal elements. It accounts for <1% of all breast malignancies. MBC has poor outcomes relative to invasive ductal carcinoma and the optimal treatment approach remains largely unknown. We aimed to examine the clinicopathological features and management of patients diagnosed with MBC in our institution over a 10-year period. Methods: All patients diagnosed with MBC between 2007 and 2017 were identified from the histopathology database. Data regarding patient demographics, mode of presentation, tumour characteristics, treatment modalities and presence of recurrence or metastatic disease were reviewed and analysed. Results: There were 21 patients diagnosed with MBC; 14 (67%) patients presented clinically while 7 (33%) were detected radiologically. The two most common histological subtypes were squamous (19%) and chondroid differentiation (19%). Most tumours were grade 3 (67%) and almost exclusively triple-negative (95%). Only 4 (19%) patients had nodal involvement. Fifteen (71%) patients had primary surgery while 4 (19%) had neoadjuvant chemotherapy with further surgery. In terms of adjuvant treatment, 6 (28%) patients received chemotherapy and 14 (67%) had radiotherapy. Four (19%) patients developed metastatic disease within 5 years of diagnosis. Conclusions: Our institutional experience in treating MBC demonstrates that these tumours are high grade with an associated high relapse rate. Further studies on the molecular characteristics of MBC may help us to identify effective therapies in the treatment of these patients.
Synthesis of novel and potent vorapaxar analogues (2016)

Vorapaxar is a first-in-class PAR-1 antagonistic drug based on the ent-himbacine scaffold. Detailed in this article are enantioselective and racemic routes to various novel vorapaxar analogues. Biological testing revealed these compounds to have moderate to excellent potencies against PAR-1 with the most potent analogue demonstrating an IC50 of 27 nM.
Neurodegenerative Diseases as Protein Misfolding Disorders (2016)

Neurodegenerative diseases (NDDs) often represent disorders of protein folding. Rather than large aggregates, recent evidence suggests that soluble oligomers of misfolded proteins are the most neurotoxic species. Emerging evidence points to small, soluble oligomers of misfolded proteins as the cause of synaptic dysfunction and loss, the major pathological correlate to disease progression in many NDDs including Alzheimer’s disease. The protein quality control machinery of the cell, which includes molecular chaperones as found in the endoplasmic reticulum (ER), the ubiquitin-proteasome system (UPS), and various forms of autophagy, can counterbalance the accumulation of misfolded proteins to some extent. Their ability to eliminate the neurotoxic effects of misfolded proteins, however, declines with age. A plausible explanation for the age-dependent deterioration of the quality control machinery involves compromise of these systems by excessive generation of reactive oxygen species (ROS), such as superoxide anion (O2-), and reactive nitrogen species (RNS), such as nitric oxide (NO). The resulting redox stress contributes to the accumulation of misfolded proteins. Here, we focus on aberrantly increased generation of NO-related species since this process appears to accelerate the manifestation of key neuropathological features, including protein misfolding. We review the chemical mechanisms of posttranslational modification by RNS such as protein S-nitrosylation of critical cysteine thiol groups and nitration of tyrosine residues, showing how they contribute to the pathogenesis of NDDs.
Machine Protection Issues and Solutions for Linear Accelerator Complexes (2012)

The workshop “Machine Protection focusing on Linear Accelerator Complexes” was held from 6-8 June 2012 at CERN. This workshop brought together experts working on machine protection systems for accelerator facilities with high brilliance or large stored beam energies, with the main focus on linear accelerators and their injectors. An overview of the machine protection systems for several accelerators was given. Beam loss mechanisms and their detection were discussed. Mitigation of failures and protection systems were presented. This paper summarises the workshop and reviews the current state of the art in machine protection systems.
In vitro anti‐tumor activity of eosinophils from cancer patients treated with subcutaneous administration of interleukin 2. Role of interleukin 5 (1993)

Interleukin 2 (IL-2) administration is known to induce marked eosinophilia. To evaluate the potential role of eosinophils as anti-tumor effectors and to understand the direct or indirect effects of IL-2 on eosinophils, the physical and functional characteristics of eosinophils obtained during IL-2 therapy were compared with those of eosinophils obtained from the same patients before IL-2 administration, or from healthy donors. The treatment schedule consisted of subcutaneous (s.c.) injections of IL-2, and was performed in 7 patients with small-cell lung cancer (SCLC) in advanced stage. A marked increase of hypodense cells in peripheral blood was found to correlate with eosinophil activation in patients undergoing IL-2 therapy. Cytotoxic activity of eosinophils against allogeneic tumor cells (SCLC, K562 and melanoma lines), as assessed by direct and antibody (Ab)-dependent cellular cytotoxicity (ADCC), was markedly increased during IL-2 therapy. Conversely, eosinophils obtained before treatment, like those of healthy donors, lacked any activity against tumor cells. Sera from IL-2-treated, but not from untreated, patients, significantly improved the in vitro survival and anti-tumor cytotoxicity of eosinophils from healthy donors. Comparable effects were obtained with eosinophils cultured with interleukin 5 (IL-5), granulocyte-macrophage colony-stimulating factor (GM-CSF) and, to a lesser extent, by tumor necrosis factor-alpha (TNF alpha), while no direct activity was mediated by IL-2. A 91% inhibition of eosinophil ADCC was found after pre-incubation of the sera of IL-2-treated patients with anti-IL-5 but not with anti-GM-CSF or anti-TNF alpha Ab. IL-5 mRNA expression was detected in peripheral-blood lymphocytes (PBL) obtained 4 hr after IL-2 injection during the second and third week of IL-2 therapy. Phenotypic analysis of eosinophils from IL-2-treated patients showed enhanced expression of activation markers, including Fc gamma RII (CD32), HLA-DR, CR3 (CD11b) and CRI (CD35). These findings suggest that a significant cytotoxicity against tumor cells can be mediated by eosinophils after indirect, IL-5-mediated in vivo activation by IL-2, and that eosinophils may be involved in the anti-tumor response(s) induced in vivo by IL-2.
Coulomb blockade and transport spectroscopy in short Si:MOSFET (1999)

Abstract We report Coulomb oscillations in short (50 nm and 100 nm) and wide Silicon MOSFETs at very low temperature, when the source‐drain conductance is below the quantum e 2 / h . the geometry is dual of a wire, where such oscillations have been previously reported. Our observations show that the dominating best conducting channel is a localized state which can accomodate several electrons. This emphasizes that Coulomb blockade appears also at low temperature in a standart short and wide transistor‐like geometry, without intentional confinement, as far as the conductance is below the quantum. Analysis of the non‐linear transport permits to evaluate both the mean one electron spacing (few kelvins) and the Coulomb energy (few tens of kelvins). At finite transport voltage the contributions of excited states are observed. Comparing the 50 nm and 100 nm series, we find that the size of the impurity quantum dot roughly scales with the source‐drain distance.