gebhart/patrepeval huggingface dataset:
Efficient Clinical Scale Gene Modification via Zinc Finger Nuclease–Targeted Disruption of the HIV Co-receptor CCR5 (2013)

Since HIV requires CD4 and a co-receptor, most commonly C-C chemokine receptor 5 (CCR5), for cellular entry, targeting CCR5 expression is an attractive approach for therapy of HIV infection. Treatment of CD4(+) T cells with zinc-finger protein nucleases (ZFNs) specifically disrupting chemokine receptor CCR5 coding sequences induces resistance to HIV infection in vitro and in vivo. A chimeric Ad5/F35 adenoviral vector encoding CCR5-ZFNs permitted efficient delivery and transient expression following anti-CD3/anti-CD28 costimulation of T lymphocytes. We present data showing CD3/CD28 costimulation substantially improved transduction efficiency over reported methods for Ad5/F35 transduction of T lymphocytes. Modifications to the laboratory scale process, incorporating clinically compatible reagents and methods, resulted in a robust ex vivo manufacturing process capable of generating >10(10) CCR5 gene-edited CD4+ T cells from healthy and HIV+ donors. CD4+ T-cell phenotype, cytokine production, and repertoire were comparable between ZFN-modified and control cells. Following consultation with regulatory authorities, we conducted in vivo toxicity studies that showed no detectable ZFN-specific toxicity or T-cell transformation. Based on these findings, we initiated a clinical trial testing the safety and feasibility of CCR5 gene-edited CD4+ T-cell transfer in study subjects with HIV-1 infection.
Neumonitis por hipersensibilidad en la ciudad de México (2000)

The NE southernmost and SE northernmost areas were associated with HP. The cause of HP may not be geographical; a garbage dump used to be located in this area, suggesting that exposure to organic particles might contribute to the development of HP in susceptible individuals.
Eugenol and isoeugenol, characteristic aromatic constituents of spices, are biosynthesized via reduction of a coniferyl alcohol ester (2006)

Phenylpropenes such as chavicol, t-anol, eugenol, and isoeugenol are produced by plants as defense compounds against animals and microorganisms and as floral attractants of pollinators. Moreover, humans have used phenylpropenes since antiquity for food preservation and flavoring and as medicinal agents. Previous research suggested that the phenylpropenes are synthesized in plants from substituted phenylpropenols, although the identity of the enzymes and the nature of the reaction mechanism involved in this transformation have remained obscure. We show here that glandular trichomes of sweet basil (Ocimum basilicum), which synthesize and accumulate phenylpropenes, possess an enzyme that can use coniferyl acetate and NADPH to form eugenol. Petunia (Petunia hybrida cv. Mitchell) flowers, which emit large amounts of isoeugenol, possess an enzyme homologous to the basil eugenol-forming enzyme that also uses coniferyl acetate and NADPH as substrates but catalyzes the formation of isoeugenol. The basil and petunia phenylpropene-forming enzymes belong to a structural family of NADPH-dependent reductases that also includes pinoresinol-lariciresinol reductase, isoflavone reductase, and phenylcoumaran benzylic ether reductase.
Novel concepts for OLED lighting (2009)

Starting from a lab-curiosity, organic light emitting diodes have matured into a promising technology that has entered commercial markets. In particular for lighting applications, OLEDs can take advantage of their outstanding properties such as a high luminous efficacy, good color quality, and new design possibilities such as illumination by at light sources. In this contribution, new results on two approaches for highly efficient white OLEDs are presented: the all-phosphorescent concept and the triplet-harvesting approach.
Inhibition of the Phosphatidylinositol 3-Kinase/Akt Pathway by Inositol Pentakisphosphate Results in Antiangiogenic and Antitumor Effects (2005)

The purpose of this study was to investigate the antiangiogenic and in vivo properties of the recently identified phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor Inositol(1,3,4,5,6) pentakisphosphate [Ins(1,3,4,5,6)P5]. Because activation of the PI3K/Akt pathway is a crucial step in some of the events leading to angiogenesis, the effect of Ins(1,3,4,5,6)P5 on basic fibroblast growth factor (FGF-2)-induced Akt phosphorylation, cell survival, motility, and tubulogenesis in vitro was tested in human umbilical vein endothelial cells (HUVEC). The effect of Ins(1,3,4,5,6)P5 on FGF-2-induced angiogenesis in vivo was evaluated using s.c. implanted Matrigel in mice. In addition, the effect of Ins(1,3,4,5,6)P5 on growth of ovarian carcinoma SKOV-3 xenograft was tested. Here, we show that FGF-2 induces Akt phosphorylation in HUVEC resulting in antiapoptotic effect in serum-deprived cells and increase in cellular motility. Ins(1,3,4,5,6)P5 blocks FGF-2-mediated Akt phosphorylation and inhibits both survival and migration in HUVEC. Moreover, Ins(1,3,4,5,6)P5 inhibits the FGF-2-mediated capillary tube formation of HUVEC plated on Matrigel and the FGF-2-induced angiogenic reaction in BALB/c mice. Finally, Ins(1,3,4,5,6)P5 blocks the s.c. growth of SKOV-3 xenografted in nude mice to the same extent than cisplatin and it completely inhibits Akt phosphorylation in vivo. These data definitively identify the Akt inhibitor Ins(1,3,4,5,6)P5 as a specific antiangiogenic and antitumor factor. Inappropriate activation of the PI3K/Akt pathway has been linked to the development of several diseases, including cancer, making this pathway an attractive target for therapeutic strategies. In this respect, Ins(1,3,4,5,6)P5, a water-soluble, natural compound with specific proapoptotic and antiangiogenic properties, might result in successful anticancer therapeutic strategies.
Flexible, aqueous-electrolyte supercapacitors based on water-processable dioxythiophene polymer/carbon nanotube textile electrodes (2017)

Water soluble-solvent resistant approach for aqueous supercapacitors.
Complementary in-vivo measurements for human body communication (2017)

The actual way of living is characterized by a large use of connected terminals and devices. This connectivity needs permanent intercommunication between terminals and requires miniaturization, power management, and intelligence. In this context, Human Body Communication (HBC) is an emerging and promising communication technique of Body Area Network (BAN) which enshrines these requirements. HBC is a non-radio frequency technique which uses the human body as a communication channel. This communication technique is in full development. However, it is controversial without consensus in terms of the propagation mechanism and characteristics even the large number of research and academic reports. This work joins the efforts to characterize the channel and for a better understanding of the communication through the human body for both galvanic and capacitive coupling. The originality in this paper is to bring up the HBC coupling, from a new point of view, by proposing in vivo measurements. In addition to the usual parameters (channel length for example), we aim to discuss the effect of the electrical contact impedance as a function of the applied force and contact gel, and the distance between the electrodes and the body.
A Physically Reconfigurable Origami Reflectarray Based on the Augmented Square Twist Pattern (2021)

This paper proposes a novel mechanically frequency reconfigurable high-gain Reflectarray Antenna (RA) design, which is based on the Augmented Square Twist (AST) origami folding pattern. The RA was designed to operate at two operating frequencies, 20 GHz (lower band) and 40 GHz (upper band) in its unfolded and folded states, respectively. The main beam is directed along φ = 90°, θ = 30° at the lower band and φ = 90°, θ = 20° at the upper band. The RA was excited by a 15 dBi linearly polarized standard gain horn antenna positioned at a focal distance of 9.6λ with a 20° offset angle. The proposed origami RA achieved a gain of 27.0 dBi and 28.6 dBi at its unfolded and folded states, respectively.
The Spectacle of Sunday Delivery (2022)

Sunday papers regularly illustrated features about their own printing and circulation. Presented as a modern spectacle, the story of delivering the paper was supported by a complex system of circulation. The high-speed cylinder printing press was an assembly line for mass reproduction. Pulitzer's New York World pressroom had a viewing gallery for all to see the paper in production, an important parallel to its slogan, “circulation books open to all.” Other papers followed suit. Mass delivery was likewise profiled with sensational self-promotion, although the semblance of local competition over circulation masked tight monopoly control in distribution. The American News Company had a throttle on national newspaper circulation, controlling many urban carrier routes, sales aboard trains, and wholesale distribution of out-of-town papers, books and magazines. City delivery relied on fleets of wagons and trucks; the regional fast train delivered Sunday papers beyond city limits. But newsboys were the public face of these continental networks of circulation. Despite newsboys' sentimental favor, the push for technologies led to coin-operated news boxes, at first called “automatic newsboys.” The fascination with newspaper delivery reminded readers that getting physical copies of the paper into their homes required conquering the limits of time and space.
Performance of enzymatic wheat gluten hydrolysis in batch and continuous processes using Flavourzyme (2014)

The aim of this study was to investigate the process performance of wheat gluten hydrolysis with Flavourzyme in the conventional batch and in an enzyme membrane reactor system. The release of amino acids and peptides from wheat gluten using Flavourzyme in a batch process (T 50 °C, pH 5) is limited due to product inhibition. Investigation of Flavourzyme inhibition kinetics by l-amino acids revealed that the strongest inhibition was observed by l-cysteine. Thus, application of an enzyme membrane reactor with continuous product removal and substrate and enzyme retention was assessed. The highest productivity in the enzyme membrane reactor system was found using a 10 kDa molecular weight cut-off polyethersulfone membrane. This resulted in an increased product enzyme ratio from 2.1 mg product/nkat in the conventional batch process to 4.9 mg product/nkat with the enzyme membrane reactor after 20 h. The enzyme membrane reactor retained 80% of the initial space-time yield (STYinit 5 g/L/h) after nine days.
Internal Cell Resistance as the Origin of Abrupt Reset Behavior in HfO2-Based Devices Determined from Current Compliance Series (2016)

The resistive switching behavior in different HfO2/TiO2 nano crossbar structures of 100 x 100 nm² size is analyzed by means of DC voltage sweeps. The devices fabricated from 3 nm thin ALD layers of HfO2 and TiO2 sandwiched between Pt and Hf or Ti electrodes show VCM-type bipolar resistive switching after electroforming. For increased compliance current (cc) during set from 50 µA to 800 µA, the set current runs into self- limitation while the reset behavior changes from gradual to abrupt. A model is defined with an internal resistance being in series with the local resistive switch. A recursive algorithm is applied to the cc series for calculation of the series resistor and evaluation of the intrinsic switching characteristic of HfO2-based cells. The intrinsic LRS turns out to be current compliance controlled and to follow the universal switching rule. Supported by compact modelling, we show that an abrupt reset behavior might arise even for materials with a gradual intrinsic reset characteristic in consequence of an internal series resistor.
Development of Polyvinyl Alcohol-Hydrogel (PVA-H) Shields with a High Water Content for Tendon Injury Repair (2001)

The main problem in tendon repair is adhesion formation between the tendon and surrounding tissue. To prevent this, we have developed adhesion preventive shields using polyvinyl alcohol hydrogel (PVA-H) with 90% water content. This implant experiment used the deep flexor tendon of the 3rd toe of the domestic fowl. Injured tendons shielded with PVA-H healed within about 3 weeks without adhesion to the surrounding tissues. Neither breakage of the PVA-H shield itself nor infection or degeneration in the surrounding tissue was observed. These results show that tendon is capable of intrinsic repair, and was able to regenerate using synovial nutrition through the PVA-H. The high water content of PVA-H may be clinically useful and applicable to adhesion preventive shields for tendon repair.
A Practical Synthesis of α‐Aryl Methyl Ketones via a Transition‐Metal‐Free Meerwein Arylation. (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Discovery of N2-(4-Amino-cyclohexyl)-9-cyclopentyl-N6-(4-morpholin-4-ylmethyl-phenyl)-9H-purine-2,6-diamine as a Potent FLT3 Kinase Inhibitor for Acute Myeloid Leukemia with FLT3 Mutations (2018)

FLT3 tyrosine kinase is a potential drug target in acute myeloid leukemia (AML) because patients with FLT3-ITD mutations respond poorly to standard cytotoxic agents and there is a clear link between the disease and the oncogenic properties of FLT3. We present novel 2,6,9-trisubstituted purine derivatives with potent FLT3 inhibitory activity. The lead compound 7d displays nanomolar activity in biochemical assays and selectively blocks proliferation of AML cell lines harboring FLT3-ITD mutations, whereas other transformed and normal human cells are several orders of magnitude less sensitive. The MV4-11 cells treated with 7d suppressed the phosphorylation of FLT3 and its downstream signaling pathways, with subsequent G1 cell cycle arrest and apoptosis. Additionally, a single dose of 7d in mice with subcutaneous MV4-11 xenografts caused sustained inhibition of FLT3 and STAT5 phosphorylation over 48 h, in contrast to the shorter effect observed after administration of the reference FLT3 inhibitor quizartinib.
A Broad Set of Chromatin Factors Influences Splicing (2016)

Several studies propose an influence of chromatin on pre-mRNA splicing, but it is still unclear how widespread and how direct this phenomenon is. We find here that when assembled in vivo, the U2 snRNP co-purifies with a subset of chromatin-proteins, including histones and remodeling complexes like SWI/SNF. Yet, an unbiased RNAi screen revealed that the outcome of splicing is influenced by a much larger variety of chromatin factors not all associating with the spliceosome. The availability of this broad range of chromatin factors impacting splicing further unveiled their very context specific effect, resulting in either inclusion or skipping, depending on the exon under scrutiny. Finally, a direct assessment of the impact of chromatin on splicing using an in vitro co-transcriptional splicing assay with pre-mRNAs transcribed from a nucleosomal template, demonstrated that chromatin impacts nascent pre-mRNP in their competence for splicing. Altogether, our data show that numerous chromatin factors associated or not with the spliceosome can affect the outcome of splicing, possibly as a function of the local chromatin environment that by default interferes with the efficiency of splicing.
8-Gbps-per-channel radiation-tolerant VCSEL drivers for the LHC detector upgrade (2015)

We present ASIC designs of VCSEL drivers for a single VCSEL (LOCld1), two individual VCSELs (LOCld2) and a four-channel VCSEL array (LOCld4). This work is for new detector readout systems needed in the Large Hadron Collider upgrade program. All ASICs are fabricated in a commercial 0.25-μ m Silicon-on-Sapphire CMOS technology. LOCld1 and LOCld2 have passed the 8-Gbps and 10-Gbps eye mask tests. Operating at 8 Gbps data rate, the measured total jitter of LOCld1 and LOCld2 is less than 30 ps, and the power comsuption is about 200 mW per channel with 6-mA bias current and 6.4-mA modulation current. The radiation tolerance of LOCld1 has been qualified with x-ray and high-energy neutron beam test.
A flexible elastic control plane for private clouds (2013)

While public cloud computing platforms have become popular in recent years, private clouds---operated by enterprises for their internal use---have also begun gaining traction. The configuration and continuous tuning of a private cloud to meet user demands is a complex task. While private cloud management frameworks provide a number of flexible configuration options for this purpose, they leave it to the administrator to determine how to best configure and tune the cloud platform for local needs. In this paper, we argue for an adaptive control plane for private clouds that simplifies the tasks of configuring and operating a private cloud such that each control plane service is adaptive to the workload seen due to end-user requests. We present a logistic regression model to automate the provisioning and dynamic reconfiguration of control plane services in a private cloud. We implement our approach for two control plane services---monitoring and messaging---for OpenStack-based private clouds. Our experimental results on a laboratory private cloud testbed and using public cloud workloads demonstrates the ability of our approach to provision and adapt such services from very small to very large private cloud configurations.
Delineate the role of plant fuorocoumarin derivatives on hepatocarcinoma, DNA Topoisomerase I and mitotic cell division (2017)

Furocoumarins are produced by plant members via the phenylpropanoid pathway. Natural and chemically synthesized furocoumarins exhibit promising anticancer activity. This work aims to increase our understanding of the mechanism by which these compounds can suppress cancer. Therefore, two medicinal plants, Apium graveolense & Ruta graveolense and 10 synthesized furocoumarin derivative compounds were tested against hepatocellular carcinoma cell line (HepG-2). Our results indicated that compound 9 exhibited the highest cytotoxic activity (IC 50 =11.9 M). Other compounds exerted less cytotoxic activity ranging from IC 50 =28.38 M for compound one to IC 50 =67.10 M in case of compound 5. The natural crude extracts exhibited the lowest cytotoxic activity on HepG-2 with values of IC 50 =312.4 and 445.7 M for Ruta graveolens and Apium graveolens, respectively. Compound 9 was found to inhibit topoisomerase I enzyme, based on the molecular docking analysis, and significantly suppressed the mitotic cell division in the meristematic cells of pea (Pisum sativum) root tips.
724. A Comprehensive Map of CNS Transduction by Eight Recombinant Adeno-Associated Virus Serotypes upon Cerebrospinal Fluid Administration in Pigs (2016)

Gene transfer of recombinant adeno-associated virus (rAAVs) holds promises to treat neurological disorders. Studies on different recombinant vector serotypes and modes of delivery to the central nervous system (CNS) showed that the combination of both rAAV serotype used and delivery routes play a key role in CNS transduction properties and thus in disease phenotype rescue outcome. However, one of the major hurdles to developing an effective clinical protocol for neurological disorders is the efficiency of vectors to reach the specific cell types in disease-specific CNS subdomains. An attractive vehicle to reach the CNS is represented by the cerebral spinal fluid (CSF) and different injection techniques (intrathecal cisterna magna, intra-ventricular and intrathecal lumbar injections) actually allow the central nervous system targeting by using the CSF flux. Along these years different AAV serotypes have been tested by intrathecal injections and some of these displayed a very specific tropism for the central nervous system. However, a quantitative and qualitative analysis of transduction patterns of the most promising rAAV serotypes for brain targeting in large animal models is missing. Here, we characterize distribution, transduction efficiency and cellular targeting of rAAV serotypes 1, 2, 5, 7, 9, rh.10, rh.39 and rh.43 delivered into the cisterna magna of wild type pigs. Despite the rAAV9 showed the highest transduction efficiency and the widest distribution capability among the vectors tested, the other serotypes showed a specific distribution pattern from the rostral to the caudal part of the CNS. rAAV9 robustly transduced both glia and neurons, including the motor neurons of the spinal cord. Relevant cell transduction specificity of the glia was observed after rAAV1 and rAAV7 delivery. rAAV7 also displayed a specific tropism to Purkinje cells. Evaluation of biochemical and hematological markers suggested that all rAAV serotypes tested were well tolerated. This study provides a comprehensive CNS transduction map in a useful pre-clinical large animal model enabling the selection of potentially clinically transferable rAAV serotypes based on disease specificity. Therefore, our data are instrumental for the clinical evaluation of these rAAV vectors in human neurodegenerative diseases.
Acenaphthylene‐Fused Cyclo[8]pyrroles with Intense Near‐IR‐Region Absorption Bands (2013)

An acenaphthylene-fused cyclo[8]pyrrole was synthesized by using an oxidative coupling reaction of the corresponding 2,2'-bipyrrole. Two conformational isomers 1 a and 1 b were isolated, and their molecular structures were elucidated by X-ray crystallographic studies. The less-polar and lower-symmetry 1 b isomer can be converted into the 1 a isomer through a thermal ring flip. Application of the perimeter model developed by Michl to magnetic circular dichroism spectroscopic data and theoretical calculations demonstrate that there is a marked redshift of the near-IR absorption maxima relative to cyclo[8]isoindole because there is a significant stabilization of the LUMO due to the differing effects of a fused ring expansion with acenaphthylene and benzene moieties on the frontier π molecular orbitals.
Exploration of tumour-infiltrating lymphocytes as a predictive biomarker for adjuvant endocrine therapy in early breast cancer (2018)

This study is the first to propose the number of CD8-positive TILs as potential predictive markers for endocrine therapy, with the low presence of CD8-positive TILs associated to benefit for exemestane-inclusive therapy. However, treatment-by-marker interactions were only significant in one cohort, indicating the need for further validation.
Fabrication of light-induced self-written waveguides with a W-shaped refractive index profile (2005)

This paper proposes a novel technique for automatic waveguide formation by means of the self-trapping effect of optical fiber irradiation into a photopolymerizing resin. We investigate experimentally the phenomenon of thin cladding layer formation surrounding the core following the core creation. In the proposed technique, a counterdiffusion effect involving polymerizing monomers via the core/cladding interface causes enrichment of a low refractive index monomer, and a resultant "W-shaped" refractive index profile is realized. The measured propagation loss of the fabricated waveguide is 1.7 dB/cm at 0.68 /spl mu/m wavelength. This technology is appropriate for the fabrication of large-core optical waveguides of greater than 0.5 mm in diameter and is useful for automating the optical fiber connection and packaging process by virtue of being an all-passive optically induced process.