gebhart/patrepeval huggingface dataset:
Allogenic T-Cells Targeting CD123 for Adoptive Immunotherapy of Acute Myeloid Leukemia (AML) (2014)

Abstract Adoptive immunotherapy using autologous T-cells endowed with chimeric antigen receptors (CARs) has emerged as a promising new approach to treating cancer. However, a limitation of this approach is that CAR T-cells must be generated on a bespoke basis. To overcome this limitation, we have developed an allogeneic based platform for large scale production of “off-the-shelf” CAR T-cells from unrelated 3rd party donors. This platform utilizes Transcription Activator-Like Effector Nuclease (TALENTM) gene editing technology to inactivate the TCRα constant (TRAC) gene, eliminating the potential for T-cells bearing alloreactive TCR’s to mediate Graft versus Host Disease (GvHD). We have previously demonstrated that editing of the TRAC gene can be achieved at high frequencies, obtaining up to 80% of TCRαβ negative cells. This allows us to efficiently produce TCR-deficient T-cells that have been shown to no longer mediate alloreactivity in a xeno-GvHD mouse model. Furthermore, the capacity to perform efficient multiplex genome editing using TALENTM offers the possibility of simultaneously rendering cells resistant to standard chemotherapy or to tumor evasion mechanisms. In this work we present the adaptation of this allogeneic platform to the production of T cells targeting CD123, the transmembrane alpha chain of the interleukin-3 receptor, which is expressed in tumor cells from the majority of patients with Acute Myeloid Leukemia (AML). In a first step, we have screened human primary T-cells harboring CARs with different antigen recognition domains in the context of multiple CAR architectures in order to identify candidates displaying specific activity against cell lines expressing variable levels of the CD123 antigen. To provide proof of concept for the general applicability of the allogeneic approach we have manufactured a TCR-deficient CD123 CAR T-cell (UCART123) and demonstrated that this product maintains a potent anti-tumoral activity in vitro. Experiments in an orthotopic AML mouse model using UCART123 cells are currently ongoing, in order to establish the absence of alloreactivity and the anti-tumoral activity in vivo. The ability to carry out large scale manufacturing of allogeneic, non alloreactive CD123 specific T Cells from a single healthy donor could thus offer the possibility of an off-the-shelf treatment that would be immediately available for administration to a large number of AML patients. Disclosures Galetto: Cellectis SA: Employment. Lebuhotel:Cellectis SA: Employment. Gouble:Cellectis SA: Employment. Schiffer-Mannioui:Cellectis SA: Employment. Smith:Cellectis SA: Employment.
Employing Arynes in Transition-Metal-Free Monoarylation of Aromatic Tertiary Amines (2013)

The highly monoselective N-arylation of aromatic tertiary amines using a transition-metal-free approach using arynes has been developed. The reaction afforded functionalized diaryl amines in moderate to excellent yield. High levels of functional group compatibility especially with halogen containing substrates, dyes and donor-acceptor systems, and high yields of products are the notable features of the present reaction.
Purification and characterization of morphinone reductase from <i>Pseudomonas putida</i> M10 (1994)

The NADH-dependent morphinone reductase from Pseudomonas putida M10 catalyses the reduction of morphinone and codeinone to hydromorphone and hydrocodone respectively. Morphinone reductase was purified from crude cell extracts to apparent homogeneity in a single affinity-chromatography step using Mimetic Yellow 2. The purified enzyme was a dimeric flavoprotein with two identical subunits of M(r) 41,100, binding non-covalently one molecule of FMN per subunit. The N-terminal sequence was PDTSFSNPGLFTPLQ. Morphinone reductase was active against morphinone, codeinone, neopinone and 2-cyclohexen-1-one, but not against morphine, codeine or isocodeine. The apparent Km values for codeinone and 2-cyclohexen-1-one were 0.26 mM and 5.5 mM respectively. The steroids progesterone and cortisone were potent competitive inhibitors; the apparent K1 for cortisone was 35 microM. The pH optimum for codeinone reduction was 8.0 in phosphate buffer. No reverse reaction could be detected, and NADPH could not be used as a reducing substrate in place of NADH. Morphinone reductase activity was strongly inhibited by 0.01 mM CuSO4 and p-hydroxymercuribenzoate, suggesting the presence of a vital thiol group. Steady-state kinetic studies suggested a Ping Pong (substituted enzyme) kinetic mechanism; however, product-inhibition patterns were inconsistent with a classical Ping Pong mechanism. Morphinone reductase may, like several other flavoprotein dehydrogenases, operate by a hybrid two-site Ping Pong mechanism.
<title>Novel condenser for EUV lithography ring-field projection optics</title> (1999)

A condenser for a ring-field extreme ultra-violet (EUV) projection lithography camera is presented. The condenser consists of a gently undulating mirror, that we refer to as a ripple plate, and which is illuminated by a collimated beam at grazing incidence. The light is incident along the ripples rather than across them, so that the incident beam is reflected onto a cone and subsequently focused onto the arc of the ring field. A quasi-stationary illumination is achieved, since any one field point receives light from points on the ripples, which are distributed throughout the condenser pupil. The design concept can easily be applied to illuminate projection cameras with various ring-field and numerical aperture specifications. Ray-tracing results are presented of a condenser for a 0.25 NA EUV projection camera.
Cyclometalated gold(iii) complexes with N-heterocyclic carbene ligands as topoisomerase I poisons (2010)

A panel of stable [Au(R-C--N--C)(N-heterocyclic carbene)](+) complexes displays prominent in vitro anticancer properties; [Au(C--N--C)(IMe)]CF(3)SO(3) (1, IMe = 1,3-dimethylimidazol-2-ylidene) significantly poisons topoisomerase I in vitro and suppresses tumor growth in nude mice model.
Determination of cerebrospinal fluid leakage by selective deletion of transferrin glycoform using an immunochromatographic assay (2019)

Cerebrospinal fluid (CSF) leakage can lead to brain and spine pathologies and there is an urgent need for a rapid diagnostic method for determining CSF leakage. Beta-2 transferrin (β2TF), asialotransferrin, is a specific CSF glycoprotein biomarker used to determine CSF leakage when distinguished from serum sialotransferrin (sTF). <b>Methods</b>: We detected β2TF using an immunochromatographic assay (ICA), which can be potentially developed as a point-of-care (POC) testing platform. Sialic acid-specific lectin selectively captures sTF in multiple deletion lines within an ICA test strip, enabling the detection of β2TF. A sample pre-treatment process efficiently captures excess sTF increasing sensitivity for CSF leakage detection. <b>Results</b>: An optimal cut-off value for determining the presence of CSF in test samples was obtained from receiver operating characteristic (ROC) analysis of the ratio of the test signal intensity and the deletion lines. On 47 clinical samples, ICA test strips discriminated CSF positive from negative samples with statistically significant (positive <i>versus</i> negative t-test; <i>P</i> =0.00027). Additional artificial positive samples, prepared by mixing CSF positive and negative clinical samples, were used as a further challenge. These positive samples were clearly discriminated from the negative samples (mixture <i>versus</i> negative t-test; <i>P</i> =0.00103) and CSF leakage was determined with 97.1% specificity and 96.2% sensitivity. <b>Conclusions</b>: ICA represents a promising approach for POC diagnosis of CSF leakage. While requiring 70 min assay time inconvenient for POC testing, our method was significantly shorter than conventional electrophoresis-based detection methods for β2TF.
Colloidal Crystallization Accomplished by Electrodeposition on Patterned Substrates (2005)

We report colloid crystal growth by using electrodeposition of charged polymer colloid particles on patterned conductive substrates. We used photolithography to create patterns with conductive grooves and dielectric ribs on indium-tin oxide surfaces. Two approaches were used to enhance long-range order in two‐dimensional colloid crystals grown on patterned surfaces: (i) patterning of substrates with features commensurate with several particle diameters and (ii) patterning of substrates with features commensurate with a single particle diameter. We demonstrate the effect of commensurability on colloid crystal growth and present the results of real‐time studies of colloid crystallization in constrained geometry during electrodeposition on patterned substrates.
A near infrared regression model for octane measurements in gasolines which contain MTBE (1990)

A 14-d short-term oral toxicity study in rats evaluated the safety of moringa isothiocyanate-1 (MIC-1)-enriched hydro-alcoholic moringa seeds extract (MSE). Rats (5 males/5 females per group) were gavaged daily for 14 d with the vehicle control or MSE, at 78 (low), 257 (mid-low), 772 (mid-high), or 2571 (high) mg/kg bw/d, standardized to MIC-1 (30, 100, 300, or 1000 mg/kg bw/d, respectively). Toxicological endpoints included body weight and weight gain, food consumption and feed efficiency, clinical observations, hematology, gross necropsy and histopathology, and relative organ weights. Mortality was only observed in the high dose group animals, both male and female, representing decreases in body weight/weight gain and food consumption/feed efficiency. Irregular respiratory patterns and piloerection were major clinical observations found primarily in the mid-high and high dose group animals. In the high dose group, gastrointestinal distention and stomach discoloration were observed in non-surviving males and females, and degeneration and necrosis of the testicular germinal cells and epididymal cells were also observed in a non-surviving male. Increased liver weights were found in females in the mid-high and high dose groups. Animals in the low and mid-low groups did not exhibit adverse effects of MSE (100 mg/kg bw/d MIC-1). A no observed adverse effect level (NOAEL) of the standardized MSE was determined as 257 mg/kg bw/d providing 100 mg/kg bw/d MIC-1.
Underlayer optimization method for EUV lithography (2020)

The combination photoresist-underlayer fulfills a central role in EUVL for patterning. Moreover, future high numerical aperture (NA) and tight pitches will require very thin layers in the lithography stack, which will increase the impact of chemical interactions at the photoresist-underlayer interface. Adhesion between these layers will be critical to overcome pattern collapse at high aspect ratios whereas at the same time the impact of interfacial effects, such as intermixing, on the lithography performance must be minimized. A fine balance must be found between several chemical interactions, which is a complex exercise with many unknown parameters. In this paper we present how the polar and dispersive components of the surface energy can be used to optimize EUV underlayers in order to achieve the best lithography performance. Subtle changes in the underlayer composition can have a large effect on the lithography performance. A PTD CAR photoresists test case will be used to demonstrate that the photoresist profile, scum formation, line width roughness, pattern collapse and stochastic defects can all be tuned into a certain direction just by tweaking the surface energies of the underlayer. The simplicity of the methodology in this study will be a powerful knob to understand and optimize underlayers for EUV photoresist-underlayer interactions.
Vascular Endothelial Growth Factor C (VEGF-C) Gene Therapy Attenuates Postoperative Lymphedema by Regenerating Collective Lymphatic Vessels (2006)

Tissue edema and secondary lymphedema are common problems in surgery. Discovery of the first lymphangiogenic growth factors now allow us to develop new targeted therapies for lymphedema. The vascular endothelial growth factor-C and -D are the first known growth factors that are capable of inducing growth of new lymphatic vessels. The authors have recently shown that insufficient signaling of VEGF-C/D causes hereditary lymphedema in some families and VEGF-C therapy shows promising effects in preclinical animal models of lymphedema).
A multi-hypothesis decoder for multiple description video coding (2008)

Multiple Description Coding (MDC) can be used as an Error Resilience (ER) technique for video coding. In case of transmission errors, Error Concealment (EC) can be combined with MDC to reconstruct the lost frame, such that the propagated error to the following frames is reduced. In this paper we propose a novel algorithm based on a Multi-hypothesis Decoder (MHD), to improve the reconstructed video quality of MDC over packet loss networks. Both subjective and objective results show that MHD can help to achieve a better video quality than a traditional EC algorithm.
Ride-Hailing Order Dispatching at DiDi via Reinforcement Learning (2020)

Order dispatching is instrumental to the marketplace engine of a large-scale ride-hailing platform, such as the DiDi platform, which continuously matches passenger trip requests to drivers at a scale of tens of millions per day. Because of the dynamic and stochastic nature of supply and demand in this context, the ride-hailing order-dispatching problem is challenging to solve for an optimal solution. Added to the complexity are considerations of system response time, reliability, and multiple objectives. In this paper, we describe how our approach to this optimization problem has evolved from a combinatorial optimization approach to one that encompasses a semi-Markov decision-process model and deep reinforcement learning. We discuss the various practical considerations of our solution development and real-world impact to the business.
Nanoengineered Ionic–Covalent Entanglement (NICE) Bioinks for 3D Bioprinting (2018)

We introduce an enhanced nanoengineered ionic-covalent entanglement (NICE) bioink for the fabrication of mechanically stiff and elastomeric 3D biostructures. NICE bioink formulations combine nanocomposite and ionic-covalent entanglement (ICE) strengthening mechanisms to print customizable cell-laden constructs for tissue engineering with high structural fidelity and mechanical stiffness. Nanocomposite and ICE strengthening mechanisms complement each other through synergistic interactions, improving mechanical strength, elasticity, toughness, and flow properties beyond the sum of the effects of either reinforcement technique alone. Herschel-Bulkley flow behavior shields encapsulated cells from excessive shear stresses during extrusion. The encapsulated cells readily proliferate and maintain high cell viability over 120 days within the 3D-printed structure, which is vital for long-term tissue regeneration. A unique aspect of the NICE bioink is its ability to print much taller structures, with higher aspect ratios, than can be achieved with conventional bioinks without requiring secondary supports. We envision that NICE bioinks can be used to bioprint complex, large-scale, cell-laden constructs for tissue engineering with high structural fidelity and mechanical stiffness for applications in custom bioprinted scaffolds and tissue engineered implants.
Glycerol citrate polyesters produced through heating without catalysis (2012)

Abstract The influence of various heating methods without catalysis to prepare polyesters from citric acid : glycerol blends were studied. In the presence of short‐term microwave treatments, i.e., 60 s at 1200 W, blends of glycerol and citric acid invariably formed solid amorphous polyesters. Fourier transform infrared spectroscopy showed that citric acid and glycerol blends can form highly stable polymers composed of ester bonds. The glycerol citrate polyester polymers exhibited the least degradation in water, more in acid solutions (0.1–1.0 M HCl), and the most deterioration in strong alkaline solutions (0.1–1.0 M NaOH) after 72 h soakings. Polyesters of glycerol and citric acid were studied with differential scanning calorimetry and thermal gravimetric analysis. The polyesters were found to be thermally stable (up to 313°C). © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Two-wavelength infrared pyrometer for large and rapid temperature changes (1982)

A two-wavelength infrared pyrometer is described which is suitable for monitoring the rapid heating of materials by cw lasers or electron beams. Other existing two-wavelength pyrometers do not appear to have the combination of features required for this application, namely fast response, large dynamic range, and high sensitivity. With the present instrument a temperature range from 600 to 3000 K may be traversed in times of down to about 100 ms, with a spatial resolution of 1 mm, and with an accuracy of a few percent. The optical system includes a transparent chopper wheel on which a pattern of transmission filters has been vacuum deposited through masks. The electronic system combines a divider circuit with a fast-response automatic-gain-control loop. Results are given of the use of the pyrometer with laser-heated plates of aluminum and titanium.
Immunogenicity of Outer Membrane Proteins in a Lipopolysaccharide-Deficient Mutant of<i>Neisseria meningitidis</i>: Influence of Adjuvants on the Immune Response (1999)

The immunogenicity of outer membrane complexes (OMCs) or heat-inactivated bacteria of a lipopolysaccharide (LPS)-deficient mutant derived from meningococcal strain H44/76 was studied. The immune response in BALB/c mice to the major outer membrane proteins was poor compared to the immune response elicited by wild-type immunogens. However, addition of external H44/76 LPS to mutant OMCs entirely restored the immune response. By using an LPS-deficient mutant, it may be possible to substitute a less toxic compound as adjuvant in meningococcal outer membrane vaccines. Therefore, a broad panel of adjuvants were tested for their potential to enhance the immunogenicity of LPS-deficient OMCs. AlPO(4), Rhodobacter sphaeroides LPS, monophosphoryl lipid A and alkali-hydrolyzed meningococcal LPS showed significantly lower adjuvant activity than did H44/76 LPS. Adjuvant activity similar to H44/76 LPS was found for Escherichia coli LPS, meningococcal icsB and rfaC LPS, QuilA, subfractions of QuilA, and MF59. Good adjuvant activity was also found with meningococcal htrB1 LPS, containing penta-acylated lipid A. Antisera elicited with the less active adjuvants showed relatively high immunoglobulin G1 (IgG1) titers, whereas strong adjuvants also induced high IgG2a and IgG2b responses in addition to IgG1. Antisera with the IgG2a and IgG2b isotypes showed high bactericidal activity, indicating that adjuvants promoting the IgG2a and IgG2b response contribute most to the protective mechanism. Thus, this study demonstrates that the immunogenicity of meningococcal LPS-deficient OMCs can be restored by using less toxic adjuvants, which opens up new avenues for development of vaccines against meningococcal disease.
Improvement of the quality factor of single crystal diamond mechanical resonators (2017)

Single-crystal diamond (SCD) has the potential to boost microelectromechanical system (MEMS) with unprecedented performance in terms of its intrinsic mechanical, chemical, and electronic properties, especially in the applications under extreme conditions. On the basis of the analysis of the energy dissipation in diamond mechanical resonators, the authors report on the marked improvement of the quality factor of SCD-MEMS resonators. Ion implantation assisted lift-off technique (IAL) is utilized to fabricate the SCD resonators. The quality factor of the resonator fabricated from the ion-damaged SCD layer alone is as low as 100–300 owing to the bulk or surface defects. The growth of homoepitaxial layers on the ion-implanted SCD substrates significantly improves the quality factor by more than 100 times. Cantilevers made of SCD epilayers of different thicknesses are examined. It is found that the quality factor increases with increasing the epilayer thickness. The maximum quality factor of the SCD cantilevers fabricated by the IAL technique reaches 3.9 × 104. A bilayer model is proposed to describe the variation of the quality factor.
Depth and lateral size control of three-dimensional images in projection integral imaging (2004)

We present a simple method to pick up (sense) large objects that are far away, and then display their three-dimensional images within the depth of focus of projection integral imaging systems. For this purpose, we propose to use either curved pickup devices or curved display devices or both. In this method, as the object distance increases, the longitudinal image depth reduces in a nonlinear way, while the lateral size reduces in a linear way. To reduce the depth of reconstructed images alone, a method to zoom in elemental images can be used. We analyze the two methods when they are used together. Experiments are presented to show the feasibility of our approach.
Blocking Survivin to Kill Cancer Cells (2003)

It has long been appreciated that dysregulation of apoptosis, or programmed cell death, plays a critical role in the onset and progression of cancer (). For the complexity of cell death pathways, this may result from deregulated overexpression of apoptosis inhibitors or loss/underrepresentation of apoptosis inducers. The net effect for both conditions is an aberrantly extended cell viability, which facilitates the acquisition of transforming mutations and the insurgence of chemoresistance (). Because of the tremendous progress recently made in elucidating apoptotic mechanisms and their relevance to human diseases, concrete therapeutic efforts are now underway to manipulate cell death pathways and eliminate survival signals that may contribute to keeping cancer cells alive (). To make an ideal drug target, an apoptosis regulator should be preferentially expressed in tumor cells but not in normal tissues, and interference with its expression/function should be sufficient to facilitate cell death, either alone, or in combination with chemotherapeutic drugs or ultraviolet/γ-irradiation. Data recently appeared in the literature suggests that the human survivin gene may fulfill both of these prerequisites. Furthermore, initial evidence in vitro and in vivo has suggested that targeting survivin may provide a viable approach to kill cancer cells selectively.
ChemInform Abstract: INFLUENCE OF THERMAL DECOMPOSITION ON THE MECHANICAL PROPERTIES OF MAGNESIA‐STABILIZED CUBIC ZIRCONIA (1983)

Abstract Die Zers. von durch MgO (14 mol‐%) stabilisiertem kubischen ZrO 2 bei 1100°C verläuft direkt zu monoklinem ZrO 2 .
Round Multifilament Bi-2212/Ag Wire Development for High Field Magnet Applications (2007)

Development efforts at Oxford Superconducting Technology (OST) have recently been aimed at manufacturing long length round wires with improvement of transport properties for high field magnet applications. Recently, significant improvements in the JE and Jc performance have been achieved by optimizing the starting precursor composition, the deformation processes, and the heat treatments. The highest JE of 1580 A/mm2 (Jc of 6140 A/mm2) at 4.2 K, 0 T, JE of 420 A/mm2 at 4.2 K, 31 T and JE of 312 A/mm2 at 20 K, 2 T were obtained in 0.81 mm wire with the optimized condition. In addition, significant progress on braided insulation has been made for enabling a robust procedure for wind-and-react Bi-2212 solenoid coils. Ic and generated field have been measured in a series of such coils of increasing dimensions. In this paper the progress on the development of Bi-2212 round wires and coils will be reported.
Towards enediyne libraries: cyclic enediynes via an intramolecular carbenoid coupling protocol (1995)

G. B. Jones, R. S. Huber and J. E. Mathews, J. Chem. Soc., Chem. Commun., 1995, 1791 DOI: 10.1039/C39950001791