gebhart/patrepeval huggingface dataset:
A phase 1 study of AR-42 in patients with advanced solid tumors, including nervous system tumors. (2016)

2558 Background: We have shown that AR-42, an oral pan-histone deacetylase inhibitor, has clinical activity in some hematologic malignancies and preclinical activity in certain solid tumors, including neurofibromatosis type 2 (NF2)-associated meningiomas and schwannomas. Therefore, this phase 1 trial was initiated to investigate the dose limiting toxicities (DLTs) and the maximum tolerated dose (MTD) in patients with advanced solid tumors. Methods: This is a single-agent, standard 3+3, phase 1 dose-escalation study, with an additional expansion cohort at the MTD; mainly enrolling patients with malignancies of interest, based on our preclinical data. AR-42 was given in a 28-day cycle (3 times weekly, 3-week on, 1-week off). Plasma samples were collected following the first dose to assess pharmacokinetics in each patient. Results: Seventeen patients were enrolled in this study. Two patients were replaced and 15 patients were evaluable for safety and response. Patients had a median age of 49 (range: 20-80) and were heavily pretreated (41% had 3 prior regimens). Primary tumor sites included NF2-associated tumors (n = 5), meningioma (n = 2), transitional cell carcinoma (n = 3), breast cancer (n = 2), and other (n = 5). The MTD was defined as 60 mg and the DLTs were two grade 3 thrombocytopenias; and one grade 4 psychiatric disorder, possibly related to AR-42 (at 80 mg). The most common toxicities were fatigue, cytopenias, electrolytes imbalance, nausea/vomiting and elevated creatinine, which were manageable. The best response was stable disease (53%, 8/15 patients) with a median progression free survival (mPFS) of 4.4 months (95% CI: 1.2-13.9). Interestingly, for NF2 and meningioma patients, the mPFS was 13.9 months. Individual plasma AR-42 Cmax and AUC0-24hr values ranged from 0.54 to 3.25 μM and 4.93 to 27.6 μM*Hr across the dose range, respectively. Conclusions: Single-agent oral AR-42 is well tolerated and associated with modest anti-tumor activity in patients with advanced solid tumors, especially those with NF2-asociated tumors and meningiomas. Pharmacokinetic data suggests active drug levels are achieved in plasma. In this study, the MTD is determined to be 60 mg, once daily, 3 times weekly, 3-week on and 1-week off. Clinical trial information: NCT01129193.
<title>Nonlinear spectrometer for characterization of organic and polymeric molecules</title> (1999)

We have developed a femtosecond continuum spectrometer to measure nonlinear absorption spectra from 300 nm in the UV to 1.7 micrometers in the IR. This method is applied for measuring NLA spectra of semiconductor, organic and polymeric materials. The pump-probe nature of the experiment also allows the temporal response to be determined, thus helping in the determining of the underlying physical mechanisms for the nonlinearity. We describe studies of two-photon absorption in a series of alkyl fluorenes and excited state absorption dynamics in a series of polymethines using this spectrometer.
ChemInform Abstract: CHEMISTRY OF THE HEXAHYDROPORPHYRINS. 3. SYNTHESIS AND REACTIONS OF 5‐CYANO‐2,2,8,8,12,13,17,18‐OCTAMETHYLISOBACTERIOCHLORINE (1980)

Abstract Die Herstellung der Titelverbindung (VIII) erfolgt ausgehend vom Thiolactam (I) wie aufgezeigt.
Structure-Guided Identification of Resistance Breaking Antimalarial N‑Myristoyltransferase Inhibitors (2019)

The attachment of myristate to the N-terminal glycine of certain proteins is largely a co-translational modification catalyzed by N-myristoyltransferase (NMT), and involved in protein membrane-localization. Pathogen NMT is a validated therapeutic target in numerous infectious diseases including malaria. In Plasmodium falciparum, NMT substrates are important in essential processes including parasite gliding motility and host cell invasion. Here, we generated parasites resistant to a particular NMT inhibitor series and show that resistance in an in vitro parasite growth assay is mediated by a single amino acid substitution in the NMT substrate-binding pocket. The basis of resistance was validated and analyzed with a structure-guided approach using crystallography, in combination with enzyme activity, stability, and surface plasmon resonance assays, allowing identification of another inhibitor series unaffected by this substitution. We suggest that resistance studies incorporated early in the drug development process help selection of drug combinations to impede rapid evolution of parasite resistance.
The safety and immunogenicity of two novel live attenuated monovalent (serotype 2) oral poliovirus vaccines in healthy adults: a double-blind, single-centre phase 1 study (2019)

Bill & Melinda Gates Foundation.
Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (2016)

We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder.
Effect of gemcitabine on specific antitumor responses of modified vaccinia Ankara (MVA) expressing survivin in a murine pancreatic carcinoma model. (2011)

256 Background: Survivin is overexpressed by 70% to 80% of pancreatic cancers, and is associated with resistance to chemotherapy and a poor prognosis. Gemcitabine has been a standard treatment for patients with advanced pancreatic cancer for a decade. Recent reports have demonstrated that gemcitabine treatment attenuates the tumor-suppressive environment by eliminating CD11b + /Gr- 1 + myeloid derived suppressor cells (MDSCs). We hypothesize that a cancer vaccine targeting survivin can achieve enhanced efficacy when combined with gemcitabine. Methods: In this study, we tested this hypothesis using modified vaccinia Ankara (MVA) expressing full-length murine survivin. The poorly immunogenic mouse pancreas adenocarcinoma cell line, Pan02, which expresses murine survivin and is syngeneic to C57BL/6, was used for this study. Results: Immunization with MVA-survivin resulted in a modest therapeutic antitumor effect on established Pan02 tumors. When administered with gemcitabine, MVA-survivin immunization resulted in significant tumor regression and prolonged survival. The enhanced vaccine efficacy was associated with decreased CD11b + /Gr-1 + MDSCs. To analyze thesurvivin specific immune response to MVA-survivin immunization, we utilizeda peptide library of 15mers with 11 residues overlapping fromfull-length murine survivin. Splencytes from miceimmunized with MVA-survivin produced intracellular γ-interferon inresponse to in vitro stimulation with the overlapping peptidelibrary. Increased survivin-specific CD8 + T cells that specifically recognized the Pan02 tumor line were seen in mice treated with MVA-survivin and gemcitabine. Conclusions: Thesedata suggestthat vaccination with MVA-survivin in combination with gemcitabine represents an attractive strategy to overcometumor-induced peripheral immune tolerance, and this effect has potential for clinical benefit in pancreatic cancer. No significant financial relationships to disclose.
Security analysis of robust data-hiding with geometrically structured codebooks (2005)

In digital media transfer, geometrical transformations desynchronize the communications between the encoder and the decoder.Therefore, an attempt to decode the message based on the direct output of the channel with random geometrical state fails.The main goal of this paper is to analyze the conditions of reliable communications based on structured codebooks in channels with geometrical transformations.Structured codebooks include codewords that have some features or statistics designed for synchronization purposes.In the design of capacity approaching data-hiding codes, host interference problem should be resolved.The solution to this problem is to perform the message coding based on random binning dependent on host-state.On the other hand, to achieve robustness to geometrical transformations, the codewords should have host independent statistics and encoding should be performed using random coding.To satisfy these conflicting requirements we propose Multiple Access Channel (MAC) framework where the message is split between two encoders designed based on the random binning and random coding principles.The message encoded according to random coding additionally serves for synchronization purposes.Sequentially, all existing methods that are proposed for reliable communications in channels with geometrical transformations are analyzed within the proposed MAC set-up.Depending on the particular codebook design, we classify these methods into two main groups: template-based codebooks and redundant codebooks.Finally, we perform the analysis of security leaks of each codebook structure in terms of complexity of the worst case attack.
Evaluation of the DORT method for the detection of microcalcifications in the breast (2004)

The DORT method (French acronym for diagonalization of the time reversal operator) is derived from the theory of iterative time reversal mirroring. It consists of a singular value decomposition of the time reversal operator obtained through single element transmissions and receptions. The number of eigenvalues relates to the number of bright point scatterers in the medium, and each eigenvector is the transmit signals that focuses on each bright scatterer. However, the signal-to-noise ratio (SNR) resulting from a single element transmit is low, which negatively impacts the sensitivity of the DORT method. This work consists of an adaptation of the DORT method to an imaging mode. Focused transmissions in the medium are used and a windowing preprocessing operation on the received signals significantly increases the sensitivity. The more robust behavior of this modified DORT method is tested on Field II simulated data and then on a phantom made of strings of different material embedded in speckle. Data on freshly excised breast surgical samples containing microcalcifications were processed and every microcalcifications was detected. Finally, results on in vivo acquisitions prove that the technique can accurately detect and locate microcalcifications in nonhomogeneous media with aberration.
Diversity Backpressure Scheduling and Routing With Mutual Information Accumulation in Wireless Ad-Hoc Networks (2016)

We suggest and analyze algorithms for routing in multi-hop wireless ad-hoc networks that exploit mutual information accumulation as the physical layer transmission scheme, and are capable of routing multiple packet streams (commodities) when only the average channel state information is present, and that only locally. The proposed algorithms are the modifications of the diversity backpressure (DIVBAR) algorithm, under which the packet whose commodity has the largest “backpressure metric” is chosen to be transmitted and is forwarded through the link with the largest differential backlog (queue length). In contrast to traditional DIVBAR, each receiving node stores and accumulates the partially received packet in a separate “partial packet queue”, thus increasing the probability of successful reception during a later possible retransmission. We present two variants of the algorithm: DIVBAR-renewal mutual information accumulation (RMIA), under which all the receiving nodes clear the received partial information of a packet once one or more receiving nodes firstly decode the packet; and DIVBAR-full mutual information accumulation (FMIA), under which all the receiving nodes retain the partial information of a packet until the packet has reached its destination. We characterize the network capacity region with the RMIA transmission scheme and prove that (under certain mild conditions) it is strictly larger than the network capacity region with the repetition (REP) transmission scheme that is used by the traditional DIVBAR. We also prove that DIVBAR-RMIA is throughput-optimal among the policies with RMIA, i.e., it achieves the network capacity region with RMIA, which in turn demonstrates that DIVBAR-RMIA outperforms traditional DIVBAR with respect to the achievable throughput. Moreover, we prove that DIVBAR-FMIA performs at least as well as DIVBAR-RMIA with respect to throughput. Simulations also confirm these results.
Nonlinear optical frequency conversion using metamaterial arrays (2023)

A method of nonlinear wavelength generation uses a nonlinear optical medium. An input flux of pump energy is applied to one or more dielectric optical resonators. Each resonator has an optical cavity comprising the nonlinear optical medium. Each resonator has at least one Mie resonance that is excited by the input flux of pump energy. The pump energy causes the generation of converted light containing at least one converted component having a frequency attainable only through a non-linear process.
Issues Raised Involving the Copper Hypotheses in the Causation of Alzheimer′s Disease (2011)

I present evidence that the epidemic of Alzheimer's disease is a new phenomenon exploding in the latter part of the 20th century in developed countries. I postulate that a major causative factor in the epidemic is the coincident use of copper plumbing, and the ingestion of inorganic copper leaching from the copper plumbing. I present evidence to support this hypothesis and discuss various objections and criticisms that have been raised about the hypothesis, and my responses to these criticisms. I conclude that the hypothesis is well supported by the evidence and deserves serious consideration, because if it is valid, it indentifies a partially preventable cause of Alzheimer's disease.
M3-13 Interfacial Thermal Resistance of Hydrophilically-Terminated Self-Assembled Monolayer and Water; Molecular Dynamics Study (M3 Micro/NanoThermo-FluidsSystem) (2009)

The interfacial thermal resistance at the interface of 11-mercapoundecanol (-S(CH_2)_<11>OH) self-assembled monolayer (SAM) adsorbed on Au(111) substrate and water was investigated using nonequilibrium molecular dynamics simulations. As a result, the interfacial thermal resistance was found to be a half of that in the system that consists of 1-dodecanthiol (-S(CH_2)_<11>OH) SAM adsorbed on Au(111) and toluene [Kikugawa, G., et al., J. Chem. Phys. (2009)]. Also the local thermal resistance between SAM and water was found to be very small. We consider that hydrogen bonds between SAM terminal and water contribute the effective thermal energy transfer from SAM to water. The detailed analysis of heat transport phenomena at the interface was performed and the influence of the bonding structure of water molecules near the interface on the thermal resistance was discussed.
Thermo‐Mechanical Responses of Liquid‐Crystal Networks with a Splayed Molecular Organization (2005)

Abstract Films of liquid‐crystal networks with a splayed molecular alignment over their cross‐section display a well‐controlled deformation as a function of temperature. The deformation can be explained in terms of differences in thermal expansion depending on the average molecular orientation of the mesogenic centers of the monomeric units. The thermal expansion of the anisotropic polymers has been characterized as a function of their molecular structure and the polymerization conditions. As a reference, films with an in‐plane 90° twist have also been studied and compared with the splayed, out‐of‐plane molecular rotation. The twisted films show a complex macroscopic deformation owing to the formation of saddle‐like geometries, whereas the deformation of the splayed structured is smooth and well controlled. The deformation behavior is anticipated to be of relevance for polymer‐based microelectromechanical system (MEMS) technology.
607 Presumed PDF Simulation of Turbulent Non-premixed Flames based on Detailed Chmeical Kinetics (2009)

5 Pres cd -PDF mode1 g Moment meth d non -pre ed combus on ISAr meth
Adaptive tree search (2002)

Combinatorial optimization and constraint satisfaction problems are ubiquitous in computer science, arising in areas as diverse as resource allocation, automated design, planning, and logical inference. Finding optimal solutions to such problems often entails searching an intractably large tree of possibilities. Problems beyond the reach of exhaustive enumeration require methods that exploit problem-specific heuristic knowledge to find the best solution possible within the time available. Previous algorithms typically follow a fixed search order, making inefficient use of heuristic information. For a new problem, it is not always clear which predetermined search order will be most appropriate. 
I propose an adaptive approach in which the search order is adjusted according to heuristic information that becomes available only during the search. By adapting to the current problem, this approach eliminates the need for pilot experiments and enables the use of good search orders that would be too complicated to program explicitly. 
To demonstrate the feasibility of the approach, I first present a simple but incomplete technique, adaptive probing. Empirical results demonstrate that the method can effectively adapt on-line, surpassing existing methods on several synthetic benchmarks. I then introduce a general framework for complete adaptive tree search, best-leaf-first search , and show how previous work can be viewed as special cases of this technique. Incorporating different sources of information into the framework leads to different search algorithms. Five different instantiations are tested empirically on challenging combinatorial optimization and constraint satisfaction benchmarks, in many cases yielding the best results achieved to date. Best-leaf-first search can be understood as an extension of traditional heuristic shortest-path algorithms to combinatorial optimization and constraint satisfaction. By extending heuristic search to these new domains, I unite these previously separate problems.
Y-Ȳ Diagram Analysis of Radial Gradient Index Lenses (1987)

The Y-Ȳ diagram of Delano 1 has been shown to be useful in understanding the relationships and constraints between first order quantities of a wide range of optical systems from Gaussian beam propagation to zoom lens synthesis 2,3,4,5,6 .
Design of current mirror integration ROIC for snapshot mode operation (2016)

Current mirror integration (CMI) read out integrated circuit (ROIC) topology provides a low input impedance to photo-detectors and provides large injection efficiency, large charge handling capacity and snapshot mode operation without in-pixel opamps. The ROIC described in this paper has been implemented with a modified current mirror circuit, with matched PMOS pairs for detector input stage and its biasing. The readout circuit has been designed for 30 × 30 μm2 pixel size, 4 × 4 array size, variable frame rate, 5 Mega pixel per second (Mpps). Experimental performance of the test chip has achieved 15 Me charge handling capacity, a high dynamic range of 83 dB, 99.8% linearity and 99.96% injection efficiency. The ROIC design has been fabricated in 3.3 V 1P6M UMC 180 nm CMOS process and tested up to 5 MHz pixel rate at room and at cryogenic temperature.
Simultaneous rapid reaction workup and catalyst recovery (2016)

By combining reaction work-up and catalyst recovery into a simple filtration procedure we have developed a substantially faster technique for organic synthesis.
Establishment of an ovarian metastasis model and possible involvement of E‐cadherin down‐regulation in the metastasis (2008)

Clinical observations of cases of ovarian metastasis suggest that there may be a unique mechanism underlying ovarian-specific metastasis. This study was undertaken to establish an in vivo model of metastasis to the ovary, and to investigate the mechanism of ovarian-specific metastasis. We examined the capacity for ovarian metastasis in eight different human carcinoma cell lines by implantation in female NOD/SCID mice transvenously and intraperitoneally. By transvenous inoculation, only RERF-LC-AI, a poorly differentiated carcinoma cell line, frequently demonstrated ovarian metastasis. By intraperitoneal inoculation, four of the eight cell lines (HGC27, MKN-45, KATO-III, and RERF-LC-AI) metastasized to the ovary. We compared E-cadherin expression among ovarian metastatic cell lines and others. All of these four ovarian metastatic cell lines and HSKTC, a Krukenberg tumor cell line, showed E-cadherin down-regulation and others did not. E-cadherin was then forcibly expressed in RERF-LC-AI, and inhibited ovarian metastasis completely. The capacity for metastasizing to the other organs was not affected by E-cadherin expression. We also performed histological investigation of clinical ovarian-metastatic tumor cases. About half of all ovarian-metastatic tumor cases showed loss or reduction of E-cadherin expression. These data suggest that E-cadherin down-regulation may be involved in ovarian-specific metastasis.
Transient behavior of organic thin film electroluminescence (1992)

Transient behavior for an organic thin film electroluminescence (EL) cell with ITO/triphenylamine derivative/tris (8-hydroxyquinolino) aluminum (Alq)/Mg:Ag structure was observed by short voltage pulse measurements. The EL response was of the order of 10−7 s, and faster than that previously measured by Tang et al. [J. Appl. Phys. 65, 3610 (1989)]. In these measurements, we could observe carrier transit time. Then we concluded this carrier transit time should be attributed to that of electrons in Alq layer and the electron mobility of (5±2)×10−5 cm2/V s was obtained above the electric field of 1 MV/cm.
Implantable MicroPump for Drug Delivery in Patients with Diabetic Macular Edema (2014)

Purpose: : To demonstrate the safety and surgical feasibility of the first-in-man ocular implant of a novel Posterior MicroPump Drug Delivery System (PMP) in patients with diabetic macular edema (DME) and to report on the device capabilities for delivering a programmable microdose. Methods: : This was a single center, single arm, open-label, prospective study. Eleven patients with DME and visual acuity equal to or worse than 20/40 were included. The PMP prefilled with ranibizumab was implanted into the subconjunctival space. After implantation, the PMP was wirelessly controlled to deliver a programmed microdose. Comprehensive ophthalmic exams and optical coherence tomography were performed biweekly for 90 days. At the end of the study, the PMP was explanted and the subjects thereafter received standard of care for DME (i.e., laser or intravitreal injections). Results: : All 11 surgical implantations were without complications and within the skill sets of a retinal surgeon. No serious adverse events occurred during the follow-up period. At no point were visual acuity and central foveal thickness worse than baseline in the implanted eye. The PMP delivered the programmed ranibizumab dosage in seven subjects. The remaining four patients received a lower than target dose, and the treatment was complemented with standard intravitreal injection. Conclusions: : This study demonstrates the first-in-man safety of the Replenish MicroPump implant for a period of 90 days and its capability to deliver a microdose into the vitreous cavity. Further studies to enable longer-term safety and to demonstrate the feasibility of multiple programmable drug delivery are necessary.
Gas Chromatography–Olfactometry Analyses of Volatiles Produced by ‘Fallglo’ and ‘US Early Pride’ Tangerines (2012)

International audience
ChemInform Abstract: Development of the Technique of Distillation from Its Beginnings up the Year 1800 (1991)

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.