gebhart/patrepeval huggingface dataset:
A Transient Increase in Eosinophils Is Associated with Prolonged Survival in Men with Metastatic Castration-Resistant Prostate Cancer Who Receive Sipuleucel-T (2014)

Sipuleucel-T is an autologous cellular immunotherapy used to treat asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Traditional short-term indicators of clinical response commonly used with chemotherapy have not correlated with survival in patients treated with sipuleucel-T. This retrospective study aimed to evaluate laboratory parameters as possible early biomarkers associated with clinical benefit following sipuleucel-T treatment. Patients treated with sipuleucel-T from three randomized, controlled, phase III clinical trials in mCRPC were considered: IMPACT (NCT00065442; n = 512), D9901 (NCT00005947; n = 127), and D9902A (NCT01133704; n = 98). Patients from these trials were included in this study if their samples were analyzed by the central laboratory and if data were available from baseline and ≥ 1 posttreatment time point (n = 377). We found that sipuleucel-T treatment was associated with a transient increase in serum eosinophil count at week 6 that resolved by week 14 in 28% of patients (105 of 377). This eosinophil increase correlated with induced immune response, longer prostate cancer-specific survival [HR, 0.713; 95% confidence interval (CI), 0.525-0.970; P = 0.031], and a trend in overall survival (HR, 0.753; 95% CI, 0.563-1.008; P = 0.057). Median serum globulin protein levels also increased transiently, which was associated with antigen-specific antibody responses; however, this finding did not correlate with longer survival. We conclude that transient increases in eosinophils at week 6 may be a useful, objective, short-term indicator of global immune activation and survival benefit with sipuleucel-T in patients with mCRPC. This observation warrants prospective evaluation in future clinical trials.
Abstract 5629: Application of a novel bispecific antibody-based scaffold for optimal redirected T-cell killing of cancer cells (2010)

Abstract Despite significant progress, improved treatment modalities are required to eradicate cancer. Cytotoxic T lymphocytes are among the most potent cell populations capable of killing target cells and considerable effort has been dedicated to developing strategies aimed at redirecting T cells toward cancer, including the generation of bispecific molecules capable of co-engaging a tumor target together with an activating receptor on T lymphocytes. Limitations of the existing technology, however, including shortcomings in manufacturability, stability, specificity and potency, have often hampered progress in harnessing the power of T cells with bi-specific molecules. We have applied a novel antibody-based scaffold, termed DART (Dual-Affinity Re-Targeting), to redirect T-cell killing toward tumor cells in the absence of cognate interactions. DART molecules are structurally comprised of a covalently linked “diabody” generated through co-expression in mammalian cells of two separate Fv-encoding chains. To evaluate the ability of the platform to redirect T-cell killing, DARTs were designed to target hematological malignancies by comprising a B-cell lineage specificity (CD19) together with T-cell recognition (CD3 or TCR), while a DART comprising specificities for the HER2 target and the TCR was used to evaluate applicability to solid tumors. All three DART molecules assembled efficiently and were evaluated in a series of redirected T-cell killing assays to evaluate potency and mechanistic aspects of cytotoxicity. Both the CD19xCD3 and CD19xTCR DART molecules demonstrated efficient co-ligation of B-cell lymphoma cells with human T cells and mediated equivalently potent redirected T-cell killing against a panel of CD19-positive B-cell lymphoma cell lines but not CD19-ve cell lines. In similar fashion, the TCRxHER2 DART revealed potent T-cell mediated killing of a panel of HER2 expressing cell lines, including those expressing low HER2 levels (1+ by HercepTest), but was inactive against HER2-negative lines. Analyses of the mechanism of T-cell mediated killing by the DART molecules revealed a dependence on the granzyme B/perforin pathways, with potent killing observed during short-term incubation of the effector populations with target cells and at low E:T ratios. Furthermore, activation of human T cells by DART molecules proceeded strictly in a target-dependent manner. Finally, analyses in xenograft models reconstituted with human peripheral blood mononuclear cells, demonstrated efficient tumor regression by TCR-based DART molecules. In conclusion, T-cell-directed DARTs represent a robust and flexible platform to recruit T-cell populations for cancer cell killing and may offer potential application toward tumor eradication in cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5629.
A multi-agent control framework for co-adaptation in brain-computer interfaces (2013)

In a closed-loop brain-computer interface (BCI), adaptive decoders are used to learn parameters suited to decoding the user's neural response. Feedback to the user provides information which permits the neural tuning to also adapt. We present an approach to model this process of co-adaptation between the encoding model of the neural signal and the decoding algorithm as a multi-agent formulation of the linear quadratic Gaussian (LQG) control problem. In simulation we characterize how decoding performance improves as the neural encoding and adaptive decoder optimize, qualitatively resembling experimentally demonstrated closed-loop improvement. We then propose a novel, modified decoder update rule which is aware of the fact that the encoder is also changing and show it can improve simulated co-adaptation dynamics. Our modeling approach offers promise for gaining insights into co-adaptation as well as improving user learning of BCI control in practical settings.
Ligand Migration in the Reaction of Titanium Complexes with AlMe3 (2007)

Five different titanium compounds cis- [Ti(η 2 -hbo) 2 (OEt) 2 ]·0.5toluene ( 1 ), cis -[TiCl 2 (η 2 -thp) 2 ] ( 2 ), [TiCl 2 (edbp) 2 ] ( 3 ), [Ti 2 (μ-OMe) 2 (edbp) 2 (Me) 2 ] ( 6) , [Ti 2 (μ-OMe) 2 (edbp) 2 (OMe) 2 ] ( 7 ) (Hhbo = 2-(2-hydroxyfenyl)benzoxazole, Hthp = tetrahydropyran-2-methanol, H 2 edbp = 2,2'-ethylidenebis(4,6-di- tert -butylphenol)), have been prepared and tested in combination with MAO as catalysts for propene polymerization and ethene and oct-1-ene copolymerization with the aim of gaining insight into the structure of the active species. Investigation of the 1 /AlMe 3 or 2 /AlMe 3 systems resulted in isolation of [Al(η 2 -hbo) 2 (Me)] ( 4 ) and [Al 2 (μ 2 -η 2 -thp) 2 (Me) 4 ] ( 5 ) in high yields. This indicates that the trimethylaluminum contained in MAO abstracts ligands from 1 or 2 , affecting thus the catalytic performance of the 1 , 2 /MAO catalysts. In contrast, compound 3 reacted with MAO affording methylated product 6 . Accordingly, the 3 /MAO catalyst differed from the above ones, furnishing at 70 °C e.g., narrow molecular weight polypropylene ( M n = 454 000; M w /M n = 2.49; T m = 158.2 °C).
Closed-Loop Vectoring Control of a Turbulent Jet Using Periodic Excitation (2003)

Closed-loop control strategies were studied experimentally at low Reynolds and incompressible Mach numbers using periodic excitation to vector a turbulent jet. Vectoring was achieved by attaching a short, wide-angle diffuser at the jet exit and introducing periodic excitation from a slot covering one quadrant of the circumference of the round turbulent jet. Closed-loop control methods were applied to transition quickly and smoothly between different jet deflection angles. The frequency response of the zero-mass-flux piezoelectric actuator was flat to about 0.5 kHz, but the jet responds up to 30-50 Hz only. This is still an order of magnitude faster than conventional thrust vectoring mechanism. System identification procedures were applied to approximate the system's transfer function. A linear controller was designed that enabled fast and smooth transitions between stationary deflection angles and maintained desired jet vectoring angles under varying system conditions. The linear controller was tested over the entire range of available deflection angles, and its performance is evaluated and discussed.
Data from JQ1 Induces DNA Damage and Apoptosis, and Inhibits Tumor Growth in a Patient-Derived Xenograft Model of Cholangiocarcinoma (2023)

&lt;div&gt;Abstract&lt;p&gt;Cholangiocarcinoma (CCA) is a fatal disease with a 5-year survival of &lt;30%. For a majority of patients, chemotherapy is the only therapeutic option, and virtually all patients relapse. Gemcitabine is the first-line agent for treatment of CCA. Patients treated with gemcitabine monotherapy survive ∼8 months. Combining this agent with cisplatin increases survival by ∼3 months, but neither regimen produces durable remissions. The molecular etiology of this disease is poorly understood. To facilitate molecular characterization and development of effective therapies for CCA, we established a panel of patient-derived xenograft (PDX) models of CCA. We used two of these models to investigate the antitumor efficacy and mechanism of action of the bromodomain inhibitor JQ1, an agent that has not been evaluated for the treatment of CCA. The data show that JQ1 suppressed the growth of the CCA PDX model CCA2 and demonstrate that growth suppression was concomitant with inhibition of c-Myc protein expression. A second model (CCA1) was JQ1-insensitive, with tumor progression and c-Myc expression unaffected by exposure to this agent. Also selective to CCA2 tumors, JQ1 induced DNA damage and apoptosis and downregulated multiple c-Myc transcriptional targets that regulate cell-cycle progression and DNA repair. These findings suggest that c-Myc inhibition and several of its transcriptional targets may contribute to the mechanism of action of JQ1 in this tumor type. We conclude that BET inhibitors such as JQ1 warrant further investigation for the treatment of CCA. &lt;i&gt;Mol Cancer Ther; 17(1); 107–18. ©2017 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Vector quantization clustering using lattice growing search (1996)

In this paper we introduce a non-iterative algorithm for vector quantization clustering based on the efficient search for the two clusters whose merging gives the minimum distortion increase. The search is performed within the K-dimensional cells of a lattice having a generating matrix that changes from one step of the algorithm to another. The generating matrix is modified gradually so that the lattice cells grow in volume, allowing the search of the two closest clusters in an enlarged neighborhood. We call this algorithm Lattice Growing Search (LGS) clustering. Preliminary results on 512 \\Theta 512 images encoded at 0:5 bits/pixel showed that the LGS technique can produce codebooks of similar quality in less than 1=10 of the time required by the LBG algorithm [9]. 1 INTRODUCTION The standard method for obtaining a codebook is the Generalized Lloyd or LBG algorithm [9], which monotonically decreases the distortion function towards a local minimum. Although conceptually simple and e...
Laser damage of silica optical windows with random antireflective structured surfaces (2018)

High intensity nanosecond laser pulses induce damage on uncoated optics and antireflection (AR) coated optics with thin film boundaries. Structured surfaces with AR performance have shown higher damage resistance than conventional AR coatings. This work explores laser-induced damage threshold (LIDT) of random antireflective surface structures (rARSS), covering interfaces of planar fused silica substrates, using a 7 ± 1 nanosecond duration, single damaging pulse at 1064-nm wavelength. The rARSS treated windows were optimized for AR at 1064 nm, and transmittance of each treated interface was increased by 3.2% per ISO 13697. Incident fluence was controlled near LIDT for both entry and exit sides. Multiple locations were tested for each fluence setting in accordance with ISO 21254 1-on-1 LIDT testing. Double-sided and single-sided rARSS, orientation with both entrance-side and exit-side treatments, were tested to determine effects random structures have in damage induced by field enhancement on the exit side. Results show that rARSS on a single side of an optic have higher resistance to onset of laser damage when located at entry (structured) side. All tests resulting in damage of polished and single-sided rARSS oriented on exit side were ballistic on beam exit facet, showing surface cracks. Results from rARSS located on beam entry side (both single- and double-side treated) showed nonballistic damage and densification of rARSS features from localized melting or reflow, capping the rARSS but still preserving effective-gradient index and rARSS transmission enhancement. This suggests that the localized melting of the rARSS optic surface does not constitute damage optically, or at least not catastrophically within the prebulk damage regime. Therefore, it is possible to foresee the onset of true damage within an optical system via tracking transmission drop, and swap optics out before catastrophic system failure. The drop in transmission acts as an early warning system, making these rARSS optics an invaluable tool in high-energy laser development.
Data Acquisition, Conditioning and Processing System for a Wearable-based Biostimulation (2022)

Data acquisition by electromyography, as well as the muscle stimulation, has become more accessible with the new developments in the wearable technology and medicine. In fact, for treatments, games or sports, it is possible to find examples of the use of muscle signals to analyse specific aspects related, e.g., to disease, injuries or movement impulses. However, these systems are usually expensive, does not integrate data acquisition with the muscle stimulation and does not exhibit an adaptive control behaviour that consider the pathology and the patient response. This paper presents a wearable system that integrates the signal acquisition and the electrostimulation using dry thin-film titanium-based electrodes. The acquired data is transmitted to a mobile application running on a smartphone by using Bluetooth Low Energy (BLE) technology, where it is analysed by employing artificial intelligence algorithms to provide customised treatments for each patient profile and type of pathology, and taking into consideration the feedback of the acquired electromyography signal. The acquired patient’s data is also stored in a secure cloud database to support the physician to analyse and follow-up the clinical results from the rehabilitation process.
Investigating Effects of Proteasome Inhibitor on Multiple Myeloma Cells Using Confocal Raman Microscopy (2016)

Due to its label-free and non-destructive nature, applications of Raman spectroscopic imaging in monitoring therapeutic responses at the cellular level are growing. We have recently developed a high-speed confocal Raman microscopy system to image living biological specimens with high spatial resolution and sensitivity. In the present study, we have applied this system to monitor the effects of Bortezomib, a proteasome inhibitor drug, on multiple myeloma cells. Cluster imaging followed by spectral profiling suggest major differences in the nuclear and cytoplasmic contents of cells due to drug treatment that can be monitored with Raman spectroscopy. Spectra were also acquired from group of cells and feasibility of discrimination among treated and untreated cells using principal component analysis (PCA) was accessed. Findings support the feasibility of Raman technologies as an alternate, novel method for monitoring live cell dynamics with minimal external perturbation.
Antimitogenic Polymer Drugs Based on AMPS: Monomer Distribution−Bioactivity Relationship of Water-Soluble Macromolecules (2010)

A number of polysulfonated molecules have demonstrated their interaction with fibroblast growth factor (FGF), hampering their binding to its receptors (low affinity heparan sulfate proteoglycans (HSPG) and high affinity tyrosine kinase FGF receptors) and inhibiting the intracellular signaling and mitogenic response in cultured endothelial cells. The aim of this work was the synthesis and characterization of new copolymers based on 2-acrylamido-2-methylpropane sulfonic acid (AMPS) with antiproliferative activity for antitumoral applications. N-Vinylpyrrolidone (VP) or butyl acrylate (BA) was copolymerized with the sulfonated monomer to obtain macromolecules with different hydrophilic/hydrophobic balance and distribution of the sulfonated groups within the macromolecules. In vitro cell culture proliferative assays showed that monomer distribution affected the inhibition of the proliferative action of FGF. Reactivity ratios of the systems were determined following the free radical copolymerization by in situ (1)H NMR, and the correlation of the monomer sequence distribution with the bioactivity is discussed.
Unanchored Lysine48-linked polyubiquitin chains positively regulate the type I IFN-mediated antiviral response (P1391) (2013)

Abstract Type-I interferons (IFN-I) are essential antiviral cytokines produced upon microbial infection. IFN-I elicits this activity through the upregulation of 100s of IFN-I stimulated genes (ISGs), many of which have known antiviral activity. The full breadth of ISG induction requires activation of a number of cellular factors including the IκB kinase epsilon (IKKϵ). However, the mechanism of IKKϵ activation upon viral infection or IFN receptor signaling remains elusive. Here we show that TRIM6, a member of the E3-ubiquitin ligase tripartite motif (TRIM) family of proteins, interacts with IKKϵ and promotes induction of IKKϵ-dependent ISGs. Some studies have suggested a role for unanchored K63-linked polyubiquitin chains, which are not conjugated to any protein, in regulation of kinase activity. However, no role has yet been established for unanchored K48-linked polyubiquitin chains in kinase activation. We show that TRIM6 and the E2-ubiquitin conjugase UbE2K cooperate in the synthesis of unanchored K48-linked polyubiquitin chains, which activate IKKϵ for subsequent STAT1 phosphorylation. Our work defines a previously unrecognized activating role of K48-linked unanchored polyubiquitin chains in kinase activation and identifies the UbE2K-TRIM6-ubiquitin axis as critical for IFN signaling and antiviral response.
A Fully Integrated 47.6% Fractional Bandwidth GaN MMIC Distributed Efficient Power Amplifier With Modified Input Matching and Power Splitting Network (2021)

This article presents a fully integrated distributed efficient power amplifier (DEPA) for fifth-generation (5G) massive multiple-input multiple-output (MIMO) applications. In conventional DEPA, an individual input matching network (IMN), power splitter, and phase compensation line are used for each auxiliary power amplifier (PA) unit, resulting in a large overall size. To facilitate integration, an energy-efficient and compact DEPA with modified input matching and power splitting network is proposed, where a distributed input matching network (DIMN) is used for the auxiliary PA. A broadband input matching, reasonable power splitting, and phase alignment can be achieved simultaneously by adjusting the dimensions of gate transmission lines (TLs) between different auxiliary PA units. An integrated DEPA is implemented in a commercial 0.25- μm GaN-HEMT process to validate the proposed architecture. The fabricated DEPA shows a saturated output power of 40.4-41.7 dBm, an 8-dB back-off drain efficiency (DE) of 35%-50%, and a saturated DE of 46%-56% from 3.2 to 5.2 GHz, with a compact size of 3.4×3.0 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . Applying a 100-MHz orthogonal frequency division multiplexing (OFDM) signal with a 7.8-dB peak-to-average power ratio (PAPR), an average efficiency of 35.7%-47% is measured over the entire bandwidth, and the adjacent channel power ratio (ACPR) is better than -46 dBc after digital predistortion (DPD). To the best of our knowledge, the proposed DEPA demonstrates the widest bandwidth among all reported fully integrated back-off efficient PAs without using digital techniques or reconfiguration.
Photocurrent switching method based on photoisomerization of diarylethene layer for nondestructive readout of photochromic optical memory (2010)

We report on photocurrent switching based on photoisomerization for the nondestructive readout of photochromic optical memory. The photoisomerization of a diarylethene (DAE) memory layer switched the photocurrent generated in a light-absorbing phthalocyanine layer upon irradiation of a laser light. This switching is based on the ionization potential change of the DAE molecules. Switching characteristics of the photocurrent were investigated for the laser light with a wavelength of 410 nm, 630 nm, or 780 nm. Excellent on-off ratios of the photocurrent were achieved by irradiation at 630 nm and 780 nm. When the pulsed laser light with a wavelength of 780 nm was repeatedly irradiated to the colored and uncolored memory devices, no change of the photocurrent signal levels was observed, even after 8 x 10(5) cycles, indicating a successful demonstration of the nondestructive readout.
The Palladium(II)‐Substituted, Lone Pair Containing Tungstoarsenates(III) [Na2(H2O)2PdWO(H2O)(α‐AsW9O33)2]10– and [Cs2Na(H2O)8Pd3(α‐AsW9O33)2]9– (2005)

Abstract The monopalladium( II )‐substituted [Na 2 (H 2 O) 2 PdWO(H 2 O)(α‐AsW 9 O 33 ) 2 ] 10– ( 1 ) and the tripalladium( II )‐substituted [Cs 2 Na(H 2 O) 8 Pd 3 (α‐AsW 9 O 33 ) 2 ] 9– ( 2 ) were synthesized in aqueous acidic medium (pH 4.8) by reaction of Pd 2+ ions with [As 2 W 19 O 67 (H 2 O)] 14– and [α‐AsW 9 O 33 ] 9– , respectively. The dimeric polyanions 1 and 2 were characterized by complete elemental analysis, FTIR, and electrochemistry. Single‐crystal X‐ray analysis was carried out on Cs 3 Na 7 [Na 2 (H 2 O) 2 PdWO(H 2 O)(α‐AsW 9 O 33 ) 2 ] · 1.5NaCl · 22H 2 O ( 1a ), which crystallizes in the triclinic system, space group P $\bar {1}$ , with a = 13.2465(16) Å, b = 16.873(2) Å, c = 23.080(3) Å, α = 107.315(2)°, β = 95.025(3)°, γ = 98.040(3)°, and Z = 2; Cs 3 Na 6 [Cs 2 Na(H 2 O) 8 Pd 3 (α‐AsW 9 O 33 ) 2 ] · NaCl · 15H 2 O ( 2a ) crystallizes in the monoclinic system, space group P 2 1 /m , with a = 13.1842(5) Å, b = 19.6584(7) Å, c = 18.2377(6) Å, β = 100.7660(10)°, and Z = 2. Polyanion 1 is composed of two [α‐AsW 9 O 33 ] 9– fragments connected by a WO(H 2 O) unit, one square‐planar palladium atom and two sodium ions, leading to a sandwich‐type structure with C s symmetry. Polyanion 2 also consists of two [α‐AsW 9 O 33 ] 9– moieties, but these are linked by three equivalent, square‐planar Pd 2+ ions, one sodium ion and two cesium ions, leading to a sandwich‐type structure with C 2 v symmetry. A cyclic voltammetric study of polyanion 2 in a pH 5 medium shows a Pd 0 deposition process on the glassy carbon electrode surface. The corresponding wave and the waves for the tungsten redox processes could be separated clearly. The thickness of the film increases with the number of potential cycles or the duration of potentiostatic electrolysis. The deposited film proved to be very stable and efficient in the electrocatalytic reduction of dioxygen. Polyanion 1 was not sufficiently stable in solution to warrant electrochemical characterization. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)