gebhart/patrepeval huggingface dataset:
International multicenter phase II study of the HDAC inhibitor (HDACi) depsipeptide (FK228) in cutaneous T-cell lymphoma (CTCL): Interim report (2006)

3063 Background: Depsipeptide, a unique bicyclic peptide histone deacetylase inhibitor (HDACi), has shown activity in a range of in vitro and in vivo tumor models and clinical activity in T-cell lymphomas and prostate cancer. This study seeks to confirm the CTCL activity previously reported by the NCI (Piekarz, et al., ASCO, 2004). Methods: Single-arm, open label study, in 25 centers in the UK, Germany, Poland and the US. Patients aged ≥18 years with biopsy-confirmed CTCL (centrally reviewed) who have failed at least one prior systemic treatment receive up to 6 cycles of depsipeptide as a 4-hour IV infusion on Days 1, 8 and 15 q 28 days. Eligibility criteria include: mycosis fungoides and Sézary syndrome plus variants, Stages IB - IVA, adequate organ function, ECOG PS ≤ 1. Patients with significant cardiovascular abnormalities are excluded in addition to those taking QTc-prolonging or CYP3A4-inhibiting drugs. The primary endpoint is overall reponse rate measured by a combination of imaging, circulating cell counts and a weighted skin average instrument, confirmed by standardized photography. A subset undergoes pharmacokinetic assessments. Correlative studies include acetylation status, apoptotic markers and proteomic analyses where possible. Target accrual is 76 to yield 64 evaluable patients. Results: 30 patients have received treatment with 17 evaluable for efficacy. Responses seen are 1 cCR, 4 PRs (duration 2+ to 6 months) 9 SD and 3 PD. 3 patients withdrew early for PD and 2 for other reasons. The remaining patients on study are too early to assess. Most frequent toxicities are: nausea/vomiting, fatigue, myelosuppression and asymptomatic ECG changes. No patient has withdrawn for toxicity and there have been no treatment-related deaths. Conclusions: The previously reported efficacy of depsipeptide in CTCL has also been seen in the present study. Duration of response is encouraging. Toxicity is manageable and the study continues to accrue. [Table: see text]
Atmospheric pressure chemical vapor deposition of gallium doped zinc oxide thin films from diethyl zinc, water, and triethyl gallium (1992)

Gallium doped zinc oxide films have been deposited in the temperature range 150 to 470 °C from 0.05% diethyl zinc, 0.8% water, and various triethyl gallium concentrations. The films are polycrystalline with crystallite sizes varying between 275 and 500 Å for undoped films and between 125 and 400 Å for doped films. Only those films deposited above 430 °C are highly oriented and have their c axes perpendicular to the substrate plane. The electron density, conductivity, and mobility always increase with temperature. Thicker films have higher conductivity and mobility than thinner films. The refractive index is reduced from 1.96 to 1.73 when the electron density is increased from zero to 3.7×1020 cm−3. For films deposited at 370 °C with a gallium concentration of about 2.5 at. %, the ratio of conductivity to visible absorption coefficient increases from 0.03 to 1.25 Ω−1 when the film thickness increases from 0.11 to 1.2 μm. A film deposited at 470 °C with a gallium concentration of 2.4 at. % and a thickness of 0.66 μm has a sheet resistance of 3.6 Ω/square and an average visible absorption of 6.8%. When the gallium concentration is less than 5.0 at. %, the band gap widening approximately follows the Burstein–Moss relation.
Using phase spectrum information for improved speech recognition performance (2002)

New acoustic features for continuous speech recognition based on the short-term Fourier phase spectrum are introduced for mono (telephone) recordings. The new phase based features were combined with standard Mel Frequency Cepstral Coefficients (MFCC), and results were produced with and without using additional linear discriminant analysis (LDA) to choose the most relevant features. Experiments were performed on the SieTill corpus for telephone line recorded German digit strings. Using LDA to combine purely phase based features with MFCCs, we obtained improvements in word error rate of up to 25% relative to using MFCCs alone with the same overall number of parameters in the system.
Bioconjugate Strategies for the Induction of Antigen-Specific Tolerance in Autoimmune Diseases (2017)

Antigen-specific immunotherapy (ASI) holds great promise for the treatment of autoimmune diseases. In mice, administration of major histocompatibility complex (MHC) binding synthetic peptides which modulate T cell receptor (TCR) signaling under subimmunogenic conditions induces selective tolerance without suppressing the global immune responses. However, clinical translation has yielded limited success. It has become apparent that the TCR signaling pathway via synthetic peptide antigen alone is inadequate to induce an effective tolerogenic immunity in autoimmune diseases. Bioconjugate strategies combining additional immunomodulatory functions with TCR signaling can amplify the antigen-specific immune tolerance and possibly lead to the development of new treatments in autoimmune diseases. In this review, we provide a summary of recent advances in the development of bioconjugates to achieve antigen-specific immune tolerance in vivo, with the discussion focused on the underlying design principles and challenges that must be overcome to target these therapies to patients suffering from autoimmune diseases.
The Ewing's sarcoma EWS/FLI-1 fusion gene encodes a more potent transcriptional activator and is a more powerful transforming gene than FLI-1. (1993)

EWS/FLI-1 is a chimeric protein formed by a tumor-specific 11;22 translocation found in both Ewing's sarcoma and primitive neuroectodermal tumor of childhood. EWS/FLI-1 has been shown to be a potent transforming gene, suggesting that it plays an important role in the genesis of these human tumors. We now demonstrate that EWS/FLI-1 has the characteristics of an aberrant transcription factor. Subcellular fractionation experiments localized the EWS/FLI-1 protein to the nucleus of primitive neuroectodermal tumor cells. EWS/FLI-1 specifically bound in vitro an ets-2 consensus sequence similarly to normal FLI-1. When coupled to a GAL4 DNA-binding domain, the amino-terminal EWS/FLI-1 region was a much more potent transcriptional activator than the corresponding amino-terminal domain of FLI-1. Finally, EWS/FLI-1 efficiently transformed NIH 3T3 cells, but FLI-1 did not. These data suggest that EWS/FLI-1, functioning as a transcription factor, leads to a phenotype dramatically different from that of cells expressing FLI-1. EWS/FLI-1 could disrupt normal growth and differentiation either by more efficiently activating FLI-1 target genes or by inappropriately modulating genes normally not responsive to FLI-1.
Design of a high-performance ATM firewall (1998)

Article Design of a high-performance ATM firewall Share on Authors: Jun Xu Department of Computer and Information Science, The Ohio State University, Columbus, OH Department of Computer and Information Science, The Ohio State University, Columbus, OHView Profile , Mukesh Singhal Department of Computer and Information Science, The Ohio State University, Columbus, OH Department of Computer and Information Science, The Ohio State University, Columbus, OHView Profile Authors Info & Claims CCS '98: Proceedings of the 5th ACM conference on Computer and communications securityNovember 1998 Pages 93–102https://doi.org/10.1145/288090.288113Online:01 November 1998Publication History 4citation653DownloadsMetricsTotal Citations4Total Downloads653Last 12 Months2Last 6 weeks1 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Partially Distinct Molecular Mechanisms Mediate Inhibitory FcγRIIB Signaling in Resting and Activated B Cells (2001)

FcgammaRIIB functions as an inhibitory receptor to dampen B cell Ag receptor signals and immune responses. Accumulating evidence indicates that ex vivo B cells require the inositol 5-phosphatase, Src homology domain 2-containing inositol 5-phosphatase (SHIP), for FcgammaRIIB-mediated inhibitory signaling. However, we report here that LPS-activated primary B cells do not require SHIP and thus differ from resting B cells. SHIP-deficient B cell blasts display efficient FcgammaRIIB-dependent inhibition of calcium mobilization as well as Akt and extracellular signal-related protein kinase phosphorylation. Surprisingly, FcgammaRIIB-dependent degradation of phosphatidylinositol 3,4,5-trisphosphate and conversion into phosphatidylinositol 3,4-bisphosphate occur in SHIP-deficient B cell blasts, demonstrating the function of an additional inositol 5-phosphatase. Further analysis reveals that while resting cells express only SHIP, B cell blasts also express the recently described inositol 5-phosphatase, SHIP-2. Finally, data suggest that both SHIP-2 and SHIP can mediate downstream biologic consequences of FcgammaRIIB signaling, including inhibition of the proliferative response.
Heat‐induced contraction of blood vessels (1982)

Heat-induced spontaneous contraction of blood vessels as observed during the application of surgical lasers was investigated experimentally. By means of extravascular irrigation of veins and arteries from the rabbit mesentery in vivo with saline that had been preheated to varying temperatures in the range of 45-90 degrees C, the temperature dependence on contraction with evaluated. It was demonstrated that lower temperature thresholds of approximately 70 degrees C and 75 degrees C exist for the shrinkage of veins and arteries, respectively. Ultrastructural investigation of the walls of contracted and of noncontracted vessels indicates that vessel contraction correlates with the denaturation of collagen fibrils. It was therefore concluded that the well-known heat shrinkage effect of denatured collagen accounts for the heat-induced vessel constriction. It is shown that on heat-induced permanent occlusion, vessels of the type that were examined cannot be achieved reliably at temperatures of up to 90 degrees C for 16 sec; in most cases relaxation takes place.
Safety and efficacy of cryopreserved autologous tumor infiltrating lymphocyte therapy (LN-144, lifileucel) in advanced metastatic melanoma patients who progressed on multiple prior therapies including anti-PD-1. (2019)

2518 Background: Treatment options are limited for patients with advanced melanoma who have progressed on checkpoint inhibitors and targeted therapies such as BRAF/MEK inhibitors (if BRAF-V600E mutated). Adoptive cell therapy utilizing tumor-infiltrating lymphocytes (TIL) has shown antitumor efficacy with durable long-term responses in heavily pretreated melanoma patients. Safety and efficacy of lifileucel (LN-144), a centrally manufactured autologous TIL therapy are presented. Methods: C-144-01 is a global Phase 2 open-label, multicenter study of the efficacy and safety of lifileucel in patients with unresectable metastatic melanoma. We report on Cohort 2 (N = 55) patients who received cryopreserved lifileucel. Tumors resected at local institutions were processed in central GMP facilities for TIL production in a 22-day process. Final TIL infusion product was cryopreserved and shipped to sites. Patients received one week of cyclophosphamide/fludarabine preconditioning lymphodepletion, a single lifileucel infusion, followed by up to 6 doses of IL-2. Results: In 55 patients with Stage IIIC/IV unresectable melanoma, 3.1 mean prior therapies (anti-PD1 100%; anti-CTLA-4 80%; BRAF/MEK inhibitor 24%), high baseline tumor burden (110 mm mean target lesion sum of diameters), ORR was 38% (2 CR, 18 PR, 1 uPR). Of 21 responders, 4 have progressed to date with median follow up of 7.4 months. Overall disease control was 76%. Improved responses in some patients were observed with longer follow up. Most (54) patients progressed on prior anti-PD1 and those with PD-L1 negative status (TPS &lt; 5%) were among responders. Mean cells infused was 28 x10 9 . Median IL-2 doses administered was 6.0. Adverse events resolved to baseline, 2 weeks post TIL infusion, a potentially important benefit of one-time TIL therapy. Conclusions: Lifileucel treatment results in 38% ORR in heavily pretreated metastatic melanoma patients with high baseline disease burden who received prior anti-PD1 and BRAF/MEK inhibitor if BRAF mutated. Based on these data, a new Cohort 4 in C-144-01 has been initiated to support lifileucel registration. Clinical trial information: NCT02360579.
The structure of zetekitoxin AB, a saxitoxin analog from the Panamanian golden frog Atelopus zeteki : A potent sodium-channel blocker (2004)

Bufonid anurans of the genus Atelopus contain both steroidal bufadienolides and various guanidinium alkaloids of the tetrodotoxin class. The former inhibit sodium-potassium ATPases, whereas the latter block voltage-dependent sodium channels. The structure of one guanidinium alkaloid, zetekitoxin AB, has remained a mystery for over 30 years. The structure of this alkaloid now has been investigated with a sample of approximately 0.3 mg, purified from extracts obtained decades ago from the Panamanian golden frog Atelopus zeteki. Detailed NMR and mass spectral analyses have provided the structure and relative stereochemistry of zetekitoxin AB and have revealed that it is an analog of saxitoxin. The proposed structure is characterized by richness of heteroatoms (C16H25N8O12S) and contains a unique 1,2-oxazolidine ring-fused lactam, a sulfate ester, and an N-hydroxycarbamate moiety. Zetekitoxin AB proved to be an extremely potent blocker of voltage-dependent sodium channels expressed in Xenopus oocytes. The IC50 values were 280 pM for human heart channels, 6.1 pM for rat brain IIa channels, and 65 pM for rat skeletal muscle channels, thus being roughly 580-, 160-, and 63-fold more potent at these channels than saxitoxin.
Optimized controlled-Z gates for two superconducting qubits coupled through a resonator (2013)

Superconducting qubits are a promising candidate for building a quantum computer. A continued challenge for fast yet accurate gates to minimize the effects of decoherence. Here we apply numerical methods to design fast entangling gates, specifically the controlled Z, in an architecture where two qubits are coupled via a resonator. We find that the gates can be sped up by a factor of two and reach any target fidelity. We also discuss how systematic errors arising from experimental conditions affect the pulses and how to remedy them, providing a strategy for the experimental implementation of our results. We discuss the shape of the pulses, their spectrum and symmetry.
Mass spectrometry of laser‐desorbed oligonucleotides (1992)

Abstract Various matrices were used for laser‐desorption ionization of mixtures of small DNA segments. Parent negative ions of 34‐mer as well as other smaller single‐stranded oligomers were observed for selected organic acids and dye compounds. Both positive and negative parent ions were observed with very little fragmentation. Effects of various matrices and the potential applications to DNA sequencing are briefly discussed.
Phosphorylation of MDMX Mediated by Akt Leads to Stabilization and Induces 14-3-3 Binding (2008)

The critical tumor suppressor p53 is mutated or functionally inactivated in nearly all cancers. We have shown previously that the MDM2-MDMX complex functions as an integral unit in targeting p53 for degradation. Here we identify the small protein 14-3-3 as a binding partner of MDMX, which binds at the C terminus (Ser367) in a phosphorylation-dependent manner. Importantly, we demonstrate that the serine/threonine kinase Akt mediates phosphorylation of MDMX at Ser367. This phosphorylation leads to stabilization of MDMX and consequent stabilization of MDM2. Previous studies have shown that Akt phosphorylates and stabilizes MDM2. Our data suggest that stabilization of MDMX by Akt may be an alternative mechanism by which Akt up-regulates MDM2 protein levels and exerts its oncogenic effects on p53 in tumor cells.
Aedes aegyptiuses RNA interference in defense against Sindbis virus infection (2008)

We show that silencing RNAi components in Ae. aegypti results in transient increases in SINV replication. Furthermore, Ae. aegypti RNAi is active during SINV infection as indicated by production of virus-specific siRNAs. Lastly, the RNAi response varies in a virus-dependent manner. These data define important features of RNAi anti-viral defense in Ae. aegypti.
On the use of hash functions for defect detection in textures for in-camera web inspection systems (2003)

Hash functions are one way functions which are used in cryptography to ensure integrity of files by creating a binary signature specific to that file. A family of special hash functions are developed, which are simple enough to fit into a small FPGA and can generate one dimensional signatures of repeating texture images. While these hash functions are sensitive enough to detect small changes and defects in texture, they are immune to change in illumination and contrast. Analyses of these signatures and determination of the parameters of the hash functions are presented.
Review: Gene-Modified Dendritic Cells for Use in Tumor Vaccines (2000)

Dendritic cells (DCs) are potent antigen-presenting cells capable of priming activation of naive T cells. Because of their immunostimulatory capacity, immunization with DCs presenting tumor antigens has been proposed as a treatment regimen for cancer. The results from translational research studies and early clinical trials point to the need for improvement of DC-based tumor vaccines before they become a more broadly applicable treatment modality. In this regard, studies suggest that genetic modification of DCs to express tumor antigens and/or immunomodulatory proteins may improve their capacity to promote an antitumor response. Because the DC phenotype is relatively unstable, nonperturbing methods of gene transfer must be employed that do not compromise viability or immunostimulatory capacity. DCs expressing transgenes encoding tumor antigens have been shown to be more potent primers of antitumor immunity both in vitro and in animal models of disease; in some measures of immune priming, gene-modified DCs exceeded their soluble antigen-pulsed counterparts. Cytokine gene modification of DCs has improved their capacity to prime tumor antigen-specific T cell responses and promote antitumor immunity in vivo. Here, we review the current status of gene-modified DCs in both human and murine studies. Although successful results have been obtained to date in experimental systems, we discuss potential problems that have already arisen and may yet be encountered before gene-modified DCs are more widely applicable for use in human clinical trials.
A Novel Signaling Complex between TROY and EGFR Mediates Glioblastoma Cell Invasion (2017)

Glioblastoma is the most frequent primary brain tumor in adults and a highly lethal malignancy with a median survival of about 15 months. The aggressive invasion of the surrounding normal brain makes complete surgical resection impossible, increases the resistance to radiation and chemotherapy, and assures tumor recurrence. Thus, there is an urgent need to develop innovative therapeutics to target the invasive tumor cells for improved treatment outcomes of this disease. Expression of TROY (TNFRSF19), a member of the tumor necrosis factor (TNF) receptor family, increases with increasing glial tumor grade and inversely correlates with patient survival. Increased expression of TROY stimulates glioblastoma cell invasion <i>in vitro</i> and <i>in vivo</i> and increases resistance to temozolomide and radiation therapy. Conversely, silencing TROY expression inhibits glioblastoma cell invasion, increases temozolomide sensitivity, and prolongs survival in an intracranial xenograft model. Here, a novel complex is identified between TROY and EGFR, which is mediated predominantly by the cysteine-rich CRD3 domain of TROY. Glioblastoma tumors with elevated TROY expression have a statistically positive correlation with increased EGFR expression. TROY expression significantly increases the capacity of EGF to stimulate glioblastoma cell invasion, whereas depletion of TROY expression blocks EGF stimulation of glioblastoma cell invasion. Mechanistically, TROY expression modulates EGFR signaling by facilitating EGFR activation and delaying EGFR receptor internalization. Moreover, the association of EGFR with TROY increases TROY-induced NF-κB activation. These findings substantiate a critical role for the TROY-EGFR complex in regulation of glioblastoma cell invasion.<b>Implications:</b> The TROY-EGFR signaling complex emerges as a potential therapeutic target to inhibit glioblastoma cell invasion. <i>Mol Cancer Res; 16(2); 322-32. ©2017 AACR</i>.
A fluorescence-based assay for 3′ → 5′ exoribonucleases: Potential applications to the study of mRNA decay (2000)

A cell-free mRNA decay assay has been adapted to permit the kinetics of 3' --> 5' exoribonuclease activities to be monitored in real time. RNA probes containing 5' caps and 3' poly(A) tails generated by transcription in vitro are 3' labeled using fluorescein-N6-ATP and poly(A) polymerase. Release of fluorescein-conjugated adenosine residues from the 3' end of the RNA substrate is monitored by a time-dependent decrease in fluorescence anisotropy in the presence of cytosolic proteins. To demonstrate the utility of the assay, an RNA probe was constructed containing a fragment of the c-myc 3' untranslated region and an 85-base poly(A) tail. Following 3' fluorescein labeling, the rate of 3'-terminal adenosine excision was monitored in the presence of an S100 cytosolic extract prepared from K562 erythroleukemia cells. Removal of the fluorescein-tagged A residues resolved to a first-order decay function, allowing the rate constant and enzyme-specific activity to be determined in this extract. Further applications and advantages of this technology are discussed.
Visualizing Information on Mobile Devices (2006)

Visualization can make a wide range of mobile applications more intuitive and productive. The mobility context and technical limitations such as small screen size make it impossible to simply port visualization applications from desktop computers to mobile devices, but researchers are starting to address these challenges. From a purely technical point of view, building more sophisticated mobile visualizations become easier due to new, possibly standard, software APIs such as OpenGLES and increasingly powerful devices. Although ongoing improvements would not eliminate most device limitations or alter the mobility context, they make it easier to create and experiment with alternative approaches.
Spatial fluctuations of optical emission from single ZnO/MgZnO nanowire quantum wells (2008)

MgZnO/ZnO quantum wells on top of ZnO nanowires were grown by pulsed laser deposition. Ensembles of spatially fluctuating and narrow cathodoluminescence peaks with single widths down to 1 meV were found at the spectral position of the quantum well emission at 4 K. In addition, the number of these narrow QW peaks increases with increasing excitation power in micro-photoluminescence, thus pointing to quantum-dot-like emission centers. Indeed, laterally strained areas of about 5 nm diameter were identified at the quantum well positions on top of the nanowires by high-resolution transmission electron microscopy.