gebhart/patrepeval huggingface dataset:
Downregulation of Cancer Stemness by Novel Diterpenoid Ovatodiolide Inhibits Hepatic Cancer Stem Cell-Like Traits by Repressing Wnt/β-Catenin Signaling (2018)

The hierarchical tumor propagation or cancer stem cells (CSCs) model of carcinogenesis postulates that like physiologic adult stem cell (ASC), the CSCs positioned at the apex of any tumor population form the crux of tumor evolution with a constitutive regenerative capacity and differentiation potential. The propagation and recurrence of the characteristically heterogeneous and therapy-resistant hepatocellular carcinoma (HCC), adds to accumulating evidence to support this CSCs model. Based on the multi-etiologic basis of HCC formation which among others, focuses on the disruption of the canonical Wnt signaling pathway, this study evaluated the role of cembrane-type phytochemical, Ovatodiolide, in the modulation of the Wnt/[Formula: see text]-catenin pathway, and its subsequent effect on liver CSCs' activities. Our fluorescence-activated cell sorting (FACS) and quantitative RT-PCR analyses of side population (SP) indicated that CD133+ cells were [Formula: see text]-catenin-overexpressing, more aggressive, and resistant to the conventional anticancer agents, Cisplatin and Doxorubicin, when compared to [Formula: see text]-catenin-downregulated group. We demonstrated that marked upregulation of [Formula: see text]-catenin and its downstream targets effectively enhanced hepatosphere formation, with an associated induction of CD133, OCT4 and Sox2 expression and also caused an significant enhancement of HCC proliferation. However, treatment with Ovatodiolide induced downregulation of [Formula: see text]-catenin and its downstream effector genes, abolished hepatosphere formation and reversed the [Formula: see text]-catenin-associated enhancement of HCC growth. In summary, we demonstrated for the first time that Ovatodiolide suppressed the canonical Wnt signaling pathway, and inhibited the generation of liver CSCs; Thus, projecting Ovatodiolide as a putatively effective therapeutic agent for anti-HCC target therapy.
All-Digital RF $I/Q$ Modulator (2012)

We present a new all-digital RF in-phase/quadrature ( <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">I</i> / <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Q</i> ) modulator, in which the orthogonal summing of the <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">I</i> and <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Q</i> phase data signals is performed in separated interleaved time slots. By employing a 25% duty cycle for the <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">I</i> and <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Q</i> signals, the modulator can directly reconstruct the continuous-time RF output signal using four digital switch arrays with a power combiner. To verify the proposed concept and its related design procedure, a 65-nm CMOS prototype is implemented. This prototype achieves 12.6-dBm peak output power with 20% peak drain efficiency at 2 GHz. The corresponding error vector magnitude (EVM) for a quadrature phase-shift keying constellation is 3.95% without any predistortion, while providing 6-dBm output power in a 64 quadrature amplitude modulation constellation with a related EVM and drain efficiency of 2.36% and 10%, respectively. The proposed circuit can be used as a pre-driver or a final transmit stage. The first-ever truly all-digital <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">I</i> / <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Q</i> RF digital-to-analog converter prototype is thus experimentally demonstrated.
Imaging Pulmonary Blood Flow Using Pseudocontinuous Arterial Spin Labeling (PCASL) With Balanced Steady‐State Free‐Precession (bSSFP) Readout at 1.5T (2020)

2 TECHNICAL EFFICACY STAGE: 2 J. MAGN. RESON. IMAGING 2020;52:1767-1782.
Abstract LB-054: Small molecule inhibitors of the hexosamine biosynthetic pathway and the cancer O-GlcNAcome (2016)

Abstract In recent years, the long-known Warburg effect–wherein cancer cells utilize abnormally high levels of glucose by forgoing oxidative phosphorylation–has been rediscovered but its impact on flux through the hexosamine biosynthetic pathway (HBP) remains relatively unexplored. In this work, we reasoned that UDP-GlcNAc, the end product of the HBP, could promote cancer by increasing the activity of O-GlcNAc transferase (OGT) and subsequently perturb global patterns of protein O-GlcNAcylation. To combat increased O-GlcNAcylation, which is increasingly being linked to cancer cell survival, metastasis, and tumor aggressiveness, most efforts to date have focused on direct inhibition of OGT. In contrast, we take an alternate approach by developing first-in-class small molecules that target UDP-N-acetylglucosamine pyrophosphorylase 1/2 (UAP1/2), the final enzyme of the HBP; this strategy has the added benefit of also potentially reducing the production of highly-branched N-glycans associated with cancer and other diseases. In our first biological tests, presented here, we show that our UAP1/2 inhibitors decrease intracellular UDP-GlcNAc levels as intended and modulate the cancer O-GlcNAcome in a way consistent with reduced viability of difficult-to-treat pancreatic and brain cancer cell lines observed in treated cells. Finally, our strategy of targeting UAP1/2 and the cancer O-GlcNAcome decreased the expression of oncoproteins such as c-Myc, YAP, and TAZ which are all linked to highly aggressive and difficult-to-treat types of cancer. In summary, we have developed first-in-class of small molecules that successfully target UAP1/2, inhibit flux through the HBP, reduce global patterns of O-GlcNAcylation, and knock-down several endpoints linked to cancer progression. Citation Format: Christopher T. Saeui, Kevin Yarema. Small molecule inhibitors of the hexosamine biosynthetic pathway and the cancer O-GlcNAcome. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-054.
Microarray-based approach identifies microRNAs and their target functional patterns in polycystic kidney disease (2008)

We find that the functional patterns of predicted miRNA targets and differentially expressed mRNAs are similar. Our results suggest an important role of miRNAs in specific pathways underlying PKD.
Controlling oxygen vacancies in doped oxide based CBRAM for improved memory performances (2014)

In this paper the concept hybrid CBRAM assisted by oxygen vacancies is presented for the 1 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">st</sup> time. Doping the resistive layer of oxide/Cu based CBRAM with < dopant species and concentrations is proposed in order to improve the memory performances. By means of experimental characterizations, numerical model and atomistic calculations, we demonstrate that increasing the doping content ease the filament formation by facilitating the Cu injection in the resistive layer. The proper choice of the doping element and concentration allows to significantly reduce the forming voltage (up to a forming free behavior), or alternatively to increase the memory window of 3 decades, with no forming voltage increase and retention degradation (stable behavior at 200°C, 260°C soldering sustained).
Figure 5 from A Compendium of Syngeneic, Transplantable Pediatric High-Grade Glioma Models Reveals Subtype-Specific Therapeutic Vulnerabilities (2023)

&lt;p&gt;&lt;b&gt;A,&lt;/b&gt; Top: penetrance of spinal dissemination in tumor-bearing mice harboring H3.3&lt;sup&gt;K27M&lt;/sup&gt;, NF1&lt;sup&gt;LOF&lt;/sup&gt;, and FGFR1&lt;sup&gt;N457K&lt;/sup&gt; mutations compared with all other genotypes. Bottom: representative bright field (BF) and fluorescence (GFP) images of GFP&lt;sup&gt;+&lt;/sup&gt; tumor cells that have disseminated into the thoracic spinal cord. Scale bars, 1 mm. &lt;b&gt;B,&lt;/b&gt; Top: penetrance of exophytic spread in tumor-bearing mice harboring FGFR1&lt;sup&gt;N457K&lt;/sup&gt;, PIK3CA&lt;sup&gt;E545K&lt;/sup&gt;, PPM1D&lt;sup&gt;ΔC&lt;/sup&gt;, and NF1&lt;sup&gt;LOF&lt;/sup&gt;. Bottom: representative BF and fluorescence images showing exophytic spread (bottom left) or a lack of exophytic spread (bottom right) of GFP&lt;sup&gt;+&lt;/sup&gt; tumor cells. Scale bars, 1 mm. &lt;b&gt;C,&lt;/b&gt; Top: penetrance of cranial nerve invasion in tumor-bearing KF, KPP, H3.1KACVPIK, and KPPMPIK mice. Bottom: representative BF and fluorescence images showing cranial nerve invasion of GFP&lt;sup&gt;+&lt;/sup&gt; tumor cells (indicated by white arrows). Scale bars, 1 mm. &lt;b&gt;D,&lt;/b&gt; Analysis of the extent of invasion of H3.1/3&lt;sup&gt;K27M&lt;/sup&gt;-driven tumors into different anatomic regions (CB, cerebellum; BS, brainstem). &lt;b&gt;E,&lt;/b&gt; Immunofluorescence and quantification of Ki-67&lt;sup&gt;+&lt;/sup&gt;/GFP&lt;sup&gt;+&lt;/sup&gt; cells in H3.1/3&lt;sup&gt;K27M&lt;/sup&gt;- and H3.3&lt;sup&gt;G34R&lt;/sup&gt;-driven tumors. GFP&lt;sup&gt;+&lt;/sup&gt; tumor cells have a mitotic index of 10 or higher. Data, mean ± SEM. Representative images showing DAPI, GFP, and Ki-67 immunofluorescence levels in a brainstem tumor are shown on the right. Scale bars, 50 μm. &lt;b&gt;F,&lt;/b&gt; Quantification of H3K27me3 immunofluorescence signal intensity in HA&lt;sup&gt;+&lt;/sup&gt; nuclei in tumors. Data, mean ± SEM; ****, &lt;i&gt;P&lt;/i&gt; &lt; 0.0001 was calculated using the one-way ANOVA test. Representative images of H3K27me3 and HA staining in a brainstem tumor are shown on the right. Scale bars, 50 μm. a.u., arbitrary units.&lt;/p&gt;
Color navigation by qualitative attributes for fashion recommendation (2018)

This paper proposes a novel method to navigate a color palette using attributes recognized from speech input. Our target application is a fashion recommender system for mobile e-commerce. Starting with a selected color, a user can request to show items of a different color by qualitative attributes (e.g. `a little cuter'). These attributes are mapped to a query vector within the Lab color space in order to select the next color. The system distinguishes 85 attributes, each with three different possible magnitudes. This color navigation by speech was demonstrated in a mobile fashion recommender system. The proposed model is validated in a user study with 196 subjects.
Triplex Hybridization of siRNA with Bifacial Glycopolymer Nucleic Acid Enables Hepatocytetargeted Silencing (2019)

We have submitted a new manuscript, entitled “Triplex hybridization of siRNA with bifacial glycopolymer nucleic acid enables hepatocyte-targeted silencing” for consideration as an article in ACS Chemical Biology. My co-authors, Xin Xia, Zhun Zhou, Chris DeSantis, John Rossi and I have agreed on the submission of this manuscript. In the current manuscript, we demonstrate the utility of polyacrylates modified with both an artificial base-triple and a sugar (GalNAc) to serve as an siRNA packaging and delivery platform to hepatocytes in culture and in vivo (mice). This work is based upon our previously published finding that base-triple modified polyacrylates can triplex hybridize with oligo T/U DNA/RNA and deliver luciferase-targeted siRNA to HeLa cells engineered to express luciferase (JACS 2015). Herein, we expand on the scope of this work by employing a well-established liver-targeting ligand (GalNAc) to silence an endogenous human target, ApoB, the primary protein component of low density lipoprotein. Our platform was found to be effective in both hepatocyte (HepG2) cell culture as well as in an animal model of cardiac disease that features elevated ApoB levels. This manuscript thus validates the use of a synthetic platform that is designed to integrate both packaging via triplex hybridization with tissue-targeting ligand display. This enabling method could be useful as a new, convenient siRNA platform that accessible through scalable synthesis. Further, this platform would improve the efficiency of screening siRNA sequences for silencing efficacy using the identical glycopolymer carrier, thus alleviating the need for covalent ligand modification of each RNA substrate as typical for competing technologies.
Direct evidence for the interaction of platelet surface membrane proteins GPIIb and III with cytoskeletal components: Protein crosslinking studies (1985)

When intact platelets are incubated at 37 degrees C with Concanavalin A (ConA), the two major surface membrane proteins GPIIb and III become associated with the Triton-insoluble cytoskeleton. Preincubation of platelets with a variety of metabolic inhibitors, including cytochalasin B, 2-deoxy-D-glucose, and antimycin A or lidocaine, had no effect on the ability of ConA to produce this effect. These results suggested that the ConA-induced anchorage of GPIIb and III to the Triton-insoluble cytoskeleton is a passive process requiring clustering of GPIIb-III molecules but not requiring the metabolic energy of an intact cell. This was supported by experiments that showed that ConA binding to plasma membrane-rich fractions at 37 degrees C could induce association of GPIIb and III with a sedimentable actin-rich, Triton-insoluble membrane matrix. Similar results were obtained when membranes were first isolated from ConA-treated cells. Adding DNAse I, an actin depolymerizing agent, into the Triton extraction buffer inhibited the ConA-induced sedimentation of GPIIb-III and actin by 50% in the presence of Mg2+-ATP. Treatment of ConA-treated membranes with dimethyl-3,3'-dithiobispropiomidate, a bifunctional, reducible protein crosslinking agent, produced Triton-insoluble crosslinked species of discrete molecular weights. When these cross-linked species were analyzed by SDS-PAGE in the presence of beta-mercaptoethanol, they were found to be composed of a 180-200 K dalton protein, GPIIb, GPIII, and actin. Crosslinking of these components was equally effective after Triton treatment and indicated as well that the species crosslinked in the intact membrane was stable after Triton extraction. Addition of crosslinker to membranes not treated with ConA produced similar crosslinked species. Analysis of their composition on reduced gels revealed that the amounts of GPIIb and III were reduced greatly (less than 10% of the total input GPIIb and III) but that the 180-200 k dalton protein and actin content were similar to that seen with ConA-treated membranes. These results are consistent with the notion that ConA clusters mobile, unanchored molecules of GPIIb-III (approximately 90-95% of the total) around a small fraction of IIb-III that is associated with a submembranous cytoskeleton.
Feasibility Study on Subcriticality Monitoring with a Digital Reactivity Meter (2002)

A conventional digital reactivity meter is based on a simple principle to solve inverse point reactor kinetics equations and it can monitor reactivity continuously on a real time basis.Then, feasibility was studied for a conventional digital reactivity meter to be used as a subcriticality monitor.It was necessary to overcome some problems; for example, the applicability of the point reactor kinetics equations must be verified for the system where neutron distribution is dependent on the subcriticality.We showed that the problems can be solved or can be taken into account.The subcriticality calculated by the reactivity meter might not be accurate for the measurement of the actual value of the subcriticality itself, however, it is accurate enough for the purpose of subcriticality monitoring.We believe that the monitoring on a real time basis is more important for subcriticality monitoring than the accuracy of the value of the monitored subcriticality.Based on the study, we proposed that a digital reactivity meter can be used as a subcriticality monitor.
Decomposition via ADMM for scenario-based Model Predictive Control (2015)

We present a scenario-decomposition based Alternating Direction Method of Multipliers (ADMM) algorithm for the efficient solution of scenario-based Model Predictive Control (MPC) problems which arise for instance in the control of stochastic systems. We duplicate the variables involved in the non-anticipativity constraints which allows to develop an ADMM algorithm in which the computations scale linearly in the number of scenarios. Further, the decomposition allows for using different values of the ADMM stepsize parameter for each scenario. We provide convergence analysis and derive the optimal selection of the parameter for each scenario. The proposed approach outperforms the non-decomposed ADMM approach and compares favorably with Gurobi, a commercial QP solver, on a number of MPC problems derived from stopping control of a transportation system.
SYNTHESIS AND ANTIVIRAL EVALUATION OF 3′-C-TRIFLUOROMETHYL NUCLEOSIDE DERIVATIVES BEARING ADENINE AS THE BASE (2001)

3'-deoxy-3'-C-trifluoromethyl- (3), 2',3'-dideoxy-3'-C-trifluoromethyl- (5) and 2',3'-dideoxy-2',3'-didehydro-3'-C-trifluoromethyladenosine (6) derivatives have been synthesized and their antiviral properties examined. All these derivatives were stereospecifically prepared by glycosylation of adenine with a trifluoromethyl sugar precursor (1), followed by appropriate chemical modifications. The prepared compounds were tested for their activity against HIV, but they did not show an antiviral effect.
Systematic Analysis and Comparison of Security Advice as Datasets (2022)

A long list of documents have been offered as security advice, codes of practice, and security guidelines for building and using security products, including Internet of Things (IoT) devices. To date, little or no systematic analysis has been carried out on the advice datasets themselves. Towards addressing this, with IoT as a case study, we begin with an informal analysis of two documents offering advice related to IoT security -- the ETSI Provisions and the UK DCMS Guidelines -- and then carry out what we believe is the first systematic analysis of these advice datasets. Our analysis explains in what ways the ETSI Provisions are a positive evolution of the UK DCMS Guidelines. We also suggest aspects of security advice warranting special attention by those offering security advice. Such parties may find the systematic analysis method, which categorizes advice into predefined categories, to be of general interest beyond IoT itself.
Characterization of the L.lambda. phase in trehalose-stabilized dry membranes by solid-state NMR and x-ray diffraction (1989)

Solid-state nuclear magnetic resonance (NMR) spectroscopy and X-ray powder diffraction were used to investigate the mechanism of trehalose (TRE) stabilization of lipid bilayers. Calorimetric investigation of dry TRE-stabilized bilayers reveals a first-order phase transition (L kappa----L lambda) at temperatures similar to the L beta'----(P beta')----L alpha transition of hydrated lipid bilayers. X-ray diffraction studies show that dry mixtures of TRE and 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) have a lamellar structure with excess crystalline TRE being present. The L kappa phase shows typical gel-phase X-ray diffraction patterns. In contrast, the L lambda-phase diffraction patterns indicate disordered hydrocarbon chains. 2H NMR of specifically 2H chain-labeled DPPC confirmed that the acyl chains are disordered in the L lambda phase over their entire lengths. 2H spectra of the choline headgroup show hindered molecular motions as compared to dry DPPC alone, and 13C spectra of the sn-2-carbonyl show rigid lattice powder patterns indicating very little motion at the headgroup and interfacial regions. Thus, the sugar interacts extensively with the hydrophilic regions of the lipid, from the choline and the phosphate moieties in the headgroup to the glycerol and carbonyls in the interfacial region. We postulate that the sugar and the lipid form an extensive hydrogen-bonded network with the sugar acting as a spacer to expand the distance between lipids in the bilayer. The fluidity of the hydrophobic region in the L lambda phase together with the bilayer stabilization at the headgroup contributes to membrane viability in anhydrobiotic organisms.
Detection of antigen‐specific T cells on p/MHC microarrays (2006)

The development of high-throughput protein microarrays for rapidly determining antigen-specific T-cell receptor repertoires of diverse T-cell populations can enable comprehensive, broad-based analyses of T-cell responses. Promising applications include medical diagnostics, vaccine development, treatment of autoimmune diseases and detection of potential agents of bioterrorism. In this study, we examined the feasibility of using peptide/major histocompatibility complex (p/MHC) microarrays to selectively capture and enumerate antigen-specific T cells. Results are presented for p/MHC microarrays consisting of a dimeric MHC-immunoglobulin complex, K(b)-Ig, loaded with either a cognate or non-cognate peptide for binding CD8(+) T cells. We quantified the sensitivity of these K(b)-Ig microarrays by measuring a lower detection limit of 0.05% antigen-specific CD8(+) T cells mixed with splenocytes from C57BL/6J mouse. A fivefold increase in this lower detection limit (0.01%) was achieved using a secondary capture anti-Ig antibody to coat the microarray surface. This higher sensitivity is comparable to that obtained using standard state-of-the-art fluorescence activated cell sorting (FACS) instruments. We also found that contacting the T-cell suspension with the K(b)-Ig microarrays under mild shear flow conditions produced more uniform distributions of captured T cells on the individual spots and better spot-to-spot reproducibility across the entire microarray.
Efficacy of nonviral gene transfer of human hepatocyte growth factor (HGF) against ischemic-reperfusion nerve injury in rats (2020)

Ischemic neuropathy is common in subjects with critical limb ischemia, frequently causing chronic neuropathic pain. However, neuropathic pain caused by ischemia is hard to control despite the restoration of an adequate blood flow. Here, we used a rat model of ischemic-reperfusion nerve injury (IRI) to investigate possible effects of hepatocyte growth factor (HGF) against ischemic neuropathy. Hemagglutinating virus of Japan (HVJ) liposomes containing plasmids encoded with HGF was delivered into the peripheral nervous system by retrograde axonal transport following its repeated injections into the tibialis anterior muscle in the right hindlimb. First HGF gene transfer was done immediately after IRI, and repeated at 1, 2 and 3 weeks later. Rats with IRI exhibited pronounced mechanical allodynia and thermal hyperalgesia, decreased blood flow and skin temperature, and lowered thresholds of plantar stimuli in the hind paw. These were all significantly improved by HGF gene transfer, as also were sciatic nerve conduction velocity and muscle action potential amplitudes. Histologically, HGF gene transfer resulted in a significant increase of endoneurial microvessels in sciatic and tibial nerves and promoted nerve regeneration which were confirmed by morphometric analysis. Neovascularization was observed in the contralateral side of peripheral nerves as well. In addition, IRI elevated mRNA levels of P2X3 and P2Y1 receptors, and transient receptor potential vanilloid receptor subtype 1 (TRPV1) in sciatic nerves, dorsal root ganglia and spinal cord, and these elevated levels were inhibited by HGF gene transfer. In conclusion, HGF gene transfer is a potent candidate for treatment of acute ischemic neuropathy caused by reperfusion injury, because of robust angiogenesis and enhanced nerve regeneration.