gebhart/patrepeval huggingface dataset:
ATRT-05. PRC1 IS AN ESSENTIAL DEPENDENCY AND THERAPEUTIC TARGET IN SMARCB1 DEFICIENT ATYPICAL TERATOID RHABDOID TUMORS (2019)

Atypical Teratoid Rhabdoid Tumors (ATRT) occur in young children with poor survival. ATRT are characterized by the absence of the chromatin remodeling protein SMARCB1 resulting in epigenetic dysregulation. To identify specific epigenetic factors essential for ATRT tumorigenesis, we performed a shRNA screen targeting 408 genes classified as epigenetic/chromatin-associated molecules in patient-derived ATRT cell lines. This unbiased screen identified BMI1, a component of the Polycomb Repressive Complex 1 (PRC1), as essential for ATRT cell viability. We hypothesized that BMI1 promotes ATRT tumorigenesis by co-operating with SMARCB1 loss to suppress scheduled transcription of pro-differentiation pathways and promote self-renewal of tumor stem cells. We found that BMI1 expression is elevated in ATRT patient samples and cell lines compared to the normal pediatric cerebellum. Genetic depletion of BMI-1 suppressed ATRT cell clonogenicity and decreased in vitro stem cell maintenance. Using RNA-seq-based gene set enrichment analysis we show that BMI1 depletion decreases c-MYC driven transcriptomic programs and induces p53 driven apoptotic programs. This suggests that BMI-1 drives ATRT tumorigenesis by promotingc-Myc driven tumor stem cell self-renewal and driving resistance to therapy by inactivating p53 mediated apoptotic pathways. Finally, we sought to evaluate whether BMI1 is a therapeutic vulnerability in ATRT. We found that PTC596, the clinical lead compound inhibitor of BMI-1, significantly inhibited clonogenic potential, decreased S-phase length and induced apoptosis in ATRT cells in vitro. Furthermore, using ChIP-seq we show that PTC596 alters chromatin occupancy of BMI1 away from differentiation associated gene promoters in ATRT cells. In vivo PTC 596 significantly decreased growth of intracranial orthotopic ATRT tumors compared to control animals as evaluated by MRI imaging. Moreover, treated mice survived significantly longer than control animals. These studies are the first pre-clinical validation of PRC1/BMI1 inhibition as a novel therapeutic approach in ATRT.
Kinesin spindle protein SiRNA slows tumor progression (2012)

The kinesin spindle protein (KSP), a member of the kinesin superfamily of microtubule-based motors, plays a critical role in mitosis as it mediates centrosome separation and bipolar spindle assembly and maintenance. Inhibition of KSP function leads to cell cycle arrest at mitosis with the formation of monoastral microtubule arrays, and ultimately, to cell death. Several KSP inhibitors are currently being studied in clinical trials and provide new opportunities for the development of novel anticancer therapeutics. RNA interference (RNAi) may represent a powerful strategy to interfere with key molecular pathways involved in cancer. In this study, we have established an efficient method for intratumoral delivery of siRNA. We evaluated short interfering RNA (siRNA) duplexes targeting luciferase as surrogate marker or KSP sequence. To examine the potential feasibility of RNAi therapy, the siRNA was transfected into pre-established lesions by means of intratumor electro-transfer of RNA therapeutics (IERT). This technology allowed cell permeation of the nucleic acids and to efficiently knock down gene expression, albeit transiently. The KSP-specific siRNA drastically reduced outgrowth of subcutaneous melanoma and ovarian cancer lesions. Our results show that intratumoral electro-transfer of siRNA is feasible and KSP-specific siRNA may provide a novel strategy for therapeutic intervention.
INSTABILITY FOLLOWING PRIMARY TKA: WOBBLE AND BUCKLE (2015)

Instability currently represents the most frequent cause for revision total knee replacement. Instability can be primary from the standpoint of inadequately performed collateral and/or posterior cruciate ligament balancing during primary total knee replacement or it may be secondary to malalignment secondary to loosening which can develop later progressive instability. Revision surgery must take into consideration any component malalignment that may have primarily contributed to instability. Care should be given to assessing collateral ligament integrity. This can be done during physical examination by manual or radiological stress testing to see if the mediolateral stress of the knee comes to a good endpoint. If there is no sense of a palpable endpoint, then the surgeon must assume structural incompetency of the medial or lateral collateral ligament or both. In posterior cruciate ligament retaining knees, anteroposterior instability must be assessed. For instability, most revisions will require a posterior cruciate substituting design or a constrained unlinked condylar design that, although sometimes a posterior cruciate ligament preserving design can be used in situations where the bone-stock is well preserved. However, if the patient displays considerable global instability, a linked, rotating platform constrained total knee replacement design will be required. Recent data has shown that the rotating hinges work quite well in restoring stability to the knee with maintenance of the clinical results over a considerable length of time. During revision surgery, laminar spreaders may be utilised to assess the flexion and extension spaces after the tibial platform is restored. If a symmetric flexion and extension space is achieved, then the collateral ligaments are intact. Depending on the remaining existing bone stock, a posterior stabilised or constrained condylar unlinked prosthesis may be used for implantation. In cases with considerable asymmetry or a large flexion/extension mismatch, then a rotating hinge design should be utilised. Intramedullary stems should be utilised in most cases when bone integrity is suspect and insufficient. Currently, stems should be placed cementless to permit easier future revision. Cementing the stems is only recommended if there is lack of intramedullary isthmic support or there is a hip prosthetic stem that prohibits a stem from engaging the isthmic cortex. However, it should be realised that later revision of the fully cemented revision implant may be quite difficult. Infection should be ruled out by aspiration off of antibiotics prior to any revision operation, especially if loosening of the components represents the cause of instability. The surgeon should attempt to restore collateral ligament balance whenever possible as this yields the best clinical result.
A Novel Non-Mirrored Buck-Boost Flying Capacitor Multilevel DC-DC Converter Topology (2022)

Enabling future electrification of air and ground transportation requires flexible, compact, and highly efficient power converters. Four-switch non-inverting bidirectional buck-boost dc-dc converters allow for wide and overlapping input and output voltage ranges, enabling integration of fuel cells and batteries whose voltages vary with state of charge and operating conditions. In this work, we propose a novel non-mirrored buck-boost (N-MBB) Flying Capacitor Multilevel (FCML) dc-dc converter. The proposed topology integrates the conventionally separated buck and boost bridge-legs, which is enabled by novel monolithic bidirectional GaN transistors featuring bipolar voltage blocking capability. Compared to the conventional mirrored buck-boost FCML converter, the proposed topology shows a higher inductor vol-ume but advantageously a lower component count, better utilization of the installed chip area and flying capacitors, and lower conduction losses. Finally we introduce a topology variant with reduced induc-tor volume, the return-path-inductor (RPI) N-MBB FCML, and a direct non-isolated single-phase dc-ac N-MBB FCML inverter.
CO 2 -fixing one-carbon metabolism in a cellulose-degrading bacterium Clostridium thermocellum (2016)

Clostridium thermocellum can ferment cellulosic biomass to formate and other end products, including CO<sub>2</sub> This organism lacks formate dehydrogenase (Fdh), which catalyzes the reduction of CO<sub>2</sub> to formate. However, feeding the bacterium <sup>13</sup>C-bicarbonate and cellobiose followed by NMR analysis showed the production of <sup>13</sup>C-formate in C. thermocellum culture, indicating the presence of an uncharacterized pathway capable of converting CO<sub>2</sub> to formate. Combining genomic and experimental data, we demonstrated that the conversion of CO<sub>2</sub> to formate serves as a CO<sub>2</sub> entry point into the reductive one-carbon (C1) metabolism, and internalizes CO<sub>2</sub> via two biochemical reactions: the reversed pyruvate:ferredoxin oxidoreductase (rPFOR), which incorporates CO<sub>2</sub> using acetyl-CoA as a substrate and generates pyruvate, and pyruvate-formate lyase (PFL) converting pyruvate to formate and acetyl-CoA. We analyzed the labeling patterns of proteinogenic amino acids in individual deletions of all five putative PFOR mutants and in a PFL deletion mutant. We identified two enzymes acting as rPFOR, confirmed the dual activities of rPFOR and PFL crucial for CO<sub>2</sub> uptake, and provided physical evidence of a distinct in vivo "rPFOR-PFL shunt" to reduce CO<sub>2</sub> to formate while circumventing the lack of Fdh. Such a pathway precedes CO<sub>2</sub> fixation via the reductive C1 metabolic pathway in C. thermocellum These findings demonstrated the metabolic versatility of C. thermocellum, which is thought of as primarily a cellulosic heterotroph but is shown here to be endowed with the ability to fix CO<sub>2</sub> as well.
Acousto-optic imaging using plane waves (Conference Presentation) (2018)

Acousto-optic imaging is a multi-modal imaging technique where coherent light diffusing in a complex medium is 'tagged' over time by a ballistic ultrasound pulse of frequency ωus. The photons which paths cross with the ultrasound pulse undergo the acousto-optic effect, resulting in the frequency shift of ωus that can be selectively detected using heterodyne interferometry. Since the ultrasounds propagate at a known velocity, a time-to-space map of the tagged photons results in an image I(x, z), where x is the lateral direction and z the depth direction of the diffuse medium. Images at propagation depths much greater than the average mean free path, typically ~1mm in biological tissue, can be obtained. In most images obtained so far, the ultrasounds are focused line after line to recover an image, and therefore limited by the probe emission rate which is ~1-10 KHz depending on the probe size and the acoustic pulse power. Therefore, in order to acquire acoustic images at frame rates greater than 1 Hz for 'direct visualization' of the system under study, it is crucial to minimize the number of individual acquisitions necessary to reconstruct an image. Here, we present an alternative probe configuration where plane waves emitted at various angles are used rather than focused waves to tag the diffuse light. This approach, first proposed by P.Kuchment and L.Kunyansky (2010), is similar to X-ray tomography since the image information is contained in the various angular scans performed for one acquisition. Because the piezo-elements on the acoustic probe are non-isotropic emitters, the angular scan is typically limited to +/20 degrees, which is sufficient to recover information and can be improved using more than one probe. An inversion algorithm based on inverse Radon-transform is than used to reconstruct the image
Supplementary Figure 3 from Transformation-Dependent Silencing of Tumor-Selective Apoptosis-Inducing TRAIL by DNA Hypermethylation Is Antagonized by Decitabine (2023)

Supplementary Figure 3 from Transformation-Dependent Silencing of Tumor-Selective Apoptosis-Inducing TRAIL by DNA Hypermethylation Is Antagonized by Decitabine
High efficiency silicon strip waveguide to plasmonic slot waveguide mode converter (2015)

high-efficiency silicon strip waveguide to plasmonic slot waveguide converter based on the hybrid silicon-gold taper is proposed and optimized. Through investigating the mode matching, the effective index matching, and the metallic absorption loss considerations, the hybrid silicon-gold taper with an overall length of 1.7 μm having a very high conversion efficiency of 93.3% at 1550nm is achieved. Besides, the configuration limitations for restricting this mode converter to achieve a 100 % conversion efficiency are also studied in this paper. Such a high efficiency converter will be an essential component in ultra-compact integrated circuits.
Análisis de MMPs en fluidos orales en el diagnóstico complementario de las enfermedades periodontales (2012)

La periodontitis constituye la infección bacteriana más prevalente a nivel mundial y representa un factor de riesgo para diversas patologías sistémicas.El estado de inflamación y destrucción periodontal se manifiestan a través de la presencia de biomarcadores en el suero y fluidos orales, tales como el fluido gingival crevicular (FGC), saliva y enjuague oral.Enzimas como las metaloproteinasas de matriz (MMP) y mieloperoxidasa, constituyen biomarcadores potenciales para ensayos moleculares complementarios a la clínica de uso en el sillón dental.A continuación se presenta una revisión de la literatura respecto de la aplicación potencial del análisis de metaloproteinasas de matriz extracelular (MMPs) en el diagnóstico complementario de las enfermedades periodontales.Se ha demostrado que los niveles de MMP-9, -13 y particularmente de MMP-8, se asocian con el grado de inflamación periodontal, y pueden diferenciar entre sujetos sanos, con gingivitis, periodontitis y peri-implantitis, mientras que la mejoría de los parámetros clínicos en respuesta al tratamiento periodontal se asocia con la reducción de la activación y niveles de estas enzimas en FGC, como así también en el suero.Se concluye que la determinación, particularmente de MMP-8 en fluidos orales presenta un elevado potencial como complemento de los métodos clínicos tradicionales para identificar a los pacientes con periodontitis o en riesgo de desarrollar la enfermedad, monitorear fases del tratamiento y mejoría de signos periodontales e incluso evaluar el estado de inflamación sistémica.
Coupled anaerobic/aerobic treatment of high-sulfate wastewater with sulfate reduction and biological sulfide oxidation (1996)

A pharmaceutical wastewater with a chemical oxygen demand (COD) concentration of 40,000 mg/l and a sulfate concentration of 5,000 mg/l was treated in a anaerobic baffled reactor. Treatment of the wastewater at 10% dilution was effective but at higher influent concentrations sulfide inhibition reduced efficacy of both COD conversion and sulfate conversion. A recycle line with an attached-film biological reactor was inserted into the anaerobic baffled reactor to facilitate biological sulfide oxidation. Recycling anaerobic effluent through a sulfide oxidizing biological system reduced inhibition in the anaerobic reactor by both reducing inhibitory sulfide concentrations within the reactor and by diluting the influent. The major product of the biological oxidation of sulfide by a Thiobacillus species appeared to be elemental sulfur. At an influent wastewater concentration of 40% and a HRT of 1 day, COD removal efficiencies were greater than 50% and the conversion of influent sulfate was greater than 95% with effluent sulfide concentrations of less than 20 mg/l. The major product observed from degradation of isopropyl acetate was acetic acid. Coupled anaerobic/aerobic provided removal of sulfur from the wastewater stream and helped to stabilize the pH in the reactor system.
A 128-Gb/s 1.3-pJ/b PAM-4 Transmitter With Reconfigurable 3-Tap FFE in 14-nm CMOS (2019)

This article describes a 128-Gb/s pulse amplitude-modulation 4-level (PAM-4) transmitter (TX) implemented in a 14-nm CMOS FinFET technology. Equalization is provided by a fully reconfigurable 3-tap baud-spaced feed-forward equalizer (FFE). The TX uses a segmented tailless current mode logic (CML) driver topology. The key architectural and circuit techniques include the thermometer-encoded driver slices, the clock phase selection circuits to perform segment reassignment to different FFE taps, and coarse–fine tuning of the FFE tap weights. The measured energy efficiencies for PAM-4 signaling are 1.33 pJ/b at 128 Gb/s with 1-V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ppd</sub> output amplitude and 1.0 pJ/b at 112 Gb/s with 0.6-V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ppd</sub> output amplitude. These results represent the highest data rate and best energy efficiencies reported to date.
Ketonic Decarboxylation Reaction Mechanism: A Combined Experimental and DFT Study (2012)

The ketonic decarboxylation of carboxylic acids has been carried out experimentally and studied theoretically by DFT calculations. In the experiments, monoclinic zirconia was identified as a good catalyst, giving high activity and high selectivity when compared with other potential catalysts, such as silica, alumina, or ceria. It was also shown that it could be used for a wide range of substrates, namely, for carboxylic acids with two to eighteen carbon atoms. The reaction mechanism for the ketonic decarboxylation of acetic acid over monoclinic zirconia was investigated by using a periodic DFT slab model. A reaction pathway with the formation of a β-keto acid intermediate was considered, as well as a concerted mechanism, involving simultaneous carbon-carbon bond formation and carbon dioxide elimination. DFT results showed that the mechanism with the β-keto acid was the kinetically favored one and this was further supported by an experiment employing a mixture of isomeric (linear and branched) pentanoic acids.
Principal component filter banks for optimal multiresolution analysis (1995)

An important issue in multiresolution analysis is that of optimal basis selection. An optimal P-band perfect reconstruction filter bank (PRFB) is derived in this paper, which minimizes the approximation error (in the mean-square sense) between the original signal and its low-resolution version. The resulting PRFB decomposes the input signal into uncorrelated, low-resolution principal components with decreasing variance. Optimality issues are further analyzed in the special case of stationary and cyclostationary processes. By exploiting the connection between discrete-time filter banks and continuous wavelets, an optimal multiresolution decomposition of L/sub 2/(R) is obtained. Analogous results are also derived for deterministic signals. Some illustrative examples and simulations are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A framework for the evaluation of intrusion detection systems (2006)

Classification accuracy in intrusion detection systems (IDSs) deals with such fundamental problems as how to compare two or more IDSs, how to evaluate the performance of an IDS, and how to determine the best configuration of the IDS. In an effort to analyze and solve these related problems, evaluation metrics such as the Bayesian detection rate, the expected cost, the sensitivity and the intrusion detection capability have been introduced. In this paper, we study the advantages and disadvantages of each of these performance metrics and analyze them in a unified framework. Additionally, we introduce the intrusion detection operating characteristic (IDOC) curves as a new IDS performance tradeoff which combines in an intuitive way the variables that are more relevant to the intrusion detection evaluation problem. We also introduce a formal framework for reasoning about the performance of an IDS and the proposed metrics against adaptive adversaries. We provide simulations and experimental results to illustrate the benefits of the proposed framework
A brief review of nanoparticles-doped PEDOT:PSS nanocomposite for OLED and OPV (2022)

Abstract In recent years, several strategies have been proposed and demonstrated to enhance the efficiency of organic light-emitting diodes (OLEDs) and organic photovoltaics (OPVs). In both types of devices, poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) is commonly used to enhance hole injection. The layer is further designed by incorporating metallic-based, carbon-based, organic, inorganic, and hybrid nanoparticles with the aim of improving the performance and hence the efficiency through the improvement of light out-coupling in OLEDs and enhancement in light absorption generation of hole-charge carriers in OPVs. This review elucidates the use of different types of nanoparticles that are doped into PEDOT:PSS and their effects on OLEDs or OPVs. The effects include surface plasmon resonance (SPR), scattering, better charge transport, improvement in surface morphology and electrical properties of PEDOT:PSS. Promising results have been obtained and can potentially lead to low cost, large-area manufacturing process.
Surface Seismic with Distributed Acoustic Sensing: Is Trenching Worthwhile? (2020)

Summary Distributed Acoustic Sensing is a maturing ground motion sensing technology based on the interrogation of a low-cost fiber optic cable to derive broad-band, potentially unaliased, strain variations over long distances. DAS is a recognized option for seismic downhole applications and one may also foresee promising surface applications, for instance by simultaneously interrogating the large cable-based communication network of modern digital point-sensor acquisition systems. However, clear recommendations on appropriate cable deployment for surface seismic are still lacking. Burial in deep trenches may benefit coupling and the overall data quality, but this is likely to be unaffordable in practice. In this study, we analyse the impact of burial depth on the DAS data quality by comparing “co-located” stretches of DAS cable buried at different depths during an active-source seismic survey. Our analysis reveals comparable data quality for cables buried at shallow (2cm) depth and cables at 40cm depth. In contrast, cables deployed on the surface provide unacceptably low data quality likely due to inadequate coupling. Our study suggests that costly deep trenching can be avoided as long as the cables are soil-covered and not directly exposed at the surface.
Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia in the Elderly: Prognostic Factors and Treatment Outcome (2004)

Data on all patients diagnosed with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) aged 55 or older, seen in our institution over a 17-year period, were studied to determine the incidence and range of clinical and biological subtypes, and the outcome of different therapeutic approaches. Twenty-five Ph+ ALL cases (median age: 64 years) were diagnosed between 1986 and 2003 (28% of all B-lineage elderly ALL seen during this period). Karyotypic analysis was performed successfully in 22 cases, while 3 were only diagnosed by molecular biology analysis. All patients had B-cell lineage ALL. Co-expression of myeloid markers was observed in 20% of tested cases. One patient died before chemotherapy could be given. All other patients received "curative" treatment according to different protocols used during the period of study. Overall the complete remission (CR) rate was 76% (95% confidence interval, CI: 55-91%). Fifteen patients achieved CR after one course of chemotherapy and 4 patients after salvage therapy. Median disease-free survival (DFS) of the entire cohort was 5.6 months (95% CI: 4.5-8.4 months) and median overall survival was 10.1 months (95% CI: 7.9-13 months). In multivariate analysis, age>or=70 years was of poor prognostic value for achieving CR (p=0.05) and hyperleukocytosis at diagnosis was of poor prognostic value for overall survival (p=0.001). Overall survival duration was not significantly influenced by achieving CR. Ph+ ALL patients did not show a significant difference in terms of outcome as compared with Philadelphia-negative ALL patients. The very poor overall outcome in elderly patients with Ph+ ALL may be significantly improved by the introduction of imatinib mesylate into current treatment regimens.