gebhart/patrepeval huggingface dataset:
Data from Targeting Myddosome Signaling in Waldenström's Macroglobulinemia with the Interleukin-1 Receptor-Associated Kinase 1/4 Inhibitor R191 (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;Waldenström's macroglobulinemia is an incurable lymphoproliferative disorder driven by an L265P mutation in the myeloid differentiation primary response gene 88 (&lt;i&gt;MYD88&lt;/i&gt;), which activates downstream NF-κB signaling through the Myddosome. As this pathway depends in part on activity of interleukin-1 receptor-associated kinases (IRAKs)-1 and -4, we sought to evaluate the potential of the IRAK1/4 inhibitor R191 in preclinical models.&lt;/p&gt;Experimental Design:&lt;p&gt;Patient-derived cell lines and primary samples were used in both &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt; experiments to model Waldenström's macroglobulinemia and its response to IRAK1/4 inhibitors.&lt;/p&gt;Results:&lt;p&gt;R191 induced a dose- and time-dependent reduction in viability of BCWM.1 and MWCL-1 Waldenström's cell lines, and suppressed activation of IRAK1/4. This was associated with cell-cycle arrest at G&lt;sub&gt;0&lt;/sub&gt;–G&lt;sub&gt;1&lt;/sub&gt;, reduced levels of cyclin-dependent kinases 4 and 6, and induction of apoptosis in cell lines and primary patient samples. Further downstream, R191 exposure led to reduced activation of NF-κB, and of protein kinase B/Akt/mammalian target of rapamycin signaling, whereas expression of a constitutively active Akt mutant induced R191 resistance. Gene expression profiling and gene set enrichment analysis revealed a signature consistent with inhibition of c-Myc and activation of the endoplasmic reticulum stress response. In both subcutaneous and systemic murine models of Waldenström's, R191 showed antitumor activity. Finally, the activity of R191 was enhanced when it was combined with novel chemotherapeutics such as bortezomib, afuresertib, and ibrutinib.&lt;/p&gt;Conclusions:&lt;p&gt;Taken together, these data support the translation of R191 as an approach to target IRAK1/4 to the clinic for patients with Waldenström's macroglobulinemia.&lt;/p&gt;&lt;/div&gt;
Loss of Thioredoxin Reductase 1 Renders Tumors Highly Susceptible to Pharmacologic Glutathione Deprivation (2010)

Tumor cells generate substantial amounts of reactive oxygen species (ROS), engendering the need to maintain high levels of antioxidants such as thioredoxin (Trx)- and glutathione (GSH)-dependent enzymes. Exacerbating oxidative stress by specifically inhibiting these types of ROS-scavenging enzymes has emerged as a promising chemotherapeutic strategy to kill tumor cells. However, potential redundancies among the various antioxidant systems may constrain this simple approach. Trx1 and thioredoxin reductase 1 (Txnrd1) are upregulated in numerous cancers, and Txnrd1 has been reported to be indispensable for tumorigenesis. However, we report here that genetic ablation of Txnrd1 has no apparent effect on tumor cell behavior based on similar proliferative, clonogenic, and tumorigenic potential. This finding reflects widespread redundancies between the Trx- and GSH-dependent systems based on evidence of a bypass to Txnrd1 deficiency by compensatory upregulation of GSH-metabolizing enzymes. Because the survival and growth of Txnrd1-deficient tumors were strictly dependent on a functional GSH system, Txnrd1-/- tumors were highly susceptible to experimental GSH depletion in vitro and in vivo. Thus, our findings establish for the first time that a concomitant inhibition of the two major antioxidant systems is highly effective in killing tumor, highlighting a promising strategy to combat cancer.
Prevalence of somatic alterations in the colorectal cancer cell genome (2002)

Although a small fraction of human cancers have increased rates of somatic mutation because of known deficiencies in DNA repair, little is known about the prevalence of somatic alterations in the vast majority of human cancers. To systematically assess nonsynonymous somatic alterations in colorectal neoplasia, we used DNA sequencing to analyze approximately 3.2 Mb of coding tumor DNA comprising 1,811 exons from 470 genes. In total, we identified only three distinct somatic mutations, comprising two missense changes and one 14-bp deletion, each in a different gene. The accumulation of approximately one nonsynonymous somatic change per Mb of tumor DNA is consistent with a rate of mutation in tumor cells that is similar to that of normal cells. These data suggest that most sporadic colorectal cancers do not display a mutator phenotype at the nucleotide level. They also have significant implications for the interpretation of somatic mutations in candidate tumor-suppressor genes.
On the performance projectability of MapReduce (2012)

A key challenge faced by users of public clouds today is how to request for the right amount of resources in the production datacenter that satisfies a target performance for a given cloud application. An obvious approach is to develop a performance model for a class of applications such as MapReduce. However, several recent studies have shown that even for the class of well-studied MapReduce jobs, their running times can be seriously affected by numerous external factors ranging from dozen or so configuration parameters, to the physical machine characteristics (CPU, memory, disk, and network bandwidth), to implementation deficiencies such as Java, garbage collection. These factors make direct performance modeling extremely difficult. In this paper, we propose a more practical systematic methodology to solve this problem. Our approach develops a projection model, based on insights into performance bottlenecks of MapReduce jobs and their scaling properties, and parameterized with component running times based on profiling on small clusters with sampled inputs. Evaluation results show our projection model can predict job running times with 2.7% of accuracy when scaling to 32 nodes.
Carbofluoresceins and Carborhodamines as Scaffolds for High-Contrast Fluorogenic Probes (2013)

Fluorogenic molecules are important tools for advanced biochemical and biological experiments. The extant collection of fluorogenic probes is incomplete, however, leaving regions of the electromagnetic spectrum unutilized. Here, we synthesize green-excited fluorescent and fluorogenic analogues of the classic fluorescein and rhodamine 110 fluorophores by replacement of the xanthene oxygen with a quaternary carbon. These anthracenyl "carbofluorescein" and "carborhodamine 110" fluorophores exhibit excellent fluorescent properties and can be masked with enzyme- and photolabile groups to prepare high-contrast fluorogenic molecules useful for live cell imaging experiments and super-resolution microscopy. Our divergent approach to these red-shifted dye scaffolds will enable the preparation of numerous novel fluorogenic probes with high biological utility.
Lattice Boltzmann modeling of contact angle and its hysteresis in two-phase flow with large viscosity difference (2015)

Contact angle hysteresis is an important physical phenomenon omnipresent in nature and various industrial processes, but its effects are not considered in many existing multiphase flow simulations due to modeling complexity. In this work, a multiphase lattice Boltzmann method (LBM) is developed to simulate the contact-line dynamics with consideration of the contact angle hysteresis for a broad range of kinematic viscosity ratios. In this method, the immiscible two-phase flow is described by a color-fluid model, in which the multiple-relaxation-time collision operator is adopted to increase numerical stability and suppress unphysical spurious currents at the contact line. The contact angle hysteresis is introduced using the strategy proposed by Ding and Spelt [Ding and Spelt, J. Fluid Mech. 599, 341 (2008)], and the geometrical wetting boundary condition is enforced to obtain the desired contact angle. This method is first validated by simulations of static contact angle and dynamic capillary intrusion process on ideal (smooth) surfaces. It is then used to simulate the dynamic behavior of a droplet on a nonideal (inhomogeneous) surface subject to a simple shear flow. When the droplet remains pinned on the surface due to hysteresis, the steady interface shapes of the droplet quantitatively agree well with the previous numerical results. Four typical motion modes of contact points, as observed in a recent study, are qualitatively reproduced with varying advancing and receding contact angles. The viscosity ratio is found to have a notable impact on the droplet deformation, breakup, and hysteresis behavior. Finally, this method is extended to simulate the droplet breakup in a microfluidic T junction, with one half of the wall surface ideal and the other half nonideal. Due to the contact angle hysteresis, the droplet asymmetrically breaks up into two daughter droplets with the smaller one in the nonideal branch channel, and the behavior of daughter droplets is significantly different in both branch channels. Also, it is found that the contact angle hysteresis is strengthened with decreasing the viscosity ratio, leading to an earlier droplet breakup and a decrease in the maximum length that the droplet can reach before the breakup. These simulation results manifest that the present multiphase LBM can be a useful substitute to Ba et al. [Phys. Rev. E 88, 043306 (2013)] for modeling the contact angle hysteresis, and it can be easily implemented with higher computational efficiency.
Magic Angle Spinning Nuclear Magnetic Resonance Characterization of Voltage-Dependent Anion Channel Gating in Two-Dimensional Lipid Crystalline Bilayers (2014)

National Institutes of Health (U.S.) (EB001960)
T-705 (favipiravir) activity against lethal H5N1 influenza A viruses (2009)

The neuraminidase inhibitors oseltamivir and zanamivi are used to treat H5N1 influenza. However, oseltamivir-resistant H5N1 viruses have been isolated from oseltamivir-treated patients. Moreover, reassortment between H5N1 viruses and oseltamvir-resistant human H1N1 viruses currently circulating could create oseltamivir-resistant H5N1 viruses, rendering the oseltamivir stockpile obsolete. Therefore, there is a need for unique and effective antivirals to combat H5N1 influenza viruses. The investigational drug T-705 (favipiravir; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has antiviral activity against seasonal influenza viruses and a mouse-adapted H5N1 influenza virus derived from a benign duck virus. However, its efficacy against highly pathogenic H5N1 viruses, which are substantially more virulent, remains unclear. Here, we demonstrate that T-705 effectively protects mice from lethal infection with oseltamivir-sensitive or -resistant highly pathogenic H5N1 viruses. Furthermore, our biochemical analysis suggests that T-705 ribofuranosyl triphosphate, an active form of T-705, acts like purines or purine nucleosides in human cells and does not inhibit human DNA synthesis. We conclude that T-705 shows promise as a therapeutic agent for the treatment of highly pathogenic H5N1 influenza patients.
Measurement of the triple-differential cross section for photon + jets production in proton-proton collisions at $ \sqrt{s} $ = 7 TeV (2014)

A measurement of the triple-differential cross section, d 3 /(dp T d d jet ), in photon+jets final states using a data sample from proton-proton collisions at s = 7 TeV is presented. This sample corresponds to an integrated luminosity of 2.14 fb -1 collected by the CMS detector at the LHC. Photons and jets are reconstructed within a pseudorapidity range of || < 2.5, and are required to have transverse momenta in the range 40 < p jet T < 300 GeV and p jet T > 30 GeV, respectively. The measurements are compared to theoretical predictions from the sherpa leading-order QCD Monte Carlo event generator and the next-to-leading-order perturbative QCD calculation from jetphox. The predictions are found to be consistent with the data over most of the examined kinematic region.
Machine-learning detector based on support vector machine for 122-Gbps multi-CAP optical communication system (2017)

In this work, we firstly apply support vector machine (SVM) detector in 122-Gbps Multi-CAP system. It can de-map the rotated constellations directly without any correction. The concrete simulations indicate such a machine-learning based detector provides considerable BER reduction for high-density CAPs in low-frequency band, compared with hard decision.
Unsupervised Learning of Terrain Appearance for Automated Coral Reef Exploration (2009)

We describe a navigation and coverage system based on unsupervised learning driven by visual input. Our objective is to allow a robot to remain continuously moving above a terrain of interest using visual feedback to avoid leaving this region. As a particular application domain, we are interested in doing this in open water, but the approach makes few domain-specific assumptions. Specifically, our system employed an unsupervised learning technique to train a k-Nearest Neighbor classifier to distinguish between images of different terrain types through image segmentation. A simple random exploration strategy was used with this classifier to allow the robot to collect data while remaining confined above a coral reef, without the need to maintain pose estimates. We tested the technique in simulation, and a live deployment was conducted in open water. During the latter, the robot successfully navigated autonomously above a coral reef during a 20 minutes period.
A novel empirical model for NBTI recovery with the modulated measurement time frame (2006)

Negative bias temperature instability (NBTI) of p-MOSFETs gets recovered immediately when the stress is removed, and hence the electrical measurement will tend to underestimate the NBTI degradation due to its unavoidable measurement time. This measurement-induced additional NBTI recovery must also be taken into account, especially during the NBTI recovery process, because it directly affects the time frames. In this work, by using different measurement time interval during the electrical characterization, this repeatable NBTI recovery phenomenon is used to extract the critical measurement time. Thereafter, with the modulated time interval, a novel empirical model for longer-time NBTI recovery is also proposed here so as to describe the entire NBTI recovery process together with previous short-time limited empirical model
Pipestelides A–C: Cyclodepsipeptides from the Pacific Marine SpongePipestela candelabra (2012)

Pipestelides A-C (2-4) are three new NRPS-PKS hybrid macrolides containing uncommon moieties, isolated from the Pacific marine sponge Pipestela candelabra. Their structures were elucidated on the basis of spectroscopic data. These cyclodepsipeptides appear to be biosynthetically related to jaspamide (aka jasplakinolide) (1) by chemical modification of the building blocks of the polyketide or peptide chains. Pipestelides A-C (2-4) contain a bromotyrosine [3-amino-3-(bromo-4-hydroxyphenyl)propanoic acid] unit, a polypropionate with a Z double bond, and a 2-hydroxyquinolinone, respectively. Revised chemical shift assignments are provided for the co-isolated known jasplakinolide C(a) (5). In addition, compounds 2 and 3 exhibited cytotoxic activities in the micromolar range.
Permutation Polynomial Interleaved DFT-s-OFDM (2023)

We propose frequency-domain interleaver for discrete Fourier transform spread orthogonal division multiplexing (DFT-s-OFDM) based on a linear-or quadratic permutation polynomial (LPP/QPP). Interleaving the Fourier coefficients (i.e., the DFT precoder output) implies that the modulation symbols become transmitted over both time-and frequency domain, which is beneficial over time-frequency selective channels. Despite that the single-carrier property is lost due to the interleaving, the peak-to-average-power ratio (PAPR) can be improved. The results show that a QPP can suppress the error floor of the bit/block error rate (BER/BLER) which occurs on channels with large Doppler spread and simultaneously reduce the PAPR. An LPP primarily decreases the PAPR, especially for BPSK, where the gain is several dB. We derive criteria of how to analytically determine the QPPs and the LPPs.
Monitoring chromatic dispersion and PMD impairments in optical differential phaseshift-keyed (DPSK) systems (2004)

We simulate and measure chromatic dispersion and polarization mode dispersion impairments, and demonstrate their monitoring by measuring clock tone power and degree of polarization in DPSK and RZ-DPSK systems.
Prognostic Significance of Venous Thrombus in Renal Cell Carcinoma. Are Renal Vein and Inferior Vena Cava Involvement Different? (2004)

For patients with pT3b disease, local tumor stage and grade are better predictors of prognosis than extent of venous involvement. Based on our data we support the current TNM classification of venous involvement with RV and IVC invasion categorized as T3b and IVC involvement above the diaphragm categorized as T3c.
Adaptive active noise control systems: algorithms and digital signal processing (DSP) implementations (1995)

Active noise control (ANC) is achieved by introducing an “anti-noise” through an appropriate array of secondary sources. These secondary sources are interconnected through an electronic system using a specific signal processing algorithm for the particular noise cancellation scheme. ANC has application to a wide variety of problems in manufacturing, industrial operations, and consumer products. This paper presents the development of ANC systems using adaptive signal processing and digital signal processors. Concise derivations and analysis of commonly used adaptive structures and algorithms for ANC applications are included.
Abrasion and fatigue resistance of PDMS containing multiblock polyurethanes after accelerated water exposure at elevated temperature (2013)

Segmented polyurethane multiblock polymers containing polydimethylsiloxane and polyether soft segments form tough and easily processed thermoplastic elastomers (PDMS-urethanes). Two commercially available examples, PurSil 35 (denoted as P35) and Elast-Eon E2A (denoted as E2A), were evaluated for abrasion and fatigue resistance after immersion in 85 °C buffered water for up to 80 weeks. We previously reported that water exposure in these experiments resulted in a molar mass reduction, where the kinetics of the hydrolysis reaction is supported by a straight forward Arrhenius analysis over a range of accelerated temperatures (37-85 °C). We also showed that the ultimate tensile properties of P35 and E2A were significantly compromised when the molar mass was reduced. Here, we show that the reduction in molar mass also correlated with a reduction in both the abrasion and fatigue resistance. The instantaneous wear rate of both P35 and E2A, when exposed to the reciprocating motion of an ethylene tetrafluoroethylene (ETFE) jacketed cable, increased with the inverse of the number averaged molar mass (1/Mn). Both materials showed a change in the wear surface when the number-averaged molar mass was reduced to ≈ 16 kg/mole, where a smooth wear surface transitioned to a 'spalling-like' pattern, leaving the wear surface with ≈ 0.3 mm cracks that propagated beyond the contact surface. The fatigue crack growth rate for P35 and E2A also increased in proportion to 1/Mn, after the molar mass was reduced below a critical value of ≈30 kg/mole. Interestingly, this critical molar mass coincided with that at which the single cycle stress-strain response changed from strain hardening to strain softening. The changes in both abrasion and fatigue resistance, key predictors for long term reliability of cardiac leads, after exposure of this class of PDMS-urethanes to water suggests that these materials are susceptible to mechanical compromise in vivo.
Mehrfachbindungen zwischen Hauptgruppenelementen und übergangsmetallen, XC. Selektive Bildung von Alkylrheniumoxiden aus Glykolat‐Komplexen (1991)

Multiple Bonds between Main Group Elements and Transition Metals, XC. – Selective Formation of Alkylrhenium Oxides from Glycolato Complexes Alkylrhenium(VII) and alkylrhenium(VI) oxides, previously not known or hardly accessible, are selectively synthesized from glycolato( O,O ') complexes. These are formed in easy terms from methyltrioxorhenium(VII) and aliphatic vic ‐diols, e.g. glycol and pinacol, by both redoxneutral and reductive condensation reactions (Re VII → Re VI ), respectively. The dinuclear glycolato complex 3 exhibits a centrosymmetric molecular structure with an octahedral core geometry around the metal atom. The mononuclear Re(VII) compound 2 forms a distorted trigonal bipyramidal structure (single crystal X‐ray diffraction).
Abstract 2241: Comparison of rare pathogenic germline variants associated with cancer predisposition syndrome in Taiwan and USA populations (2018)

Abstract Objective To evaluate the analytical performance of a 98-gene NGS panel designed to detect highly- penetrant, rare pathogenic germline variants, strongly linked to predisposition of cancers in Taiwan and USA. Methods This 98-gene panel was developed following an extensive review of genes with a strong clinical and genetic linkage evidence for cancer predisposition. Probes covering the exon sequences from these 98 genes were validated using 19 samples obtained from the Platinum Genomes Project and the Genome In A Bottle Consortium. Analytical sensitivity and specificity for the detection of clinically important variants within multiple cancers types were demonstrated in 30 reference samples derived from patients with familial cancers. Additionally, two clinical cohorts of 1885 and 374 subjects from Taiwan and USA, respectively, were screened for detection of rare pathogenic germline variants in our CAP accredited laboratory in Taiwan, and CLIA certified laboratory in the USA. Results The analytical sensitivity and specificity of the assay panel were 99.95% and 100%, respectively. Similarly, the reportable variants for all 30 DNA samples containing clinically important SNVs in BRCA1/2, RET, APC, MEN1 and PTEN were called with no false positives. The concordance for the use of either blood (reference lab) or saliva (internal lab) as a sample source was found to be 99.9%. The mean age of the Taiwan cohort was 43, with 58% males and 42% females, while the US cohort had a mean age of 58 with 40% males and 60% females. Germline pathogenic variants were detected in 47/1885 (2.5%) and 25/374 (6.7%) individuals respectively. Outside of BRCA1 and BRCA2 positive cases in Taiwan (8.5% and 17%) and US (4% and 0%), the remaining germline positive cohort had pathogenic variants detected in MUTYH, MLH1, RET, ATM, APC, CHEK2, ERCC2, PALB2, PTCH1, WRN, BARD1, BRIP1, PMS2, PTEN, RAD51D, SDHD, RUNX1, BLM, HOXB13, and MSH6. Stratification of pathogenic variants among high risk and average risk individuals suggests these variants are distributed in both risk groups. Using a multigene approach, we identified 35/47 (87%) and 24/25 (96%) additional cases with rare pathogenic mutations respectively which would not have been identified if we were only looking for BRCA1/2 mutations. Conclusion We have demonstrated in 2 clinical cohorts the analytical and clinical validity of a 98-gene panel for the detection of pathogenic germline variants predisposing to cancer. High sensitivity and specificity of this panel was demonstrated irrespective of the use of blood or saliva as samples. Citation Format: Zulfiqar Gulzar, Julian Lucas, Alex Atkins, stephen Su, Oscar Segurado, Rui Mei. Comparison of rare pathogenic germline variants associated with cancer predisposition syndrome in Taiwan and USA populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2241.