gebhart/patrepeval huggingface dataset:
Pharmacoproteomics Identifies PLK1 As Vulnerability for Aggressive B-Cell Lymphomas (2018)

Abstract Background: c-MYC is a transcription factor that promotes oncogenesis by activating and repressing its target genes that control cell growth, metabolism, and proliferation. MYC is deregulated in a large proportion of aggressive B-cell lymphomas. A typical example is the Double-Hit Lymphoma (DHL) and Double-Expression Lymphoma (DEL) which present with a rapidly progressing clinical course, refractory to treatment, poor clinical outcome, and currently considered incurable. Nevertheless, MYC is considered as an "undruggable" target since it has no "active site" amenable to binding by conventional small molecule inhibitors. Moreover, MYC has a broad spectrum of functions in cell proliferation, survival, metabolism, and others, so direct inhibition would likely cause severe side effects. Besides direct inhibition, another practical strategy is to target druggable proteins that are essential for the viability of MYC-driven tumors, inducing MYC-dependent "synthetic lethality". The advantage of such approach is a capability of killing tumor cells discriminately, while leaving non-tumor cells intact or less influenced. This study is designed to identify such targets and explore practical novel strategies to treat MYC-driven lymphomas, especially DHL/DEL. Methods and Results: By integrating activity-based proteomic profiling and drug screens in isogenic MYC on/off lymphoma cells, we identified polo-like kinase-1 (PLK1) as an essential regulator of the MYC-dependent kinome in DHL/DEL. Notably, PLK1 was expressed at high levels in DHL, correlated with MYC expression and connoted poor outcome. Further, PLK1 is directly activated by MYC on transcriptional level and in turn, PLK1 signaling augmented MYC protein stability by promoting its phosphorylation and suppressing its degradation. Thus, MYC and PLK1 form a feed-forward circuit in lymphoma cells. Finally, both in vitro and in vivo studies demonstrated that inhibition of PLK1 triggered degradation of MYC and of the anti-apoptotic protein MCL1, and PLK1 inhibitors showed synergy with BCL-2 antagonists in blocking DHL/DEL cell growth, survival, and tumorigenicity. These data support that PLK1 is a promising therapeutic target in MYC-driven lymphomas. Brief summary: Functional pharmacoproteomics identified PLK1 as a therapeutic vulnerability for MYC-driven lymphoma, which was a synthetic lethal for DHL/DEL when targeted with BCL-2 inhibitors. Disclosures Vose: Roche: Honoraria; Merck Sharp &amp; Dohme Corp.: Research Funding; Acerta Pharma: Research Funding; Seattle Genetics, Inc.: Research Funding; Novartis: Honoraria, Research Funding; Kite Pharma: Research Funding; Bristol Myers Squibb: Research Funding; Epizyme: Honoraria; Legend Pharmaceuticals: Honoraria; Abbvie: Honoraria; Celgene: Research Funding; Incyte Corp.: Research Funding.
Quantitative Analysis of Mixture Preparation Processes in New Direct-Injection Spark Ignition Engines(S.I. Engines, Stratified-Charge Combustion) (2004)

Visualization plays an effective role in the establishment of a new combustion concept by helping to find the optimal results quickly among many different parameters and contributing to a shorter development period. Laser-induced fluorescence, Raman scattering and infrared absorption were used to measure the air/fuel ratio quantitatively in a three generation direct-injection gasoline (DIG) engine including a spray-guided mixture formation process and comparisons were made with the mixture formation concepts of the first- and second-generation DIG engines. The optimum combination of fuel spray, gas flow and combustion chamber configuration was found to be different for the three generations of DIG engines. The characteristics of the stable combustion region for obtaining higher thermal efficiency and cleaner exhaust emissions differed among the three mixture formation concepts.
Qualitative assessment of intrinsic mode functions of empirical mode decomposition (2008)

The 'empirical mode decomposition' (EMD) method has been recently proposed to deal with nonlinear and non- stationary data, which decomposes signals into 'well-behaved' intrinsic mode functions (IMFs). An assessment on the qualitative performance of the EMD method in terms of the degree of signal nature preservation of individual IMF is provided. This is archived by means of the recently proposed signal characterisation method, based upon examining the signal predicability in phase space. It is shown that the first IMF always performs best in terms of signal nature preserving. Simulation results on both linear and nonlinear benchmark signals support the analysis.
Cartilage repair using bone morphogenetic protein 4 and muscle‐derived stem cells (2006)

Local delivery of BMP-4 by genetically engineered MDSCs enhanced chondrogenesis and significantly improved articular cartilage repair in rats.
Role of the Cell Wall Microenvironment in Expression of a Heterologous SpaP-S1 Fusion Protein by Streptococcus gordonii (2010)

The charge density in the cell wall microenvironment of Gram-positive bacteria is believed to influence the expression of heterologous proteins. To test this, the expression of a SpaP-S1 fusion protein, consisting of the surface protein SpaP of Streptococcus mutans and a pertussis toxin S1 fragment, was studied in the live vaccine candidate bacterium Streptococcus gordonii. Results showed that the parent strain PM14 expressed very low levels of SpaP-S1. By comparison, the dlt mutant strain, which has a mutation in the dlt operon preventing d-alanylation of the cell wall lipoteichoic acids, and another mutant strain, OB219(pPM14), which lacks the LPXTG major surface proteins SspA and SspB, expressed more SpaP-S1 than the parent. Both the dlt mutant and the OB219(pPM14) strain had a more negatively charged cell surface than PM14, suggesting that the negative charged cell wall played a role in the increase in SpaP-S1 production. Accordingly, the addition of Ca(2+), Mg(2+), and K(+), presumably increasing the positive charge of the cell wall, led to a reduction in SpaP-S1 production, while the addition of bicarbonate resulted in an increase in SpaP-S1 production. The level of SpaP-S1 production could be correlated with the level of PrsA, a peptidyl-prolyl cis/trans isomerase, in the cells. PrsA expression appears to be regulated by the cell envelope stress two-component regulatory system LiaSR. The results collectively indicate that the charge density of the cell wall microenvironment can modulate heterologous SpaP-S1 protein expression in S. gordonii and that this modulation is mediated by the level of PrsA, whose expression is regulated by the LiaSR two-component regulatory system.
Cover Picture: 2‐Phenoxy‐nicotinamides are Potent Agonists at the Bile Acid Receptor GPBAR1 (TGR5) (ChemMedChem 4/2013) (2013)

The front cover picture shows a 3D homology model of the human G protein-coupled bile acid receptor (GPBAR1; carbon atoms in green). The full receptor structure is shown (top right) with the proposed binding site of GPBAR1 agonists indicated (red ellipse). The main picture shows a zoom of this binding site into which taurolithocholic acid (TLCA; carbon atoms in cyan) and a 2-phenoxy-nicotinamide agonist (carbon atoms in magenta) are docked. The alignment of TLCA with our advanced lead compounds enabled the identification of the optimal attachment point for a polar vector, which was critical to improve the physicochemical properties of the series. For more details, see the Communication by Rainer E. Martin et al. on p. 569 ff.
TECHNICAL ADVANCE: Indel arrays: an affordable alternative for genotyping (2007)

Natural variation and induced mutations are important resources for gene discovery and the elucidation of genetic circuits. Mapping such polymorphisms requires rapid and cost-efficient methods for genome-wide genotyping. Here we report the development of a microarray-based method that assesses 240 unique markers in a single hybridization experiment at a cost of less than US$50 in materials per line. Our genotyping array is built with 70-mer oligonucleotide elements representing insertion/deletion (indel) polymorphisms between the Arabidopsis thaliana accessions Columbia-0 (Col) and Landsberg erecta (Ler). These indel polymorphisms are recognized with great precision by comparative genomic hybridization, eliminating the need for array replicates and complex statistical analysis. Markers are present genome-wide, with an average spacing of approximately 500 kb. PCR primer information is provided for all array indels, allowing rapid single-locus inquiries. Multi-well chips allow groups of 16 lines to be genotyped in a single experiment. We demonstrate the utility of the array for accurately mapping recessive mutations, RIL populations and mixed genetic backgrounds from accessions other than Col and Ler. Given the ease of use of shotgun sequencing to generate partial genomic sequences of unsequenced species, this approach is readily transferable to non-model organisms.
A Journey Towards a Converged 5G Architecture & Beyond (2021)

Mobile network architectures and standards have evolved over a period of time. However, to improve the average revenue per user (ARPU), an efficient and simplified network architecture is needed. Network designers and operators are working towards an optimized network architecture and a simplified 5G deployment framework. In this paper, we present our approach towards the logical evolution of the next-generation 5G network from the perspective of access, core networks, and data analytics convergence for effective traffic steering and moving towards enterprise-focused private 5G deployment models. As a step forward, we propose novel mechanism on how a user can switch between different types of access technologies (Wi-Fi, LoRA-WAN, 5G, SatCom, etc.) and how convergence of analytics can help achieve end-to-end use case optimization.
Using Biomass Gasification Mineral Residue as Catalyst to Produce Light Olefins from CO, CO2, and H2 Mixtures (2022)

Gasification is a process to transform solids, such as agricultural and municipal waste, into gaseous feedstock for making transportation fuels. The so-called coarse solid residue (CSR) that remains after this conversion process is currently discarded as a process solid residue. In the context of transitioning from a linear to a circular society, the feasibility of using the solid process residue from waste gasification as a solid catalyst for light olefin production from CO, CO<sub>2</sub> , and H<sub>2</sub> mixtures was investigated. This CSR-derived catalyst converted biomass-derived syngas, a H<sub>2</sub> -poor mixture of CO, CO<sub>2</sub> , H<sub>2</sub> , and N<sub>2</sub> , into methane (57 %) and C<sub>2</sub> -C<sub>4</sub> olefins (43 %) at 450 °C and 20 bar. The main active ingredient of CSR was Fe, and it was discovered with operando X-ray diffraction that metallic Fe, present after pre-reduction in H<sub>2</sub> , transformed into an Fe carbide phase under reaction conditions. The increased formation of Fe carbides correlated with an increase in CO conversion and olefin selectivity. The presence of alkali elements, such as Na and K, in CSR-derived catalyst increased olefin production as well.
The Radiation Tolerance of Specific Optical Fibers for the LHC Upgrades (2012)

Optical fibers in the readout system for the Large Hadron Collider (LHC) upgrades will operate in a harsh radiactive environment. The fibers within 12 meters from the front-end detectors are exposed up to total ionizing dose of 250 kGy(Si) in their 10 year operational lifetime. In some applications, the fibers within the tracking volume are kept in a cold environment near -25 °C. The paper presents the identification of suitable optical fibers for the LHC detector upgrades. Several optical fibers have been tested to 650 kGy(Si) at room temperature with various dose rates of 60Co gamma rays. Two multi-mode fibers and one single-mode fiber have been qualified for use in the LHC upgrades for warm operations. Four optical fibers have been tested to 500 kGy(Si) at -25 °C with 27 kGy(Si)/hr 60Co gamma rays. Two SM fibers have been qualified for the LHC upgrades for cold operations. Several optical fibers, including two MM fibers, have been tested up to 11 kGy(Si) at -25 °C with 70 Gy(Si)/hr 60Co gamma rays and exhibited moderate radiation induced attenuation (RIA, indicating that all tested fibers are potential candidates for the LHC upgrades for warm and cold operations.
Regional distribution of tetrahydroisoquinoline derivatives in rodent, human, and parkinson’s disease brain (2008)

Several members of the tetrahydroisoquinoline (TIQ) family of monoamine alkaloids can be formed from dopamine or its oxidized metabolites and may be involved in the pathogenesis of monoaminergic cell death in Parkinson's disease (PD). Using enantiomeric-selective high-performance liquid chromatography with electrochemical detection and liquid chromatography with tandem mass spectroscopy, the regional concentrations of several TIQ derivatives, including salsolinols, were determined in mouse, rat, normal human, and PD brain. TIQ derivatives were detected in all regions subjected to analysis. In general, salsolinols were present at higher concentrations than TIQ and its benzyl and methyl derivatives, especially in human brain. Moreover, salsolinols were concentrated in areas with increased dopamine synthesis and turnover such as the ventral midbrain and striatum, respectively. A possible consequence of nigrostriatal dopaminergic cell death, significantly lower levels of (R)salsolinol, (S)salsolinol, N-methyl-(R)salsolinol and N-methyl-(S)salsolinol were found in the caudate nuclei of PD in comparison with normal human brain. Our data support the hypothesis of endogenous synthesis of salsolinols and provide evidence for their accumulation in catecholaminergic neurons.
Somatostatin Receptor Subtype 1 Selective Activation in Human Growth Hormone (GH)- and Prolactin (PRL)-Secreting Pituitary Adenomas: Effects on Cell Viability, GH, and PRL Secretion (2003)

Somatostatin (SRIF) analogs interacting with SRIF receptor subtype (SSTR) 2 and SSTR5 are known to reduce secretion in GH-secreting pituitary adenomas. We investigated the effects of SRIF and a SSTR1 selective agonist, BIM-23926, on GH and prolactin (PRL) secretion and cell viability in primary cultures deriving from 15 GH- and PRL-secreting adenomas expressing SSTR1. Quantitative RT-PCR showed SSTR1 mRNA mean levels of 6 +/- 2.2 x 10(4) molecules/ microg reverse-transcribed total RNA. SSTR2 and SSTR5 were frequently expressed (93.3%), on the contrary of SSTR3 (53.3%) and SSTR4 (6.7%). GH secretion was significantly reduced by SRIF and BIM-23926 (45 +/- 8.6% and 32 +/- 18.1% inhibition, respectively) as well as PRL secretion (16.1 +/- 4% and 19.7 +/- 3.5% inhibition, respectively). After treatment with SRIF and BIM-23926, cell viability was significantly reduced by 17.5 +/- 5% and 20 +/- 3.9%, respectively. SSTR1 mRNA levels correlated with the degree of GH and PRL secretion inhibition. These results demonstrate that SSTR1 selective activation inhibits hormone secretion and cell viability in GH- and PRL-secreting adenomas in vitro and suggest that SRIF analogs with affinity for SSTR1 may be useful to control hormone hypersecretion and reduce neoplastic growth of pituitary adenomas.
Contrast-enhanced ultrasound detects changes in microvascular blood flow in adults with sickle cell disease (2019)

In patients with sickle cell disease (SCD), poor outcome measures compromise the potential success of clinical trials. Contrast-enhanced ultrasound (CEUS) is a technique that can noninvasively quantify deep tissue microvascular blood flow. We tested the hypothesis that CEUS of forearm skeletal muscle could be used to: 1) assess microvascular abnormalities that occur during vaso-occlusive crisis; and 2) test new therapies for SCD that are targeted to improving the status of the microcirculation. We performed a prospective study, CEUS perfusion imaging of resting forearm muscle was performed in adults with SCD: 1) during and after a pain episode, and 2) before, during, and after a 24-hour infusion of the investigative agent, regadenoson, an adenosine A 2A agonist. CEUS destruction-replenishment timeintensity data were analyzed to measure microvascular blood flow, as well as its components, microvascular blood volume and flux rate. Serial CEUS measurements were obtained in 32 adults with SCD. For the studies during crisis, there was a 30% reduction in microvascular blood flow compared to steady-state (p = 0.031), a reduction that was largely due to microvascular flux rate. For the regadenoson group, a non-significant 25% increase in flux rate and 9% increase in microvascular blood flow compared to baseline were detected during infusion. In a study of adults with SCD, CEUS detected changes in microvascular blood flow associated with vaso-occlusive crises. No changes were found during an infusion of the adenosine A 2A agonist, regadenoson. This study provides preliminary evidence that CEUS could detect blood flow changes consistent with SCD physiology.
Sacral Stress Fractures (2003)

Sacral stress fractures are an underrecognized cause of low-back and gluteal pain in distance runners. The combination of low bone density and increased activity blurs the boundary between fatigue and insufficiency fractures in many runners. MRI is the preferred radiologic technique because of its ability to localize the site of injury and rule out tumors, disk disease, or sacroiliitis. By identifying the condition early, clinicians contribute to a favorable outcome and help most athletes return to full activity in 12 to 14 weeks.
Gradient Descent Direction Random Walk MIMO Detection Using Intermediate Search Point (2023)

In this paper, multi-input multi-output (MIMO) signal detection with random walk along a gradient descent direction using an intermediate search point is presented. As a low complexity MIMO signal detection schemes, a gradient descent algorithm with Metropolis-Hastings (MH) methods has been proposed. Random walk along a gradient descent direction speeds up the MH based search using the gradient of a least-squares cost function. However, the gradient vector may be discarded through QAM constellation quantization in some cases. For further performance improvement, this paper proposes an improved search scheme in which the gradient vector is stored for the next search iteration to generate an intermediate search point. The performance of the proposed scheme improves with higher order modulation symbols as compared with that of a conventional scheme. Numerical results obtained through computer simulation show that a bit error rate (BER) performance improves by 5dB at a BER of 10-3 for 64QAM symbols in a 16×16 MIMO system.
Preface to SISSY 2016 (2016)

Presents the introductory welcome message from the conference proceedings. May include the conference officers' congratulations to all involved with the conference event and publication of the proceedings record.
A data-driven statistical framework for post-grasp manipulation (2014)

Grasping an object is usually only an intermediate goal for a robotic manipulator. To finish the task, the robot needs to know where the object is in its hand and what action to execute. This paper presents a general statistical framework to address these problems. Given a novel object, the robot learns a statistical model of grasp state conditioned on sensor values. The robot also builds a statistical model of the requirements for a successful execution of the task in terms of uncertainty in the state of the grasp. Both of these models are constructed by offline experiments. The online process then grasps objects and chooses actions to maximize likelihood of success. This paper describes the framework in detail, and demonstrates its effectiveness experimentally in placing, dropping, and insertion tasks. To construct statistical models, the robot performed over 8,000 grasp trials, and over 1,000 trials each of placing, dropping, and insertion.
Targeted Drug Delivery in Oncology: Current Paradigm and Challenges (2013)

Targeted drug delivery seeks to improve the therapeutic index, that is, lower the toxicity but increase the efficacy of a drug. Some designs try to minimize side effects to allow a higher dose and increased therapeutic effects. Other designs focus on increasing efficacy to require less drug that cou...
Immunology of HIV-1 (2005)

Abstract This chapter serves as a bridge between the molecular and structural biology of the human immunodeficiency virus type one (HIV-1) and the immunological consequences that viral infection produces. These are critical components of how nervous system disease is caused and may someday be prevented. HIV is a retrovirus that belongs to the family of lentiviruses. HIV-1, like other retroviruses, is an enveloped virus (Fig. 1). The outer envelope consists of a lipid bilayer membrane containing the viral envelope glycoproteins. The outer envelope lipid bilayer membrane is derived from the infected cell and contains many cellular components such as Β2- microglobulin and the Α and Β chains of the human lymphocyte antigen DR (HLA-DR, product of the class II major histocompatibility complex (MHC)).
Feeder location did not affect performance of weanling pigs in large groups. (2000)

Crossbred pigs weaned at 17 d of age (n = 1,760; mean initial BW = 5.6 +/- 0.7 kg) were used in two 4-wk trials (four replicates per trial) to evaluate the effects of three pen designs on pig performance. The designs were 1) large group size (100 pigs/pen) with five two-sided feeders in a single, central location in the pen; 2) large group size (100 pigs/pen) with five two-sided feeders in multiple (five) locations in the pen; and 3) small group size (20 pigs/pen) with a single two-sided feeder in a central location in the pen. Each feeder provided two 20.3-cm-wide feeding places on each side. Pigs had free access to feed and water. Feeder-trough space (4 cm/pig) and floor-area allowance (0.17 m2/pig) were the same for all treatments. Pigs in the large-group treatments were lighter (15.6 and 15.6 vs 16.0 kg; P < 0.01) at the end of wk 4 and had lower ADG (358 and 357 vs 373 g; P < 0.01) and ADFI (510 and 521 vs 544 g; P < 0.01) during wk 2 through 4 than pigs in small groups. Gain:feed ratio was similar (P > 0.05) for all treatment groups throughout the study. For large groups, feed disappearance from each of the five feeders was similar (P > 0.05) for both multiple- and single-location treatments. In summary, large group size reduced pig growth performance, but the approach to providing multiple feeding locations that was employed in this experiment did not increase feed intake or growth performance of pigs in the large groups.
Data transmission using transmitter side channel estimation in wireless power transfer system (2014)

In recent years, wireless power transfer has been attracting a great deal of attention. In order to realize efficient power transfer, it is necessary to communicate data such as a frequency, required power, or error tolerance. In the proposed system, because of the use of the same antennas for power transmission and data transmission, the frequency response of a channel for the data transmission changes owing to load fluctuation and the distance between antennas. This paper investigates data transmission performance in the wireless power transfer system with frequency response estimation at the transmitter side. The numerical results obtained through computer simulation show that the proposed scheme can estimate the frequency response of the channel and the difference between the expected bit error rate (BER) and the BER with the estimation error is less than 0.5 dB at the BER of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-3</sup> .