gebhart/patrepeval huggingface dataset:
Noncoding RNA danger motifs bridge innate and adaptive immunity and are potent adjuvants for vaccination (2002)

The adaptive immune response is triggered by recognition of T and B cell epitopes and is influenced by "danger" motifs that act via innate immune receptors.This study shows that motifs associated with noncoding RNA are essential features in the immune response reminiscent of viral infection, mediating rapid induction of proinflammatory chemokine expression, recruitment and activation of antigen-presenting cells, modulation of regulatory cytokines, subsequent differentiation of Th1 cells, isotype switching, and stimulation of cross-priming.The heterogeneity of RNA-associated motifs results in differential binding to cellular receptors, and specifically impacts the immune profile.Naturally occurring double-stranded RNA (dsRNA) triggered activation of dendritic cells and enhancement of specific immunity, similar to selected synthetic dsRNA motifs.Based on the ability of specific RNA motifs to block tolerance induction and effectively organize the immune defense during viral infection, we conclude that such RNA species are potent danger motifs.We also demonstrate the feasibility of using selected RNA motifs as adjuvants in the context of novel aerosol carriers for optimizing the immune response to subunit vaccines.In conclusion, RNA-associated motifs produced during viral infection bridge the early response with the late adaptive phase, regulating the activation and differentiation of antigen-specific B and T cells, in addition to a short-term impact on innate immunity.
Motion-Compensated Frame-Accumulating Method to Improve Quality of Carotid Artery Images (2007)

The motion-compensated frame-accumulating method (MCFAM) was carried out to improve B-mode image quality for plaque diagnosis. The effect of MCFAM on the imaging of the carotid intima, one of the potential predictors of plaque growth, was examined using the carotid of a healthy volunteer. MCFAM was found to be effective in imaging the carotid intima clearly as a contiguous object, although conventional imaging failed to visualize the entire intima. Quantitatively, the deviation of the echo signal intensity along the carotid intima, which corresponded to the discontinuity of the intima image, was 31% in the MCFAM image, 48% smaller than that in the conventional image. The deviation became lower with an increase in the number of accumulating frames in MCFAM, and was almost constant when more than 16 frames were accumulated. Because of the relatively small number of frames required, MCFAM was suggested to have the potential to contribute to quantitative plaque diagnosis by enabling accurate measurements of the carotid intima.
The Impact of Recent Advances in Endoscopic Ultrasound-Guided Tissue Acquisition on the Management of Pancreatic Cancer (2020)

Over the last few decades, endoscopic ultrasound (EUS)-guided tissue acquisition has become the method of choice for the pathological diagnosis of solid pancreatic lesions. Due to its high diagnostic yield and low complication rate, EUS-guided tissue acquisition has surpassed percutaneous sampling techniques. For many years, EUS-guided fine-needle aspiration (EUS-FNA) was traditionally used to obtain cytological aspirates of solid pancreatic lesions, with sensitivity values ranging from 80 to 90% for the diagnosis of malignancy. Nevertheless, despite numerous technical advances, EUS-FNA still presents some limitations. Therefore, EUS-guided fine-needle biopsy (EUS-FNB) has been introduced to provide tissue core biopsies, allowing histological assessment. A newly developed generation of FNB needles has demonstrated an outstanding diagnostic accuracy of over 95% for solid pancreatic lesions and provides samples appropriate for ancillary testing, such as immunohistochemistry and tumour molecular profiling. As a result, EUS-FNB is rapidly replacing EUS-FNA and is now the recommended technique for EUS-guided tissue acquisition in pancreatic cancer. Furthermore, with the recent expansion of neoadjuvant treatment criteria and with the advent of novel and personalised anti-cancer therapies, EUS-FNB is gaining a pivotal role in pancreatic cancer management and might soon be generalised to all patients, independent of disease stage. In this article, the authors present an updated review of the role of EUS-guided tissue acquisition in pancreatic cancer. Current indications, several technical aspects and new applications of EUS-FNA and EUS-FNB are discussed.
Cryo-EM reveals architecture and domain interactions of putative tumor suppressor ALDH1L1, a product of natural fusion of three unrelated genes (2021)

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DNA Polymerase Theta Protects Leukemia Cells from Metabolic-Induced DNA Damage (2022)

Leukemia cells accumulate DNA damage but altered DNA repair mechanisms protect them from apoptosis. We showed here that formaldehyde generated by serine/one-carbon cycle metabolism contributed to accumulation of toxic DNA-protein crosslinks (DPCs) in leukemia cells, especially in driver clones harboring oncogenic tyrosine kinases [OTKs: FLT3(ITD), JAK2(V617F), BCR/ABL1]. To counteract this effect, OTKs enhanced the expression of DNA polymerase theta (POLθ) by ERK1/2 serine/threonine kinase-dependent inhibition of c-CBL E3 ligase-mediated ubiquitination of POLθ and its proteasomal degradation. Overexpression of POLθ in OTK-positive cells resulted in efficient repair of DPC-containing DNA double-strand breaks (DSBs) by POLθ-mediated end-joining (TMEJ). Transforming activity of OTKs and other leukemia-inducing oncogenes, especially of those causing inhibition of BRCA1/2 -mediated homologous recombination (HR) with and without concomitant inhibition of DNA-PK -dependent non-homologous end-joining (D-NHEJ), was abrogated in Polq-/- murine bone marrow cells. Genetic and pharmacological targeting of POLθ polymerase and helicase activities revealed that both activities are promising targets in leukemia cells. Moreover, OTK inhibitor or DPC-inducing drug etoposide enhanced anti-leukemia effect of POLθ inhibitor (POLθi) in vitro and in vivo. POLθ can interplay with PARP1 (alternative NHEJ) and RAD52 (alternative HR) to repair DSBs. Remarkably, transformation potential of the oncogenes inducing HR and NHEJ deficiencies (BCR-ABL1 and AML1-ETO) was severely limited in Polq-/-;Parp1-/- and Polq-/-;Rad52-/- cells when compared to single knockouts. Moreover, simultaneous targeting of POLθ and PARP1 or RAD52 exerted dual synthetic lethality against HR deficient leukemias. In conclusion, we demonstrated that POLθ plays an essential role in protecting leukemia cells from metabolically induced toxic DNA lesions and it can be targeted to achieve therapeutic effect. Figure 1. POLθ is required to resolve DPCs caused by formaldehyde generated by serine/1C cycle metabolism in OTKs-positive hematological malignancies. A scheme illustrating functional pathway where OTKs - reprogrammed serine/1C cycle - produced formaldehyde induces DPCs which are likely repaired by POLθ-mediated end-joining (TMEJ). OTKs also enhance the expression of POLθ by stimulating ERK1/2 serine/threonine kinases, which inhibit c-CBL E3 ligase-dependent ubiquitination of POLθ and its proteasomal degradation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal
Multichannel filtering for optimum noise reduction in microphone arrays (2002)

Introduces an optimization criterion for the design of microphone arrays, and derives an optimum filter based on this criterion. The algorithm computes two separate correlation matrices for the signal: one for when only background noise is present, and one for when both noise and signal are present. A filter is then computed based on these matrices, optimizing the proposed weighted mean-square error criterion. A block-recursive version of the algorithm is presented, using LMS-like adaptation of the multichannel filters, with a computational complexity under 40 MIPS for a typical application with four microphones. Simulation results with typical office noise show improvements of up to 20 dB in signal-to-noise ratio, even in low-noise environments.
ChemInform Abstract: Autocatalytic Oxidation of Ethers with Sodium Bromate. (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Cyclic Plasma Treatment during ALD Hf1-xZrxO2Deposition (2014)

Effect of slot plane antenna (SPA) Ar plasma on the reliability of intermediate plasma (DSDS) treated ALD Hf1-xZrxO2 samples with x = 0, 0.31, 0.8 were investigated. The metal oxide semiconductor capacitors (MOSCAP) were subjected to a constant field stress of 27.5 MV/cm in the gate injection mode and the stress-induced flatband voltage shifts and stress induced leakage currents were monitored. The dielectric film deposited without any intermediate step (As-Dep), having the same number of atomic layer deposition (ALD) cycles as DSDS samples was used as the control sample. It was observed that plasma exposure enhances the quality of high-κ film by reducing the number of intrinsic traps in the film and Zr addition further enhances the reliability. Breakdown characteristics also confirm this behavior. Electron affinity variation in HfO2 and ZrO2 and Zr variation seems to contribute to the improvement in DSDS Hf1-xZrxO2 (x = 0.8) by suppressing the oxide trap formation as observed in the Weibull characteristics. DSDS Hf1-xZrxO2 with x = 0.8, therefore, demonstrates a superior equivalent oxide thickness (EOT) downscaling ability and good reliability performance.
Age-Related Susceptibility to Haemophilus influenzae Type b Disease in Rabbits (1971)

Anti-type b antibodies were detected in newborns and in most 6- to 8-week-old rabbits, similar to those observed in humans. Culture of the pharynx and rectum of rabbits at varied ages failed to yield Haemophilus influenzae type b. Bacteria with cross-reacting antigens were observed in both the pharyngeal and rectal cultures from rabbits of varied ages. Rabbits without preexisting serum anti-type b antibodies were highly susceptible to septicemia and death after injection of small numbers of H. influenzae type b. Passively acquired antibody, whether observed in newborns or injected into animals without preexisting antibodies, conferred a high degree of protection against H. influenzae type b.
Trends in radical prostatectomy: centralization, robotics, and access to urologic cancer care (2011)

Over the past decade, the number of radical prostatectomies performed has risen substantially. These procedures have been increasingly centralized at high-volume centers, leading to longer patient travel distances. Few prostatectomies are now performed at hospitals that do not offer robotic surgery.
Identification of small-molecule protein–protein interaction inhibitors for NKG2D (2023)

NKG2D (natural-killer group 2, member D) is a homodimeric transmembrane receptor that plays an important role in NK, γδ<sup>+</sup>, and CD8<sup>+</sup> T cell-mediated immune responses to environmental stressors such as viral or bacterial infections and oxidative stress. However, aberrant NKG2D signaling has also been associated with chronic inflammatory and autoimmune diseases, and as such NKG2D is thought to be an attractive target for immune intervention. Here, we describe a comprehensive small-molecule hit identification strategy and two distinct series of protein-protein interaction inhibitors of NKG2D. Although the hits are chemically distinct, they share a unique allosteric mechanism of disrupting ligand binding by accessing a cryptic pocket and causing the two monomers of the NKG2D dimer to open apart and twist relative to one another. Leveraging a suite of biochemical and cell-based assays coupled with structure-based drug design, we established tractable structure-activity relationships with one of the chemical series and successfully improved both the potency and physicochemical properties. Together, we demonstrate that it is possible, albeit challenging, to disrupt the interaction between NKG2D and multiple protein ligands with a single molecule through allosteric modulation of the NKG2D receptor dimer/ligand interface.
Thermotogales (2008)

Abstract Members of the order Thermotogales have an outstanding phylogenetic position within the domain Bacteria, based on their 16S rRNA (ribosomal ribonucleic acid ) genes sequences. Some Thermotogales organisms are hyperthermophiles with the upper temperature limit of growth at 90°C whereas others are extreme or moderate thermophiles. All Thermotogales are obligately anaerobic organotrophs with a fermentative metabolism. Many thermostable enzymes of Thermotogales were characterized and could be used in different fields of biotechnology.
The Influence of Geometrically Configured Sol-Gel Derived Hydroxyapatite Substrates on Osteoblast Response (2005)

Good quality crystalline sol-derived Hydroxyapatite (HA) thin films of thickness ~350 nm on titanium substrates with underlying micro-channels were prepared by microwave annealing at a temperature of 400 °C for 30 min. A comprehensive in-vitro study was conducted to assess the osteoblast adhesive response to the well-defined micro-scale topographical features on HA coated and uncoated surfaces. The study confirmed the osteoblast’s response to the HA coated micro-channels with an elongated morphology. The effects to morphology suggest that osteoblast adhesion can be improved through optimal micro-channel design and may provide baseline design cues for improving the longterm performance of prosthetic orthopedic and dental implants.
Electroconductive Paste Based on Thermally Expanded Graphite for Screen Printed Electrodes of Medical Applications (2022)

In this paper, the influence of carbon components in the composition of graphite paste on the electrical resistivity of a screen-printed carbon electrode is investigated. Graphite pastes with different contents of thermally expanded graphite (4.5–7.0 wt %), fine-grained graphite (0–6 wt %) and carbon black (0–12 wt %) are investigated. The creation of a polydisperse conducting system requires the application of carbon materials with different physical properties and particle sizes. This will lead to improvement in the screen-printing quality and reduce the resistivity of screen-printed carbon electrodes.
Profit Aware Circuit Design Under Process Variations Considering Speed Binning (2008)

In this paper, a profit-aware design metric is proposed to consider the overall merit of a design in terms of power and performance. A statistical design methodology is then developed to improve the economic merit of a design considering frequency binning and product price profile. A low-complexity sensitivity-based gate sizing algorithm is developed to improve economic gain of a design over its initial yield-optimized design. Finally, we present an integrated design methodology for simultaneous sizing and bin boundary determination to enhance profit under an area constraint. Experiments on a set of ISCAS'85 benchmarks show in average 19% improvement in profit for simultaneous sizing and bin boundary determination, considering both leakage power dissipation and delay bounds compared to a design initially optimized for 90% yield at iso-area in 70-nm bulk CMOS technology.
Non-tenera Contamination and the Economic Impact of SHELL Genetic Testing in the Malaysian Independent Oil Palm Industry (2016)

Oil palm (Elaeis guineensis) is the most productive oil bearing crop worldwide. It has three fruit forms, namely dura (thick-shelled), pisifera (shell-less) and tenera (thin-shelled), which are controlled by the SHELL gene. The fruit forms exhibit monogenic co-dominant inheritance, where tenera is a hybrid obtained by crossing maternal dura and paternal pisifera palms. Commercial palm oil production is based on planting thin-shelled tenera palms, which typically yield 30% more oil than dura palms, while pisifera palms are female-sterile and have little to no palm oil yield. It is clear that tenera hybrids produce more oil than either parent due to single gene heterosis. The unintentional planting of dura or pisifera palms reduces overall yield and impacts land utilization that would otherwise be devoted to more productive tenera palms. Here, we identify three additional novel mutant alleles of the SHELL gene, which encode a type II MADS-box transcription factor, and determine oil yield via control of shell fruit form phenotype in a manner similar to two previously identified mutant SHELL alleles. Assays encompassing all five mutations account for all dura and pisifera palms analyzed. By assaying for these variants in 10,224 mature palms or seedlings, we report the first large scale accurate genotype-based determination of the fruit forms in independent oil palm planting sites and in the nurseries that supply them throughout Malaysia. The measured non-tenera contamination rate (10.9% overall on a weighted average basis) underscores the importance of SHELL genetic testing of seedlings prior to planting in production fields. By eliminating non-tenera contamination, comprehensive SHELL genetic testing can improve sustainability by increasing yield on existing planted lands. In addition, economic modeling demonstrates that SHELL gene testing will confer substantial annual economic gains to the oil palm industry, to Malaysian gross national income and to Malaysian government tax receipts.
Nonholonomic path-planning with obstacle avoidance: a path-space approach (2002)

For the problem of nonholonomic motion planning in the presence of obstacles, a path-iteration algorithm with an "exterior penalty" function has recently been proposed. The convergence of the iterative algorithm requires the avoidance of singular controls. With the inclusion of a penalty function, the set of singular control may increase substantially. In this paper, we propose a specific guideline for choosing the penalty function which does not introduce additional singular controls. In the case of the N-trailer system, this result can be used to guarantee the convergence of the path planning algorithm. To demonstrate the effectiveness of the proposed algorithm, simulation results are included.
An Approximate Dynamic Model of LCL- <formula formulatype="inline"><tex Notation="TeX">$T$</tex></formula>-Based Inductive Power Transfer Power Supplies (2014)

This paper analyzes the dynamics of an LCL-T-based inductive power transfer power supply, and aims to improve its reference tracking performance for dynamic roadway wireless powering applications using a digital PI controller. An approximate small-signal model of the power supply that describes how the power supply reacts to a perturbation in its input is derived using the generalized state-space averaging technique. The model is verified experimentally and shown to capture the supply dynamics. Limitations of the model and their implications are also discussed. Using the small-signal model, a closed-loop digital PI controller is designed to ensure a fast turn-on of a 20 kHz power supply at no-load in approximately 300 μs with no overshoot in the track current.
ECG:Derived Markers to Identify Patients Prone to Atrial Fibrillation (2016)

This study was undertaken to determine the ability of different markers extracted from single lead ECG recorded in sinus rhythm to identify patients prone to atrial fibrillation (AF). For this purpose, 5-minute ECGs recorded in sinus rhythm from two populations were compared: patients with a history of AF and healthy subjects without any history of AF. Several features based on P-waves and RR-intervals were extracted from the ECG. Among the extracted features, the most discriminative ones to identify the AF susceptibility were the P-wave duration, the standard deviation of the beatto-beat Euclidean distance between successive P-waves and the sample entropy of the RR-intervals. The discriminative power of the aforementioned features was assessed using a classification tree approach. The results showed that the combination of P-wave duration, beat-tobeat Euclidean distance between P-waves and sample entropy could efficiently separate the two populations and therefore be used as an effective detection tool of patients at risk to develop AF.
Safety evaluation of two α-amylase enzyme preparations derived from Bacillus licheniformis expressing an α-amylase gene from Cytophaga species (2018)

A safety assessment was conducted for a symthetic variant Cytophaga sp. α-amylase enzyme expressed in Bacillus licheniformis and formulated into two distinct product formats: whole broth (a preparation in which the production organism is completely inactivated, but containing residual cell debris) and clarified preparation (from which the production organism is completely removed). The enzyme was improved via modern biotechnology techniques for use in the endohydrolysis of starch, glycogen, related polysaccharides and oligosaccharides. Applications range from carbohydrate processing, including the manufacture of sweeteners, fermentation to produce organic acids, amino acids and their salts, and potable or fuel alcohol, with resulting co-products (distillers' grains and corn gluten feed/meal) destined for use in animal feed. The toxicological studies summarized in this article (90-day rodent oral gavage and in vitro genotoxicity studies) noted no test article-related adverse effects and thus substantiate the safety of the α-amylase in not only the clarified form but also as a whole-broth preparation. Consistent with the decision tree analysis for enzymes produced with modern biotechnology techniques, this paper provides supporting information that this variant amylase with homology to an amylase from a potentially pathogenic organism (Cytophaga sp.) can be safely produced in an expression host that belongs to a Safe Strain Lineage, for safe use as processing aid to manufacture human and animal food.
Oxidizing potential of endosomes and lysosomes limits intracellular cleavage of disulfide-based antibody–drug conjugates (2005)

Antibody-drug conjugate therapy entails targeted killing of cancer cells with cytotoxic compounds covalently linked to tumor-specific antibodies and shows promise in the treatment of several human cancers. Current antibody-drug conjugate designs that incorporate a disulfide linker between the antibody and cytotoxic drug are inspired by indirect evidence suggesting that the redox potential within the endosomal system is reducing. It is presumed that antigen-dependent endocytosis leads to disulfide linker reduction and intracellular release of free drug, but direct demonstration of such a mechanism is lacking. To determine whether the disulfide N-succinimidyl 4-(2-pyridyldithio)pentanoate (SPP) linker would be reduced during endocytic recycling of the anti-HER2 antibody trastuzumab (Herceptin, Genentech), we synthesized a trastuzumab-SPP-Rhodamine red conjugate and developed a linker cleavage assay by using the self-quenching property of this fluorophore. In breast carcinoma SKBr3 cells, no SPP linker cleavage was observed, as detected by fluorescence dequenching upon internalization. By contrast, the conjugate did display fluorescence dequenching when diverted to the lysosomal pathway by geldanamycin, an effect partly due to proteolytic degradation rather than disulfide reduction. To understand why linker reduction was inefficient, we measured redox potentials of endocytic compartments by expressing a redox-sensitive variant of GFP fused to various endocytic proteins. Unexpectedly, we found that recycling endosomes, late endosomes, and lysosomes are not reducing, but oxidizing and comparable with conditions in the endoplasmic reticulum. These results suggest that intracellular reduction is unlikely to account for the potency of disulfide-linked antibody-drug conjugates.