gebhart/patrepeval huggingface dataset:
RNA modifications can affect RNase H1-mediated PS-ASO activity (2022)

Phosphorothioate modified antisense oligonucleotides (PS-ASOs) can reduce gene expression through hybridization to target RNAs and subsequent cleavage by RNase H1. Target reduction through this mechanism is influenced by numerous features of the RNA, which modulate PS-ASO binding affinities to the RNA target, and how the PS-ASO-RNA hybrid is recognized by RNase H1 for RNA cleavage. Endogenous RNAs are frequently chemically modified, which can regulate intra- and intermolecular interactions of the RNA. The effects of PS-ASO modifications on antisense activity have been well studied; however, much less is known regarding the effects of RNA modifications on PS-ASO hybridization and RNase H1 cleavage activity. Here, we determine the effects of three different RNA modifications on PS-ASO binding and antisense activity in recombinant and cell-based systems. Some RNA modifications can reduce PS-ASO hybridization, the cleavage activity of RNase H1, or both, while other modifications had minimal effects on PS-ASO function. In addition to these direct effects, RNA modifications can also change the RNA structure, which may affect PS-ASO accessibility in a cellular context. Our results elucidate the effects of three prevalent RNA modifications on PS-ASO-mediated RNase H1 cleavage activity, and such findings will help improve PS-ASO target site selection.
Hot melt extrusion as an approach to improve solubility, permeability and oral absorption of a psychoactive natural product, piperine (2016)

These results demonstrated that increasing the bioavailability of piperine may be achieved as demonstrated by findings in this study.
When it gets more difficult, use both hands: exploring bimanual curve manipulation (2005)

In this paper we investigate the relationship between bimanual (two-handed) manipulation and the cognitive aspects of task integration, divided attention and epistemic action. We explore these relationships by means of an empirical study comparing a bimanual technique versus a unimanual (one-handed) technique for a curve matching task. The bimanual technique was designed on the principle of integrating the visual, conceptual and input device space domain of both hands. We provide evidence that the bimanual technique has better performance than the unimanual technique and, as the task becomes more cognitively demanding, the bimanual technique exhibits even greater performance benefits. We argue that the design principles and performance improvements are applicable to other task domains. Key words: two-handed input, bimanual input, curve editing, task integration, divided attention. 1
Computed Tomography of Rounded Atelectasis (1988)

High resolution CT of a fixed-inflated air-dried lung was obtained from a patient with rounded atelectasis. The dense periphery of the mass was shown to correspond to an invagination of the pleura, and the central lucency to slightly aerated atelectatic lung parenchyma.
Loss of MIG-6 results in endometrial progesterone resistance via ERBB2 (2022)

Female subfertility is highly associated with endometriosis. Endometrial progesterone resistance is suggested as a crucial element in the development of endometrial diseases. We report that MIG-6 is downregulated in the endometrium of infertile women with endometriosis and in a non-human primate model of endometriosis. We find ERBB2 overexpression in the endometrium of uterine-specific Mig-6 knockout mice (Pgr<sup>cre/+</sup>Mig-6<sup>f/f</sup>; Mig-6<sup>d/d</sup>). To investigate the effect of ERBB2 targeting on endometrial progesterone resistance, fertility, and endometriosis, we introduce Erbb2 ablation in Mig-6<sup>d/d</sup> mice (Mig-6<sup>d/d</sup>Erbb2<sup>d/d</sup> mice). The additional knockout of Erbb2 rescues all phenotypes seen in Mig-6<sup>d/d</sup> mice. Transcriptomic analysis shows that genes differentially expressed in Mig-6<sup>d/d</sup> mice revert to their normal expression in Mig-6<sup>d/d</sup>Erbb2<sup>d/d</sup> mice. Together, our results demonstrate that ERBB2 overexpression in endometrium with MIG-6 deficiency causes endometrial progesterone resistance and a nonreceptive endometrium in endometriosis-related infertility, and ERBB2 targeting reverses these effects.
A4.3 - The Infineon Silicon MEMS Microphone (2013)

This paper reports on the state of the art silicon micromachined microphone utilizing a dual poly silicon membrane system. MEMS chips from 1.4mm down to 1.0mm side length are applied for mobile communication. Design aspects related with key performance parameters such as sensitivity, signal to noise ration and distortion are discussed. Sensitivity of -38BV/Pa is achieved for different microphone membrane diameters. A maximum signal to noise ration of 66dB(A) for the largest system could be achieved. The perfect fit of simulation versus measurements enables deeper analysis and balancing of noise contributors. Environmental noise suppression of 5dB by acoustical high pass design is demonstrated.
Immersive 3D Visualization of the Collective Behavior of Particles and Crystal Dislocations Using Virtual Reality Technology (2014)

In this article, we present a three-dimensional visualization technique that has been developed in order to establish an interactive immersive environment to visualize the particles in granular materials and dislocations in crystals. Simple elementary objects often exhibit complex collective behavior. Understanding of such behaviors and developments of coarse-scale theories, often requires insight into collective behavior that can only be obtained through immersive visualization. By displaying the computational results in a virtual environment with three-dimensional perception, one can immerse inside the model and analyze the intricate and very complex behavior of individual particles and dislocations. We built the stereographic images of the models using OpenGL rendering technique and then combine with the Virtual Reality technology in order to immerse in the three-dimensional model. A head mounted display has been used to allow the user to immerse inside the models and a flock of birds tracking device that allows the movements around and within the immersive environment.
Metal coated glasses by sputtering and their microfouling properties (2014)

Some elements as contaminant tend to be concentrated in biofilm. In order to prevent the fogging of glass, it is very important to control biofilm formation by metal dissolution. In this study, Metals were deposited on glass substrate by Helicon-wave-excited-plasma sputtering process. Sample was very thin metals layer like as half mirror, it could transmit light. The results of biofilm formation test, biofilm formation were inhibited on Cu, Sn and Cr, and light transmission of these samples was not degradation. It could be said that inhibition of biofilm formation was effective to suppressing cloudiness.
Satisfaction with therapy among patients treated with MMXTM mesalamine for maintenance of remission in patients with mild-to-moderate ulcerative colitis (2008)

For patients with mild-to-moderate ulcerative colitis (UC), 5-aminosalicylic acid (5-ASA) represents the mainstay of their therapy. However, many of the current 5-ASA formulations require multiple-daily dosing, which can lead to poor adherence, particularly among those with quiescent disease, and increased risk of disease exacerbation. MMX mesalamine (LialdaTM [MezavantTM XL in the UK and Ireland; MezavantTM elsewhere]) is a novel, oral formulation of 5-ASA designed for once-daily (QD) dosing. During a 12-month maintenance study (SPD476-303) among patients with mild-to-moderate UC, patient satisfaction with MMX mesalamine treatment was assessed. Patients with mild-to-moderate UC who attained remission following MMX mesalamine treatment (2.4g/day given QD or as 1.2g twice daily [BID], or 4.8g/day given QD) in either of two, 8-week, phase III studies (SPD476-301 and -302), or an 8-week extension study (in which patients received MMX mesalamine 4.8g/day [given as 2.4g BID] as part of study SPD476-303), could enter a 12-month maintenance phase of study SPD476-303. Patients entering the maintenance phase of this open-label study were randomized to MMX mesalamine 2.4g/day given QD or as 1.2g BID. Patients completed a voluntary treatment satisfaction questionnaire after 6 months or at study withdrawal. Satisfaction was assessed using a 5-grade scale ranging from extremely satisfied to extremely dissatisfied. The satisfaction questionnaire was completed by 79/225 patients who received the QD regimen and by 73/234 patients who received the BID regimen. 96.2% of patients in the QD group and 91.8% in the BID group reported being somewhat/extremely satisfied with the number of times per day they were required to take medication. Values for overall satisfaction were 98.7% and 95.9%, respectively. The majority of patients receiving MMX mesalamine 2.4g/d (whether given QD or BID) maintenance therapy were satisfied with their treatment. Satisfaction with MMX mesalamine, particularly if given QD, is expected to improve adherence rates and thus overall treatment success.
Refinement of Ontology-Constrained Human Pose Classification (2014)

In this paper, we propose an image classification method that recognizes several poses of idol photographs. The proposed method takes unannotated idol photos as input, and classifies them according to their poses based on spatial layouts of the idol in the photos. Our method has two phases, the first one is to estimate the spatial layout of ten body parts (head, torso, upper and lower arms and legs) using Eichner's Stickman Pose Estimation. The second one is to classify the poses of the idols using Bayesian Network classifiers. In order to improve accuracy of the classification, we introduce Pose Guide Ontology (PGO). PGO contains useful background knowledge, such as semantic hierarchies and constraints related to the positional relationship between the body parts. The location information of body parts is amended by PGO. We also propose iterative procedures for making further refinements of PGO. Finally, we evaluated our method on a dataset consisting of 400 images in 8 poses, and the final results indicated that F-measure of the classification has become 15% higher than non-amended results.
Elongated conformers of charge states +11 to +15 of bovine ubiquitin studied using ESI-FAIMS-MS (2001)

Recent advancements in high-field asymmetric waveform ion mobility spectrometry (FAIMS) have led to significant improvements in the application of this technology to the study of protein conformers. Compared with previous work, the maximum value of the separation voltage (i.e., the dispersion voltage) has increased, thereby enabling multiple, elongated conformers of individual charge states of bovine ubiquitin to be separated in the gas phase (e.g., four conformers of each of the +11 and +12 charge states were separated). The use of a carrier gas mixture of 40% nitrogen and 60% helium changed the separation selectivity compared with pure nitrogen and enhanced the signal intensity, especially for the +14 and +15 charge states (the latter was not detected in a nitrogen carrier gas). Conformer cross sections were determined using the FAIMS/energy-loss method and found to be similar within a given charge state. The cross sections for conformers of charge states +13, + 14, and +15 plateau at about 2000 A2 suggesting that the structure of bovine ubiquitin is essentially unfolded after the addition of the 13th proton.
Experimental investigations of 28-GHz-Band power amplifier for massive MIMO transmitter (2017)

This paper presents experimental results of 28-GHz-band power amplifier for Massive MIMO transmitter. The power amplifier consists of the amplifier path and delay line path, which corresponds to a signal cancellation loop of feed-forward power amplifier. From this configuration, the power amplifier can provide extremely low deviation on gain and phase when changing the output power level. Experimental results confirm that the fabricated 28-GHz-band power amplifier achieves the gain and phase deviations of under 0.1 dB and 1.0 degree, respectively. The proposed power amplifier can offer extremely low gain and phase deviations at quasi-millimeter wave band. Therefore, the array calibration cost of Massive MIMO transmitter can reduce regardless of the output power level. The proposed power amplifier is suitable for Massive MIMO transmitter application.
In Vivo Senescence in the Sbds-Deficient Murine Pancreas: Cell-Type Specific Consequences of Translation Insufficiency (2015)

Genetic models of ribosome dysfunction show selective organ failure, highlighting a gap in our understanding of cell-type specific responses to translation insufficiency. Translation defects underlie a growing list of inherited and acquired cancer-predisposition syndromes referred to as ribosomopathies. We sought to identify molecular mechanisms underlying organ failure in a recessive ribosomopathy, with particular emphasis on the pancreas, an organ with a high and reiterative requirement for protein synthesis. Biallelic loss of function mutations in SBDS are associated with the ribosomopathy Shwachman-Diamond syndrome, which is typified by pancreatic dysfunction, bone marrow failure, skeletal abnormalities and neurological phenotypes. Targeted disruption of Sbds in the murine pancreas resulted in p53 stabilization early in the postnatal period, specifically in acinar cells. Decreased Myc expression was observed and atrophy of the adult SDS pancreas could be explained by the senescence of acinar cells, characterized by induction of Tgfβ, p15(Ink4b) and components of the senescence-associated secretory program. This is the first report of senescence, a tumour suppression mechanism, in association with SDS or in response to a ribosomopathy. Genetic ablation of p53 largely resolved digestive enzyme synthesis and acinar compartment hypoplasia, but resulted in decreased cell size, a hallmark of decreased translation capacity. Moreover, p53 ablation resulted in expression of acinar dedifferentiation markers and extensive apoptosis. Our findings indicate a protective role for p53 and senescence in response to Sbds ablation in the pancreas. In contrast to the pancreas, the Tgfβ molecular signature was not detected in fetal bone marrow, liver or brain of mouse models with constitutive Sbds ablation. Nevertheless, as observed with the adult pancreas phenotype, disease phenotypes of embryonic tissues, including marked neuronal cell death due to apoptosis, were determined to be p53-dependent. Our findings therefore point to cell/tissue-specific responses to p53-activation that include distinction between apoptosis and senescence pathways, in the context of translation disruption.
Mechanism of Apoptotic Cell Death by 2,4,3',5'-Tetramethoxystilbene in Human Promyelocytic Leukemic HL-60 Cells (2007)

We have previously shown that 2,4,3',5'-tetramethoxystilbene (TMS), a synthetic trans-stilbene analogue acting as a potent inhibitor of human cytochrome P450 1B1, induces apoptotic cell death in human cancer cells. In the present studies, we report the mechanisms of apoptotic cell death by TMS in human promyelocytic leukemic HL-60 cells. We found that treatment of HL-60 cells with TMS suppressed the cell growth in a concentration-dependent manner with <TEX>$IC_{50}$</TEX> value of about 0.8 <TEX>${\mu}M$</TEX>. Immunoblot experiments revealed that DMHS-induced apoptosis was associated with cleavage of poly (ADP-ribose) polymerase. The release of cytochrome c from mitochondria into the cytosol was significantly increased in response to TMS. TMS caused activation of caspase-3 in a concentration-dependent manner and TMS-mediated caspase-3 activation was partially prevented by the caspase inhibitor, zVAD-fmk. Interestingly, we found that the cytotoxic effect of anticancer drugs such as paclitaxel, docetaxel, or etoposide was enhanced in the presence of TMS. Simultaneous treatment with TCDD also significantly increased cytotoxic effects of TMS alone or TMS and anti-cancer agents. Taken together, our present results indicated that TMS leads to apoptotic cell death in HL-60 cells through activation of caspase-3 activity and release of cytochrome c into cytosol. The ability of TMS to increase cytotoxic effect of anticancer drugs may contribute to its usefulness for cancer chemotherapy.
Regulation of microtubule dynamics by inhibition of the tubulin deacetylase HDAC6 (2009)

We studied the role of a class II histone deacetylase, HDAC6, known to function as a potent alpha-tubulin deacetylase, in the regulation of microtubule dynamics. Treatment of cells with the class I and II histone deacetylase inhibitor TSA, as well as the selective HDAC6 inhibitor tubacin, increased microtubule acetylation and significantly reduced velocities of microtubule growth and shrinkage. siRNA-mediated knockdown of HDAC6 also increased microtubule acetylation but, surprisingly, had no effect on microtubule growth velocity. At the same time, HDAC6 knockdown abolished the effect of tubacin on microtubule growth, demonstrating that tubacin influences microtubule dynamics via specific inhibition of HDAC6. Thus, the physical presence of HDAC6 with impaired catalytic activity, rather than tubulin acetylation per se, is the factor responsible for the alteration of microtubule growth velocity in HDAC6 inhibitor-treated cells. In support of this notion, HDAC6 mutants bearing inactivating point mutations in either of the two catalytic domains mimicked the effect of HDAC6 inhibitors on microtubule growth velocity. In addition, HDAC6 was found to be physically associated with the microtubule end-tracking protein EB1 and a dynactin core component, Arp1, both of which accumulate at the tips of growing microtubules. We hypothesize that inhibition of HDAC6 catalytic activity may affect microtubule dynamics by promoting the interaction of HDAC6 with tubulin and/or with other microtubule regulatory proteins.
Expansion and Characterization of Human Embryonic Stem Cell-Derived Osteoblast-Like Cells (2010)

Human embryonic stem cells (hESCs) have the potential to serve as a repository of cells for the replacement of damaged or diseased tissues and organs. However, to use hESCs in clinically relevant scenarios, a large number of cells are likely to be required. The aim of this study was to demonstrate an alternative cell culture method to increase the quantity of osteoblast-like cells directly derived from hESCs (hESCs-OS). Undifferentiated hESCs were directly cultivated and serially passaged in osteogenic medium (hESC-OS), and exhibited similar expression patterns of osteoblast-related genes to osteoblast-like cells derived from mesenchymal stem cells derived from hESCs (hESCs-MSCs-OS) and human bone marrow stromal cells (hBMSCs-OS). In comparison to hESCs-MSCs-OS, the hESCs-OS required a shorter expansion time to generate a homogenous population of osteoblast-like cells that did not contain contaminating undifferentiated hESCs. Identification of human specific nuclear antigen (HuNu) in the newly formed bone in calvarial defects verified the role of the transplanted hESCs-OS as active bone forming cells in vivo. Taken together, this study suggests that osteoblast-like cells directly derived from hESCs have the potential to serve as an alternative source of osteoprogenitors for bone tissue engineering strategies.
Three-Dimensional Microfluidic Tumor Vascular Model for Investigating Breast Cancer Metastasis (2017)

Metastasis is one of the primary reasons for the high mortality rates in female patients diagnosed with breast cancer. It involves the migration of cancer cells into the circulatory system allowing for the dissemination of cancer cells in distal tissues. Understanding the major processes that occur in cells and tissues during metastasis can help improve currently existing therapeutic methods. In order to understand such mechanisms, developing physiologically relevant tissue models is crucial. Advancements in microfluidics have led to the fabrication of 3D culture models with shear stress gradients and flow control that can recapitulate aspects of the tumor microenvironment in vitro. However, most of these 3D culture models were fabricated using photolithography techniques performed in a clean room, which requires extensive training and can be cost prohibitive. Other studies have used more accessible techniques such as mold casting to construct a vessel-like microchannel. The main drawback of this method is that it limits the usage of high magnification objective lenses. Here, we propose a simple, high-fidelity and cost-effective approach in fabricating in vitro tissue platforms using a 3D printer that is optimal for live-cell imaging. To demonstrate proof-of-concept, we imaged endothelial and fibroblast cells cultured inside the 3D microfluidic collagen hydrogel, which was compared with the control group cultured in the 2D platform. The integrity of the microchannel fabricated inside the collagen hydrogel was imaged by using confocal reflectance microscopy. This feature has broader implications to bioengineered tissue fabrication and should be further explored in depth in the future.
Scaffold Hopping Affords a Highly Selective in vitro and in vivo T-Type Calcium Inhibitor Probe Free From IP Issues (2013)

A scaffold hopping approach afforded ML218 (CID 45115620) a selective T-Type Ca2+ (Cav3.1, Cav3.2, Cav3.3) inhibitor (Cav3.2, IC50 = 150 nM in Ca2+ flux; Cav3.2 IC50 = 310 nM and Cav3.3 IC50 = 270 nM in patch clamp electrophysiology) suitable for in vitro and in vivo studies. ML218 possess excellent dystrophia myotonica protein kinase (DMPK) properties, acceptable in vivo rat PK, excellent brain levels and was efficacious upon oral dosing in a preclinical Parkinsonian model. Thus, ML218 is a powerful new probe to study T-Type Ca2+ function in vitro and in vivo.
EVALUATION OF SPECIFICITY OF MONOCLONAL ANTIBODIES TO SIROLIMUS (1999)

Malcolm, A; Huster, M; Abel, M; Naicker, S; Yatscoff, R; Haley, C; Kasper, K Author Information
Long-read isoform sequencing reveals survival-associated splicing in breast cancer (2020)

Summary Tumors display widespread transcriptome alterations, but the full repertoire of isoform-level alternative splicing in cancer is not known. We developed a long-read RNA sequencing and analytical platform that identifies and annotates full-length isoforms, and infers tumor-specific splicing events. Application of this platform to breast cancer samples vastly expands the known isoform landscape of breast cancer, identifying thousands of previously unannotated isoforms of which ~30% impact protein coding exons and are predicted to alter protein localization and function, including of the breast cancer-associated genes ESR1 and ERBB2 . We performed extensive cross-validation with -omics data sets to support transcription and translation of novel isoforms. We identified 3,059 breast tumor-specific splicing events, including 35 that are significantly associated with patient survival. Together, our results demonstrate the complexity, cancer subtype-specificity, and clinical relevance of novel isoforms in breast cancer that are only annotatable by LR-seq, and provide a rich resource of immuno-oncology therapeutic targets.