gebhart/patrepeval huggingface dataset:
Hypoxia-Induced Phosphorylation of Chk2 in an Ataxia Telangiectasia Mutated–Dependent Manner (2005)

Chk2 is a serine/threonine kinase that signals to cell cycle arrest, DNA repair, and apoptotic pathways following DNA damage. It is activated by phosphorylation in response to ionizing radiation, UV light, stalled replication forks, and other types of DNA damage. Hypoxia is a common feature of solid tumors and has been shown to affect the regulation of many genes, including several DNA repair factors. We show here that Chk2 is phosphorylated on Thr68 and thereby activated in cells in response to hypoxia, and that this phosphorylation is dependent on the damage response kinase ataxia telangiectasia mutated (ATM) but not on the related kinase ATM and Rad3-related. Moreover, phosphorylation of Chk2 under hypoxia was attenuated in cells deficient in the repair factors MLH1 or NBS1. Finally, Chk2 serves to protect cells from apoptosis under hypoxic growth conditions. These results identify hypoxia as a new stimulus for Chk2 activation in an ATM-, MLH1-, and NBS1-dependent manner, and they suggest a novel pathway by which tumor hypoxia may influence cell survival and DNA repair.
The Role of Opioid Receptors in Immune System Function (2019)

Research on the effects of opioids on immune responses was stimulated in the 1980s by the intersection of use of intravenous heroin and HIV infection, to determine if opioids were enhancing HIV progression. The majority of experiments administering opioid alkaloids (morphine and heroin) <i>in vivo</i>, or adding these drugs to cell cultures <i>in vitro</i>, showed that they were immunosuppressive. Immunosuppression was reported as down-regulation: of Natural Killer cell activity; of responses of T and B cells to mitogens; of antibody formation <i>in vivo</i> and <i>in vitro</i>; of depression of phagocytic and microbicidal activity of neutrophils and macrophages; of cytokine and chemokine production by macrophages, microglia, and astrocytes; by sensitization to various infections using animal models; and by enhanced replication of HIV <i>in vitro</i>. The specificity of the receptor involved in the immunosuppression was shown to be the mu opioid receptor (MOR) by using pharmacological antagonists and mice genetically deficient in MOR. Beginning with a paper published in 2005, evidence was presented that morphine is immune-stimulating via binding to MD2, a molecule associated with Toll-like Receptor 4 (TLR4), the receptor for bacterial lipopolysaccharide (LPS). This concept was pursued to implicate inflammation as a mechanism for the psychoactive effects of the opioid. This review considers the validity of this hypothesis and concludes that it is hard to sustain. The experiments demonstrating immunosuppression were carried out <i>in vivo</i> in rodent strains with normal levels of TLR4, or involved use of cells taken from animals that were wild-type for expression of TLR4. Since engagement of TLR4 is universally accepted to result in immune activation by up-regulation of NF-κB, if morphine were binding to TLR4, it would be predicted that opioids would have been found to be pro-inflammatory, which they were not. Further, morphine is immunosuppressive in mice with a defective TLR4 receptor. Morphine and morphine withdrawal have been shown to permit leakage of Gram-negative bacteria and LPS from the intestinal lumen. LPS is the major ligand for TLR4. It is proposed that an occult variable in experiments where morphine is being proposed to activate TLR4 is actually underlying sepsis induced by the opioid.
Distinct patterns of intratumoral immune cell infiltrates in patients with HPV-associated compared to non-virally induced head and neck squamous cell carcinoma (2014)

Human papillomavirus (HPV) infection is one of the most important etiologic causes of oropharyngeal head and neck squamous cell carcinoma (HNSCC). Patients with HPV-positive HNSCC were reported to have a better clinical outcome than patients with HPV-negative cancers. However, little is known about the possible causes of different clinical outcomes. In this study, we analyzed a detailed immune profile of tumor samples from HNSCC patients with respect to their HPV status. We analyzed the characteristics of immune cell infiltrates, including the frequency and distribution of antigen-presenting cells and naïve, regulatory and effector T cells and the cytokine and chemokine levels in tumor tissue. There was a profound difference in the extent and characteristics of intratumoral immune cell infiltrates in HNSCC patients based on their HPV status. In contrast to HPV-negative tumor tissues, HPV-positive tumor samples showed significantly higher numbers of infiltrating IFNγ<sup>+</sup> CD8<sup>+</sup> T lymphocytes, IL-17<sup>+</sup> CD8<sup>+</sup> T lymphocytes, myeloid dendritic cells and proinflammatory chemokines. Furthermore, HPV-positive tumors had significantly lower expression of <i>Cox-2</i> mRNA and higher expression of PD1 mRNA compared to HPV-negative tumors. The presence of a high level of intratumoral immune cell infiltrates might play a crucial role in the significantly better response of HPV-positive patients to standard therapy and their favorable clinical outcome. Furthermore, characterization of the HNSCC immune profile might be a valuable prognostic tool in addition to HPV status and might help identify novel targets for therapeutic strategies, including cancer immunotherapy.
Palm-leaf Manuscript Libraries in Southern India Around the Thirteenth Century: The Sarasvatī Library in Chidambaram (2023)

Palm-leaf as a medium of writing occupies a major place in ancient India because of the long period of its use. Its vulnerability however required frequent copying. It seems to have been initially used to preserve and disseminate administrative and political documents; its use for transmitting literature, particularly religious literature, is accessory, late and even accidental. Libraries of manuscripts, archives, mnemonic collections (mnémothèques), and epigraphic collections (lithothèques) are four entities with various kinds of interrelationship. Two Tamil inscriptions from the thirteenth century, which attest to the activities and transformations of the Sarasvatī Library in the temple of Naṭarāja in Chidambaram, illustrate connections between these four entities.
Novel neutral atomic fluorine laser lines in a high-pressure mixture of F2 and He (1979)

Many intense neutral atomic fluorine laser lines in the visible (λ=7037.5–7552.2 Å) have been obtained from a gas mixture of F2 and He at total pressures up to 3 atm, driven by a fast Blumlein discharge. At high pressures, three new laser lines have been found and were assigned to the quartet manifold: 7425.7 Å (3p4P01/2→3s4P3/2), 7482.7 Å (3p4P03/2→3s4P3/2), and 7515.0 Å (3p4P01/2→3s4P1/2). The number of lines observed and their relative intensities were found to depend strongly on the pressue of the F2/He gas mixture.
KRAS and GNAS Co-Mutation in Metastatic Low-Grade Appendiceal Mucinous Neoplasm (LAMN) to the Ovaries: A Practical Role for Next-Generation Sequencing (2017)

BACKGROUND Low-grade appendiceal mucinous neoplasms (LAMNs) are cytologically low-grade tumors of the appendix and are a frequent cause of pseudomyxoma peritonei. They can become a diagnostic challenge when they metastasize to the ovaries, where they may mimic primary ovarian mucinous tumors. CASE REPORT We report the case of a patient with very large bilateral ovarian mucinous tumors and a concurrent minute LAMN incidentally discovered in a grossly normal appendix. A primary ovarian tumor was suspected, but histological analysis of the ovaries suggested an appendiceal origin. Immunohistochemical studies were not informative and a consensus regarding the source of the ovarian tumors could not be reached within our department. Subsequent next-generation sequencing of tumors from the right ovary, left ovary, appendix, and matched normal tissue demonstrated identical somatic point mutations in KRAS and GNAS present in all tumors. The patient was diagnosed with metastatic LAMN and did not receive further treatment. She remains disease-free after 15 months of close observation. CONCLUSIONS Determining the tissue of origin in low-grade mucinous tumors of the ovaries can be challenging when a concurrent LAMN is identified in the appendix. In cases where histology and immunohistochemistry are insufficient to render a diagnosis, the presence of concurrent KRAS and GNAS mutations in both tumors strongly favors a diagnosis of metastatic LAMN. We emphasize the utility of targeted next-generation sequencing to establish tissue of origin in challenging cases when LAMN is suspected as the source of mucinous ovarian tumors.
Double First-Order Plus Time Delay Models To Tune Proportional–Integral Controllers (2016)

The first-order plus time delay (FOPTD) model-based method is a standard approach to tune proportional–integral (PI) controllers in plants. The FOPTD model can be obtained easily from step responses. However, because of their structural limitations, FOPTD models suffer from difficulties in approximating step responses for some processes including processes with overshoot, resulting in PI controllers with unacceptable performance. To remove these drawbacks, models combining two FOPTD models that can be obtained easily from step responses are proposed to tune PI controllers. Several simulations and experimental examples are given, illustrating the improved performance of the proposed method.
The Interaction of Geometry and Local Flow Phenomena in Compliant End-to-Side Anastomosis Models (1996)

Abstract Intimal thickening (IT) and consecutive occlusions preferentially occurring at the distal anastomosis are important complications in the clinical application of bypass grafts. Experimental and numerical studies have shown that there is a correlation between IT and hemodynamic factors, such as flow stagnation, separation and recirculation and low pulsatile wall shear stress (Bassiouny et al., 1992, Hofer et al., 1996). The present study aims to investigate the relationship between flow characteristics and IT in a conventional type end-to-side anastomosis using a PTFE graft. Due to the important influence of the geometry on the anastomotic flow field anatomically correct modelling is applied.
[Intensity-modulated radiation therapy (IMRT)]. (2010)

Intensity-modulated radiation therapy (IMRT) is a new type of conformal radiotherapy which is based on the use of non-uniform radiation beam intensities, optimized by inverse planning. IMRT can achieve the optimal dose distributions and may improve the clinical outcomes dramatically. However, it is not easy to deliver IMRT properly because of its complexity. If IMRT is used inadequately, the outcome might be worse than conventional therapies. This is why the clinical and physical quality assurance (QA) should be done strictly to deliver IMRT. The clinical use of IMRT is permitted only for prostate cancers, head and neck cancers and brain tumors as health insurance treatments in Japan. IMRT is available in only about 50 institutions for now in Japan.
Design principles for nuclease-deficient CRISPR-based transcriptional regulators (2018)

The engineering of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated proteins continues to expand the toolkit available for genome editing, reprogramming gene regulation, genome visualisation and epigenetic studies of living organisms. In this review, the emerging design principles on the use of nuclease-deficient CRISPR-based reprogramming of gene expression will be presented. The review will focus on the designs implemented in yeast both at the level of CRISPR proteins and guide RNA (gRNA), but will lend due credits to the seminal studies performed in other species where relevant. In addition to design principles, this review also highlights applications benefitting from the use of CRISPR-mediated transcriptional regulation and discusses the future directions to further expand the toolkit for nuclease-deficient reprogramming of genomes. As such, this review should be of general interest for experimentalists to get familiarised with the parameters underlying the power of reprogramming genomic functions by use of nuclease-deficient CRISPR technologies.
Tutorial T3: DFM, DFT, Silicon Debug and Diagnosis -- The Loop to Ensure Product Yield (2012)

Semiconductor yield has traditionally been limited by random particle-defect based issues. However, as the feature sizes reduced to 90nm and below, systematic mechanism-limited yield loss began to appear as a substantial component in yield loss. In addition, it is becoming clear that ramping yield would take longer and final yields would not reach historical norms. A key factor for not reaching previously attained yield levels is the interaction between design and manufacturing. Yield losses in the newer processes include functional defects, parametric defects and issues with testing. Each of these sources of yield loss needs to be analyzed and understood by designers and tool developers. In addition, new techniques and methods must be devised to minimize the impact of these yield loss mechanisms. After an introduction of the issues involved in the first section, the second section covers Design-for- Manufacturing (DFM) techniques to analyze the design content, flag areas of design that could limit yield, and make changes to improve yield. However, once the changes are made it is necessary to quantify their impact so that knowledge about yield contribution of different features can be fed back to design and DFM tools. Test presents an opportunity to close the loop by crafting test patterns to expose the defect prone features during automatic test pattern generation (ATPG) and by analyzing silicon failures through diagnosis to determine the features that are actually causing yield loss and their relative impact. The third section covers design techniques (DFX) to improve testability, debuggability and diagnosability, and DFM and defect-aware test generation to both meet product quality and expose yield issues at test. Section four covers the basic concepts and theoretical aspects of debug and diagnosis including algorithmic IC diagnosis, scan chain diagnosis, critical path based techniques and diagnosis of delay defects. The applications of the basic concepts and techniques for silicon debug are covered in section five. Section six covers the application of statistical diagnosis techniques to determine the features that are actually causing yield loss and their relative impact. Finally, in section seven, future trends, challenges and directions are covered. The proposed tutorial includes the basics to be of interest to students, new engineers and managers but covers new and recent advances in hot topics in Design-for-Manufacturing, yield, test and diagnosis to be of interest to researchers and practicing engineers. The selection of topics cover a broad spectrum and will be of interest to a wide audience including design, test, product, validation, yield, debug and FA engineers.
Bifunctional Oxygen Reduction/Oxygen Evolution Activity of Mixed Fe/Co Oxide Nanoparticles with Variable Fe/Co Ratios Supported on Multiwalled Carbon Nanotubes (2018)

A facile strategy is reported for the synthesis of Fe/Co mixed metal oxide nanoparticles supported on, and embedded inside, high purity oxidized multiwalled carbon nanotubes (MWCNTs) of narrow diameter distribution as effective bifunctional catalysts able to reversibly drive the oxygen evolution reaction (OER) and the oxygen reduction reaction (ORR) in alkaline solutions. Variation of the Fe/Co ratio resulted in a pronounced trend in the bifunctional ORR/OER activity. Controlled synthesis and in-depth characterization enabled the identification of an optimal Fe/Co composition, which afforded a low OER/OER reversible overvoltage of only 0.831 V, taking the OER at 10 mA cm<sup>-2</sup> and the ORR at -1 mA cm<sup>-2</sup> . Importantly, the optimal catalyst with a Fe/Co ratio of 2:3 exhibited very promising long-term stability with no evident change in the potential for both the ORR and the OER after 400 charge/discharge (OER/ORR) cycles at 15 mA cm<sup>-2</sup> in 6 m KOH. Moreover, detailed investigation of the structure, size, and phase composition of the mixed Fe/Co oxide nanoparticles, as well as their localization (inside of or on the surface of the MWCNTs) revealed insight of the possible contribution of the individual catalyst components and their synergistic interaction in the catalysis.
Microcephalia with mandibular and dental dysplasia in adult Zmpste24‐deficient mice (2008)

ZMPSTE24 (also called FACE-1) is a zinc-metalloprotease involved in the post-translational processing of prelamin A to mature lamin A, a major component of the nuclear envelope. Mutations in the ZMPSTE24 gene or in that encoding its substrate prelamin A (LMNA) result in a series of human inherited diseases known collectively as laminopathies and showing regional or systemic manifestations (i.e. the Hutchinson-Gilford progeria syndrome). Typically, patients suffering some laminopathies show craniofacial or mandible anomalies, aberrant dentition or facial features characteristic of aged persons. To analyse whether Zmpste24(-/-) mice reproduce the cranial phenotype observed in humans due to mutations in ZMPSTE24 or LMNA, we conducted a craniometric study based on micro-computer tomography (microCT) images. Furthermore, using simple radiology, microCT, microCT-densitometry and scanning electron microscopy, we analysed the mandible and the teeth from Zmpste24(-/-) mice. Finally, the structure of the lower incisor was investigated using an H&E technique. The results demonstrate that Zmpste24(-/-) mice are microcephalic and show mandibular and dental dysplasia affecting only the mandible teeth. In all cases, the lower incisor of mice lacking Zmpste24 was smaller than in control animals, showed cylindrical morphology and a transverse fissure at the incisal edge, and the pulpal cavity was severely reduced. Structurally, the dental layers were normally arranged but cellular layers were disorganized. The inferior molars showed a reduced cusp size. Taken together, these data strongly suggest that Zmpste24(-/-) mice represent a good model to analyse the craniofacial and teeth malformations characteristic of lamin-related pathologies, and might contribute to a better understanding of the molecular events underlying these diseases.
Regional Distribution and Relative Frequency of Gastrointestinal Endocrine Cells in the ddN Mice: An Immunohistochemical Study (2010)

The distributions and frequencies of some endocrine cells in the eight portions of the gastrointestinal (GI) tract - fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum of the ddN mouse, were studied with immunohistochemical method using seven types of antisera against chromogranin (Cg) A serotonin, somatostatin, glucagon, gastrin, cholecystokinin (CCK)-8 and human pancreatic polypeptide (hPP). In the GI tract of ddN mice, CgA, serotonin, somatostatin, glucagon, gastrin, CCK-8 immunoreactive (IR) cells were identified with various frequencies, but hPP-IR cells were not observed in this study. Most of IR cells in the intestinal portion were generally spherical or spindle in shape (open type cell) whereas cells showing round in shape (close type cell) were found in the intestinal gland and stomach regions occasionally. They showed the highest frequency in the pylorus or colon. CgA-IR cells were observed from the pylorus to ileum. Serotonin-IR cells were detected throughout the whole GI tract except for the fundus. Somatostatin-IR cells were demonstrated throughout the whole GI tract except for the cecum and colon. Gastrin and CCK-8-IR cells were restricted to the pylorus and duodenum. In addition, a few glucagon-IR cells were restricted to the fundus and rectum. In conclusion, the general distribution patterns and relative frequency of GI endocrine cells of the ddN mouse was similar to that of other strains of mice. However, some strain and/or species-dependent unique distributions and frequencies of endocrine cells were also observed in the present study.
On the equivalence between SOVA and max-log-MAP decodings (1998)

It is shown that after a proper simple modification, the soft-output Viterbi algorithm (SOVA) proposed by Hagenauer and Hoeher (1989) becomes equivalent to the max-log-maximum a posteriori (MAP) decoding algorithm. Consequently, this modified SOVA allows to implement the max-log-MAP decoding algorithm by simply adjusting the conventional Viterbi algorithm. Hence, it provides an attractive solution to achieve low-complexity near-optimum soft-input soft-output decoding.
Alopecia areata – Current understanding and management (2022)

Alopecia areata (AA) is a chronic, immune-mediated disease characterized by acute or chronic non-scarring hair loss, with a heterogeneity in clinical manifestations ranging from patchy hair loss to complete scalp and body hair loss. An overview of the up-to-date pathophysiology and the underlying signaling pathways involved in AA together with diagnostic and therapeutic recommendations will be provided. Current treatments, including topical, systemic and injectable interventions show varying response and frequent relapses reflecting the unmet clinical need. Thus, the new emerging concepts and therapeutic approaches, including Janus kinase inhibitors are eagerly awaited. Traditional and emerging therapies of AA will be discussed, in order to provide physicians with guidance for AA management. Since the latter is so challenging and often tends to take a chronic course, it can have an enormous psychosocial burden on patients, compromising their quality of life and often causing depression and anxiety. Therefore, the psychosocial aspects of the disease need to be evaluated and addressed, in order to implement appropriate psychological support when needed.
A selective sensor based on a glassy carbon electrode modified with carbon nanotubes and ruthenium oxide/hexacyanoferrate film for simultaneous determination of ascorbic acid, epinephrine and uric acid (2011)

The development of a highly selective sensor for voltammetric determination of ascorbic acid (AA), epinephrine (EP) and uric acid (UA) in the same solution has been achieved by a glassy carbon electrode modified with multi-walled carbon nanotubes and ruthenium oxide hexacyanoferrate film. The modified electrode showed effective catalytic activity toward the electro-oxidation of AA, EP and UA by separating their oxidation peak potentials and producing larger anodic peak currents than those at unmodified electrodes. The electron transfer efficiency and rate constant of the oxidation process were studied using electrochemical impedance spectroscopy. The electro-catalytic peak currents of differential pulse voltammograms increased linearly with AA, EP and UA concentrations in the ranges of 0.2–15.0 μM, 0.1–10.0 μM and 0.90–250 μM with a detection limit of 0.087, 0.052 and 0.599 μM, respectively. The modified electrode showed good sensitivity, selectivity and stability for the voltammetric determination of these important biological compounds. The modified electrode was satisfactorily used for simultaneous determination of AA, EP and UA in pharmaceutical and biological samples.