gebhart/patrepeval huggingface dataset:
Abstract 2586: Therapeutic potential of the topical treatment ofmiR-634ointment for cutaneous squamous cell carcinoma (2019)

Cutaneous squamous cell carcinoma (CSCC) is the second most common nonmelanoma skin cancers. Surgery represents the gold standard for CSCC treatment, however it is needed to develop the noninvasive and effective treatments as the nonsurgical options for CSCC patients whose conditions are not suitable for or who refuse operation. On the other hand, microRNAs (miRs) are endogenous small non-coding RNAs negatively regulate gene expression by interfering with the translation or stability of target transcripts. Some tumor-suppressive miRs can target multiple cancer-promoting genes concurrently and may be useful as a therapeutic agent for cancer therapy. We have previously found that overexpression of miR-634 activated the mitochondrial apoptotic pathway by directly targeting genes associated with cytoprotective processes, including mitochondrial homeostasis, anti-apoptosis, antioxidant ability, and autophagy, in various cancer cells. The development of drug delivery system (DDS) is critical for the implementation of miR-based therapeutics. While topical pharmacotherapy represents a nonsurgical option to consider in CSCC, we validated the therapeutic potential of topical treatment of miR-634 ointment in mice model of CSCC. In xenograft tumors of A431 cells, a human epidermoid carcinoma cell line, in mice the topical treatment of ointment incorporated double-strand miR-634 mimics significantly reduced tumor growth. Furthermore, the topical treatment of miR-634-ointment also inhibited tumor growth in carcinogen-induced mouse skin papilloma model. Taken together, these findings suggest that topical treatment of miR-634-ointment may be useful as a noninvasive and effective treatments for CSCC.Citation Format: Jun Inoue, Kentaro Gokita, Masahiro Kishikawa, Hidetoshi Hamamoto, Katsunori Kobayashi, Kyoko Fujiwara, Takahiro Asakage, Kazuyuki Kojima, Johji Inazawa. Therapeutic potential of the topical treatment of miR-634 ointment for cutaneous squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2586.
Long‐term outcomes for men with high‐risk prostate cancer treated definitively with external‐beam radiotherapy with or without androgen deprivation (2013)

The author reports on outcomes of high‐dose radiation and hormonal therapy for high‐risk prostate cancer. The article would be improved by systematically collecting and reporting the adverse effects of treatment.
Quantitative systems pharmacology model of GITR‐mediated T cell dynamics in tumor microenvironment (2023)

T cell interaction in the tumor microenvironment is a key component of immuno-oncology therapy. Glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related protein (GITR) is expressed on immune cells including regulatory T cells (Tregs) and effector T cells (Teffs). Preclinical data suggest that agonism of GITR in combination with Fc-γ receptor-mediated depletion of Tregs results in increased intratumoral Teff:Treg ratio and tumor shrinkage. A novel quantitative systems pharmacology (QSP) model was developed for the murine anti-GITR agonist antibody, DTA-1.mIgG2a, to describe the kinetics of intratumoral Tregs and Teffs in Colon26 and A20 syngeneic mouse tumor models. It adequately captured the time profiles of intratumoral Treg and Teff and serum DTA-1.mIgG2a and soluble GITR concentrations in both mouse models, and described the response differences between the two models. The QSP model provides a quantitative understanding of the trade-off between maximizing Treg depletion versus Teff agonism, and offers insights to optimize drug design and dose regimen.
Effect of 1,3,3,5,5-pentaziridino-1-thia-2,4,6-triaza-3,5-diphosphorine-1-oxide, a new antitumor agent with inorganic ring, on various experimental tumors. (1982)

1,3,3,5,5-Pentaziridino-1-thia-2,4,6-triaza-3,5-diphosphorine-1-oxide (SOAz), a new antitumor agent, was evaluated for antitumor activity against various mouse- and rat-tumor systems. The optimal treatment regimens of SOAz (i.p.) gave 262% and 134% increase in life span (ILS) in mice with P388 leukemia and L1210 leukemia implanted intraperitoneally, respectively, and 239% ILS in rats with Yoshida sarcoma of which 86% survived for 60 d after intraperitoneal tumor implantation. The compound showed a definite activity against Lewis lung carcinoma implanted intravenously. The compound also exhibited 80-100% inhibition of tumor local growth in all of four experimental tumor systems used in the present study. In contrast to cyclophosphamide, SOAz was active against B16 melanoma and Meth A, and demonstrated high activity against a subline of L1210 leukemia resistant to cyclophosphamide.
Front Cover: Polythiolactone‐Decorated Silica Particles: A Versatile Approach for Surface Functionalization, Catalysis and Encapsulation (Chem. Eur. J. 28/2021) (2021)

The cover image illustrates the “universal” post-modification of silica particles coated with a polythiolactone polymer shell, which can be used for molecular functionalization, incorporation of nanoparticle catalysts, and formation of nanocapsules for triggered payload release. The sun symbolizes the precursor particles and the planets are some of the potential functional derivatives. The design was conceived by Dustin Kurka and composed by Nina Knubel at the University of Münster. More information can be found in the Full Paper by B. J. Ravoo et al. (DOI: 10.1002/chem.202100547).
Influenza C virus NS1 protein counteracts RIG-I-mediated IFN signalling (2011)

The nonstructural proteins 1 (NS1) from influenza A and B viruses are known as the main viral factors antagonising the cellular interferon (IFN) response, inter alia by inhibiting the retinoic acid-inducible gene I (RIG-I) signalling. The cytosolic pattern-recognition receptor RIG-I senses double-stranded RNA and 5'-triphosphate RNA produced during RNA virus infections. Binding to these ligands activates RIG-I and in turn the IFN signalling. We now report that the influenza C virus NS1 protein also inhibits the RIG-I-mediated IFN signalling. Employing luciferase-reporter assays, we show that expression of NS1-C proteins of virus strains C/JJ/50 and C/JHB/1/66 considerably reduced the IFN-β promoter activity. Mapping of the regions from NS1-C of both strains involved in IFN-β promoter inhibition showed that the N-terminal 49 amino acids are dispensable, while the C-terminus is required for proper modulation of the IFN response. When a mutant RIG-I, which is constitutively active without ligand binding, was employed, NS1-C still inhibited the downstream signalling, indicating that IFN inhibitory properties of NS1-C are not necessarily linked to an RNA binding mechanism.
Human Body (2019)

Association of American Publishers (AAP) Finalist for the 2020 PROSE Award Association of American Publishers (AAP) Subject Category Winner for the 2020 PROSE Award 2019 Taylor & Francis Award Winner for Outstanding Professional Book! Human Body: A Wearable Product Designer's Guide, unlike other anatomy books, is divided into sections pertinent to wearable product designers. Two introductory chapters include many definitions, an introduction to anatomical terminology, and brief discussions of the body's systems, setting the stage for the remaining chapters. The book is extensively referenced and has a large glossary with both anatomical and design terms making it maximally useful for interdisciplinary collaborative work. The book includes 200 original illustrations and many product examples to demonstrate relationships between wearable product components and anatomy. Exercises introduce useful anatomical, physiological, and biomechanical concepts and include design challenges. Features Includes body region chapters on head and neck, upper torso and arms, lower torso and legs, the mid-torso, hands, feet, and a chapter on the body as a whole Contains short sections on growth and development, pregnancy, and aging as well as sections on posture, gait, and designing total body garments Describes important regional muscles and their actions as well as joint range of motion (ROM) definitions and data with applications to designing motion into wearable products Presents appendices correlating to each body region's anatomy with instructions for landmarking and measuring the body, a valuable resource for a lifetime of designing For product design examples based on the book go to: https://www.uosportsproductdesign.com/humananatomy-sportsproductdesign-sokolowski-labat
The Spontaneous Return of Sensibility in Breasts Reconstructed with Autologous Tissues (1997)

Some spontaneous return of sensibility following autologous tissue breast reconstruction is often suspected but not well documented. In the present study, objective touch-pressure, pain, temperature, and vibratory sensibilities were recorded in 33 autologous breast reconstructions at an average of 25.2 months postoperatively. Correlation of the sensory return with patients' satisfaction toward reconstruction was done by a detailed questionnaire. All except one patient regained a variety of sensibilities touch pressure in 97 percent of patients (averaging 81.05 gm/mm2 versus control of 7.98 gm/mm2), pain in 88 percent of patients, heat in 64 percent of patients (45 percent of quadrants), cold in 82 percent of patients (67 percent of quadrants), and high- and low-frequency vibration in 100 percent of patients (high in 90 percent of quadrants, low in 96 percent). Subjectively, 94 percent considered their chest comfortable to touch following reconstruction compared with 34 percent following mastectomy. On a scale from 1 to 10, patients rated their reconstructions an average of 9.3. Our findings confirm the spontaneous return of sensibility following a variety of autologous tissue breast reconstructions. The value of the sensory return is suggested by the high degree of satisfaction in nearly all patients. Further attempts to correlate the degree of sensory return with the degree of satisfaction were inconclusive because of the uniformly high satisfaction reported by the patients. The mechanism of reinnervation appears to come both from the skin margins and from the deep surface of the flap. Future developments in breast reconstruction should take into consideration the eventual quality of sensory return.
A repetitive high-current pulsed accelerator—TPG700 (2008)

The design and construction of a repetitive high-current pulsed accelerator-TPG700 is described in this paper. The accelerator consists of a Tesla transformer with 40 ohm build-in coaxial pulse forming line. The triggered high-pressure switch of TPG700 has the capability of conducting current of 17.5kA in 35ns' duration at 100 pps. The transformer was designed to operate at 1.4MV, when its primary capacitors were charged to approximately 1000V. Under the working state of 100pps, the jitter of breakdown of the switch voltages is lower than 1% on average. To enhance the overall efficiency of the pulser, resonant charging technology based on IGBTs was utilized. As the experimental results indicate, the total efficiency of the pulser, when measured on matched dummy load, is close to 75%. The experimental results indicate that in matching case, the output of 700kV, 17kA for 40Ω resistive load is obtained. Moreover, some experiments such as long lifetime cathode testing and high power microwave (HPM) generation using backward oscillator (BWO) have been conducted on TPG700.
Faculty Opinions recommendation of Evolution of enzymatic activities in the enolase superfamily: N-succinylamino acid racemase and a new pathway for the irreversible conversion of D- to L-amino acids. (2006)

Read the full review for this Faculty Opinions recommended article: Evolution of enzymatic activities in the enolase superfamily: N-succinylamino acid racemase and a new pathway for the irreversible conversion of D- to L-amino acids.
Biphasic JNK–Erk Signaling Separates Induction and Maintenance of Cell Senescence after DNA Damage (2022)

SUMMARY Genotoxic stress in mammalian cells, including that caused by anti-cancer chemotherapy, can induce temporary cell cycle arrest, DNA damage-induced senescence (DDIS) or apoptotic cell death. Despite obvious clinical importance, it is unclear how the signals emerging from DNA damage are integrated together with other cellular signaling pathways monitoring the cell’s environment and/or internal state to control these different cell fates. Here, using a combination of single cell-based signaling measurements and tensor PLSR/PCA computational approaches, we show that the JNK and Erk MAPK signaling pathways regulate the initiation of senescence through the transcription factor AP-1 at early times after extrinsic DNA damage, and the Senescence Associated Secretory Phenotype, a hallmark of DDIS, at late times after damage. These results identify a time-based separation of function for the same signaling pathways beyond the classic DNA damage response that control the cell senescence decision and modulate the tumor microenvironment following genotoxic stress, and reveal a fundamental similarity between signaling mechanisms responsible for oncogene-induced senescence and senescence caused by extrinsic DNA damaging agents.
CoSi2 heteroepitaxy on patterned Si(100) substrates (1996)

The influence of starting surface topography on the nucleation and growth of epitaxial silicide layers was investigated. CoSi2 layers were grown via the template technique on one-dimensionally patterned Si(100) substrates. These substrates contained mesa stripes, running parallel to Si[011], and exhibited either a number of Si {hkl} facets, or ‘‘smoothly varying’’ sinusoidal profiles. Conventional plan view and high resolution cross section transmission electron microscopy showed that the orientation and morphology of the CoSi2 grains depend on the angle (θ) between the CoSi2/Si interface normal and Si(100). CoSi2(100) grains nucleated on mesa tops and trench bottoms, where θ&amp;lt;5°, and formed atomically sharp interfaces. CoSi2(110) and CoSi2(221) grains nucleated along sidewalls of the mesa structures, in regions where 5°&amp;lt;θ&amp;lt;11° and θ≳5°, respectively. CoSi2(110) grains formed highly stepped interfaces with the substrate which were punctuated by step bunches at the grain boundary/substrate triple points. CoSi2(221) grains formed rough interfaces with the substrate which were punctuated by facets and B-type silicide/substrate interfaces along Si{111} planes. Analysis of these data suggests that nucleation of CoSi2(110) grains is associated with the presence of double height steps and step bunches with small surface misorientation, and that nucleation of CoSi2(221) grains is associated with Si{111} facets, Si{311} facets, and step bunches with larger surface misorientation.
Chemokine (2016)

The evolution that has taken place in medicinal chemistry practice as a result of major advances in genomics and molecular biology arising from the Human Genome Project has carried with it an extensive additional working vocabulary that has become both integrated and essential terminology for the medicinal chemist. Some of this augmented terminology has been adopted from the many related and interlocked scientific disciplines with which the modern medicinal chemist must be conversant, but many other terms have been introduced to define new concepts and ideas as they have arisen. In this supplementary Glossary, we have attempted to collate and define many of the additional terms that are now considered to be essential components of the medicinal chemist’s expanded repertoire.
Modulation of fetal and placental metabolic pathways in response to maternal thyroid and glucocorticoid hormone excess. (1994)

Triiodothyronine (T3) treatment of pregnant rats for 6 days, 10 micrograms/100 g, resulted in a pronounced induction of enzymes related to gluconeogenesis and lipogenesis and of mitochondrial FAD-glycerophosphate dehydrogenase in the maternal liver, as previously observed in male rats. There was virtually no change in the activity of these enzymes in the placenta. However, there was a distinct induction of these enzymes in the fetal liver, even if increments in fetal serum and liver T3 were much smaller than on the maternal side. This indicates that changes in hepatic enzyme activities are a more sensitive index of fetal hyperthyroidism than T3 levels. The increased lipogenic capacity was expressed by greater incorporation of a tritium tracer into fatty acids. Administration of triamcinolone, 2 mg/100 g, for the last 5 days of gestation resulted in marked induction of maternal hepatic enzymes of lipogenesis, gluconeogenesis and of aspartate aminotransferase (ASAT), known to occur in male rats, as well as in a metabolic pattern of insulin resistance. The response of placental enzymes was limited to a small elevation in ASAT and phosphoenolpyruvate carboxykinase (PEPCK) activity. In the fetal liver there was no stimulation of lipogenic enzymes, but a marked induction of PEPCK and ASAT. The changes in the lipogenic capacity were confirmed by tritium incorporation into serum and liver fatty acids. These results demonstrate the marked sensitivity of specific fetal enzyme systems to the maternal iatrogenic hyperthyroidism or hypercorticism. The limited alterations in placental enzyme activities are in accord with the concept that placental metabolic stability fulfils a protective function toward the fetus.
Geostationary, Multi-Carrier Mesh Network Enabled by On Orbit Reprogrammable Commercial FPGAs (2023)

This paper describes the development and qualification of spaceflight hardware which serves as the core of a mesh network from a geostationary (GEO) orbit. The design builds upon our heritage for a high-performance single board computer (HP-SBC). Instead of a single radiation hardened Field Programmable Gate Array (FPGA), the HP-SBC uses a commercial multi-die FPGA, which greatly expands the quantity of logic cells available for firmware and also provides radiation mitigation strategies such as internal configuration scrubbing. The signal processing power of the modern commercial FPGAs is an absolute necessity and outweighs the added radiation susceptibility. Each of the four receive channels was shown to process 153 Mbps for a composite uplink and downlink rate of 1.2 Gbps. The four receive channels have 80 MHz bandwidth and are capable of demodulating 36 continuous carriers each, or they can be operated in a time division multiplexed (TDM) format depending on the firmware implementation. The system maintained Network Clock Reference (NCR) stability better than 1 part in 10 billion during an endurance test. The thermal management system was shown to dissipate loads reaching 250 Watts without issue.
Activite in vivo de ribozymes en tete de marteau contre l'arn du vih-1 dans un modele d'expression cytoplasmique par le virus de la vaccine (1995)

Les ribozymes sont des molecules d'arn qui sont capables de couper de facon catalytique des arn a des sites definis. Ils sont utilises pour inhiber specifiquement l'expression d'un gene ou le developpement d'un virus. Nous avons etudie l'activite d'un ribozyme en tete de marteau dans le cytoplasme des cellules hela infectees par un recombinant de virus de la vaccine exprimant la polymerase du phage t7, et cotransfectees avec deux plasmides exprimant chacun le ribozyme ou la cible (arn du vih-1, position +1 a +692) sous le controle d'un promoteur t7. Nous avons teste deux ribozymes de 181 nt (rz181) et 132 nt (rz132) contenant la sequence-coeur du ribozyme (35 nt). L'arn de 181 nt (rz181m) presente une mutation d'une base dans le coeur catalitique qui le rend inactive in vitro. Comme controle nous avons utilise le plasmide d'origine pet-3, exprimant un arn de 134 nt sans insert, ainsi que le prz181m exprimes en exces de 50 fois sur la cible, les ribozymes rz181 et rz132 diminuent le niveau de l'arn-cible du vih-1 present dans les cellules (mesure par rt-pcr), tandis que le ribozyme mute rz181m est sans effet, eliminant ainsi un effet antisense. Cependant, des mesures par rt-pcr competitive montrent qu'il faut un exces de 300 fois de ribozyme sur la cible pour obtenir une inhibition importante (85 %) de l'arn cible. Dans les memes conditions d'expression le rz181m presente un faible effet antisens. Le rz132 plus court, obtenu par une deletion de 49 nt de rz181, est plus active in vivo. Cependant, les rz181 et rz132 ne coupent pas in vitro une cible de 14-mer ou de 256 nt, alors qu'un miniribozyme de 35 nt est tres efficace.
Renal neoplasms in tuberous sclerosis mice are neurocristopathies (2021)

Tuberous sclerosis (TS) is a rare disorder exhibiting multi-systemic benign neoplasms. We hypothesized the origin of TS neoplastic cells derived from the neural crest given the heterogeneous ecto-mesenchymal phenotype of the most common TS neoplasms. To test this hypothesis, we employed Cre-loxP lineage tracing of myelin protein zero (Mpz)-expressing neural crest cells (NCCs) in spontaneously developing renal tumors of <i>Tsc2</i> <sup><i>+/-</i></sup> /<i>Mpz(Cre)</i>/TdT <sup><i>fl/fl</i></sup> reporter mice. In these mice, ectopic renal tumor onset was detected at 4 months of age increasing in volume by 16 months of age with concomitant increase in the subpopulation of tdTomato<sup>+</sup> NCCs from 0% to 6.45% of the total number of renal tumor cells. Our results suggest that <i>Tsc2</i> <sup><i>+/-</i></sup> mouse renal tumors arise from domiciled proliferative progenitor cell populations of neural crest origin that co-opt tumorigenesis due to mutations in <i>Tsc2</i> loci. Targeting neural crest antigenic determinants will provide a potential alternative therapeutic approach for TS pathogenesis.
Generation of human induced pluripotent stem cell lines with HMOX1 promoter polymorphism and CRISPR/Cas9-mediated deletion of exon 50 of DMD gene (2022)

Duchenne muscular dystrophy (DMD), originating from the lack of functional dystrophin, clinically manifests as devastating disease of skeletal muscles with progressive cardiac involvement. HMOX1 promoter polymorphism may reflect different activity of heme oxygenase-1 (HO-1) that may be critical for DMD progression. Here we generated human induced pluripotent stem cell (hiPSC) lines from healthy donors-derived peripheral blood mononuclear cells with different variants of HMOX1 promoter (GT repeats), and engineered by CRISPR/Cas9-mediated deletion of exon 50 of DMD gene. Such in vitro model could add to molecular understanding of DMD and verify the prognostic value of HMOX1 promoter polymorphism.
Partial Restoration of Replication of Simian Immunodeficiency Virus by Point Mutations in either the Dimerization Initiation Site (DIS) or Gag Region after Deletion Mutagenesis within the DIS (2001)

We used the simian immunodeficiency virus (SIV) molecular clone SIVmac239 to generate a deletion construct, termed SD2, in which we eliminated 22 nucleotides at positions +398 to +418 within the putative dimerization initiation site (DIS) stem. This SD2 deletion severely impaired viral replication, due to adverse effects on the packaging of viral genomic RNA, the processing of Gag proteins, and viral protein patterns. However, long-term culture of SD2 in either C8166 or CEMx174 cells resulted in restoration of replication capacity, due to two different sets of three compensatory point mutations, located within both the DIS and Gag regions. In the case of C8166 cells, both a K197R and a E49K mutation were identified within the capsid (CA) protein and the p6 protein of Gag, respectively, while the other point mutation (A423G) was found within the putative DIS loop. In the case of CEMx174 cells, two compensatory mutations were present within the viral nucleocapsid (NC) protein, E18G and Q31K, in addition to the same A423G substitution as observed with C8166 cells. A set of all three mutations was required in each case for restoration of replication capacity, and either set of mutations could be substituted for the other in both the C8166 and CEMx174 cell lines.