gebhart/patrepeval huggingface dataset:
p90 ribosomal S6 kinase 2 promotes invasion and metastasis of human head and neck squamous cell carcinoma cells (2010)

Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of human cancer and frequently metastasizes to LNs. Identifying metastasis-promoting factors is of immense clinical interest, as the prognosis for patients with even a single unilateral LN metastasis is extremely poor. Here, we report that p90 ribosomal S6 kinase 2 (RSK2) promotes human HNSCC cell invasion and metastasis. We determined that RSK2 was overexpressed and activated in highly invasive HNSCC cell lines compared with poorly invasive cell lines. Expression of RSK2 also correlated with metastatic progression in patients with HNSCC. Ectopic expression of RSK2 substantially enhanced the invasive capacity of HNSCC cells, while inhibition of RSK2 activity led to marked attenuation of invasion in vitro. Additionally, shRNA knockdown of RSK2 substantially reduced the invasive and metastatic potential of HNSCC cells in vitro and in vivo in a xenograft mouse model, respectively. Mechanistically, we determined that cAMP-responsive element-binding protein (CREB) and Hsp27 are phosphorylated and activated by RSK2 and are important for the RSK2-mediated invasive ability of HNSCC cells. Our findings suggest that RSK2 is involved in the prometastatic programming of HNSCC cells, through phosphorylation of proteins in a putative signaling network. Moreover, targeting RSK2 markedly attenuates in vitro invasion and in vivo metastasis of HNSCC cells, suggesting that RSK2 may represent a therapeutic target in the treatment of metastatic HNSCC.
Cutting Edge: CD96 (Tactile) Promotes NK Cell-Target Cell Adhesion by Interacting with the Poliovirus Receptor (CD155) (2004)

The poliovirus receptor (PVR) belongs to a large family of Ig molecules called nectins and nectin-like proteins, which mediate cell-cell adhesion, cell migration, and serve as entry receptors for viruses. It has been recently shown that human NK cells recognize PVR through the receptor DNAM-1, which triggers NK cell stimulation in association with beta(2) integrin. In this study, we show that NK cells recognize PVR through an additional receptor, CD96, or T cell-activated increased late expression (Tactile). CD96 promotes NK cell adhesion to target cells expressing PVR, stimulates cytotoxicity of activated NK cells, and mediates acquisition of PVR from target cells. Thus, NK cells have evolved a dual receptor system that recognizes nectins and nectin-like molecules on target cells and mediates NK cell adhesion and triggering of effector functions. As PVR is highly expressed in certain tumors, this receptor system may be critical for NK cell recognition of tumors.
3D motion tracking of pulmonary lesions using CT fluoroscopy images for robotically assisted lung biopsy (2004)

We are developing a prototype system for robotically assisted lung biopsy. For directing the robot in biopsy needle placement, we propose a non-invasive algorithm to track the 3D position of the target lesion using 2D CT fluoroscopy image sequences. A small region of the CT fluoroscopy image is registered to a corresponding region in a pre-operative CT volume to infer the position of the target lesion with respect to the imaging plane. The registration is implemented in a coarse to fine fashion. The local deformation between the two regions is modeled by an affine transformation. The sum-of-squared-differences (SSD) between the two regions is minimized using the Levenberg-Marquardt method. Multi-resolution and multi-start strategies are used to avoid local minima. As a result, multiple candidate transformations between the two regions are obtained, from which the true transformation is selected by similarity voting. The true transformation of each frame of the CT fluoroscopy image is then incorporated into a Kalman filter to predict the lesion’s position for the next frame. Tests were completed to evaluate the performance of the algorithm using a respiratory motion simulator and a swine animal study.
Three-component synthesis of spiro compounds with a carbamate functionality (2011)

1,3-Dipolar cycloaddition of methyl 4-[2-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)acetyl]phenylcarbamate to non-stabilized azomethine ylides generated by decarboxylation of α-amino acid (sarcosine and proline) adducts with ketones (isatin and ninhydrin) occurred regioselectively with formation of the corresponding spiro compounds having a carbamate moiety.
Expression of Pulmonary Surfactant Protein D in Rat Gastric Mucosa (1995)

Gastric mucosa is protected from an acidic lumenal environment by an extracellular layer composed in part of phospholipids that are similar in composition to the phospholipids of lung surfactant. The function and metabolic processing of lung surfactant is regulated, in part, by surfactant specific proteins. We speculated that the gastric extracellular acid barrier might be regulated by such proteins. We demonstrate by RNA blot analysis, RT-PCR, and immunostaining and protein blot the synthesis of surfactant protein D (SP-D) in mucus-secreting cells of the gastric mucosa. SP-D protein and mRNA were not detected in the duodenum and the remainder of the gastrointestinal tract. We speculate that SP-D may participate in the regulation of secretion or assembly of the gastric acid barrier. Alternatively, SP-D may participate in gastric mucosal host defense.
Cardiac Glycosides Exert Anticancer Effects by Inducing Immunogenic Cell Death (2012)

Some successful chemotherapeutics, notably anthracyclines and oxaliplatin, induce a type of cell stress and death that is immunogenic, hence converting the patient's dying cancer cells into a vaccine that stimulates antitumor immune responses. By means of a fluorescence microscopy platform that allows for the automated detection of the biochemical hallmarks of such a peculiar cell death modality, we identified cardiac glycosides (CGs) as exceptionally efficient inducers of immunogenic cell death, an effect that was associated with the inhibition of the plasma membrane Na(+)- and K(+)-dependent adenosine triphosphatase (Na(+)/K(+)-ATPase). CGs exacerbated the antineoplastic effects of DNA-damaging agents in immunocompetent but not immunodeficient mice. Moreover, cancer cells succumbing to a combination of chemotherapy plus CGs could vaccinate syngeneic mice against a subsequent challenge with living cells of the same type. Finally, retrospective clinical analyses revealed that the administration of the CG digoxin during chemotherapy had a positive impact on overall survival in cohorts of breast, colorectal, head and neck, and hepatocellular carcinoma patients, especially when they were treated with agents other than anthracyclines and oxaliplatin.
Unraveling the clinicopathological features driving the emergence of ESR1 mutations in metastatic breast cancer (2018)

<i>ESR1</i> mutations were recently found to be an important mechanism of endocrine resistance in ER-positive (ER + ) metastatic breast cancer. To determine the clinicopathological features driving the emergence of the <i>ESR1</i> mutations we studied plasma cfDNA and detailed clinical data collected from patients with metastatic breast cancer. Droplet Digital PCR was performed for the detection of the most common <i>ESR1</i> mutations and <i>PIK3CA</i> mutations. Among the patients with ER + /HER2- disease, <i>ESR1</i> mutations were detected in 30% of the patients. There were no associations between the pathological features of the primary disease or time to distant recurrence and the emergence of <i>ESR1</i> mutations in metastatic disease. The prevalence of the <i>ESR1</i> mutations was significantly associated with prior treatment with an aromatase inhibitor in the adjuvant or metastatic setting. The prevalence of the <i>ESR1</i> mutations was also positively associated with prior fulvestrant treatment. Conversely, the prevalence of <i>ESR1</i> mutations was lower after treatment with a CDK4/6 inhibitor. There were no significant associations between specific systemic treatments and the prevalence of <i>PIK3CA</i> mutations. These results support the evolution of the <i>ESR1</i> mutations under the selective pressure of treatment with aromatase inhibitors in the adjuvant and metastatic settings and have important implications in the optimization of adjuvant and metastatic treatment in ER + breast cancer.
Automated transistor sizing algorithm for minimizing spurious switching activities in CMOS circuits (2002)

In this paper a new approach for minimizing glitches in the combinational parts of static CMOS circuits is presented. Delay balancing is applied in order to guarantee synchronously arriving signal slopes at the inputs of the logic gates. Thus, glitching can be avoided. The delay of a logic gate depends directly on the transistor sizes, i.e. the channel-widths and -lengths (W and L). Specific variation of the transistor sizes allows one to equalize different path delays without influencing the total propagation delay of the circuit. Besides the delay, the total capacitance and the short-circuit power consumption of a circuit also depend on the transistor sizes. In order to take this fact into account when sizing transistors for delay balancing, the method is formulated as a multiobjective optimization problem, where the path delay differences and the power consumption are the design objectives. A program GliMATS for automated circuit optimization has been implemented. Experimental results show that significant power savings can be achieved with this method.
Frontiers of Medicinal Chemistry (2016)

Journal of Medicinal Chemistry deals with the study of pharmaceutical analysis and the chemical analysis of compounds for the medicinal value. It also involves developing new chemical entities or compounds from existing agents, which are of medicinal and therapeutic significance. The current medicinal chemistry Volume 6, Issue 7, of the journal publishes 11 research articles, mini review and review article which are relevant to the current interest of medicinal chemistry.
Detection of B lymphoma cells undergoing apoptosis by Annexin-V assay. (2002)

Annexin-V assay is a specific, sensitive, accurate, reproductive and quantitative method for analyzing apoptotic cells.
Phase II study of 5-azacytidine in sarcomas of bone (1982)

Eight patients with osteogenic sarcoma and seven patients with Ewing's sarcoma, all with advanced metastatic disease refractory to conventional therapy, were treated with 5-azacytidine (NSC-102816) intravenously at a dosage of 150 mg/m2 in three divided doses daily X 5 days. The courses were repeated q 4 weeks and the dosage was escalated to 200 mg/m2/day, as tolerated. Fourteen patients were evaluable for response. Major toxicities wee hematologic and gastrointestinal. 5-azacytidine had no demonstrable antitumor activity.
Rapid runtime system verification using automatic source code instrumentation (2011)

This paper describes a tool set for on-line and off-line runtime formal verification of system of systems (SoS) using rapid source-code instrumentation of complex C, C++, and Java applications. The tool set consists of two Eclipse plugins: an automatic source code instrumentation tool and an XML-to-JUnit log-file converter. The automatic instrumentation tool inserts code snippets in the source code of the system under test. During the SUT's execution the code snippets create a log stream (file or socket stream) in XML format. The XML-to-JUnit log-file converter transforms this stream into equivalent JUnit tests within the Eclipse environment. These test scenarios are then executed against state chart-assertion formal specifications, thereby performing runtime verification. The tool set enables runtime verification of formal specifications that contain real-time constraints and is capable of performing such verification for applications running on most popular real-time operating systems.
Oligonucleotides as transcription factor decoys. (1999)

Cellular and molecular research has been focused to develop a means to regulate gene expression in an effort to treat and cure a variety of diseases and abnormal physiological conditions. A successful oligonucleotide-based approach has been the use of synthetic oligonucleotides containing an enhancer element that can penetrate cells, bind sequence-specific DNA-binding proteins and interfere with transcription in vivo. This review describes such decoy oligonucleotides that exhibit high affinity for a target transcription factor and successfully interfere with transcription in vivo. Evidence presented here shows that the decoy oligonucleotide technology offers great promise as a tool for defining cellular regulatory processes and for treating cancer, viral diseases and other pathological conditions.
The History of Radio Wave Propagation up to the End of World War I (1962)

Hertz in the 1880's demonstrated electromagnetic wave propagation predicted by Maxwell from his equations in 1864. Heaviside and Kennelly postulated the ionosphere to explain Marconi's historical transatlantic reception of radio waves in 1901. Austin derived the first formula for radio propagation in 1911 from experimental data in the kilometer wavelength range taken in the daytime. Much theoretical effort was expended on the effect of the electrical properties of the ground but the problem was not resolved until a later date. Watson, however, cleared up the problem of diffraction around a perfectly conducting sphere in 1919. Up to the end of World War I, it was generally believed that radio transmission improved with increase in wavelength so the experimental data is concentrated in this region.
Chemical regulation of distance. Characterization of the first natural host germination stimulant for Striga asiatica (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemical regulation of distance. Characterization of the first natural host germination stimulant for Striga asiaticaMayland. Chang, David H. Netzly, Larry G. Butler, and David G. LynnCite this: J. Am. Chem. Soc. 1986, 108, 24, 7858–7860Publication Date (Print):November 1, 1986Publication History Published online1 May 2002Published inissue 1 November 1986https://pubs.acs.org/doi/10.1021/ja00284a074https://doi.org/10.1021/ja00284a074research-articleACS PublicationsRequest reuse permissionsArticle Views394Altmetric-Citations127LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Mineral Composition at the Tendon-to-Bone Insertion and Its Role in Stress Transfer (2007)

Musculoskeletal injuries are a common cause of pain and disability, and result in significant health care costs. Rotator cuff injuries, which make up the majority of soft tissue injuries to the upper extremity, commonly require surgical repair to the humeral head. At the rotator cuff, for example, the recurrence of tears to surgically repaired tendons has been reported to be as high as 94% [1]. The most dramatic feature of the failed tendon-to-bone healing scenarios is the lack of a transition zone between the tendon and bone that existed before the injury [2].
Modulation of involucrin and envelope competence in human keratinocytes by hydrocortisone, retinyl acetate, and growth arrest. (1983)

Involucrin accumulation and ionophore-assisted envelope formation, markers of keratinocyte differentiation, were found to be highly dependent on culture conditions in the malignant epidermal keratinocyte line, SCC-13, derived from a human squamous cell carcinoma. In confluent cultures, approximately one-half of the cells were competent to form envelopes when grown in medium without hydrocortisone or retinyl acetate supplementation. Addition of hydrocortisone to the medium during growth resulted in up to 90% competence, while addition of retinyl acetate instead resulted in as low as 10% competence. Hydrocortisone partially antagonized the effect of retinyl acetate when both agents were added together. Involucrin levels, measured by radioimmunoassay, were modulated essentially in parallel with envelope competence under the various conditions tested. When the cells were grown in medium supplemented with hydrocortisone, the levels shortly after confluence were over 50-fold higher than in sparse cultures. Regardless of hydrocortisone or retinyl acetate addition, less than 1% of the cells were competent in sparse cultures of growing cells, but up to 90% exhibited this property after growth arrest in serum-free medium containing hydrocortisone. High levels of competence were correlated with cessation of cell division but not with loss of colony-forming efficiency; under optimal conditions, two-thirds of the cells were capable of both envelope formation and colony initiation. Normal human epidermal cells showed a 4- to 5-fold increase in envelope competence from sparse to confluent culture but were insensitive to the suppressive effect of retinyl acetate. The results suggest that some potential differentiated character of malignant keratinocytes may be suppressed in vivo by physiological agents such as vitamin A.
Dynamics of Information Packaging in Korean (2000)

This paper discusses deletion and movement operations in Korean from the perspective of information packaging, and claims that each operation is a systematic process of information packaging to generate the most optimized information structure. This paper argues that there is neither free word order nor free deletion in Korean. This paper explicitly illustrates that old arguments cannot stand still in information structure, but must undergo some kind of structural changes or deletion. This paper proposes a constraint on information packaging that covers both operations and gives an explanation of underlying motivation for them. It is also suggested to decompose each component of information structure into a feature complex. 1.
Secular Variation Across the Oceans: a Retrospective Study from 35 Years of Shipboard Total Field Measurements in the NE Atlantic (1992)

This is a pilot study to determine whether secular variation information can be retrieved from underway shipboard total field measurements with sufficient accuracy to complement geomagnetic data from land-based observatories. Applying the various new techniques described in this report, we extracted values of the total field at 42,677 crossovers or ship track intersection points contained in data sets collected between 18 degrees N and 50 degress N in the NE Atlantic, and extending temporally from 1955 to 1990. We used an edited subset of these total field values to derive the secular variation at 30,140 different locations in the study area, and compared the results with DGRF secular variation over the study area, calculated at 5 year intervals. The derived and DGRF values agree well, showing that indeed marine data can be a source for secular variations. However the analysis demonstrated that due to inherent noise in the marine data, only minor improvements on the DGRF values for the secular variation can be achieved.
The BH4 domain of Bcl-2 inhibits ER calcium release and apoptosis by binding the regulatory and coupling domain of the IP3 receptor (2009)

Although the presence of a BH4 domain distinguishes the antiapoptotic protein Bcl-2 from its proapoptotic relatives, little is known about its function. BH4 deletion converts Bcl-2 into a proapoptotic protein, whereas a TAT-BH4 fusion peptide inhibits apoptosis and improves survival in models of disease due to accelerated apoptosis. Thus, the BH4 domain has antiapoptotic activity independent of full-length Bcl-2. Here we report that the BH4 domain mediates interaction of Bcl-2 with the inositol 1,4,5-trisphosphate (IP3) receptor, an IP3-gated Ca(2+) channel on the endoplasmic reticulum (ER). BH4 peptide binds to the regulatory and coupling domain of the IP3 receptor and inhibits IP3-dependent channel opening, Ca(2+) release from the ER, and Ca(2+)-mediated apoptosis. A peptide inhibitor of Bcl-2-IP3 receptor interaction prevents these BH4-mediated effects. By inhibiting proapoptotic Ca(2+) signals at their point of origin, the Bcl-2 BH4 domain has the facility to block diverse pathways through which Ca(2+) induces apoptosis.
Synthetic Biology Moving into the Clinic (2011)

Synthetic biology is an emerging field focused on engineering biomolecular systems and cellular capabilities for a variety of applications. Substantial progress began a little over a decade ago with the creation of synthetic gene networks inspired by electrical engineering. Since then, the field has designed and built increasingly complex circuits and constructs and begun to use these systems in a variety of settings, including the clinic. These efforts include the development of synthetic biology therapies for the treatment of infectious diseases and cancer, as well as approaches in vaccine development, microbiome engineering, cell therapy, and regenerative medicine. Here, we highlight advances in the biomedical application of synthetic biology and discuss the field's clinical potential.
Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor (2000)

STI 571 (formerly known as CGP 57148B) is a known inhibitor of the c-abl, bcr-abl, and platelet-derived growth-factor receptor (PDGFR) tyrosine kinases. This compound is being evaluated in clinical trials for the treatment of chronic myelogenous leukemia. We sought to extend the activity profile of STI 571 by testing its ability to inhibit the tyrosine kinase activity of c-kit, a receptor structurally similar to PDGFR. We treated a c-kit expressing a human myeloid leukemia cell line, M-07e, with STI 571 before stimulation with Steel factor (SLF). STI 571 inhibited c-kit autophosphorylation, activation of mitogen-activated protein (MAP) kinase, and activation of Akt without altering total protein levels of c-kit, MAP kinase, or Akt. The concentration that produced 50% inhibition for these effects was approximately 100 nmol/L. STI 571 also significantly decreased SLF-dependent growth of M-07e cells in a dose-dependent manner and blocked the antiapoptotic activity of SLF. In contrast, the compound had no effect on MAP kinase activation or cellular proliferation in response to granulocyte-macrophage colony-stimulating factor. We also tested the activity of STI 571 in a human mast cell leukemia cell line (HMC-1), which has an activated mutant form of c-kit. STI 571 had a more potent inhibitory effect on the kinase activity of this mutant receptor than it did on ligand-dependent activation of the wild-type receptor. These findings show that STI 571 selectively inhibits c-kit tyrosine kinase activity and downstream activation of target proteins involved in cellular proliferation and survival. This compound may be useful in treating cancers associated with increased c-kit kinase activity.