gebhart/patrepeval huggingface dataset:
FM-laser operation of the Nd:YAG laser (1970)

The FM-laser or frequency-sweeping mode of laser oscillation has been demonstrated in a Nd :YAG 1.06-μ laser with an intracavity LiNbO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> phase modulator. The experimental results are in excellent agreement with the theoretical expression <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\Delta= (\Delta\Omega/\Delta\nu) (\delta/\pi)</tex> where δ= peak single-pass phase retardation in the modulator, <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\Delta\Omega</tex> = axial mode spacing, <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\Delta\nu</tex> =modulator detuning, and Δ=resulting FM index of the laser output. Modulation indices as large as <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\Delta \approx 230</tex> rad have been obtained, in which case the instantaneous laser frequency is sweeping over a full spectral range of <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2\Delta \cdot f_{m} \approx 120</tex> GHz (≈ 4 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> ) at a repetition frequency <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">f_{m} \approx 260</tex> MHz, with a time-bandwidth product per period <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\approx 2\Delta \approx 460</tex> . The coherently mode-locked spectral bandwidth thus obtained in the FM-laser case is very much wider than can be achieved in the pulsed mode-locked case with the same Nd:YAG laser. Some possible ways of using this broad-band coherent FM spectrum are suggested.
Distribution of Telomere-Associated Sequences on Natural Chromosomes in Saccharomyces cerevisiae (1988)

Pulsed-field gel electrophoresis was used to examine the distribution of telomere-associated sequences on individual chromosomes in four strains of Saccharomyces cerevisiae. The pattern of X and Y' distribution was different for each strain. At least one chromosome in each strain lacked Y', and in some strains, chromosome I, the smallest yeast chromosome, lacked detectable amounts of both X and Y'.
Common Musculoskeletal Tumors of Childhood and Adolescence (1999)

Common malignant tumors of the musculoskeletal system in children, adolescents, and young adults (<30 years old) include rhabdomyosarcoma, osteosarcoma, and Ewing's sarcoma. Together they constitute about 10 percent of newly diagnosed cancers in children, adolescents, and young adults (about 1000 cases annually in the United States). Although relatively common in young persons, these tumors are rare in older people.Rhabdomyosarcomas constitute more than half of all soft-tissue sarcomas in children.1 Other soft-tissue sarcomas are highly heterogeneous and individually rare (e.g., synovial sarcoma and sarcomas of soft parts); thus, they are not discussed further. Osteosarcoma comprises several high-grade histologic variants and . . .
GluR2-Dependent Properties of AMPA Receptors Determine the Selective Vulnerability of Motor Neurons to Excitotoxicity (2002)

AMPA receptor-mediated excitotoxicity has been implicated in the selective motor neuron loss in amyotrophic lateral sclerosis. In some culture models, motor neurons have been shown to be selectively vulnerable to AMPA receptor agonists due to Ca(2+) influx through Ca(2+)-permeable AMPA receptors. Because the absence of GluR2 in AMPA receptors renders them highly permeable to Ca(2+) ions, it has been hypothesized that the selective vulnerability of motor neurons is due to their relative deficiency in GluR2. However, conflicting evidence exists about the in vitro and in vivo expression of GluR2 in motor neurons, both at the mRNA and at the protein level. In this study, we quantified electrophysiological properties of AMPA receptors, known to be dependent on the relative abundance of GluR2: sensitivity to external polyamines, rectification index, and relative Ca(2+) permeability. Cultured rat spinal cord motor neurons were compared with dorsal horn neurons (which are resistant to excitotoxicity) and with motor neurons that survived an excitotoxic insult. Motor neurons had a higher sensitivity to external polyamines, a lower rectification index, and a higher relative Ca(2+) permeability ratio than dorsal horn neurons. These findings confirm that motor neurons are relatively deficient in GluR2. The AMPA receptor properties correlated well with each other and with the selective vulnerability of motor neurons because motor neurons surviving an excitotoxic event had similar characteristics as dorsal horn neurons. These data indicate that the relative abundance of GluR2 in functional AMPA receptors may be a major determinant of the selective vulnerability of motor neurons to excitotoxicity in vitro.
DAMPening Inflammation by Modulating TLR Signalling (2010)

Damage-associated molecular patterns (DAMPs) include endogenous intracellular molecules released by activated or necrotic cells and extracellular matrix (ECM) molecules that are upregulated upon injury or degraded following tissue damage. DAMPs are vital danger signals that alert our immune system to tissue damage upon both infectious and sterile insult. DAMP activation of Toll-like receptors (TLRs) induces inflammatory gene expression to mediate tissue repair. However, DAMPs have also been implicated in diseases where excessive inflammation plays a key role in pathogenesis, including rheumatoid arthritis (RA), cancer, and atherosclerosis. TLR activation by DAMPs may initiate positive feedback loops where increasing tissue damage perpetuates pro-inflammatory responses leading to chronic inflammation. Here we explore the current knowledge about distinct signalling cascades resulting from self TLR activation. We also discuss the involvement of endogenous TLR activators in disease and highlight how specifically targeting DAMPs may yield therapies that do not globally suppress the immune system.
Correlated Perovskites as a New Platform for Super‐Broadband‐Tunable Photonics (2016)

The electron-doping-induced phase transition of a prototypical perovskite SmNiO<sub>3</sub> induces a large and non-volatile optical refractive-index change and has great potential for active-photonic-device applications. Strong optical modulation from the visible to the mid-infrared is demonstrated using thin-film SmNiO<sub>3</sub> . Modulation of a narrow band of light is demonstrated using plasmonic metasurfaces integrated with SmNiO<sub>3</sub> .
Reprogramming Malignant Cancer Cells toward a Benign Phenotype following Exposure to Human Embryonic Stem Cell Microenvironment (2017)

The embryonic microenvironment is well known to be non-permissive for tumor development because early developmental signals naturally suppress the expression of proto-oncogenes. In an analogous manner, mimicking an early embryonic environment during embryonic stem cell culture has been shown to suppress oncogenic phenotypes of cancer cells. Exosomes derived from human embryonic stem cells harbor substances that mirror the content of the cells of origin and have been reported to reprogram hematopoietic stem/progenitor cells via horizontal transfer of mRNA and proteins. However, the possibility that these embryonic stem cells-derived exosomes might be the main effectors of the anti-tumor effect mediated by the embryonic stem cells has not been explored yet. The present study aims to investigate whether exosomes derived from human embryonic stem cells can reprogram malignant cancer cells to a benign stage and reduce their tumorigenicity. We show that the embryonic stem cell-conditioned medium contains factors that inhibit cancer cell growth and tumorigenicity in vitro and in vivo. Moreover, we demonstrate that exosomes derived from human embryonic stem cells display anti-proliferation and pro-apoptotic effects, and decrease tumor size in a xenograft model. These exosomes are also able to transfer their cargo into target cancer cells, inducing a dose-dependent increase in SOX2, OCT4 and Nanog proteins, leading to a dose-dependent decrease of cancer cell growth and tumorigenicity. This study shows for the first time that human embryonic stem cell-derived exosomes play an important role in the tumor suppressive activity displayed by human embryonic stem cells.
Engineering mammalian chromosomes (1998)

Construction of a mammalian artificial chromosome (MAC) will develop our understanding of the requirements for normal chromosome maintenance, replication and segregation while offering the capacity for introducing genes into cells. Construction of MACs with telomere, centromere and replication function has been approached by two methods. The 'top down' strategy uses artificially induced chromosome truncations as a means to define a minimal chromosome that retains the mitotic properties of a normal chromosome. The 'build up' approach has focused on attempts to assemble MAC vectors containing functionally defined telomere repeats together with candidate centromere and replication origin sequences. Here we report on significant advances in both areas, with particular emphasis on two reports showing that stable, low copy number MACs containing a functional centromere can be produced following transfection of naked DNA into the human HT1080 cell line. One approach used a transfection mixture of cloned synthetic alpha-satellite arrays up to 1 Mb in length and unlinked telomeric DNA, in either the presence or absence of random human genomic DNA fragments. In the second approach, MACs were formed from a defined yeast artificial chromosome (YAC) DNA molecule containing 100 kb of highly homo- geneous alphoid DNA retrofitted with human telomere repeats. These results demonstrate for the first time that alpha-satellite DNA can seed de novo centromeres in human cells, indicating that this repetitive sequence family plays an important role in centromere function. The stability of these MACs suggests that they have potential to be developed as gene delivery vectors.
Quantitative Methods for Assessing Drug Synergism (2011)

Two or more drugs that individually produce overtly similar effects will sometimes display greatly enhanced effects when given in combination. When the combined effect is greater than that predicted by their individual potencies, the combination is said to be synergistic. A synergistic interaction allows the use of lower doses of the combination constituents, a situation that may reduce adverse reactions. Drug combinations are quite common in the treatment of cancers, infections, pain, and many other diseases and situations. The determination of synergism is a quantitative pursuit that involves a rigorous demonstration that the combination effect is greater than that which is expected from the individual drug's potencies. The basis of that demonstration is the concept of dose equivalence, which is discussed here and applied to an experimental design and data analysis known as isobolographic analysis. That method, and a related method of analysis that also uses dose equivalence, are presented in this brief review, which provides the mathematical basis for assessing synergy and an optimization strategy for determining the dose combination.
Characterization of a Series of Self-Assembled Monolayers of Alkylated 1-Thiaoligo(ethylene oxides)4-8 on Gold (2000)

Self-assembled monolayers of a series of linear thiols containing a 1-thiaoligo(ethylene oxide) (TOEO) moiety, i.e., HS(EO)xR (where R = C10H21, EO = −CH2CH2O−, and x = 4−8), were prepared on polycrystalline gold and characterized by visible spectroscopic ellipsometry (SE), infrared spectroscopic ellipsometry, and surface plasmon resonance. The TOEO segment was found to adopt a 7/2 helical structure oriented normal to the substrate for x = 5−7. Different structures were found for the other compounds in this series. When x = 4, the TOEO segment adopts a predominantly trans-extended conformation, whereas when x = 8, the TOEO appears to be disordered with some helical conformation. Monolayer thicknesses determined by SE are consistent with these structural changes. The significant increase in disorder with extension of the hydrophilic segment by two ethylene oxide units from 6 to 8 is potentially valuable for protein reconstitution in supported hybrid bilayer constructs.
ShareJIT: JIT code cache sharing across processes and its practical implementation (2018)

Just-in-time (JIT) compilation coupled with code caching are widely used to improve performance in dynamic programming language implementations. These code caches, along with the associated profiling data for the hot code, however, consume significant amounts of memory. Furthermore, they incur extra JIT compilation time for their creation. On Android, the current standard JIT compiler and its code caches are not shared among processes—that is, the runtime system maintains a private code cache, and its associated data, for each runtime process. However, applications running on the same platform tend to share multiple libraries in common. Sharing cached code across multiple applications and multiple processes can lead to a reduction in memory use. It can directly reduce compile time. It can also reduce the cumulative amount of time spent interpreting code. All three of these effects can improve actual runtime performance. In this paper, we describe ShareJIT, a global code cache for JITs that can share code across multiple applications and multiple processes. We implemented ShareJIT in the context of the Android Runtime (ART), a widely used, state-of-the-art system. To increase sharing, our implementation constrains the amount of context that the JIT compiler can use to optimize the code. This exposes a fundamental tradeoff: increased specialization to a single process’ context decreases the extent to which the compiled code can be shared. In ShareJIT, we limit some optimization to increase shareability. To evaluate the ShareJIT, we tested 8 popular Android apps in a total of 30 experiments. ShareJIT improved overall performance by 9% on average, while decreasing memory consumption by 16% on average and JIT compilation time by 37% on average.
Conformation-specific monoclonal antibodies directed against the calcium-stabilized structure of human prothrombin (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConformation-specific monoclonal antibodies directed against the calcium-stabilized structure of human prothrombinRichard M. Lewis, Barbara C. Furie, and Bruce FurieCite this: Biochemistry 1983, 22, 4, 948–954Publication Date (Print):February 15, 1983Publication History Published online1 May 2002Published inissue 15 February 1983https://pubs.acs.org/doi/10.1021/bi00273a037https://doi.org/10.1021/bi00273a037research-articleACS PublicationsRequest reuse permissionsArticle Views72Altmetric-Citations38LEARN 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
Synthesis, antiulcer and antidepressive activity of 4-(4-halophenyl)-2-phenyl-1,2,3,4-tetrahydroisoquinolines. (1994)

4-(4-halophenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinolines 2a-c have been synthesized by two methods and their biochemical and pharmacological properties have been studied. Biochemical investigations showed that all the compounds are strong inhibitors of DA, NE and 5-HT reuptake, the strongest effect being observed with compound 2b (R = Br). 2a-c exhibited a strong antiulcer activity on an experimental model of stress-induced ulcers with minimal doses (0.1 to 3.0 mg/kg), the effect of 2b being 30 times higher as compared to the H2-antagonist Ranitidin. At higher doses (10 to 30 mg/kg) 2b and 2c inhibited the Reserpinptosis. The most active compound in the reuptake inhibition 2b, expressed a high antidepressive activity in some other tests, comparable to that of the antidepressant Nomifensin. 2b has been selected for further pharmacological testing under the code name AN12.
Effect of Sodium Benzoate on Blood Ammonia Response To Oral Glutamine Challenge in Cirrhotic Patients: A Note of Caution (2000)

Benzoate increased both the basal and post-glutamine ammonia levels. These results confirm what has already been observed in experimental animals and suggest a note of caution in the use of sodium benzoate in cirrhotic patients.
Thalidomide inhibits tumor necrosis factor alpha, decreases nitric oxide synthesis, and ameliorates the hyperdynamic circulatory syndrome in portal-hypertensive rats (1996)

A hyperdynamic circulatory state frequently is observed in portal hypertension with liver failure or extensive portal-systemic shunting. Tumor necrosis factor alpha (TNF) causes marked hypotension in mammals by inducing nitric oxide synthesis and has been shown to play a role in the development of the hemodynamic changes observed in portal hypertension. Thalidomide selectively inhibits TNF production by enhancing messenger RNA degradation. We investigated the systemic and portal hemodynamic effects of thalidomide in a prehepatic model of portal hypertension and evaluated whether suppressing TNF synthesis decreases NO production. Portal hypertension was induced by partial ligation of the portal vein (PVL). Animals received thalidomide (T) (50 mg/kg/d) + water or water alone (W), orally, daily for 2 days before and 13 days after PVL operation, at which time hemodynamic studies were performed and TNF plasma levels were obtained. Sham-operated animals were studied identically. In an additional group of PVL animals, 24-hour urinary excretion of NO2- and NO3- was measured during treatment. PVL animals receiving T presented with a significantly higher mean arterial pressure and systemic vascular resistance and significantly lower portal pressure, TNF plasma levels, and 24-hour urinary excretion of NO2- and NO3-, in comparison with rats receiving W. A significant correlation (r = -0.61) was observed between TNF plasma levels and mean arterial pressure among PVL animals. Thalidomide did not have any significant effects on sham rats. Thalidomide inhibits TNF synthesis and reduces NO production, blunts the development of the hyperdynamic circulation, and decreases portal pressure in PVL-operated rats. (Hepatology 1996 Jun;23(6):1616-21)
Digital background subtraction for fluorescence imaging (1986)

A method of enhancing contrast in fluorescence imaging has been devised, based on real-time digital subtraction of a background video image from a signal-plus-background video image. Color filters are used to differentiate signal from background. The technique has been applied to detection of small tumors labeled with the tumor specific fluorescent drug hematoporphyrin derivative.
Subacute NO generation induced by Alzheimer's beta-amyloid in the living brain: reversal by inhibition of the inducible NO synthase (2000)

Glial activation contiguous to deposits of amyloid peptide (Abeta) is a characteristic feature in Alzheimer's disease. We performed complementary in vitro and in vivo experiments to study the extent, kinetics, and mechanisms of microglial generation of nitric oxide (NO) induced by challenge with Abeta. We showed that Abeta fibrils dose-dependently induced a marked release of stable metabolites of NO in vivo that was strikingly similar regarding extent and temporal profile to the one in the parallel designed microglial cell culture experiments. However, costimulation with interferon gamma, which was a prerequisite for Abeta-induced NO generation in vitro, was not required in vivo, demonstrating that factors are present in the living brain that activate glial cells synergistically with Abeta. Therefore, in Alzheimer's disease, deposits of Abeta fibrils alone may be sufficient to induce a chronic release of neurotoxic microglial products, explaining the progressive neurodegeneration associated with this disease. Our observation that systemic administration of selective iNOS inhibitors abolishes Abeta-induced NO generation in vivo may have implications for therapy of Alzheimer's disease.
Expression of the insulin-like growth factors and their receptors in adenocarcinoma of the colon (1999)

This study confirms that in adenocarcinoma of the human colon there is increased expression of IGF-I receptor and IGF-II. Furthermore, IGF-II/Man-6-P receptor message is increased and the increase in IGF-II message is accompanied by a doubling of the IGF-II protein in the tumour tissue compared with the adjacent normal tissue. These findings suggest that the IGF-II/Man-6-P receptor may also be involved in development of adenocarcinoma of the colon. There is rapidly accumulating evidence implicating the IGF system in the development of malignancy of the large bowel.
The Discovery of N-[5-(4-Bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N′-propylsulfamide (Macitentan), an Orally Active, Potent Dual Endothelin Receptor Antagonist (2012)

Starting from the structure of bosentan (1), we embarked on a medicinal chemistry program aiming at the identification of novel potent dual endothelin receptor antagonists with high oral efficacy. This led to the discovery of a novel series of alkyl sulfamide substituted pyrimidines. Among these, compound 17 (macitentan, ACT-064992) emerged as particularly interesting as it is a potent inhibitor of ET(A) with significant affinity for the ET(B) receptor and shows excellent pharmacokinetic properties and high in vivo efficacy in hypertensive Dahl salt-sensitive rats. Compound 17 successfully completed a long-term phase III clinical trial for pulmonary arterial hypertension.