gebhart/patrepeval huggingface dataset:
The organization of the seventh lumbar spinal ganglion of the cat (1973)

Abstract The organization of the seventh lumbar dorsal root ganglion (DRG) of the cat has been investigated both anatomically and electrophysiologically. In the first two series of experiments an attempt was made to relate the topographic location of identified groups of cells in the ganglion with the rostro‐caudal position of their central processes in the filaments of the dorsal root. 3 H‐proline was injected into various sectors of the ganglion and the distribution of the axonically transported proteins, in individual dorsal rootlets, was determined by means of liquid scintillation spectroscopy and the location of the injections was determined by autoradiography of the sectioned ganglia. The projection pattern was also determined by antidromically activating DRG cells in various parts of the ganglion by sequentially stimulating each of six dorsal root filaments. The results of both groups of experiments indicate that cells located in the medial (caudal) parts of the ganglion project into the most caudal rootlets of the dorsal root; cells in the most lateral (rostral) parts of the ganglion project into the most rostral rootlets, while cells in the intermediate parts of the ganglion project into the middle rootlets. In a third series of experiments, a shifting pattern of overlapping receptive fields was demonstrated for a series of recordings that traversed the ganglion from medial to lateral. This pattern was shown to be nearly equivalent to the organization of receptive fields previously demonstrated by Kuhn ('53) for a rostral to caudal sequence of dorsal rootlets, i.e., foot and leg preaxial fields predominated in the lateral sectors, while postaxial fields were found in the medial sectors of the ganglion.
Raloxifene (LY156758) produces antimetastatic responses and extends survival in the paiii rat prostatic adenocarcinoma model (1995)

The benzothiophene antiestrogen, raloxifene (LY156758), has selective estrogen pharmacological antagonist activity in rats. The PAIII rat prostatic adenocarcinoma model was used to evaluate the effects of this agent on the lymphatic and pulmonary metastasis and survival in tumor-bearing male Lobund-Wistar (LW) rats. Raloxifene was inactive against colony formation of PAIII cells in vitro. Similarly, following subcutaneous (s.c.) implantation of 10(6) PAIII cells in the tail, s.c. administration of raloxifene (2.0, 10.0, or 20.0 mg/kg/day) for 30 days failed to demonstrate cytoreductive activity against primary tumor growth in the tail. However, in these same animals, raloxifene administration produced significant (P < 0.05) inhibition of PAIII metastasis from the primary tumor in the tail to the gluteal and iliac lymph nodes (maximal responses = 89% and 81% from control values, respectively). PAIII metastasis to the lungs was significantly inhibited by raloxifene treatment. Numbers of pulmonary foci in PAIII-bearing rats were significantly (P < 0.05) reduced by raloxifene administration in a dose-related manner (maximal reduction = 97% from control values). In these animals, maximal regression of 20% for ventral prostate and 21% for seminal vesicle were also seen after raloxifene administration (P < 0.05 for both). Coadministration of E2B and raloxifene had no consistent antagonistic effect upon the antitumor responses produced by raloxifene. Raloxifene (40.0 mg/kg/day for 28 days) produced marked decreases in PAIII metastasis in the lymphatic and pulmonary components. Continued administration of the compound produced significant (P < 0.05) extension of survival of PAIII-bearing rats. Further studies are needed to define the maximal antitumor efficacy and the mechanism of action of raloxifene in urogenital solid tumor animal models. These data support the contention that raloxifene represents a class of active antimetastatic agents with potential efficacy in the treatment of hormone-insensitive human prostatic cancer.
Ability of the Nociception Level, a Multiparameter Composite of Autonomic Signals, to Detect Noxious Stimuli during Propofol–Remifentanil Anesthesia (2015)

The NoL is a reliable measure of moderate and intense noxious stimulation and outperforms HR and MAP in differentiating noxious from nonnoxious stimuli. In contrast to HR and MAP, the NoL was not affected by hemodynamic effects of remifentanil.
A new and efficient synthesis of cytidine and adenosine derivatives by dimethyldioxirane oxidation of thiopyrimidine and thiopurine nucleosides (1994)

Dimethyldioxirane oxidation of thiopyrimidine and thiopurine nucleosides, in the presence of amines in stoichiometric amount, afforded selectively and under mild experimental conditions cytidine and adenosine nucleosides.
The Limited Deterrent (1983)

If the Super-Powers decide not to use nuclear weapons against each other's metropolitan territory, then, so it was suggested in the previous chapter, the possession of an independent and survivable force of submarine launched ballistic missiles could preserve the British Isles from nuclear attack in limited war. In these circumstances deterrence would be a useful task for the Royal Navy.KeywordsNuclear WeaponBritish IsleBallistic MissileDefence SpendingDefence BudgetThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Detection of the tumour‐associated antigens recognized by the monoclonal antibodies hmfg‐1 and 2 in serum from patients with breast cancer (1984)

The levels of the human milk fat globule 1 and 2 antigens have been measured in the sera of patients with advanced breast cancer, using a "sandwich" type radioimmune assay which exploits the carbohydrate nature of the antigenic determinants. In the series studied, 30% of sera from advanced breast cancer patients contained elevated levels of the HMFG-I antigen as compared with 6% of sera from healthy control women, whereas 53% of the advanced breast cancer patients showed elevated levels of HMFG-2 antigen compared with 16,6% of the controls. By means of the immune blotting technique, the components carrying the antigenic determinants in sera have been identified and compared for size with those molecules expressing the determinants in primary and secondary breast tumours. Both antibodies react with similar molecular weight components of 320kd and 280kd which are present in serum and tumour samples, although lower molecular weight bands of 230kd and 190kd can be seen in some tumours. These components are much smaller than the glycoprotein (greater than 400kd) present in the human milk fat globule, which carries the antigenic determinants recognized by HMFG-I and 2.
Improving the Thermostability of Raw-Starch-Digesting Amylase from a Cytophaga sp. by Site-Directed Mutagenesis (2003)

A heat-stable raw-starch-digesting amylase (RSDA) was generated through PCR-based site-directed mutagenesis. At 65 degrees C, the half-life of this mutant RSDA, which, compared with the wild-type RSDA, lacks amino acids R178 and G179, was increased 20-fold. While the wild type was inactivated completely at pH 3.0, the mutant RSDA still retained 41% of its enzymatic activity. The enhancement of RSDA thermostability was demonstrated to be via a Ca(2+)-independent mechanism.
Discovery of Rogaratinib (BAY 1163877): a pan‐FGFR Inhibitor (2018)

Rogaratinib (BAY 1163877) is a highly potent and selective small-molecule pan-fibroblast growth factor receptor (FGFR) inhibitor (FGFR1-4) for oral application currently being investigated in phase 1 clinical trials for the treatment of cancer. In this publication, we report its discovery by de novo structure-based design and medicinal chemistry optimization together with its pharmacokinetic profile.
In Vivo Expression Pattern of MICA and MICB and Its Relevance to Auto-Immunity and Cancer (2007)

Non-conventional MHC class I MIC molecules interact not with the TCR, but with NKG2D, a C-type lectin activatory receptor present on most NK, gammadelta and CD8(+) alphabeta T cells. While this interaction is critical in triggering/calibrating the cytotoxic activity of these cells, the actual extent of its in vivo involvement, in man, in infection, cancer or autoimmunity, needs further assessment. The latter has gained momentum along with the reported expansion of peripheral CD4(+)CD28(-)NKG2D(+) T cells in rheumatoid arthritis (RA). We first initiated to extend this report to a larger cohort of not only RA patients, but also those affected by systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). In RA and SS, this initial observation was further tested in target tissues: the joint and the salivary glands, respectively. In conclusion and despite occasional and indiscriminate expansion of the previously incriminated T cell subpopulation, no correlation could be observed between the CD4(+)CD28(-)NKG2D(+) and auto-immunity. Moreover, in situ, the presence of NKG2D matched that of CD8(+), but not that of CD4(+) T cells. In parallel, a total body tissue scan of both MICA and MICB transcription clearly shows that despite original presumptions, and with the exception of the central nervous system, both genes are widely transcribed and therefore possibly translated and membrane-bound. Extending this analysis to a number of human tumors did not reveal a coherent pattern of expression vs. normal tissues. Collectively these data question previous assumptions, correlating a tissue-specific expression/induction of MIC in relevance to auto-immune or tumor processes.
Stress and depression: possible links to neuron death in the hippocampus (2002)

Recent intriguing reports have shown an association between major depression and selective and persistent loss of hippocampal volume, prompting considerable speculation as to its underlying causes. In this paper we focus on the hypothesis that overt hippocampal neuron death could cause this loss and review current knowledge about how hippocampal neurons die during insults. We discuss (a) the trafficking of glutamate and calcium during insults; (b) oxygen radical generation and programmed cell death occurring during insults; (c) neuronal defenses against insults; (d) the role of energy availability in modulating the extent of neuron loss following such insults. The subtypes of depression associated with hippocampal atrophy typically involve significant hypersecretion of glucocorticoids, the adrenal steroids secreted during stress. These steroids have a variety of adverse affects, direct and indirect, in the hippocampus. Thus glucocorticoids may play a contributing role toward neuron death. We further discuss how glucocorticoids cause or exacerbate cellular changes associated with hippocampal neuron loss in the context of the events listed above.
Characterization of human cardiac Na + channel mutations in the congenital long QT syndrome (1996)

The congenital long QT syndrome (LQTS) is an inherited disorder characterized by a prolonged cardiac action potential. This delay in cellular repolarization can lead to potentially fatal arrhythmias. One form of LQTS (LQT3) has been linked to the human cardiac voltage-gated sodium channel gene (SCN5A). Three distinct mutations have been identified in the sodium channel gene. The biophysical and functional characteristics of each of these mutant channels were determined by heterologous expression of a recombinant human heart sodium channel in a mammalian cell line. Each mutation caused a sustained, non-inactivating sodium current amounting to a few percent of the peak inward sodium current, observable during long (> 50 msec) depolarizations. The voltage dependence and rate of inactivation were altered, and the rate of recovery from inactivation was changed compared with wild-type channels. These mutations in diverse regions of the ion channel protein, all produced a common defect in channel gating that can cause the long QT phenotype. The sustained inward current caused by these mutations will prolong the action potential. Furthermore, they may create conditions that promote arrhythmias due to prolonged depolarization and the altered recovery from inactivation. These results provide insights for successful intervention in the disease.
Purification of marginal plates from bovine renal peroxisomes: identification with L-alpha-hydroxyacid oxidase B. (1991)

The matrix of mammalian peroxisomes frequently contains crystalline inclusions. The most common inclusions are membrane associated plate-like "marginal plates" of hitherto unknown nature in renal peroxisomes and central polytubular "cores" composed of urate oxidase in hepatic peroxisomes. In bovine kidney, peroxisomes of proximal tubules exhibit peculiar angular shapes that are caused by multiple marginal plates (Zaar, K., and H.D. Fahimi. 1990. Cell Tissue Res. 260:409-414). Enriched or highly purified peroxisome preparations from this source were used to purify and characterize marginal plates. By SDS-PAGE, one major polypeptide of Mr 33,500 was observed that corresponded to the marginal plate protein. This polypeptide was identified by its enzymatic activity as well as by immunoblotting and preembedding immunocytochemistry as the isozyme B of L-alpha-hydroxyacid oxidase (EC 1.4.3.2). Morphologically, marginal plates were revealed to consist of rectangular straight-edged sheets, exhibiting a defined crystalline lattice structure. The sheets apparently are composed of a single layer of protomers which associate laterally to form a plate-like structure. As deduced from the negative staining results and the additional information of the thickness of marginal plates, each protomer seems to consist of eight subunits forming a cube-like array. The tendency of L-alpha-hydroxyacid oxidase B to self-associate in vitro (Philips, D.R., J.A. Duley, D.J. Fennell, and R.S. Holmes. 1976. Biochim. Biophys. Acta. 427:679-687) corresponds to the mode of association of cubical protomers to form the so-called marginal plates in renal peroxisomes.
Induction of gamma-interferon activity by elevated temperatures in human B-lymphoblastoid cell lines. (1984)

When the human B-lymphoblastoid cell lines GM3299 and GM4408 were heat shocked, elevated levels of antiviral activity were detected. This antiviral activity has been characterized as the result of de novo synthesis of interferon (IFN) gamma. Levels of antiviral activity as high as 20,000 units/ml per 10(6) cells were found after heat treatment. By using anti-IFN-alpha and anti-IFN-gamma sera, it was shown that the high antiviral activity in GM3299 after heat shock is due to a synergistic effect of constitutively produced IFN-alpha and induced IFN-gamma.
Applying ‘Options Thinking’ To R&D Valuation (1996)

OVERVIEW:There are situations in which options pricing theory provides a better basis for the valuation of R&D projects than the traditional discounted cash flow techniques used in most business cases. R&D managers need to be able to recognize those situations in which the two approaches are likely to give different answers, and they need to be aware of the different computational techniques that can be used for an options valuation of R&D projects. It is also important to understand the implications of an options approach for the formulation of both business and R&D strategy. “Options thinking” represents a practical way to apply the lessons from options pricing theory to some of the central problems of R&D management.
Coupling of cerebral blood flow to neuronal activation: role of adenosine and nitric oxide (1994)

We studied the role and relationship of the putative mediators of coupling of cerebral blood flow (CBF) and neuronal activation, adenosine (Ado) and nitric oxide (NO). Topical brain application over the whisker barrel cortex of anesthetized rats (n = 24) of the Ado receptor antagonist theophylline (Theo, 5 x 10(-5) M) for 30 min reduced the CBF response to deflection of the contralateral whiskers from 17.9 +/- 3.0% of baseline to 10.6 +/- 2.7% (P < 0.05). Coapplication of Theo (5 x 10(-5) M) and the NO synthase blocker N omega-nitro-L-arginine (L-NNA, 10(-3) M) for 30 min led to a further reduction in the CBF response to whisker stimulation to 7.5 +/- 1.3% (P < 0.05 compared with Theo alone). The CBF effect of sodium nitroprusside (10(-5) M) was not affected by Theo-L-NNA coapplication (122 +/- 25 vs. 140 +/- 25%, n = 5). Application of adenosine deaminase (1 U/ml, n = 5) reduced the CBF response to whisker stimulation from 18.2 +/- 0.7 to 10.7 +/- 1.9% (P < 0.05). Superfusion of L-NNA (10(-3) M, 30 min, n = 7) attenuated the CBF response to application of Ado (10(-4) M) from 39.4 +/- 10.4 to 22.9 +/- 10.5% (P < 0.05). N omega-nitro-D-arginine did not affect the CBF response to Ado (n = 5). We conclude that 1) Ado is involved in coupling of CBF to neuronal activation, 2) NO is involved in this response as well, and 3) there is an interaction between the vasodilator pathways of Ado and NO.
TEM horn antenna for the time domain shielding effectiveness measurement (1997)

The design and construction of a TEM horn antenna to be used for the time domain measurement of the shielding effectiveness of materials is described and measurement results of its characteristics in time domain and frequency domain using the two-antenna method are compared. The constructed TEM horn has the bandwidth of above 2 GHz.
How markets slowly digest changes in supply and demand (2008)

In this article we revisit the classic problem of tatonnement in price formation from a microstructure point of view, reviewing a recent body of theoretical and empirical work explaining how fluctuations in supply and demand are slowly incorporated into prices. Because revealed market liquidity is extremely low, large orders to buy or sell can only be traded incrementally, over periods of time as long as months. As a result order flow is a highly persistent long-memory process. Maintaining compatibility with market efficiency has profound consequences on price formation, on the dynamics of liquidity, and on the nature of impact. We review a body of theory that makes detailed quantitative predictions about the volume and time dependence of market impact, the bid-ask spread, order book dynamics, and volatility. Comparisons to data yield some encouraging successes. This framework suggests a novel interpretation of financial information, in which agents are at best only weakly informed and all have a similar and extremely noisy impact on prices. Most of the processed information appears to come from supply and demand itself, rather than from external news. The ideas reviewed here are relevant to market microstructure regulation, agent-based models, cost-optimal execution strategies, and understanding market ecologies.
Anion exchange of oxygen by sulfur in GeO 2 -based glasses (2003)

Germanium-based glasses containing heavy metal oxides (Sb2O 3) have been investigated. These materials are good candidates for near infrared (IR) applications due to their mid-wave IR cut-off wavelength (5 ≈ 7 μm). Among inorganic glasses, sulfide materials exhibit the largest third-order optical nonlinear susceptibility and good IR transparency but suffer from low thermal-mechanical stability and photo-induced degradation upon exposure to near-bandgap radiation. The preparation of oxysulfide materials for optical applications offers a unique trade off between the superb chemical stability of the oxide and the attractive optical properties of sulfide. In this presentation we describe a new chemical route for the preparation of oxysulfide glasses for optical applications. The evidence of glass network structural modification is confirmed using infrared and Raman spectroscopy. Film deposition based on sputtering techniques compatible with synthesis of such materials has been performed. The initial characterization of the resulting films has been performed and findings are described.
Engineering in genomics-automating the Genome Center (1994)

Engineering enters genomics principally through the development of hardware and software tools or processes (operations research) to aid the biologist/geneticist to take different, more, or higher quality data. The Human Genome Project, in order to meet its goals for mapping and sequencing, is pushing to advance the state of the art in instrumentation, automation and computational biology. The focus of the project was to develop the necessary strategies, hardware, and software to complete the identification of all the genes, and obtain the sequence for the entire genome for humans and a select set of relevant organisms (mouse, fruit fly, yeast, E.coli, etc.) by the year 2006. The project has already produced a significant amount of data, is contributing to medicine and is ahead of schedule. But to keep on track, laboratories conducting research in genomics must move into a period where production data gathering is performed in a factory-like setting. The author focuses on some of the research activities of his group, which is developing automation and informatics systems for the Human Genome Project, specifically human genome centers where the production mapping and sequencing will be done. A multidisciplinary group has been assembled from personnel from the Salk Institute (a biological research organization) and General Atomics (an energy and basic sciences research company). The center is conducting research to map and sequence chromosome 11 and Giardia, for starters, and becoming more highly automated daily.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
In vivo optical frequency domain imaging of human retina and choroid (2006)

Optical frequency domain imaging (OFDI) using swept laser sources is an emerging second-generation method for optical coherence tomography (OCT). Despite the widespread use of conventional OCT for retinal disease diagnostics, until now imaging the posterior eye segment with OFDI has not been possible. Here we report the development of a highperformance swept laser at 1050 nm and an ophthalmic OFDI system that offers an A-line rate of 18.8 kHz, sensitivity of >92 dB over a depth range of 2.4 mm with an optical exposure level of 550 muW, and deep penetration into the choroid. Using these new technologies, we demonstrate comprehensive human retina, optic disc, and choroid imaging in vivo. This advance enables us to view choroidal vasculature in vivo without intravenous injection of fluorescent dyes and may provide a useful tool for evaluating choroidal as well as retinal diseases.