gebhart/patrepeval huggingface dataset:
Expression of epidermal growth factor and its receptor in the human ovary during follicular growth and regression (1993)

Immunohistochemical studies were performed using specific antibodies to epidermal growth factor (EGF) and EGF receptor to determine their presence and cellular localization in the human ovary during follicular growth and regression. There was no immunostaining for EGF or EGF receptor in primordial follicles. In the preantral follicle stage, immunostaining for EGF and EGF receptor was observed only in the oocyte. The staining intensity of the oocyte increased as the oocyte reached the preovulatory stage. In the antral follicle stage, immunostaining for EGF and EGF receptor became apparent in the granulosa and theca interna cell layers, without appreciable staining in the surrounding stromal cells. The immunostaining for EGF and EGF receptor in the granulosa cells and theca interna cells persisted in preovulatory follicles and corpus luteum, and intensified in the midluteal phase. The stromal cells surrounding the corpus luteum were negative for EGF and EGF receptor staining. In the regressing corpus luteum, immunostaining for EGF and EGF receptor was present in the peripheral lutein cells adjacent to the central core of scar tissue, but absent in the scar tissue of the central core. Corpus albicans showed no staining for EGF and EGF receptor. By contrast, the stromal cells surrounding the corpus albicans in the cortex region demonstrated intense staining for EGF and EGF receptor, while the stromal cells surrounding the corpus albicans in the medullary region were negative for immunostaining. In the case of atretic follicles, the theca interna cells showed intense staining for EGF and EGF receptor, but immunostaining in the scattered granulosa cells was negligible. This is the first study to demonstrate a remarkable change in the expression of EGF and EGF receptor in the oocyte, granulosa cells, thecal cells, and surrounding stromal cells over the course of follicular growth and regression. The results obtained support EGF participation in oocyte maturation and in follicular growth and atresia. The intense immunostaining for EGF and EGF receptor observed in the theca interna cells in atretic follicles and the stromal cells surrounding corpus albicans in the cortex region raises the possibility of EGF involvement in transformation of thecal cells into stromal cells. Furthermore, the cell type-specific simultaneous expression of EGF and EGF receptor in follicular and stromal compartments in the various stages of follicular development suggests that an autocrine mode of EGF action may exist to regulate follicular growth and regression in the human ovary.
Ultrastructure of Senile Plaque Using Thick Sections in the Brain with Alzheimer's Disease (1991)

The subjects used in the present study consisted of 8 cases with Alzheimer's disease. Senile plaques which seemed to have no relation with the capillaries were examined in thick serial sections (3,000-5,000 A) by electron microscope. The results obtained were as follows: All of those senile plaques had amyloid angiopathy with amyloid fibrils and these amyloid fibrils formed the main elements of senile plaques. From these findings, it was confirmed that the amyloid fibrils in all plaques are produced from the capillaries.
Copy-move forgery detection in digital images based on local dimension estimation (2012)

Copy-move forgery is one of the most commonly used forgeries in digital images, in which some regions of a digital image is coped and pasted to another part of the image with the aim of concealing certain features or objects in the original images. In this paper, a novel copy-move forgery detection scheme in digital images is proposed. It treats the digital images as high dimensional data and uses the intrinsic dimension estimation method first to segment the image and then identify the copy-move forgeries in the image regions with the same texture. Experimental results show that the proposed method is efficient and robust to retouching and many other operations, such as lossy compression, blurring, filtering, etc.
Pharmacological characterization of oxime agonists of the histamine H4 receptor (2009)

Pharmacological characterization of oxime agonists of the histamine H4 receptor Fuqu Yu, Ronald L Wolin, Jianmei Wei, Pragnya J Desai, Patricia M McGovern, Paul J Dunford, Lars Karlsson, Robin L ThurmondJohnson & Johnson Pharmaceutical Research and Development, L.L.C., San Diego, CA, USAAbstract: The histamine H4 receptor (H4R) has generated excitement as a potential target for the development of novel anti-inflammatory therapies. However, many of its physiological functions are still being uncovered and the development of new pharmacological tools is crucial to help facilitate this work. Previously, indole and benzimidazole piperazines have been described as potent and selective H4R antagonists. Using this as a starting point we have identified new indole and benzimidazole oxime piperidines as ligands for the H4R. These compounds have a high affinity for the human H4R with Ki values ranging from 17–53 nM. They also have high to moderate affinity for the H4R from mouse, rat, guinea pig, and monkey, but poor affinity for the dog homologue. In addition to the high affinity for the H4R, these compounds also exhibit excellent selectivity against other histamine receptors as well as many other receptor targets. These oxime ligands act as agonists of the human H4R in transfected reporter systems, although the degree of agonism depends on the system utilized. Agonistic activity was also observed in human eosinophils as evidenced by their ability to induce a shape change in these cells, although the degree of agonism ranges from full agonist to partial agonist depending on the test conditions. In contrast to their activity at the human H4R, all of the oxime compounds act as full agonists at the mouse receptor regardless of the test system including the ability to induce a calcium response in mouse bone marrow-derived mast cells. Finally the most selective compound, JNJ 28610244, was shown to induce scratching in mice indicating that it can also function as an agonist in vivo.Keywords: H4 receptor, eosinophils, mast cells, pruritus
Forecasting mobile transmission reliability using crowd-sourced cellular coverage data (2014)

As smartphones work their way into mission-critical applications, there is a need to gain knowledge of access network speeds and their variability at different locations. This information is vital to ensuring the efficient transmission of time-sensitive data and can mean the difference between life and death for some patients [1]. However, the decision to adopt smartphone applications (apps) that provide advanced communication services is complicated by the uncertainty of whether they will actually perform well in the field. Reliable operation in the field is hard to assess from laboratory demonstrations with reliable network coverage. Even if performance can be related to simple measures of network connectivity (e.g. the number of "bars"), objective 3rd-party assessments are difficult to obtain short of extensive field testing. This paper presents preliminary work toward an empirical model that predicts the number of bars in specific geographical locations using "crowd-sourced" signal strength data. Preliminary field test data was used to illustrate a Geographical Information System (GIS)-based end-to-end process by which signal strength (number of bars) in rural areas can be predicted from available signal strength measurements on major thorough fairs. Two linear models for predicting signal strength were developed using predictor variables that are easily assessed using standard GIS software. While the results presented here fail to achieve a high degree of statistical significance, the basic feasibility of the approach is established, and the factors that contribute to success or failure of the approach are discussed.
Self-maintaining web pages: an overview (2001)

Data-intensive web-based information systems usually employ database systems to store the contents forming the basis for web page construction. Generating web pages on the fly, especially in peak times, can lead to severe performance problems. Thus, pre-generation of web pages has been suggested to be ready for prime time, allowing to reliably deliver several hundred pre-generated pages per second. Maintaining the consistency of these web pages with respect to changes within the database in an efficient way, however, represents a major challenge. This paper presents a novel approach for self maintaining web pages that is, different to previous approaches, characterized by a simple (and thus, easy to maintain) database-to-web page mapping and very low page regeneration costs. This is achieved by utilizing fragmentation techniques from distributed databases, by allocating parameterized fragments to web page classes (rather than individual fragments to single web pages), and using the Extensible Markup Language (XML) as an intermediate layer between the database and the final web pages.
Characterization of a Gemcitabine-Resistant Murine Leukemic Cell Line (2004)

Resistance to cytotoxic nucleoside analogues is a major problem in cancer treatment. The cellular mechanisms involved in this phenomenon have been studied for several years, and some factors have been identified. Various strategies to overcome resistance have been suggested, but none has yet shown efficacy in vivo. We developed a gemcitabine-resistant cell line (L1210 10K) from the murine leukemic L1210 strain (L1210 wt) by continuous exposure to increasing concentrations of gemcitabine. L1210 10K is highly resistant to gemcitabine (14,833-fold), 1-beta-D-arabinofuranosylcytosine (ara-C; 2,100-fold), troxacitabine (>200-fold), and cladribine (160-fold) and slightly resistant to trimidox (7.22-fold), but does not display cross-resistance to fludarabine or nonnucleoside anticancer drugs. Deoxycytidine kinase mRNA was not detected by quantitative real-time reverse transcription-PCR in L1210 10K cells, whereas expression of thymidine kinase 1 and ribonucleotide reductase subunit R2 gene was moderately reduced. L1210 10K cells also demonstrated in vivo resistance to nucleoside analogues: gemcitabine- or ara-C-treated mice carrying L1210 10K had significantly shorter survival than gemcitabine- or ara-C-treated mice carrying L1210 wt (P < 0.05). UA911, a mononucleotide prodrug (pronucleotide) of ara-C was found to significantly sensitize L1210 10K cells in vitro. These results suggest that reduced deoxycytidine kinase expression is a mechanism of resistance to gemcitabine that is relevant in vivo and can be circumvented by a prodrug approach.
Optical properties of a low-loss polarization-maintaining photonic crystal fiber (2001)

A low-loss and highly birefringent polarization maintaining photonic crystal fiber has been fabricated. The fiber loss and modal birefringence at 1550 nm were 1.3 dB/km and 1.4x10 -3 , respectively.
Distance dependent head-related transfer function database of KEMAR (2008)

The measurement and structure of a database of distance-dependent head-related transfer function is introduced in this paper. This database was setup by measuring a high spatial resolution head-related transfer function at a total of 6344 space points, with distance from 20 to 160 cm, elevation from -40 to 90 degrees, and azimuth from 0 to 360 degrees. The databasepsilas reliability was confirmed by the object and subject evaluations.
Na+ entry through heteromeric TRPC4/C1 channels mediates (−)Englerin A-induced cytotoxicity in synovial sarcoma cells (2017)

The sesquiterpene (-)Englerin A (EA) is an organic compound from the plant Phyllanthus engleri which acts via heteromeric TRPC4/C1 channels to cause cytotoxicity in some types of cancer cell but not normal cells. Here we identified selective cytotoxicity of EA in human synovial sarcoma cells (SW982 cells) and investigated the mechanism. EA induced cation channel current (Icat) in SW982 cells with biophysical characteristics of heteromeric TRPC4/C1 channels. Inhibitors of homomeric TRPC4 channels were weak inhibitors of the Icat and EA-induced cytotoxicity whereas a potent inhibitor of TRPC4/C1 channels (Pico145) strongly inhibited Icat and cytotoxicity. Depletion of TRPC1 converted Icat into a current with biophysical and pharmacological properties of homomeric TRPC4 channels and depletion of TRPC1 or TRPC4 suppressed the cytotoxicity of EA. A Na<sup>+</sup>/K<sup>+</sup>-ATPase inhibitor (ouabain) potentiated EA-induced cytotoxicity and direct Na<sup>+</sup> loading by gramicidin-A caused Pico145-resistant cytotoxicity in the absence of EA. We conclude that EA has a potent cytotoxic effect on human synovial sarcoma cells which is mediated by heteromeric TRPC4/C1 channels and Na<sup>+</sup> loading.
Lymphokine(s) from isolated T lymphocyte subpopulations support multilineage hematopoietic colony and megakaryocytic colony formation (1986)

Conditioned medium derived from peripheral mononuclear low-density cells stimulated with phytohemagglutinin (PHA) supports the growth of noncommitted hematopoietic progenitors from marrow and peripheral blood cells. These immature progenitors (CFU-GEMM) can be identified in culture as multilineage hematopoietic colonies containing erythroblasts, eosinophilic, basophilic and neutrophilic granulocytes, megakaryocytes, macrophages, and T and B lymphocytes. In this report, we describe the effect of lymphokines released from purified T lymphocyte preparations of helper (T4) and suppressor/cytotoxic (T8) phenotype derived from peripheral blood on the growth of multilineage hematopoietic colonies and megakaryocytic colonies. It was found that PHA-stimulated lymphocytes of T4 phenotype and, to a lesser extent, of T8 phenotype elaborate lymphokine(s) that support the growth and development of multilineage colonies (CFU-GEMM), granulopoietic colonies (CFU-C), erythroid bursts (BFU-E) and megakaryocytic colonies (CFU-M) by nonadherent and T cell-depleted bone marrow cells.
Systemic interferon therapy of multiple sclerosis: the pros. (1988)

The rationale for the use of interferon (IFN) in the treatment of multiple sclerosis (MS) is based on its recognized antiviral and immunomodulating actions. The pathogenesis of MS is generally believed to be due to an immunologic response in a genetically predisposed individual, localized within the CNS white matter, and triggered by exposure to an environmental agent such as a virus. In a randomized, double-blind, placebo-controlled, crossover trial of systemic natural alpha IFN in 24 patients with exacerbating-remitting MS, patients with a strictly exacerbating-remitting course showed a reduction in the frequency and severity of exacerbations, while those with exacerbations superimposed upon a chronic progressive course did not benefit from this treatment, primarily because of side effects that included fever, malaise, and fatigue. Since the performance of this study, it has been shown that the preparation of natural human alpha interferon used in this trial may lead to side effects in some individuals through the production of immune complexes (ICs). These ICs were due to the generation of antibodies reacting with residual Sendai virus proteins used in the preparation of the IFN, and retained in the final formulation. The encouraging results of this and other preliminary studies of alpha or beta IFN but not gamma IFN therapy in MS, coupled with the current availability of more highly purified interferon preparations, warrants further clinical trials of IFN in MS, focusing on beta interferon preparations in particular.
Precision frequency measurements with interferometric weak values (2010)

We demonstrate an experiment which utilizes a Sagnac interferometer to measure a change in optical frequency of 129 $\ifmmode\pm\else\textpm\fi{}$ 7 $\text{kHz}/\sqrt{\text{Hz}}$ with only 2 mW of continuous-wave, single-mode input power. We describe the measurement of a weak value and show how even higher-frequency sensitivities may be obtained over a bandwidth of several nanometers. This technique has many possible applications, such as precision relative frequency measurements and laser locking without the use of atomic lines.
SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice (2013)

Our previous work has shown that gene knockout of the sodium-glucose cotransporter SGLT2 modestly lowered blood glucose in streptozotocin-diabetic mice (BG; from 470 to 300 mg/dl) and prevented glomerular hyperfiltration but did not attenuate albuminuria or renal growth and inflammation. Here we determined effects of the SGLT2 inhibitor empagliflozin (300 mg/kg of diet for 15 wk; corresponding to 60-80 mg·kg(-1)·day(-1)) in type 1 diabetic Akita mice that, opposite to streptozotocin-diabetes, upregulate renal SGLT2 expression. Akita diabetes, empagliflozin, and Akita + empagliflozin similarly increased renal membrane SGLT2 expression (by 38-56%) and reduced the expression of SGLT1 (by 33-37%) vs. vehicle-treated wild-type controls (WT). The diabetes-induced changes in SGLT2/SGLT1 protein expression are expected to enhance the BG-lowering potential of SGLT2 inhibition, and empagliflozin strongly lowered BG in Akita (means of 187-237 vs. 517-535 mg/dl in vehicle group; 100-140 mg/dl in WT). Empagliflozin modestly reduced GFR in WT (250 vs. 306 μl/min) and completely prevented the diabetes-induced increase in glomerular filtration rate (GFR) (255 vs. 397 μl/min). Empagliflozin attenuated increases in kidney weight and urinary albumin/creatinine ratio in Akita in proportion to hyperglycemia. Empagliflozin did not increase urinary glucose/creatinine ratios in Akita, indicating the reduction in filtered glucose balanced the inhibition of glucose reabsorption. Empagliflozin attenuated/prevented the increase in systolic blood pressure, glomerular size, and molecular markers of kidney growth, inflammation, and gluconeogenesis in Akita. We propose that SGLT2 inhibition can lower GFR independent of reducing BG (consistent with the tubular hypothesis of diabetic glomerular hyperfiltration), while attenuation of albuminuria, kidney growth, and inflammation in the early diabetic kidney may mostly be secondary to lower BG.
Safety and efficacy of growth hormone treatment in small for gestational age children (2008)

Growth hormone treatment in small for gestational age children has been found to be well tolerated and is an important advance in the treatment of short stature in pediatrics. Treatment of short prematurely born infants with growth hormone may offer similar efficacy and safety as growth hormone treatment in small for gestational age infants.
Acute and chronic systemic CB<sub>1</sub>cannabinoid receptor blockade improves blood pressure regulation and metabolic profile in hypertensive (mRen2)27 rats (2014)

We investigated acute and chronic effects of CB1 cannabinoid receptor blockade in renin-angiotensin system-dependent hypertension using rimonabant (SR141716A), an orally active antagonist with central and peripheral actions. In transgenic (mRen2)27 rats, a model of angiotensin II-dependent hypertension with increased body mass and insulin resistance, acute systemic blockade of CB1 receptors significantly reduced blood pressure within 90 min but had no effect in Sprague-Dawley rats. No changes in metabolic hormones occurred with the acute treatment. During chronic CB1 receptor blockade, (mRen2)27 rats received daily oral administration of SR141716A (10 mg/kg/day) for 28 days. Systolic blood pressure was significantly reduced within 24 h, and at Day 21 of treatment values were 173 mmHg in vehicle versus 149 mmHg in drug-treated rats (P < 0.01). This accompanied lower cumulative weight gain (22 vs. 42 g vehicle; P < 0.001), fat mass (2.0 vs. 2.9% of body weight; P < 0.05), and serum leptin (2.8 vs. 6.0 ng/mL; P < 0.05) and insulin (1.0 vs. 1.9 ng/mL; P < 0.01), following an initial transient decrease in food consumption. Conscious hemodynamic recordings indicate twofold increases occurred in spontaneous baroreflex sensitivity (P < 0.05) and heart rate variability (P < 0.01), measures of cardiac vagal tone. The beneficial actions of CB1 receptor blockade in (mRen2)27 rats support the interpretation that an upregulated endocannabinoid system contributes to hypertension and impaired autonomic function in this angiotensin II-dependent model. We conclude that systemic CB1 receptor blockade may be an effective therapy for angiotensin II-dependent hypertension and associated metabolic syndrome.
A Short, Efficient Synthesis of 6-Cyano-1-tetralones (1993)

Abstract A new, short and high-yield synthesis of 6-cyano-1-tetralones is described. Triflate intermediates 8 and 9 are versatile intermediates for the synthesis of other 6-substituted tetralones.
Comprehensive Security Framework for Global Threats Analysis (2009)

Cyber criminality activities are changing and becoming more and more professional. With the growth of financial flows through the Internet and the Information System (IS), new kinds of thread arise involving complex scenarios spread within multiple IS components. The IS information modeling and Behavioral Analysis are becoming new solutions to normalize the IS information and counter these new threads. This paper presents a framework which details the principal and necessary steps for monitoring an IS. We present the architecture of the framework, i.e. an ontology of activities carried out within an IS to model security information and User Behavioral analysis. The results of the performed experiments on real data show that the modeling is effective to reduce the amount of events by 91%. The User Behavioral Analysis on uniform modeled data is also effective, detecting more than 80% of legitimate actions of attack scenarios.
12(S)-hydroxyeicosatetraenoic acid and 13(S)-hydroxyoctadecadienoic acid regulation of protein kinase C-alpha in melanoma cells: role of receptor-mediated hydrolysis of inositol phospholipids. (1995)

Protein kinase C (PKC) isoenzymes are essential components of cell signaling. In this study, we investigated the regulation of PKC-alpha in murine B16 amelanotic melanoma (B16a) cells by the monohydroxy fatty acids 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] and 13(S)-hydroxyoctadecadienoic acid [13(S)-HODE]. 12(S)-HETE induced a translocation of PKC-alpha to the plasma membrane and focal adhesion plaques, leading to enhanced adhesion of B16a cells to the matrix protein fibronectin. However, 13(S)-HODE inhibited these 12(S)-HETE effects on PKC-alpha. A receptor-mediated mechanism of action for 12(S)-HETE and 13(S)-HODE is supported by the following findings. First, 12(S)-HETE triggered a rapid increase in cellular levels of diacylglycerol and inositol trisphosphate in B16a cells. 13(S)-HODE blocked the 12(S)-HETE-induced bursts of both second messengers. Second, the 12(S)-HETE-increased adhesion of B16a cells to fibronectin was sensitive to inhibition by a phospholipase C inhibitor and pertussis toxin. Finally, a high-affinity binding site (Kd = 1 nM) for 12(S)-HETE was detected in B16a cells, and binding of 12(S)-HETE to B16a cells was effectively inhibited by 13(S)-HODE (IC50 = 4 nM). In summary, our data provide evidence that regulation of PKC-alpha by 12(S)-HETE and 13(S)-HODE may be through a guanine nucleotide-binding protein-linked receptor-mediated hydrolysis of inositol phospholipids.