gebhart/patrepeval huggingface dataset:
Amyloid precursor protein secretion and βA4 amyloid generation are not mutually exclusive (1994)

The cellular factors regulating the generation of beta A4 from the amyloid precursor protein (APP) are unknown. Protein phosphorylation by protein kinase C (PKC) has been found to influence the processing and metabolism of APP. In this report, we show that in the human neuroblastoma cell line SY5Y, beta A4 generation from full-length APP is not changed by PKC activation whereas production of the non-amyloidogenic secretory fragment (APPsec) and of the C-terminal fragment of beta A4 (p3) are stimulated. In addition, beta A4 generation from the membrane inserted C-terminal 100 residues (SPA4CT) of APP is stimulated by PKC activation. Accordingly attempts to divert APP processing from the amyloidogenic, beta A4-generating, to the non-amyloidogenic, secretory, pathway, have to address the nature and regulation of the two pathways and/or of the process leading to the cleavage of APP at the C-terminus of the beta A4 domain. The data reported here suggest that these mechanisms are cell-type specific.
Defining the roles of parathyroid hormone-related protein in normal physiology (1996)

Parathyroid hormone-related protein (PTHrP) was discovered as a result of a search for the circulating factor secreted by cancers which causes the common paraneoplastic syndrome humoral hypercalcemia of malignancy. Since the identification of the peptide in 1982 and the cloning of the cDNA in 1987, it has become clear that PTHrP is a prohormone that is posttranslationally cleaved by prohormone convertases to yield a complex family of peptides, each of which is believed to have its own receptor. It is also clear that the PTHrP gene is expressed not only in cancers but also in the vast majority of normal tissues during adult and/or fetal life. In contrast to the situation in humoral hypercalcemia of malignancy in which PTHrP plays the role of a classical "endocrine" hormone, under normal circumstances PTHrP plays predominantly paracrine and/or autocrine roles. These apparent physiological functions are also complex and appear to include 1) regulation of smooth muscle (vascular, intestinal, uterine, bladder) tone, 2) regulation of transepithelial (renal, placental, oviduct, mammary gland) calcium transport, and 3) regulation of tissue and organ development, differentiation, and proliferation. In this review, the discovery of PTHrP, the structure of its gene and its cDNAs, and the posttranslational processing of the initial translation products are briefly reviewed. Attention is then focused on a detailed organ system-oriented review of the normal physiological functions of PTHrP.
The GeneMine system for genome/proteome annotation and collaborative data mining (2001)

As genome data and bioinformatics resources grow exponentially in size and complexity, there is an increasing need for software that can bridge the gap between biologists with questions and the worldwide set of highly specialized tools for answering them. The GeneMine system for small- to medium-scale genome analysis provides: (1) automated analysis of DNA (deoxyribonucleic acid) and protein sequence data using over 50 different analysis servers via the Internet, integrating data from homologous functions, tissue expression patterns, mapping, polymorphisms, model organism data and phenotypes, protein structural domains, active sites, motifs and other features, etc., (2) automated filtering and data reduction to highlight significant and interesting patterns, (3) a visual data-mining interface for rapidly exploring correlations, patterns, and contradictions within these data via aggregation, overlay, and drill-down, all projected onto relevant sequence alignments and three-dimensional structures, (4) a plug-in architecture that makes adding new types of analysis, data sources, and servers (including anything on the Internet) as easy as supplying the relevant URLs (uniform resource locators), (5) a hypertext system that lets users create and share “live” views of their discoveries by embedding three-dimensional structures, alignments, and annotation data within their documents, and (6) an integrated database schema for mining large GeneMine data sets in a relational database. The value of the GeneMine system is that it automatically brings together and uncovers important functional information from a much wider range of sources than a given specialist would normally think to query, resulting in insights that the researcher was not planning to look for. In this paper we present the architecture of the software for integrating and mining very diverse biological data, and cross-validation of gene function predictions. The software is freely available at www.bioinformatics.ucla.edu/genemine.
Glucagon‐like peptide‐1 cells in the gastrointestinal tract and pancreas of rat, pig and man (1992)

A highly specific monoclonal antibody directed against the C-terminal part of glucagon-like peptide-1 (GLP-1) was raised to immunohistochemically evaluate the distribution of GLP-1 containing cells in the entire gastrointestinal tract including pancreas of rat, pig and man. In the pancreas GLP-1-immunoreactive cells were found variously shaped and predominantly located in the periphery of the islets. Ultrastructurally, GLP-1 was co-localized with glucagon in the alpha-granula of A-cells and was mainly restricted to the electrondense core. In the intestine open type cells reaching the lumen via a slender apical process were stained with the GLP-1 antibody. They occurred in all parts of the crypts but predominantly in the basal portion. The density of GLP-1 immunoreactive cells varied between species in a characteristic order: rat greater than pig greater than man. In pig and human gut a large number of cells occurred in the distal jejunum and ileum. A continuous increase of cell densities was found from the proximal to the distal colon resulting in highest numbers in the rectum. In rats the highest cell density occurred in the ileum. Again, a continuous increase of GLP-1-positive cell numbers was evident from the proximal to the distal portion of small and large bowel. GLP-1 was partly co-localized with PYY. The GLP-1 positive cells appeared electronmicroscopically as L-cells with the typical large granula. This morphological data indicates that GLP-1-releasing cells in the small intestine are appropriately positioned in the distal part to sense and respond to the presence of nutrients that have escaped the absorptive surface of the upper small intestine.
Steroidal Alkaloid Teratogens: Molecular Probes for Investigation of Craniofacial Malformations (1996)

Holoprosencephaly, a malformation sequence that results from impaired midline cleavage of the embryonic forebrain, is expressed as a spectrum of craniofacial anomalies of which cyclopia is the most severe. The Veratrum alkaloids are the most prominent of the teratogenic agents known to induce holoprosencephaly in mammals. Jervine and 11-deoxojervine (cyclopamine) are potent steroidal alkaloid teratogens from Veratrum californicum that are responsible for inducing cyclopic malformations in sheep.Extensive structure-terata investigations of jervanes, solanidanes, and spirosolanes have shown that teratogenicity induced upon oral administration of all three structural types is significantly higher if the C-5, C-6 bond is unsaturated. Research in progress on the pathogenesis of holoprosencephalic malformations in both hamsters and humans offers the potential to provide information on the receptors involved in the expressions of these craniofacial syndromes. A clearer understanding of steroidal alkaloid-induced teratogenesis will emerge when appropriate receptor sites are revealed with which teratogenic alkaloids of slightly different structure can interact.
Tamoxifen and estrogen lower circulating lipoprotein(a) concentrations in healthy postmenopausal women. (1994)

Data in the literature suggest that circulating levels of lipoprotein(a) [Lp(a)] and insulinlike growth factor I (IGF-I) respond similarly to therapy with growth hormone, estrogen, or tamoxifen. To more clearly document these relations, we designed a randomized, double-blind, placebo-controlled study of the effects of tamoxifen and continuous estrogen on circulating levels of Lp(a), IGF-I, and IGF binding protein 3 (IGFBP-3) in healthy postmenopausal women. Both estrogen and tamoxifen decreased serum levels of IGF-I to 30% below baseline during the 3 months of treatment, while IGFBP-3 levels were unchanged. Plasma Lp(a) levels decreased to 24% below baseline after 1 month of treatment with either estrogen or tamoxifen (P < .05 for estrogen only); after 3 months Lp(a) decreased to 34% below baseline with tamoxifen therapy (P < .05) but returned to only 16% below baseline with estrogen. The correlation between Lp(a) and IGF-I was highly significant (P < .0001). We conclude that (1) tamoxifen lowers plasma Lp(a) levels in healthy postmenopausal women, (2) the suppressive effects of tamoxifen and estrogen on circulating Lp(a) concentration diverge after the first month of therapy, and (3) circulating levels of Lp(a) and IGF-I are strongly correlated with each other, an indication that they may share regulatory influences.
A Study on the Circadian Rhythm of Glucocorticoid Receptor (1991)

Circadian rhythm in glucocorticoid receptor (GR) was studied in the rat liver and human peripheral leukocytes. For rats exposed to a natural environmental photic cycle or a 12L:12D artificial light regime, peak values of hepatic GR were detected between 23:00 and 02:00 h. Except for a 4-hour advancement of the peak, a similar circadian rhythm of hepatic GR was detected in rats reared under a reversed lighting regimen (12D:12L; lights on between 18:30 and 06:30 h). In human leukocytes, the peak value of GR was found to parallel that of plasma cortisol with high and low values detected at 04:00-08:00 h and 23:00-24:00 h, respectively. In patients suffering from Cushing's syndrome, the circadian rhythm of plasma cortisol either disappeared or was inverted while that of GR did not significantly deviate from the normal subjects. For apoplexic patients with lesions localized to the base of the brain as indicated by computerized tomography, the diurnal variation of GR was abolished. Conversely, diurnal rhythmicity persisted in apoplexy patients whose lesions were in the cerebral cortex. Thus, we postulated that the circadian modification of GR was independent of the diurnal fluctuations in plasma cortisol level or the circadian variations in environmental lighting and that the rhythmicity might be regulated by the 'circadian pacemaker' located in the human basal brain. These diurnal variations in GR might serve to coordinate the reactivity of the target cells to cortisol because the diurnal rhythms of a GR-mediated response, the fractional inhibition of chemotactic migration rate of polymorphonuclear leukocytes by cortisol, were found to be synchronous with those of GR.
Placental Abnormalities and Preeclampsia in Trisomy 13 Pregnancies (2009)

Women who are carrying a trisomy 13 fetus are prone to have an abnormal placenta as well as to develop preeclampsia in the second and third trimesters. This article provides a comprehensive review of placental abnormalities, such as small placental volume, reduced placental vascularization, a partial molar appearance of the placenta and placental mesenchymal dysplasia, and preeclampsia associated with trisomy 13 pregnancies. The candidate preeclampsia-causing genes on chromosome 13, such as sFlt1, COL4A2 and periostin, are discussed.
Myocardial electrical impedance as a predictor of the quality of RF-induced linear lesions (2008)

Production of complete (i.e. continuous and transmural) cardiac lesions by radiofrequency (RF) ablation can cure certain cardiac arrhythmias. However, a predictor of lesion completeness that is reliable and can be measured intraoperatively is needed in order to maximize effectiveness of ablation therapy. Predictors that require membrane excitation or response to stimulation are not always practical. This study tested whether changes of myocardial impedance across the lesion can predict completeness. RF energy was applied epicardially on perfused rabbit ventricles to produce linear lesions that were complete (n = 25) or incomplete (noncontinuous or nontransmural, n = 25). Before and after creation of each lesion, the magnitude and phase of impedance at 1 kHz were measured with a four-electrode epicardial array across the lesion. For 16 of the lesions, the translesion stimulus-excitation delay was also measured. Lesion completeness was evaluated with 2,3,5-triphenyltetrazolium chloride stain. Complete lesions increased resistivity by 26 Omega cm (21% of the preablation value, p = 0.0007, n = 17) when the inactive RF electrode remained on the epicardium during impedance measurements. When the RF electrode was removed during measurements, the rise of resistivity by complete lesions increased to 58 Omega cm (30% of the preablation value, p = 0.022, n = 8). For incomplete lesions, resistivity did not change significantly. Ablation did not significantly alter the phase of impedance. Accuracies of predictions of lesion completeness by the change in resistivity or the change in translesion stimulus-excitation delay were comparable (Youden's index 0.75 and 0.625, respectively, n = 16). Thus, RF ablation increases myocardial resistivity. The resistivity can predict lesion completeness and may provide an alternative to predictors based on excitation.
A thin, flexible multielectrode grid for high-density surface EMG (2004)

Although the value of high-density surface electromyography (sEMG) has already been proven in fundamental research and for specific diagnostic questions, there is as yet no broad clinical application. This is partly due to limitations of construction principles and application techniques of conventional electrode array systems. We developed a thin, highly flexible, two-dimensional multielectrode sEMG grid, which is manufactured by using flexprint techniques. The material used as electrode carrier (Polyimid, 50 microm thick) allows grids to be cut out in any required shape or size. One universal grid version can therefore be used for many applications, thereby reducing costs. The reusable electrode grid is attached to the skin by using specially prepared double-sided adhesive tape, which allows the selective application of conductive cream only directly below the detection surfaces. To explore the practical possibilities, this technique was applied in single motor unit analysis of the facial musculature. The high mechanical flexibility allowed the electrode grid to follow the skin surface even in areas with very uneven contours, resulting in good electrical connections in the whole recording area. The silverchloride surfaces of the electrodes and their low electrode-to-skin impedances guaranteed high baseline stability and a low signal noise level. The electrode-to-skin attachment proved to withstand saliva and great tensile forces due to mimic contractions. The inexpensive, universally adaptable and minimally obstructive sensor allows the principal advantages of high-density sEMG to be extended to all skeletal muscles accessible from the skin surface and may lay the foundation for more broad clinical application of this noninvasive, two-dimensional sEMG technique.
Inhibition of growth of subcutaneous xenografts and metastasis of human breast carcinoma by swainsonine: modulation of tumor cell HLA class I antigens and host immune effector mechanisms. (1991)

Swainsonine, an indolizidine alkaloid, can decrease the organ colonization potential of metastatic murine tumor cells by augmentation of host immune effector mechanisms. In this report the above findings were extended by the demonstration that systemic administration of swainsonine strongly suppressed the growth of human breast carcinoma subcutaneous xenografts and experimentally induced lung metastases. This inhibition was not due to a direct effect of swainsonine on cell growth. However swainsonine treatment of tumor cells resulted in enhanced expression of HLA Class I antigens, and HLA class I mRNA. Swainsonine was a potent immunodulator as evidenced by the increased (a) cytotoxicity of splenocytes and macrophages, and, (b) proliferative potential of splenocytes and bone marrow cells. These data suggest that swainsonine-induced inhibition of tumor growth and metastases may be mediated via activation of host effector cells and/or alteration of tumor cell antigenicity.
A Study on the Process of the Achievement Concerned with “Hachirogata” Reclamation Project (2001)

[in Japanese]
Case 42-1978 (1978)

Secretary of Commerce and Labor George B. Cortelyou announces to President Roosevelt that he is resigning from the Cabinet to become the chairman of the Republican National Committee. Cortelyou also expresses his respect for Roosevelt and the job he has done.
Synthesis and characterization of various unsubstituted and mono-N-substituted tetraazamacrocycles (1995)

Syntheses of tetraazamacrocycles have been carried out by using p-toluenesulfonyl chloride as protective group. The [14(ane) N4] and [15(ane) N4] were also obtained by the template synthesis. Mono-N-functionalization of tetraazamacrocycles was accomplished by reaction of a fivefold excess of the free macrocycles with 1 equivalent of a suitable alkylating or arylating reagent. The key point of the synthesis lies in the use of an excess of the macrocycle over the substituting reactants to reduce the formation of polysubstituted derivatives, and in the easy separation of the excess of unreacted macrocycle. All the products were characterized on the basis of spectral studies ( 1 H and l3 C NMR, including 2D NMR and NOE difference studies) and mass spectrometry. Keywords: tetraazamacrocycles, improved synthesis, protective group, N-tosylation, template synthesis, NOE difference spectroscopy.
Engineering genes for predictable protein expression (2012)

The DNA sequence used to encode a polypeptide can have dramatic effects on its expression. Lack of readily available tools has until recently inhibited meaningful experimental investigation of this phenomenon. Advances in synthetic biology and the application of modern engineering approaches now provide the tools for systematic analysis of the sequence variables affecting heterologous expression of recombinant proteins. We here discuss how these new tools are being applied and how they circumvent the constraints of previous approaches, highlighting some of the surprising and promising results emerging from the developing field of gene engineering.
The Notch Signaling Pathway Is Related to Neurovascular Progression of Pancreatic Cancer (2005)

The Notch pathway most likely regulates neurovascular development in pancreatic cancer. Activation of this signaling pathway by constitutive Notch-1 mutants and by Jagged-1 causes an angiogenic and invasive tumor phenotype. Specific blockade of Notch signaling may therefore be beneficial for patients with pancreatic cancer.
Compliant substrate versus plastic relaxation effects in Ge nanoheteroepitaxy on free-standing Si(001) nanopillars (2011)

We report on the structural characterization of Ge clusters selectively grown by chemical vapor deposition on free-standing 50 nm wide Si(001) nanopillars. Synchrotron based x-ray diffraction studies and transmission electron microscopy were performed to experimentally verify the nanoheteroepitaxy theory as a technique to grow high quality Ge on Si(001). Although the structure dimensions are comparable to the theoretical values required for the strain partitioning phenomenon, the compliant character of Si is not unambiguously proven. In consequence, the strain is relieved by nucleation of misfit dislocations at the Ge/Si interface. By gliding out of threading arms, high quality Ge nanostructures are achieved.
Construction of Recombinant Vaccinia Viruses Using PUV-Inactivated Virus as a Helper (2001)

Recombinant vaccinia viruses (VVs) are widely used as expression vectors in molecular biology and immunology and are now under evaluation for gene therapy. The current techniques for inserting foreign DNA into the large VV genome are based on either homologous recombination between transfer plasmids and VVgenomes or direct DNA ligation and packaging using replication-deficient poxviruses. Here, we describe efficient new versions of both methods that produce 90%-100% of the recombinant viruses. In the new homologous recombination method, VV DNA "arms" obtained by NotI digestion and intact transfer plasmids were used for co-transfection. In the direct DNA ligation method, foreign DNA was inserted into a unique NotI restriction site of the VVgenome. In both methods, the generation of recombinant viruses was carried out in cells infected with a non-replicating, psoralen-UV (PUV)-inactivated helper VV. The convenience of these new techniques is demonstrated by the construction of recombinant VVs that produce E. coli beta-galactosidase. An important feature of these strategies is that any VV strain can be used as a helper virus after PUV inactivation.
An Empirical Study on the Capacity and Performance of 3G Networks (2008)

This paper presents the findings of an extensive measurement study on multiple commercial 3G networks. We have investigated the performance of those 3G networks in terms of their data throughput, latency, video and voice calls handling capacities, and their ability to provide service guarantees to different traffic classes under saturated and lightly-loaded network conditions. Our findings point to the diverse nature of the network resources allocation mechanisms and the call admission control policies adopted by different operators. It is also found that the 3G network operators seem to have extensively customized their network configurations in a cell-by-cell manner according to the individual site's local demographics, projected traffic demand and the target coverage area of the cell. As such, the cell capacity varies widely not only across different operators but also across different measurement sites of the same operator. The results also show that it is practically impossible to predict the actual capacity of a cell based on known theoretical models and standard parameters, even when supplemented by key field measurements such as the received signal-to-noise ratio (Ec/N0)
Histological and Ultrastructural Effects of Ultrasound-induced Cavitation on Human Skin Adipose Tissue (2013)

This study further strengthens the current notion that noninvasive transcutaneous ultrasound cavitation is a promising and safe technology for localized reduction of fat and provides experimental evidence for its specific mechanism of action on the adipocytes.
A Monoclonal Antibody to Human Transitional Cell Carcinoma of the Bladder: Production and Characterization (1987)

In order to detect bladder tumor specific antigens, monoclonal antibodies (MoAbs) to human transitional cell carcinoma of the bladder (TCCB) were obtained. Hybridomas were cloned after being prepared by cell fusion between mouse myeloma cell line X63Ag 8.653 and the spleen cells of BALB/c mice hyperimmune to the bladder cancer cells (grade 2) from a patient. Subsequently 12 MoAb-producing clones were obtained for the panel screening by enzyme immunoassay (EIA) and three MoAbs (no. 10, 11 and 14) were selected for reactivity to bladder cancer cells from patients, including normal epithelia. Finally No. 10 was selected as the most appropriate MoAb for this study and determined IgM with kappa-light chains by EIA. We accurately tested MoAb No. 10's reactivity with 71 malignant tumors by immunoperoxidase staining (IIP). No. 10 reacted to most TCCB cells (36/43), but did not react to any of the other tissues, including five normal epithelia, two brain tumors and three sarcomas. It was also shown by both IIP and immunofluorescent staining (IIF) that No. 10's reactivity was limited to the cancer cell membrane. These results suggest that the antigen recognized by MoAb No. 10 is one of the tumor-associated antigens and that some heterogeneity exists in its distribution.