gebhart/patrepeval huggingface dataset:
Skin Metabolite, Farnesyl Pyrophosphate, Regulates Epidermal Response to Inflammation, Oxidative Stress, and Migration (2016)

Skin produces cholesterol and a wide array of sterols and non-sterol mevalonate metabolites, including isoprenoid derivative farnesyl pyrophosphate (FPP). To characterize FPP action in epidermis, we generated transcriptional profiles of primary human keratinocytes treated with zaragozic acid (ZGA), a squalene synthase inhibitor that blocks conversion of FPP to squalene resulting in endogenous accumulation of FPP. The elevated levels of intracellular FPP resulted in regulation of epidermal differentiation and adherens junction signaling, insulin growth factor (IGF) signaling, oxidative stress response and interferon (IFN) signaling. Immunosuppressive properties of FPP were evidenced by STAT-1 downregulation and prominent suppression of its nuclear translocation by IFNγ. Furthermore, FPP profoundly downregulated genes involved in epidermal differentiation of keratinocytes in vitro and in human skin ex vivo. Elevated levels of FPP resulted in induction of cytoprotective transcriptional factor Nrf2 and its target genes. We have previously shown that FPP functions as ligand for the glucocorticoid receptor (GR), one of the major regulator of epidermal homeostasis. Comparative microarray analyses show significant but not complete overlap between FPP and glucocorticoid regulated genes, suggesting that FPP may have wider transcriptional impact. This was further supported by co-transfection and chromatin immunoprecipitation experiments where we show that upon binding to GR, FPP recruits β-catenin and, unlike glucocorticoids, recruits co-repressor GRIP1 to suppress keratin 6 gene. These findings have many clinical implications related to epidermal lipid metabolism, response to glucocorticoid therapy as well as pleiotropic effects of cholesterol lowering therapeutics, statins. J. Cell. Physiol. 231: 2452-2463, 2016. © 2016 Wiley Periodicals, Inc.
Use of a sampled Bragg grating as an in-fiber optical resonator for the realization of a referencing optical frequency scale for WDM communications (2002)

Standardization for absolute laser frequency assignment in projected dense wavelength-division multiplexing (DWDM) networks has become a very important issue. Recently, we have proposed a referencing scale of standard optical frequencies that are exact multiples of 100 GHz. Such a scale is independent of the atomic or molecular reference used to set the absolute value and is uniformly applicable to all spectral ranges. Here, we propose the use of sampled Bragg gratings to realize the optical resonator. This resonator is adaptable, robust, potentially cost efficient and readily compatible with the fiber network.
The evolving science of atherothrombotic disease (2016)

Atherosclerosis is a systemic inflammatory disease characterized by the accumulation of inflammatory cells in the intima of large arteries. The presence of platelets at the site of inflammation and endothelial injury has been known since the early 1960s. In the following years, it was generally accepted that rupture or erosion of advanced atherosclerotic lesions initiates platelet activation and aggregation on the thrombo-genic surface of a disrupted atherosclerotic plaque. Thrombotic vascular occlusion is associated with ischaemic episodes in the retina, brain, heart, and other organs. While it is widely accepted that platelets play a significant role in thromboembolic events generated by atherosclerotic lesions (atherothrombosis), their involvement in the initiation of the atherosclerotic process has not been widely recognized by the scientific community. An expanding body of evidence on the role of platelets in the development of atherosclerotic lesions continues to build. Platelets bind to leukocytes and endothelial cells, and initiate the transformation of monocytes into macrophages. Additionally, platelets internalize oxidized phospholipids and promote foam cell formation, as well as recruit progenitor cells that are able to differentiate into foam or endothelial cells. In total, platelets play a key role in the initiation, development, and total extent of atherosclerotic lesions.
RSQO asynchronous serial multiplier and spreading codes generator for multiuser detector (2003)

Serial multiplier and serial spreading code generators are vital elements of the RSFQ multiuser detector. We have designed different versions of both circuits to achieve maximum speed and at the same time minimize Josephson junction count. Comparison of different serial multipliers architectures supporting signed multiplication favored for asynchronous shifting over zero circuits based on carry save adder and co-flow distribution of the partial product and the clock. A 25-bit spreading code generator supporting parallel input/output has been designed for 4 kA/cm/sup 2/ (TRW) and for 1 kA/cm/sup 2/ (HYPRES) processes. The corresponding maximum simulated clock speed of 52 GHz and 26 GHz and effective device area of 1/spl times/0.12 mm/sup 2/ and 1.9/spl times/0.2 mm/sup 2/.
The effect of antibody-dependent enhancement on the transmission dynamics and persistence of multiple-strain pathogens (1999)

Cross-reactive antibodies produced by a mammalian host during infection by a particular microparasitic strain usually have the effect of reducing the probability of the host being infected by a different, but closely related, pathogen strain. Such cross-reactive immunological responses thereby induce between-strain competition within the pathogen population. However, in some cases such as dengue virus, evidence suggests that cross-reactive antibodies act to enhance rather than restrict the severity of a subsequent infection by another strain. This cooperative mechanism is thought to explain why pre-existing immunity to dengue virus is an important risk factor for the development of severe disease (i.e., dengue shock syndrome and dengue hemorrhagic fever). In this paper, we explore the effect of antibody-dependent enhancement on the transmission dynamics of multistrain pathogen populations. We show that enhancement frequently may generate complex and persistent cyclical or chaotic epidemic behavior. Furthermore, enhancement acts to permit the coexistence of all strains where in its absence only one or a subset would persist.
Cloning and expression of porcine β1,4 N‐acetylgalactosaminyl transferase encoding a new xenoreactive antigen (2014)

The functional isolation of the porcine B4GALNT2 gene from a PAEC expression library, the pattern of B4GALNT2 gene expression and its sensitization of HEK-B4T cells to antibody binding and complement mediated lysis indicates that the enzymatic activity of porcine B4GALNT2 produces a new immunogenic non-Gal glycan which contributes in part to the non-Gal immune response detected after pig-to-baboon cardiac xenotransplantation.
Workpiece form accuracy in-process measurement and control system -- a discussion of key parts and preliminary experimentation (1993)

Precision machining can achieve high levels of accuracy through the use of a highly accurate spindle, straight feed mechanisms, a rigid base and a single-point diamond tool. Research is underway aimed at achieving even higher levels of accuracy by adding computers, non-contact sensors and piezoelectric actuators for in-process measurement and control to the workpiece. Based upon such idea, a workpiece form accuracy in-process measurement and control system is proposed in this paper. The principle and a few key techniques for the system are discussed and some preliminary experiments are given in the paper.
Sterol Biosynthesis (1986)

Crop loss due to soil salinization is an increasing threat to agriculture worldwide. This review provides an overview of cellular and physiological mechanisms in plant responses to salt. We place cellular responses in a time- and tissue-dependent context ...Read More
Increased aortic stiffness assessed by pulse wave velocity in apolipoprotein E-deficient mice (2000)

Atherosclerosis develops and progresses spontaneously in apolipoprotein E-knockout (apoE-KO) mice. A direct consequence of atherosclerosis is an increase in vascular stiffness. Pulse wave velocity (PWV) has been used to assess the stiffness of large vessels and was found to be increased in patients with atherosclerosis. In the present study, aortic stiffness was assessed by PWV in 4- and 13-mo-old apoE-KO mice and age-matched controls (C57BL/6J). In 13-mo-old apoE-KO mice with extensive atherosclerotic lesions in the aorta (61 +/- 4%), PWV increased significantly (3.8 +/- 0.2 m/s) compared with controls (2.9 +/- 0.2 m/s). Endothelial nitric oxide (EDNO)-mediated vasorelaxation in response to ACh was markedly diminished in the aortic rings isolated from 13-mo-old apoE-KO mice compared with age-matched controls. In contrast, in 4-mo-old apoE-KO mice with only moderate atherosclerotic lesions in the aorta (23 +/- 5%), there were no significant changes in PWV and EDNO-mediated relaxation compared with controls. Blood pressure was not different among the four groups of mice. There were no significant differences in endothelium-independent vascular responses to sodium nitroprusside among different groups investigated. Histological evaluation revealed focal fragmentation of the elastic laminae in the aortic walls of 13-mo-old apoE-KO mice. These results demonstrate for the first time that aortic stiffness determined by PWV increases in 13-mo-old apoE-KO mice. Endothelial dysfunction and elastic destruction in vascular wall caused by atherosclerosis may have contributed.
Transforming growth factors in the urine of normal, pregnant, and tumor-bearing humans. (1982)

Transforming growth factor (TGF) activities could be detected in the urine of normal, pregnant, and tumor-bearing humans. These acid- and heat-stable polypeptides competed for binding to epidermal growth factor (EGF) membrane receptors and promoted the anchorage-independent growth of nontransformed rodent cells. They differed from human EGF in their apparent molecular weights and soft-agar growth-stimulating activity. The urine from pregnant females contained TGF activities with apparent molecular weight(s) (relative) (Mr) of 10,000 ad 17,000--20,000. In the case of a lung cancer patient, an additional major activity of approximately 30,000--35,000 Mr was found. All urine specimens examined also contained a "common" 8,000-Mr soft-agar growth-stimulating activity, which competed for binding to EGF membrane receptors and which was chromatographically separable from EGF (urogastrone). Thus urine may provide a convenient and readily available source for the biochemical characterization of these TGF-like activities, some of which may be clinically useful biologic markers for certain types of cancer.
Analytical and Experimental Study of Gearbox Mechanical Effect on the Induction Machine Stator Current Signature (2009)

The aim of this paper is the analytical and experimental study of a gearbox by using the stator current signature analysis in the driving induction machines. The mechanical study using the vibration signal analysis has been well studied before. Recently, some works have been performed to observe the vibration components of the mechanical part in the stator current spectrum for an induction machine but without any theoretical development. This paper proposes a theoretical framework based on torque oscillations due to the characteristic torsional vibrations in a gearbox, and the source of mesh and rotating frequency components in the stator current is presented. To verify the theoretical development, a test bed based on a 5.5-kW three-phase squirrel-cage machine connected to a gearbox has been used.
Embryological Development of Primordial Germ-cells in the Mouse: Influence of a New Mutation, Wj (1957)

ABSTRACT Twenty-seven mouse embryos at days from matings of Wjw × Wjw were examined in order to establish the embryological basis of the germ-cell deficiency found in the WjWj genotype at birth. Elective staining of primordial germ-cells was obtained with the azo dye coupling histochemical technique for alkaline phosphatase. Numbers and locations of these cells were recorded in complete serial sections. Formation of germ-cells occurs, as in normals, in all members of the 8-day group. At 9 days and later, during gonial migration from yolk sac toward germinal ridges, two distinct populations of individuals are recognizable. In one, the number of germ-cells increases; in the other, totals remain very low. The latter would be expected to characterize the WjWj class. Observed incidence of such cases was close to the theoretical frequency of 25 per cent, defective offspring. These findings support the earlier proof (Mintz &amp; Russell, 1955, 1957) that the cells observed are the primordial germ-cells and are of extra-gonadal origin. In defectives, migratory retardation of germ-cells accompanies their mitotic insufficiency. The effects of Wj are compared with those of the alleles W and Wv, and the significance of the study for the problem of pleiotropic gene action is considered.
Dendrimeric Molecular Transporters:  Synthesis and Evaluation of Tunable Polyguanidino Dendrimers That Facilitate Cellular Uptake (2005)

[reaction: see text] Nine fluorescently labeled structurally varied polyguanidino dendrimers based on diamino acid monomeric units were individually synthesized in an efficient, scalable sequence using a trifluoroacetamide protecting group-perguanidinylation strategy. While the dendrimers varied significantly in their ability to enter a human lymphocyte cell line, the best transporters out-performed an oligoarginine reference standard.
Melanoma Cell Adhesion Molecule (MCAM) expression in the myogenic lineage during early chick embryonic development. (2002)

We describe the expression pattern of cMCAM, a cell adhesion molecule of the immunoglobulin superfamily, in early chick embryonic development by in situ hybridisation. An initial ectodermal domain of expression is subsequently expanded, and cMCAM is expressed in the neural crest cells, otic vesicle, heart primordium, notochord and endoderm. In addition, cMCAM expression localises in the myotome once the somite cells have been specified. An in vitro murine cellular system allowed us to confirm that MCAM expression coincides with the onset of myogenic cell determination.
Tuberculosis vaccines: past, present and future (2006)

For more than 80 years now no new tuberculosis vaccine has successfully been developed. There is now renewed optimism that vaccines superior to BCG can be developed in the coming years. The goal is to obtain a new generation of vaccines effective against more transmissible forms of tuberculosis. As a first step, good candidate vaccines able to boost BCG and improve BCG protection could be a reality in the near future. Tuberculosis vaccine candidates, able to replace the currently used BCG and make the eradication of tuberculosis feasible, can be expected in the mid-term, and live vaccines are reliable and promising candidates.
Maneb enhances MPTP neurotoxicity in mice. (1989)

The effects of acute administration of maneb (30 mg/kg, i.p.), an agricultural fungicide, combined with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP 50 mg/kg, i.p.), a dopaminergic neurotoxin, were examined on mouse locomotor activity and catalepsy test. The pretreatment with maneb significantly exacerbated the effects of MPTP on locomotion and catalepsy in mice. These results suggest that exposure to some pesticides might enhance motor dysfunction.
In vitro generation and transplantation of precursor‐derived human dopamine neurons (2001)

The use of in vitro expanded human CNS precursors has the potential to overcome some of the ethical, logistic and technical problems of fetal tissue transplantation in Parkinson disease. Cultured rat mesencephalic precursors proliferate in response to bFGF and upon mitogen withdrawal, differentiate into functional dopamine neurons that alleviate motor symptoms in Parkinsonian rats (Studer et al. [1998] Nat. Neurosci. 1:290-295). The successful clinical application of CNS precursor technology in Parkinson disease will depend on the efficient in vitro generation of human dopaminergic neurons. We demonstrate that human dopamine neurons can be generated from both midbrain and cortical precursors. Transplantation of midbrain precursor-derived dopamine neurons into Parkinsonian rats resulted in grafts rich in tyrosine hydroxylase positive neurons 6 weeks after transplantation. No surviving tyrosine hydroxylase positive neurons could be detected when dopamine neurons derived from cortical precursors were grafted. Our data demonstrate in vitro derivation of human dopamine neurons from expanded CNS precursors and encourage further studies that systematically address in vivo function and clinical potential.
Disrupting the hydrophobic patches at the antibody variable/constant domain interface: improved in vivo folding and physical characterization of an engineered scFv fragment (1997)

By constructing Fv and single-chain Fv (scFv) fragments of antibodies, the variable domains are taken out of their natural context in the Fab fragment, where they are associated with the constant domains of the light (CL) and heavy chain (CH1). As a consequence, all residues of the former variable/constant domain interface become solvent exposed. In an analysis of 30 non-redundant Fab structures it was found that at the former variable/constant domain interface of the Fv fragment the frequency of exposed hydrophobic residues is much higher than in the rest of the Fv fragment surface. We investigated the importance of these residues for different properties such as folding in vivo and in vitro, thermodynamic stability, solubility of the native protein and antigen affinity. The experimental model system was the scFv fragment of the anti-fluorescein antibody 4-4-20, of which only 2% is native when expressed in the periplasm of Escherichia coli. To improve its in vivo folding, a mutagenesis study of three newly exposed interfacial residues in various combinations was carried out. The replacement of one of the residues (V84D in VH) led to a 25-fold increase of the functional periplasmic expression yield of the scFv fragment of the antibody 4-4-20. With the purified scFv fragment it was shown that the thermodynamic stability and the antigen binding constant are not influenced by these mutations, but the rate of the thermally induced aggregation reaction is decreased. Only a minor effect on the solubility of the native protein was observed, demonstrating that the mutations prevent aggregation during folding and not of the native protein. Since the construction of all scFv fragments leads to the exposure of these residues at the former variable/constant domain interface, this strategy should be generally applicable for improving the in vivo folding of scFv fragments and, by analogy, also the in vivo folding of other engineered protein domains.
Effective Parenting Interventions to Reduce Youth Substance Use: A Systematic Review (2016)

This review suggests that relatively low-intensity group parenting interventions are effective at reducing or preventing adolescent substance use and that protection may persist for multiple years. There is a need for additional evidence in clinical and other community settings using an expanded set of delivery methods.
Adiponectin and Breast Cancer Risk (2004)

Adiponectin, an adipocyte-secreted hormone, is closely and inversely associated with insulin resistance and was recently found to be inversely and independently associated with endometrial cancer. Because insulin resistance in the setting of obesity has also been associated with the development of breast cancer, we have hypothesized that decreased adiponectin levels might underlie the association between breast cancer and obesity/insulin resistance. We evaluated the association of adiponectin with the occurrence of breast cancer in a case-control study comprising 174 women with newly diagnosed, histologically confirmed breast cancer and 167 controls. We found an inverse, fairly strong, and statistically significant association of serum adiponectin with breast cancer (odds ratio, 0.84; 95% confidence interval, 0.71-0.99). Importantly, despite a fairly robust inverse association of adiponectin with breast cancer risk among postmenopausal women (odds ratio, 0.82; 95% confidence interval, 0.67-1.00), no such significant association between adiponectin and breast cancer was found among premenopausal women. The observed associations were independent of possible effects of major components of the IGF system, leptin, body mass index, sociodemographic variables, and known risk factors for breast cancer. Future studies are needed to prove causality and provide further insights into both the mechanisms underlying the actions of this hormone and its potential role in breast cancer.
A new space-time-frequency MIMO-OFDM scheme with cyclic delay diversity (2004)

In traditional multiple input multiple output-orthogonal frequency division multiplexing (MIMO-OFDM) system, cyclic delay can increase frequency selectivity of the channel seen by the receiver, which results in cyclic delay diversity (CDD) and achieves spatial diversity. Space frequency coded scheme is another effective method to improve bit error performance of the whole wireless system. While both cyclic delay diversity and space frequency coded technology is put into traditional MIMO-OFDM system, a new space-time-frequency MIMO-OFDM scheme with cyclic delay diversity is proposed in this paper. Spatial diversity is achieved by cyclic delay diversity and frequency diversity is exploited by space frequency coded method in our scheme. Tests show that the new scheme can achieve excellent diversity gains and bit error performance. The new scheme also has obvious advantages on its simple and flexible structure.
Expression of CCR2 in Both Resident and Bone Marrow-Derived Microglia Plays a Critical Role in Neuropathic Pain (2007)

Neuropathic pain resulting from damage to or dysfunction of peripheral nerves is not well understood and difficult to treat. Although CNS hyperexcitability is a critical component, recent findings challenge the neuron-centric view of neuropathic pain etiology and pathology. Indeed, glial cells were shown to play an active role in the initiation and maintenance of pain hypersensitivity. However, the origins of these cells and the triggers that induce their activation have yet to be elucidated. Here we show that, after peripheral nerve injury induced by a partial ligation on the sciatic nerve, in addition to activation of microglia resident to the CNS, hematogenous macrophage/monocyte infiltrate the spinal cord, proliferate, and differentiate into microglia. Signaling from chemokine monocyte chemoattractant protein-1 (MCP-1, CCL2) to its receptor CCR2 is critical in the spinal microglial activation. Indeed, intrathecal injection of MCP-1 caused activation of microglia in wild-type but not in CCR2-deficient mice. Furthermore, treatment with an MCP-1 neutralizing antibody prevented bone marrow-derived microglia (BMDM) infiltration into the spinal cord after nerve injury. In addition, using selective knock-out of CCR2 in resident microglia or BMDM, we found that, although total CCR2 knock-out mice did not develop microglial activation or mechanical allodynia, CCR2 expression in either resident microglia or BMDM is sufficient for the development of mechanical allodynia. Thus, to effectively relieve neuropathic pain, both CNS resident microglia and blood-borne macrophages need to be targeted. These findings also open the door for a novel therapeutic strategy: to take advantage of the natural ability of bone marrow-derived cells to infiltrate selectively affected CNS regions by using these cells as vehicle for targeted drug delivery to inhibit hypersensitivity and chronic pain.