Miracle-dz/UniFAR-FTUs huggingface dataset:
Nitric oxide: a key mediator in the early and late phase of carrageenan‐induced rat paw inflammation

1 The role of nitric oxide (NO) derived from constitutive and inducible nitric oxide synthase (cNOS and iNOS) and its relationship to oxygen‐derived free radicals and prostaglandins (PG) was investigated in a carrageenan‐induced model of acute hindpaw inflammation. 2 The intraplantar injection of carrageenan elicited an inflammatory response that was characterized by a time‐dependent increase in paw oedema, neutrophil infiltration, and increased levels of nitrite/nitrate (NO2−/NO3−) and prostaglandin E2(PGE2) in the paw exudate. 3 Paw oedema was maximal by 6 h and remained elevated for 10 h following carrageenan administration. The non‐selective cNOS/iNOS inhibitors, NG‐ monomethyl‐L‐arginine (L‐NMMA) and NG‐nitro‐L‐arginine methyl ester (L‐NAME) given intravenously (30–300 mg kg−1) 1 h before or after carrageenan administration, inhibited paw oedema at all time points. 4 The selective iNOS inhibitors, N‐iminoethyl‐L‐lysine (L‐NIL) or aminoguanidine (AG), failed to inhibit carrageenan‐induced paw oedema during the first 4 h following carrageenan administration, but inhibited paw oedema at subsequent time points (from 5–10 h). iNOS mRNA was detected between 3 to 10 h following carrageenan administration using ribonuclease protection assays. iNOS protein was first detected 6 h and was maximal 10 h following carrageenan administration as shown by Western blot analysis. Administration of the iNOS inhibitors 5 h after carrageenan (a time point where iNOS was expressed) inhibited paw oedema at all subsequent time points. Infiltrating neutrophils were not the source of iNOS since pretreatment with colchicine (2 mg kg−1) suppressed neutrophil infiltration, but did not inhibit the iNOS mRNA expression or the elevated NO2−/NO3− levels in the paw exudate. 5 Inhibition of paw oedema by the NOS inhibitors was associated with attenuation of both the NO2−/NO3− and PGE2 levels in the paw exudate. These inhibitors also reduced the neutrophil infiltration at the site of inflammation. 6 Recombinant human Cu/Zn superoxide dismutase coupled to polyethyleneglycol (PEGrhSOD;12 × 103 u kg−1), administered intravenously either 30 min prior to or 1 h after carrageenan injection, inhibited paw oedema and neutrophil infiltration, but had no effect on NO2−/NO3− or PGE2 production in the paw exudate. The administration of catalase (40 × 103 u kg−1), given intraperitoneally 30 min before carrageenan administration, had no effect on paw oedema. Treatment with desferrioxamine (300 mg kg−1), given subcutaneously 1 h before carrageenan, inhibited paw oedema during the first 2 h after carrageenan administration, but not at later times. 7 These results suggest that the NO produced by cNOS is involved in the development of inflammation at early time points following carrageenan administration and that NO produced by iNOS is involved in the maintenance of the inflammatory response at later time points. The potential interactions of NO with superoxide anion and PG is discussed.
Variability in the Raman Spectrum of Unpolished Growth and Fracture Surfaces of Pyrite Due to Laser Heating and Crystal Orientation

Two probable causes of variability in the Raman spectrum of unpolished pyrite are well recognized, in principle, but not always in practice, namely: (1) downshifting of band positions due to laser heating; and (2) variations in the ratios of band intensities due to crystallographic orientation of the sample with respect to the laser’s dominant polarization plane. The aims of this paper are to determine whether these variations can be used to acquire additional information about pyrites. Here, using laser Raman microprobe analysis of natural, unpolished pyrite samples, we investigate the magnitude of downshifting of band positions associated with laser heating of different sizes of pyrite grains. We demonstrate that the magnitude of this effect can be large (up to ∼10 cm−1), negatively proportional to grain size, of greater magnitude than the effect typically attributable to natural intersample differences in trace element (TE) solid solution, and of similar magnitude among bands. Through Raman analysis of naturally occurring faces on pyrite samples at various angles of rotation, we also demonstrate that the three most common faces on pyrite can be distinguished by the ratio of the intensities of the dominant bands. We conclude that for unpolished samples, laser Raman microprobe analysis is most effective as a means of identifying pyrite, and the presence of solid solution therein, when laser power is low enough to avoid substantial heating. Once pyrite has been identified, higher laser powers can be used to produce spectra whose ratios of band intensities indicate the face or crystallographic plane being irradiated.
Rapid and Simple Identification of Pork in Meat Products by Using the Isothermal Target and Probe Amplification Assay

Species identification of animal tissues in meat products is an important issue to protect the consumer from illegal and/or undesirable adulteration, for economic, religious and health reasons. For example, pork DNA was found in halal chicken sausages served in a primary school in Westminster, central London, the local authority had stated on 14 March 2015. PCR is one of the most widely used techniques in diagnostic applications because it allows a sensitive and rapid diagnosis. However, this technique is not suitable for routine identification of pork in meat products because of the need for expensive thermal cycler equipment and complex operations. The isothermal target and probe amplification (iTPA) analysis has been developed for identifying pork species in meat samples. In this study, the isothermal target and probe amplification assay was developed for rapid, simple and highly specific identification of pork DNA. For the assay, the mitochondrial 16S ribosomal RNA gene and the FRET-based signal probe were amplified at 61oC, followed by measurement of the fluorescent signal. As little as 1 pg of template DNA could be detected without any cross-reactivity with non-target species. Meat mixtures prepared by mixing pork meat with other meats at different ratios (0.01% 10%) were tested, and the iTPA assay allowed detection of as little as 0.01% pork in meat mixtures. Thus, this work showed that the iTPA assay could be used for specific identification of pork species. This assay only requires a heat block and a fluorescence reader for amplification and detection, respectively, and it has great potential for use as a hand-held device or point-of-care-testing system. The iTPA assay is sensitive and specific for rapid screening of fraudulent adulteration/substitution of meat products.
Impact of anxiety and depressive symptoms on perceptions of stigma in persons living with HIV disease in rural versus urban North Carolina

ABSTRACT This analysis examined the relationships between HIV-related stigma, depression, and anxiety in rural and urban sites. Participants were HIV-positive urban (n = 100) and rural (n = 100) adult residents of a US southern state, drawn from a sample for a larger international study of self-esteem and self-compassion. Measures included demographic and health information, the HIV Stigma Scale, the Center for Epidemiology Studies Depression Scale (CES-D), and the Symptom Checklist 90 Revised (SCL-R-90) anxiety scale. Independent sample t-tests showed no significant differences between urban/rural groups on measures of HIV-related stigma, anxiety, or depression, except that rural participants reported greater disclosure concerns (t = 2.11, df = 196, p = .036). Both groups indicated high levels of depression and anxiety relative to published norms and clinically relevant cut-off scores. Hierarchical regression analyses were conducted for the HIV Stigma Scale including its four subscales and total stigma scores. Block 1 (control) contained health and demographic variables known to predict HIV-related stigma. Block 2 included the CES-D and the SCL-R-90, and Block 3 was urban/rural location. Mental health symptom scores contributed a significant amount to explained variance in total stigma scores (5.5%, FΔ = 6.020, p < .01), personalized stigma (4.8%, FΔ = 5.035, p < .01), negative self-image (9.7%, FΔ = 12.289, p < .001), and concern with public attitudes (4.9%, FΔ = 5.228, p < .01), but not disclosure concerns. Urban/rural location made significant additional contributions to the variance for total stigma (1.7%, FΔ = 3.899, p < .05), disclosure concerns (2.6%, FΔ = 5.446, p < .05), and concern with public attitudes (1.9%, FΔ = 4.169, p < .05) but not personalized stigma or negative self-image. Depression scores consistently and significantly predicted perceived stigma total and subscale scores. Findings suggest that mental health symptoms and urban/rural location play important roles in perceived stigma, and treatment implications are presented.
Mutant p53 promotes epithelial‐mesenchymal plasticity and enhances metastasis in mammary carcinomas of WAP‐T mice

To study the postulated mutant p53 (mutp53) “gain of function” effects in mammary tumor development, progression and metastasis, we crossed SV40 transgenic WAP‐T mice with mutant p53 transgenic WAP‐mutp53 mice. Compared to tumors in monotransgenic WAP‐T mice, tumors in bitransgenic WAP‐T x WAP‐mutp53 mice showed higher tumor grading, enhanced vascularization, and significantly increased metastasis. Bitransgenic tumors revealed a gene signature associated with the oncogenic epithelial‐mesenchymal transition pathway (EMT gene signature). In cultures of WAP‐T tumor‐derived G‐2 cancer cells, which are comprised of subpopulations displaying “mesenchymal” and “epithelial” phenotypes, this EMT gene signature was associated with the “mesenchymal” compartment. Furthermore, ectopic expression of mutp53 in G‐2 cells sufficed to induce a strong EMT phenotype. In contrast to these in vitro effects, monotransgenic and bitransgenic tumors were phenotypically similar suggesting that in vivo the tumor cell phenotype might be under control of the tumor microenvironment. In support, orthotopic transplantation of G‐2 cells as well as of G‐2 cells expressing ectopic mutp53 into syngeneic mice resulted in tumors with a predominantly epithelial phenotype, closely similar to that of endogenous primary tumors. We conclude that induction of an EMT gene signature by mutp53 in bitransgenic tumors primarily promotes tumor cell plasticity, that is, the probability of tumor cells to undergo EMT processes under appropriate stimuli, thereby possibly increasing their potential to disseminate and metastasize.
Soy Promotes Juvenile Granulosa Cell Tumor Development in Mice and in the Human Granulosa Cell Tumor-Derived COV434 Cell Line1

ABSTRACT Soy attracts attention for its health benefits, such as lowering cholesterol or preventing breast and colon cancer. Soybeans contain isoflavones, which act as phytoestrogens. Even though isoflavones have beneficial health effects, a role for isoflavones in the initiation and progression of diseases including cancer is becoming increasingly recognized. While data from rodent studies suggest that neonatal exposure to genistein (the predominant isoflavone in soy) disrupts normal reproductive function, its role in ovarian cancers, particularly granulosa cell tumors (GCT), is largely unknown. Our study aimed to define the contribution of a soy diet in GCT development using a genetically modified mouse model for juvenile GCTs (JGCT; Smad1 Smad5 conditional double knockout mice) as well as a human JGCT cell line (COV434). While dietary soy cannot initiate JGCT development in mice, we show that it has dramatic effects on GCT growth and tumor progression compared to a soy-free diet. Loss of Smad1 and Smad5 alters estrogen receptor alpha (Esr1) expression in granulosa cells, perhaps sensitizing the cells to the effects of genistein. In addition, we found that genistein modulates estrogen receptor expression in the human JGCT cell line and positively promotes cell growth in part by suppressing caspase-dependent apoptosis. Combined, our work suggests that dietary soy consumption has deleterious effects on GCT development.
A Trust Based Distributed Intrusion Detection Mechanism for Internet of Things

Many Internet of Things (IoT) networks comprise tiny devices with limited processing power and tight energy restrictions. These limitations make it difficult to use established security mechanisms protecting the devices against malicious attacks. This holds particularly for Intrusion Detection Systems (IDS) that help to detect various net-based attacks but often demand significant network and computing resources. In this article, we design and evaluate some IDS mechanisms for IoT Networks that are suited to small devices. They use a trust management mechanism that allows devices to manage reputation information about their neighbors. This mechanism makes it possible to single out maliciously behaving units in a processing and energy-friendly way. The approach is explained in the context of the healthcare domain.
Synthesis of the Mammalian Telomere Lagging Strand in Vitro *

Using a synthetic telomere DNA template and whole cell extracts, we have identified proteins capable of synthesizing the telomere complementary strand. Synthesis of the complementary strand required a DNA template consisting of 10 repeats of the human telomeric sequence d(TTAGGG) and deoxy- and ribonucleosidetriphosphates and was inhibited by neutralizing antibodies to DNA polymerase α. No evidence for RNA-independent synthesis of the lagging strand was observed, suggesting that a stable DNA secondary structure capable of priming the lagging strand is unlikely. Purified DNA polymerase α/primase was capable of catalyzing synthesis of the lagging strand with the same requirements as those observed in crude cell extracts. A ladder of products was observed with an interval of six bases, suggesting a unique RNA priming site and site-specific pausing or dissociation of polymerase α on the d(TTAGGG)10 template. Removal of the RNA primers was observed upon the addition of purified RNase HI. By varying the input rNTP, the RNA priming site was determined to be opposite the 3′ thymidine nucleotide generating a five-base RNA primer with the sequence 5′-AACCC. The addition of UTP did not increase the efficiency of priming and extension, suggesting that the five-base RNA primer is sufficient for extension with dNTPs by DNA polymerase α. This represents the first experimental evidence for RNA priming and DNA extension as the mechanism of mammalian telomeric lagging strand replication.
Subcellular relationships between cholinergic terminals and estrogen receptor‐α in the dorsal hippocampus

Cholinergic septohippocampal neurons are affected by circulating estrogens. Previously, we found that extranuclear estrogen receptor‐α (ERα) immunoreactivity in presynaptic profiles had an overlapping distribution with cholinergic afferents in the rat hippocampal formation. To determine the subcellular relationships between cholinergic presynaptic profiles and ERα, hippocampal sections were dually immunolabeled for vesicular acetylcholine transporter (VAChT) and ERα and examined by electron microscopy. Within the hippocampal formation, immunoreactivities for VAChT and ERα both were presynaptic, although their subcellular targeting was distinct. VAChT immunoreactivity was found exclusively within presynaptic profiles and was associated with small synaptic vesicles, which usually filled axon terminals. VAChT‐labeled presynaptic profiles were most concentrated in stratum oriens of the hippocampal CA1 region and dentate inner molecular layer and hilus. In contrast, ERα immunoreactivity was found in clusters affiliated either with select vesicles or with the plasmalemma within preterminal axons and axon terminals. ERα‐immunoreactive (IR) presynaptic profiles were more evenly distributed between hippocampal lamina than VAChT‐IR profiles. Quantitative ultrastructural analysis revealed that VAChT‐IR presynaptic profiles contained ERα immunoreactivity (ranging from 3% to 17%, depending on the lamina). Additionally, VAChT‐IR presynaptic profiles apposed ERα‐IR dendritic spines, presynaptic profiles, and glial profiles; many of the latter two types of profiles abutted unlabeled dendritic spines that received asymmetric (excitatory‐type) synapses from unlabeled terminals. The presence of ERα immunoreactivity in cholinergic terminals suggests that estrogen could rapidly and directly affect the local release and/or uptake of acetylcholine. The affiliation of cholinergic terminals with excitatory terminals near ERα‐labeled dendritic spines or glial profiles suggests that alterations in acetylcholine release could indirectly affect estrogen‐modulated structural plasticity. J. Comp. Neurol. 463:390–401, 2003. © 2003 Wiley‐Liss, Inc.
Compact OCT endomicroscopic catheter using flip-chip bonded Lissajous scanned electrothermal MEMS fiber scanner

We report a compact optical coherence tomography (OCT) endomicroscope with a Lissajous scanned electrothermal MEMS fiber scanner. Two-dimensional Lissajous scanning was realized by Joule heating of the electrothermal MEMS fiber scanner. The compact packaging of MEMS scanner has a primary challenge, particularly in inserting it into an endomicroscopic catheter. The electrothermal MEMS fiber scanner was precisely designed and flip-chip bonded with a thin printed circuit board and completely packaged with 1.65 mm diameter housing tube, 1 mm diameter GRIN lens, and a single mode optical fiber. A 1.65 mm diameter OCT endomicroscopic catheter was successfully combined with a spectral-domain OCT system. Two-dimensional OCT image of a finger nail was successfully obtained with the endomicroscopic catheter.
Visual Bubble: Protecting Privacy in Wearable Cameras

Wearable cameras are being used more frequently in many different consumer applications, including entertainment, law enforcement, and health care. To protect the privacy of the environment and bystanders, we introduce a new visual privacy paradigm called the visual bubble. In contrast to most existing visual privacy schemes, the visual bubble is based on depth estimation to determine the extent of privacy protection. To demonstrate this concept, we built a wearable privacy stereo-camera system using the Raspberry Pi platform. The effectiveness of our system in protecting privacy was demonstrated with experimental results on multiple data sets.
Genetically Engineered Mouse Models of Ovarian Cancer and Their Utility in Drug Discovery

Ovarian cancer is the fourth most common cancer in women and the most lethal gynecological malignancy. The high mortality rate is attributable to the asymptomatic nature of the early stage of the disease, the lack of reliable screening tests, and the development of drug resistance. Approximately 90% of ovarian cancers are thought to originate from the ovarian surface epithelia (OSE). Development of in vivo experimental models that accurately recapitulate genetic events that occur during human epithelial ovarian cancer (EOC) initiation and progression is crucial for a better understanding of EOC pathogenesis, identification of early disease markers, and development of more effective therapy. Historically, one of the most challenging problems in developing genetically engineered mouse models (GEMMs) of EOC has been the lack of tissue‐specific promoters that regulate transgene expression exclusively in adult OSE cells. Recent improvements in gene delivery technology have greatly accelerated development of GEMMs of EOC. This unit describes two distinct methods of transforming OSE cells in GEMMs and the potential applications of these models in oncology drug discovery and development. Curr. Protoc. Pharmacol. 45:14.11. 1‐14.11. 14. © 2009 by John Wiley & Sons, Inc.
Affinity, Specificity, Diversity: A Challenge for the ABC Transporter TAP in Cellular Immunity

The immune system is a perfect piece of machinery that serves only one purpose: to protect and defend our organism. The fact that we are still alive, although surrounded by a hostile environment, demonstrates impressively how well the immune system performs this task. Over the past decades our knowledge about the functions and components of the immune system has increased exponentially. Especially for the humoral immune system and its key players, the antibodies, a detailed knowledge about structure and function as well as regulation and communication between the individual components exists. In case of the cellular immune system that knowledge is not as profound as for the humoral counterpart. In this article we do not intend to give a complete overview about both branches of the immune system. Rather, we want to focus on an essential protein of the cellular immune system, the transporter associated with antigen processing (TAP). This transmembrane protein complex displays unique properties with respect to recognition and translocation of a vast spectrum of antigenic peptides. Its important role within the major histocompatibility complex (MHC) class I mediated immune response has been utilized by some viruses which target TAP to hide and escape from a deadly attack by the immune system. Here we summarize the existing data and analyze structural and mechanistic aspects of recognition and transport by which this transporter performs its task.
From Drinking Group Norms to Individual Drinking Consequences: A Moderated Mediation Model Examining the Role of Members’ Status, Identification with the Group and with Emerging Adulthood

ABSTRACT Background: Emerging adults consume alcohol most often with their peer drinking groups. Yet, little is known about the role of drinking group norms on individual members' drinking consequences, nor about the mechanisms that underlie this association. Objectives: We examined the indirect relationship between drinking group descriptive norms (perceived frequency of group heavy episodic drinking; HED) and individual drinking consequences via individual HED. We also examined key moderators, including the extent to which individuals occupied high status positions within their drinking groups, the strength of their identification with the group, and the degree to which they identified with emerging adulthood, a developmental period associated with heightened alcohol consumption. Methods: Participants were 280 and 340 (replication study) emerging adults (18–29 years) who were recruited via an online crowdsourcing site to complete a survey. Results: Across studies, higher status was associated with more individual HED and drinking consequences. Further, group identification and identification with emerging adulthood strengthened the relation between group and individual HED. Finally, the indirect relation between group HED and individual drinking consequences was significant and stronger for individuals who identified more with their drinking groups and with emerging adulthood. Conclusions/Importance: Findings contribute to a more nuanced understanding of the impact of descriptive peer norms on heavy drinking and related consequences in emerging adulthood and help identify drinking group members most at risk for internalizing descriptive group norms for HED. Key implications for prevention and intervention programming are discussed.