Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNA‐34a is an important component of PRIMA‐1‐induced apoptotic network in human lung cancer cells

Restoration of p53 function in tumor cells would be an attractive strategy for lung cancer therapy because p53 mutations are found in more than 50% of lung cancers. The small molecule PRIMA‐1 has been shown to restore the tumor suppression function of p53 and to induce apoptosis in human tumor cells. The mechanism of apoptosis induced by PRIMA‐1 remains unclear. We investigated the effects of PRIMA‐1 in apoptosis with Western immunoblot analysis, TaqMan microRNA real‐time PCR, cell viability analysis and flow cytometry using human lung cancer cell lines containing mutant (H211 and H1155), wild‐type (A549) or null (H1299) p53. PRIMA‐1 induced massive apoptosis in the H211 and H1155 cells, but was less toxic to the A549 and H1299 cells. Western immunoblot analysis showed cleavage of PARP in H211 and H1155 cells but not in A549 and H1299 cells following treatment with PRIMA‐1. In addition, p53 protein was also phosphorylated in H211 and H1155 cells. TaqMan microRNA assay showed that the expression of microRNA‐34a was increased in the H211 and H1155 cells posttreatment. Knockdown microRNA‐34a decreased the rate of apoptosis caused by PRIMA‐1. The above results suggest that microRNA‐34a is one of the important components of PRIMA‐1‐induced apoptotic network in the cancer cells harboring mutant p53.
Energy consumption analysis of ZigBee-based energy harvesting wireless sensor networks

Energy consumption is one of the most important practical properties for deploying an energy harvesting wireless sensor network. This paper presents the energy consumption analysis of ZigBee-based energy harvesting wireless sensor networks to understand the energy requirements to the energy harvesting technologies from a practical aspect. Three kinds of energy consumption are analyzed to investigate the main factors influencing the design of energy harvesting technology: the energy consumption of end devices and of routers in power up mode, the energy consumption of data transmission with/without application acknowledgement requirements, and the energy consumption of routers supporting different node density. Based on the measurements, the key metrics influencing the lifetime of wireless sensor networks are summarized and an energy consumption model is proposed to evaluate the lifetime of a sensor node. Moreover, the potential energy-saving solutions are discussed for ZigBee-based energy harvesting wireless sensor networks.
EULAR recommendations for the management of large vessel vasculitis

Objectives: To develop European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis. Methods: An expert group (10 rheumatologists, 3 nephrologists, 2 immunolgists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search through a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of large vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. Results: Seven recommendations were made relating to the assessment, investigation and treatment of patients with large vessel vasculitis. The strength of recommendations was restricted by the low level of evidence and EULAR standardised operating procedures. Conclusions: On the basis of evidence and expert consensus, management recommendations for large vessel vasculitis have been formulated and are commended for use in everyday clinical practice.
Low Birth Weight Is Associated With Higher Adult Total Cholesterol Concentration in Men: Findings From an Occupational Cohort of 25 843 Employees

Background—The majority of studies investigating the association between birth weight and adult total cholesterol (TC) concentration have been small and underpowered: not surprisingly, the findings have been inconsistent. We aimed to determine whether birth weight predicted adult TC in a large sample population. Methods and Results—Between 1994 and 1996, 132 000 British Telecom employees undertook voluntary occupational health screening. Birth weight and lifestyle factors were self-reported; TC concentration and body size were measured by occupational health nurses. Complete measurements were available for 18 286 men and 7557 women (age range, 17 to 64 years). We found that sex and birth weight significantly interacted to predict adult TC (birth weight/sex interaction term, P=0.002). In men, lower birth weight was associated with higher adult TC levels (a −0.07 reduction in TC for each 1-kg increase in birth weight; 95% CI, −0.09 to −0.04 mmol/L; P<0.001), whereas no association was observed in women. Adjustment for potential confounding factors, including current body size and menopausal status, did not alter the findings. Analysis by SD score showed that in men, a 1-SD decrease in body mass index lowered TC concentration ≈5-fold more than a 1-SD increase in birth weight. Conclusions—This is the largest study to investigate the association between birth weight and TC and suggests that the association may be dependent on sex. The absence of an association in women was not explained by menopausal status. The influence of fetal environment on adult TC is small compared with the influence of adult adiposity.
In Vivo Gene Transfer Using a Nonprimate Lentiviral Vector Pseudotyped with Ross River Virus Glycoproteins

ABSTRACT Vectors derived from lentiviruses provide a promising gene delivery system. We examined the in vivo gene transfer efficiency and tissue or cell tropism of a feline immunodeficiency virus (FIV)-based lentiviral vector pseudotyped with the glycoproteins from Ross River Virus (RRV). RRV glycoproteins were efficiently incorporated into FIV virions, generating preparations of FIV vector, which after concentration attain titers up to 1.5 × 108 TU/ml. After systemic administration, RRV-pseudotyped FIV vectors (RRV/FIV) predominantly transduced the liver of recipient mice. Transduction efficiency in the liver with the RRV/FIV was ca. 20-fold higher than that achieved with the vesicular stomatitis virus G protein (VSV-G) pseudotype. Moreover, in comparison to VSV-G, the RRV glycoproteins caused less cytotoxicity, as determined from the levels of glutamic pyruvic transaminase and glutamic oxalacetic transaminase in serum. Although hepatocytes were the main liver cell type transduced, nonhepatocytes (mainly Kupffer cells) were also transduced. The percentages of the transduced nonhepatocytes were comparable between RRV and VSV-G pseudotypes and did not correlate with the production of antibody against the transgene product. After injection into brain, RRV/FIV preferentially transduced neuroglial cells (astrocytes and oligodendrocytes). In contrast to the VSV-G protein that targets predominantly neurons, <10% of the brain cells transduced with the RRV pseudotyped vector were neurons. Finally, the gene transfer efficiencies of RRV/FIV after direct application to skeletal muscle or airway were also examined and, although transgene-expressing cells were detected, their proportions were low. Our data support the utility of RRV glycoprotein-pseudotyped FIV lentiviral vectors for hepatocyte- and neuroglia-related disease applications.
Chemotherapy for Endometrial Cancer in Adjuvant and Advanced Disease Settings.

: Level I evidence exists for use of adjuvant chemotherapy in stage IIIC endometrial cancer (positive lymph nodes), although results of randomized trials have varied. Chemotherapy is also often recommended for high-risk subsets of stage I disease, such as serous carcinomas, although prospective trial data to validate this practice are lacking. Carboplatin plus paclitaxel is the current standard regimen, based on extrapolation of data from the metastatic setting. Several clinical trials have compared adjuvant pelvic radiotherapy alone to a combination of radiotherapy and chemotherapy with mixed results. One of the largest of these trials, Postoperative Radiation Therapy in Endometrial Carcinoma 3 (PORTEC-3), has completed accrual and is awaiting data maturation. Metastatic disease is not curable. For tumors of low-grade endometrioid histology with a prolonged time to recurrence, endocrine therapy with a progestin-based regimen is appropriate. Chemotherapy will be used in most other cases, and the standard first-line regimen is carboplatin and paclitaxel. Few chemotherapy agents have been shown to produce meaningful response rates in the second-line setting. Molecularly targeted therapies such as mTOR inhibitors and antiangiogenic agents including bevacizumab have been studied but their role in the armamentarium remains uncertain. IMPLICATIONS FOR PRACTICE Following surgical resection and staging for endometrial cancer, adjuvant chemotherapy with carboplatin and paclitaxel can be administered to patients with a high risk for recurrence. This includes patients with stage IIIC disease with positive lymph nodes, and high-risk subsets of stage I disease such as serous carcinomas. In the metastatic setting, endocrine therapy can be considered, particularly for patients with lower-grade disease and a prolonged time to recurrence. Combined therapy with carboplatin and paclitaxel is the standard of care used for front-line chemotherapy. Antiangiogenic agents are clearly active, but how they should be integrated into treatment is not yet determined. Immunotherapy is a promising direction for patients with mismatch repair-deficient or polymerase ε-mutated tumors.
Validity of hospital admission as an outcome measure of services for first-episode psychosis.

OBJECTIVE The objective of this study was to assess the external validity of hospitalization as an outcome measure for first-episode psychosis services. METHODS A two-year, prospective cohort design was used to examine the associations between hospitalization, general psychopathology, and quality of life in a cohort of 606 participants treated for a first episode of psychosis. RESULTS In bivariate analyses, general psychopathology and quality of life were each significantly associated with hospitalization at both time points. After analyses controlled for all covariates in the logistic models, both clinical measures continued to be significantly correlated with hospitalization at both one and two years. CONCLUSIONS These results validate hospitalization as an outcome measure for first-episode psychosis services, and they extend the existing research showing a relationship between hospitalization and process measures to include other valid and reliable clinical measures.
A study of the effect of diffraction and rough surface scatter modeling on ray tracing results in an urban environment at 60 GHz

Channel characterization is an important step in the design of wireless communication systems. While channel sounding procedures are a useful method in determining channel behavior, they also require expensive and time consuming procedures and equipment. Ray tracing has been an important substitute for measurement in deterministic channel modeling and characterization of the wireless channel. Much has been done to improve the precision and efficiency of this method for lower frequency bands (generally below 5 GHz) over the years. Recently, with the worldwide announcement of a broad unlicensed band in the millimeter wave spectrum around 60 GHz, a great amount of attention has been paid to this frequency band, previously considered un-utilizable ([1, 2]). However some basic dissimilarity between the 60 GHz and UHF bands has brought about the need for modification of the methods previously used. In this paper the focus has been placed on two propagation mechanisms: diffraction and rough surface scattering, and the impact of each on over-all channel response predictions have been investigated.
Convergent repression of Foxp2 3′UTR by miR-9 and miR-132 in embryonic mouse neocortex: implications for radial migration of neurons

MicroRNAs (miRNAs) are rapidly emerging as a new layer of regulation of mammalian brain development. However, most of the miRNA target genes remain unidentified. Here, we explore gene expression profiling upon miRNA depletion and in vivo target validation as a strategy to identify novel miRNA targets in embryonic mouse neocortex. By this means, we find that Foxp2, a transcription factor associated with speech and language development and evolution, is a novel miRNA target. In particular, we find that miR-9 and miR-132 are able to repress ectopic expression of Foxp2 protein by targeting its 3′ untranslated region (3′UTR) in vivo. Interestingly, ectopic expression of Foxp2 in cortical projection neurons (a scenario that mimics the absence of miRNA-mediated silencing of Foxp2 expression) delays neurite outgrowth in vitro and impairs their radial migration in embryonic mouse neocortex in vivo. Our results uncover a new layer of control of Foxp2 expression that may be required for proper neuronal maturation.
Expression of CYP1A1 and CYP1A2 genes in human liver.

Immunoblot analysis of human livers using a monospecific antibody to rat CYP1A2 section demonstrated that the expression of CYP1A2 protein is highly variable in human liver. Quantitative PCR analysis was then employed to examine the interindividual variability of both CYP1A1 and CYP1A2 mRNAs in human liver. Hepatic content of CYP1A2 mRNA correlated significantly with levels of CYP1A2 protein as analysed by immunoblot analysis (r = 0.58; p < 0.01). CYP1A2 mRNA content varied > 40-fold among individuals while CYP1A1 content varied > 20-fold. CYP1A2 mRNA was higher than CYP1A1 mRNA (approximately two to 30-fold) in livers of different individuals. The individual with the highest CYP1A1 and CYP1A2 mRNA amounts was a current smoker, but mRNA expression in two other smokers was within the range observed among nonsmokers. The expression of the two CYP1A mRNAs correlated highly (r = 0.72; p < 0.0005) when smokers were included, but the correlation was less significant (r = 0.62; p < 0.05) in nonsmokers. We amplified a full-length CYP1A2 cDNA clone by PCR from a liver which expressed extremely low amounts of CYP1A2 protein. Sequence analysis indicated that exon 4 was missing in this clone, but no other sequence changes were found. PCR analysis demonstrated that both the normally spliced mRNA and abnormally spliced mRNA could be detected in all human livers examined, but the normally spliced mRNA was more abundant than the splice variant. Therefore, sequence changes in the coding region of CYP1A2 did not account for the poor expression of CYP1A2 in this individual.
Gating of nicotinic ACh receptors; new insights into structural transitions triggered by agonist binding that induce channel opening

Nicotinic acetylcholine receptors (nAChRs) are in the superfamily of Cys‐loop ligand‐gated ion channels, and are pentameric assemblies of five subunits, with each subunit arranged around the central ion‐conducting pore. The binding of ACh to the extracellular interface between two subunits induces channel opening. With the recent 4 Å resolution of the Torpedo nAChR, and the crystal structure of the related molluscan ACh binding protein, much has been learned about the structure of the ligand binding domain and the channel pore, as well as major structural rearrangements that may confer channel opening. For example, the putative pathway coupling agonist binding to channel gating may include a major rearrangement of the C‐loop within the ligand binding pocket, and the disruption of a salt bridge between an arginine residue at the end of the β10 strand and a glutamate residue in the β1–β2 linker. Here we will review and discuss the latest structural findings aiming to further refine the transduction pathway linking binding to gating for the nAChR channels, and discuss similarities and differences among the different members of this Cys‐loop superfamily of receptors.
Privacy-Preserving Interest Matching for Mobile Social Networking

The success of online social networking has resulted in increased attention to mobile social networking research and applications. In mobile social networking, instead of looking for friends over the Internet, people look for friends who are physically located close and also based on other self-defined criteria. For example, a person could find other people who are nearby and who also share the same interests with her by using mobile social networking. As a result, they have common topics to talk about and may eventually become friends. There are two main approaches in the existing works. One approach focuses on efficiently establishing friendship and ignores the protection of private information of the participants. For example, some applications simply broadcast users’ personal information to everybody and rely on the other users to report the matches. From a privacy point of view, this approach is bad, since it makes the users vulnerable to context-aware attacks. The other approach requires a central server to participate in each matchmaking process. For example, an application deploys a central server, which stores the profile information of all users. When two nearby client devices query the central server at the same time, the central server fetches the profile information of both devices from the server’s database, performs matching based on the information, and reports the result back to the clients. However, a central server is not always available, so this approach does not scale. In addition, the central server not only learns all users’ personal information, it also learns which users become friends. This thesis proposes a privacy-preserving architecture for users to find potential friends with the same interests. The architecture has two matchmaking protocols to prevent privacy leaks. Our protocols let a user learn only the interests she has in common with the other party. One protocol is simpler, but works only if some assumptions hold. The other protocol is more secure, but requires longer execution time. Our architecture does not require any central server that is involved in the matchmaking process. We describe how the protocols work, analyze how secure the protocols are under different assumptions, and implement the protocols in a BlackBerry application. We test the efficiency of the protocols by conducting a number of experiments. We also consider the cheating-detection and friend-recognition problems.
Effects of Obsessive-Compulsive Symptoms on Neuropsychological Test Performance: Complicating an Already Complicated Story

Theoretical models of obsessive-compulsive disorder (OCD) implicate neurocognitive dysfunction, particularly deficits in nonverbal memory and executive functioning, in the pathogenesis of the disorder. The opposite hypothesis (poor performance in neuropsychological test as an epiphenomenon of OCD symptoms) has rarely been contemplated although checking behavior, obsessional doubt, lack of motivation, and slowness as well as preoccupation with touching objects may result in secondary test impairment and mimic manifestations of neural dysfunction. A total of 60 patients with OCD and 30 healthy controls were tested with a multi-functional neuropsychological battery. At the end of the testing participants were asked about their effort and the severity of OCD symptoms during task execution. Up to one fourth of the OCD patients affirmed OCD-related worries and motivational problems during task execution. Poor motivation and checking were significantly associated with enhanced objective performance deficits. Whereas the present study does not negate a role of neurocognitive deficits in the formation of OCD, in our view the reverse relationship should be contemplated as well. We advise researchers to pay closer attention to possible confounds that may mediate the relationship between OCD and neurocognition. Limitations of the study are discussed.
Signaling events underlying thrombus formation

Summary. Recent in vivo studies have highlighted the dynamic and complex nature of platelet thrombus growth and the requirement for multiple adhesive receptor–ligand interactions in this process. In particular, the importance of von Willebrand factor (VWF) in promoting both primary adhesion and aggregation under high shear conditions is now well established. In general, the efficiency with which platelets adhere and aggregate at sites of vessel wall injury is dependent on the synergistic action of various adhesive and soluble agonist receptors, with the contribution of each of the individual receptors dependent on the prevailing blood flow conditions. In this review, we will discuss the major platelet adhesive interactions regulating platelet thrombus formation under high shear, with specific focus on the VWF (GPIb and integrin αIIbβ3) and collagen receptors (GPVI and integrin α2β1). We will also discuss the signaling mechanisms utilized by these receptors to induce platelet activation with specific emphasis on the role of cytosolic calcium flux in regulating platelet adhesion dynamics. The role of soluble agonists in promoting thrombus growth will be highlighted and a model to explain the synergistic requirement for adhesive and soluble stimuli for efficient platelet aggregation will be discussed.
Potentiation of Endothelium‐Dependent Hyperpolarization to Serotonin by Dietary Intake of NC 020, a Defined Fish Oil, in the Porcine Coronary Artery

The membrane potential of vascular smooth muscle cells of the porcine coronary artery was measured to examine whether serotonin evokes endothelium-dependent hyperpolarization, and if it does, whether the electrical responses are modulated by the chronic dietary intake of NC 020, a defined fish oil. Serotonin induced transient, concentration-dependent hyperpolarizations of coronary arterial smooth muscle cells. The hyperpolarization was observed in tissues with, but not in those without endothelium. In coronary arteries obtained from pigs fed chronically with NC 020, serotonin induced significantly larger hyperpolarizations than those observed in control arteries. These results suggest that endothelium-dependent hyperpolarization may contribute to the endothelium-dependent relaxation evoked by serotonin and to its potentiation by the dietary intake of fish oil (NC 020).
Role of Host Nutrition in Symbiont Regulation: Impact of Dietary Nitrogen on Proliferation of Obligate and Facultative Bacterial Endosymbionts of the Pea Aphid Acyrthosiphon pisum

ABSTRACT The impact of host nutrition on symbiont regulation in the pea aphid Acyrthosiphon pisum was investigated. The population density of the obligate symbiont Buchnera aphidicola positively correlated with dietary nitrogen levels. In contrast, the population density of the facultative symbiont Serratia symbiotica increased in aphids reared on low-nitrogen diets, indicating distinct regulatory mechanisms in the same insect host.