Miracle-dz/UniFAR-FTUs huggingface dataset:
Overexpression of Oncoprotein 18 Correlates with Poor Differentiation in Lung Adenocarcinomas*

We examined the expression of oncoprotein 18 (Op18) in 93 lung adenocarcinomas and 10 uninvolved lung samples using quantitative two-dimensional PAGE analysis with confirmation by mass spectrometry and two-dimensional Western blot analysis. mRNA expression was examined using oligonucleotide microarrays, and the cellular localization of the Op18 protein was examined using immunohistochemical analysis of tissue microarrays. Three phosphorylated forms and one unphosphorylated form of the Op18 protein were identified and found to be overexpressed in lung adenocarcinomas as compared with normal lung. The percentage of phosphorylated to total Op18 protein isoforms increased from 3.2% in normal lung to 7.9% in lung tumors. Both the phosphorylated and unphosphorylated Op18 proteins were significantly increased in poorly differentiated tumors as compared with moderately or well differentiated lung adenocarcinomas (p < 0.03), suggesting that up-regulated expression of Op18 reflects a poor differentiation status and higher cell proliferation rates. This was further verified in A549 and SKLU1 lung adenocarcinoma cell lines by examining Op18 levels and phosphorylation status following treatment that altered either cell proliferation or differentiation. The increased expression of Op18 protein was significantly correlated with its mRNA level indicating that increased transcription likely underlies elevated expression of Op18. The overexpression of Op18 proteins in poorly differentiated lung adenocarcinomas and the elevated expression of the phosphorylated forms of Op18 may offer a new target for drug- or gene-directed therapy and may have potential utility as a tumor marker.
Phosphoenolpyruvate Carboxykinase Is Necessary for the Integration of Hepatic Energy Metabolism

ABSTRACT We used an allelogenic Cre/loxP gene targeting strategy in mice to determine the role of cytosolic phosphoenolpyruvate carboxykinase (PEPCK) in hepatic energy metabolism. Mice that lack this enzyme die within 3 days of birth, while mice with at least a 90% global reduction of PEPCK, or a liver-specific knockout of PEPCK, are viable. Surprisingly, in both cases these animals remain euglycemic after a 24-h fast. However, mice without hepatic PEPCK develop hepatic steatosis after fasting despite up-regulation of a variety of genes encoding free fatty acid-oxidizing enzymes. Also, marked alterations in the expression of hepatic genes involved in energy metabolism occur in the absence of any changes in plasma hormone concentrations. Given that a ninefold elevation of the hepatic malate concentration occurs in the liver-specific PEPCK knockout mice, we suggest that one or more intermediary metabolites may directly regulate expression of the affected genes. Thus, hepatic PEPCK may function more as an integrator of hepatic energy metabolism than as a determinant of gluconeogenesis.
A cancer gene therapy approach utilizing an anti-erbB-2 single-chain antibody-encoding adenovirus (AD21): a phase I trial.

The purpose of this Phase I study was to determine the feasibility of using an anti-erbB-2-encoding adenovirus (Ad21) to treat erbB-2-overexpressing ovarian cancer. Recurrent ovarian cancer patients were treated i.p. with Ad21 in dosages ranging from 1 x 10(9) to 1 x 10(11) pfu. Patients were monitored after treatment for evidence of clinical toxicity and efficacy. Peritoneal aspirates and serum samples were obtained to assess for evidence of gene transfer/expression, for generation of wild-type vector, and antiadenoviral humoral response. Fifteen patients were treated per study specifications. Treatment-specific grade 1/2 fever was experienced by 9 of 15 (60%) patients. Other transient grade 1/2 constitutional, pain, and gastrointestinal symptoms were also experienced. No dose-limiting vector-related toxicity was experienced. Of 13 patients evaluable for response, 5 (38%) had stable disease and 8 (61%) had evidence of progressive disease. One patient with nonmeasurable disease normalized her CA125 at the 8-week evaluation, and one patient with nonmeasurable disease remained without clinical evidence of disease for 6 months after treatment. PCR analysis of peritoneal aspirates demonstrated the presence of Ad21 in 84.6%, 84.6%, and 61.6% of evaluable specimens at days 2, 14, and 56 after treatment, respectively. No wild-type virus was detected. Reverse transcription-PCR analysis demonstrated expression of the anti-erbB-2 sFv-encoding gene in 10 of 14 evaluable patients at day 2. Five of six evaluable patients had an increase in antiadenovirus antibody titer. This study suggests that adenoviral-mediated gene therapy using an anti-erbB-2-directed intrabody is feasible in the context of human ovarian cancer.
STAT1 deficiency unexpectedly and markedly exacerbates the pathophysiological actions of IFN-α in the central nervous system

Although signal transducer and activator of transcription 1 (STAT1) is an essential signaling molecule in many IFN-α-regulated processes, some biological responses to IFN-α can occur independently of STAT1. To establish the role of STAT1 in mediating the biological actions of IFN-α in the CNS, transgenic mice [termed glial fibrillary acidic protein (GFAP)-IFN-α] with astrocyte production of IFN-α were bred to be null for the STAT1 gene. Surprisingly, GFAP-IFN-α mice deficient for STAT1 developed earlier onset and more severe neurological disease with increased lethality compared with GFAP-IFN-α mice sufficient for STAT1. Whereas the brain of 2- to 3-month-old GFAP-IFN-α mice showed little, if any abnormality, the brain from GFAP-IFN-α mice deficient for STAT1 had severe neurodegeneration, inflammation, calcification with increased apoptosis, and glial activation. However, the cerebral expression of a number of IFN-regulated STAT1-dependent genes increased in GFAP-IFN-α mice but was reduced markedly in GFAP-IFN-α STAT1-null mice. Of many other signaling molecules examined, STAT3 alone was activated significantly in the brain of GFAP-IFN-α STAT1-null mice. Thus, in the absence of STAT1, alternative signaling pathways mediate pathophysiological actions of IFN-α in the living brain, giving rise to severe encephalopathy. Finally, STAT1 or a downstream component of the JAK/STAT pathway may protect against such IFN-α-mediated injury in the CNS.
Gamma-Ray Computed Tomography in Soil Science: Some Applications

The first computed tomography (CT) apparatus was developed by Godfrey Hounsfield, at the beginning of the seventies of the last century (Hounsfield, 1973). For its development Hounsfield and Allan M. Cormack (Cormack, 1963), who developed the mathematical basis of image reconstruction, were rewarded by the Nobel Prize in medicine in 1979. Cormack’s developments were basically focused in the reconstruction of bodies with geometries with no medical interest, like for instance, the human head. After these first developments, some CT scanners were developed and gradually introduced into other areas of knowledge like engineering, agronomy, biology, physics, chemistry, etc. Most of the modern scanners make use of gamma and X-ray sources. However some instruments make use of neutron and positron ray sources. Recent developments describe the use of synchrotron X-ray beams to investigate fluid transport at the pore scale (Coles et al., 1998). Some other applications of CT involve: investigation on morphological changes in small animals (Stenstrom et al., 1998); determination of soil macroporosity by chemical mapping (Brandsma et al., 1999); and dental analysis of the anatomy and some restorative materials through X-ray microtomography (Braz et al., 2001). More recently, Vontobel et al. (2006) and Winkler et al. (2006) presented the use of neutron tomography to investigate the morphology or structure of rocks and metal melts. CT allowed demonstrating the behaviour of metal melts with different densities. Voronov et al. (2010) used the micro CT (with micrometric resolution) to analyze the distribution of flow-induced stresses in highly porous media of interest for bioengineering. Flow-induced stresses have been found to stimulate the growth of cells. Reports describing the use of the CT in soil science were published few years later of the invention of the first tomography scanner system by Hounsfield. Petrovic et al. (1982) followed by Hainsworth and Aylmore (1983) and Crestana et al. (1985) successfully reported the use of CT scanners for soil bulk density studies, soil water content and water movement measurements. CT is a non destructive and non invasive investigation technique used to assess some attributes in the interior of an object of interest. It is essentially based on the principle of the attenuation of an electromagnetic radiation beam by the object. CT technique has been well
In Silico Assigned Resistance Genes Confer Bifidobacterium with Partial Resistance to Aminoglycosides but Not to Β-Lactams

Bifidobacteria have received significant attention due to their contribution to human gut health and the use of specific strains as probiotics. It is thus not surprising that there has also been significant interest with respect to their antibiotic resistance profile. Numerous culture-based studies have demonstrated that bifidobacteria are resistant to the majority of aminoglycosides, but are sensitive to β-lactams. However, limited research exists with respect to the genetic basis for the resistance of bifidobacteria to aminoglycosides. Here we performed an in-depth in silico analysis of putative Bifidobacterium-encoded aminoglycoside resistance proteins and β-lactamases and assess the contribution of these proteins to antibiotic resistance. The in silico-based screen detected putative aminoglycoside and β-lactam resistance proteins across the Bifidobacterium genus. Laboratory-based investigations of a number of representative bifidobacteria strains confirmed that despite containing putative β-lactamases, these strains were sensitive to β-lactams. In contrast, all strains were resistant to the aminoglycosides tested. To assess the contribution of genes encoding putative aminoglycoside resistance proteins in Bifidobacterium sp. two genes, namely Bbr_0651 and Bbr_1586, were targeted for insertional inactivation in B. breve UCC2003. As compared to the wild-type, the UCC2003 insertion mutant strains exhibited decreased resistance to gentamycin, kanamycin and streptomycin. This study highlights the associated risks of relying on the in silico assignment of gene function. Although several putative β-lactam resistance proteins are located in bifidobacteria, their presence does not coincide with resistance to these antibiotics. In contrast however, this approach has resulted in the identification of two loci that contribute to the aminoglycoside resistance of B. breve UCC2003 and, potentially, many other bifidobacteria.
Single-crystal α-MnO2 nanorods: synthesis and electrochemical properties

Single-crystal α-MnO2 nanorods were prepared by hydrothermal reaction of single KMnO4 under acidic conditions. The nanorods have a diameter of 30–70 nm and a length up to 2 µm. The formation mechanism for the α-MnO2 nanorods was investigated. Electrochemical properties of the MnO2 nanomaterials prepared for different hydrothermal times were characterized by galvanostatic charge/discharge tests and cyclic voltammetry (CV) studies. The results indicate that the MnO2 nanorods prepared for 5 and 8 h show fine capacitive behaviour with high specific capacitances of 71.1 and 70.9 F g−1, respectively.
Long-range projection neurons of the mouse ventral tegmental area: a single-cell axon tracing analysis

Pathways arising from the ventral tegmental area (VTA) release dopamine and other neurotransmitters during the expectation and achievement of reward, and are regarded as central links of the brain networks that create drive, pleasure, and addiction. While the global pattern of VTA projections is well-known, the actual axonal wiring of individual VTA neurons had never been investigated. Here, we labeled and analyzed the axons of 30 VTA single neurons by means of single-cell transfection with the Sindbis-pal-eGFP vector in mice. These observations were complemented with those obtained by labeling the axons of small populations of VTA cells with iontophoretic microdeposits of biotinylated dextran amine. In the single-cell labeling experiments, each entire axonal tree was reconstructed from serial sections, the length of terminal axonal arbors was estimated by stereology, and the dopaminergic phenotype was tested by double-labeling for tyrosine hydroxylase immunofluorescence. We observed two main, markedly different VTA cell morphologies: neurons with a single main axon targeting only forebrain structures (FPN cells), and neurons with multibranched axons targeting both the forebrain and the brainstem (F + BSPN cells). Dopaminergic phenotype was observed in FPN cells. Moreover, four “subtypes” could be distinguished among the FPN cells based on their projection targets: (1) “Mesocorticolimbic” FPN projecting to both neocortex and basal forebrain; (2) “Mesocortical” FPN innervating the neocortex almost exclusively; (3) “Mesolimbic” FPN projecting to the basal forebrain, accumbens and caudateputamen; and (4) “Mesostriatal” FPN targeting only the caudateputamen. While the F + BSPN cells were scattered within VTA, the mesolimbic neurons were abundant in the paranigral nucleus. The observed diversity in wiring architectures is consistent with the notion that different VTA cell subpopulations modulate the activity of specific sets of prosencephalic and brainstem structures.
The Assembly of the Plasmodial PLP Synthase Complex Follows a Defined Course

Background Plants, fungi, bacteria and the apicomplexan parasite Plasmodium falciparum are able to synthesize vitamin B6 de novo, whereas mammals depend upon the uptake of this essential nutrient from their diet. The active form of vitamin B6 is pyridoxal 5-phosphate (PLP). For its synthesis two enzymes, Pdx1 and Pdx2, act together, forming a multimeric complex consisting of 12 Pdx1 and 12 Pdx2 protomers. Methodology/Principal Findings Here we report amino acid residues responsible for stabilization of the structural and enzymatic integrity of the plasmodial PLP synthase, identified by using distinct mutational analysis and biochemical approaches. Residues R85, H88 and E91 (RHE) are located at the Pdx1:Pdx1 interface and play an important role in Pdx1 complex assembly. Mutation of these residues to alanine impedes both Pdx1 activity and Pdx2 binding. Furthermore, changing D26, K83 and K151 (DKK), amino acids from the active site of Pdx1, to alanine obstructs not only enzyme activity but also formation of the complex. In contrast to the monomeric appearance of the RHE mutant, alteration of the DKK residues results in a hexameric assembly, and does not affect Pdx2 binding or its activity. While the modelled position of K151 is distal to the Pdx1:Pdx1 interface, it affects the assembly of hexameric Pdx1 into a functional dodecamer, which is crucial for PLP synthesis. Conclusions/Significance Taken together, our data suggest that the assembly of a functional Pdx1:Pdx2 complex follows a defined pathway and that inhibition of this assembly results in an inactive holoenzyme.
Complex resonances and trapped modes in ducted domains

Owing to radiation losses, resonances in open systems, i.e. solution domains which extend to infinity in at least one direction, are generally complex valued. However, near symmetric centred objects in ducted domains, or in periodic arrays, so-called trapped modes can exist below the cut-off frequency of the first non-trivial duct mode. These trapped modes have no radiation loss and correspond to real-valued resonances. Above the first cut-off frequency isolated trapped modes exist only for specific parameter combinations. These isolated trapped modes are termed embedded, because their corresponding eigenvalues are embedded in the continuous spectrum of an appropriate differential operator. Trapped modes are of considerable importance in applications because at these parameters the system can be excited easily by external forcing. In the present paper directly computed embedded trapped modes are compared with numerically obtained resonances for several model configurations. Acoustic resonances are also computed in two-dimensional models of a butterfly and a ball-type valve as examples of more complicated geometries.
A Comparative Analysis of Methods for Pruning Decision Trees

In this paper, we address the problem of retrospectively pruning decision trees induced from data, according to a top-down approach. This problem has received considerable attention in the areas of pattern recognition and machine learning, and many distinct methods have been proposed in literature. We make a comparative study of six well-known pruning methods with the aim of understanding their theoretical foundations, their computational complexity, and the strengths and weaknesses of their formulation. Comments on the characteristics of each method are empirically supported. In particular, a wide experimentation performed on several data sets leads us to opposite conclusions on the predictive accuracy of simplified trees from some drawn in the literature. We attribute this divergence to differences in experimental designs. Finally, we prove and make use of a property of the reduced error pruning method to obtain an objective evaluation of the tendency to overprune/underprune observed in each method.
Carbamazepine‐induced anticonvulsant hypersensitivity syndrome—pathogenic and diagnostic considerations

Two epileptic patients developed an infectious mononucleosis‐like illness which subsequently proved to be a carbamazepine‐induced anticonvulsant hypersensitivity syndrome. Patch testing to carbamazepine 3 years later was positive in the one patient tested and negative in normal controls. The second patient died a few weeks after the illness, secondary to long‐standing cardiac disease without having undergone patch testing. A skin biopsy was, however, consistent with an immune complex mediated drug reaction. Patch testing for systemically administered drugs is generally believed to be of little value in diagnosing drug allergies. However, we reinforce a previous suggestion that this investigation may be helpful in some cases of anticonvulsant hypersensitivity syndrome caused by carbamazepine.1 The pathogenic role of type 3 and 4 hypersensitivity is also discussed.
Securing Android

Recent years have seen a global adoption of smart mobile devices, particularly those based on Android. However, Android’s widespread adoption is marred with increasingly rampant malware threats. This article gives a survey and taxonomy of existing works that secure Android devices. Based on Android app deployment stages, the taxonomy enables us to analyze schemes that share similar objective and approach and to inspect their key differences. Additionally, this article highlights the limitations of existing works and current challenges. It thus distills the state of the art in Android security research and identifies potential research directions for safeguarding billions (and keep counting) of Android-run devices.
Mechanism of bending with kinking of a single-walled carbon nanotube

This paper explores the mechanism of bending with kinking of a long single-walled carbon nanotube under pure bending with moderate bending angles. The prebuckling response was modeled using the existing continuum mechanics theory accounting for the ovalization of the cross section. The post-buckling behavior was characterized by the development of an elastic kink mechanism, considering the van der Waals force. It was found that the post-buckling strain energy increases almost linearly with the bending angle. The van der Waals force facilitates the kink development and its effect becomes more pronounced at large bending angles.
MicroRNA-218 Regulates Vascular Patterning by Modulation of Slit-Robo Signaling

Rationale: Establishment of a functional vasculature requires the interconnection and remodeling of nascent blood vessels. Precise regulation of factors that influence endothelial cell migration and function is essential for these stereotypical vascular patterning events. The secreted Slit ligands and their Robo receptors constitute a critical signaling pathway controlling the directed migration of both neurons and vascular endothelial cells during embryonic development, but the mechanisms of their regulation are incompletely understood. Objective: To identify microRNAs regulating aspects of the Slit-Robo pathway and vascular patterning. Methods and Results: Here, we provide evidence that microRNA (miR)-218, which is encoded by an intron of the Slit genes, inhibits the expression of Robo1 and Robo2 and multiple components of the heparan sulfate biosynthetic pathway. Using in vitro and in vivo approaches, we demonstrate that miR-218 directly represses the expression of Robo1, Robo2, and glucuronyl C5-epimerase (GLCE), and that an intact miR-218–Slit–Robo regulatory network is essential for normal vascularization of the retina. Knockdown of miR-218 results in aberrant regulation of this signaling axis, abnormal endothelial cell migration, and reduced complexity of the retinal vasculature. Conclusions: Our findings link Slit gene expression to the posttranscriptional regulation of Robo receptors and heparan sulfate biosynthetic enzymes, allowing for precise control over vascular guidance cues influencing the organization of blood vessels during development.
Atlas of Genetics and Cytogenetics in Oncology and Haematology

D40/CASC5 mRNA expression is dominant in normal human testis and slight expression are observed in other organs, such as placenta. At least two alternative isoforms of cDNA were identified. Northern blotting analysis on testis shows two band s with size of approximately 6 and 8.5 kb which are probably derived from the two isoforms. Analysis on cancer cell lines, such as HeLa, gave single band w ith 8.5 kb. There is another alternative splicing site at the 5’ side of this gene that generates a short exon wi th 78 bp in cDNA. There are potential other alternative splicing at c ancer cell lines.