Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of c-MYC and E2F1 Gene Silencing and of 5-Azacytidine Treatment on Telomerase Activity in Pancreatic Cancer-Derived Cell Lines

Background: The gene promoter region of human telomerase reverse transcriptase (hTERT) contains binding sites for c-myc and E2F1 as well as CpG islands, suggesting regulation by genetic factors and epigenetically by methylation. Hence, the effect of the demethylating agent 5-azacytidine and silencing of c-MYC and E2F1 genes on its expression and consequently on telomerase activity were studied in pancreatic cancer-derived cell lines. Methods: MIaPaCa-2 and PANC-1 cell lines were transfected with SiRNA against E2F1 and c-MYC genes separately as well as along with 5-azacytidine treatment. The hTERT gene methylation status was determined by methylation-specific PCR and telomerase activity quantitated by TRAP-PCR-ELISA. Results: Demethylation by 5-azacytidine resulted in hTERT inhibition with a reduction in telomerase activity to 37–49% of controls. Silencing of E2F-1 or c-MYC also decreased the hTERT transcript and telomerase activity with a more pronounced effect with respect to c-MYC silencing. There was a synergistic effect of demethylation and gene silencing on the inhibition of hTERT mRNA expression which resulted in undetectable levels of telomerase activity. Conclusion: Telomerase activity, which is necessary for cellular immortalization, can be shut down by a combined approach using SiRNA-mediated gene silencing and demethylating agents, which has therapeutic implications.
WKB wave functions with the induced gravity theory

The Wheeler–DeWitt equation for the induced gravity theory is constructed in the mini superspace approximation, and then solved using the WKB method under three types of boundary condition proposed respectively by Hartle & Hawking ("no boundary"), Linde and Vilenkin ("tunneling from nothing"). It is found that no matter how the gravitational and cosmological "constants" vary in the classical models, they will acquire constant values when the universe comes from quantum creation, and that, in particular, the resulting tunneling wave function under the Linde or Vilenkin boundary condition reaches its maximum value if the cosmological constant vanishes.
Investigation of the accuracy and roughness in the laser powder bed fusion process

ABSTRACT Laser powder bed fusion (L-PBF) process has had a rapid growth in the industrial fields because of the capability to manufacture metallic complex shapes. The purpose of this study is to investigate the accuracy and surface roughness of parts manufactured by L-PBF in the AlSi10Mg alloy. The results showed that the choice of parameters of conversion from the CAD model to STL file and the setting of process parameters can affect the accuracy. In the L-PBF process, the staircase effect, inherent in additive manufacturing technologies due to the layered nature of the process, is not visible due to the melting of thin layers of metal powder. The surface roughness is mainly caused by the process parameters, orientation and position of the part with respect to the recoating blade and by the presence of partially fused particles that adhere to the molten part.
Cch1 and Mid1 Are Functionally Required for Vegetative Growth under Low-Calcium Conditions in the Phytopathogenic Ascomycete Botrytis cinerea

ABSTRACT In the filamentous phytopathogen Botrytis cinerea, the Ca2+/calcineurin signaling cascade has been shown to play an important role in fungal growth, differentiation, and virulence. This study deals with the functional characterization of two components of this pathway, the putative calcium channel proteins Cch1 and Mid1. The cch1 and mid1 genes were deleted, and single and double knockout mutants were analyzed during different stages of the fungal life cycle. Our data indicate that Cch1 and Mid1 are functionally required for vegetative growth under conditions of low extracellular calcium, since the growth of both deletion mutants is strongly impaired when they are exposed to the Ca2+-chelating agents EGTA and 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA). The impact of external Ca2+ was investigated by supplementing with CaCl2 and the ionophore A23187, both of which resulted in elevated growth for all mutants. However, deletion of either gene had no impact on germination, sporulation, hyphal morphology, or virulence. By use of the aequorin reporter system to measure intracellular calcium levels, no differences between the mutant strains and the wild type were obtained. Localization studies revealed a subcellular distribution of the Mid1–green fluorescent protein (GFP) fusion protein in network-like filaments, probably the endoplasmic reticulum (ER) membranes, indicating that Mid1 is not a plasma membrane-located calcium channel in B. cinerea.
Spectral Theory of Laplace and Schrödinger Operators ( 13 w 5059 )

Geometrically sharp “isoperimetric” estimates on eigenvalues of the Laplacian and the Schrödinger operator help us understand how frequencies and energies of physical systems are constrained by the shape and size of the domain in which the physical process takes place. For example, the Faber–Krahn inequality (Rayleigh’s conjecture) tells us precisely how low the frequency of a drum can be, if the area of the drumhead is given but we are free to choose its shape. In three dimensions, the same inequality tells us the minimal energy a quantum particle can possess when it is confined to a region of given volume. The minimum is attained in each case by a domain with symmetry — the disk in two dimensions, and the ball in three dimensions. Let us describe some recent progress and notable open problems that were presented both formally and informally during the Workshop.
Monadic encapsulation in ML

In a programming language with procedures and assignments, it is often important to isolate uses of state to particular program fragments. The frameworks of type, region, and effect inference, and monadic state are technologies that have been used to state and enforce the property that an expression has no visible side-effects. This property has been exploited to justify the deallocation of memory regions despite the presence of dangling pointers. Starting from an idea developed in the context of monadic state in flaskelI, we develop an ML-like language with full assignments and an operator that enforces the encapsulation of effects. Using this language, we formalize and prove the folklore connection between effect masking and monadic encapsulation. Then, by employing a novel set of reductions to deal with dangling pointers, we establish the soundness of the type-based encapsulation with a proof based on a standard subject reduction argument.
Compound K, a Metabolite of Ginseng Saponin, Induces Mitochondria-Dependent and Caspase-Dependent Apoptosis via the Generation of Reactive Oxygen Species in Human Colon Cancer Cells

The objective of this study was to elucidate the cytotoxic mechanism of Compound K, with respect to the involvement of reactive oxygen species (ROS) and the mitochondrial involved apoptosis, in HT-29 human colon cancer cells. Compound K exhibited a concentration of 50% growth inhibition (IC50) at 20 μg/mL and cytotoxicity in a time dependent manner. Compound K produced intracellular ROS in a time dependent fashion; however, N-acetylcysteine (NAC) pretreatment resulted in the inhibition of this effect and the recovery of cell viability. Compound K induced a mitochondria-dependent apoptotic pathway via the modulation of Bax and Bcl-2 expressions, resulting in the disruption of the mitochondrial membrane potential (Δψm). Loss of the Δψm was followed by cytochrome c release from the mitochondria, resulting in the activation of caspase-9, -3, and concomitant poly ADP-ribosyl polymerase (PARP) cleavage, which are the indicators of caspase-dependent apoptosis. The apoptotic effect of Compound K, exerted via the activation of c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), was abrogated by specific MAPK inhibitors. This study demonstrated that Compound K-mediated generation of ROS led to apoptosis through the modulation of a mitochondria-dependent apoptotic pathway and MAPK pathway.
Automatic toolset for fault tolerant design: results demonstration on a running industrial application

This paper describes an automatic toolset to validate fault tolerant designs. The toolset has been produced as a demonstrator for the AMATISTA European project (IST project 11762), to test the effectiveness of the new FT (Fault Tolerant) tools, developed as the main target of the project. The toolset has been applied on a typical automotive application already modified by the insertion of FT structures. This paper describes the set-up of the demonstrator and the significant results obtained.
Highly Specific Alternative Splicing of Transcripts Encoding BK Channels in the Chicken's Cochlea Is a Minor Determinant of the Tonotopic Gradient

ABSTRACT The frequency sensitivity of auditory hair cells in the inner ear varies with their longitudinal position in the sensory epithelium. Among the factors that determine the differential cellular response to sound is the resonance of a hair cell's transmembrane electrical potential, whose frequency correlates with the kinetic properties of the high-conductance Ca2+-activated K+ (BK) channels encoded by a Slo (kcnma1) gene. It has been proposed that the inclusion of specific alternative axons in the Slo transcripts along the cochlea underlies the gradient of BK-channel kinetics. By analyzing the complete sequences of chicken Slo gene (cSlo) cDNAs from the chicken's cochlea, we show that most transcripts lack alternative exons. Transcripts with more than one alternative exon constitute only 10% of the total. Although the fraction of transcripts containing alternative exons increases from the cochlear base to the apex, the combination of alternative exons is not regulated. There is also a clear increase in the expression of BK transcripts with long carboxyl termini toward the apex. When long and short BK transcripts are expressed in HEK-293 cells, the kinetics of single-channel currents differ only slightly, but they are substantially slowed when the channels are coexpressed with the auxiliary β subunit that occurs more widely at the apex. These results argue that the tonotopic gradient is not established by the selective inclusion of highly specific cSlo exons. Instead, a gradient in the expression of β subunits slows BK channels toward the low-frequency apex of the cochlea.
Set theory

0009 Most mathematicians think of set theory as providing the basic foundations for mathematics. So how does this really work? For example, how do we translate the sentence “X is a scheme” into set theory? Well, we just unravel the definitions: A scheme is a locally ringed space such that every point has an open neighbourhood which is an affine scheme. A locally ringed space is a ringed space such that every stalk of the structure sheaf is a local ring. A ringed space is a pair (X,OX) consisting of a topological space X and a sheaf of rings OX on it. A topological space is a pair (X, τ) consisting of a set X and a set of subsets τ ⊂ P(X) satisfying the axioms of a topology. And so on and so forth.
Extracorporeal Shock Wave Therapy Combined with Vascular Endothelial Growth Factor-C Hydrogel for Lymphangiogenesis

Background/Aims: Lymphedema is a clinically incurable disease that occurs commonly after lymph node dissection and/or irradiation. Several studies have recently demonstrated that extracorporeal shock wave therapy (ESWT) could promote lymphangiogenesis associated with expression of vascular endothelial growth factor (VEGF)-C. This research concerned primarily the synergistic effect of ESWT combined with VEGF-C incorporated hydrogel (VEGF-C hydrogel) combination therapy for promoting lymphangiogenesis and ultimately alleviating lymphedema. Methods: The VEGF-C hydrogel was applied to the injury site in a mouse model of lymphedema and then regularly underwent ESWT (0.05 mJ/mm2, 500 shots) every 3 days for 4 weeks. Results: Four weeks after the treatment, mice treated with VEGF-C hydrogel and ESWT showed signs of the greatest decrease in edema/collagenous deposits when compared with the other experimental group. LYVE-1-positive vessels also revealed that the VEGF-C/ESWT group had significantly induced the growth of new lymphatic vessels compared to the other groups. Western blot analysis showed that expression of VEGF-C (1.24-fold) and VEGF receptor-3 (1.41-fold) was significantly increased in the VEGF-C/ESWT group compared to the normal group. Conclusion: These results suggested that VEGF-C and ESWT had a synergistic effect and were very effective in alleviating the symptoms of lymphedema and promoting lymphangiogenesis.
[Psychology of the child].

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Perioperative Glycine Treatment Attenuates Ischemia/Reperfusion Injury and Ameliorates Smooth Muscle Dysfunction in Intestinal Transplantation

Background. Ischemia/reperfusion evokes a functionally relevant inflammatory response within the muscularis propria of small bowel grafts by activation of resident macrophages and leukocyte recruitment. We hypothesized that immunomodulatory perioperative treatment with glycine attenuates the proinflammatory cascade and improves smooth muscle dysfunction of small bowel grafts. Methods. Orthotopic SBTx was performed in Lewis rats. Glycine (1 mg/g body weight) was infused (0.1 mL/g/hr) for 2 hr before harvest as preconditioning in the donor, and for 2 hr from the onset of reperfusion in the recipient. Transplanted vehicle (isotonic saline)-treated animals and naive animals served as controls. Rats were sacrificed after 3 hr and 24 hr. Leukocyte infiltration was investigated in muscularis whole mounts by immunohistochemistry. Mediator mRNA expression was determined by real-time-PCR. Jejunal circular smooth muscle contractility was assessed in a standard organ bath. Results. Compared with vehicle controls, glycine-treated graft muscularis expressed a significant alleviation in mRNA peak expression for IL-6, IL-1&bgr;, ICAM-1, MCP-1, TNF&agr;, COX-2, and iNOS. Also glycine-treated grafts exhibited significantly less infiltration with ED-1-positive macrophages and MPO-positive neutrophils as well as reduced apoptosis. Concurrent to these results, vehicle controls showed an 80% decrease in smooth muscle contractility, whereas glycine-treated animals exhibited only a 40% decrease in contractile activity compared with controls. Conclusions. The data indicate that perioperative glycine treatment reduces the molecular and cellular inflammatory response within the grafts and improves smooth muscle dysfunction after transplantation. Therefore, the glycine-activated chloride channel on resident and infiltrating leukocytes could be a promising pharmacologic target to attenuate ischemia/reperfusion injury after ITx.
Monitoring of group C rotavirus in children with acute gastroenteritis in Brazil: An emergent epidemiological issue after rotavirus vaccine?

Group C rotavirus (GpCRV) has a worldwide distribution; however, its epidemiology and ecology are still unclear. Evidence for a possible zoonotic role has been postulated recently for Brazilian children strains. The aim of this study was to monitor GpCRV in children ≤15 years with acute gastroenteritis during the 2007–2010 national Brazilian rotavirus surveillance, and to undertake the molecular characterization of the major VP6 capsid protein. A total of 3,019 fecal samples were first screened for Group A rotavirus (GpARV). A total of 2,205 GpARV ELISA negative samples were tested further for the presence of GpCRV by SDS–PAGE, electronic microscopy, and RT‐PCR for the VP6 gene. The genetic diversity of GpCRV was carried out by sequencing the VP6 gene. GpARV and GpCRV infections were detected in 24.6% (742/3,019) and 0.3% (8/3,019), respectively. The GpCRV detection rate increased from 0.2% (1/422) in 2007 to 1% (7/708) in 2008, and GpCRV cases were not detected in 2009 and 2010. The phylogenetic analysis indicated that the strains belonged to the human lineage, and showed a genetic relationship with the GpCRV strain from Japan isolated in 2009. None of the study sequences was related closely to animal GpCRV strains. This study provides further evidence that GpCRV is a minor cause of acute childhood gastroenteritis in Brazil, and does not suggest that GpCRV may assume epidemiological importance in the future, even after the introduction of a GpARV vaccine. In addition, the molecular analyses of the GpCRV samples in this study do not support the zoonotic hypothesis. J. Med. Virol. 83:1631–1636, 2011. © 2011 Wiley‐Liss, Inc.
The Complexity of Linear Dependence Problems in Vector Spaces

We study extensions of the k-SUM problem to vector spaces over finite fields. Given a subset S ⊆ Fq of size r ≤ q, an integer k, 2 ≤ k ≤ n, and a vector v ∈ (Fq \ {0}), we define the TARGETSUM problem to be the problem of finding k elements xi1 , . , xik ∈ S for which ∑k j=1 vjxij = z, where z may either be an input or a fixed vector. We also study a variant of this, where instead of finding xi1 , . , xik ∈ S for which ∑k j=1 vjxij = z, we require that z be in span(xi1 , . . . , xik), which we call the (k, r)-LINDEPENDENCEq problem. These problems are natural generalizations of well-studied problems that occur in coding theory and property testing. Indeed, the (k, r)-LINDEPENDENCEq problem is just the MAXIMUM LIKELIHOOD DECODING problem for linear codes. Also, in the TARGETSUM problem, if instead of general z we require z = 0, then this is the WEIGHT DISTRIBUTION problem for linear codes. In property testing, these problems have been implicitly studied in the context of testing linear-invariant properties. We give nearly optimal bounds for TARGETSUM and (k, r)-LINDEPENDENCEq for every r, k, and constant q. Namely, assuming 3-SAT requires exponential time, we show that any algorithm for these problems must run in min(2, r) time. Moreover, we give deterministic upper bounds that match this complexity, up to constant factors in the exponent. Our lower bound strengthens and simplifies an earlier min(2, r 1/4)) lower bound for both the MAXIMUM LIKELIHOOD DECODING and WEIGHT DISTRIBUTION problems. We also give upper and lower bounds for variants of these problems, e.g., for the problem for which we must find xi1 , . , xik for which z ∈ span(xi1 , . . . , xik) but z is not spanned by any proper subset of these vectors, and for the counting version of this problem.
Block-Based High Capacity Multilevel Image Steganography

This paper proposes a block-based high capacity steganography technique for digital images. The cover image is decomposed into blocks of equal size and the largest pixel of each block is found to embed the secret data bits and also the smallest pixel of each block is used for embedding to enhance the capacity. Embedding of secret data is performed using the concept that the pixel of a cover image has only two states — even and odd. Multilevel approach is also combined in the proposed technique to achieve high embedding capacity. In order to make the proposed technique more secure, a key is generated using embedding levels, block size, pixel embedding way, encryption parameters, and starting blocks of each embedding levels. Embedding capacity and visual quality of stego images generated by the proposed steganography technique are higher than the existing techniques. Steganalysis tests have been performed to show the un-detectability and imperceptibility of the proposed technique.
Gross morphology of the vastus lateralis muscle: An anatomical review

To understand the role of the vastus lateralis (VL) muscle in the pathogenesis of common knee disorders such as patellofemoral joint syndrome, knowledge of its anatomical structure is essential. The aim of this study was to review currently available information on the gross morphology of VL. A structured literature review was undertaken and 36 references, comprising 22 scientific papers and 14 anatomical textbooks, were included. Results of this literature review show that most of the included studies exhibited methodological limitations, and focused on different parameters of the VL muscle. Hence, reproducibility of these studies and comparison of results was difficult. This review also demonstrates a dearth of information on the muscle architecture, compartmentalization, nerve supply and fusion of VL, and that there has been no investigation of the muscle as a whole unit. Further research is required of the architecture and innervation of the VL muscle to better understand its function. Clin. Anat. 22:436–450, 2009. © 2009 Wiley‐Liss, Inc.
Executing Nested Queries

Optimization of nested queries, in particular finding equivalent “flattened” queries for queries that employ the SQL sub-query construct, has been researched extensively. In contrast, with the exception of nested loops join, execution of nested plans has found little interest. Nested execution plans may result from a failure to flatten nested SQL expressions but just as likely are created by a query optimizer to exploit all available indexes as effectively as possible. In fact, if materialized views and index tuning perform as expected, few queries should require large operations such as parallel scans, sorts and hash joins, and most actual query plans will rely entirely on navigating indexes on tables and views. Note that only index navigation plans scale truly gracefully, i.e., perform equally well on large and on very large databases, whereas sorting and hashing scale at best linearly. Since a typical index navigation plan employs nested iteration, this paper describes techniques to execute such plans efficiently as well as means to cleanly implement these techniques. Taken together, these techniques can improve query performance by orders of magnitude, giving them obvious practical importance.
heart failure . plus glyceryl trinitrate paste in hydrallazine and of hydrallazine Haemodynamic effects of

In a study designed to investigate potential non-parenteral treatment for chronic heart failure, hydrallazine, 225 to 300 mg per day, was given orally to 9 patients. There was no significant change in heart rate or mean arterial pressure as cardiac output increased. Left ventricular stroke work increased significantly and pulmonary artery wedge pressure fell. Systemic and pulmonary vascular resistances fell. With the addition of 2 per cent glyceryl trinitrate paste, there was a further decline in