Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Tumor Promotion by Parthenolide: Epigenetic Modulation of p21

The promotion stage in the multistep process of epidermal tumorigenesis is NF-кB–dependent, epigenetically regulated, and reversible, thus, a suitable target for chemoprevention. We investigated whether the NF-кB inhibitor, parthenolide, currently in cancer clinical trials, attenuates tumor promotion by modulating the epigenetically regulated NF-кB target genes, p21 and cyclin D1. Parthenolide selectively inhibited the growth of neoplastic keratinocytes while sparing normal ones. Specifically, in JB6P+ cells, a model of tumor promotion, noncytotoxic parthenolide concentrations abrogated tumor promoter–induced cell proliferation and anchorage-independent growth. Furthermore, parthenolide decreased tumor promoter–induced NF-кB activity, increased p21, and decreased cyclin D1 expression. In parthenolide-treated cells, p21 transcription correlated with relaxed chromatin and p65/NF-кB binding at the p21 promoter. However, cyclin D1 transcription correlated more with p65/NF-кB binding than with chromatin structure at the cyclin D1 promoter. Epigenetic regulation by parthenolide seemed specific, as parthenolide did not alter global histone acetylation and methylation and histone deacetylase activity. Because p21 expression by parthenolide was sustained, we used p21-siRNA and p21 −/− cancer cells and showed that the loss of p21 is cytoprotective against parthenolide. Low parthenolide concentrations (0.25 mg/kg) inhibited tumor growth of promoted JB6P+ cells in xenograft immunocompromised mice using two different chemoprevention protocols. Tissue microarray of mouse tumors showed that parthenolide decreased scores of the cell proliferation marker Ki67 and p65/NF-кB, whereas it increased p21 expression. These results show that low doses of parthenolide inhibit tumor promotion and epigenetically modulate p21 expression, highlighting the potential role of this drug as a chemopreventive agent and in epigenetic cancer therapy. Cancer Prev Res; 5(11); 1298–309. ©2012 AACR.
Atomic Force Microscopy Analysis of the Role of Major DNA-Binding Proteins in Organization of the Nucleoid in Escherichia coli

Bacterial genomic DNA is packed within the nucleoid of the cell along with various proteins and RNAs. We previously showed that the nucleoid in log phase cells consist of fibrous structures with diameters ranging from 30 to 80 nm, and that these structures, upon RNase A treatment, are converted into homogeneous thinner fibers with diameter of 10 nm. In this study, we investigated the role of major DNA-binding proteins in nucleoid organization by analyzing the nucleoid of mutant Escherichia coli strains lacking HU, IHF, H–NS, StpA, Fis, or Hfq using atomic force microscopy. Deletion of particular DNA-binding protein genes altered the nucleoid structure in different ways, but did not release the naked DNA even after the treatment with RNase A. This suggests that major DNA-binding proteins are involved in the formation of higher order structure once 10-nm fiber structure is built up from naked DNA.
The heat is on: impact of endobronchial electrosurgery on the need for Nd-YAG laser photoresection.

STUDY OBJECTIVES Advances in bronchoscopic electrosurgery have allowed its application in the outpatient setting in patients who otherwise would have required Nd-YAG laser photoresection (LPR) in the operating room. We intended to evaluate the impact of endobronchial electrosurgery (EBES) on the need for Nd-YAG LPR on patients with symptomatic airway lesions. DESIGN Prospective observational case series. PARTICIPANTS One hundred eighteen evaluations for LPR were performed. Forty-seven evaluations (40%) were considered to be amendable to EBES and were treated during the initial bronchoscopy. The remaining patients underwent LPR. SETTING Outpatient bronchoscopy suite at the Cleveland Clinic Foundation, Cleveland, OH. RESULTS Of the 47 procedures, 42 (89%) were successful in alleviating the obstruction, thus eliminating the need for LPR. No major complications were encountered. CONCLUSION EBES can be performed safely in the outpatient setting and is an effective procedure in treating select endobronchial lesions. EBES eliminated the need for LPR in 36% of such procedures with a potential for significant time and cost savings.
Analysis of gene expression during the transition to climacteric phase in carnation flowers (Dianthus caryophyllus L.)

It has been generally thought that in ethylene-sensitive plants such as carnations, senescence proceeds irreversibly once the tissues have entered the climacteric phase. While pre-climacteric petal tissues have a lower sensitivity to ethylene, these tissues are converted to the climacteric phase at a critical point during flower development. In this study, it is demonstrated that the senescence process initiated by exogenous ethylene is reversible in carnation petals. Petals treated with ethylene for 12h showed sustained inrolling and senescence, while petals treated with ethylene for 10h showed inrolling followed by recovery from inrolling. Reverse transcription–PCR analysis revealed differential expression of genes involved in ethylene biosynthesis and ethylene signalling between 10h and 12h ethylene treatment. Ethylene treatment at or beyond 12h (threshold time) decreased the mRNA levels of the receptor genes (DcETR1, DcERS1, and DcERS2) and DcCTR genes, and increased the ethylene biosynthesis genes DcACS1 and DcACO1. In contrast, ethylene treatment under the threshold time caused a transient decrease in the receptor genes and DcCTR genes, and a transient increase in DcACS1 and DcACO1. Sustained DcACS1 accumulation is correlated with decreases in DcCTR genes and increase in DcEIL3 and indicates that tissues have entered the climacteric phase and that senescence proceeds irreversibly. Inhibition of ACS (1-aminocyclopropane-1-carboxylic acid synthase) prior to 12h ethylene exposure was not able to prevent reduction in transcripts of DcCTR genes, yet suppressed transcript of DcACS1 and DcACO1. This leads to the recovery from inrolling of the petals, indicating that DcACS1 may act as a signalling molecule in senescence of flowers.
Structural and Functional Characterization of a Secreted Hookworm Macrophage Migration Inhibitory Factor (MIF) That Interacts with the Human MIF Receptor CD74*

Hookworms, parasitic nematodes that infect nearly one billion people worldwide, are a major cause of anemia and malnutrition. We hypothesize that hookworms actively manipulate the host immune response through the production of specific molecules designed to facilitate infection by larval stages and adult worm survival within the intestine. A full-length cDNA encoding a secreted orthologue of the human cytokine, Macrophage Migration Inhibitory Factor (MIF) has been cloned from the hookworm Ancylostoma ceylanicum. Elucidation of the three-dimensional crystal structure of recombinant AceMIF (rAceMIF) revealed an overall structural homology with significant differences in the tautomerase sites of the human and hookworm proteins. The relative bioactivities of human and hookworm MIF proteins were compared using in vitro assays of tautomerase activity, macrophage migration, and binding to MIF receptor CD74. The activity of rAceMIF was not inhibited by the ligand ISO-1, which was previously determined to be an inhibitor of the catalytic site of human MIF. These data define unique immunological, structural, and functional characteristics of AceMIF, thereby establishing the potential for selectively inhibiting the hookworm cytokine as a means of reducing parasite survival and disease pathogenesis.
Constraining Cosmological Models by the Cluster Mass Function

We present a comparison between two observational mass functions and three theoretical mass functions for eight cosmological models suggested by the data from the recently completed BOOMERANG-98 and MAXIMA-1 cosmic microwave background (CMB) anisotropy experiments as well as from peculiar velocities (PVs) and Type Ia supernova (SN) observations. The cosmological models have been proposed as the best-fit models by several groups. We show that no model is in agreement with the abundances of X-ray clusters at ~1014.7 h-1 M☉. On the other hand, we find that the BOOM + MAX + COBE: I, Refined Concordance, and ΛMDM models are in a good agreement with the abundances of optical clusters. The P11 model and especially the Concordance model predict slightly lower abundances than observed at ~1014.6 h-1 M☉. The BOOM + MAX + COBE: II and PV + CMB + SN models predict slightly higher abundances than observed at ~1014.9 h-1 M☉. The nonflat MAXIMA-1 is in a fatal conflict with the observational cluster abundances and can be safely ruled out.
Prediction of whole-body metabolic clearance of drugs through the combined use of slices from rat liver, lung, kidney, small intestine and colon

1. The aim was to investigate whether precision-cut rat tissue slices could be used to predict metabolic drug clearance in vivo. To obtain a complete picture, slices not only from liver, but also from lung, kidney, small intestine and colon were included. 2. The metabolic clearances of 7-ethoxycoumarin, 7-hydroxycoumarin, testosterone, methyltestosterone and warfarin were determined by measuring the disappearance of these compounds during incubation with slices prepared from liver, lung, kidney, small intestine and colon. 3. The total in vitro metabolic clearance was determined by adding the individual in vitro organ clearances from the slices. Prediction based on the in vitro clearance was within an order of magnitude to the corresponding in vivo values. Interestingly, the relative contribution of extrahepatic metabolic clearance of the studied compounds to total clearance was remarkably high, ranging from 35 to 72% of the total metabolic clearance. 4. It is concluded that the model of multi-organ precision-cut slices is a useful in vitro tool for prediction of in vivo metabolic clearance. In addition, it provides information about the relative contribution of the liver, lung, kidney, small intestine and colon to the total metabolic clearance.
Adaptive Bandwidth Management and Joint Call Admission Control to Enhance System Utilization and QoS in Heterogeneous Wireless Networks

The coexistence of different cellular networks in the same area necessitates joint radio resource management for enhanced QoS provisioning and efficient radio resource utilization. We propose adaptive bandwidth management and joint call admission control (JCAC) scheme for heterogeneous cellular networks. The objectives of the proposed adaptive JCAC scheme are to enhance average system utilization, guarantee QoS requirements of all accepted calls, and reduce new call blocking probability and handoff call dropping probability in heterogeneous wireless networks. We develop a Markov chain model for the adaptive JCAC scheme and derive new call blocking probability, handoff call dropping probability, and average system utilization. Performance of the proposed adaptive JCAC scheme is compared with that of nonadaptive JCAC scheme in the same heterogeneous wireless network. Results show an improvement in average system utilization of up to 20%. Results also show that connection-level QoS can be significantly improved by using the proposed adaptive JCAC scheme.
Therapeutic Doses of Oral Methylphenidate Significantly Increase Extracellular Dopamine in the Human Brain

Methylphenidate (Ritalin) is the most commonly prescribed psychoactive drug in children for the treatment of attention deficit hyperactivity disorder (ADHD), yet the mechanisms responsible for its therapeutic effects are poorly understood. Whereas methylphenidate blocks the dopamine transporter (main mechanism for removal of extracellular dopamine), it is unclear whether at doses used therapeutically it significantly changes extracellular dopamine (DA) concentration. Here we used positron emission tomography and [(11)C]raclopride (D2 receptor radioligand that competes with endogenous DA for binding to the receptor) to evaluate whether oral methylphenidate changes extracellular DA in the human brain in 11 healthy controls. We showed that oral methylphenidate (average dose 0.8 +/- 0.11 mg/kg) significantly increased extracellular DA in brain, as evidenced by a significant reduction in B(max)/K(d) (measure of D2 receptor availability) in striatum (20 +/- 12%; p < 0.0005). These results provide direct evidence that oral methylphenidate at doses within the therapeutic range significantly increases extracellular DA in human brain. This result coupled with recent findings of increased dopamine transporters in ADHD patients (which is expected to result in reductions in extracellular DA) provides a mechanistic framework for the therapeutic efficacy of methylphenidate. The increase in DA caused by the blockade of dopamine transporters by methylphenidate predominantly reflects an amplification of spontaneously released DA, which in turn is responsive to environmental stimulation. Because DA decreases background firing rates and increases signal-to-noise in target neurons, we postulate that the amplification of weak DA signals in subjects with ADHD by methylphenidate would enhance task-specific signaling, improving attention and decreasing distractibility. Alternatively methylphenidate-induced increases in DA, a neurotransmitter involved with motivation and reward, could enhance the salience of the task facilitating the "interest that it elicits" and thus improving performance.
Surgical Revascularization Reverses Cerebral Cortical Thinning in Patients With Severe Cerebrovascular Steno-Occlusive Disease

Background and Purpose— Chronic deficiencies in regional blood flow lead to cerebral cortical thinning without evidence of gross tissue loss at the same time as potentially negatively impacting on neurological and cognitive performance. This is most pronounced in patients with severe occlusive cerebrovascular disease in whom affected brain areas exhibit “steal physiology,” a paradoxical reduction of cerebral blood flow in response to a global vasodilatory stimulus intended to increase blood flow. We tested whether surgical brain revascularization that eliminates steal physiology can reverse cortical thinning. Methods— We identified 29 patients from our database who had undergone brain revascularization with pre- and postoperative studies of cerebrovascular reactivity using blood oxygen(ation) level-dependent MRI and whose preoperative study exhibited steal physiology without MRI-evident structural abnormalities. Cortical thickness in regions corresponding to steal physiology, and where applicable corresponding areas in the normal hemisphere, were measured using Freesurfer software. Results— At an average of 11 months after surgery, cortical thickness increased in every successfully revascularized hemisphere (n=30). Mean cortical thickness in the revascularized regions increased by 5.1% (from 2.40±0.03 to 2.53±0.03; P<0.0001). Conclusions— Successful regional revascularization and reversal of steal physiology is followed by restoration of cortical thickness.
Seismic Fragility Assessment of Local and Global Failures in Low-rise Non-ductile Existing RC Buildings: Empirical Shear-Axial Modelling vs. ASCE/SEI 41 Approach

The brittle behavior of older non-ductile reinforced concrete buildings such as shear-axial failure in columns can cause lateral instability or gravity collapse. Hence, the attempt is to assess the collapse potential through fragility curves. Current research focuses on fragility assessment of these buildings emphasizing on shear-axial failure using two well-established methods; empirical limit state material versus ASCE/SEI 41-13 recommendations. To this aim, two 2D reinforced concrete models (3 and 5-story) according to typical detail of existing buildings in Iran were modeled using two aforementioned modeling approaches and analyzed under monotonic analysis and incremental dynamic analysis (IDA). In the following, seismic fragility assessment were carried out by means of obtained results from IDA. The results of fragility curves showed that, collapse capacity of buildings modelled by ASCE/SEI 41-13 are more than empirical method and fewer cases can pass the level of safety probability of failure suggested by ASCE/SEI-41.
The imprinted polycomb group gene Sfmbt2 is required for trophoblast maintenance and placenta development

Imprinted genes play important roles in placenta development and function. Parthenogenetic embryos, deficient in paternally expressed imprinted genes, lack extra-embryonic tissues of the trophoblast lineage. Parthenogenetic trophoblast stem cells (TSCs) are extremely difficult to derive, suggesting that an imprinted gene(s) is necessary for TSC establishment or maintenance. In a candidate study, we were able to narrow the list to one known paternally expressed gene, Sfmbt2. We show that mouse embryos inheriting a paternal Sfmbt2 gene trap null allele have severely reduced placentae and die before E12.5 due to reduction of all trophoblast cell types. We infected early embryos with lentivirus vectors expressing anti-Sfmbt2 shRNAs and found that TSC derivation was significantly reduced. Together, these observations support the hypothesis that loss of SFMBT2 results in defects in maintenance of trophoblast cell types necessary for development of the extra-embryonic tissues, the placenta in particular.
Randomized Block Subgradient Methods for Convex Nonsmooth and Stochastic Optimization

Block coordinate descent methods and stochastic subgradient methods have been extensively studied in optimization and machine learning. By combining randomized block sampling with stochastic subgradient methods based on dual averaging, we present stochastic block dual averaging (SBDA)---a novel class of block subgradient methods for convex nonsmooth and stochastic optimization. SBDA requires only a block of subgradients and updates blocks of variables and hence has significantly lower iteration cost than traditional subgradient methods. We show that the SBDA-based methods exhibit the optimal convergence rate for convex nonsmooth stochastic optimization. More importantly, we introduce randomized stepsize rules and block sampling schemes that are adaptive to the block structures, which significantly improves the convergence rate w.r. t. the problem parameters. This is in sharp contrast to recent block subgradient methods applied to nonsmooth deterministic or stochastic optimization. For strongly convex objectives, we propose a new averaging scheme to make the regularized dual averaging method optimal, without having to resort to any accelerated schemes.
Porphyromonas gingivalis: keeping the pathos out of the biont

The primary goal of the human microbiome initiative has been to increase our understanding of the structure and function of our indigenous microbiota and their effects on human health and predisposition to disease. Because of its clinical importance and accessibility for in vivo study, the oral biofilm is one of the best-understood microbial communities associated with the human body. Studies have shown that there is a succession of select microbial interactions that directs the maturation of a defined community structure, generating the formation of dental plaque. Although the initiating factors that lead to disease development are not clearly defined, in many individuals there is a fundamental shift from a health-associated biofilm community to one that is pathogenic in nature and a central player in the pathogenic potential of this community is the presence of Porphyromonas gingivalis. This anaerobic bacterium is a natural member of the oral microbiome, yet it can become highly destructive (termed pathobiont) and proliferate to high cell numbers in periodontal lesions, which is attributed to its arsenal of specialized virulence factors. Hence, this organism is regarded as a primary etiologic agent of periodontal disease progression. In this review, we summarize some of the latest information regarding what is known about its role in periodontitis, including pathogenic potential as well as ecological and nutritional parameters that may shift this commensal to a virulent state. We also discuss parallels between the development of pathogenic biofilms and the human cellular communities that lead to cancer, specifically we frame our viewpoint in the context of ‘wounds that fail to heal’.
A Single-Inductor Step-Up DC-DC Switching Converter with Bipolar Outputs for Active Matrix OLED Mobile Display Panels

A single-chip dual-output step-up DC-DC converter is implemented for active-matrix OLED mobile display panels. The bipolar outputs are regulated independently and integrated with a boost and a charge-pump topology sharing a single inductor. The chip is 4.1mm2 fabricated in a 0.5 mum power BiCMOS process and operates at 1MHz with a maximum efficiency of 82.3% at an output power of 330mW.
Semi-infinite linear programming approaches to semidefinite programming problems∗

Interior point methods, the traditional methods for the SDP , are fairly limited in the size of problems they can handle. This paper deals with an LP approach to overcome some of these shortcomings. We begin with a semi-infinite linear programming formulation of the SDP and discuss the issue of its discretization in some detail. We further show that a lemma due Pataki on the geometry of the SDP , implies that no more than O( √ k) (where k is the number of constraints in the SDP ) linear constraints are required. To generate these constraints we employ the spectral bundle approach due to Helmberg and Rendl. This scheme recasts any SDP with a bounded primal feasible set as an eigenvalue optimization problem. These are convex nonsmooth problems that can be tackled by bundle methods for nondifferentiable optimization. Finally we present the rationale for using the columns of the bundle P maintained by the spectral bundle approach, as our linear constraints. We present numerical experiments that demonstrate the efficiency of the LP approach on two combinatorial examples, namely the max cut and min bisection problems. The LP approach potentially allows one to approximately solve large scale semidefinite programs using state of the art linear solvers. This work was supported in part by NSF grant numbers CCR–9901822 and DMS9872019 Department of Mathematical Sciences, Rensselaer Polytechnic Institute, 110 8th Street, Troy, New York, 12180 (kartis@rpi.edu). Department of Mathematical Sciences, Rensselaer Polytechnic Institute, 110 8th Street, Troy, New York, 12180 (mitchj@rpi.edu).
Blue Diatoms: Global Phenomenon of ˝Greening˝ in Shellfish and Record of Planktonic Haslea Species in the South Adriatic Sea

Diatoms are unicellular, photoautotrophic eukaryotic microorganisms, often forming colonies and can be found in most aquatic and moist terrestrial habitats. All known diatoms today have specific golden-brown pigment fucoxanthin that masks chlorophylls in diatom plastid, but one genus represents an exception, having the additional specific pigment marennine due to whom the cells appear blue. Blue diatoms from genus Haslea cause a global phenomenon of ˝greening˝ in shellfish (mostly oysters) affecting them in both positive and negative ways. In this study, historical and recent review regarding blue diatoms and physiological and behavioural effect of marennine as well as challenges in shellfish farming from diatom perspective is addressed. This study is also a first record of blue Haslea diatom in the South Adriatic Sea during BIOTA (Bio-tracing Adriatic Water Masses) cruise in March 2016. Investigated blue diatom was cultured in laboratory and morphologically analysed with light microscopy. Diatom investigations are very important for better understanding of the ecology of specific marine area, but also for the economy, aquaculture and tourism. The emergence of green coloured flesh of shellfish in the Adriatic Sea has not been recorded yet, but this finding of the blue diatom from genus Haslea does not rule out this possibility in the future.