The majority of ultraluminous X-ray sources are point sources that are spatially offset from the nuclei of nearby galaxies and whose X-ray luminosities exceed the theoretical maximum for spherical ...infall (the Eddington limit) onto stellar-mass black holes. Their X-ray luminosities in the 0.5-10 kiloelectronvolt energy band range from 10(39) to 10(41) ergs per second. Because higher masses imply less extreme ratios of the luminosity to the isotropic Eddington limit, theoretical models have focused on black hole rather than neutron star systems. The most challenging sources to explain are those at the luminous end of the range (more than 10(40) ergs per second), which require black hole masses of 50-100 times the solar value or significant departures from the standard thin disk accretion that powers bright Galactic X-ray binaries, or both. Here we report broadband X-ray observations of the nuclear region of the galaxy M82 that reveal pulsations with an average period of 1.37 seconds and a 2.5-day sinusoidal modulation. The pulsations result from the rotation of a magnetized neutron star, and the modulation arises from its binary orbit. The pulsed flux alone corresponds to an X-ray luminosity in the 3-30 kiloelectronvolt range of 4.9 × 10(39) ergs per second. The pulsating source is spatially coincident with a variable source that can reach an X-ray luminosity in the 0.3-10 kiloelectronvolt range of 1.8 × 10(40) ergs per second. This association implies a luminosity of about 100 times the Eddington limit for a 1.4-solar-mass object, or more than ten times brighter than any known accreting pulsar. This implies that neutron stars may not be rare in the ultraluminous X-ray population, and it challenges physical models for the accretion of matter onto magnetized compact objects.
Abstract
The role of evolutionarily conserved homeobox-containing
HOX
genes as transcriptional regulators in the developmental specification of organisms is well known. The contribution of
HOX
genes ...involvement in oral cancer phenotype has yet to be fully ascertained. TCGA-HNSC HTSeq-counts and clinical data were retrieved from the GDC portal for oral cavity neoplasms. GEO datasets (GSE72627, GSE30784, GSE37991) were accessed and analyzed using GEO2R. Differential
HOX
gene expression was profiled using the DESeq2 R package with a log2 fold change cut-off (− 1 and + 1) and Benjamini–Hochberg
p
-adjusted value at ≤ 0.01. Gene set over-representation analysis and semantic analysis associated with the disease ontology was performed using the ClusterProfiler R package, and pathway over-representation analysis was performed using IMPaLa. HOX protein interaction network was constructed using the Pathfind R package.
HOX
phenotype associations were performed using Mammalian Phenotype Ontology, Human Phenotype Ontology, PhenGenI associations, Jensen tissues, and OMIM entries. Drug connectivity mapping was carried out with Dr. Insight R package.
HOXA2
was upregulated in oral dysplasia but silenced during tumor progression. Loss of
HOXB2
expression was consistent in the potentially malignant oral lesions as well as in the primary tumor.
HOXA7, HOXA10, HOXB7, HOXC6, HOXC10, HOXD10,
and
HOXD11
were consistently upregulated from premalignancy to malignancy and were notably associated with risk factors. Overrepresentation analysis suggested
HOXA10
was involved in the transcriptional misregulation contributing to the oral cancer phenotype.
HOX
genes subnetwork analysis showed crucial interactions with cell cycle regulators, growth responsive elements, and proto-oncogenes. Phenotype associations specific to the oral region involving
HOX
genes provide intrinsic cues to tumor development. The 5′
HOX
genes were aberrantly upregulated during oral carcinogenesis reflecting their posterior prevalence.
Locally advanced oral squamous cell carcinoma poses a significant challenge in oncology due to its rising incidence and mortality rates. Despite therapeutic progress, understanding molecular ...intricacies is essential. This study explored the role of PON2, a multifunctional enzyme implicated in antiapoptotic mechanisms. Aberrant PON2 expression in oral cancers raises questions regarding its involvement in evading programmed cell death and treatment resistance. Patients with locally advanced disease were enrolled, and molecular analyses were undertaken on the collected tumor and normal tissues. Utilizing computational datasets, this study used in silico gene expression analysis, differential gene expression analysis in our patient cohort, survival analysis, and gene set enrichment analysis to unravel role of PON2 in disease prognosis. The results showed elevated PON2 levels in advanced tumor stages, correlating with factors such as tobacco exposure, higher tumor grade, and nodal metastasis. Survival analysis revealed prognostic relevance of PON2, with lower expression linked to extended survival rates. Gene set enrichment analysis identified pathways aiding in cancer metastasis influenced by PON2. This study underscores the significance of PON2 expression as a prognostic marker for oral malignancies, with increased expression associated with advanced disease stages. Understanding the molecular profile of the PON2 gene suggests its potential as a valuable biomarker for the management of cancer.
Role of PON2 in regulating diverse molecular pathways influenced by PON2 during cancer progression and metastasis.
We elaborate on a general method that we recently introduced for characterizing the “natural” structures in complex physical systems via
multi-scale
network analysis. The method is based on ...“community detection” wherein interacting particles are partitioned into an “ideal gas” of optimally decoupled groups of particles. Specifically, we construct a set of network representations (“replicas”) of the physical system based on interatomic potentials and apply a multiscale clustering (“multiresolution community detection”) analysis using information-based correlations among the replicas. Replicas may i) be different representations of an identical static system, ii) embody dynamics by considering replicas to be time separated snapshots of the system (with a tunable time separation), or iii) encode general correlations when different replicas correspond to different representations of the entire history of the system as it evolves in space-time. Inputs for our method are the inter-particle potentials or experimentally measured two (or higher order) particle correlations. We apply our method to computer simulations of a binary Kob-Andersen Lennard-Jones system in a mixture ratio of A
80
B
20
, a ternary model system with components “A”, “B”, and “C” in ratios of A
88
B
7
C
5
(as in Al
88
Y
7
Fe
5
, and to atomic coordinates in a Zr
80
Pt
20
system as gleaned by reverse Monte Carlo analysis of experimentally determined structure factors. We identify the dominant structures (disjoint or overlapping) and general length scales by analyzing extrema of the information theory measures. We speculate on possible links between i) physical transitions or crossovers and ii) changes in structures found by this method as well as phase transitions associated with the computational complexity of the community detection problem. We also briefly consider continuum approaches and discuss rigidity and the shear penetration depth in amorphous systems; this latter length scale increases as the system becomes progressively rigid.
Recent decades have experienced the discovery of numerous complex materials. At the root of the complexity underlying many of these materials lies a large number of contending atomic- and largerscale ...configurations. In order to obtain a more detailed understanding of such systems, we need tools that enable the detection of pertinent structures on all spatial and temporal scales. Towards this end, we suggest a new method that applies to both static and dynamic systems which invokes ideas from network analysis and information theory. Our approach efficiently identifies basic unit cells, topological defects, and candidate natural structures. The method is particularly useful where a clear definition of order is lacking, and the identified features may constitute a natural point of departure for further analysis.
Studies on the antibacterial potentiality of isoflavones Dastidar, Sujata G; Manna, A; Kumar, K.Asok ...
International journal of antimicrobial agents,
2004, 2004-Jan, 2004-01-00, 20040101, Volume:
23, Issue:
1
Journal Article
Peer reviewed
The isoflavonoid compounds ‘YS11–YS21’ were screened for possible antimicrobial property against 12 known Gram-positive and Gram-negative sensitive bacteria. YS11 and YS16 failed to show ...antimicrobial activity and YS12, 13, 14, 15, 17, 18 and 20 had moderate antimicrobial action. Compounds YS19 and YS21 showed pronounced antimicrobial property. YS19 and YS21 were then tested in vitro against 214 strains of bacteria from one Gram-positive and six Gram-negative genera. The minimum inhibitory concentration (MIC) of YS19 and YS21 was determined by agar dilution method and ranged from 25 to 200
mg/l in most strains. At concentrations of 30 and 60
μg/mouse these compounds offered significant protection to mice challenged with 50 median lethal dose (MLD) of a virulent strain of
Salmonella Typhimurium.
Most strains of Gram-positive and Gram-negative bacteria were inhibited by 50–100 mg/l of the anti-inflammatory agent, diclofenac sodium (Dc). In vivo test using 30 or 50 μg Dc per 20 g mouse (Swiss ...Albino variety) significantly (
P <0.001) protected the animals when challenged with 50 MLD of a virulent
Salmonella typhimurium. The anti-bacterial action of Dc was found to be due to inhibition of DNA synthesis which was demonstrated using 2 μ Ci (
3H) deoxythymidine uptake.
Trifluoperazine showed some significant antimicrobial activity when tested against 293 strains from two Gram-positive and eight Gram-negative genera. Minimum inhibitory concentrations of the drug ...were measured using an agar dilution technique. Forty six of 55 strains of
Staphylococcus aureus were inhibited by 10–50 μg/ml of trifluoperazine. This drug also inhibited strains of
Shigella spp.,
Vibrio cholerae and
V. parahaemolyticus at a concentration of 10–100 μg/ml. Other bacteria including
Pseudomonas spp. were moderately sensitive to trifluoperazine. In the in vivo studies this compound offered significant protection to Swiss albino mice at a concentration of 30 μg/mouse (
P<0.001) when challenged with 50 median lethal dose of
Salmonalla typhimurium NCTC 74.
Objectives
We aim to elucidate the interaction of long noncoding RNAs with HOX genes and their regulatory role and potential drug candidates in oral cancer.
Materials and Methods
The interaction ...network was constructed using RNA Interactome and the RNA Interactome from the Sequencing Experiments database. The differential expression of HOX genes and HOX interacting lncRNAs was assessed using the TCGA‐Head and Neck Squamous Cell Carcinoma oral cancer dataset using DESeq2 R‐package. Further, the functional enrichment analysis was performed for the differentially expressed HOX genes and HOX‐interacting lncRNAs using Gene Ontology, long noncoding RNA Set Enrichment Analysis, lncRNA ontology annotation extractor and repository (Lantern), and LncRNA Ontology tools. Drug‐lncRNA interaction and the effect of drugs on lncRNA expression were assessed from the D‐lnc tool.
Results
A total of 78 unique interactions were identified between HOX and lncRNAs. Differential expression analysis showed 27 HOX genes and 10 HOX‐interacting lncRNAs in oral cancer. HOX genes and HOX‐interacting lncRNAs were involved in crucial regulatory processes like cell cycle regulation, cell proliferation and migration, epithelial‐mesenchymal transition, angiogenesis, and cell signaling pathways. Cancer hallmark analysis from using long noncoding RNA Set Enrichment Analysis showed the involvement of HOTAIR, HOTTIP MIR503HG, and CDKN2B‐AS1 in proliferation, migration, and invasion. Panobinostat was the common drug that influenced the expression of HOTAIR, HOTAIRM1, HOTTIP and CDKN2B‐AS1.
Conclusions
Differentially expressed HOX‐interacting lncRNAs are involved in various regulatory biological processes and cancer hallmark events in oral cancer.
Clinical Relevance
The creation of interaction networks may expand the existing knowledge of oral cancer signaling pathways and the discovery of novel targets.
Ten cardiovascular drugs, having diverse pharmacological action, were screened for possible antimicrobial property against known eight sensitive bacteria, belonging to Gram positive and Gram negative ...types. Although five drugs failed to show antimicrobial activity and three had moderate antimicrobial action, oxyfedrine HCl and dobutamine were seen to possess pronounced antimicrobial property. Oxyfedrine was further tested
in vitro against 471 strains of bacteria from two Gram positive and fourteen Gram negative genera. The minimum inhibitory concentration (MIC) of oxyfedrine was determined by agar dilution method, which ranged from 50–200 μg/ml in most of the strains, while some strains were inhibited at even lower concentrations. In animal experiments, this compound was capable of offering significant protection to Swiss strain of white mice, challenged with 50 median lethal dose (MLD) of a virulent strain of
Salmonella typhimurium at concentrations of 15, 30 and 60 μg/mouse. The
in vivo results were highly significant according to chi-square test.
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