Miracle-dz/UniFAR-FTUs huggingface dataset:
Selenium Metabolism in Cancer Cells: The Combined Application of XAS and XFM Techniques to the Problem of Selenium Speciation in Biological Systems

Determining the speciation of selenium in vivo is crucial to understanding the biological activity of this essential element, which is a popular dietary supplement due to its anti-cancer properties. Hyphenated techniques that combine separation and detection methods are traditionally and effectively used in selenium speciation analysis, but require extensive sample preparation that may affect speciation. Synchrotron-based X-ray absorption and fluorescence techniques offer an alternative approach to selenium speciation analysis that requires minimal sample preparation. We present a brief summary of some key HPLC-ICP-MS and ESI-MS/MS studies of the speciation of selenium in cells and rat tissues. We review the results of a top-down approach to selenium speciation in human lung cancer cells that aims to link the speciation and distribution of selenium to its biological activity using a combination of X-ray absorption spectroscopy (XAS) and X-ray fluorescence microscopy (XFM). The results of this approach highlight the distinct fates of selenomethionine, methylselenocysteine and selenite in terms of their speciation and distribution within cells: organic selenium metabolites were widely distributed throughout the cells, whereas inorganic selenium metabolites were compartmentalized and associated with copper. New data from the XFM mapping of electrophoretically-separated cell lysates show the distribution of selenium in the proteins of selenomethionine-treated cells. Future applications of this top-down approach are discussed.
The Effect of Damping and Stiffness of Bearing on the Natural Frequencies of Rotor-bearing System

In this paper, the effectiveness of stiffness and damping of bearing is investigated on the natural frequencies of the rotor-bearing system. The rotor-bearing system consists of a shaft, two bearings and a disk between two bearings. Parallel spring-damper in horizental and vertical directions is considered for modeling the stiffness and damping of bearings. The gyroscopic effect is also considered in derivation of equations, together with its dependence on speed. Numerical results contain the critical speed of shaft for various values of bearing stiffness and damping. Moreover, the first six natural frequencies of rotor are presented in Campbell diagrams.
Kupffer Cells Hasten Resolution of Liver Immunopathology in Mouse Models of Viral Hepatitis

Kupffer cells (KCs) are widely considered important contributors to liver injury during viral hepatitis due to their pro-inflammatory activity. Herein we utilized hepatitis B virus (HBV)-replication competent transgenic mice and wild-type mice infected with a hepatotropic adenovirus to demonstrate that KCs do not directly induce hepatocellular injury nor do they affect the pathogenic potential of virus-specific CD8 T cells. Instead, KCs limit the severity of liver immunopathology. Mechanistically, our results are most compatible with the hypothesis that KCs contain liver immunopathology by removing apoptotic hepatocytes in a manner largely dependent on scavenger receptors. Apoptotic hepatocytes not readily removed by KCs become secondarily necrotic and release high-mobility group box 1 (HMGB-1) protein, promoting organ infiltration by inflammatory cells, particularly neutrophils. Overall, these results indicate that KCs resolve rather than worsen liver immunopathology.
Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes

The synthesis of fatty acids and cholesterol, the building blocks of membranes, is regulated by three membrane-bound transcription factors: sterol regulatory element-binding proteins (SREBP)-1a, -1c, and -2. Their function in liver has been characterized in transgenic mice that overexpress each SREBP isoform and in mice that lack all three nuclear SREBPs as a result of gene knockout of SREBP cleavage-activating protein (SCAP), a protein required for nuclear localization of SREBPs. Here, we use oligonucleotide arrays hybridized with RNA from livers of three lines of mice (transgenic for SREBP-1a, transgenic for SREBP-2, and knockout for SCAP) to identify genes that are likely to be direct targets of SREBPs in liver. A total of 1,003 genes showed statistically significant increased expression in livers of transgenic SREBP-1a mice, 505 increased in livers of transgenic SREBP-2 mice, and 343 showed decreased expression in Scap–/– livers. A subset of 33 genes met the stringent combinatorial criteria of induction in both SREBP transgenics and decreased expression in SCAP-deficient mice. Of these 33 genes, 13 were previously identified as direct targets of SREBP action. Of the remaining 20 genes, 13 encode enzymes or carrier proteins involved in cholesterol metabolism, 3 participate in fatty acid metabolism, and 4 have no known connection to lipid metabolism. Through application of stringent combinatorial criteria, the transgenic/knockout approach allows identification of genes whose activities are likely to be controlled directly by one family of transcription factors, in this case the SREBPs.
Echocardiographic Detection of Coronary Artery Disease During Dobutamine Infusion

BackgroundTwo-dimensional echocardiography performed during dobutamine infusion hasbeen proposed as a potentially useful method for detecting coronary artery disease. However, the safety and diagnostic value of dobutamine stress echocardiography has not been established. Methods and ResultsIn this study, echocardiograms were recorded during step-wise infusion of dobutamine to a maximum dose of 30 gg/kg/min in 103 patients who also underwent quantitative coronary angiography. The echocardiograms were digitally stored and displayed in a format that allowed simultaneous analysis of rest and stress images. Development of a new abnormality in regional function was used as an early end point for the dobutamine infusion. No patient had a symptomatic arrhythmia or complications from stress-induced ischemia. Significant coronary artery disease (<50% diameter stenosis) was present in 35 of 55 patients who had normal echocardiograms at rest. The sensitivity and specificity of dobutamine-induced wall motion abnormalities for coronary artery disease was 89% (31 of 35) and 85% (17 of 20), respectively. The sensitivity was 81% (17 of 21) in those with one-vessel disease and 100% (14 of 14) in those with multivessel or left main disease. Forty-one of 48 patients with abnormal echocardiograms at baseline had localized rest wall motion abnormalities. Fifteen had coronary artery disease confined to regions that had abnormal rest wall motion, and 26 had disease remote from these regions. Thirteen of 15 patients (87%) without remote disease did not develop remote stress-induced abnormalities, and 21 of 26 (81%) who had remote disease developed corresponding abnormalities. ConclusionsEchocardiography combined with dobutamine infusion is a safe and accurate method for detecting coronary artery disease and for predicting the extent of disease in those who have localized rest wall motion abnormalities.
Segment based Detection and Quantification of Kidney Stones and its symmetric Analysis using Texture Properties based on Logical Operators with Ultra Sound Scanning

In this research work a fully automated and given to automatic algorithm to detect Quantification of Kidney Stones by using symmetric analysis, which is proposed in this paper. Here we detect the renal-stones, segment the renal regions and calculate the area of the renal which is occupied by kidney stones. The quantitative analysis of kidney stones allows obtaining useful key indicators of disease progression. The stone detection is often an essential preliminary phase to solve the segmentation problem successfully. Thus, the user eventually notices that it is hard to detect the boundary of the kidney in the US image; even it’s done by the trained sonographers. In addition, human error might occur during the interpretation of ultrasound image by untrained sonographer, especially when taking measurement. Therefore, in order to reduce the dependability to the sonographers’ expertise, some image processing can be done which can automatically detect the centroid of human kidney and stones. Ultra Sound (US) is one of the modality of first choice in kidney image processing. US can be used to measure the size and appearance of the kidneys and to detect stones, congenital anomalies, swelling and blockage of urine flow. As this imaging technique is non-invasive, portable, and affordable and does not require radiation, most of the medical practitioner chosen US for primary screening of kidneys’ condition. Three kinds of Ultrasound kidney images namely, Normal (NR), Medical Renal Diseases (MRD) and Cortical Cysts (CC) images are classified based on texture properties. This algorithm involves only convolution and simple arithmetic in various stages which leads faster implementation. The efficient feature space is created for textures as well as US kidney stone classification. Firstly, some techniques of speckle noise reduction were implemented consist of median filter, Wiener filter and Gaussian low-pass filter. Then texture analysis was performed by calculating the local entropy of the image, continued with the threshold selection, morphological operations, object windowing, determination of seed point and ROI generation. This method was performed to several kidney ultrasound images with different speckle noise reduction techniques and different threshold value selection. Based on the result, it shows that for median filter, threshold value of 0.6 gave the highest TRUE ROIs which were 70%. For Wiener filter, threshold value of 0.8 gave highest TRUE ROIs which were 80% and for Gaussian low-pass filter, threshold value of 0.7 gave highest TRUE ROIs which were 100%. By using the previous methods result, this method has been tested also to more than 200 kidney stone ultrasound images. Therefore, we conducted a texture analysis to the kidney stone images. As the result, the renal sinus, the central area of the kidney stone appeared brighter compared to the other part of the renal, and in the texture analysis, it also appear as the most common region detected in kidney stones.
Mechanisms of Supersensitivity to Sympathomimetic Amines in the Chronically Denervated Heart of the Conscious Dog

Mechanisms of denervation supersensitivity to sympathomimetic amines were studied in conscious animals. Norepinephrine, 0.1 μg/kg increased left ventricular dP/dt significantly more (4208 ± 828 mm Hg/sec) in dogs with cardiac denervation than in intact dogs (1029 ± 280 mm Hg/sec), P < 0.01, whereas responses to isoproterenol were similar in both groups. Denervation supersensitivity to isoproterenol could be demonstrated only after opposing reflex effects were blocked. After ganglionic blockade, norepinephrine still induced 2- to 3-fold greater increases in left ventricular dP/dt and 3- to 7-fold greater increases in heart rate in cardiacdenervated dogs, whereas isoproterenol and prenalterol, not taken up by presynaptic nerve endings, elicited only 40%–50% greater increases in left ventricular dP/dt and heart rate in dogs with cardiac denervation. The density of β-adrenergic receptors ([3H]dihydroalprenolol) was elevated (P < 0.01) in denervated left ventricles (105 ± 6.9 fmol/mg protein, n = 8) compared to normal left ventricles (70 ± 6.3 fmol/mg protein, n = 12). This was accompanied by enhanced isoproterenol-mediated adenylate cyclase activity. However, muscarinic cholinergic receptor density, ([3H]quinuclidinyl benzilate), decreased from control levels of 251 ± 11 fmol/mg protein (n = T) to 193 ± 14 fmol/mg protein (n = 6). Thus, chronic cardiac denervation results in up-regulation of the β-adrenergic receptor and down-regulation of the muscarinic receptor. The increased β-adrenergic receptor density and adenylate cyclase stimulation correlated well with the amount of denervation supersensitivity to isoproterenol and prenalterol, but accounted for only a minor fraction of denervation supersensitivity to norepinephrine. The major mechanism of denervation supersensitivity to norepinephrine appears to involve lack of the norepinephrine reuptake.
MK-1775, a Potent Wee1 Inhibitor, Synergizes with Gemcitabine to Achieve Tumor Regressions, Selectively in p53-Deficient Pancreatic Cancer Xenografts

Purpose: Investigate the efficacy and pharmacodynamic effects of MK-1775, a potent Wee1 inhibitor, in both monotherapy and in combination with gemcitabine (GEM) using a panel of p53-deficient and p53 wild-type human pancreatic cancer xenografts. Experimental Design: Nine individual patient-derived pancreatic cancer xenografts (6 with p53-deficient and 3 with p53 wild-type status) from the PancXenoBank collection at Johns Hopkins were treated with MK-1775, GEM, or GEM followed 24 hour later by MK-1775, for 4 weeks. Tumor growth rate/regressions were calculated on day 28. Target modulation was assessed by Western blotting and immunohistochemistry. Results: MK-1775 treatment led to the inhibition of Wee1 kinase and reduced inhibitory phosphorylation of its substrate Cdc2. MK-1775, when dosed with GEM, abrogated the checkpoint arrest to promote mitotic entry and facilitated tumor cell death as compared to control and GEM-treated tumors. MK-1775 monotherapy did not induce tumor regressions. However, the combination of GEM with MK-1775 produced robust antitumor activity and remarkably enhanced tumor regression response (4.01-fold) compared to GEM treatment in p53-deficient tumors. Tumor regrowth curves plotted after the drug treatment period suggest that the effect of the combination therapy is longer-lasting than that of GEM. None of the agents produced tumor regressions in p53 wild-type xenografts. Conclusions: These results indicate that MK-1775 selectively synergizes with GEM to achieve tumor regressions, selectively in p53-deficient pancreatic cancer xenografts. Clin Cancer Res; 17(9); 2799–806. ©2011 AACR.
Two populations of double minute chromosomes harbor distinct amplicons, the MYC locus at 8q24.2 and a 0.43-Mb region at 14q24.1, in the SW613-S human carcinoma cell line

High-level amplifications observed in tumor cells are usually indicative of genes involved in oncogenesis. We report here a high resolution characterization of a new amplified region in the SW613-S carcinoma cell line. This cell line contains tumorigenic cells displaying high-level MYC amplification in the form of double minutes (DM+ cells) and non tumorigenic cells exhibiting low-level MYC amplification in the form of homogeneously staining regions (DM– cells). Both cell types were studied at genomic and functional levels. The DM+ cells display a second amplification, corresponding to the 14q24.1 region, in a distinct population of DMs. The 0.43-Mb amplified and overexpressed region contains the PLEK2, PIGH, ARG2, VTI1B, RDH11, and ZFYVE26 genes. Both amplicons were stably maintained upon in vitro and in vivo propagation. However, the 14q24.1 amplicon was not found in cells with high-level MYC amplification in the form of HSRs, either obtained after spontaneous integration of endogenous DM MYC copies or after transfection of DM– cells with a MYC gene expression vector. These HSR-bearing cells are highly tumorigenic. The 14q24.1 amplification may not play a role in malignancy per se but might contribute to maintaining the amplification in the form of DMs.
Open Problem: Kernel methods on manifolds and metric spaces. What is the probability of a positive definite geodesic exponential kernel?

Radial kernels are well-suited for machine learning over general geodesic metric spaces, where pairwise distances are often the only computable quantity available. We have recently shown that geodesic exponential kernels are only positive deﬁnite for all bandwidths when the input space has strong linear properties. This negative result hints that radial kernel are perhaps not suitable over geodesic metric spaces after all. Here, however, we present evidence that large intervals of bandwidths exist where geodesic exponential kernels have high probability of being positive deﬁnite over ﬁnite datasets, while still having signiﬁcant predictive power. From this we formulate conjectures on the probability of a positive deﬁnite kernel matrix for a ﬁnite random sample, depending on the geometry of the data space and the spread of the sample.
Determining Prominent Subdomains in Medicine

We discuss an automated method for identifying prominent subdomains in medicine. The motivation is to enhance the results of natural language processing by focusing on sublanguages associated with medical specialties concerned with prevalent disorders. At the core of our approach is a statistical system for topical categorization of medical text. A method based on epidemiological evidence is compared to another that considers frequency of occurrence of Medline citations. We suggest the isolation of UMLS terminology peculiar to individual medical specialties as a way of enhancing natural language processing systems in the biomedical domain.
The Open University ’ s repository of research publications and other research outputs Data wranglers : human interpreters to help close the feedback loop Conference Item

Closing the feedback loop to improve learning is at the heart of good learning analytics practice. However, the quantity of data, and the range of different data sources, can make it difficult to take systematic action on that data. Previous work in the literature has emphasised the need for and value of human meaning-making in the process of interpretation of data to transform it in to actionable intelligence. This paper describes a programme of human Data Wranglers deployed at the Open University, UK, charged with making sense of a range of data sources related to learning, analysing that data in the light of their understanding of practice in individual faculties/departments, and producing reports that summarise the key points and make actionable recommendations. The evaluation of and experience in this programme of work strongly supports the value of human meaning-makers in the learning analytics process, and suggests that barriers to organisational change in this area can be mitigated by embedding learning analytics work within strategic contexts, and working at an appropriate level and granularity of analysis.
THE PROTECTION OF INTRACELLULAR BRUCELLA AGAINST THERAPEUTIC AGENTS AND THE BACTERICIDAL ACTION OF SERUM

A method for the in vitro study of intracellular brucella has been described. Exudative leukocytes containing intracellular brucella have been maintained in vitro in a synthetic tissue culture medium or in human or animal serum. Intracellular brucella are protected in vitro against the lethal action of therapeutic agents or the bactericidal action of serum. This protection of intracellular brucella is dependent upon the presence of an intact, viable host cell. None of the currently available therapeutic agents, whether used alone or in combinations, were capable of killing all intracellular brucella in vitro in 24 hours. A remarkable protection of intracellular brucella against streptomycin has been demonstrated. The most effective reduction in the number of viable intracellular brucella was accomplished by exposure of the host cells to streptomycin plus aureomycin, terramycin, or chloramphenicol. The available evidence suggests that the ability of brucella to localize and remain viable within the cells of an infected host is an important biologic factor in establishing and perpetuating brucella infections, despite therapeutic measures or the operation of the host's humoral defense mechanisms. Reduction of neotetrazolium by leukocytes and brucella in vitro provides a method for assessing the metabolic status of the host cell, but does not discriminate with any degree of certainty a viable from a non-viable intracellular organism.
Versatility of Ozone Therapy in Dentistry : A Literature Review

Ozone (O3) acts as a protective layer in the environment from harmful UV rays. Over 100 years, ozone has been used in the medicine. Due to its unique property, noninvasive nature and wide spectrum of action, it has been used in dentistry also. Ozone has been used in treatment of alveolitis, osteoradionecrosis of jaw, bacterial and viral infections, implantology. It also inhibits plaque formation, thereby make a good prognosis of periodontal therapy. Ozone has also been used in dental unit water line to disinfect water. It is atraumatic. More trials are needed for precise indications and guidelines for successful dental treatment.
Breast carcinoma: effect of preoperative contrast-enhanced MR imaging on the therapeutic approach.

PURPOSE To determine if magnetic resonance (MR) imaging can help determine the therapeutic approach in women with breast cancer. MATERIALS AND METHODS Preoperative contrast-enhanced MR imaging of the breast was performed in 463 patients with probably benign lesions (n = 63), suspicious lesions (n = 230), or lesions highly suggestive of malignancy (n = 170) per established clinical, mammographic, and/or ultrasonographic (US) criteria. T1-weighted fast low-angle shot MR imaging was performed before and after administration of gadopenetetate dimeglumine. MR imaging findings were correlated with other imaging results and histopathologic findings. Special attention was paid to multifocality and multicentricity. RESULTS Histopathologic analysis revealed 143 benign and 405 malignant lesions. The sensitivity, specificity, and accuracy were 58%, 76%, and 62% for clinical examination; 86%, 32%, and 72% for conventional mammography; 75%, 80%, and 76% for US; and 93%, 65%, and 85% for contrast-enhanced MR imaging. Multifocality in 30 of 42 patients, multicentricity in 24 of 50 patients, and additional contralateral carcinomas in 15 of 19 patients were depicted with MR imaging alone. Due to the MR imaging findings, therapy was changed correctly in 66 patients (14.3%); unnecessary open biopsy was performed in 16 patients (3.5%). CONCLUSION Contrast-enhanced MR imaging of the breast is highly sensitive for invasive breast cancer. MR imaging may reveal unsuspected multifocal, multicentric, or contralateral breast carcinoma and result in therapy changes.
Composing contracts: an adventure in financial engineering (functional pearl)

Financial and insurance contracts do not sound like promising territory for functional programming and formal semantics, but in fact we have discovered that insights from programming languages bear directly on the complex subject of describing and valuing a large class of contracts.We introduce a combinator library that allows us to describe such contracts precisely, and a compositional denotational semantics that says what such contracts are worth. We sketch an implementation of our combinator library in Haskell. Interestingly, lazy evaluation plays a crucial role.