Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypoxia-Induced Reactive Oxygen Species Cause Chromosomal Abnormalities in Endothelial Cells in the Tumor Microenvironment

There is much evidence that hypoxia in the tumor microenvironment enhances tumor progression. In an earlier study, we reported abnormal phenotypes of tumor-associated endothelial cells such as those resistant to chemotherapy and chromosomal instability. Here we investigated the role of hypoxia in the acquisition of chromosomal abnormalities in endothelial cells. Tumor-associated endothelial cells isolated from human tumor xenografts showed chromosomal abnormalities, >30% of which were aneuploidy. Aneuploidy of the tumor-associated endothelial cells was also shown by simultaneous in-situ hybridization for chromosome 17 and by immunohistochemistry with anti-CD31 antibody for endothelial staining. The aneuploid cells were surrounded by a pimonidazole-positive area, indicating hypoxia. Human microvascular endothelial cells expressed hypoxia-inducible factor 1 and vascular endothelial growth factor A in response to either hypoxia or hypoxia-reoxygenation, and in these conditions, they acquired aneuploidy in 7 days. Induction of aneuploidy was inhibited by either inhibition of vascular endothelial growth factor signaling with vascular endothelial growth factor receptor 2 inhibitor or by inhibition of reactive oxygen species by N-acetyl-L-cysteine. These results indicate that hypoxia induces chromosomal abnormalities in endothelial cells through the induction of reactive oxygen species and excess signaling of vascular endothelial growth factor in the tumor microenvironment.
Men at work.

THE UK'S nursing workforce now includes more than 10 per cent of male nurses. Next week the Nursing and Midwifery Council will publish its annual breakdown of new registrant figures which show 10.21 per cent of nurses (65,755) are men - the highest ever level. The proportion of men on the register has been rising steadily over the past decade and it is expected the figure will double in the next decade as more men opt to study nursing at university.
The prevalence of bovine trypanosomes in parts of Benue state, north-central Nigeria.

Tsetse-borne African animal trypanosomiasis remains a serious threat to livestock production in sub-Saharan Africa. The disease limits the full potential of agricultural development in 36 endemic countries of Africa 1,2 . In Nigeria, livestock production is limited by trypanosomiasis as tsetse flies infest about 75% of the nation’s land mass 3 subjecting the animal population at great risk of the disease. In the absence of vaccine against the disease, case detection, treatment and vector control remain strategic control options. Previous reports on trypanosomiasis showed that Benue state was a known human African trypanosomiasis (HAT)/sleeping sickness endemic focus 4,5 . In addition, trypanosomes of veterinary importance had also been recorded 6 . A recent survey on HAT in Benue state showed that the areas surveyed were no longer endemic for sleeping sickness 7 . Our purpose was to investi
Plasma and dietary magnesium and risk of sudden cardiac death in women.

BACKGROUND Magnesium has antiarrhythmic properties in cellular and experimental models; however, its relation to sudden cardiac death (SCD) risk is unclear. OBJECTIVE We prospectively examined the association between magnesium, as measured in diet and plasma, and risk of SCD. DESIGN The analysis was conducted within the Nurses' Health Study. The association for magnesium intake was examined prospectively in 88,375 women who were free of disease in 1980. Information on magnesium intake, other nutrients, and lifestyle factors was updated every 2-4 y through questionnaires, and 505 cases of sudden or arrhythmic death were documented over 26 y of follow-up. For plasma magnesium, a nested case-control analysis including 99 SCD cases and 291 controls matched for age, ethnicity, smoking, and presence of cardiovascular disease was performed. RESULTS After multivariable adjustment for confounders and potential intermediaries, the relative risk of SCD was significantly lower in women in the highest quartile compared with those in the lowest quartile of dietary (relative risk: 0.63; 95% CI: 0.44, 0.91) and plasma (relative risk: 0.23; 95% CI: 0.09, 0.60) magnesium. The linear inverse relation with SCD was strongest for plasma magnesium (P for trend = 0.003), in which each 0.25-mg/dL (1 SD) increment in plasma magnesium was associated with a 41% (95% CI: 15%, 58%) lower risk of SCD. CONCLUSIONS In this prospective cohort of women, higher plasma concentrations and dietary magnesium intakes were associated with lower risks of SCD. If the observed association is causal, interventions directed at increasing dietary or plasma magnesium might lower the risk of SCD.
REBULF super junction MOSFET with N + buried layer

A reduced bulk field (REBULF) super junction metal-oxide semiconductor field-effect transistor is designed for the first time with N+ buried layer in the P-type high resistance substrate. The substrate-assisted depletion effect, resulting from charge imbalance between the N and P-type pillars when the super junction is implemented on the P-type substrate, is suppressed due to the charge compensation by the N+ buried layer. The high electric field around the drain is reduced, thanks to the REBULF effect which causes the redistribution of the electric field in the drift region; thus the breakdown voltage is improved because the substrate supports more biases. The new structure features high breakdown voltage, low specific on-resistance and charge balance in drift region.
Unique continuation and decay for the Korteweg-de Vries equation with localized damping

This work is devoted to prove the exponential decay for the energy of solutions of the Korteweg-de Vries equation in a bounded interval with a localized damping term. Following the method in Menzala (2002) which combines energy estimates, multipliers and compactness arguments the problem is reduced to prove the unique continuation of weak solutions. In Menzala (2002) the case where solutions vanish on a neighborhood of both extremes of the bounded interval where equation holds was solved combining the smoothing results by T. Kato (1983) and earlier results on unique continuation of smooth solutions by J.C. Saut and B. Scheurer (1987). In this article we address the general case and prove the unique continuation property in two steps. We first prove, using multiplier techniques, that solutions vanishing on any subinterval are necessarily smooth. We then apply the existing results on unique continuation of smooth solutions.
DNA double-strand break repair in cell-free extracts from Ku80-deficient cells: implications for Ku serving as an alignment factor in non-homologous DNA end joining

Non-homologous DNA end joining (NHEJ) is considered the major pathway of double-strand break (DSB) repair in mammalian cells and depends, among other things, on the DNA end-binding Ku70/80 hetero-dimer. To investigate the function of Ku in NHEJ we have compared the ability of cell-free extracts from wild-type CHO-K1 cells, Ku80-deficient xrs6 cells and Ku80-cDNA-complemented xrs6 cells (xrs6-Ku80) to rejoin different types of DSB in vitro. While the two Ku80-proficient extracts were highly efficient and accurate in rejoining all types of DNA ends, the xrs6 extract displayed strongly decreased NHEJ efficiency and accuracy. The lack of accuracy is most evident in non-homologous terminus configurations containing 3'-overhangs that abut a 5'-overhang or blunt end. While the sequences of the 3'-overhangs are mostly preserved by fill-in DNA synthesis in the Ku80-proficient extracts, they are always completely lost in the xrs6 extract so that, instead, small deletions displaying microhomology patches at their breakpoints arise. In summary, our results are consistent with previous results from Ku-deficient yeast strains and indicate that Ku may serve as an alignment factor that not only increases NHEJ efficiency but also accuracy. Furthermore, a secondary NHEJ activity is present in the absence of Ku which is error-prone and possibly assisted by base pairing interactions.
Integrated 3D conducting polymer-based bioelectronics for capture and release of circulating tumor cells.

Here we develop a novel fabrication approach for producing three-dimensional (3D) conducting polymer-based bioelectronic interfaces (BEIs) that can be integrated on electronic devices for rare circulating tumor cell (CTC) isolation, detection, and collection via an electrically triggered cell released from chips. Based on the chemical oxidative polymerization of carboxylic acid-modified 3,4-ethylenedioxythiophene and modified poly(dimethylsiloxane) (PDMS) transfer printing technology, the high-aspect-ratio structures of poly(3,4-ethylenedioxythiophene) (PEDOT)-based "nanorod" arrays can be fabricated on indium tin oxide (ITO) electrodes when using the Si "microrod" arrays as masters. Furthermore, we integrated the biotinylated poly-(l)-lysine-graft-poly-ethylene-glycol (PLL-g-PEG-biotin) coating with 3D PEDOT-based BEIs for dynamic control of the capture/release performance of CTCs on chips; this combination exhibited an optimal cell-capture yield cells of ∼45 000 cells cm-2 from EpCAM-positive MCF7 while maintaining resistance from the adhesion of EpCAM-negative HeLa cells at a density of ∼4000 cells cm-2. By taking advantage of the electrochemical doping/dedoping properties of PEDOT materials, the captured CTCs can be triggered to be electrically released through the desorption phenomena of the PLL-g-PEG-biotin. More than 90% of the captured cells can be released while maintaining very high cell viability. Therefore, it is conceivable that the use of a 3D PEDOT-based BEI platform will meet the requirements for the development of downstream characterization of CTCs, as well as the next generation of bioelectronics for biomedical applications.
Tumor‐infiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma

Cells with deficient DNA mismatch repair develop microsatellite instability. Extensive microsatellite instability (MSI‐high) is characteristic of colorectal carcinomas in hereditary nonpolyposis colorectal carcinoma (HNPCC) and in 10–% 15% of sporadic colorectal carcinomas. Microsatellite instability‐high colorectal carcinomas differ from others in important clinical and pathologic features. However, MSI typing is expensive and not widely available. Microsatellite instability type may be predicted by tumor‐infiltrating lymphocytes (TILs), which can be evaluated with ordinary light microscopy.
Structural refinement of protein segments containing secondary structure elements: Local sampling, knowledge‐based potentials, and clustering

In this article, we present an iterative, modular optimization (IMO) protocol for the local structure refinement of protein segments containing secondary structure elements (SSEs). The protocol is based on three modules: a torsion‐space local sampling algorithm, a knowledge‐based potential, and a conformational clustering algorithm. Alternative methods are tested for each module in the protocol. For each segment, random initial conformations were constructed by perturbing the native dihedral angles of loops (and SSEs) of the segment to be refined while keeping the protein body fixed. Two refinement procedures based on molecular mechanics force fields — using either energy minimization or molecular dynamics — were also tested but were found to be less successful than the IMO protocol. We found that DFIRE is a particularly effective knowledge‐based potential and that clustering algorithms that are biased by the DFIRE energies improve the overall results. Results were further improved by adding an energy minimization step to the conformations generated with the IMO procedure, suggesting that hybrid strategies that combine both knowledge‐based and physical effective energy functions may prove to be particularly effective in future applications. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Nutritional programming in sea bass 1 2 3 Ontogenic effects of early feeding of sea bass ( Dicentrarchus labrax ) larvae with a range 4 of dietary n-3 HUFA levels on the functioning of PUFA desaturation pathways 5 6 7

Nutritional programming in sea bass 1 2 3 Ontogenic effects of early feeding of sea bass (Dicentrarchus labrax) larvae with a range 4 of dietary n-3 HUFA levels on the functioning of PUFA desaturation pathways 5 6 7 Marie Vagner a1 c1 , Abstract 19 20 Four replicated groups of sea bass larvae were fed XH (3.7% EPA+DHA), HH (1.7%), 21 LH (0.7%) or XLH (0.5%) diets from d-6 to d-45 (XH1, HH1, LH1, XLH1; exp.1). After a 22 subsequent one-month period feeding a commercial diet (2.7% EPA+DHA), the capacity of 23 the four initial groups to adapt to an n-3 HUFA-Restricted diet (0.3% EPA+DHA; R-groups: 24 XH2 R , HH2 R , LH2 R , XLH2 R) was tested for 35 days. Larval dietary treatments had no effect 25 on larval and juvenile survival rates. Wet weight of d-45 larvae was higher in XH1 and HH1 26 (P<0.001), but the R-juvenile mass gains were similar in all treatments. Delta-6-desaturase 27 (∆6D) mRNA level was higher in LH1 and XLH1 at d-45 (P<0.001), and higher in LH2 R and 28 XLH2 R , with a significant increase at d-118. Concomitantly, PPAR α and β mRNA levels 29 were higher in XLH1 at d-45, and PPAR β and γ mRNA levels were higher in the XLH2 R at 30 d-118, suggesting possible involvement of PPARs in stimulation of ∆6D expression, when 31 drastic dietary larval conditioning occurred. The low DHA content in phospholipid (PL) of 32 LH1 and XLH1 revealed an n-3-HUFA deficiency in these groups. Larval conditioning did 33 not affect DHA content in PL of R-juveniles. This study showed (i) a persistent ∆6D mRNA 34 2 enhancement in juveniles pre-conditioned with an n-3 HUFA deficient larval diet, over the 35 one-month intermediate period, and (ii) brought new findings suggesting the involvement of 36 PPARs in the ∆6D mRNA level stimulation. However such nutritional conditioning had no 37 significant effect on juvenile growth and lipid composition. 38 39 Introduction 40
Comparing Advanced Graph-based and Transition-based Dependency Parsers

In this paper, we compare a higher order graph-based parser and a transitionbased parser with beam search. These parsers provide a higher accuracy than a second order MST parser and a deterministic transition-based parser. We apply and compare the output on languages, which have not been in the research focus of Shared Tasks. The parser are implemented in a uniform framework. The transitionbased parser was newley implemented and we revised the graph-based parser. The graph-based parser has to our knowlege the highest published scores for French and Czech with 90.40 and 81.43 labeled accuracy score.
Early and delayed afterdepolarizations in rabbit heart Purkinje cells viewed by confocal microscopy.

We investigated action potentials and Ca(2+) transients in rabbit Purkinje myocytes using whole cell patch clamp recordings and a confocal microscope. Purkinje cells were loaded with 5 microM Fluo-3/AM for 30min. Action potentials were elicited by application of a stimulus delivered through the recording pipettes. When Purkinje cells were stimulated in 2.0mM Ca(2+), transverse XT line scans revealed a symmetrical 'U'-shaped Ca(2+) transient demonstrating that the transient was initiated at the cell periphery. When Purkinje cells were superfused with 1 microM isoprenaline, both early and delayed afterdepolarizations were induced. XT line scans of cells exhibiting early afterdepolarizations showed a second symmetrical 'U'-shaped transient. This Ca(2+) transient was initiated at the cell periphery suggesting reactivation of the Ca(2+) current. In contrast, in Purkinje cells exhibiting delayed afterdepolarizations and a corresponding transient inward current, XT line scans revealed a heterogenous rise in Ca(2+) at both peripheral and central regions of the cell. Immunofluorescence staining of Purkinje cells with an antibody to ryanodine receptors (RyRs) revealed that RyRs are located at regularly spaced intervals throughout the interior of Purkinje cells. These results suggest that, although RyRs are located throughout Purkinje cells, only peripheral RyRs are activated to produce transients, sparks and early afterdepolarizations. During delayed afterdepolarizations, we observed a heterogenous rise in Ca(2+) at both peripheral and central regions of the cell as well as large central increases in Ca(2+). Although the latter may result from central release, we cannot exclude the possibility that it reflects Ca(2+) diffusion from subsarcolemmal sites.
miR-126 Is Downregulated in Cystic Fibrosis Airway Epithelial Cells and Regulates TOM1 Expression

Cystic fibrosis (CF) is one of the most common lethal genetic diseases in which the role of microRNAs has yet to be explored. Predicted to be regulated by miR-126, TOM1 (target of Myb1) has been shown to interact with Toll-interacting protein, forming a complex to regulate endosomal trafficking of ubiquitinated proteins. TOM1 has also been proposed as a negative regulator of IL-1β and TNF-α–induced signaling pathways. MiR-126 is highly expressed in the lung, and we now show for the first time differential expression of miR-126 in CF versus non-CF airway epithelial cells both in vitro and in vivo. MiR-126 downregulation in CF bronchial epithelial cells correlated with a significant upregulation of TOM1 mRNA, both in vitro and in vivo when compared with their non-CF counterparts. Introduction of synthetic pre–miR-126 inhibited luciferase activity in a reporter system containing the full length 3′-untranslated region of TOM1 and resulted in decreased TOM1 protein production in CF bronchial epithelial cells. Following stimulation with LPS or IL-1β, overexpression of TOM1 was found to downregulate NF-κB luciferase activity. Conversely, TOM1 knockdown resulted in a significant increase in NF-κB regulated IL-8 secretion. These data show that miR-126 is differentially regulated in CF versus non-CF airway epithelial cells and that TOM1 is a miR-126 target that may have an important role in regulating innate immune responses in the CF lung. To our knowledge, this study is the first to report of a role for TOM1 in the TLR2/4 signaling pathways and the first to describe microRNA involvement in CF.
The alpha v beta 6 integrin promotes proliferation of colon carcinoma cells through a unique region of the beta 6 cytoplasmic domain

Cell-matrix interactions are assumed to be important in regulating differentiation and tumor cell growth; however, the precise roles of individual matrix receptors in producing cellular responses are still unclear. We have previously described the alpha v beta 6 integrin, an epithelial cell fibronectin receptor expressed in many carcinoma cell lines. Here we show that heterologous expression of alpha v beta 6 in a human colon carcinoma cell line (SW480) enhances the proliferative capacity of these cells, both in vitro and in vivo in nude mice. This property of alpha v beta 6 correlates with the presence of an 11-amino acid region at the COOH terminus of the beta 6 cytoplasmic domain. This 11-amino acid sequence is required for the growth stimulatory effect, but not for other functions of the beta 6 cytoplasmic domain, such as promoting cell adhesion and focal contact localization.
Nuclear cysteine cathepsin variants in thyroid carcinoma cells

Abstract The cysteine peptidase cathepsin B is important in thyroid physiology by being involved in thyroid prohormone processing initiated in the follicular lumen and completed in endo-lysosomal compartments. However, cathepsin B has also been localized to the extrafollicular space and is therefore suggested to promote invasiveness and metastasis in thyroid carcinomas through, e.g., ECM degradation. In this study, immunofluorescence and biochemical data from subcellular fractionation revealed that cathepsin B, in its single- and two-chain forms, is localized to endo-lysosomes in the papillary thyroid carcinoma cell line KTC-1 and in the anaplastic thyroid carcinoma cell lines HTh7 and HTh74. This distribution is not affected by thyroid stimulating hormone (TSH) incubation of HTh74, the only cell line that expresses a functional TSH-receptor. Immunofluorescence data disclosed an additional nuclear localization of cathepsin B immunoreactivity. This was supported by biochemical data showing a proteolytically active variant slightly smaller than the cathepsin B proform in nuclear fractions. We also demonstrate that immunoreactions specific for cathepsin V, but not cathepsin L, are localized to the nucleus in HTh74 in peri-nucleolar patterns. As deduced from co-localization studies and in vitro degradation assays, we suggest that nuclear variants of cathepsins are involved in the development of thyroid malignancies through modification of DNA-associated proteins.
Evidence for a stem cell hierarchy in the adult human breast

Cellular pathways that contribute to adult human mammary gland architecture and lineages have not been previously described. In this study, we identify a candidate stem cell niche in ducts and zones containing progenitor cells in lobules. Putative stem cells residing in ducts were essentially quiescent, whereas the progenitor cells in the lobules were more likely to be actively dividing. Cells from ducts and lobules collected under the microscope were functionally characterized by colony formation on tissue culture plastic, mammosphere formation in suspension culture, and morphogenesis in laminin-rich extracellular matrix gels. Staining for the lineage markers keratins K14 and K19 further revealed multipotent cells in the stem cell zone and three lineage-restricted cell types outside this zone. Multiparameter cell sorting and functional characterization with reference to anatomical sites in situ confirmed this pattern. The proposal that the four cell types are indeed constituents of an as of yet undescribed stem cell hierarchy was assessed in long-term cultures in which senescence was bypassed. These findings identify an adult human breast ductal stem cell activity and its earliest descendants.
Mixing fixed and reconfigurable logic for array processing

This paper describes the architecture of the MIX system that was designed to investigate the trade-off between the use of reconfigurable and fixed logic. The calculation of the dot-product of two vectors of 32 bit floating point numbers, that forms the basis of array processing in many engineering applications, is used as the basic algorithm for the investigation. The results indicate that fixed logic is more suited for floating point units and memories while reconfigurable logic is useful for implementing control logic providing significant flexibility. It was also found that the additional delay in reconfigurable logic can effectively overlap with the operating time of the fixed logic subsystems. The advantage of reconfigurability of the control is therefore combined with the high bandwidth properties of the fixed logic.
17 Dimensional Measurement for Dentistry

Dentistry requires development in hand skills throughout the undergraduate and postgraduate programs both in the pre-clinical and clinical settings (Allred, 1977). The level of expertise achieved depends on the level of training, the natural ability of the dentist and also experience. Tooth preparation for a crown is a common procedure in general dental practice and it is essential that dental students are able to perform this procedure competently before they graduate. The skill training of these techniques is in itself subjective, as there is use of “eyeballing” of the preparation rather than a definite measure. There is clearly a need to obtain more formal dimensional assessment of crown preparations. This will assist in the feedback to and the training of dentists and also in the practise of dentistry.