julilili42/papers huggingface dataset:
Hepatitis B virus‐induced hepatocellular carcinoma: functional roles of MICA variants
2013-05-07

Summary Hepatitis B virus infection is a high‐risk factor for hepatocellular carcinoma. The human major histocompatibility complex class I chain‐related gene A ( MICA ) is a ligand of the NKG2D receptor that modulates the NK and T ‐cell‐mediated immune responses and is associated with several diseases. This study determined the effects of MICA polymorphisms during HBV infection and HBV ‐induced HCC . We conducted a case–controlled study in a Vietnamese cohort and genotyped ten functional MICA polymorphisms including the microsatellite motif in 552 clinically classified hepatitis B virus patients and 418 healthy controls. The serum soluble MICA levels ( sMICA ) were correlated with MICA variants and liver enzyme levels. We demonstrated a significant contribution of MICA rs2596542G/A promoter variant and nonsynonymous substitutions MICA‐129Met/Val , MICA‐251Gln/Arg, MICA‐175Gly/Ser , triplet repeat polymorphism and respective haplotypes with HBV ‐induced HCC and HBV persistence. The circulating sMICA levels in HBV patient groups were elevated significantly compared with healthy controls. A significant contribution of studied MICA variants to sMICA levels was also observed. The liver enzymes alanine amino transferase ( ALT ), aspartate transaminase ( AST ), total bilirubin and direct bilirubin were positively correlated with sMICA levels suggesting sMICA as a biomarker for liver injury. We conclude that MICA polymorphisms play a crucial role in modulating innate immune responses, tumour surveillance and regulate disease susceptibility during HBV infection.
Hypoxia-Inducible Factor 1-Regulated Lysyl Oxidase Is Involved in Staphylococcus aureus Abscess Formation
2013-05-07

ABSTRACT Hypoxia-inducible factor 1 (HIF-1) is the key transcription factor involved in the adaptation of mammals to hypoxia and plays a crucial role in cancer angiogenesis. Recent evidence suggests a leading role for HIF-1 in various inflammatory and infectious diseases. Here we describe the role of HIF-1 in Staphylococcus aureus infections by investigating the HIF-1-dependent host cell response. For this purpose, transcriptional profiling of HIF-1α-deficient HepG2 and control cells, both infected with Staphylococcus aureus , was performed. Four hours after infection, the expression of 190 genes, 24 of which were regulated via HIF-1, was influenced. LOX (encoding lysyl oxidase) was one of the upregulated genes with a potential impact on the course of S. aureus infection. LOX is an amine oxidase required for biosynthetic cross-linking of extracellular matrix components. LOX was upregulated in vitro in different cell cultures infected with S. aureus and also in vivo , in kidney abscesses of mice intravenously infected with S. aureus and in clinical skin samples from patients with S. aureus infections. Inhibition of LOX by β-aminopropionitrile (BAPN) did not affect the bacterial load in kidneys or blood but significantly influenced abscess morphology and collagenization. Our data provide evidence for a crucial role of HIF-1-regulated LOX in abscess formation.
Pentacene-based nanorods on Au(111) single crystals: Charge transfer, diffusion, and step-edge barriers
2013-05-07

We investigate nanorod assemblies of two δ 4-substituted pentacenes, namely (2,3-X 2-9,10-Y 2)-substituted pentacenes with X = Y = OCH3 (MOP) and with X = F, Y = OCH3 (MOPF), grown on Au(111) single crystals. By using a multi-technique approach based on ultraviolet photoelectron spectroscopy, X-ray photoelectron spectroscopy, and X-ray absorption, we find evidence for charge transfer screening at the interface with gold. Furthermore, the MOP and MOPF nanorods show a rough surface morphology, which was investigated with atomic force microscopy. We use molecular simulation techniques to investigate the energetic barriers to diffusion and to traverse step-edges to estimate their influence on the nanorod roughness. We find that barriers to surface diffusion on a terrace are anisotropic and that their direction favors the formation of nanorods in these materials.
Application of a rotating bioreactor consisting of low‐cost and ready‐to‐use medical disposables for in vitro evaluation of the endothelialization efficiency of small‐caliber vascular prostheses
2013-05-07

Abstract The incomplete endothelialization of especially small‐caliber vascular prostheses after implantation in patients is a major disadvantage in cardiovascular interventions. The lack of an endothelium leads to the occurrence of thrombosis at the luminal surface of artificial vascular prostheses. Thus, the development of new graft materials and coatings for induction of complete endothelialization on the implant surfaces is a promising approach to improve hemocompatibility and maintain long‐term graft patency. In this study, we designed a rotation model to evaluate the early endothelial cell (EC) seeding efficiency of different small‐caliber vascular devices, such as stents and vascular grafts. The suitability of the designed rotation model for endothelialization studies was investigated by seeding and cultivation of prostheses with ECs followed by scanning electron microscopy. Furthermore, the viability of attached ECs was determined by calcein acetoxymethyl ester (AM) staining. The rotation model consisting of low‐cost medical disposables enabled sterile incubation and cultivation of ECs with vascular devices. Simultaneously, the rotation of the bioreactor ensured a uniform distribution and adhesion of cells to the devices. Calcein AM staining of adherent cells on prostheses revealed excellent cell viability. Moreover, using the designed rotation model, an influence of different coatings and materials on the adhesion and spreading of ECs was demonstrated. The rotating bioreactor described and used in this study not only saves time and money but is also eminently useful for the accelerated preclinical evaluation of the endothelialization efficiency of different materials and surface coatings of small‐caliber vascular devices. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.
A Rare Case of Synchronous Renal Cell Carcinoma of the Bladder Presenting with Gross Hematuria
2013-05-07

A 57-year old man was referred to the Urology Department due to gross hematuria; abdominal ultrasound revealed an unspecific solid tumor of the left bladder wall. Ultrasound, transurethral resection of the bladder mass with subsequent histological analysis, thoracic and abdominal computed tomography-scan and brain magnetic resonance imaging were performed. He was diagnosed with a bladder metastasis of clear cell renal cell carcinoma (RCC) with concomitant bone, pulmonary, and cerebral metastatic disease of a primary RCC of the right kidney. Management: Transurethral resection of the bladder mass, cerebral and bone radiotherapy, removal of the primary tumor, targeted systemic therapy with mTOR followed by tyrosine kinase inhibition.
Holocene climate variability in the Winter Rainfall Zone of South Africa
2013-05-07

Abstract. We established a multi-proxy time series comprising analyses of major elements in bulk sediments, Sr and Nd isotopes and grain size of terrigenous fraction, and δ18O and δ13C in tests of Neogloboquadrina pachyderma (sinistral) from a marine sediment sequence recovered off the Orange River. The records reveal coherent patterns of variability that reflect changes in wind strength, precipitation over the river catchments, and upwelling of cold and nutrient-rich coastal waters off western South Africa. The wettest episode of the Holocene in the Winter Rainfall Zone (WRZ) of South Africa occurred during the "Little Ice Age" (700–100 yr BP). Wet phases were accompanied by strengthened coastal water upwellings, a decrease of Agulhas water leakage into the southern Atlantic, and a reduced dust incursion over Antarctica. A continuous aridification trend in the WRZ and a weakening of the southern Benguela Upwelling System (BUS) between 9000 and 5500 yr BP parallel with increase of dust deposition over Antarctica and an enhanced leakage of warm Agulhas water into the southeastern Atlantic. The temporal relationship between precipitation changes in the WRZ, the thermal state of the coastal surface water, and leakage of warm water in southern Atlantic, and variation of dust incursion over Antarctica suggests a causal link that most likely was related to latitudinal shifts of the Southern Hemisphere westerlies. Our results of the mid-Holocene time interval may serve as an analogue to a possible long-term consequence of the current and future southward shift of the westerlies that may result in a decline of rainfall over southwest Africa and a weakened upwelling with implication for phytoplankton productivity and fish stocks. Furthermore, warming of the coastal surface water as a result of warm Agulhas water incursion into the southern BUS may affect coastal fog formation that is critical as moisture source for the endemic flora of the Namaqualand.
Five gene products are required for assembly of the central pyrrole moiety of coumermycin A1
2013-05-07

Abstract Coumermycin A1 is an aminocoumarin antibiotic produced by Streptomyces rishiriensis. It exhibits potent antibacterial and anticancer activity. The coumermycin A1 molecule contains two terminal 5-methyl-pyrrole-2-carboxylic acid moieties and one central 3-methylpyrrole-2,4-dicarboxylic acid moiety (CPM). While the biosynthesis of the terminal moieties has been elucidated in detail, the pathway leading to the CPM remains poorly understood. In this work, the minimal set of genes required for the generation of the CPM scaffold was identified. It comprises the five genes couR1, couR2a, couR2b, couR3, and couR4 which are grouped together in a contiguous 4.7 kb region within the coumermycin A1 biosynthetic gene cluster. The DNA fragment containing these genes was cloned into an expression plasmid and heterologously expressed in Streptomyces coelicolor M1146. Thereupon, the formation of CPM could be shown by HPLC and by HPLC-MS/MS, in comparison to an authentic CPM standard. This proves that the genes couR1–couR4 are sufficient to direct the biosynthesis of CPM, and that the adjacent genes couR5 and couR6 are not required for this pathway. The enzyme CouR3 was expressed in Escherichia coli and purified to near homogeneity. The protein exhibited an ATPase activity similar to that reported for its close ortholog, the threonine kinase PduX. However, we could not show a threonine kinase activity of CouR3, and; therefore, the substrate of CouR3 in CPM biosynthesis is still unknown and may be different from threonine.
OnKant's Conception of Inner Sense: Self‐Affection by the Understanding
2013-05-08

Abstract Among the extensive literature on the first C ritique , very few commentators offer a thorough analysis of K ant's conception of inner sense. This is quite surprising since the notion is central to K ant's theoretical philosophy, and it is very difficult to provide a consistent interpretation of this notion. In this paper, I first summarize K ant's claims about inner sense in the T ranscendental A esthetic and show why existing interpretations have been unable to dissolve the tensions arising from the conjunction of these claims. Secondly, I present my own reconstruction of K ant's model of inner sense, relying essentially on K antian considerations found in the B ‐version of the T ranscendental D eduction. My main idea is that inner sense, for K ant, is a passive faculty that gets affected by the understanding performing its figurative synthesis on material given in outer sense. In the remainder of the paper, I highlight a few consequences of my interpretation and outline ways to deal with some objections.
The impact of climate change on the structure of Pleistocene food webs across the mammoth steppe
2013-05-08

Species interactions form food webs, impacting community structure and, potentially, ecological dynamics. It is likely that global climatic perturbations that occur over long periods of time have a significant influence on species interaction patterns. Here, we integrate stable isotope analysis and network theory to reconstruct patterns of trophic interactions for six independent mammalian communities that inhabited mammoth steppe environments spanning western Europe to eastern Alaska (Beringia) during the Late Pleistocene. We use a Bayesian mixing model to quantify the contribution of prey to the diets of local predators, and assess how the structure of trophic interactions changed across space and the Last Glacial Maximum (LGM), a global climatic event that severely impacted mammoth steppe communities. We find that large felids had diets that were more constrained than those of co-occurring predators, and largely influenced by an increase in Rangifer abundance after the LGM. Moreover, the structural organization of Beringian and European communities strongly differed: compared with Europe, species interactions in Beringian communities before—and possibly after—the LGM were highly modular. We suggest that this difference in modularity may have been driven by the geographical insularity of Beringian communities.
Different Types of Laughter Modulate Connectivity within Distinct Parts of the Laughter Perception Network
2013-05-08

Laughter is an ancient signal of social communication among humans and non-human primates. Laughter types with complex social functions (e.g., taunt and joy) presumably evolved from the unequivocal and reflex-like social bonding signal of tickling laughter already present in non-human primates. Here, we investigated the modulations of cerebral connectivity associated with different laughter types as well as the effects of attention shifts between implicit and explicit processing of social information conveyed by laughter using functional magnetic resonance imaging (fMRI). Complex social laughter types and tickling laughter were found to modulate connectivity in two distinguishable but partially overlapping parts of the laughter perception network irrespective of task instructions. Connectivity changes, presumably related to the higher acoustic complexity of tickling laughter, occurred between areas in the prefrontal cortex and the auditory association cortex, potentially reflecting higher demands on acoustic analysis associated with increased information load on auditory attention, working memory, evaluation and response selection processes. In contrast, the higher degree of socio-relational information in complex social laughter types was linked to increases of connectivity between auditory association cortices, the right dorsolateral prefrontal cortex and brain areas associated with mentalizing as well as areas in the visual associative cortex. These modulations might reflect automatic analysis of acoustic features, attention direction to informative aspects of the laughter signal and the retention of those in working memory during evaluation processes. These processes may be associated with visual imagery supporting the formation of inferences on the intentions of our social counterparts. Here, the right dorsolateral precentral cortex appears as a network node potentially linking the functions of auditory and visual associative sensory cortices with those of the mentalizing-associated anterior mediofrontal cortex during the decoding of social information in laughter.
Multiple Protein Analysis of Formalin-fixed and Paraffin-embedded Tissue Samples with Reverse phase Protein Arrays
2013-05-08

Reverse-phase protein arrays (RPPAs) have become an important tool for the sensitive and high-throughput detection of proteins from minute amounts of lysates from cell lines and cryopreserved tissue. The current standard method for tissue preservation in almost all hospitals worldwide is formalin fixation and paraffin embedding, and it would be highly desirable if RPPA could also be applied to formalin-fixed and paraffin embedded (FFPE) tissue. We investigated whether the analysis of FFPE tissue lysates with RPPA would result in biologically meaningful data in two independent studies. In the first study on breast cancer samples, we assessed whether a human epidermal growth factor receptor (HER) 2 score based on immunohistochemistry (IHC) could be reproduced with RPPA. The results showed very good concordance between the IHC and RPPA classifications of HER2 expression. In the second study, we profiled FFPE tumor specimens from patients with adenocarcinoma and squamous cell carcinoma in order to find new markers for differentiating these two subtypes of non-small cell lung cancer. p21-activated kinase 2 could be identified as a new differentiation marker for squamous cell carcinoma. Overall, the results demonstrate the technical feasibility and the merits of RPPA for protein expression profiling in FFPE tissue lysates.
A Luminescent Material: La3Cl(CN2)O3 Doped with Eu3+ or Tb3+ Ions
2013-05-08

Abstract The new carbodiimide compound La 3 Cl(CN 2 )O 3 was obtained by a solid‐state metathesis reaction from LaOCl and Li 2 (CN 2 ) at 750 °C in a fused tube. Differential scanning calorimetry of the reaction mixture was performed. The crystal structure of La 3 Cl(CN 2 )O 3 was determined by single‐crystal X‐ray diffraction studies (space group Cmcm , No. 63). The luminescent properties of the Eu 3+ ‐ and Tb 3+ ‐doped compounds are reported.
Antiproliferative and Cytotoxic Properties of Moxifloxacin on Rat Retinal Ganglion Cells
2013-05-08

These results suggest a dose-dependent cytotoxic and antiproliferative effect of moxifloxacin on RGC5. Therefore, intracameral application of moxifloxacin should be used cautiously in patients with increased risk of retinal ganglion cells damage, particularly in glaucoma patients.
Unwanted baggage
2013-05-08

An elderly woman with a rapidly progressing lower leg ulcer presented with features of systemic inflammatory response syndrome (SIRS). The ulcer had occurred after hitting her leg against a piece of luggage. The causative pathogen in our case was by Corynebacterium ulcerans , demonstrated in bacterial cultures and by PCR. Disease progression was stopped only by Linezolid intravenous. after several other antibiotics failed to help. Diphtheria is known to most physicians as a respiratory disease caused by Corynebacterium diphtheria which is occurring in the developed world infrequently because of widespread use of immunisation programmes. However, cutaneous infection with diphtheria is increasingly being diagnosed.
Well‐Defined Molecular Magnesium Hydride Clusters: Relationship between Size and Hydrogen‐Elimination Temperature
2013-05-09

Abstract A new tetranuclear magnesium hydride cluster, [{ NN ‐(MgH) 2 } 2 ], which was based on a NN‐coupled bis‐β‐diketiminate ligand ( NN 2− ), was obtained from the reaction of [{ NN ‐(Mg n Bu) 2 } 2 ] with PhSiH 3 . Its crystal structure reveals an almost‐tetrahedral arrangement of Mg atoms and two different sets of hydride ions, which give rise to a coupling in the NMR spectrum ( J =8.5 Hz). To shed light on the relationship between the cluster size and H 2 release, the thermal decomposition of [{ NN ‐(MgH) 2 } 2 ] and two closely related systems that were based on similar ligands, that is, an octanuclear magnesium hydride cluster and a dimeric magnesium hydride species, have been investigated in detail. A lowering of the H 2 ‐desorption temperature with decreasing cluster size is observed, in line with previously reported theoretical predictions on (MgH 2 ) n model systems. Deuterium‐labeling studies further demonstrate that the released H 2 solely originates from the oxidative coupling of two hydride ligands and not from other hydrogen sources, such as the β‐diketiminate ligands. Analysis of the DFT‐computed electron density in [{ NN ‐(MgH) 2 } 2 ] reveals a counterintuitive interaction between two formally closed‐shell H − ligands that are separated by 3.106 Å. This weak interaction could play an important role in H 2 desorption. Although the molecular product after H 2 release could not be characterized experimentally, DFT calculations on the proposed decomposition product, that is, the low‐valence tetranuclear Mg(I) cluster [( NN ‐Mg 2 ) 2 ], predict a structure with two almost‐parallel, localized MgMg bonds. As in a previously reported β‐diketiminate Mg I dimer, the MgMg bond is not characterized by a bond critical point, but instead displays a local maximum of electron density midway between the atoms, that is, a non‐nuclear attractor (NNA). Interestingly, both of the NNAs in [( NN ‐Mg 2 ) 2 ] are connected through a bond path that suggests that there is bonding between all four Mg I atoms.
Simultaneously Acquired MR/PET Images Compared with Sequential MR/PET and PET/CT: Alignment Quality
2013-05-09

The alignment of hybrid datasets acquired in simultaneous whole-body MR/PET was more accurate than retrospective fusion in all investigated abdominal organs, and more accurate than PET/CT in the urinary bladder; the alignment of thoracic MR/PET with expiratory breath hold or free-breathing MR was more exact than with inspiratory MR. However in this preliminary work the clinical importance of these degrees of misalignment was not assessed.
Immunohistochemical detection of Helicobacter pylori without association of TLR5 expression in oral squamous cell carcinoma
2013-05-09

Background Approximately 15% of human deaths from cancer are associated with chronic viral or bacterial infections. Helicobacter pylori ( HP ), a flagellated, Gram‐negative, spiral, microaerophilic bacteria is considered to be the most common chronic bacterial infection in humans. Toll‐like receptor 5 ( TLR 5) is involved in recognition of bacterial flagella and is thought to promote tumour growth through inflammation‐dependent mechanisms in epithelial cells. Methods Expression of HP and TLR 5 was analysed in OSCC specimen ( n = 191) by immunohistochemistry. TLR 5 expression specificity was conducted by Western blotting in cancer cell lines ( BICR 3, BICR 56). TLR 5‐stained sections were scanned and digitally analysed using ImageJ and the immunomembrane plug‐in. HP expression and TLR 5 expression were associated with clinicopathological characteristics and impact on survival. Results Helicobacter pylori detection was significantly associated with recurrence of the tumour, whereas TLR 5 expression was not. Multivariate analysis demonstrated HP expression as an independent prognostic factor ( P = 0.0260). TLR 5 specificity was confirmed by W estern blot analysis. Conclusions For the first time, this study provides evidence that immunohistochemically detected HP expression in OSCC is associated with reduced disease‐free survival in a large patient cohort. Although TLR 5 was not associated with any clinicopathological characteristics or impact on survival, investigation of the TLR family seems to be reasonable due to the possible existence of other pathogenic bacterial or viral compounds in oral cavity cancer.
Synthesis and characterization of [1,4-bis(α,β-galactopyranos-6-yl)phthalocyaninato]zinc(II)
2013-05-10

Herein we present the synthesis and full characterization of the water-soluble [1,4-bis(α,β-galactopyranos-6-yl)phthalocyaninato]zinc(II) (8). For a cross-condensation with phthalonitrile in presence of zinc bromide, bisglycosylated phthalonitrile (5) has been synthesized by nucleophilic displacement of triflyl groups or fluorine atoms by acetonide protected galactose in the appropriated phthalonitriles 1 and 2. Furthermore we prepared 3,6-bis(1,2:3,4-di-O-isopropylidene-α-D-galactopyranos-6-yl)phthalonitrile (5) starting from 2,3-dicyanohydroquinone and 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose using a Mitsunobu protocol. UV-vis spectra of 8 were measured in DMSO, water and PBS-buffer at different concentrations.