julilili42/papers huggingface dataset:
Female-typical Subjects and their Effect on Wage Inequalities among Higher Education Graduates in Germany
2012-12-05

ABSTRACT In the search for an explanation of wage inequalities between men and women, it is often argued that women's disadvantages on the labour market are the result of their lower investment in human capital. However, this argument loses for at a time when highly educated women are outperforming men in terms of educational attainment. But even within the group of higher education graduates, gender differences remain in the form of gender-typical enrolment in academic subjects. The present article analyses the wage effects of how graduation in typically female subjects and subsequent work in typically female occupations generate wage inequalities 1 and 5 years after graduation. For understanding these effects, it follows the hypothesis of a socio-cultural devaluation of female-dominated subjects and occupations. Based on the 1997 HIS Absolventenpanel, we estimate gross hourly wages of male and female higher education graduates as they enter the German labour market. Results show that, 1 year after graduation, men receive a higher wage penalty than women for graduating in a female-dominated subject. However, working in typically female occupations affects women's wages more strongly than it does men's immediately after graduation. In addition, women have fewer possibilities to compensate for this penalty in subsequent years.
The GM2 Glycan Serves as a Functional Coreceptor for Serotype 1 Reovirus
2012-12-06

Viral attachment to target cells is the first step in infection and also serves as a determinant of tropism. Like many viruses, mammalian reoviruses bind with low affinity to cell-surface carbohydrate receptors to initiate the infectious process. Reoviruses disseminate with serotype-specific tropism in the host, which may be explained by differential glycan utilization. Although α2,3-linked sialylated oligosaccharides serve as carbohydrate receptors for type 3 reoviruses, neither a specific glycan bound by any reovirus serotype nor the function of glycan binding in type 1 reovirus infection was known. We have identified the oligosaccharide portion of ganglioside GM2 (the GM2 glycan) as a receptor for the attachment protein σ1 of reovirus strain type 1 Lang (T1L) using glycan array screening. The interaction of T1L σ1 with GM2 in solution was confirmed using NMR spectroscopy. We established that GM2 glycan engagement is required for optimal infection of mouse embryonic fibroblasts (MEFs) by T1L. Preincubation with GM2 specifically inhibited type 1 but not type 3 reovirus infection of MEFs. To provide a structural basis for these observations, we defined the mode of receptor recognition by determining the crystal structure of T1L σ1 in complex with the GM2 glycan. GM2 binds in a shallow groove in the globular head domain of T1L σ1. Both terminal sugar moieties of the GM2 glycan, N-acetylneuraminic acid and N-acetylgalactosamine, form contacts with the protein, providing an explanation for the observed specificity for GM2. Viruses with mutations in the glycan-binding domain display diminished hemagglutination capacity, a property dependent on glycan binding, and reduced capacity to infect MEFs. Our results define a novel mode of virus-glycan engagement and provide a mechanistic explanation for the serotype-dependent differences in glycan utilization by reovirus.
Lipoic acid inhibits cell proliferation of tumor cells in vitro and in vivo
2012-12-06

Cancer cells convert glucose preferentially to lactate even in the presence of oxygen (aerobic glycolysis-Warburg effect). New concepts in cancer treatment aim at inhibition of aerobic glycolysis. Pyruvate dehydrogenase converts pyruvate to acetylCoA thus preventing lactate formation. Therefore, the aim of this study was to evaluate compounds that could activate pyruvate dehydrogenase in cancer cells. We investigated the effects of (R)-(+)-α-lipoic acid (LPA) and dichloroacetate (DCA), possible activators of pyruvate dehydrogenase, on suppression of aerobic glycolysis and induction of cell death. The neuroblastoma cell lines Kelly, SK-N-SH, Neuro-2a and the breast cancer cell line SkBr3 were incubated with different concentrations (0.1-30 mM) of LPA and DCA. The effects of both compounds on cell viability/proliferation (WST-1 assay), [18F]-FDG uptake, lactate production and induction of apoptosis (flow cytometric detection of caspase-3) were evaluated. Furthermore, NMRI nu/nu mice that had been inoculated s.c. with SkBr3 cells were treated daily for four weeks with LPA (i.p, 18.5 mg/kg) starting at day 7 p.i.. Tumor development was measured with a sliding caliper and monitored via [18F]-FDG-PET. Residual tumors after therapy were examined histopathologically. These data suggests that LPA can reduce (1) cell viability/proliferation, (2) uptake of [18F]-FDG and (3) lactate production and increase apoptosis in all investigated cell lines. In contrast, DCA was almost ineffective. In the mouse xenograft model with s.c. SkBr3 cells, daily treatment with LPA retarded tumor progression. Therefore, LPA seems to be a promising compound for cancer treatment.
Stimulation of Suicidal Erythrocyte Death by Fumagillin
2012-12-06

Abstract Fumagillin, a cyclohexane isolated from fungus Aspergillus fumigatus , has anti‐infective and anti‐cancer potency. Fumagillin is at least partially effective by inducing suicidal death or apoptosis. In analogy to apoptosis of nucleated cells, eryptosis is the suicidal death of erythrocytes characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Stimulators of eryptosis include increase of cytosolic Ca 2+ ‐activity ([Ca 2+ ] i ) and ceramide. The present study explored whether fumagillin (5–100 μM) could stimulate eryptosis. To this end, [Ca 2+ ] i was estimated from Fluo3 fluorescence, ceramide by utilizing specific antibodies, cell volume from forward scatter, phosphatidylserine exposure from annexin V binding and haemolysis from haemoglobin release. As a result, a 48‐hr exposure to fumagillin significantly increased [Ca 2+ ] i (≥10 μM), enhanced ceramide abundance (100 μM), triggered annexin V binding (≥10 μM) and decreased forward scatter (≥10 μM). Fumagillin exposure was followed by slight but significant increase of haemolysis. Removal of extracellular Ca 2+ significantly blunted but did not abolish the effect of fumagillin (100 μM) on annexin V binding. The present observations disclose a novel effect of fumagillin, that is, stimulation of eryptosis, paralleled by Ca 2+ entry, ceramide formation, phosphatidylserine exposure and decrease of cell volume.
No anticorrelation between cyclotron line energy and X-ray flux in 4U 0115+634
2012-12-06

We report on an outburst of the high mass X-ray binary 4U 0115+634 with a pulse period of 3.6 s in 2008 March/April as observed with RXTE and INTEGRAL. During the outburst the neutron star’s luminosity varied by a factor of 10 in the 3–50 keV band. In agreement with earlier work we find evidence of five cyclotron resonance scattering features at ~10.7, 21.8, 35.5, 46.7, and 59.7 keV. Previous work had found an anticorrelation between the fundamental cyclotron line energy and the X-ray flux. We show that this apparent anticorrelation is probably due to the unphysical interplay of parameters of the cyclotron line with the continuum models used previously, e.g., the negative and positive exponent power law (NPEX). For this model, we show that cyclotron line modeling erroneously leads to describing part of the exponential cutoff and the continuum variability, and not the cyclotron lines. When the X-ray continuum is modeled with a simple exponentially cutoff power law modified by a Gaussian emission feature around 10 keV, the correlation between the line energy and the flux vanishes, and the line parameters remain virtually constant over the outburst. We therefore conclude that the previously reported anticorrelation is an artifact of the assumptions adopted in the modeling of the continuum.
Gαi2 Is the Essential Gαi Protein in Immune Complex–Induced Lung Disease
2012-12-06

Abstract Heterotrimeric G proteins of the Gαi family have been implicated in signaling pathways regulating cell migration in immune diseases. The Gαi-protein–coupled C5a receptor is a critical regulator of IgG FcR function in experimental models of immune complex (IC)–induced inflammation. By using mice deficient for Gαi2 or Gαi3, we show that Gαi2 is necessary for neutrophil influx in skin and lung Arthus reactions and agonist-induced neutrophilia in the peritoneum, whereas Gαi3 plays a less critical but variable role. Detailed analyses of the pulmonary IC-induced inflammatory response revealed several shared functions of Gαi2 and Gαi3, including mediating C5a anaphylatoxin receptor–induced activation of macrophages, involvement in alveolar production of chemokines, transition of neutrophils from bone marrow into blood, and modulation of CD11b and CD62L expression that account for neutrophil adhesion to endothelial cells. Interestingly, C5a-stimulated endothelial polymorphonuclear neutrophil transmigration, but not chemotaxis, is enhanced versus reduced in the absence of neutrophil Gαi3 or Gαi2, respectively, and knockdown of endothelial Gαi2 caused decreased transmigration of wild-type neutrophils. These data demonstrate that Gαi2 and Gαi3 contribute to inflammation by redundant, overlapping, and Gαi-isoform–specific mechanisms, with Gαi2 exhibiting unique functions in both neutrophils and endothelial cells that appear essential for polymorphonuclear neutrophil recruitment in IC disease.
Targeting EpCAM (CD326) for immunotherapy in hepatoblastoma
2012-12-06

Hepatoblastoma (HB) is the most common liver cancer in children. Recurrence of HB after chemotherapy and surgery is frequent among high-risk patients and is associated with chemoresistance. Immunotherapy may improve poor treatment outcomes in HB patients. Cytotoxic leukocytes of the innate and adaptive immune system including different populations of cytotoxic T cells play a major role in fighting developing tumors. In this setting, monoclonal antibodies may be employed to specifically direct immune responses toward tumor cells. We addressed this issue by using humanized antibodies that recognize the cell surface molecule EpCAM (CD326, overexpressed in hepatic tumor cells) to enhance immune responses against HB. EpCAM was constantly expressed on HB cells and its expression was independent of previous therapy based on the DNA-damaging agent cisplatin. Co-culture assays performed with two well-described HB cell lines and tumor tissue cultures demonstrated that tumor cell lysis by γδ T cells can be dramatically augmented by applying EpCAM-specific monoclonal antibodies. These data emphasize the value of antitumor immune responses and encourage adapting immunotherapeutic regimens to improve the outcome of high risk HB.
Adhesion of klotho‐deficient eryptotic erythrocytes to endothelial cells
2012-12-06

Abstract Aim Suicidal erythrocyte death or eryptosis is characterized by cell shrinkage and phosphatidylserine exposure at the cell surface. Eryptotic erythrocytes may adhere to the vascular wall by binding of phosphatidylserine to endothelial CXC chemokine ligand 16 ( CXCL 16). Triggers of eryptosis include osmotic shock or energy depletion. Susceptibility to eryptosis is modified by Klotho, a protein with profound effect on ageing and lifespan. Klotho deficiency leads to accelerated ageing and early death. The percentage of eryptotic erythrocytes is significantly larger in klotho‐deficient mice ( klotho −/− ) than in their wild‐type littermates ( klotho +/+ ). The present study explored whether the accelerated eryptosis of klotho‐deficient mice is paralleled by enhanced adhesion. Methods Phosphatidylserine‐exposing erythrocytes were identified by measurement of annexin V binding and adhesion to human umbilical vein endothelial cells ( HUVEC ) from trapping of labelled erythrocytes in a flow chamber. Results Annexin V binding was higher in klotho −/− erythrocytes than in klotho +/+ erythrocytes. Osmotic shock for 1 h (addition of 550 m m sucrose) and energy depletion (12‐h glucose depletion) increased annexin V binding to values again significantly larger in klotho −/− erythrocytes than in klotho +/+ erythrocytes. klotho −/− erythrocytes were particularly sensitive to osmotic shock. Both osmotic shock and energy depletion enhanced erythrocyte adhesion, an effect again more pronounced in klotho −/− erythrocytes than in klotho +/+ erythrocytes. The adhesion was significantly decreased by coating of phospatidylserine with annexin V (5 μL mL − 1 ) or by coating of CXCL16 with neutralizing antibodies (4 μg mL − 1 ). Conclusions klotho −/− erythrocytes are particularly sensitive to osmotic shock, and enhanced eryptosis of klotho −/− erythrocytes is paralleled by enhanced adhesion to endothelial CXCL 16.
A Domain of RubC1 of Rubradirin Biosynthesis Can Functionally Replace MbtH‐Like Proteins in Tyrosine Adenylation
2012-12-06

Master of your domain: A domain of the bifunctional enzyme RubC1 catalyzes the adenylation of tyrosine. This domain can be activated not only by MbtH-like proteins but also by another domain of RubC1 that has no similarity to MbtH-like proteins.
How Many Sputum Culture Results Do We Need To Monitor Multidrug-Resistant-Tuberculosis (MDR-TB) Patients during Treatment?
2012-12-06

ABSTRACT Discharge of a hospital patient after a single negative sputum culture may save money when treating multidrug-resistant tuberculosis. However, after initial sputum conversion in 336 South Africans, 11.6% and 5.4% reconverted after 1 and 2 months, respectively. These findings endorse the WHO definitions of 2 negative cultures taken ≥30 days apart after sputum culture conversion.
Online Adaptation of a c-VEP Brain-Computer Interface(BCI) Based on Error-Related Potentials and Unsupervised Learning
2012-12-07

The goal of a Brain-Computer Interface (BCI) is to control a computer by pure brain activity. Recently, BCIs based on code-modulated visual evoked potentials (c-VEPs) have shown great potential to establish high-performance communication. In this paper we present a c-VEP BCI that uses online adaptation of the classifier to reduce calibration time and increase performance. We compare two different approaches for online adaptation of the system: an unsupervised method and a method that uses the detection of error-related potentials. Both approaches were tested in an online study, in which an average accuracy of 96% was achieved with adaptation based on error-related potentials. This accuracy corresponds to an average information transfer rate of 144 bit/min, which is the highest bitrate reported so far for a non-invasive BCI. In a free-spelling mode, the subjects were able to write with an average of 21.3 error-free letters per minute, which shows the feasibility of the BCI system in a normal-use scenario. In addition we show that a calibration of the BCI system solely based on the detection of error-related potentials is possible, without knowing the true class labels.
Genetics and iron in the systems biology of Parkinson’s disease and some related disorders
2012-12-07

The systems biology approach to complex diseases recognises that a potentially large number of biochemical network elements may be involved in disease progression, especially where positive feedback loops can be identified. Most of these network elements will be encoded by genes, for which different alleles may affect the network(s) differentially. A primary requirement is therefore to determine the relevant gene-network relationships. A corollary of this is that identification of the network should thereby allow one to 'explain' or account for any genetic associations. We apply this approach to Parkinson's disease, a disease characterised by apoptotic death of neurons of the substantia nigra, and coupled significantly to a derangement of iron metabolism. We thereby account for the involvement of various genes and biochemical pathways associated with Parkinsonism, including seemingly unconnected ones involving iron, α-synuclein, parkin, mitochondrial respiration and biology, ceramide production, lysosome biology, Lewy body formation, and so on. Although such an analysis necessarily recognises that there is no unitary 'cause' of Parkinson's, it also recognises that each of the elements contributing can or does effectively converge on a particular mode of apoptotic cell death in dopaminergic neurons, often involving iron-mediated hydroxyl radical formation. Overall, the systems biology approach allows us to propose at least one coherent synthesis of the rather disparate literature surrounding the aetiology of Parkinson's disease, and thereby to suggest some (synergistic) targets for ameliorating the disease and its progression.
Multiproxy Analyses of Stratigraphy and Palaeoenvironment of the Late Palaeolithic Grabow Floodplain Site, Northern Germany
2012-12-07

Changing river courses and fluctuations of the water table were some of the most fundamental environmental changes that humans faced during the Late Glacial, particularly as these changes affected areas intensively used for settlement and resource exploitation. Unfortunately, only a few stratigraphies have been documented in the North European plain that show the interaction between river development, vegetation history, and occupation by Late Palaeolithic humans. Here, we present the results of detailed stratigraphical studies (pedology, archaeology, chrono‐, tephra‐, and palynostratigraphy) at the Federmesser site Grabow 15 located in the broad Elbe River valley. The research aimed to produce a model of site formation based on a multiproxy approach, relating the local evidence to the palaeoenvironmental and settlement history of the wider region. After deposition of fluvial sands during the Late Pleniglacial in a braided setting, the river course developed locally toward a meandering system at the transition from the Older Dryas to the Allerød, while periodic flooding led to the deposition of floodplain sediments during the early Allerød. The floodplain was settled by people of the earliest “Federmessergruppen,” who are believed to have chosen this open floodplain area along the river for collecting and processing amber of local origin. Their artifacts became embedded in the aggrading floodplain sediments. In the late Allerød, floodplain sedimentation ceased and a Fluvisol‐type soil developed, indicating a trend toward geomorphic stability. The Fluvisol was then covered by silty floodplain sediments due to a rising water level during the late Younger Dryas resulting in the cessation of human occupation in the area. Subsequent organic‐rich Late Glacial/Holocene sediments preserved the settlement remains to the present.
Insulin Receptor Isoforms A and B as well as Insulin Receptor Substrates-1 and -2 Are Differentially Expressed in Prostate Cancer
2012-12-10

We found significant differences in the insulin signaling cascade between benign prostate tissue and prostate cancer. Histological benign tissue adjacent to cancer showed expression patterns similar to the malignancies. Our findings suggest a role of the insulin signaling pathway in prostate cancer and surrounding tissue and can hence be relevant for both novel diagnostic and therapeutic approaches in this malignancy.
In vitro effect of molluscan hemocyanins on CAL-29 and T-24 bladder cancer cell lines
2012-12-10

The aim of this study was to investigate the anti-tumor effects of molluscan hemocyanins (Hcs) isolated from the marine snail <i>Rapana venosa</i> (RvH) and the garden snail <i>Helix lucorum</i> (HlH) on human bladder cancer cell lines. The antitumor effect of the native molecules of the above-mentioned Hcs and their subunits were examined in comparison to keyhole limpet hemocyanin (KLH), which is the most thoroughly studied Hc. The experiments were conducted using 2 human bladder cancer cell lines: CAL-29 and T-24. Doxorubicin hydrochloride (DOX) and mitomycin-C (MIT-C), which are routinely used in clinical practice to treat bladder cancer, were used for comparison. The viability of the 2 bladder cancer cell lines, used at a concentration of 20,000 cells/well, was measured by WST-1 assay at 24, 48 and 72 h after treatment with the above-mentioned Hcs and their isoforms at a concentration ranging from 0.8 to 500 <i>μ</i>g/ml. A direct growth inhibitory effect on the tumor cells was observed mainly after treatment with the native molecule of HlH and the structural subunit, RvH1, at a concentration of 500 <i>μ</i>g/ml. The native molecule of RvH exhibited an efficacy similar to that of KLH. However, the observed growth inhibitory effect of HlH was superior to that observed for KLH and RvH, when used at the same concentration. These findings demonstrate the antitumor effect of other Hcs, apart from KLH. Our data suggest that the native molecule of HlH and the subunit, RvH1, are alternative candidates for the treatment of human superficial bladder cancer.
Challenges of non‐commercial multicentre North‐South collaborative clinical trials
2012-12-10

Abstract The last decade has witnessed a substantial increase of multi‐centre, public health‐oriented clinical trials in poor countries. However, non‐commercial research groups have less staff and financial resources than traditional commercial sponsors, so the trial teams have to be creative to comply with Good Clinical Practices ( GCP ) requirements. According to the recent experience of a large multicentre trial on antimalarials, major challenges result from the complexity of multiple ethical review, the costs of in‐depth monitoring at several sites, setting up an adequate Good Clinical Laboratory Practices ( GCLP ) framework, lack of insurers in host countries, and lack of adequate non‐commercial data management software. Public research funding agencies need to consider these challenges in their funding policies. They also could support common spaces where North‐South collaborative research groups may share critical information, such as on research insurance and open‐source, GCP ‐compliant software. WHO should update its GCP guidelines, which date back to 1995, to incorporate the perspectives and needs of non‐commercial clinical research.
Exploring Third Metacarpal Capitate Facet Shape in Early Hominins
2012-12-10

Abstract The joint between the capitate and third metacarpal plays an important role in stabilizing the manus during hand use in great apes and humans. Researchers have examined the morphology of this region in humans, our fossil relatives, and other extant primates to try to understand the importance of this joint in human evolution. The first goal of our research was to explore shape variation of the third metacarpal capitate facet across extant anthropoids, including hominoids, cercopithecoids, and platyrrhines. This analysis allowed us to examine the range of variation in the capitate facet and the degree to which locomotor behavior, phylogeny, and size explained shape variation. We also examined capitate facet shape in the early hominin fossil record in order to explore how the shape of this articular surface has changed during early hominin evolution. We captured six landmark coordinates on the edge of the capitate facet in extant anthropoids and fossil specimens to quantify and visualize shape variation in this region. We used principal components analysis, Procrustes distances, and multivariate regression analysis to investigate different possible influences on shape variation. We found that shape variation corresponded to function, phylogeny, and size. With the exception of brachiation, shape variation did not clearly correspond with any specific locomotor behavior. However, we identified a shift in the relative mediolateral breadth of the capitate facet during early hominin evolution, which is most likely one of several adaptations for a more stable joint surface. Anat Rec, 2013. © 2012 Wiley Periodicals, Inc.