julilili42/papers huggingface dataset:
Differential Effects of Dehydroepiandrosterone and Testosterone in Prostate and Colon Cancer Cell Apoptosis: The Role of Nerve Growth Factor (NGF) Receptors
2013-05-21

Abstract Tumor growth is fostered by inhibition of cell death, which involves the receptiveness of tumor to growth factors and hormones. We have recently shown that testosterone exerts proapoptotic effects in prostate and colon cancer cells through a membrane-initiated mechanism. In addition, we have recently reported that dehydroepiandrosterone (DHEA) can control cell fate, activating nerve growth factor (NGF) receptors, namely tropomyosin-related kinase (Trk)A and p75 neurotrophin receptor, in primary neurons and in PC12 tumoral cells. NGF was recently involved in cancer cell proliferation and apoptosis. In the present study, we explored the cross talk between androgens (testosterone and DHEA) and NGF in regulating apoptosis of prostate and colon cancer cells. DHEA and NGF strongly blunted serum deprivation-induced apoptosis, whereas testosterone induced apoptosis of both cancer cell lines. The antiapoptotic effect of both DHEA and NGF was completely reversed by testosterone. In line with this, DHEA or NGF up-regulated, whereas testosterone down-regulated, the expression of TrkA receptor. The effects of androgens were abolished in both cell lines in the presence of TrkA inhibitor. DHEA induced the phosphorylation of TrkA and the interaction of p75 neurotrophin receptor with its effectors, Rho protein GDP dissociation inhibitor and receptor interacting serine/threonine-protein kinase 2. Conversely, testosterone was unable to activate both receptors. Testosterone acted as a DHEA and NGF antagonist, by blocking the activation of both receptors by DHEA or NGF. Our findings suggest that androgens may influence hormone-sensitive tumor cells via their cross talk with NGF receptors. The interplay between steroid hormone and neurotrophins signaling in hormone-dependent tumors offers new insights in the pathophysiology of these neoplasias.
Nanomechanics of Molecules and Living Cells with Scanning Ion Conductance Microscopy
2013-05-21

Hydrodynamic flow through a nanopipet in a scanning ion conductance microscope (SICM) can exert localized forces on a sample surface. These forces can be used for trapping of molecules in lipid bilayers and for mapping the mechanical properties of living cells.
Broad-Spectrum Antimalarial Activity of Peptido Sulfonyl Fluorides, a New Class of Proteasome Inhibitors
2013-05-21

ABSTRACT Despite declining numbers of cases and deaths, malaria remains a major public health problem in many parts of the world. Today, case management relies heavily on a single class of antimalarial compounds: artemisinins. Hence, development of resistance against artemisinins may destroy current malaria control strategies. Beyond malaria control are elimination and eradication programs that will require drugs with good activity against acute infection but also with preventive and transmission-blocking properties. Consequently, new antimalarials are needed not only to ensure malaria control but also for elimination and eradication efforts. In this study, we introduce peptido sulfonyl fluorides (PSF) as a new class of compounds with antiplasmodial activity. We show that PSF target the plasmodial proteasome and act on all asexual stages of the intraerythrocytic cycle and on gametocytes. PSF showed activities at concentrations as low as 20 nM against multidrug-resistant and chloroquine-sensitive Plasmodium falciparum laboratory strains and clinical isolates from Gabon. Structural requirements for activity were identified, and cytotoxicity in human HeLa or HEK 293 cells was low. The lead PSF PW28 suppressed growth of Plasmodium berghei in vivo but showed signs of toxicity in mice. Considering their modular structure and broad spectrum of activity against different stages of the plasmodial life cycle, proteasome inhibitors based on PSF have a great potential for further development as preclinical candidate compounds with improved species-specific activity and less toxicity.
Threshold resummation for polarized (semi-)inclusive deep inelastic scattering
2013-05-21

We explore the effects of the resummation of large logarithmic perturbative\\ncorrections to double-longitudinal spin asymmetries for inclusive and\\nsemi-inclusive deep inelastic scattering in fixed-target experiments. We find\\nthat the asymmetries are overall rather robust with respect to the inclusion of\\nthe resummed higher-order terms. Significant effects are observed at fairly\\nhigh values of x, where resummation tends to decrease the spin asymmetries.\\nThis effect turns out to be more pronounced for semi-inclusive scattering. We\\nalso investigate the potential impact of resummation on the extraction of\\npolarized valence quark distributions in dedicated high-x experiments.\\n
Temporal Wilson loop in the Hamiltonian approach in Coulomb gauge
2013-05-21

We investigate the temporal Wilson loop using the Hamiltonian approach to Yang-Mills theory.In simple cases such as the Abelian theory or the non-Abelian theory in (1+1) dimensions, the known results can be derived using unitary transformations to take care of time evolution.Alternatively, the exact solution can also be found in Coulomb gauge using the exact ground state wave functional which is known explicitly in these simple cases.The Coulomb gauge technique can also be applied to the more realistic case of Yang-Mills theory in (3+1) dimensions, where one has to rely on the approximate vacuum wave functional obtained e.g. in recent variational approaches.We use this formulation to compute the temporal Wilson loop in (3+1) dimensional Yang-Mills theory, and find that the Wilson and Coulomb string tension agree within this approximation scheme.Possible improvements of these findings are briefly discussed.
Gap and Bethe-Salpeter equations in Coulomb gauge
2013-05-21

I will discuss the gap and Bethe-Salpeter equations for quantum chromodynamics in Coulomb gauge under a leading order truncation scheme. Within this scheme, the role of charge conservation and the cancellation of infrared divergences becomes particularly clear. The quark gap equation exhibits not only chiral symmetry breaking, but explicitly reproduces the heavy quark limit. The corresponding gluon equation has a massive solution with interesting nonperturbative renormalization properties. I will further discuss various aspects of the Bethe-Salpeter equation for pseudoscalar and vector mesons with arbitrary quark masses and present numerical results for the meson masses and leptonic decay constants.
Hamiltonian Dyson-Schwinger Equations of QCD
2013-05-21

The general method for treating non-Gaussian wave functionals in the Hamiltonian formulation of a quantum field theory, which was previously developed and applied to Yang‐Mills theory in Coulomb gauge, is generalized to full QCD. The Hamiltonian Dyson‐Schwinger equations as well as the quark and gluon gap equations are derived and analysed in the IR and UV momentum regime. The back-reaction of the quarks on the gluon sector is investigated.
Lattice Coulomb propagators, effective energy and confinement
2013-05-21

We show that in the lattice Hamiltonian limit all Coulomb gauge propagators are consistent with the Gribov-Zwanziger confinement mechanism, with an IR enhanced effective energy for quarks and gluons and a diverging ghost form factor compatible with a dual-superconducting vacuum.Multiplicative renormalizability is ensured for all static correlators, while for non-static ones their energy dependence plays a crucial role in this respect.Moreover, from the Coulomb potential we can extract the Coulomb string tension σ C ∼ 2σ .
Cognitive Control of Distinct Vocalizations in Rhesus Monkeys
2013-05-22

Abstract Whether nonhuman primates can decouple their innate vocalizations from accompanied levels of arousal or specific events in the environment to achieve cognitive control over their vocal utterances has been a matter of debate for decades. We show that rhesus monkeys can be trained to elicit different call types on command in response to arbitrary visual cues. Furthermore, we report that a monkey learned to switch between two distinct call types from trial to trial in response to different visual cues. A controlled behavioral protocol and data analysis based on signal detection theory showed that noncognitive factors as a cause for the monkeys' vocalizations could be excluded. Our findings also suggest that monkeys also have rudimentary control over acoustic call parameters. These findings indicate that monkeys are able to volitionally initiate their vocal production and, therefore, are able to instrumentalize their vocal behavior to perform a behavioral task successfully.
A Novel Transgenic Rat Model for Spinocerebellar Ataxia Type 17 Recapitulates Neuropathological Changes and SuppliesIn VivoImaging Biomarkers
2013-05-22

Spinocerebellar ataxia 17 (SCA17) is an autosomal-dominant, late-onset neurodegenerative disorder caused by an expanded polyglutamine (polyQ) repeat in the TATA-box-binding protein (TBP). To further investigate this devastating disease, we sought to create a first transgenic rat model for SCA17 that carries a full human cDNA fragment of the TBP gene with 64 CAA/CAG repeats (TBPQ64). In line with previous observations in mouse models for SCA17, TBPQ64 rats show a severe neurological phenotype including ataxia, impairment of postural reflexes, and hyperactivity in early stages followed by reduced activity, loss of body weight, and early death. Neuropathologically, the severe phenotype of SCA17 rats was associated with neuronal loss, particularly in the cerebellum. Degeneration of Purkinje, basket, and stellate cells, changes in the morphology of the dendrites, nuclear TBP-positive immunoreactivity, and axonal torpedos were readily found by light and electron microscopy. While some of these changes are well recapitulated in existing mouse models for SCA17, we provide evidence that some crucial characteristics of SCA17 are better mirrored in TBPQ64 rats. Thus, this SCA17 model represents a valuable tool to pursue experimentation and therapeutic approaches that may be difficult or impossible to perform with SCA17 transgenic mice. We show for the first time positron emission tomography (PET) and diffusion tensor imaging (DTI) data of a SCA animal model that replicate recent PET studies in human SCA17 patients. Our results also confirm that DTI are potentially useful correlates of neuropathological changes in TBPQ64 rats and raise hope that DTI imaging could provide a biomarker for SCA17 patients.
Anthropometric influences on dynamic foot shape: Measurements of plantar three-dimensional foot deformation
2013-05-22

Abstract Purpose: Advances in scanner technology enable the capture of feet during walking. Knowledge of dynamic deformation is essential for fundamental research and application-oriented improvements in terms of comfortable and functional footwear. The core hypothesis of our study is that there is a relationship between dynamic foot measures and the anthropometric dimensions age, gender and body mass index. Methods: We measured the dynamic foot shape of 129 subjects (77 female, 52 male) with a plantar dynamic scanner system. During stance phase we captured maximum values (MaxDyn) and changes (ΔDyn) of length, width, and height measures as well as angles and indices of feet. We identified relationships between foot measures and anthropometric dimensions by two statistical methods: analysis of variance (ANOVA) between matched groups and multiple regression analysis within whole sample size. Results: MaxDyn values of foot width measures are higher in overweight subjects. Most important predictors of MaxDyn are static measures and gender, regarding values that characterise the longitudinal arch as well as lateral ball length. More dynamic deformation was found in ball and arch angle as well as medial ball length and ball width of overweight subjects and in width measures of women. Multiple regression analysis detects body weight as an important predictor for changes in foot width measures as well as arch height and angle. Conclusion: The ability to collect foot measures during natural walking is the basis for the following findings. First, our study confirms that static foot measures can be used as basic design criteria for footwear. Second, our study points out the influence of factors like gender and body weight on dynamic foot morphology. Consideration of these additional factors can essentially improve design methods and particularly the fit of footwear. Keywords: dynamic scanningdynamic foot deformationfootwear designanthropometrycomfortcustomisation Notes * = p < 0.05; critical p-value for inclusion of variables = p ≤ 0.025; Static = static value of foot measure.
Focus on the Lateral Incisural Space: Where is the Trochlear Nerve?
2013-05-22

Objective To define the entrance point of the trochlear nerve in the free edge of the tentorium, giving a topographical description in relation to supratentorial and infratentorial reference points. Method The study was performed on seven formaldehyde-fixed specimens (14 sides). The distance from supratentorial and infratentorial reference points to the entrance point of the trochlear nerve into the free tentorial edge was measured. Results The cisternal segment of the trochlear nerve, the tentorial entry point, and the reference points could be clearly identified in all specimens. The assessed distances measured from the tentorial entry point of the trochlear nerve to the anterior clinoid process was 14 to 28 mm, to the posterior clinoid process was 9 to 19 mm, to the posterior lip of the inner auditory canal was 25 to 29 mm, to the posterior border of the Meckel cave was 9 to 14 mm, and to the oculomotor triangle was 5 to 16 mm. Conclusions The cisternal length of the trochlear nerve shows a marked variability and may be further distorted by tumors, whereas the entry point into the tentorium is a stable landmark. Therefore, it might be an important reference point for identifying the nerve before cutting the tentorium.
Comment on “ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models”
2013-05-23

Cramer et al . (Reports, 23 March 2012, p. 1503; published online 9 February 2012) reported that bexarotene rapidly reduces β-amyloid (Aβ) levels and plaque burden in two mouse models of Aβ deposition in Alzheimer’s disease (AD). We now report that, although bexarotene reduces soluble Aβ 40 levels in one of the mouse models, the drug has no impact on plaque burden in three strains that exhibit Aβ amyloidosis.
Repression of the Equilibrative Nucleoside Transporters Dampens Inflammatory Lung Injury
2013-05-23

Acute lung injury (ALI) is a devastating disorder of the lung that is characterized by hypoxemia, overwhelming pulmonary inflammation, and a high mortality in the critically ill. Adenosine has been implicated as an anti-inflammatory signaling molecule, and previous studies showed that extracellular adenosine concentrations are increased in inflamed tissues. Adenosine signaling is terminated by the uptake of adenosine from the extracellular into the intracellular compartment via equilibrative nucleoside transporters (ENTs). However, their role in controlling adenosine signaling during pulmonary inflammation remains unknown. After inflammatory in vitro experiments, we observed a repression of ENT1 and ENT2 that was associated with an attenuation of extracellular adenosine uptake. Experiments using short, interfering RNA silencing confirmed a significant contribution of ENT repression in elevating extracellular adenosine concentrations during inflammation. Furthermore, an examination of the ENT2 promoter implicated NF-κB as a key regulator for the observed ENT repression. Additional in vivo experiments using a murine model of inflammatory lung injury showed that the pharmacological inhibition of ENT1 and ENT2 resulted in improved pulmonary barrier function and reduced signs of acute inflammation of the lung. Whereas experiments on Ent1(-/-) or Ent2(-/-) mice revealed lung protection in LPS-induced lung injury, an examination of bone marrow chimeras for ENTs pointed to the nonhematopoetic expression of ENTs as the underlying cause of dampened pulmonary inflammation during ALI. Taken together, these findings reveal the transcriptional repression of ENTs as an innate protective response during acute pulmonary inflammation. The inhibition of ENTs could be pursued as a therapeutic option to ameliorate inflammatory lung injury.
A Plant Extract of Ribes nigrum folium Possesses Anti-Influenza Virus Activity In Vitro and In Vivo by Preventing Virus Entry to Host Cells
2013-05-23

Infections with influenza A viruses (IAV) are still amongst the major causes of highly contagious severe respiratory diseases not only bearing a devastating effect to human health, but also significantly impact the economy. Besides vaccination that represents the best option to protect from IAV infections, only two classes of anti-influenza drugs, inhibitors of the M2 ion channel and the neuraminidase, often causing resistant IAV variants have been approved. That is why the need for effective and amply available antivirals against IAV is of high priority. Here we introduce LADANIA067 from the leaves of the wild black currant (Ribes nigrum folium) as a potent compound against IAV infections in vitro and in vivo. LADANIA067 treatment resulted in a reduction of progeny virus titers in cell cultures infected with prototype avian and human influenza virus strains of different subtypes. At the effective dose of 100 μg/ml the extract did not exhibit apparent harming effects on cell viability, metabolism or proliferation. Further, viruses showed no tendency to develop resistance to LADANIA067 when compared to amantadine that resulted in the generation of resistant variants after only a few passages. On a molecular basis the protective effect of LADANIA067 appears to be mainly due to interference with virus internalisation. In the mouse infection model LADANIA067 treatment reduces progeny virus titers in the lung upon intranasal application. In conclusion, an extract from the leaves of the wild black currant might be a promising source for the development of new antiviral compounds to fight IAV infections.
Chiral Transition‐Metal Complexes of Phenanthro‐Annulated N‐Heterocyclic Carbenes – Synthesis and Reactivity
2013-05-23

Abstract A straightforward route to chiral Ag I and Ru II complexes with phenanthrene‐fused N‐heterocyclic carbene (NHC) ligands is described. The chiral imidazole derivative 1 was prepared in high yield by a simple one‐pot reaction starting from commercially available 9,10‐phenanthrenequinone. Imidazolium salts 2 and 3 were obtained by alkylation of 1 with alkyl bromides and subsequent anion exchange with Amberlyst A21 resin. Deprotonation with KO t Bu led to the corresponding free carbenes 4 and 5 , which were isolated without dimerization. Stirring carbene 4 in acetonitrile resulted in CH insertion. Ag I complexes were obtained by treatment of the imidazolium salts with Ag 2 O and showed an interesting low‐temperature behavior in the 1 H NMR spectrum. Transmetalation with a Ru precursor led to the corresponding Ru II complexes.
Clonal evolution in relapsed NPM1-mutated acute myeloid leukemia
2013-05-24

Key Points Relapsed AML with NPM1 mutation is genetically related to the primary leukemia and characterized by an increase in high-risk aberrations. DNMT3A mutations show the highest stability and thus may precede NPM1 mutations.
Neutrophilic myeloid-derived suppressor cells in cord blood modulate innate and adaptive immune responses
2013-05-24

Summary Neonates show an impaired anti-microbial host defence, but the underlying immune mechanisms are not understood fully. Myeloid-derived suppressor cells (MDSCs) represent an innate immune cell subset characterized by their capacity to suppress T cell immunity. In this study we demonstrate that a distinct MDSC subset with a neutrophilic/granulocytic phenotype (Gr-MDSCs) is highly increased in cord blood compared to peripheral blood of children and adults. Functionally, cord blood isolated Gr-MDSCs suppressed T cell proliferation efficiently as well as T helper type 1 (Th1), Th2 and Th17 cytokine secretion. Beyond T cells, cord blood Gr-MDSCs controlled natural killer (NK) cell cytotoxicity in a cell contact-dependent manner. These studies establish neutrophilic Gr-MDSCs as a novel immunosuppressive cell subset that controls innate (NK) and adaptive (T cell) immune responses in neonates. Increased MDSC activity in cord blood might serve as key fetomaternal immunosuppressive mechanism impairing neonatal host defence. Gr-MDSCs in cord blood might therefore represent a therapeutic target in neonatal infections.
Impact of an Altered Wnt1/β-Catenin Expression on Clinicopathology and Prognosis in Clear Cell Renal Cell Carcinoma
2013-05-24

In renal cell carcinoma (RCC), single members of the Wnt/β-catenin signaling cascade were recently identified to contribute to cancer progression. However, the role of Wnt1, one of the key ligands in β-catenin regulation, is currently unknown in RCC. Therefore, alterations of the Wnt1/β-catenin axis in clear cell RCC (ccRCC) were examined with regard to clinicopathology, overall survival (OS) and cancer specific survival (CSS). Corresponding ccRCCs and benign renal tissue were analyzed in 278 patients for Wnt1 and β-catenin expression by immunohistochemistry in tissue microarrays. Expression scores, including intensity and percentage of stained cells, were compared between normal kidney and ccRCCs. Data was categorized according to mean expression scores and correlated to tumor and patients’ characteristics. Survival was analyzed according to the Kaplan-Meier and log-rank test. Univariable and multivariable Cox proportional hazard regression models were used to explore the independent prognostic value of Wnt1 and β-catenin. In ccRCCs, high Wnt1 was associated with increased tumor diameter, stage and vascular invasion (p ≤ 0.02). High membranous β-catenin was associated with advanced stage, vascular invasion and tumor necrosis (p ≤ 0.01). Higher diameter, stage, node involvement, grade, vascular invasion and sarcomatoid differentiation (p ≤ 0.01) were found in patients with high cytoplasmic β-catenin. Patients with a high cytoplasmic β-catenin had a significantly reduced OS (hazard ratio (HR) 1.75) and CSS (HR 2.26), which was not independently associated with OS and CSS after adjustment in the multivariable model. Increased ccRCC aggressiveness was reflected by an altered Wnt1/β-catenin signaling. Cytoplasmic β-catenin was identified as the most promising candidate associated with unfavorable clinicopathology and impaired survival. Nevertheless, the shift of membranous β-catenin to the cytoplasm with a subsequently increased nuclear expression, as shown for other malignancies, could not be demonstrated to be present in ccRCC.
GRO J1008−57: an (almost) predictable transient X-ray binary
2013-05-24

A study of archival RXTE, Swift, and Suzaku pointed observations of the transient high-mass X-ray binary GRO J1008−57 is presented. A new orbital ephemeris based on pulse arrival-timing shows the times of maximum luminosities during outbursts of GRO J1008−57 to be close to periastron at orbital phase − 0.03. This makes the source one of a few for which outburst dates can be predicted with very high precision. Spectra of the source in 2005, 2007, and 2011 can be well described by a simple power law with high-energy cutoff and an additional black body at lower energies. The photon index of the power law and the black-body flux only depend on the 15–50 keV source flux. No apparent hysteresis effects are seen. These correlations allow us to predict the evolution of the pulsar’s X-ray spectral shape over all outbursts as a function of just one parameter, the source’s flux. If modified by an additional soft component, this prediction even holds during GRO J1008−57’s 2012 type II outburst.