High Temperature Mixed State c−c-Axis Dissipation in Low Carrier Density Y0.54Pr0.46Ba2Cu3O7−δY_{0.54}Pr_{0.46}Ba_{2}Cu_{3}O_{7-\delta}

The nature of the out-of-plane dissipation was investigated in underdoped $Y_{0.54}Pr_{0.46}Ba_{2}Cu_{3}O_{7-\delta}$ single crystals at temperatures close to the critical temperature. For this goal, temperature and angle dependent out-of-plane resistivity measurements were carried out both below and above the critical temperature. We found that the Ambegaokar-Halperin relationship [V. Ambegaokar, and B. I. Halperin, Phys. Rev. Lett. \textbf{22}, 1364 (1969)] depicts very well the angular magnetoresistivity in the investigated range of field and temperature. The main finding is that the in-plane phase fluctuations decouple the layers above the critical temperature and the charge transport is governed only by the quasiparticles. We also have calculated the interlayer Josephson critical current density, which was found to be much smaller than the one predicted by the theory of layered superconductors. This discrepancy could be a result of the d-wave symmetry of the order parameter and/or of the non BCS temperature dependence of the c-axis penetration length.Comment: Will appear in PR

Physics of cuprates with the two-band Hubbard model - The validity of the one-band Hubbard model

We calculate the properties of the two-band Hubbard model using the Dynamical Cluster Approximation. The phase diagram resembles the generic phase diagram of the cuprates, showing a strong asymmetry with respect to electron and hole doped regimes, in agreement with experiment. Asymmetric features are also seen in one-particle spectral functions and in the charge, spin and d-wave pairing susceptibility functions. We address the possible reduction of the two-band model to a low-energy single-band one, as it was suggested by Zhang and Rice. Comparing the two-band Hubbard model properties with the single-band Hubbard model ones, we have found similar low-energy physics provided that the next-nearest-neighbor hopping term t' has a significant value ($t'/t \approx 0.3$). The parameter t' is the main culprit for the electron-hole asymmetry. However, a significant value of t' cannot be provided in a strict Zhang and Rice picture where the extra holes added into the system bind to the existing Cu holes forming local singlets. We notice that by considering approximate singlet states, such as plaquette ones, reasonable values of t', which capture qualitatively the physics of the two-band model can be obtained. We conclude that a single-band t-t'-U Hubbard model captures the basic physics of the cuprates concerning superconductivity, antiferromagnetism, pseudogap and electron-hole asymmetry, but is not suitable for a quantitative analysis or to describe physical properties involving energy scales larger than about 0.5 eV.Comment: 14 pages, 16 figure

Temperature and magnetic-field dependence of the conductivity of YBaCuO films in the vicinity of superconducting transition: Effect of Tc-inhomogeneity

Temperature and magnetic field dependences of the conductivity of YBaCuO films in the transition region are analyzed taking into account spatial inhomogeneity in transition temperature, Tc. (i) An expression for the superconducting contribution to conductivity, \sigma_s(T,H,Tc), of a homogeneous superconductor for H<<Hc2(T=0) is obtained using the solution of the Ginzburg-Landau equation in form of perturbation expansions [S.Ullah, A.T.Dorsey, PRB 44, 262 (1991)]. (ii) The error in \sigma_s(T,H,Tc) occurring due to the presence of Tc-inhomogeneity is calculated and plotted on an H-T plane diagram. These calculations use an effective medium approximation and a Gaussian distribution of Tc. (iii) Measuring the temperature dependences of a voltage, induced by a focused electron beam, we determine spatial distributions of the critical temperature for YBaCuO microbridges with a 2 micron resolution. A typical Tc-distribution dispersion is found to be approximately 1K. For such dispersion, error in \sigma_s(T,H,Tc) due to Tc-inhomogeneity exceeds 30% for magnetic fields H < 1 T and temperatures |T-Tc| < 0.5 K. (iv) Experimental R(T,H) dependences of resistance are well described by a numerical solution of a set of Kirchoff equations for the resistor network based on the measured spatial distributions of Tc and the expression for \sigma_s(T,H,Tc).Comment: REVTeX, 12 pages including 7 figures, resubmitted to Phys. Rev.

Dynamics of Flux Creep in Underdoped Single Crystals of Y_1-xPr_xBa_2Cu_3O_7-d

Transport as well as magnetic relaxation properties of the mixed state were studied on strongly underdoped Y_1-xPr_xBa_2Cu_3O_7-d crystals. We observed two correlated phenomena - a coupling transition and a transition to quantum creep. The distribution of transport current below the coupling transition is highly nonuniform, which facilitates quantum creep. We speculate that in the mixed state below the coupling transition, where dissipation is nonohmic, the current distribution may be unstable with respect to self-channeling resulting in the formation of very thin current-carrying layers.Comment: 11 pages, 9 figures, Submitted to Phys. Rev.

Triple sign reversal of Hall effect in HgBa_{2}CaCu_{2}O_{6} thin films after heavy-ion irradiations

Triple sign reversal in the mixed-state Hall effect has been observed for the first time in ion-irradiated HgBa_{2}CaCu_{2}O_{6} thin films. The negative dip at the third sign reversal is more pronounced for higher fields, which is opposite to the case of the first sign reversal near T_c in most high-T_c superconductors. These observations can be explained by a recent prediction in which the third sign reversal is attributed to the energy derivative of the density of states and to a temperature-dependent function related to the superconducting energy gap. These contributions prominently appear in cases where the mean free path is significantly decreased, such as our case of ion-irradiated thin films.Comment: 4 pages, 3 eps figures, submitted Phys. Rev. Let

Rapid and efficient cancer cell killing mediated by high-affinity death receptor homotrimerizing TRAIL variants

The tumour necrosis factor family member TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in a variety of cancer cells through the activation of death receptors 4 (DR4) and 5 (DR5) and is considered a promising anticancer therapeutic agent. As apoptosis seems to occur primarily via only one of the two death receptors in many cancer cells, the introduction of DR selectivity is thought to create more potent TRAIL agonists with superior therapeutic properties. By use of a computer-aided structure-based design followed by rational combination of mutations, we obtained variants that signal exclusively via DR4. Besides an enhanced selectivity, these TRAIL-DR4 agonists show superior affinity to DR4, and a high apoptosis-inducing activity against several TRAIL-sensitive and -resistant cancer cell lines in vitro. Intriguingly, combined treatment of the DR4-selective variant and a DR5-selective TRAIL variant in cancer cell lines signalling by both death receptors leads to a significant increase in activity when compared with wild-type rhTRAIL or each single rhTRAIL variant. Our results suggest that TRAIL induced apoptosis via high-affinity and rapid-selective homotrimerization of each DR represent an important step towards an efficient cancer treatment

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field