Effect of Cutaneous Hypoxia upon Erythema and Pigment Responses to UVA, UVB, and PUVA (8-MOP + UVA) in Human Skin**Persented in part at the Annual Meeting of The Society for Investigative Dermatology, Inc., Washington, D.C., May 7–9, 1984 (J Invest Dermatol 82:420, 1984).

The effect of oxygen deprivation upon UVA-, UVB-, and PUVA- induced pigment and erythema responses in normal human skin was examined. Before exposure, varying degrees of hypoxia in the skin of the forearm were achieved by inflating sphygmomanometer cuff applied to the upper arm. After the transcutaneously measured pO2 had stabilized, sites on the inner forearm were exposed to UVA, UVB, or 8-MOP + UVA radiation, to determine dose thresholds for the induction of erythema and pigmentation at different cuff pressures. Inflation of the cuff to greater than systolic pressure completely inhibited immediate and delayed pigment responses (IPD, DT) to UVA doses greater than 10 times the normal pigmentation threshold dose. UVA-induced delayed erythema responses were partially inhibited by cuff inflation: 2.7 times the minimal erythema dose of UVA was necessary to cause an erythema response when exposure occurred during vascular occlusion. In contrast, erythema and pigments responses to UVB and PUVA were unaltered by cuff pressures exceeding systolic pressure during exposure. Inhibition of UVA-induced erythema and pigment responses by vascular occlusion were reversed by the transcutaneous diffusion of 100% O2. These findings indicate that the cutaneous responses to UVA and UVB occur by separate pathways differing with respect to O2-dependence. Our findings agree with those of other studies which indicate that PUVA-induced phototoxicity and melanogenesis are not O2-dependent

Molecular impact of launch related dynamic vibrations and static hypergravity in planarians

Although many examples of simulated and real microgravity demonstrating their profound effect on biological systems are described in literature, few reports deal with hypergravity and vibration effects, the levels of which are severely increased during the launch preceding the desired microgravity period. Here, we used planarians, flatworms that can regenerate any body part in a few days. Planarians are an ideal model to study the impact of launch-related hypergravity and vibration during a regenerative process in a “whole animal” context. Therefore, planarians were subjected to 8.5 minutes of 4 g hypergravity (i.e. a human-rated launch level) in the Large Diameter Centrifuge (LDC) and/or to vibrations (20–2000 Hz, 11.3 Grms) simulating the conditions of a standard rocket launch. The transcriptional levels of genes (erg-1, runt-1, fos, jnk, and yki) related with the early stress response were quantified through qPCR. The results show that early response genes are severely deregulated after static and dynamic loads but more so after a combined exposure of dynamic (vibration) and static (hypergravity) loads, more closely simulating real launch exposure profiles. Importantly, at least four days after the exposure, the transcriptional levels of those genes are still deregulated. Our results highlight the deep impact that short exposures to hypergravity and vibration have in organisms, and thus the implications that space flight launch could have. These phenomena should be taken into account when planning for well-controlled microgravity studies

Copy number alterations in pancreatic cancer identify recurrent PAK4 amplification

Pancreatic cancer is one of the most lethal of all cancers. The median survival is 6 months, and less than 5% of those diagnosed survive 5-years. Recurrent genetic deletions and amplifications in 73 pancreatic adenocarcinomas, the largest sample set analyzed to date for pancreatic cancer, were defined using comparative genomic hybridization The recurrent genetic alterations identified target a number of previously well-characterized genes, as well as regions that contain possible new oncogenes and tumor suppressor genes. We have focused on chromosome 19q13, a region frequently found amplified in pancreatic cancer, and demonstrate how boundaries of common regions of mutation can be mapped, and how a gene, in this case PAK4 amplified on chromosome19q13, can be functionally validated. We show that although the PAK4 gene is not activated by mutation in cell lines with gene amplification, an oncogenic form of the KRAS2 gene is present in these cells, and oncogenic KRAS2 can activate PAK4. In fact in the three samples we identified with PAK4 gene amplification, the KRAS2 gene was activated and genomically amplified. The kinase activity of the PAK4 protein is significantly higher in cells with genomic amplification as compared to cells without amplification. Our study demonstrates the utility of analyzing copy number data in a large set of neoplasms to identify genes involved in cancer. We have generated a useful dataset which will be particularly useful for the pancreatic cancer community as efforts are undertaken to sequence the pancreatic cancer genome

Realism and Objectivism in Quantum Mechanics

The present study attempts to provide a consistent and coherent account of what the world could be like, given the conceptual framework and results of contemporary quantum theory. It is suggested that standard quantum mechanics can, and indeed should, be understood as a realist theory within its domain of application. It is pointed out, however, that a viable realist interpretation of quantum theory requires the abandonment or radical revision of the classical conception of physical reality and its traditional philosophical presuppositions. It is argued, in this direction, that the conceptualization of the nature of reality, as arising out of our most basic physical theory, calls for a kind of contextual realism. Within the domain of quantum mechanics, knowledge of 'reality in itself', 'the real such as it truly is' independent of the way it is contextualized, is impossible in principle. In this connection, the meaning of objectivity in quantum mechanics is analyzed, whilst the important question concerning the nature of quantum objects is explored.Comment: 20 pages. arXiv admin note: substantial text overlap with arXiv:0811.3696, arXiv:quant-ph/0502099, arXiv:0904.2702, arXiv:0904.2859, arXiv:0905.013

Review of recent experimental progresses in Foundations of Quantum Mechanics and Quantum Information obtained in Parametric Down Conversion Experiments at IENGF

We review some recent experimental progresses concerning Foundations of Quantum Mechanics and Quantum Information obtained in Quantum Optics Laboratory "Carlo Novero" at IENGF. More in details, after a short presentation of our polarization entangled photons source (based on precise superposition of two Type I PDC emission) and of the results obtained with it, we describe an innovative double slit experiment where two degenerate photons produced by PDC are sent each to a specific slit. Beyond representing an interesting example of relation between visibility of interference and "welcher weg" knowledge, this configuration has been suggested for testing de Broglie-Bohm theory against Standard Quantum Mechanics. Our results perfectly fit SQM results, but disagree with dBB predictions. Then, we discuss a recent experiment addressed to clarify the issue of which wave-particle observables are really to be considered when discussing wave particle duality. This experiments realises the Agarwal et al. theoretical proposal, overcoming limitations of a former experiment. Finally, we hint to the realization of a high-intensity high-spectral-selected PDC source to be used for quantum information studies

Impact of Previously Unrecognized HLA Mismatches Using Ultrahigh Resolution Typing in Unrelated Donor Hematopoietic Cell Transplantation

PURPOSE: Ultrahigh resolution (UHR) HLA matching is reported to result in better outcomes following unrelated donor hematopoietic cell transplantation, improving survival and reducing post-transplant complications. However, most studies included relatively small numbers of patients. Here we report the findings from a large, multicenter validation study. METHODS: UHR HLA typing was available on 5,140 conventionally 10 out of 10 HLA-matched patients with malignant disease transplanted between 2008 and 2017. RESULTS: After UHR HLA typing, 82% of pairs remained 10 out of 10 UHR-matched; 12.3% of patients were 12 out of 12 UHR HLA-matched. Compared with 12 out of 12 UHR-matched patients, probabilities of grade 2-4 acute graft-versus-host disease (aGVHD) were significantly increased with UHR mismatches (overall P = .0019) and in those patients who were HLA-DPB1 T-cell epitope permissively mismatched or nonpermissively mismatched (overall P = .0011). In the T-cell-depleted subset, the degree of UHR HLA mismatch was only associated with increased transplant-related mortality (TRM) (overall P = .0068). In the T-cell-replete subset, UHR HLA matching was associated with a lower probability of aGVHD (overall P = .0020); 12 out of 12 UHR matching was associated with reduced TRM risk when compared with HLA-DPB1 T-cell epitope permissively mismatched patients, whereas nonpermissive mismatching resulted in a greater risk (overall P = .0003). CONCLUSION: This study did not confirm that UHR 12 out of 12 HLA matching increases the probability of overall survival but does demonstrate that aGVHD risk, and in certain settings TRM, is lowest in UHR HLA-matched pairs and thus warrants consideration when multiple 10 out of 10 HLA-matched donors of equivalent age are available

Reentrant AC magnetic susceptibility in Josephson-junction arrays: An alternative explanation for the paramagnetic Meissner effect

The paramagnetic Meissner effect (PME) measured in high $T_{C}$ granular superconductors has been attributed to the presence of $\pi$-junctions between the grains. Here we present measurements of complex AC magnetic susceptibility from two-dimensional arrays of conventional (non $\pi$) Nb/Al/AlOx/Nb Josephson junctions. We measured the susceptibility as a function of the temperature $T$, the AC amplitude of the excitation field, $h_{AC}$, and the external magnetic field, $H_{DC}$. The experiments show a strong paramagnetic contribution from the multi-junction loops, which manifests itself as a reentrant screening at low temperature, for values of $h_{AC}$ higher than 50 mOe. A highly simplified model, based on a single loop containing four junction, accounts for this paramagnetic contribution and the range of parameters in which it appears. This model offers an alternative explanation of PME which does not involve $\pi$-junctions.Comment: PDF file, 6 two-columns pages, 9 figure

GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia.

We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P \u3c .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P \u3c .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors. © 2019 American Society of Hematology. All rights reserved