Einstein, Planck and Vera Rubin: Relevant Encounters Between the Cosmological and the Quantum Worlds

In Cosmology and in Fundamental Physics there is a crucial question like: where the elusive substance that we call Dark Matter is hidden in the Universe and what is it made of? that, even after 40 years from the Vera Rubin seminal discovery [1] does not have a proper answer. Actually, the more we have investigated, the more this issue has become strongly entangled with aspects that go beyond the established Quantum Physics, the Standard Model of Elementary particles and the General Relativity and related to processes like the Inflation, the accelerated expansion of the Universe and High Energy Phenomena around compact objects. Even Quantum Gravity and very exotic Dark Matter particle candidates may play a role in framing the Dark Matter mystery that seems to be accomplice of new unknown Physics. Observations and experiments have clearly indicated that the above phenomenon cannot be considered as already theoretically framed, as hoped for decades. The Special Topic to which this review belongs wants to penetrate this newly realized mystery from different angles, including that of a contamination of different fields of Physics apparently unrelated. We show with the works of this ST that this contamination is able to guide us into the required new Physics. This review wants to provide a good number of these \u201cpaths or contamination\u201d beyond/among the three worlds above; in most of the cases, the results presented here open a direct link with the multi-scale dark matter phenomenon, enlightening some of its important aspects. Also in the remaining cases, possible interesting contacts emerges. Finally, a very complete and accurate bibliography is provided to help the reader in navigating all these issues

Angiotensin for septic shock unresponsive to noradrenaline

Two children with severe septic shock are reported. One had meningococcal septicaemia and the other Escherichia coli septicaemia. They remained hypotensive despite high concentrations of conventional inotropes and vasopressors. In one child, using a pulmonary artery catheter, extended haemodynamic variables were measured. To restore blood pressure, in both cases, an infusion of angiotensin II was used; there was significant improvement in clinical status, resulting in a rapid reduction in the concentration of inotropes required. Both patients successfully survived their septic episodes. Angiotensin II in cases of severe refractory septic hypotension in the paediatric population offers an extra therapeutic manoeuvre.


Evaluation of the Surface Wind Field over Land in WRF Simulations of Hurricane Wilma (2005). Part II: Surface Winds, Inflow Angles, and Boundary Layer Profiles

AbstractThis is the second of a two-part study that explores the capabilities of a mesoscale atmospheric model to reproduce the near-surface wind fields in hurricanes over land. The Weather Research and Forecasting (WRF) Model is used with two planetary boundary layer parameterizations: the Yonsei University (YSU) and the Mellor–Yamada–Janjić (MYJ) schemes. The first part presented the modeling framework and initial conditions used to produce simulations of Hurricane Wilma (2005) that closely reproduced the track, intensity, and size of its wind field as it passed over South Florida. This part explores how well these simulations can reproduce the winds at fixed points over land by making comparisons with observations from airports and research weather stations. The results show that peak wind speeds are remarkably well reproduced at several locations. Wind directions are evaluated in terms of the inflow angle relative to the storm center, and the simulated inflow angles are generally smaller than observed. Localized peak wind events are associated with vertical vorticity maxima in the boundary layer with horizontal scales of 5–10 km. The boundary layer winds are compared with wind profiles obtained by velocity–azimuth display (VAD) analyses from National Weather Service Doppler radars at Miami and Key West, Florida; results from these comparisons are mixed. Nonetheless the comparisons with surface observations suggest that when short-term hurricane forecasts can sufficiently predict storm track, intensity, and size, they will also be able to provide useful information on extreme winds at locations of interest

Matrix Metalloproteinase-9, A Potential Biological Marker in Invasive Pituitary Adenomas

Object We analyzed MMP-9 expression using mRNA and protein level determinations and explored the possibility that Matrix metalloproteinase-9 (MMP-9) is a potential biological marker of pituitary adenoma invasiveness and whether MMP-9 could be used to discriminate the extent of invasiveness among different hormonal subtypes, tumor sizes, growth characteristics, and primary versus recurrent tumors. Materials and methods 73 pituitary tumor specimens were snap frozen in liquid nitrogen immediately after surgical resection. RNA and protein were extracted. MMP-9 mRNA transcripts were analyzed by quantitative RT-PCR. MMP-9 protein activity was analyzed by gelatin zymography and validated by western blot analysis. Immunohistochemistry was performed to identify the presence and localization of MMP-9 in pituitary adenomas. Statistical differences between results were determined using Student’s t-test or one way ANOVA. Results Comparing different hormonal subtypes of noninvasive and invasive pituitary tumors, MMP-9 mRNAexpression was significantly increased in the majority of invasive adenomas. Considering the protein levels, our data also showed a significant increase in MMP-9 activity in the majority of invasive adenomas and these differences were confirmed by western blot analysis and immunohistochemistry. In addition, consistent differences in MMP-9expression levels were found according to tumor subtype, tumor size, tumor extension and primary versus redo-surgery. Conclusions MMP-9 expression can consistently distinguish invasive pituitary tumors from noninvasive pituitary tumors and would reflect the extent of invasiveness in pituitary tumors according to tumor subtype, size, tumor extension, primary and redo surgery, even at early stages of invasiveness. MMP-9 may be considered a potential biomarker to determine and predict the invasive nature of pituitary tumors

H-Ras Increases Urokinase Expression and Cell Invasion in Genetically Modified Human Astrocytes through Ras/Raf/MEK signaling pathway

Previous study reported that the activation of Ras pathway cooperated with E6/E7-mediated inactivation of p53/pRb to transform immortalized normal human astrocytes (NHA/hTERT) into intracranial tumors strongly resembling human astrocytomas. The mechanism of how H-Ras contributes to astrocytoma formation is unclear. Using genetically modified NHA cells (E6/E7/hTERT and E6/E7/hTERT/Ras cells) as models, we investigated the mechanism of Ras-induced tumorigenesis. The overexpression of constitutively active H-RasV12 in E6/E7/hTERT cells robustly increased the levels of urokinase plasminogen activator (uPA) mRNA, protein, activity and invasive capacity of the E6/E7/hTERT/Ras cells. However, the expressions of MMP-9 and MMP-2 did not significantly change in the E6/E7/hTERT and E6/E7/hTERT/Ras cells. Furthermore, E6/E7/hTERT/Ras cells also displayed higher level of uPA activity and were more invasive than E6/E7/hTERT cells in 3D culture, and formed an intracranial tumor mass in a NOD-SCID mouse model. uPA specific inhibitor (B428) and uPA neutralizing antibody decreased uPA activity and invasion in E6/E7/hTERT/Ras cells. uPA-deficient U-1242 glioblastoma cells were less invasive in vitro and exhibited reduced tumor growth and infiltration into normal brain in xenograft mouse model. Inhibitors of Ras (FTA), Raf (Bay 54−9085) and MEK (UO126), but not of phosphatidylinositol 3-kinase (PI3K) (LY294002) and of protein kinase C (BIM) pathways, inhibited uPA activity and cell invasion. Our results suggest that H-Ras increased uPA expression and activity via the Ras/Raf/MEK signaling pathway leading to enhanced cell invasion and this may contribute to increased invasive growth properties of astrocytomas

Protein Kinase C-α–Mediated Regulation of Low-Density Lipoprotein Receptor–Related Protein and Urokinase Increases Astrocytoma Invasion

Aggressive and infiltrative invasion is one of the hallmarks of glioblastoma. Low-density lipoprotein receptor–related protein (LRP) is expressed by glioblastoma, but the role of this receptor in astrocytic tumor invasion remains poorly understood. We show that activation of protein kinase C-α (PKC-α) phosphorylated and down-regulated LRP expression. Pretreatment of tumor cells with PKC inhibitors, phosphoinositide 3-kinase (PI3K) inhibitor, PKC-α small interfering RNA (siRNA), and short hairpin RNA abrogated phorbol 12-myristate 13-acetate–induced down-regulation of LRP and inhibited astrocytic tumor invasion in vitro. In xenograft glioblastoma mouse model and in vitro transmembrane invasion assay, LRP-deficient cells, which secreted high levels of urokinase-type plasminogen activator (uPA), invaded extensively the surrounding normal brain tissue, whereas the LRP-overexpressing and uPA-deficient cells did not invade into the surrounding normal brain. siRNA, targeted against uPA in LRP-deficient clones, attenuated their invasive potential. Taken together, our results strongly suggest the involvement of PKC-α/PI3K signaling pathways in the regulation of LRP-mediated astrocytoma invasion. Thus, a strategy of combining small molecule inhibitors of PKC-α and PI3K could provide a new treatment paradigm for glioblastomas

Matrix Metalloproteinase-9 Is Differentially Expressed in Nonfunctioning Invasive and Noninvasive Pituitary Adenomas and Increases Invasion in Human Pituitary Adenoma Cell Line

The complete resection of pituitary adenomas (PAs) is unlikely when there is an extensive local dural invasion and given that the molecular mechanisms remain primarily unknown. DNA microarray analysis was performed to identify differentially expressed genes between nonfunctioning invasive and noninvasive PAs. Gene clustering revealed a robust eightfold increase in matrix metalloproteinase (MMP)-9 expression in surgically resected human invasive PAs and in the (nonfunctioning) HP75 human pituitary tumor-derived cell line treated with phorbol-12-myristate-13-acetate; these results were confirmed by real-time polymerase chain reaction, gelatin zymography, reverse transcriptase-polymerase chain reaction, Western blot, immunohistochemistry, and Northern blot analyses. The activation of protein kinase C (PKC) increased both MMP-9 activity and expression, which were blocked by some PKC inhibitors (Gö6976, bisindolylmaleimide, and Rottlerin), PKC-α, and PKC-δ small interfering (si)RNAs but not by hispidin (PKC-β inhibitor). In a transmembrane invasion assay, phorbol-12-myristate-13-acetate (100 nmol/L) increased the number of invaded HP75 cells, a process that was attenuated by PKC inhibitors, MMP-9 antibody, PKC-α siRNA, or PKC-δ siRNA. These results demonstrate that MMP-9 and PKC-α or PKC-δ may provide putative therapeutic targets for the control of PA dural invasion