AQUILA: A laboratory facility for the irradiation of astrochemical ice analogs by keV ions.

The detection of various molecular species, including complex organic molecules relevant to biochemical and geochemical processes, in astronomical settings, such as the interstellar medium or the outer solar system, has led to the increased need for a better understanding of the chemistry occurring in these cold regions of space. In this context, the chemistry of ices prepared and processed at cryogenic temperatures has proven to be of particular interest due to the fact that many interstellar molecules are believed to originate within the icy mantles adsorbed on nano- and micro-scale dust particles. The chemistry leading to the formation of such molecules may be initiated by ionizing radiation in the form of galactic cosmic rays or stellar winds, and thus, there has been an increased interest in commissioning experimental setups capable of simulating and better characterizing this solid-phase radiation astrochemistry. In this article, we describe a new facility called AQUILA (Atomki-Queen's University Ice Laboratory for Astrochemistry), which has been purposefully designed to study the chemical evolution of ices analogous to those that may be found in the dense interstellar medium or the outer solar system as a result of their exposure to keV ion beams. The results of some ion irradiation studies of CH3OH ice at 20 K are discussed to exemplify the experimental capabilities of the AQUILA as well as to highlight its complementary nature to another laboratory astrochemistry setup at our institute.

Efficacy and Safety of FOLFIRINOX in Locally Advanced Pancreatic Cancer. A Single Center Experience.

The management of locally advanced pancreatic cancer (LAPC) is a major challenge. Although new drugs are available for the treatment of metastatic disease, the optimal treatment of non-metastatic cases remains controversial. The role of neoadjuvant therapy is still a question of debate in this setting. The aim of the study was to prospectively collect and analyse data on efficacy and safety of a modified FOLFIRINOX regimen in LAPC patients treated in a single institution. Another major objective was to assess the capability of FOLFIRINOX to render primary non-resectable cancer to resectable. No bolus fluorouracil was given and a 20% dose reduction of oxaliplatin and irinotecan was applied. Primary G-CSF prophylaxis was applied to prevent febrile neutropenia. Thirty-two patients (mean age 60.2 years, range: 40-77 years) have been enrolled into the study. All patients had ECOG performance status of 0 or 1. Best response to therapy was stable disease (SD) or partial regression (PR) in 18 (56.2%) and 6 (18.8%) cases. Two patients (6.3%) underwent surgical resection (100% R0). The most frequent grade 3/4 adverse events were nausea (18.8%), fatigue (12.5%) and diarrhea (12.5%). The incidence of severe neutropenia was 28.1%, with only one documented case of febrile neutropenia. The probability of disease progression was 25% and 50% after 75 and 160 days with 88.4% of possibility of disease progression after 500 days. OS probability was 92.1, 71.5% and 49.5% at 180-, 365 and 540 days. Our data does not support the capability of FOLFIRINOX to render primary non-resectable cancer to resectable. However, due to the high disease control rate observed, FOLFRINOX might be recommended as first line option for the palliative treatment of LAPC. Despite reduced chemotherapy doses significant toxicity has been seen.

Sorafenib with or without everolimus in patients with advanced hepatocellular carcinoma (HCC): a randomized multicenter, multinational phase II trial (SAKK 77/08 and SASL 29).

BACKGROUND: Sorafenib (S), a multitargeted tyrosine kinase inhibitor, is the standard of care for first-line systemic treatment of advanced hepatocellular carcinoma (HCC). Everolimus (E) is a potent inhibitor of mTOR, a pathway frequently activated in HCC. Preclinical data suggest that the combination S + E has additive effects compared with single-agent S. PATIENTS AND METHODS: Patients with unresectable or metastatic HCC and Child-Pugh ≤7 liver dysfunction were randomized to receive daily S 800 mg alone or with E 5 mg until progression or unacceptable toxicity. The primary end point was progression-free survival at 12 weeks (PFS12). The secondary end points included response rate, PFS, time to progression (TTP), overall survival (OS), duration of disease stabilization (DDS), safety, and quality-of-life (QoL) assessments. RESULTS: A total of 106 patients were randomized: 46 patients received S and 60 patients received S + E. Ninety-three patients were assessable for the primary end point and 105 patients for the safety analysis. The PFS12 rate was 70% [95% confidence interval (CI) 54-83] and 68% (95% CI 53-81) in patients randomized to S and S + E, respectively. The RECIST (mRECIST) response rate was 0% (23%) in the S arm and 10% (35%) in the S + E arm. Median PFS (6.6 versus 5.7 months), TTP (7.6 versus 6.3 months), DDS (6.7 versus 6.7 months), and OS (10 versus 12 months) were similar in the S and S + E arms, respectively. Grade 3/4 adverse events occurred in 72% and 86% of patients in arm S and arm S + E, respectively. Patients had similar QoL scores over time, except for a greater worsening in physical well-being and mood in the arm S + E. CONCLUSIONS: No evidence was found that S + E improves the efficacy compared with S alone. Combining 5 mg E with full-dose S is feasible, but more toxic than S alone. Further testing of this drug combination in molecularly unselected HCCs appears unwarranted. CLINICALTRIALSGOV: NCT01005199.

Stochastic self-assembly of incommensurate clusters.

Nucleation and molecular aggregation are important processes in numerous physical and biological systems. In many applications, these processes often take place in confined spaces, involving a finite number of particles. Analogous to treatments of stochastic chemical reactions, we examine the classic problem of homogeneous nucleation and self-assembly by deriving and analyzing a fully discrete stochastic master equation. We enumerate the highest probability steady states, and derive exact analytical formulae for quenched and equilibrium mean cluster size distributions. Upon comparison with results obtained from the associated mass-action Becker-Döring equations, we find striking differences between the two corresponding equilibrium mean cluster concentrations. These differences depend primarily on the divisibility of the total available mass by the maximum allowed cluster size, and the remainder. When such mass "incommensurability" arises, a single remainder particle can "emulsify" the system by significantly broadening the equilibrium mean cluster size distribution. This discreteness-induced broadening effect is periodic in the total mass of the system but arises even when the system size is asymptotically large, provided the ratio of the total mass to the maximum cluster size is finite. Ironically, classic mass-action equations are fairly accurate in the coarsening regime, before equilibrium is reached, despite the presence of large stochastic fluctuations found via kinetic Monte-Carlo simulations. Our findings define a new scaling regime in which results from classic mass-action theories are qualitatively inaccurate, even in the limit of large total system size.

Structure and adsorption of water in nonuniform cylindrical nanopores.

Grand canonical Monte Carlo simulations are used to examine the adsorption and structure of water in the interior of cylindrical nanopores in which the axial symmetry is broken either by varying the radius as a function of position along the pore axis or by introducing regions where the characteristic strength of the water-nanopore interaction is reduced. Using the extended simple point charge (SPC∕E) model for water, nanopores with a uniform radius of 6.0 Å are found to fill with water at chemical potentials approximately 0.5 kJ∕mol higher than the chemical potential of the saturated vapor. The water in these filled pores exists in either a weakly structured fluidlike state or a highly structured uniformly polarized state composed of a series of stacked water clusters with pentagonal cross sections. This highly structured state can be disrupted by creating hydrophobic regions on the surface of the nanopore, and the degree of disruption can be systematically controlled by adjusting the size of the hydrophobic regions. In particular, hydrophobic banded regions with lengths larger than 9.2 Å result in a complete loss of structure and the formation of a liquid-vapor coexistence in the tube interior. Similarly, the introduction of spatial variation in the nanopore radius can produce two condensation transitions at distinct points along the filling isotherm.

Application of water framework directive in Hungary: development of biological classification systems.

The classification according to the Water Framework Directive (WFD) includes numerous challenges in contrast with the previously applied water qualification standards. The most important element of the ecological status, the biological one, is based on five groups of living organisms: phytoplankton, phytobenthon, macrophytes, macro-invertebrates and fish. The results of a three-year research project financed by the Ministry of Environment and Water (MoEW) and the Hungarian Academy of Sciences (HAS) are reported in this work. The objective of the project was the elaboration of a proposal for biological classification according to the WFD for the related groups of living organisms. In the course of the project the biological characteristics to be measured were selected for each of the above listed groups which served as the basic data for Biological Quality Elements (BQEs). In the BQEs we estimated the type-specific reference values for most of the Hungarian surface water types. Then we created the structure of the qualification system for these groups, including specification of class boundaries between the five classes for the Environmental Quality Ratio (EQR) values on the basis of expert estimation. A Non-Taxonomic Periphyton Index (NTPI, not included in the WFD) was also developed and tested for qualification. The elaborated classification systems were tested on the basis of existing scarce data for numerous Hungarian water types.

Water adsorption in ion-bearing nanopores.

Grand canonical Monte Carlo simulations are used to examine the adsorption of water into cylindrical nanopores containing single ions. The isotherms for water adsorbing into nanopores with radii of 0.44, 0.54, 0.64, and 0.74 nm and containing Na+, K+, Ca2+, Cl-, or F- at 298 K are computed. In all cases the nanopores are found to fill at reservoir chemical potentials below the chemical potential of saturated water vapor at 298 K. The threshold chemical potential is found to be sensitive to both the size of the channel and the ion species, with the anion-bearing pores filling at lower chemical potentials. Additionally, the filling threshold chemical potential is found to decrease as the radius of the pores is decreased. Pores with K+ and Cl- are compared, and the Cl- pores are found to exhibit higher water densities in the filled states and a more energetically favorable water structure while yielding lower per particle entropies. Sample simulation configurations are also examined and indicate that at low chemical potentials, the adsorbed water forms a cluster around the ion. Finally, the influence of the choice of water model on the adsorption isotherms is examined.

The relationship between splanchnic oxygen consumption and blood supply.

Our experimental study has proved, that the increase in the intestinal and splanchnic metabolism is associated with raised blood flow. However, it has been found that so called primary increase of the blood flow by the administration of vasodilatators is not associated with raised metabolism, i.e. no increase in the oxygen uptake has been noted. Injection of Glucagon into the superior mesenteric artery raised both the splanchnic (portal vein) and the intestinal (superior mesenteric artery) blood flow. However, while the intestinal oxygen consumption increases along with the blood flow, when the blood flow to the whole splanchnic area has risen the oxygen consumption has not increased moreover it has decreased. This means, that while the Glucagon quickens the metabolism of the small bowel, that in the other abdominal organs has dropped. This means that while there is not any difference in the vascular effect of the intestinal and total splanchnic area, the metabolic effect shows a disparity, this can be regarded as an evidence, that the alterations in the splanchnic metabolism are not primarily determined by haemodynamic changes. The blood flow is adjusted to the oxygen demand and the physiological changes in the blood flow protect against cellular hypoxia under various circumstances.