The pressure-temperature phase diagram of tetramorphic pyrazinamide

The phase behaviour of drug molecules is important for the control over the desired polymorph in drug formulations, whether it is to ensure better stability or better solubility. In the case of pyrazinamide, a drug against tuberculosis, stability studies have been complicated due to the very slow transition kinetics observed in DSC measurements. Using vapour pressure measurements, in which the reluctance of phase transformation is in fact an advantage, all solid–solid phase transformation temperatures have been determined. This method has been key to map the phase behaviour of pyrazinamide. The use of high-pressure measurements with synchrotron X-ray diffraction has allowed the construction of the pressure–temperature phase diagram of the four solid phases of pyrazinamide and the liquid phase. The a form was found to be the stable form at room temperature. One striking feature of pyrazinamide is that one polymorph, the d form, has a very large thermal expansion and extreme compressibility not found in the other three forms. This gives rise to curved solid–solid transition equilibria in the pressure–temperature phase diagram, which is not commonly observed in the pressure range of 0 to 1 GPa. Using the phase diagram, polymorph ß could be obtained in its stable temperature domain.Peer ReviewedPostprint (published version

Chronic Overexpression of Bradykinin in Kidney Causes Polyuria and Cardiac Hypertrophy

Acute intra-renal infusion of bradykinin increases diuresis and natriuresis via inhibition of vasopressin activity. However, the consequences of chronically increased bradykinin in the kidneys have not yet been studied. A new transgenic animal model producing an excess of bradykinin by proximal tubular cells (KapBK rats) was generated and submitted to different salt containing diets to analyze changes in blood pressure and other cardiovascular parameters, urine excretion, and composition, as well as levels and expression of renin-angiotensin system components. Despite that KapBK rats excrete more urine and sodium, they have similar blood pressure as controls with the exception of a small increase in systolic blood pressure (SBP). However, they present decreased renal artery blood flow, increased intrarenal expression of angiotensinogen, and decreased mRNA expression of vasopressin V1A receptor (AVPR1A), suggesting a mechanism for the previously described reduction of renal vasopressin sensitivity by bradykinin. Additionally, reduced heart rate variability (HRV), increased cardiac output and frequency, and the development of cardiac hypertrophy are the main chronic effects observed in the cardiovascular system. In conclusion: (1) the transgenic KapBK rat is a useful model for studying chronic effects of bradykinin in kidney; (2) increased renal bradykinin causes changes in renin angiotensin system regulation; (3) decreased renal vasopressin sensitivity in KapBK rats is related to decreased V1A receptor expression; (4) although increased renal levels of bradykinin causes no changes in mean arterial pressure (MAP), it causes reduction in HRV, augmentation in cardiac frequency and output and consequently cardiac hypertrophy in rats after 6 months of age

Thousands of Rab GTPases for the Cell Biologist

Rab proteins are small GTPases that act as essential regulators of vesicular trafficking. 44 subfamilies are known in humans, performing specific sets of functions at distinct subcellular localisations and tissues. Rab function is conserved even amongst distant orthologs. Hence, the annotation of Rabs yields functional predictions about the cell biology of trafficking. So far, annotating Rabs has been a laborious manual task not feasible for current and future genomic output of deep sequencing technologies. We developed, validated and benchmarked the Rabifier, an automated bioinformatic pipeline for the identification and classification of Rabs, which achieves up to 90% classification accuracy. We cataloged roughly 8.000 Rabs from 247 genomes covering the entire eukaryotic tree. The full Rab database and a web tool implementing the pipeline are publicly available at www.RabDB.org. For the first time, we describe and analyse the evolution of Rabs in a dataset covering the whole eukaryotic phylogeny. We found a highly dynamic family undergoing frequent taxon-specific expansions and losses. We dated the origin of human subfamilies using phylogenetic profiling, which enlarged the Rab repertoire of the Last Eukaryotic Common Ancestor with Rab14, 32 and RabL4. Furthermore, a detailed analysis of the Choanoflagellate Monosiga brevicollis Rab family pinpointed the changes that accompanied the emergence of Metazoan multicellularity, mainly an important expansion and specialisation of the secretory pathway. Lastly, we experimentally establish tissue specificity in expression of mouse Rabs and show that neo-functionalisation best explains the emergence of new human Rab subfamilies. With the Rabifier and RabDB, we provide tools that easily allows non-bioinformaticians to integrate thousands of Rabs in their analyses. RabDB is designed to enable the cell biology community to keep pace with the increasing number of fully-sequenced genomes and change the scale at which we perform comparative analysis in cell biology

Pregled znanstvenih napredaka u učinskoj elektronici usmjerenih ka osiguravanju efikasnog rada i dužeg životnog vijeka PEMgorivih ćelija

This article focuses on the main issues that affect the lifetime and performance of proton-exchange membrane fuel cells. The short lifespans of these fuel cells represent a barrier to their massive commercialization and usage in mobile and stationary applications. As fuel cell is a very complex system, a lot of knowledge of different areas is required, such as chemistry, electricity and mechanics, in order to completely understand its operation and all the problems that can occur during it. It is for this reason that an interdisciplinary approach needs to be taken when designing fuel-cell energy systems. This paper focuses on identifying and solving those issues that negatively affect the lifetime and performance of fuel cells. It is hoped that this article would be a valuable aid for power electronics’ researchers and engineers for better understanding the presented issues and a useful guide for solving them with the use of proper power electronic-devices. Initially, the basic operation and structure of a proton-exchange membrane fuel cell is explained. Three main issues that can occur during operation of a mobile or stationary fuel cell energy system are pointed out and discussed in details, on the basis of the state-of-the-art on fuel cell technology. These issues are poor water management, reactant gas starvation and fuel cell current ripple. This article provides answers as to why they occur, how they affect the fuel cell, how they can be mitigated, and what are the future trends within this research field.Članak se osvrće na ključna pitanja koja utječu na vrijeme rada i performanse gorivih ćelija s polimernom membranom kao elektrolitom. Kratak životni vijek gorivih ćelija takve vrste prepreka je njihovoj komercijalizaciji i masovnoj upotrebi u mobilnim i stacionarnim stanicama. Budući da su gorive ćelije komplicirani sustavi potrebno je znanje iz raznih područja kemije, elektrotehnike i mehanike da bi se u potpunosti mogao razumjeti njihov način rada i problemi koji se događaju. Upravo je zbog toga multidisciplinarni pristup nužnost pri razvoju sustava koji koriste gorive ćelije. Ovaj je članak usmjeren prema identifikaciji i rješavanju onih problema koji negativno utječu na životni vijek i performanse gorivih ćelija. Autori se nadaju da će se članak pokazati kao korisna pomoć i vodič istraživačima i inženjerima u domeni učinske elektronike pri susretu s navedenim problemima. Objašnjen je način rada i struktura gorive ćelije s polimernom membranom kao elektrolitom. Izložena su, i diskutirana do u detalje, tri glavna problema sa stajališta trenutačnih spoznaja u području učinske elektronike. Ti problemi su: loše upravljanje vodom, nestanak reaktantnog plina i strujni trzaji u gorivim ćelijama. Objašnjeno je zašto se ovi problemi događaju, kako utječu na gorivu ćeliju, kako ih se može spriječiti i koje su buduće perspektive istraživanja

The phase behavior of pyrazinamide

International audienc

The phase behavior of pyrazinamide

International audienc