Monte Carlo study of kink effect in isolated-gate InAs/AlSb high electron mobility transistors

A semiclassical two-dimensional ensemble Monte Carlo simulator is used to perform a physical analysis of the kink effect in InAs/AlSb high electron mobility transistors (HEMTs). Kink effect, this is, an anomalous increase in the drain current I-D when increasing the drain-to-source voltage V-DS, leads to a reduction in the gain and a rise in the level of noise, thus limiting the utility of these devices for microwave applications. Due to the small band gap of InAs, InAs/AlSb HEMTs are very susceptible to suffer from impact ionization processes, with the subsequent hole transport through the structure, both implicated in the kink effect. The results indicate that, when V-DS is high enough for the onset of impact ionization, holes thus generated tend to pile up in the buffer (at the gate-drain side) due to the valence-band energy barrier between the buffer and the channel. Due to this accumulation of positive charge the channel is further opened and I-D increases, leading to the kink effect in the I-V characteristics and eventually to the device electrical breakdown. The understanding of this phenomenon provides useful information for the development of kink-effect-free InAs/AlSb HEMTs

Monte Carlo studies of the intrinsic time-domain response of nanoscale three-branch junctions

We present a Monte Carlo time-domain study of nanostructured ballistic three-branch junctions (TBJs) excited by both step-function and Gaussian picosecond transients. Our TBJs were based on InGaAs 2-dimensional electron gas heterostructures and their geometry followed exactly the earlier experimental studies. Time-resolved, picosecond transients of both the central branch potential and the between-the-arms current demonstrate that the bandwidth of the intrinsic TBJ response reaches the THz frequency range, being mainly limited by the large-signal, intervalley scattering, when the carrier transport regime changes from ballistic to diffusive

High-resolution macromolecular crystallography at the FemtoMAX beamline with time-over-threshold photon detection

Protein dynamics contribute to protein function on different time scales. Ultrafast X-ray diffraction snapshots can visualize the location and amplitude of atom displacements after perturbation. Since amplitudes of ultrafast motions are small, high-quality X-ray diffraction data is necessary for detection. Diffraction from bovine trypsin crystals using single femtosecond X-ray pulses was recorded at FemtoMAX, which is a versatile beamline of the MAX IV synchrotron. The time-over-threshold detection made it possible that single photons are distinguishable even under short-pulse low-repetition-rate conditions. The diffraction data quality from FemtoMAX beamline enables atomic resolution investigation of protein structures. This evaluation is based on the shape of the Wilson plot, cumulative intensity distribution compared with theoretical distribution, I/σ, Rmerge /Rmeas and CC1/2 statistics versus resolution. The FemtoMAX beamline provides an interesting alternative to X-ray free-electron lasers when studying reversible processes in protein crystals

Small molecule anionophores promote transmembrane anion permeation matching CFTR activity

Anion selective ionophores, anionophores, are small molecules capable of facilitating the transmembrane transport of anions. Inspired in the structure of natural product prodigiosin, four novel anionophores 1a-d, including a 1,2,3-triazole group, were prepared. These compounds proved highly efficient anion exchangers in model phospholipid liposomes. The changes in the hydrogen bond cleft modified the anion transport selectivity exhibited by these compounds compared to prodigiosin and suppressed the characteristic high toxicity of the natural product. Their activity as anionophores in living cells was studied and chloride efflux and iodine influx from living cells mediated by these derivatives was demonstrated. These compounds were shown to permeabilize cellular membranes to halides with efficiencies close to the natural anion channel CFTR at doses that do not compromise cellular viability. Remarkably, optimal transport efficiency was measured in the presence of pH gradients mimicking those found in the airway epithelia of Cystic Fibrosis patients. These results support the viability of developing small molecule anionophores as anion channel protein surrogates with potential applications in the treatment of conditions such as Cystic Fibrosis derived from the malfunction of natural anion transport mechanisms.European Union’s Horizon 2020 research and innovation programme under grant agreement No. 667079, La Marató de TV3 Foundation (20132730), Consejería de Educación de la Junta de Castilla y León (Projects BU340U13 and BU092U16

2024 European Society of Hypertension clinical practice guidelines for the management of arterial hypertension

Practice Guidelines: 2024 European Society of Hypertension clinical practice guidelines for the management ofarterial hypertension. Endorsed by the European Federation of Internal Medicine (EFIM), European Renal Association (ERA), and International Society ofHypertension (ISH)</p

Dual mechanism of daunorubicin-induced cell death in both sensitive and MDR-resistant HL-60 cells

Exposure of some acute myeloid leukaemia (AML) cells to daunorubicin leads to rapid cell death, whereas other AML cells show natural drug resistance. This has been attributed to expression of functional P-glycoprotein resulting in reduced drug accumulation. However, it has also been proposed that P-glycoprotein-expressing multidrug-resistant (MDR) cells are inherently defective for apoptosis. To distinguish between these different possibilities, we have compared the cell death process in a human AML cell line (HL-60) with a MDR subline (HL-60/Vinc) at doses that yield either similar intracellular daunorubicin concentrations or comparable cytotoxicity. Adjustment of the dose to obtain the same intracellular drug accumulation in the two cell lines did not result in equal cytotoxicity, suggesting the presence of additional resistance mechanisms in the P-glycoprotein-expressing HL-60/Vinc cells. However, at equitoxic doses, similar cell death pathways were observed. In HL-60 cells, daunorubicin induced rapid apoptosis at 0.5–1 μM and delayed mitotic cell death at 0.1 μM. These concentrations are within the clinical dose range. Similarly, HL-60/Vinc cells underwent apoptosis at 50–100 μM daunorubicin and mitotic cell death at 10 μM. These results show, for the first time, that anthracyclines can induce cell death by a dual mechanism in both sensitive and MDR cells. Our results also show that not only the cytotoxicity, but also the kinetics and mechanism of cell death, are dose dependent. Interestingly, regrowth was observed only in association with delayed cell death and the formation of enlarged, often polyploid, cells with micronucleation, suggesting that morphological criteria may be useful to evaluate treatment efficacy in patients with myeloid leukaemias. © 1999 Cancer Research Campaig

Sources and sinks of nutrients and pollutants in Cullera Bay

[EN] Water quality plays a very important role in the ecological balance and economic development of coastal and estuarine areas. However, these areas have been progressively degraded in recent decades due to different factors, including an increase in nutrient and pollutant loads introduced into the system, which may cause eutrophication problems. This paper analyzes the water quality of one such area, Cullera Bay, located on the Spanish Mediterranean coast. This study focuses on the main sources and sinks of pollutant substances and the relationship between the distribution of these substances within the bay and local meteorological and oceanographic conditions. Two main sources of nutrients and pollutants were identified: the discharges of the Júcar River and the marine outfall, although other secondary sources are also present. The river discharge varies greatly depending on the season. The freshwater it carries is very rich in nutrients due to the presence of fertilizers and pesticides from its agricultural use. The domestic wastewater discharged through the marine outfall is occasionally untreated, particularly in the summer, when the tourist population increases and the capacity of the water treatment plant is exceeded. This study is based on data recorded during nine field campaigns carried out in the area in 2002 and 2003 and numerical simulations of hydrodynamics and pollutant dispersion. By analyzing the field data and the numerical simulation results, wind is identified as the main driving factor in the bay because the other possible driving factors either have negligible effects (tide), affect only a very localized area (waves, usual river discharges) or are infrequent (storm surges, river floods).The European Community funded this study as a part of the ECOSUD ‘‘Estuaries and Coastal Areas. Basis and Tools for a More Sustainable Development’’ (reference no. ICA4-CT-2001-10027) and AQUAS ‘‘Water quality and sustainable aquaculture. Links and implications’’ (reference no. INCOCT-2005-015105) projects. It was also funded by the Spanish Ministry of Science and Technology, through the project ‘‘Desarrollo y optimizacio´n de te´cnicas para gestionar los vertidos de aguas residuales de emisarios submarinos (ARTEMISA)’’(Reference no. REN2003-07585-C02-01/MAR).Sierra, J.; Mösso, C.; González Del Rio Rams, J.; Mestres, M.; Cupul, L.; Sánchez-Arcilla, A.; Rodilla Alamá, M.... (2007). Sources and sinks of nutrients and pollutants in Cullera Bay. Journal of Coastal Research. SI47:31-39. doi:10.2112/1551-5036-47.sp1.31S3139SI4

Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO): Study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III)

Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age 65 36 weeks and a birth weight 65 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. Trial registration: NCT03162653, www.ClinicalTrials.gov, May 22, 2017