Experimental ionization of atomic hydrogen with few-cycle pulses

We present the first experimental data on strong-field ionization of atomic hydrogen by few-cycle laser pulses. We obtain quantitative agreement at the 10% level between the data and an {\it ab initio} simulation over a wide range of laser intensities and electron energies

Polycation-π Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family

Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al

Prediction of ventricular arrhythmia in phospholamban p.Arg14del mutation carriers-reaching the frontiers of individual risk prediction

AIMS: This study aims to improve risk stratification for primary prevention implantable cardioverter defibrillator (ICD) implantation by developing a new mutation-specific prediction model for malignant ventricular arrhythmia (VA) in phospholamban (PLN) p.Arg14del mutation carriers. The proposed model is compared to an existing PLN risk model. METHODS AND RESULTS: Data were collected from PLN p.Arg14del mutation carriers with no history of malignant VA at baseline, identified between 2009 and 2020. Malignant VA was defined as sustained VA, appropriate ICD intervention, or (aborted) sudden cardiac death. A prediction model was developed using Cox regression. The study cohort consisted of 679 PLN p.Arg14del mutation carriers, with a minority of index patients (17%) and male sex (43%), and a median age of 42 years [interquartile range (IQR) 27–55]. During a median follow-up of 4.3 years (IQR 1.7–7.4), 72 (10.6%) carriers experienced malignant VA. Significant predictors were left ventricular ejection fraction, premature ventricular contraction count/24 h, amount of negative T waves, and presence of low-voltage electrocardiogram. The multivariable model had an excellent discriminative ability {C-statistic 0.83 [95% confidence interval (CI) 0.78–0.88]}. Applying the existing PLN risk model to the complete cohort yielded a C-statistic of 0.68 (95% CI 0.61–0.75). CONCLUSION: This new mutation-specific prediction model for individual VA risk in PLN p.Arg14del mutation carriers is superior to the existing PLN risk model, suggesting that risk prediction using mutation-specific phenotypic features can improve accuracy compared to a more generic approach

Valorisation of sawdust through the combined microwave-assisted hydrothermal pre-treatment and fermentation using an oleaginous yeast

Oleaginous yeast, cultured on second-generation lignocellulosic resources, has the potential to be a key part of the future energy sector. However, the multiple unit operations necessary to produce concentrated hydrolysates, with a minimum of fermentation inhibitors, limit the applicability to date. In this study, a simple microwave-assisted hydrothermal pre-treatment step of oak or beech sawdust was deployed to produce an oligosaccharide-rich hydrolysate. This was then catabolised by the oleaginous yeast, Metschnikowia pulcherrima, avoiding the need for costly enzymatic or further chemical steps in the processing. Up to 85% of the sawdust’s hemicelluloses could be solubilised under these conditions, and 8 g/L DCW yeast with a 42% lipid content produced. While a number of studies have demonstrated that oleaginous yeasts possess high inhibitor tolerance, using this real lignocellulosic hydrolysate, we demonstrate that lipid production is actually very sensitive to inhibitor and carbon availability, and the optimal system is not the one that gives the highest hydrolysate or cell biomass. Indeed, the yeast was shown to detoxify the inhibitors in the process, but at high inhibitor loading, this leads to very poor lipid production, especially at high furfural levels. These findings clearly highlight the importance of considering multiple variables when real, complex lignocellulosic media are involved, tuning process conditions based on the desired fermentation outcomes

Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins

<p>Abstract</p> <p>Aim</p> <p>The aim of our study was to evaluate survival outcomes in malignant mixed Mullerian tumors (MMMT) of the uterus with respect to the role of cell cycle and apoptotic regulatory proteins in the carcinomatous and sarcomatous components.</p> <p>Methods</p> <p>23 cases of uterine MMMT identified from the Saskatchewan Cancer Agency (1970-1999) were evaluated. Immunohistochemical expression of Bad, Mcl-1, bcl-x, bak, mdm2, bax, p16, p21, p53, p27, EMA, Bcl-2, Ki67 and PCNA was correlated with clinico-pathological data including survival outcomes.</p> <p>Results</p> <p>Histopathological examination confirmed malignant epithelial component with homologous (12 cases) and heterologous (11 cases) sarcomatous elements. P53 was strongly expressed (70-95%) in 15 cases and negative in 5 cases. The average survival in the p53+ve cases was 3.56 years as opposed to 8.94 years in p53-ve cases. Overexpression of p16 and Mcl-1 were observed in patients with longer survival outcomes (> 2 years). P16 and p21 were overexpressed in the carcinomatous and sarcomatous elements respectively. Cyclin-D1 was focally expressed only in the carcinomatous elements.</p> <p>Conclusions</p> <p>Our study supports that a) cell cycle and apoptotic regulatory protein dysregulation is an important pathway for tumorigenesis and b) p53 is an important immunoprognostic marker in MMMT of the uterus.</p

Nanoscale STM-patterning and chemical modification of the Si(100) surface

Nanoscale patterning of the Si(100)-2x1:H monohydride surface has been achieved using an ultrahigh vacuum (UHV) scanning tunneling microscope (STM). The monohydride surface, prepared in UHV by exposure of a heated sample (650 K) to an atomic hydrogen flux, serves as an effective resist for STM patterning and exposure to O 2 and NH 3. Operating the STM in field emission causes hydrogen to be desorbed from the surface, exposing atomically clean silicon. There is no evidence for repassivation of the surface after patterning, suggesting that hydrogen may desorb as H 2. Hydrogen desorption can also be achieved at tunneling biases (~3-4 V) by using larger currents. Nanometer-scale linewidths can be achieved with this technique; single dimer rows have in fact been depassivated. The patterned areas display the same chemical reactivity as clean Si, suggesting the possibility of selective chemical modification of the surface at nanometer scales. This STM-depassivation technique shows considerable potential as a means for nanostructure fabrication

Nanoscale patterning and selective chemistry of silicon surfaces by ultrahigh-vacuum scanning tunneling microscopy

Nanometer scale patterning of the monohydride surface has been achieved by using an ultrahigh-vacuum (UHV) scanning tunneling microscope (STM) to selectively desorb the hydrogen. After preparing high-quality H-passivated surfaces in the UHV chamber, patterning is achieved by operating the STM in field emission. The field-emitted electrons stimulate the desorption of molecular hydrogen, restoring clean in the patterned area. This depassivation mechanism seems to be related to the electron kinetic energy for patterning at higher voltages and electron current for low-voltage patterning. The patterned linewidth varies linearly with tip bias, achieving a minimum of less than 10 A at -4.5 V. The linewidth dependence on electron dose is also studied. For positive tip biases up to 10 V no patterning occurs. The selective chemical reactivity of the patterned surface has been explored by oxygen and ammonia dosing. For the oxygen case, initial oxidation of the patterned area is observed. Ammonia dosing, on the other hand, repassivates the surface in a manner different from that of atomic hydrogen. In both cases the pattern resolution is retained and the surrounding H-passivated areas remain unaffected by the dosing

Nanometer scale patterning and oxidation of silicon surfaces with an ultrahigh vacuum scanning tunneling microscope

Nanoscale patterning of the Si(100)‐2×1 monohydride surface has been achieved by using an ultrahigh vacuum (UHV) scanning tunneling microscope (STM) to selectively desorb the hydrogen passivation. Hydrogen passivation on silicon represents one of the simplest possible resist systems for nanolithography experiments. After preparing high quality H‐passivated surfaces in the UHV chamber, patterning is achieved by operating the STM in field emission. The field emitted electrons stimulate the desorption of molecular hydrogen, restoring clean Si(100)‐2×1 in the patterned area. This depassivation mechanism seems to be related to the electron kinetic energy for patterning at higher voltages and the electron current for low voltage patterning. The patterned linewidth varies linearly with the applied tip bias achieving a minimum of \u3c10 Å at −4.5 V. The dependence of linewidth on electron dose is also studied. For positive tip biases up to 10 V no patterning occurs. The restoration of clean Si(100)‐2×1 is suggestive of selective area chemical modifications. This possibility has been explored by exposing the patterned surface to oxygen and ammonia. For the oxygen case, initial oxidation of the patterned area is observed. Ammonia dosing, on the other hand, repassivates the surface in a manner different from that of atomic hydrogen. In both cases the pattern resolution is retained and the surrounding H‐passivated areas remain unaffected by the dosing