1,264 research outputs found
Discrepancy between sub-critical and fast rupture roughness: a cumulant analysis
We study the roughness of a crack interface in a sheet of paper. We
distinguish between slow (sub-critical) and fast crack growth regimes. We show
that the fracture roughness is different in the two regimes using a new method
based on a multifractal formalism recently developed in the turbulence
literature. Deviations from monofractality also appear to be different in both
regimes
Sound and light from fractures in scintillators
Prompted by intriguing events observed in certain particle-physics searches
for rare events, we study light and acoustic emission simultaneously in some
inorganic scintillators subject to mechanical stress. We observe
mechanoluminescence in , and ,
in various mechanical configurations at room temperature and ambient pressure.
We analyze how the light emission is correlated to acoustic emission during
fracture. For , we set a lower bound on the energy of
the emitted light, and deduce that the fraction of elastic energy converted to
light is at least
Upgrades of beam diagnostics in support of emittance-exchange experiments at the Fermilab A0 photoinjector
The possibility of using electron beam phase space manipulations to support a
free-electron laser accelerator design optimization has motivated our research.
An on-going program demonstrating the exchange of transverse horizontal and
longitudinal emittances at the Fermilab A0 photoinjector has benefited recently
from the upgrade of several of the key diagnostics stations. Accurate
measurements of these properties upstream and downstream of the exchanger
beamline are needed. Improvements in the screen resolution term and reduced
impact of the optical system's depth-of-focus by using YAG:Ce single crystals
normal to the beam direction will be described. The requirement to measure
small energy spreads (<10 keV) in the spectrometer and the exchange process
which resulted in bunch lengths less than 500 fs led to other diagnostics
performance adjustments and upgrades as well. A longitudinal to transverse
exchange example is also reported.Comment: 16 p
Visualizing Pyrazinamide Action by Live Single-Cell Imaging of Phagosome Acidification and Mycobacterium tuberculosis pH Homeostasis.
Mycobacterium tuberculosis segregates within multiple subcellular niches with different biochemical and biophysical properties that, upon treatment, may impact antibiotic distribution, accumulation, and efficacy. However, it remains unclear whether fluctuating intracellular microenvironments alter mycobacterial homeostasis and contribute to antibiotic enrichment and efficacy. Here, we describe a live dual-imaging approach to monitor host subcellular acidification and M. tuberculosis intrabacterial pH. By combining this approach with pharmacological and genetic perturbations, we show that M. tuberculosis can maintain its intracellular pH independently of the surrounding pH in human macrophages. Importantly, unlike bedaquiline (BDQ), isoniazid (INH), or rifampicin (RIF), the drug pyrazinamide (PZA) displays antibacterial efficacy by disrupting M. tuberculosis intrabacterial pH homeostasis in cellulo. By using M. tuberculosis mutants, we confirmed that intracellular acidification is a prerequisite for PZA efficacy in cellulo. We anticipate this imaging approach will be useful to identify host cellular environments that affect antibiotic efficacy against intracellular pathogens. IMPORTANCE We still do not completely understand why tuberculosis (TB) treatment requires the combination of several antibiotics for up to 6 months. M. tuberculosis is a facultative intracellular pathogen, and it is still unknown whether heterogenous and dynamic intracellular populations of bacteria in different cellular environments affect antibiotic efficacy. By developing a dual live imaging approach to monitor mycobacterial pH homeostasis, host cell environment, and antibiotic action, we show here that intracellular localization of M. tuberculosis affects the efficacy of one first-line anti-TB drug. Our observations can be applicable to the treatment of other intracellular pathogens and help to inform the development of more effective combined therapies for tuberculosis that target heterogenous bacterial populations within the host
The 40s Omega-loop plays a critical role in the stability and the alkaline conformational transition of cytochrome c
The structural and redox properties of a non-covalent complex reconstituted upon mixing two non-contiguous fragments of horse cytochrome c, the residues 1 - 38 heme-containing N-fragment with the residues 57 - 104 C-fragment, have been investigated. With respect to native cyt c, the complex lacks a segment of 18 residues, corresponding, in the native protein, to an omega ( W)loop region. The fragment complex shows compact structure, native-like alpha-helix content but a less rigid atomic packing and reduced stability with respect to the native protein. Structural heterogeneity is observed at pH 7.0, involving formation of an axially misligated low-spin species and consequent partial displacement of Met80 from the sixth coordination position of the heme-iron. Spectroscopic data suggest that a lysine ( located in the Met80-containing loop, namely Lys72, Lys73, or Lys79) replaces the methionine residue. The residues 1 - 38/57 - 104 fragment complex shows an unusual biphasic alkaline titration characterized by a low (pK(a1)= 6.72) and a high pK(a)-associated state transition (pK(a2)= 8.56); this behavior differs from that of native cyt c, which shows a monophasic alkaline transition ( pK(a)= 8.9). The data indicate that the 40s Omega-loop plays an important role in the stability of cyt c and in ensuring a correct alkaline conformational transition of the protein
pH-dependent redox and CO binding properties of chelated protoheme-L-histidine and protoheme-glycyl-L-histidine complexes
The pH dependence of redox properties, spectroscopic features and CO binding kinetics for the chelated protohemin-6(7)-L-histidine methyl ester (heme-H) and the chelated protohemin-6(7)-glycyl-L-histidine methyl ester (heme-GH) systems has been investigated between pH 2.0 and 12.0. The two heme systems appear to be modulated by four protonating groups, tentatively identified as coordinated H2O, one of heme's propionates, N epsilon of the coordinating imidazole, and the carboxylate of the histidine residue upon hydrolysis of the methyl ester group (in acid medium). The pK(a) values are different for the two hemes, thus reflecting structural differences. In particular, the different strain at the Fe-N-epsilon bond, related to the different length of the coordinating arm, results in a dramatic alteration of the bond strength, which is much smaller in heme-H than in heme-GH. It leads to a variation in the variation of the pKa for the protonation of the N-epsilon of the axial imidazole as well as in the proton-linked behavior of the other protonating groups, envisaging a cross-talk communication mechanism among different groups of the heme, which can be operative and relevant also in the presence of the protein matrix
Proteome profile of peritoneal effluents in children on glucose- or icodextrin-based peritoneal dialysis
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Percutaneous CT-guided microwave ablation combined with pedicle screw fixation followed by vertebroplasty (MASFVA): initial experience of a minimally invasive treatment of vertebral metastases with extension to the vertebral pedicle
Background: The aim of this study was to retrospectively evaluate the safety and efficacy of a combined CT-guided percutaneous microwave ablation (MWA) and pedicle screw fixation followed by vertebroplasty (MASFVA) for the treatment and stabilization of painful vertebral metastases with vertebral pedicle involvement. (2) Methods: from January 2013 to January 2017 11 patients with 16 vertebral metastatic lesions (7 men and 5 women; mean age, 65 +/- 11 years) with vertebral metastases underwent CT-guided microwave ablation and screw fixation followed by vertebroplasty (MASFVA). Technical success, complication rate, pain evaluation using a visual analogue scale (VAS), Oswestry Disability Index (ODI) and local tumor control were examined. (3) Results: Technical success rate was 100%. No procedure-related major complications occurred. VAS score decreased from 6.8 +/- 0.7 to 0.6 +/- 0.6. ODI score decreased from 3.1 +/- 0.7 to 1.2 +/- 0.4. All patients could walk independently without neurological complication after one week from the procedure. No new bone fractures or local disease recurrence occurred during a median follow-up of 12 months. (4) Conclusions: Our results suggest that MWA and percutaneous pedicle screw fixation followed by vertebroplasty for the treatment of painful vertebral metastases is a safe and effective procedure for painful vertebral metastases with vertebral pedicle involvement, allowing pain relief and local tumor control
Morphology of two dimensional fracture surface
We consider the morphology of two dimensional cracks observed in experimental
results obtained from paper samples and compare these results with the
numerical simulations of the random fuse model (RFM). We demonstrate that the
data obey multiscaling at small scales but cross over to self-affine scaling at
larger scales. Next, we show that the roughness exponent of the random fuse
model is recovered by a simpler model that produces a connected crack, while a
directed crack yields a different result, close to a random walk. We discuss
the multiscaling behavior of all these models.Comment: slightly revise
Role of lysines in cytochrome c â cardiolipin interaction
Cytochrome c undergoes structural variations during the apoptotic process; such changes have been related with modifications occurring in the protein when it forms a complex with cardiolipin, one of the phospholipids constituting the mitochondrial membrane. Although several studies have been performed to identify the site(s) of the protein involved in the cytochrome c/cardiolipin interaction, to date the location of this hosting region(s) remains unidentified and is a matter of debate. To gain a deeper insight into the reaction mechanism, we investigate the role that the Lys72, Lys73 and Lys79 residues play in the cytochrome c/cardiolipin interaction, as these side chains appear to be critical for cytochrome c/cardiolipin recognition. The Lys72Asn, Lys73Asn, Lys79Asn, Lys72/73Asn and Lys72/73/79Asn mutants of horse heart cytochrome c were produced and characterized by circular dichroism, UV-visible and resonance Raman spectroscopies, and the effects of the mutations on the interaction of the variants with cardiolipin have been investigated. The mutants are characterized by a subpopulation with non-native axial coordination, and are less stable than the wild type protein. Furthermore, the mutants lacking Lys72 and/or Lys79 do not bind cardiolipin and those lacking Lys73, although they form a complex with the phospholipid, do not show any peroxidase activity. These observations indicate that the Lys72, Lys73 and Lys79 residues stabilize the native axial Met80-Fe(III) coordination as well as the tertiary structure of cytochrome c. Moreover, while Lys72 and Lys79 are critical for cytochrome c/cardiolipin recognition, the simultaneous presence of Lys72, Lys73 and Lys79 is necessary for peroxidase activity of cardiolipin-bound cytochrome c
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