917 research outputs found
Defective ribosomal products challenge nuclear function by impairing nuclear condensate dynamics and immobilizing ubiquitin
Nuclear protein aggregation has been linked to genome instability and disease. The main source of aggregation-prone proteins in cells is defective ribosomal products (DRiPs), which are generated by translating ribosomes in the cytoplasm. Here, we report that DRiPs rapidly diffuse into the nucleus and accumulate in nucleoli and PML bodies, two membraneless organelles formed by liquid\u2013liquid phase separation. We show that nucleoli and PML bodies act as dynamic overflow compartments that recruit protein quality control factors and store DRiPs for later clearance. Whereas nucleoli serve as constitutive overflow compartments, PML bodies are stress-inducible overflow compartments for DRiPs. If DRiPs are not properly cleared by chaperones and proteasomes due to proteostasis impairment, nucleoli undergo amyloidogenesis and PML bodies solidify. Solid PML bodies immobilize 20S proteasomes and limit the recycling of free ubiquitin. Ubiquitin depletion, in turn, compromises the formation of DNA repair compartments at fragile chromosomal sites, ultimately threatening cell survival
Sum rules for X-ray magnetic circular dichroism spectra in strongly correlated ferromagnets
It is proven that the sum rules for X-ray magnetic dichroism (XMCD) spectra
that are used to separate spin and orbital contributions to the magnetic moment
are formally correct for an arbitrary strength of electron-electron
interactions. However, their practical application for strongly correlated
systems can become complicated due to the spectral density weight spreading
over a broad energy interval. Relevance of incoherent spectral density for the
XMCD sum rules is illustrated by a simple model of a ferromagnet with orbital
degrees of freedom.Comment: 4 pages, final versio
Autochthonous cases of mucosal leishmaniasis in Northeastern Italy: clinical management and novel treatment approaches
Mucosal leishmaniasis (ML) is a rare clinical variant of tegumentary leishmaniasis in Mediterranean Europe. Here we report on three autochthonous cases of head and neck ML in patients living in Northeastern Italy. Patients presented with non-specific, long-standing symptoms of upper respiratory tract involvement, mimicking other diseases. Parasitological diagnosis was reached by histopathology, immunohistochemistry and molecular biology on tissue specimens. Leishmania infantum was identified by molecular typing in all three cases. All patients reached a complete remission with protracted multivalent antileishmanial drugs; in one case, a novel approach of combined medical and endoscopic surgical treatment was carried out. High clinical suspicion led to a prompt diagnosis and deployment of a multivalent treatment. ML should be considered in the differential diagnosis of nasal, oral, and pharyngolaryngeal lesions in endemic areas. A prompt diagnosis is mandatory to establish a correct management; different antileishmanial medications as well as endoscopic surgical options may be required to reach a complete remission
Design and Vertical Tests of SPS-series Double-Quarter Wave (DQW) Cavity Prototypes for the HL-LHC Crab Cavity System
Crab crossing is essential for high-luminosity colliders. The High Luminosity
Large Hadron Collider (HL-LHC) will equip one of its Interaction Points (IP1)
with Double-Quarter Wave (DQW) crab cavities. A DQW cavity is a new generation
of deflecting RF cavities that stands out for its compactness and broad
frequency separation between fundamental and first high-order modes. The
deflecting kick is provided by its fundamental mode. Each HL-LHC DQW cavity
shall provide a nominal deflecting voltage of 3.4 MV, although up to 5.0 MV may
be required. A Proof-of-Principle (PoP) DQW cavity was limited by quench at 4.6
MV. This paper describes a new, highly optimized cavity, designated DQW
SPS-series, which satisfies dimensional, cryogenic, manufacturing and impedance
requirements for beam tests at SPS and operation in LHC. Two prototypes of this
DQW SPS-series were fabricated by US industry and cold tested after following
conventional SRF surface treatment. Both units outperformed the PoP cavity,
reaching a deflecting voltage of 5.3-5.9 MV. This voltage - the highest reached
by a DQW cavity - is well beyond the nominal voltage of 3.4 MV and may even
operate at the ultimate voltage of 5.0MVwith sufficient margin. This paper
covers fabrication, surface preparation and cryogenic RF test results and
implications
Rare earth contributions to the X-ray magnetic circular dichroism at the Co K edge in rare earth-cobalt compounds investigated by multiple-scattering calculations
The X-ray magnetic circular dichroism (XMCD) has been measured at the Co K
edge in Co-hcp and R-Co compounds (R=La, Tb, Dy). The structure of the
experimental XMCD spectra in the near-edge region has been observed to be
highly sensitive to the magnetic environment of the absorbing site.
Calculations of the XMCD have been carried out at the Co K edge in Co metal,
LaCo and TbCo within the multiple-scattering framework including the
spin-orbit coupling. In the three systems, the XMCD spectra in the near-edge
region are well reproduced. The possibility to separate and quantitatively
estimate the local effects from those due to the neighboring atoms in the XMCD
cross section makes possible a more physical understanding of the spectra. The
present results emphasize the major role played by the states of the Tb
ions in the XMCD spectrum at the Co K edge in the TbCo compound.Comment: 34 pages, revtex, 10 eps figures included with epsf, after referee
revie
Electronic and Magnetic Structures of Sr2FeMoO6
We have investigated the electronic and magnetic structures of Sr2FeMoO6
employing site-specific direct probes, namely x-ray absorption spectroscopy
with linearly and circularly polarized photons. In contrast to some previous
suggestions, the results clearly establish that Fe is in the formal trivalent
state in this compound. With the help of circularly polarized light, it is
unambiguously shown that the moment at the Mo sites is below the limit of
detection (< 0.25mu_B), resolving a previous controversy. We also show that the
decrease of the observed moment in magnetization measurements from the
theoretically expected value is driven by the presence of mis-site disorder
between Fe and Mo sites.Comment: To appear in Physical Review Letter
A Systematic Review of Non-pharmacological Strategies to Reduce the Risk of Violence in Patients With Schizophrenia Spectrum Disorders in Forensic Settings
Background: The purpose of this systematic review is to systematically investigate
which non-pharmacological interventions are effective in reducing violence risk among
patients with schizophrenia spectrum disorders (SSD) in forensic settings.
Methods: Six electronic data bases were searched. Two researchers independently
screened 6,003 abstracts resulting in 143 potential papers. These were analyzed in detail
by two independent researchers yielding 10 articles that could be used.
Results: Of the 10 articles, four were non-randomized controlled trials, three were
pre-post studies without controls, and one was observational. Only two studies applied
a randomized controlled trial design. Cognitive behavioral treatment programs were
investigated in three studies. A broad range of other interventions were studied. Often
outcome measures were specific to each study and sample sizes were small. Frequently,
important methodological information was missing from the papers. It was not possible
to carry out a meta-analysis due to the heterogeneity of the study designs and
outcome measures.
Conclusion: Because of methodological limitations it is difficult to draw firm conclusions
about the effectiveness of non-pharmacological interventions to reduce the risk
of violence in patents with SSD in forensic psychiatry settings. Studies applying
better methods in terms of study design, sample sizes and outcome measures are
urgently needed
Robotic multiquadrant colorectal procedures: A single-center experience and a systematic review of the literature
Purpose: Robotic surgery has been progressively implemented for colorectal procedures but is still limited for multiquadrant abdominal resections. The present study aims to describe our experience in robotic multiquadrant colorectal surgeries and provide a systematic review and meta-analysis of the literature investigating the outcomes of robotic total proctocolectomy (TPC), total colectomy (TC), subtotal colectomy (STC), or completion proctectomy (CP) compared to laparoscopy. Methods: At our institution 16 consecutive patients underwent a 2- or 3-stage totally robotic total proctocolectomy (TPC) with ileal pouch-anal anastomosis. A systematic review of the literature was performed to select studies on robotic and laparoscopic multiquadrant colorectal procedures. Meta-analyses were used to compare the two approaches. Results: In our case series, 14/16 patients underwent a 2-stage robotic TPC for ulcerative colitis with a mean operative time of 271.42 (SD:37.95) minutes. No conversion occurred. Two patients developed postoperative complications. The mean hospital stay was 8.28 (SD:1.47) days with no readmissions. Mortality was nil. All patients underwent loop-ileostomy closure, and functional outcomes were satisfactory. The literature appraisal was based on 23 retrospective studies, including 736 robotic and 9,904 laparoscopic multiquadrant surgeries. In the robotic group, 36 patients underwent STC, 371 TC, 166 TPC, and 163 CP. Pooled data analysis showed that robotic TC and STC had a lower conversion rate (OR = 0.17;95% CI, 0.04–0.82; p = 0.03) than laparoscopic TC and STC. The robotic approach was associated with longer operative time for TC and STC (MD = 104.64;95% CI, 18.42–190.87; p = 0.02) and TPC and CP (MD = 38.8;95% CI, 18.7–59.06; p = 0.0002), with no differences for postoperative complications and hospital stay. Reports on urological outcomes, sexual dysfunction, and quality of life were missing. Conclusions: Our experience and the literature suggest that robotic multiquadrant colorectal surgery is safe and effective, with low morbidity and mortality rates. Nevertheless, the overall level of evidence is low, and functional outcomes of robotic approach remain largely unknown. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022303016
X-Ray Magnetic Circular Dichroism at the K edge of Mn3GaC
We theoretically investigate the origin of the x-ray magnetic circular
dichroism (XMCD) spectra at the K edges of Mn and Ga in the ferromagnetic phase
of Mn3GaC on the basis of an ab initio calculation. Taking account of the
spin-orbit interaction in the LDA scheme, we obtain the XMCD spectra in
excellent agreement with the recent experiment. We have analyzed the origin of
each structure, and thus elucidated the mechanism of inducing the orbital
polarization in the p symmetric states. We also discuss a simple sum rule
connecting the XMCD spectra with the orbital moment in the p symmetric states.Comment: 5 pages, 5 figures, accepted for publication in Physical Review
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