Intracellular bacteria have developed numerous strategies to hijack host vesicular trafficking pathways to form their unique replicative niches. To promote intracellular replication, the bacteria ...must interact with host organelles and modulate host signaling pathways to acquire nutrients and membrane for the growing parasitophorous vacuole all while suppressing activation of the immune response. To facilitate host cell subversion, bacterial pathogens use specialized secretion systems to deliver bacterial virulence factors, termed effectors, into the host cell that mimic, agonize, and/or antagonize the function of host proteins. In this review we will discuss how bacterial effector proteins from
serovar Typhimurium,
, and
manipulate the endocytic and secretory pathways. Understanding how bacterial effector proteins manipulate host processes not only gives us keen insight into bacterial pathogenesis, but also enhances our understanding of how eukaryotic membrane trafficking is regulated.
State capitalism is experiencing a revival as a term to capture the current capitalist constellations and departures from neoliberalism. Unlike, neoliberalism, however, the term state capitalism has ...a long history reaching back to the age of imperialism in the late 19th century. Although state capitalism has been used as a prerogative term by Marxists, liberals, and neoliberals alike, it has served as a programmatic label for developmentalist and neomercantilist projects in reaction to imperialism in the periphery. This paper argues that we need to bring the intellectual history of state capitalism into the ‘new state capitalism’ debate. China has played a major role in the revival of state capitalism in the social sciences, but the long history of China's engagement with state capitalism as a concept and program dating back to the late Qing reformers has been overlooked for the most part. State capitalism is by no means new to China, from Liang Qichao, Sun Yatsen, and Mao Zedong to Deng Xiaoping, the idea that China had to create a modern nation-state and industrial capitalism in the name of economic progress and to get ahead in the global competition is a recurring theme. What is new is that for the first time, the ambition to use state capitalism as a means to catch up with the West is bearing fruits in ways that could undermine the predominance of Western economies.
Determining the brain perfusion is an important task for diagnosis of vascular diseases such as occlusions and intracerebral haemorrhage. Even after successful diagnosis, there is a high risk of ...restenosis or rebleeding such that patients need intense attention in the days after treatment. Within this work, we present a diagnostic tomographic imager that allows access to brain perfusion quantitatively in short intervals. The device is based on the magnetic particle imaging technology and is designed for human scale. It is highly sensitive and allows the detection of an iron concentration of 263 pmol
ml
, which is one of the lowest iron concentrations imaged by MPI so far. The imager is self-shielded and can be used in unshielded environments such as intensive care units. In combination with the low technical requirements this opens up a variety of medical applications and would allow monitoring of stroke on intensive care units.
The ultrafast photoinduced ring-opening of 1,3-cyclohexadiene constitutes a textbook example of electrocyclic reactions in organic chemistry and a model for photobiological reactions in vitamin D ...synthesis. Although the relaxation from the photoexcited electronic state during the ring-opening has been investigated in numerous studies, the accompanying changes in atomic distance have not been resolved. Here we present a direct and unambiguous observation of the ring-opening reaction path on the femtosecond timescale and subångström length scale using megaelectronvolt ultrafast electron diffraction. We followed the carbon-carbon bond dissociation and the structural opening of the 1,3-cyclohexadiene ring by the direct measurement of time-dependent changes in the distribution of interatomic distances. We observed a substantial acceleration of the ring-opening motion after internal conversion to the ground state due to a steepening of the electronic potential gradient towards the product minima. The ring-opening motion transforms into rotation of the terminal ethylene groups in the photoproduct 1,3,5-hexatriene on the subpicosecond timescale.
NT-proBNP seems to be affected more by worsening renal function than BNP. Besides diminished renal clearance, higher prevalence of concomitant left ventricular alterations such as left ventricular ...hypertrophy, diastolic and systolic dysfunction as well as fluid overload might contribute to elevated BNP and NT-proBNP concentrations. Role of BNP and NT-proBNP in clinical routine: key points B-type natriuretic peptide (BNP) and NT-proBNP are reliable biomarkers, reflecting myocardial stress caused by various cardiovascular diseases Both markers are stable in whole blood and can be measured in clinical routine using fully automated commercially available assays The diagnostic performance of BNP and NT-proBNP is comparable and there is no meaningful difference between the two The particular strength of BNP and NT-proBNP is to rule out heart failure in patients with shortness of breath in the emergency department Both markers provide prognostic information in patients with heart failure, coronary artery disease, and valvular heart disease Additional references appear on the Heart website- http://www.heartjnl.com/supplemental
Research in the field of electronics of 1D group-IV semiconductor structures has attracted increasing attention over the past 15 years. The exceptional combination of the unique 1D electronic ...transport properties with the mature material know-how of highly integrated silicon and germanium technology holds the promise of enhancing state-of-the-art electronics. In addition of providing conduction channels that can bring conventional field effect transistors to the uttermost scaling limits, the physics of 1D group IV nanowires endows new device principles. Such unconventional silicon and germanium nanowire devices are contenders for beyond complementary metal oxide semiconductor (CMOS) computing by virtue of their distinct switching behavior and higher expressive value. This review conveys to the reader a systematic recapitulation and analysis of the physics of silicon and germanium nanowires and the most relevant CMOS and CMOS-like devices built from silicon and germanium nanowires, including inversion mode, junctionless, steep-slope, quantum well and reconfigurable transistors.
Stereotactic body radiation therapy (SBRT) provides high rates of local control (LC) and margin-negative (R0) resections for locally advanced pancreatic cancer (LAPC) and borderline resectable ...pancreatic cancer (BRPC), respectively, with minimal toxicity.
A single-institution retrospective review was performed for patients with nonmetastatic pancreatic cancer treated with induction chemotherapy followed by SBRT. SBRT was delivered over 5 consecutive fractions using a dose painting technique including 7-10 Gy/fraction to the region of vessel abutment or encasement and 5-6 Gy/fraction to the remainder of the tumor. Restaging scans were performed at 4 weeks, and resectable patients were considered for resection. The primary endpoints were overall survival (OS) and progression-free survival (PFS).
Seventy-three patients were evaluated, with a median follow-up time of 10.5 months. Median doses of 35 Gy and 25 Gy were delivered to the region of vessel involvement and the remainder of the tumor, respectively. Thirty-two BRPC patients (56.1%) underwent surgery, with 31 undergoing an R0 resection (96.9%). The median OS, 1-year OS, median PFS, and 1-year PFS for BRPC versus LAPC patients was 16.4 months versus 15 months, 72.2% versus 68.1%, 9.7 versus 9.8 months, and 42.8% versus 41%, respectively (all P>.10). BRPC patients who underwent R0 resection had improved median OS (19.3 vs 12.3 months; P=.03), 1-year OS (84.2% vs 58.3%; P=.03), and 1-year PFS (56.5% vs 25.0%; P<.0001), respectively, compared with all nonsurgical patients. The 1-year LC in nonsurgical patients was 81%. We did not observe acute grade ≥3 toxicity, and late grade ≥3 toxicity was minimal (5.3%).
SBRT safely facilitates margin-negative resection in patients with BRPC pancreatic cancer while maintaining a high rate of LC in unresectable patients. These data support the expanded implementation of SBRT for pancreatic cancer.
Previous studies demonstrated the relevance of focal lesions (FL) in whole-body magnetic resonance imaging (wb-MRI) at the initial workup of patients with smoldering multiple myeloma (SMM). The aim ...of this study was to assess the effects of longitudinal wb-MRIs on progression into multiple myeloma (MM). Sixty-three patients with SMM were analyzed who received at least two wb-MRIs for follow-up before progression into MM. Radiological progressive disease (MRI-PD) was defined as detection of new FL or increase in diameter of existing FL and a novel or progressive diffuse infiltration. Radiological stable disease (MRI-SD) was defined by no change compared with the prior MRI. Patients were followed-up every 3-6 months, including a serological and clinical evaluation. One Hundred and eighty-two wb-MRIs were analyzed. MRI-PD occurred in 31 patients (49%), and 25 (40%) patients developed MM. MRI-PD was highly significantly associated with progression into MM, regardless of findings at the initial MRI. In multivariate analysis, MRI-PD remained a risk factor, independent of relevant baseline parameters like serum monoclonal protein or ⩾95% aberrant plasma cells in the bone marrow. Patients with MRI-SD had no higher risk of progression, even when FL were present at the initial MRI. Therefore, MRI is suitable for the follow-up of patients with SMM.
The photoinduced ring-conversion reaction when cyclopentadiene (CP) is excited at 5.10 eV is simulated using surface-hopping semiclassical trajectories with XMS(3)-CASPT2(4,4)/cc-pVDZ electronic ...structure theory. In addition, PBE0/def2-SV(P) is employed for ground state propagation of the trajectories. The dynamics is propagated for 10 ps, mapping both the nonadiabatic short-time dynamics (<300 fs) and the increasingly statistical dynamics on the electronic ground state. The short-time dynamics yields a mixture of hot CP and bicyclo2.1.0pentene (BP), with the two products reached
via
different regions of the same conical intersection seam. On the ground state, we observe slow conversion from BP to CP which is modelled by RRKM theory with a transition state determined using PBE0/def2-TZVP. The CP products are furthermore associated with ground state hydrogen shifts and some H-atom dissociation. Finally, the prospects for detailed experimental mapping using novel ultrafast X-ray scattering experiments are discussed and observables for such experiments are predicted. In particular, we assess the possibility of retrieving electronic states and their populations alongside the structural dynamics.
The photochemistry of cyclopentadiene is investigated using nonadiabatic dynamics simulations. Observables for ultrafast X-ray scattering experiments are predicted and mapped onto the structural dynamics.
Context. The rotation curve, the total mass and the gravitational potential of the Galaxy are sensitive measurements of the dark matter halo profile. Aims. Cuspy and cored DM halo profiles are ...analysed with respect to recent astronomical constraints in order to constrain the shape of the Galactic DM halo and the local DM density. Methods. All Galactic density components (luminous matter and DM) are parametrized. Then the total density distribution is constrained by astronomical observations: 1) the total mass of the Galaxy, 2) the total matter density at the position of the Sun, 3) the surface density of the visible matter, 4) the surface density of the total matter in the vicinity of the Sun, 5) the rotation speed of the Sun and 6) the shape of the velocity distribution within and above the Galactic disc. The mass model of the Galaxy is mainly constrained by the local matter density (Oort limit), the rotation speed of the Sun and the total mass of the Galaxy from tracer stars in the halo. Results. We showed from a statistical $\chi^2$ fit to all data that the local DM density is strongly positively (negatively) correlated with the scale length of the DM halo (baryonic disc). Since these scale lengths are poorly constrained the local DM density can vary from 0.2 to 0.4 GeV cm-3 ($0.005{-}0.01~M_\odot$ pc-3) for a spherical DM halo profile and allowing total Galaxy masses up to $2 \times 10^{\mathrm{12}}~M_\odot$. For oblate DM haloes and dark matter discs, as predicted in recent N-body simulations, the local DM density can be increased significantly.
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