We present new measurements of the temperature of the intergalactic medium (IGM) derived from the Lyα forest over 2.0 ≤z≤ 4.8. The small-scale structure in the forest of 61 high-resolution ...quasi-stellar object spectra is quantified using a new statistic, the curvature, and the conversion to temperature calibrated using a suite of hydrodynamic simulations. At each redshift, we focus on obtaining the temperature at an optimal overdensity probed by the Lyα forest,
, where the temperature is nearly a one-to-one function of the curvature regardless of the slope of the temperature-density relation. The median 2σ statistical uncertainty in these measurements is 8 per cent, though there may be comparable systematic errors due to the unknown amount of Jeans smoothing in the IGM. We use our
results to infer the temperature at the mean density, T
0. Even for a maximally steep temperature-density relation, T
0 must increase from ∼8000 K at z≃ 4.4 to ≳12 000 K at z≃ 2.8. This increase is not consistent with the monotonic decline in T
0 expected in the absence of He ii reionization. We therefore interpret the observed rise in temperature as evidence of He ii reionization beginning at z≳ 4.4. The evolution of T
0 is consistent with an end to He ii reionization at z∼ 3, as suggested by opacity measurements of the He ii Lyα forest, although the redshift at which T
0 peaks will depend somewhat on the evolution of the temperature-density relation. These new temperature measurements suggest that the heat input due to the reionization of He ii dominates the thermal balance of the IGM over an extended period with Δz≳ 1.
The ability to induce a defense response after pathogen attack is a critical feature of the immune system of any organism. Nucleotide-binding leucine-rich repeat receptors (NLRs) are key players in ...this process and perceive the occurrence of nonself-activities or foreign molecules. In plants, coevolution with a variety of pests and pathogens has resulted in repertoires of several hundred diverse NLRs in single individuals and many more in populations as a whole. However, the mechanism by which defense signaling is triggered by these NLRs in plants is poorly understood. Here, we show that upon pathogen perception, NLRs use their N-terminal domains to transactivate other receptors. Their N-terminal domains homo- and heterodimerize, suggesting that plant NLRs oligomerize upon activation, similar to the vertebrate NLRs; however, consistent with their large number in plants, the complexes are highly heterometric. Also, in contrast to metazoan NLRs, the N-terminus, rather than their centrally located nucleotide-binding (NB) domain, can mediate initial partner selection. The highly redundant network of NLR interactions in plants is proposed to provide resilience to perturbation by pathogens.
Effective hemodynamic monitoring Pinsky, Michael R.; Cecconi, Maurizio; Chew, Michelle S. ...
Critical care (London, England),
09/2022, Letnik:
26, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Hemodynamic monitoring is the centerpiece of patient monitoring in acute care settings. Its effectiveness in terms of improved patient outcomes is difficult to quantify. This review focused on ...effectiveness of monitoring-linked resuscitation strategies from: (1) process-specific monitoring that allows for non-specific prevention of new onset cardiovascular insufficiency (CVI) in perioperative care. Such goal-directed therapy is associated with decreased perioperative complications and length of stay in high-risk surgery patients. (2) Patient-specific personalized resuscitation approaches for CVI. These approaches including dynamic measures to define volume responsiveness and vasomotor tone, limiting less fluid administration and vasopressor duration, reduced length of care. (3) Hemodynamic monitoring to predict future CVI using machine learning approaches. These approaches presently focus on predicting hypotension. Future clinical trials assessing hemodynamic monitoring need to focus on process-specific monitoring based on modifying therapeutic interventions known to improve patient-centered outcomes.
Mitochondrial complex I is the largest multi-protein enzyme complex of the oxidative phosphorylation system. Seven subunits of this complex are encoded by the mitochondrial and the remainder by the ...nuclear genome. We review the natural disease course and signs and symptoms of 130 patients (four new cases and 126 from literature) with mutations in nuclear genes encoding structural complex I proteins or those involved in its assembly. Complex I deficiency caused by a nuclear gene defect is usually a non-dysmorphic syndrome, characterized by severe multi-system organ involvement and a poor prognosis. Age at presentation may vary, but is generally within the first year of life. The most prevalent symptoms include hypotonia, nystagmus, respiratory abnormalities, pyramidal signs, dystonia, psychomotor retardation or regression, failure to thrive, and feeding problems. Characteristic symptoms include brainstem involvement, optic atrophy and Leigh syndrome on MRI, either or not in combination with internal organ involvement and lactic acidemia. Virtually all children ultimately develop Leigh syndrome or leukoencephalopathy. Twenty-five percent of the patients died before the age of six months, more than half before the age of two and 75 % before the age of ten years. Some patients showed recovery of certain skills or are still alive in their thirties . No clinical, biochemical, or genetic parameters indicating longer survival were found. No clear genotype-phenotype correlations were observed, however defects in some genes seem to be associated with a better or poorer prognosis, cardiomyopathy, Leigh syndrome or brainstem lesions.
Deterministic creation of multiple ferroelectric states with intermediate values of polarization remains challenging due to the inherent bi-stability of ferroelectric switching. Here we show the ...ability to select any desired intermediate polarization value via control of the switching pathway in (111)-oriented PbZr
Ti
O
films. Such switching phenomena are driven by kinetic control of the volume fraction of two geometrically different domain structures which are generated by two distinct switching pathways: one direct, bipolar-like switching and another multi-step switching process with the formation of a thermodynamically-stable intermediate twinning structure. Such control of switching pathways is enabled by the competition between elastic and electrostatic energies which favors different types of ferroelastic switching that can occur. Overall, our work demonstrates an alternative approach that transcends the inherent bi-stability of ferroelectrics to create non-volatile, deterministic, and repeatedly obtainable multi-state polarization without compromising other important properties, and holds promise for non-volatile multi-state functional applications.
The growth and characterization of functional oxide thin films that are ferroelectric, magnetic, or both at the same time are reviewed. The evolution of synthesis techniques and how advances in
in ...situ characterization have enabled significant acceleration in improvements to these materials are described. Methods for enhancing the properties of functional materials or creating entirely new functionality at interfaces are covered, including strain engineering and layering control at the atomic-layer level. Emerging applications of these functional oxides such as achieving electrical control of ferromagnetism and the future of these complex functional oxides is discussed.
Tay-Sachs disease (TSD) is an inherited neurological disorder caused by deficiency of hexosaminidase A (HexA). Here, we describe an adeno-associated virus (AAV) gene therapy expanded-access trial in ...two patients with infantile TSD (IND 18225) with safety as the primary endpoint and no secondary endpoints. Patient TSD-001 was treated at 30 months with an equimolar mix of AAVrh8-HEXA and AAVrh8-HEXB administered intrathecally (i.t.), with 75% of the total dose (1 × 10
vector genomes (vg)) in the cisterna magna and 25% at the thoracolumbar junction. Patient TSD-002 was treated at 7 months by combined bilateral thalamic (1.5 × 10
vg per thalamus) and i.t. infusion (3.9 × 10
vg). Both patients were immunosuppressed. Injection procedures were well tolerated, with no vector-related adverse events (AEs) to date. Cerebrospinal fluid (CSF) HexA activity increased from baseline and remained stable in both patients. TSD-002 showed disease stabilization by 3 months after injection with ongoing myelination, a temporary deviation from the natural history of infantile TSD, but disease progression was evident at 6 months after treatment. TSD-001 remains seizure-free at 5 years of age on the same anticonvulsant therapy as before therapy. TSD-002 developed anticonvulsant-responsive seizures at 2 years of age. This study provides early safety and proof-of-concept data in humans for treatment of patients with TSD by AAV gene therapy.
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