Calcium additional to that bound to the transport sites is required for full activation of the sarcoplasmic reticulum Ca-ATPase from skeletal muscle

The sarcoplasmic reticulum Ca-ATPase is fully activated when approximately 1 microM [Ca2+] saturates the two transport sites; higher [Ca] inhibits the ATPase by competition of Ca-ATP with Mg-ATP as substrates. Here we describe a novel effect of EGTA and other chelators, raising the possibility of an additional activating effect of Ca in the sub- or low microM range. Sarcoplasmic reticulum membranes were isolated from rabbit skeletal muscles. The ATPase activity was measured after incubation at 37 degreesC in 3 mM ATP, 3 mM MgCl2, 50 mM MOPS-Tris (pH 7.2), 100 mM KCl, and variable CaCl2, EGTA and calcimycin. In the absence of added EGTA and Ca the ATPase activity is high due to contaminant Ca. The determination of the ATPase activity in the presence of increasing amounts of EGTA, without added Ca, yields a decreasing sigmoidal function. Ki ranged between 20 and 100 microM, depending on the enzyme concentration. Pi production is linear with time for several [EGTA] yielding suboptimal ATPase activities, which are inhibited by thapsigargin. These suboptimal Ca-ATPase activities are inhibited by preincubation of the enzyme in EGTA, at pH 7.2. This effect increases upon increasing EGTA concentration and preincubation time. The inhibitory effect of the previous exposure of the enzyme to EGTA is partially but significantly reverted by increasing [Ca2+] during incubations. Calcimycin and EDTA have similar effects as EGTA when added in preincubations. The effect of calcimycin is fully reverted by optimal [Ca2+] in incubations. The effects of EGTA, EDTA and calcimycin in preincubation are not additive. The results suggest that an additional calcium, lost during preincubations from a site with affinity near 1 microM, is necessary for full activation of the ATPase.     

Factors controlling cracking of concrete affected by reinforcement corrosion

The present paper tries to contribute to quantifying the relationship between the amount of corrosion and cover cracking. The variables studied were: cover/diameter (c/ø), proportions of cement, w/c, cast position of the bar, transverse reinforcement and corrosion rate. The corrosion is accelerated by applying constant currents causing the rebar to act as an anode. The results indicate that the cracking process develops in two steps: generation and propagation. Radius losses of about 15–50 μm are necessary to generate the first visible crack (<0.1 mm width). The propagation follows a behaviour of the type: w (crack width in mm)=a+bx (radius loss in μm).     

Mumps orchitis; review of 8 cases]

The occurrence of secondary hypogonadism is a common finding in males who seek help with erectile dysfunction, although the relationship to diminished testosterone is unclear. Two possibilities exist regarding both the genesis and maintenance of the hypogonadotropic hypogonadal state. First, a defect in hypothalamic function, resulting in downregulation as well as in alterations of anterior pituitary function; second, estradiol inhibition of gonadotropin release, both of which result in decreased testosterone production. As testosterone levels decrease and estradiol levels increase, the ratio of free testosterone to estradiol reaches a critical point and the estrogenic gonadotropin suppressive effects predominate. This ratio may signal the biological point of no return and could become one of the criteria for defining the separation of the transitional hypogonadal state from the final 'end stage' hypogonadotropic hypogonadal state. As the aging process continues, there is a relative accumulation of fatty tissue, and aromatization accelerates the conversion of testosterone to estradiol. This additional secondary estradiol inhibition results in the maintenance of the testosterone deficient state, and the aging process continues uncontested.     

STATISTICAL ANALYSIS ON COKE YIELDS IN VACUUM RESIDS AS A FUNCTION OF COMPOUND CLASSES AND ELEMENTAL ANALYSIS

This paper describes the statistical analysis of data on coke formation (measured by microcarbon residue) in five resids, as a function of compound classes, in order to identify variables wiih a significant effect on the former. In this sense, the SAS VARCLUS and Principal Component Analysis were used. The analysis carried out leads to a lineal combination of the H/C ratio, vanadium and nitrogen content as a model to explain coke yield, under non-catalytic conditions, as determined by MCR. Of all these factors, the H/C ratio has the most important contribution.     

A panoramic view and swot analysis of artificial intelligence for achieving the sustainable development goals by 2030: progress and prospects

Applied Intelligence - The17 Sustainable Development Goals (SDGs) established by the United Nations Agenda 2030 constitute a global blueprint agenda and instrument for peace and prosperity...     

Passive internet-based crane teleoperation with haptic aids

Crane operation is a challenging task, due to the combined problem of obstacle avoidance and load swing suppression in underactuated conditions. This paper presents a human-machine interface that increases the operator’s perception of a gantry crane’s workspace. With this aim, a virtual environment resembling the workspace is connected with a haptic device. This allows the user to receive not only visual but also tactile feedback, thus increasing maneuvering safety. Additionally, this capability is integrated in a teleoperation setup, adopting a passivity-based control approach that guarantees overall stability. This includes also the design of controllers by means of the IDA-PBC method. Experimental results carried out with a laboratory crane show its feasibility for internet-based teleoperation and demonstrate the improvements on the system performance.     

Strong accumulators from collision-resistant hashing

Accumulator schemes were introduced in order to represent a large set of values as one short value called the accumulator. These schemes allow one to generate membership proofs, that is, short witnesses that a certain value belongs to the set. In universal accumulator schemes, efficient proofs of non-membership can also be created. Li et?al. (Proceedings of applied cryptography and network security—ACNS ’07, LNCS, vol 4521, 2007), building on the work of Camenisch and Lysyanskaya (Advances in cryptology—proceedings of Crypto ’02, LNCS, vol 2442. Springer, Berlin, pp 61–76, 2002), proposed an efficient accumulator scheme, which relies on a trusted accumulator manager. Specifically, a manager that correctly performs accumulator updates. In this work, we introduce the notion of strong universal accumulator schemes, which are similar in functionality to universal accumulator schemes, but do not assume the accumulator manager is trusted. We also formalize the security requirements for such schemes. We then give a simple construction of a strong universal accumulator scheme, which is provably secure under the assumption that collision-resistant hash functions exist. The weaker requirement on the accumulator manager comes at a price; our scheme is less efficient than known universal accumulator schemes—the size of (non)membership witnesses is logarithmic in the size of the accumulated set in contrast to constant in the scheme of Camenisch and Lysyanskaya. Finally, we show how to use strong universal accumulators to solve a problem of practical relevance, the so-called e-Invoice Factoring Problem.     

Methamphetamine Blocks Adenosine A2A Receptor Activation via Sigma 1 and Cannabinoid CB1 Receptors

Methamphetamine is, worldwide, one of the most consumed drugs of abuse. One important side effect is neurodegeneration leading to a decrease in life expectancy. The aim of this paper was to check whether the drug affects one of the receptors involved in neurodegeneration/neuroprotection events, namely the adenosine A_2A receptor (A_2AR). First, we noticed that methamphetamine does not affect A_2A functionality if the receptor is expressed in a heterologous system. However, A_2AR becomes sensitive to the drug upon complexes formation with the cannabinoid CB₁ receptor (CB₁R) and the sigma 1 receptor (σ₁R). Signaling via both adenosine A_2AR and cannabinoid CB₁R was affected by methamphetamine in cells co-expressing the two receptors. In striatal primary cultures, the A_2AR–CB₁R heteromer complex was detected and methamphetamine not only altered its expression but completely blocked the A_2AR- and the CB₁R-mediated activation of the mitogen activated protein kinase (MAPK) pathway. In conclusion, methamphetamine, with the participation of σ₁R, alters the expression and function of two interacting receptors, A_2AR, which is a therapeutic target for neuroprotection, and CB₁R, which is the most abundant G protein-coupled receptor (GPCR) in the brain.     

Antisense Oligonucleotide-Based Rescue of Aberrant Splicing Defects Caused by 15 Pathogenic Variants in ABCA4

The discovery of novel intronic variants in the ABCA4 locus has contributed significantly to solving the missing heritability in Stargardt disease (STGD1). The increasing number of variants affecting pre-mRNA splicing makes ABCA4 a suitable candidate for antisense oligonucleotide (AON)-based splicing modulation therapies. In this study, AON-based splicing modulation was assessed for 15 recently described intronic variants (three near-exon and 12 deep-intronic variants). In total, 26 AONs were designed and tested in vitro using a midigene-based splice system. Overall, partial or complete splicing correction was observed for two variants causing exon elongation and all variants causing pseudoexon inclusion. Together, our results confirm the high potential of AONs for the development of future RNA therapies to correct splicing defects causing STGD1.     

The Role of LGR4 (GPR48) in Normal and Cancer Processes

Leucine-rich repeats containing G protein-coupled receptor 4 (LGR4) is a receptor that belongs to the superfamily of G protein-coupled receptors that can be activated by R-spondins (RSPOs), Norrin, circLGR4, and the ligand of the receptor activator of nuclear factor kappa-B (RANKL) ligands to regulate signaling pathways in normal and pathological processes. LGR4 is widely expressed in different tissues where it has multiple functions such as tissue development and maintenance. LGR4 mainly acts through the Wnt/β-catenin pathway to regulate proliferation, survival, and differentiation. In cancer, LGR4 participates in tumor progression, invasion, and metastasis. Furthermore, recent evidence reveals that LGR4 is essential for the regulation of the cancer stem cell population by controlling self-renewal and regulating stem cell properties. This review summarizes the function of LGR4 and its ligands in normal and malignant processes.