scholarly journals IT Evaluation of Foundation Healthcare Group NHS Vanguard programme: IT simultaneously an enabler and a rate limiting factor

Author(s):  
Archana Tapuria ◽  
Maria Kordowicz ◽  
Mark Ashworth ◽  
Ewan Ferlie ◽  
Vasa Curcin ◽  
...  
1989 ◽  
Vol 157 ◽  
Author(s):  
P.A. Stolk ◽  
A. Polman ◽  
W.C. Sinke

ABSTRACTPulsed laser irradiation is used to induce epitaxial explosive crystallization of amorphous silicon layers buried in a (100) oriented crystalline matrix. This process is mediated by a self-propagating liquid layer. Time-resolved determination of the crystallization speed combined with numerical calculation of the interface temperature shows that freezing in silicon saturates at 16 m/s for large undercooling (> 130 K). A comparison between data and different models for melting and freezing indicates that the crystallization behavior at large undercooling can be described correctly if the rate-limiting factor is assumed to be diffusion in liquid Si at the solid/liquid interface.


Diagnostics ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 151
Author(s):  
Elena Di Pierro ◽  
Francesca Granata ◽  
Michele De Canio ◽  
Mariateresa Rossi ◽  
Andrea Ricci ◽  
...  

Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are inherited disorders resulting from defects in two different enzymes of the heme biosynthetic pathway, i.e., ferrochelatase (FECH) and delta-aminolevulinic acid synthase-2 (ALAS2), respectively. The ubiquitous FECH catalyzes the insertion of iron into the protoporphyrin ring to generate the final product, heme. After hemoglobinization, FECH can utilize other metals like zinc to bind the remainder of the protoporphyrin molecules, leading to the formation of zinc protoporphyrin. Therefore, FECH deficiency in EPP limits the formation of both heme and zinc protoporphyrin molecules. The erythroid-specific ALAS2 catalyses the synthesis of delta-aminolevulinic acid (ALA), from the union of glycine and succinyl-coenzyme A, in the first step of the pathway in the erythron. In XLP, ALAS2 activity increases, resulting in the amplified formation of ALA, and iron becomes the rate-limiting factor for heme synthesis in the erythroid tissue. Both EPP and XLP lead to the systemic accumulation of protoporphyrin IX (PPIX) in blood, erythrocytes, and tissues causing the major symptom of cutaneous photosensitivity and several other less recognized signs that need to be considered. Although significant advances have been made in our understanding of EPP and XLP in recent years, a complete understanding of the factors governing the variability in clinical expression and the severity (progression) of the disease remains elusive. The present review provides an overview of both well-established facts and the latest findings regarding these rare diseases.


Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2667
Author(s):  
Andrea Angeletti ◽  
Stefano Volpi ◽  
Maurizio Bruschi ◽  
Francesca Lugani ◽  
Augusto Vaglio ◽  
...  

Neutrophil extracellular traps (NETs) are macromolecular structures programmed to trap circulating bacteria and viruses. The accumulation of NETs in the circulation correlates with the formation of anti-double-stranded (ds) DNA antibodies and is considered a causative factor for systemic lupus erythematosus (SLE). The digestion of DNA by DNase1 and DNases1L3 is the rate- limiting factor for NET accumulation. Mutations occurring in one of these two DNASE genes determine anti-DNA formation and are associated with severe Lupus-like syndromes and lupus nephritis (LN). A second mechanism that may lead to DNase functional impairment is the presence of circulating DNase inhibitors in patients with low DNase activity, or the generation of anti-DNase antibodies. This phenomenon has been described in a relevant number of patients with SLE and may represent an important mechanism determining autoimmunity flares. On the basis of the reviewed studies, it is tempting to suppose that the blockade or selective depletion of anti-DNase autoantibodies could represent a potential novel therapeutic approach to prevent or halt SLE and LN. In general, strategies aimed at reducing NET formation might have a similar impact on the progression of SLE and LN.


2021 ◽  
Author(s):  
Carola Sparn ◽  
Eleni Dimou ◽  
Annalena Meyer ◽  
Roberto Saleppico ◽  
Sabine Wegehingel ◽  
...  

Fibroblast Growth Factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. Cell surface heparan sulfate proteoglycans are known to play an essential role in this process. Unexpectedly, we found that among the diverse sub-classes consisting of syndecans, perlecans, glypicans and others, Glypican-1 (GPC1) is both the principle and rate-limiting factor that drives unconventional secretion of FGF2. By contrast, we demonstrate GPC1 to be dispensable for FGF2 signaling into cells. We provide first insights into the structural basis for GPC1-dependent FGF2 secretion, identifying disaccharides with N-linked sulfate groups to be enriched in the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity. Our findings have broad implications for the role of GPC1 as a key molecule in tumor progression.


2020 ◽  
pp. 119-178
Author(s):  
Gerard J. Mulder ◽  
Klaas R. Krijgsheld

1975 ◽  
Vol 28 (4) ◽  
pp. 339 ◽  
Author(s):  
Alan G Clark ◽  
KarI M Rogers

The kinetics of the biliary excretion of both bromocresol green and amaranth are better described in terms of rate equations that are functions of the cumulative volume of bile excreted rather than of time. The rate of disappearance of bromocresol green from the liver also appears to depend on the volume of bile excreted rather than on time. It is proposed that bromocresol green, and probably also amaranth, rapidly equilibrates between the hepatic and biliary compartments as a result of reabsorption from the biliary tree and that the rate-limiting factor in the biliary excretion of these dyes is the removal of dye from the biliary tree by bulk flow.


Gene ◽  
2020 ◽  
Vol 727 ◽  
pp. 144231
Author(s):  
Zahra Jalali ◽  
Najmeh Parvaz

1994 ◽  
Vol 266 (1) ◽  
pp. C157-C164 ◽  
Author(s):  
P. Burgener-Kairuz ◽  
I. Corthesy-Theulaz ◽  
A. M. Merillat ◽  
P. Good ◽  
K. Geering ◽  
...  

In fully grown Xenopus oocytes, the synthesis of beta-subunits is limiting for the formation of functional Na(+)-K(+)-adenosinetriphosphatase alpha/beta-complexes (Geering, K. FEBS Lett. 285: 189-193, 1991). In the present study, we show that during oocyte growth (from stage I to stage VI) alpha 1-, but not beta 1- or beta 3-isoform, mRNAs accumulate. In addition, beta-mRNAs are apparently sequestered in an untranslated pool in fully grown oocytes (stage VI). From fertilization to morulation, the total pools of alpha 1-, beta 1-, or beta 3-mRNAs vary little. Whereas polyadenylated [poly(A)+] alpha 1- and beta 3-isoform mRNAs did not change significantly, poly(A)+ beta 1-mRNA abundance increased three- to fourfold at morulation, accompanied by a parallel increase in beta 1-protein synthesis. After midblastula transition (i.e., at early gastrula) and during neurulation, poly(A)+ alpha 1- and beta 3-mRNAs accumulated rapidly, whereas poly(A)+ beta 1-mRNA accumulation was delayed by approximately 2 h, beginning only at early neurula. Our results indicate that 1) the abundance of poly(A)+ beta 1-mRNA is rate limiting during embryonic development for the assembly of alpha 1/beta 1-heterodimers, shown to be involved in the vectorial transport of sodium in kidney cells, and 2) the polyadenylation of beta 1-mRNA is a rate-limiting factor during morulation for the synthesis and assembly of new sodium pumps at the time of blastocoel fluid formation. The 3'-untranslated region of beta 1-mRNA (but not of alpha 1-mRNA) expresses cytoplasmic polyadenylation elements (CPEs) with the consensus sequence AXX-AUUUU(A/U)(A/U)(A/U). A role of CPE in the differential polyadenylation of alpha 1- and beta 1-mRNA is proposed.


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