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1.
Pigeon hemoglobin has eight reactive sulphydryl groups per (tetramer) molecule, as determined by Boyer titration with p-chloromercuribenzoate. However, only four of these are titratable with 5,5'-dithiobis(2-nitrobenzoate) under the same experimental conditions. The time course of the reaction of pigeon hemoglobin with 5,5'-dithiobis(2-nitrobenzoate) is biphasic. In the pH range 6-9, the fast phase is between one and two orders of magnitude faster than the slow phase. For the fast phase, kapp, the apparent second-order rate constant, increases monotonously with pH. Quantitative analysis reveals that the reaction of the sulphydryl group responsible for this phase is coupled to the ionization of two groups with pKa values of 6.15 +/- 0.1 and 8.5 +/- 0.1. These pKa values are assigned to HisHC3(146) beta and to the CysF9(93) beta sulphydryl group, respectively. For the slow phase the kapp vs. pH profiles are bowl-shaped. Analysis reveals that the reaction of the sulphydryl group to which this phase may be attributed is coupled to the ionization of two groups with mean pKa values of 6.53 +/- 0.1 and 8.25 +/- 0.1. Examination of the structure of hemoglobin allows us to assign these values to HisG19(117) beta and CysB5(23) beta, respectively. The CysB5(23) beta sulphydryl is in the region of the molecule where amino acid substitutions have been found to give rise to significant changes in the oxygen affinity of hemoglobin [Huang et al. (1990), Biochemistry 29, 7020-7023].  相似文献   
2.
BACKGROUND: X-linked severe combined immunodeficiency (SCIDXI) is an inherited immune defect which leads to death in infancy from severe infections. The defect is caused by mutations of the IL-2RG gene that encodes for the common gamma chain shared by several cytokine receptors. The disease is characterised by lack of T and NK cells with normal numbers of B cells. SCIDXI can be cured by bone marrow transplantation (BMT) or prevented by abortion after prenatal diagnosis. METHODS: A male fetus was diagnosed as having SCIDXI by molecular, immunophenotypic, and functional analyses. The fetus was injected intraperitoneally under ultrasound guidance with CD34 haematopoietic progenitor cells purified from paternal bone marrow and T-cell depleted by E rosetting. Chimerism analysis was by HLA-DQ alpha typing and gamma-chain staining on cord blood. FINDINGS: A healthy 3.6 kg boy was delivered by caesarean section at 38 weeks of gestation with no clinical or laboratory signs of graft-versus-host disease. Engraftment of donor-derived CD2 cells was found at birth. At 3.5 months of age the infant is well and his T-cell counts and function are normal. INTERPRETATION: In-utero transplantation of haematopoietic progenitor cells allowed immune reconstitution of a fetus with SCIDXI and may be an alternative to elective abortion. Our report should encourage applications of this method to other inherited disorders curable by BMT.  相似文献   
3.
Mevalonic acid (mevalonate or MVA), is an obligate precursor in the biosynthetic pathway of cholesterol. It is partially metabolized by the kidneys and its plasma concentrations are an index of endogenous cholesterol synthesis. The aim of the present study was to evaluate plasma MVA concentrations in uremic patients with different degrees of chronic renal failure (CRF; group A), and the effects of a single hemodialysis treatment on plasma MVA in a group of patients with end-stage renal disease (ESRD; group B). CRF patients exhibited a higher mean basal mevalonate concentration (13.3 +/- 6.5 ng/ml) than control subjects (4.68 +/- 1.32 ng/ml; P < 0.001). A statistically significant direct correlation was evident in CRF patients between mevalonate and creatinine plasma levels (r = 0.86; P < 0.001). A single hemodialysis treatment was associated with a significant reduction of plasma mevalonate concentrations four hours after the hemodialysis session (-57%; P < 0.001) and an increase up to the basal values 24 hours after the end of the treatment. In conclusion, our results demonstrated: (i) higher plasma MVA concentrations in patients with decreased renal function; (ii) a direct relationship between plasma MVA levels and the degree of kidney failure as expressed by creatinine plasma concentrations; and (iii) a clear cut reduction of elevated plasma MVA levels after a single hemodialysis treatment.  相似文献   
4.
We consider the carrier frequency offset estimation in a digital burst-mode satellite transmission affected by phase noise. The corresponding Cramer-Rao lower bound is analyzed for linear modulations under a Wiener phase noise model and in the hypothesis of knowledge of the transmitted data. Even if we resort to a Monte Carlo average, from a computational point of view the evaluation of the Cramer-Rao bound is very hard. We introduce a simple but very accurate approximation that allows to carry out this task in a very easy way. As it will be shown, the presence of the phase noise produces a remarkable performance degradation of. the frequency estimation accuracy. In addition, we provide asymptotic expressions of the Cramer-Rao bound, from which the effect of the phase noise and the dependence on the system parameters of the frequency offset estimation accuracy clearly result. Finally, as a by-product of our derivations and approximations, we derive a couple of estimators specifically tailored for the phase noise channel that will be compared with the classical Rife and Boorstyn algorithm, gaining in this way some important hints on the estimators to be used in this scenario  相似文献   
5.
The architectural complexes composed by the two main pyramids of Giza together with their temples are investigated from an interdisciplinary point of view, taking into account their astronomical alignments as well as their relationships with the visible landscape. Combining already known facts together with new clues, the work strongly supports the idea that the two complexes were conceived as parts of a common project.  相似文献   
6.
Silver-based products have been proven to be effective in retarding and preventing bacterial growth since ancient times. In the field of restorative dentistry, the use of silver ions/nanoparticles has been explored to counteract bacterial infections, as silver can destroy bacterial cell walls by reacting with membrane proteins. However, it is also cytotoxic towards eukaryotic cells, which are capable of internalizing nanoparticles. In this work, we investigated the biological effects of Chitlac-nAg, a colloidal system based on a modified chitosan (Chitlac), administered for 24–48?h to a co-culture of primary human gingival fibroblasts and Streptococcus mitis in the presence of saliva, developed to mimic the microenvironment of the oral cavity. We sought to determine its efficiency to combat oral hygiene-related diseases without affecting eukaryotic cells. Cytotoxicity, reactive oxygen species production, apoptosis induction, nanoparticles uptake, and lysosome and autophagosome metabolism were evaluated. In vitro results show that Chitlac-nAg does not exert cytotoxic effects on human gingival fibroblasts, which seem to survive through a homoeostasis mechanism involving autophagy. That suggests that the novel biomaterial Chitlac-nAg could be a promising tool in the field of dentistry.  相似文献   
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Innovation in Industrial Districts: Evidence from Italy   总被引:1,自引:0,他引:1  
The aim of this paper is to show that Italian manufacturing firms belonging to Marshallian industrial districts carry out a higher innovative effort than is usually acknowledged. The empirical analysis makes use of a panel of 1,218 district and non-district firms belonging to traditional sectors. Data refers to the years 1992 and 1995. We have estimated an augmented Cobb-Douglas production function. The estimates make it possible to empirically identify three different determinants of firms' productivity: (i) the intentional innovative activity; (ii) the “district effect”; and (iii) the joint district and innovation effect. The results show that firms' membership in industrial districts and product innovations are key factors in explaining the productivity of firms working in traditional Italian sectors.  相似文献   
10.
In recent years nanotechnology has opened exciting opportunities in the struggle against cancer. In 2007 Dawson and coworkers demonstrated that nanomaterials exposed to biological fluids are coated with plasma proteins that form the so-called “protein corona”. A few years later our joint research team made of physicists, chemists, biotechnologists, surgeons, oncologists, and bioinformaticians introduced the concept of “personalized protein corona” and demonstrated that it is unique for each human condition. This concept paved the way for the development of nano-enabled blood (NEB) tests for the diagnosis of pancreatic ductal adenocarcinoma (PDAC). These studies gave an impetus to serious work in the field that came to maturity in the late 2010s. In this special issue, we provide the reader with a comprehensive overview of the most significant discoveries of our research team in the field of PDAC detection. We focus on the main achievements with an emphasis on the fundamental aspects of this arena and how they shaped the integration of different scientific backgrounds towards the development of advanced diagnostic technologies. We conclude the review by outlining future perspectives and opportunities to transform the NEB tests into a reliable clinical diagnostic technology for early diagnosis, follow-up, and management of PDAC patients.  相似文献   
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