Increased expression of decorin in experimental hydronephrosis

Transforming growth factor (TGF)-beta1 is a potential mediator of tubulointerstitial (TI) fibrosis in the rat unilateral ureteral obstruction (UUO) model. Decorin is a protein composed of a core protein and a chondroitin sulfate side chain and is capable of inactivating TGF-beta. Since TGF-beta strongly induces the synthesis of decorin in experimental glomerulonephritis, it was our intent to investigate whether altered decorin expression is operant in the rat UUO model. Renal cortical decorin mRNA levels initially became elevated (2.5-fold) in obstructed kidney (OBK) versus contralateral unobstructed kidney (CUK) 24 hours post-UUO and remained greater in the OBK specimens at 48 (2.3-fold), 96 (2.2-fold), and 168 (1.9-fold) hours post-ureteral ligation. Whole-body X-irradiation 11 days prior to UUO significantly reduced decorin mRNA at 24 and 96 hours post-UUO. On immunolabeling, decorin was only evident in the adventitia of blood vessels in CUK specimens at any time point after UUO. In contrast, OBK specimens initially demonstrated periglomerular and peritubular interstitial localization of decorin at 96 hours post-ureteral ligation, which became even more intense and diffuse in the tubulointerstitium at 168 hours post-UUO. On Western analysis, there were highly significant increases in decorin protein expression in the OBK versus the CUK specimens at 96 and 168 hours post-UUO. Levels of active TGF-beta1 in the renal cortex of OBK were 1.9- and 3.6-fold higher than CUK at 48 and 96 hours post-UUO. In summary, we demonstrated that post-UUO, decorin mRNA and protein expression is up-regulated in the renal cortex of OBK, but not CUK, specimens in a temporal parallel with active TGF-beta1 levels and macrophage infiltration. We postulate that the development of TI fibrosis in this model may be related to only a physiologic induction of decorin by TGF-beta, and that pharmacologic levels may be required to retard or prevent scarring via TGF-beta inhibition.     

Ambulatory mental health treatment under universal coverage: policy insights from Israel

Untested assumptions concerning ambulatory treatment have shaped mental health policies for decades. Three opinions prevail: (1) all use is alike; (2) any use leads to high use; and (3) all high use is discretionary and therefore excessive. These assumptions were tested, using data from a nationwide survey of ambulatory utilizers in Israel, a country that has universal coverage. The findings, based on detailed clinical and treatment records, challenge all three assumptions. Moreover, they document a diversity of clinical needs while also verifying substantial variations in the type, frequency, and duration of treatment provided to meet those needs. In brief, Israeli data do not confirm continuing concerns by policy makers about uncontrollable use of services with expanded mental health coverage. Special policy limitations on mental health treatment should be reconsidered in light of empirical evidence from a system without the restrictions that exist in the United States.     

Hereditary lymphedema: evidence for linkage and genetic heterogeneity

Hereditary or primary lymphedema is a developmental disorder of the lymphatic system which leads to a disabling and disfiguring swelling of the extremities. Hereditary lymphedema generally shows an autosomal dominant pattern of inheritance with reduced penetrance, variable expression and variable age at onset. Three multigeneration families demonstrating the phenotype of hereditary lymphedema segregating as an autosomal dominant trait with incomplete penetrance were genotyped for 366 autosomal markers. Linkage analysis yielded a two-point LOD score of 6.1 at straight theta = 0. 0 for marker D5S1354 and a maximum multipoint LOD score of 8.8 at marker D5S1354 located at chromosome 5q34-q35. Linkage analysis in two additional families using markers from the linked region showed one family consistent for linkage to distal chromosome 5. In the second family, linkage to 5q was excluded for all markers in the region with LOD scores Z < -2.0. The vascular endothelial growth factor C receptor ( FLT4 ) was mapped to the linked region, and partial sequence analysis identified a G-->A transition at nucleotide position 3360 of the FLT4 cDNA, predicting a leucine for proline substitution at residue 1126 of the mature receptor in one nuclear family. This study localizes a gene for primary lymphedema to distal chromosome 5q, identifies a plausible candidate gene in the linked region, and provides evidence for a second, unlinked locus for primary lymphedema.     

Generation of complex microwave and millimeter-wave pulses using dispersion and Kerr effect in optical fiber systems

We study a new method to synthesize high-frequency complex microwave and millimeter-wave pulses using dispersion, Kerr effect, and group velocity delay in optical fiber systems. The profile of the generated pulses can be controlled by changing the parameters of the optical system. Nonlinear propagation effect in fibers can be used to generate electrical pulses with an extremely broad spread spectrum. Soliton trapping can be used to generate electrical pulses with a controllable frequency. Implicit results are given when dispersion or nonlinear effect can be neglected. Generation of electrical pulses with a controllable microwave frequency is demonstrated experimentally using a Mach-Zehnder interferometer and a chirped fiber Bragg grating.     

意大利阿克雅建筑师事务所

当意大利的建筑学杂志开始报道一栋位于意大利科尔诺(Curno)的建筑时,人们立刻意识到一个新事物出现了。这栋建筑是由阿克雅事务所设计的名为“停止线”(Stop Line)的娱乐中心。这栋坐落在空旷地区的舞厅,外观非常独特,显示出解读和构思建筑的新思路——以面对国际上的争论所采     

Enhancing the weldability of CP titanium friction stir welds with elemental foils

ABSTRACT

Friction stir welding (FSW) has proven to be a viable technique for joining a wide variety of alloys. However, thick section welding of alpha and near-alpha Ti alloys has proven particularly challenging. Previous research at the Naval Research Laboratory using Ni markers in CP Ti friction stir welds indicated that elemental additions of Ni to the joint line can provide substantial benefits for improved weldability of these alloys. The current study surveys the effects of Ni and other elemental additions to CP Ti friction stir welds to determine their influence on the resultant weld microstructure, weld surface finish, and welding machine forces. These results reveal that Ni provides the most benefits for the concentrations examined, but other elements may also provide benefits at lower concentrations. The addition of these elements may improve the weldability and weld quality for FSW of CP Ti, enabling thick section welding of this and similar alloys.     

Preimplantation genetic testing for Marfan syndrome

Marfan syndrome (MFS) is an autosomal dominant disease that affects the skeletal, ocular and cardiovascular systems. Defects in the gene that codes for fibrillin (FBN-1) are responsible for MFS. Here we report the world's first use of preimplantation genetic testing (PGT) to achieve a clinical pregnancy and live birth of a baby free of a Marfan mutation. One or two blastomeres from each embryo were tested for a CA repeat within the FBN-1 gene. The prospective mother is homozygous for the CA repeat (2/2) and has two normal copies of the FBN-1 gene, while the prospective father is heterozygous for the CA repeat (1/2), and is affected with the Marfan syndrome. In the father's family, allele 2 segregates with the mutated FBN-1 gene. For PGT, any embryo diagnosed as heterozygous for the CA repeat (1/2) would be presumed to have inherited normal FBN-1 genes from the father and the mother and be unaffected. One in-vitro fertilization (IVF) cycle yielded 12 embryos for preimplantation testing; six of the embryos were heterozygous for the CA repeat (1/2) and presumed to be free of the Marfan mutation. Five of the six embryos were subsequently transferred into the uterus. The fetus was tested by chorionic villus sampling and found to be free of the Marfan mutation by the same linkage analysis, had a normal fetal echocardiogram, and was normal at birth.