Congenic rats reveal three independent Copenhagen alleles within the Mcs1 quantitative trait locus that confer resistance to mammary cancer

It has previously been shown that the Copenhagen (COP) rat contains several genetic loci that contribute to its mammary tumor-resistant phenotype after 7,12-dimethylbenz(a)anthracene (DMBA) administration. One of these loci, mammary carcinoma susceptibility 1 (Mcs1), is located on the centromeric end of chromosome 2 and appears to act in a semidominant fashion. To confirm the existence and independent action of this locus and also aid in the identification of the physical location of the Mcs1 gene, congenic lines were generated by transferring the Mcs1 COP allele onto a Wistar Furth (WF) genetic background. Male carriers were genotyped using microsatellite markers spanning 20-30 cM of the Mcs1 locus. One of the congenic lines minimally retained the COP allele at D2Mit29 on the centromeric end of chromosome 2 and extended distally to D2Rat201. Heterozygous Mcs1 carrier rats were interbred, and the female offspring were treated with DMBA. The female rats from the Mcs1 congenic line that carried one or two COP alleles of the Mcs1 region had a significantly reduced (65 and 85%, respectively) tumor development (P < 0.001) compared with rats carrying zero COP alleles at this locus. A WF.COP-D2Mit29/D2Rat201 homozygous congenic strain derived at the N10 generation was treated with DMBA, and the COP homozygous rats developed 1.5 +/- 0.3 carcinomas/rat versus 6.3 +/- 0.5 in WF control rats (P < 0.0001). Fine mapping of this congenic interval using several recombinant lines identified three genetic loci within the Mcs1 congenic region that independently supported a tumor resistance phenotype. These genetic loci have been termed Mcs1a, Mcs1b, and Mcs1c. In rats for which each locus was homozygous for the COP allele, tumor development was reduced by approximately 60% compared with littermate controls. The identification of these independent loci within the Mcs1 COP allele provide a model of the genetic complexity of cancer.     

89-GHz fT room-temperature silicon MOSFETs

The authors report the implementation of deep-submicrometer Si MOSFETs that at room temperature have a unity-current-gain cutoff frequency (f_T) of 89 GHz, for a drain-to-source bias of 1.5 V, a gate-to-source bias of 1 V, a gate oxide thickness of 40 Å, and a channel length of 0.15 μm. The fabrication procedure is mostly conventional, except for the e-beam defined gates. The speed performance is achieved through an intrinsic transit time of only 1.8 ps across the active device region     

Role of cholesterol in regulating apolipoprotein B secretion by the liver

The review examines the evidence that the supply of cholesterol available for incorporation into nascent lipoprotein particles exerts a regulatory influence on apolipoprotein (apo) B secretion by the liver. Support for this hypothesis comes both from in vitro experiments and from recent observations in normal subjects and patients with dyslipidemia associated with familial hypercholesterolemia, obesity, noninsulin dependent diabetes mellitus, growth hormone deficiency and cholesteryl ester storage disease. The findings do not negate a role for triglyceride synthesis in determining apoB secretion in very low density lipoprotein, but the inhibitory effects on the latter process of pharmacological blockade of cholesterol synthesis or esterification suggest that it is conditional upon an adequate supply of cholesteryl ester.     

Successful engraftment of haploidentical stem cell transplant for familial haemophagocytic lymphohistiocytosis using both bone marrow and peripheral blood stem cells

Familial haemophagocytic lymphohistiocytosis (HLH) is a disease with a very poor prognosis unless patients receive a bone marrow transplant. It is often difficult to find an HLA-matched donor and haploidentical familial donors may be considered. The main complication of this type of transplant is graft rejection. We describe a patient with familial HLH who received a haploidentical transplant using both mobilized peripheral blood and bone marrow stem cells in an attempt to overcome graft rejection by increasing the stem cell dose. The peripheral blood stem cell inoculum was CD34 enriched using a Cellpro column and T-cell depleted by Campath-1M, the patient received conditioning for a matched sibling donor transplant with the addition of Campath 1G. There was rapid and full engraftment and the patient remains disease free at 5 months. This technique may be applicable for other fatal inborn errors in the absence of an HLA-matched donor.     

Dimensional scaling for impact cratering and perforation

The issue of generic scaling laws able to adequately predict (within better than 20%) cratering in semi-infinite targets and perforations through finite thickness targets was revisited. The approach used was to apply physical logic for hydrodynamics in a consistent manner able to account for chunky-body impacts such that the only variables needed are those directly related to known material properties for both the impactor and target. The analyses were compared and verified versus CTH hydrodynamic code calculations and existing experimental data. Comparisons with previous scaling laws were also performed to identify which (if any) were good for generic purposes. This paper is a short synopsis of the full report [1] available through the NASA Langley Research Center, LDEF Science Office.     

Geographic distribution and clinical description of leishmaniasis cases in Peru

Asymmetric acetylcholinesterase (AChE) is anchored to the basal lamina (BL) of cholinergic synapses via its collagenic tail, yet the complement of matrix receptors involved in its attachment remains unknown. The development of a novel overlay technique has allowed us to identify two Torpedo BL components that bind asymmetric AChE: a polypeptide of approximately 140 kDa and a doublet of 195-215 kDa. These were found to stain metachromatically with Coomassie blue R-250, were solubilized by acetic acid, and were sensitive to collagenase treatment. Upon sequence analysis, the 140 kDa polypeptide yielded a characteristic collagenous motif. Another AChE-binding BL constituent, identified by overlay, corresponded to a heparan sulfate proteoglycan. Lastly, we established that this proteoglycan, but not the collagenous proteins, interacted with at least one heparin binding domain of the collagenic tail of AChE. Our results indicate that at least two BL receptors are likely to exist for asymmetric AChE in Torpedo electric organ.     

Experimental evidence for mode shape influence on acceleration-induced frequency shifts in quartz resonators

Experimental results are presented to support the hypothesis that the shape and location of the active region of vibration in a thickness shear mode quartz resonator are the dominant factors in determining the acceleration sensitivity of the resonator. The shape and location of the mode in a real world resonator vary sufficiently from unit to unit (due to material and processing variations) that all other considerations are overwhelmed. It is shown experimentally that the mode shape and/or location can be trimmed with energy trapping by judicious addition or subtraction of mass to produce resonators with improved acceleration sensitivity.     

Formation of cadmium-containing W-type hexagonal ferrite

The main steps of the phase formation processes which take place in samples of W-type hexaferrites containing cadmium, prepared by chemical coprecipitation, have been analysed. The processes were followed by Mössbauer spectroscopy, powder X-ray diffraction, thermomagnetic analysis and magnetic measurements. For samples heated in the temperature range 1000–1100°C, the phase formation processes are the same as those verified for the other zinc, nickel, cobalt W-type compounds: forT _h=1000°C the only phases present are SrFe₁₂O₁₉ (M-type ferrite) and CdFe₂O₄ (spinel ferrite); in contrast, forT _h>1100°C, the solid state reaction between the M-type and the spinel phases does not take place and the spinel phase decomposes, leading to the formation of -Fe₂O₃.