Mechanical properties of freely suspended semiconducting graphene-like layers based on MoS2

We fabricate freely suspended nanosheets of molybdenum disulphide (MoS₂) which are characterized by quantitative optical microscopy and high-resolution friction force microscopy. We study the elastic deformation of freely suspended nanosheets of MoS₂ using an atomic force microscope. The Young''s modulus and the initial pre-tension of the nanosheets are determined by performing a nanoscopic version of a bending test experiment. MoS₂ sheets show high elasticity and an extremely high Young''s modulus (0.30 TPa, 50% larger than steel). These results make them a potential alternative to graphene in applications requiring flexible semiconductor materials.PACS, 73.61.Le, other inorganic semiconductors, 68.65.Ac, multilayers, 62.20.de, elastic moduli, 81.40.Jj, elasticity and anelasticity, stress-strain relations.     

Maternal regulation of embryonic growth: the role of vasoactive intestinal peptide

Vasoactive intestinal peptide (VIP) is an important growth regulator of the embryonic day (E)9-E11 mouse. In comparably aged rat embryos, VIP messenger RNA (mRNA) is not detectable; however, peak concentrations of VIP in maternal rat serum indicate a nonembryonic source. In the current study, mouse maternal and embryonic tissues were examined from E6-E12. Although RT-PCR revealed VIP mRNA in E6-E7 conceptuses, by E8 (when extraembryonic tissues could be separated from the embryo), VIP mRNA was detected only in the decidua/trophoblast. Decidual/trophoblastic VIP mRNA decreased until E10, after which it was not detectable. VIP mRNA was not apparent in the embryo until E11-E12. At E9, VIP immunoreactivity was localized to abundant, diffuse cells in the decidua basalis, which were also immunoreactive for T cell markers. VIP binding sites were dense in the decidua/trophoblast at E6, but gradually decreased until E10, after which they were not apparent. VIP binding sites were detected in embryonic neuroepithelium by E9. The transient presence of VIP binding sites and mRNA in the decidua/trophoblast correlate with the critical period of VIP growth regulation, when VIP mRNA is absent in the embryo. These findings suggest that maternal lymphocytes are the source of VIP's regulating early postimplantation embryonic growth.     

Proteolysis of native proteins. Trapping of a reaction intermediate

When limited proteolysis of the mouse major urinary proteins by trypsin was stopped by rapid denaturation of the proteinase, a covalent adduct of the two proteins was observed. The formation of this complex required active trypsin, was favored at low pH, and could be reversed by the addition of covalent or non-covalent trypsin inhibitors. Electrospray mass spectrometry of the complex demonstrated that it was an acyl-enzyme complex, formed after an unusual exopeptidase attack on the C-terminal-Arg-Glu-OH sequence by trypsin. The complex could sequester over 50% of the trypsin in a digestion mixture, and as anticipated, the protein was an effective trypsin inhibitor.     

The role of state policies and programs in buffering the effects of poverty on children's immunization receipt

OBJECTIVES: This study assessed the influence of public policies on the immunization status of 2-year old children in the United States. METHODS: Up-to-dateness for the primary immunization series was assessed in a national sample of 8100 children from the 1988 National Maternal and Infant Health Survey and its 1991 Longitudinal Follow-Up. RESULTS: Documented immunization rates of this sample were 33% for poor children and 44% for others. More widespread Medicated coverage was associated with greater likelihood of up-to-dateness among poor children. Up-to-dateness was more likely for poor children with public rather than private sources of routine pediatric care, but all children living in states where most immunizations were delivered in the public sector were less likely to be up to date. Poor children in state with partial vaccine replacement programs were less likely to be up to date than those in free-market purchase states. CONCLUSIONS: While state policies can enhance immunization delivery for poor children, heavy reliance on public sector immunization does not ensure timely receipt of vaccines. Public- and private-sector collaboration is necessary to protect children from vaccine-preventable diseases.     

Can the age limit for endoscopy be increased in dyspepsia patients who do not have alarm symptoms?

We studied the interictal EEG of 50 epileptic patients (28 males, 22 females) who had parenchymal neurocysticercosis, diagnosed by CAT/MRI of the brain, positive immunological reaction for cysticercosis in cerebral spinal fluid or both. Age ranged from 5 to 61 years old; the mean age of onset was 24.2 +/- 12.2 years. Thirty-six patients had generalized seizures, 13 partial seizures with secondarily generalized seizures, and 1 had complex partial seizures. Twenty-two patients had parenchymal calcifications (inactive form); 21 had parenchymal cysts (active form) and 7 had both. EEG was abnormal in 14 patients (28%): 8 had focal slowing, 3 had focal sharp or spike activity, and 3 had both. The EEG was normal in patients with inactive forms of neurocysticercosis. The EEG was abnormal in 50% of patients with active and mixed forms of neurocystercosis and in 48% of patients with active form only. We conclude that the active forms of neurocysticercosis should be suspected when the EEG is found to be abnormal. In additional, EEG abnormality does not depend on the number of lesions, but rather on location and viability of the cysts, and on host response.     

Functional analysis of conserved cysteines in heparan sulfate N-deacetylase-N-sulfotransferases

N-Deacetylase-N-sulfotransferases (NDANST) catalyze the two initial modifications of the polysaccharide precursor in the biosynthesis of heparin and heparan sulfate. These modifications are the gating steps in establishing growth factor protein-binding domains of these glycosaminoglycans. We have undertaken a structure-activity analysis of the 841-amino acid Golgi-luminal portion of the rat liver NDANST to localize the two enzymatic functions. Each activity can be assayed in vitro independently of the other when provided with the appropriate substrate, and N-ethylmaleimide treatment selectively inactivates the deacetylase activity. In this study, dithiothreitol treatment of the rat liver NDANST was shown to inactivate the sulfotransferase function, while stimulating deacetylase activity 2-3-fold over the native protein. Site-directed mutagenesis of the eight cysteine (Cys) residues in the rat liver NDANST that are conserved in the mouse mastocytoma protein produced three important findings regarding the localization of each enzymatic function: 1) derivatization of Cys486 with N-ethylmaleimide resulted in total inactivation of the deacetylase activity based on steric hindrance of the active site (this residue was shown not to be involved in enzymatic catalysis), 2) substitution of either Cys159 or Cys486 with alanine resulted in enhanced activity of the deacetylase to the level obtained by dithiothreitol treatment, and 3) alanine substitution of Cys818 or Cys828 completely inactivated the sulfotransferase activity, while substitution of Cys586 or Cys601 resulted in a 90% loss in activity. These findings suggest that the two enzymatic domains within the NDANST localize to different portions of the protein, with two disulfide pairs toward the COOH-terminal half of the protein necessary for the sulfotransferase activity, and Cys residues within the NH2-terminal half influencing or located near the active site of the deacetylase functionality.     

Hepatic transcatheter arterial chemoembolization alternating with systemic protracted continuous infusion 5-fluorouracil for gastrointestinal malignancies metastatic to liver: a phase II trial of the Puget Sound Oncology Consortium (PSOC 1104)

We assessed a regimen of alternating regional and systemic therapy in patients with gastrointestinal malignancies with liver-dominant metastases for feasibility, toxicity, response rate, response duration, patterns of progression, and progression-free and overall survival. Regional therapy comprised selective hepatic transcatheter arterial chemoembolization (TACE) using a suspension of cisplatin and particulate polyvinyl alcohol. This procedure was delivered between cycles of protracted continuous infusion 5-fluorouracil (PCI-5FU) as systemic chemotherapy. Patient eligibility criteria included: (a) having histologically documented adenocarcinoma arising from a gastrointestinal primary site with unresectable liver metastases bidimensionally measurable on computerized tomography scan; (b) age greater than 18 years; and (c) performance status 0-2 (Zubrod). PCI-5FU (250 mg/m2/day) was administered i.v. for 28 days, followed by the first TACE (TACE 1) delivered to the hepatic artery supplying the lobe with the greatest tumor burden. Restaging was performed before TACE 2 and TACE 3, which followed at monthly intervals. PCI-5FU for 21 days was sandwiched between each of the TACE treatments. After the final TACE, maintenance PCI-5FU was given for 28 days of each 35-day cycle until toxicity or progression. Between December 23, 1991, and January 19, 1995, 32 patients were registered in this trial, of whom 27 were eligible; 20 completed one or more treatment cycles and were evaluable for radiographic response. Patients with colorectal liver metastases predominated (74%). Twelve (44%) of 27 patients had failed one or more prior treatment regimens. There were no treatment-related deaths, and hematological and hepatic toxicities were generally manageable and reversible. Two patients, however, developed hepatic abscesses requiring drainage, and one patient developed an infarcted gallbladder, which necessitated cholecystectomy. There were no patients with complete responses; there were 8 (40%) with partial responses, 4 (20%) with minor responses, 2 (10%) with stable disease, and 6 (30%) who progressed on the treatment. The median duration of response for partial responders was 4.2 months (127 days; range, 56-245 days). The median reduction in carcinoembryonic antigen for responders was 87.5%. Two patients underwent subsequent resection of residual metastases; one of them is still alive at 58.4 months follow-up. The predominant site of disease progression was the liver; 25% of the patients progressed in extrahepatic sites. The median overall survival for the whole group is 14.3 months (95% confidence interval, 7.2-16.2). Actuarial overall survival for the whole group at 1 year and 2 years is 57 and 19%, respectively. Alternating systemic PCI-5FU and regional TACE (cisplatin/polyvinyl alcohol) is an active and feasible regimen with manageable toxicities in patients with metastatic gastrointestinal malignancies with liver-dominant disease and merits further investigation. The complications seen were in line with those reported at other specialized centers.     

Comparative structural and immunochemical properties of leghaemoglobins

Circular dichroism studies on leghaemoglobins from snake bean, lupin, serradella and other plants show that, in common with soybean (reported earlier) they have a similar overall polypeptide chain conformation and haem environment and orientation. Immunochemical studies, on the other hand, suggest that the antigenic determinants on the surface of the leghaemoglobins vary considerably. Thus, firstly the alpha-helix content of the leghaemoglobins as a class is very similar (60-65%) and approaches that of the myoglobins, secondly, the sign, magnitude and shape of their circular dichroism spectra in the near ultraviolet, Soret and visible regions suggest close similarities in the environment and orientation of a structurally important tryptophan residue and of the haem moiety, and thirdly, there is comparatively weak haem-protein interaction. The extent of immuno cross-reactivity was found to be best deomonstrated using the Farr radioimmunoassay procedure. The results were (a) 5 leghaemoglobins from one plant (soybean) crossreacted completely but with varying affinities. (b) The extent of cross reactivity between leghaemoglobins from different plants was compared to that within a single plant; the reaction of antiserum to a soybean leghaemoglobin with a serradella leghaemoglobin was weak, with a snake bean leghaemoglobin still weaker (and incomplete) while lupin leghaemoglobins showed no cross reactivity at all. (c) The "rapid" attenuation of cross reactivity among different plant leghaemoglobins is explicable in terms of the extensive amino acid substitutions which have been demonstrated in the literature and in the present studies. (d) In view of this rapid divergence it is not surprising that sperm whale and horse heart myoglobins showed no cross reactivity with soybean leghaemoglobins. In summary, amino acid substitutions in the leghaemoglobin family are conformationally but not immunochemically conservative.