First Measurement of the Nuclear-Recoil Ionization Yield in Silicon at 100 eV.

We measured the nuclear-recoil ionization yield in silicon with a cryogenic phonon-sensitive gram-scale detector. Neutrons from a monoenergetic beam scatter off of the silicon nuclei at angles corresponding to energy depositions from 4 keV down to 100 eV, the lowest energy probed so far. The results show no sign of an ionization production threshold above 100 eV. These results call for further investigation of the ionization yield theory and a comprehensive determination of the detector response function at energies below the keV scale.

Light Dark Matter Search with a High-Resolution Athermal Phonon Detector Operated above Ground.

We present limits on spin-independent dark matter-nucleon interactions using a 10.6 g Si athermal phonon detector with a baseline energy resolution of σ_{E}=3.86±0.04(stat)_{-0.00}^{+0.19}(syst) eV. This exclusion analysis sets the most stringent dark matter-nucleon scattering cross-section limits achieved by a cryogenic detector for dark matter particle masses from 93 to 140 MeV/c^{2}, with a raw exposure of 9.9 g d acquired at an above-ground facility. This work illustrates the scientific potential of detectors with athermal phonon sensors with eV-scale energy resolution for future dark matter searches.

Constraints on Lightly Ionizing Particles from CDMSlite.

The Cryogenic Dark Matter Search low ionization threshold experiment (CDMSlite) achieved efficient detection of very small recoil energies in its germanium target, resulting in sensitivity to lightly ionizing particles (LIPs) in a previously unexplored region of charge, mass, and velocity parameter space. We report first direct-detection limits calculated using the optimum interval method on the vertical intensity of cosmogenically produced LIPs with an electric charge smaller than e/(3×10^{5}), as well as the strongest limits for charge ≤e/160, with a minimum vertical intensity of 1.36×10^{-7} cm^{-2} s^{-1} sr^{-1} at charge e/160. These results apply over a wide range of LIP masses (5 MeV/c^{2} to 100 TeV/c^{2}) and cover a wide range of ßγ values (0.1-10^{6}), thus excluding nonrelativistic LIPs with ßγ as small as 0.1 for the first time.

Triple Junction at the Triple Point Resolved on the Individual Particle Level.

At the triple point of a repulsive screened Coulomb system, a fcc crystal, a bcc crystal, and a fluid phase coexist. At their intersection, these three phases form a liquid groove, the triple junction. Using confocal microscopy, we resolve the triple junction on a single-particle level in a model system of charged PMMA colloids in a nonpolar solvent. The groove is found to be extremely deep and the incommensurate solid-solid interface to be very broad. Thermal fluctuations hence appear to dominate the solid-solid interface. This indicates a very low interfacial energy. The fcc-bcc interfacial energy is quantitatively determined based on Young's equation and, indeed, it is only about 1.3 times higher than the fcc-fluid interfacial energy close to the triple point.

Paget's disease of bone in a 85-year-old woman.

Paget's disease of bone is a rare disorder in India. Patients are usually asymptomatic and incidental radiological investigation invariably clinches the diagnosis. Increased alkaline phosphatase, X-ray, CT scan and scintiscan of bone can be done to confirm the diagnosis. Here we report a case of an 85-yr-old lady who had bilateral hearing loss for last 10 yrs, was admitted incidentally for some other complaints and on investigation diagnosed to have advanced Paget's disease of bone.

Factor interactions with the simian virus 40 early pre-mRNA influence branch site selection and alternative splicing.

To study the interaction of splicing factors with the simian virus 40 early-region pre-RNA, which can be alternatively spliced to produce large T and small t mRNAs, we used an in vitro RNase protection assay that defines the 5' boundaries of factor-RNA interactions. Protection products reflecting factor interactions with the large T and small t 5' splice sites and with the multiple lariat branch site region were characterized. All protection products were detected very early in the splicing reaction, before the appearance of spliced RNAs. However, protection of the large T 5' splice site was detected well before small t 5' splice site and branch site protection products, which appeared simultaneously. Oligonucleotide-targeted degradation of small nuclear RNAs (snRNAs) revealed that protection of the branch site region, which occurred at multiple sites, required intact U2 snRNA and was enhanced by U1 snRNA, while protection of the large T and small t 5' splice sites required both U1 and U2 snRNAs. Analysis of several pre-RNAs containing mutations in the branch site region suggests that factor interactions involving the multiple copies of the branch site consensus determine the selection of branch points, which is an important factor in the selection of alternative splicing pathways.

SH2 domains exhibit high-affinity binding to tyrosine-phosphorylated peptides yet also exhibit rapid dissociation and exchange.

src homology 2 (SH2) domains of intracellular signaling molecules such as phospholipase C-gamma and phosphatidylinositol 3'-kinase-associated protein p85 represent recognition motifs for specific phosphotyrosine-containing regions on activated growth factor receptors. The binding of SH2 domains to activated growth factor receptors controls the interaction with signaling molecules and the regulation of their activities. In this report, we describe the kinetic parameters and binding affinities of SH2 domains of p85 toward short phosphotyrosine-containing peptides with the amino acid sequence motif YMXM, derived from a major insulin receptor substrate, IRS-1, by using real time biospecific interaction analysis (BIAcore). Associations were specific and of very high affinity, with dissociation constants of 0.3 to 3 nM, between phosphopeptides and the two separate SH2 domains contained within p85. Nonphosphorylated peptides showed no measurable binding, and the interactions were specific for the primary sequence very close to the phosphotyrosine residue. Moreover, the interactions between phosphopeptides and SH2 domains of other signaling molecules were of much lower affinity. Interestingly, the binding of the SH2 domains to the tyrosine-phosphorylated peptides was of high affinity as a result of a very high on rate, of 3 x 10(7) to 40 x 10(7)/M/s; at the same time, the rate of dissociation, of 0.11 to 0.19/s, was rapid, allowing for rapid exchange of associating proteins with the tyrosine phosphorylation sites.

Quasi-two-dimensional complex plasma containing spherical particles and their binary agglomerates.

A unique type of quasi-two-dimensional complex plasma system was observed which consisted of monodisperse microspheres and their binary agglomerations (dimers). The particles and their dimers levitated in a plasma sheath at slightly different heights and formed two distinct sublayers. The system did not crystallize and may be characterized as a disordered solid. The dimers were identified based on their characteristic appearance in defocused images, i.e., rotating interference fringe patterns. The in-plane and interplane particle separations exhibit nonmonotonic dependence on the discharge pressure.

Dust interferometers in plasmas.

An interferometric imaging technique has been proposed to instantly measure the diameter of individual spherical dust particles suspended in a gas discharge plasma. The technique is based on the defocused image analysis of both spherical particles and their binary agglomerates. Above a critical diameter, the defocused images of spherical particles contain stationary interference fringe patterns and the fringe number increases with particle diameters. Below this critical diameter, the particle size has been measured using the rotational interference fringe patterns which appear only on the defocused images of binary agglomerates. In this case, a lower cutoff limit of particle diameter has been predicted, below which no such rotational fringe patterns are observed for the binary agglomerates. The method can be useful as a diagnostics for complex plasma experiments on earth as well as under microgravity conditions.

cDNA sequence of the small subunit of the hamster ribonucleotide reductase.

Ribonucleotide reductase activity is markedly elevated in cell lines selected for resistance to hydroxyurea, a cytotoxic drug known specifically to inhibit ribonucleotide reductase. From a cDNA library constructed from a highly hydroxyurea-resistant hamster lung cell line, 600H in which the activity is elevated more than 80-fold, we have isolated a full length cDNA for the small subunit of the reductase. The cDNA is 3.48 kb long with an open reading frame of 1158 nucleotides and a long 3' flanking region of 2169 nucleotides from the termination codon. The derived polypeptide sequence is closely similar to the small subunit of the mouse, differing from it in 20 amino acid positions. Most of these replacements occur in the N-terminal segment of the protein. The hamster subunit does not contain 4 amino acid residues found in the mouse small subunit near the C-terminal end. RNA blots probed with the cDNA show two poly(A)+ RNA species which are elevated in hydroxyurea-resistant cells.

Cloning and characterization of a novel serine/threonine protein phosphatase type 5 from Trypanosoma brucei.

Reversible protein phosphorylation is essential for the regulation of numerous cellular functions and differentiation. The haemo-flagellated parasitic protozoan Trypanosoma brucei, the causative agent for African trypanosomiasis undergoes various stages of cellular differentiation during its digenetic life cycle. A complete cDNA of a unique serine/threonine phosphatase type five (TbPP5) was cloned and characterized from T. brucei. TbPP5 contains an open reading frame of 1416 bp that encodes a protein of about 53 kDa and exists as a single copy gene in the T. brucei genome. The deduced amino acid sequence showed 45-48% overall identity and 60-65% similarity with protein phosphatase 5's (PP5) from different species. Analysis of the primary sequence revealed that TbPP5 contains three TPR motifs at the N-terminal region (amino acid residues 7-107) while the phosphatase catalytic domain occurs in the C-terminal region (amino acid residues 210-410). A TbPP5 cDNA hybridized with a transcript of 2.5 kb which is present at similar levels in the procyclic and the bloodstream forms. However, the level of expression of the TbPP5 protein (52 kDa) detected by an antibody developed against a recombinant protein produced in E. coli was about 2-fold higher in the procyclic than the bloodstream form. The TbPP5 transcript level gradually decreased in cells grown in the logarithmic phase to the stationary phase in culture. Moreover, 18 h serum starvation of the procyclic forms decreased the level of the specific transcript about 3-fold suggesting that this protein may play a role during the active growth phase of the organism. The recombinant protein showed phosphatase activity which was stimulated about 2.6-fold by arachidonic acid with half-maximal activity at 75 microM. Indirect immuno-fluorescence of permeabilized cells revealed that the protein is localized in the cytosol and the nucleus This is the first report for the identification of a type 5 serine/threonine protein phosphatase in an ancient eukaryote such as T. brucei.

The capability for regulation of insulin secretion by somatostatin in purified pancreatic islet B cells during aging.

Pancreatic islet B cells from Sprague-Dawley and Fisher 344 rats aged 3-27 months were separated from A and D cells by centrifugation over a linear percoll density gradient, and incubated in vitro with various concentrations of glucose and somatostatin. Elevation of glucose concentration in the incubation medium from 2.6 to 16.7 mM provokes an insulin secretory response that is independent of rat donor age. Inhibition of the insulin secretory response by somatostatin is independent of rat donor age beyond 12 months. These data indicate that the impaired regulation of insulin secretion during aging observed previously in vivo and in vitro in intact islets may not be intrinsic to the B cells, but instead reflect changes in islet paracrine regulatory mechanisms that relate to the quality and/or quantity of endogenous somatostatin and/or glucagon.

Biochemical and molecular properties of the Trypanosoma brucei alternative oxidase.

The protozoal parasite Trypanosoma brucei depends on a mitochondrial non-cytochrome terminal oxidase known as the trypanosome alternative oxidase (TAO) in its mammalian host. We have recently cloned the cDNA from T. brucei bloodstream form and have characterized a 33 kDa mitochondrial protein as TAO. Here we report that the TAO is a single copy gene in T. brucei and its expression is down regulated at the level of transcript abundance during differentiation from the bloodstream to the procyclic trypanosomes. Like other alternative oxidases (AOXs) cloned from different plants and fungi, TAO possesses the conserved sequences at the centrally located predicted membrane spanning domains and the signature sequence at the C-terminal hydrophilic domain for a pair of putative iron binding motifs (E-X-X-H). Phylogenetic analysis of the deduced protein sequences of eight different alternative oxidases cloned from different plants and fungi revealed that TAO is more closely related to the alternative oxidases of the fungi clade than that of plants. TAO has been functionally expressed in Escherichia coli. In the first of the two putative iron binding motifs, site-directed mutagenesis of E215 to A, L, N and Q resulted in the loss of the ability of the TAO gene to complement the heme deficiency of the E. coli mutants (SASX41B and GE1387) by conferring on them a CN-insensitive pathway of respiration. The conservative substitution of E215 by aspartate and histidine reduced the growth of the E. coli auxotrophs by approximately 80%. The mutations apparently did not have any effect on the stability of the expressed protein as revealed by the immunoblot analysis of the bacterial protein using TAO monoclonal antibody, which we have developed. Together, these points suggest that E215 plays an important role in the function of TAO. The steady state level of TAO mRNA is down-regulated in the procyclic stage presumably accounting for the low levels of TAO protein in these forms.

Acute upper gastrointestinal hemorrhage in older people: a prospective study in two neighboring districts.

OBJECTIVE: To study the distribution of mucosal lesions and outcomes in older people with acute upper gastrointestinal hemorrhage (UGIH). DESIGN: Prospective case study. SETTING: Two neighboring district hospitals with similar admission policies. SUBJECTS: Consecutive patients aged 75 years or older admitted with hematemesis and/or melena during the study period. OUTCOME MEASURES: Length of hospital stay, mortality, surgical intervention, and transfusion requirements. RESULTS: A total of 109 patients were entered into the study. Of these, 106 (97%) underwent gastroscopy, and bleeding sites were identified in 98%. Upper gut malignancies were identified in eight patients, ulcerative esophagitis in 32, benign gastric ulcers in 24, and duodenal ulcers in 23 patients. Forty-seven percent had severe anemia on admission (Hb < 10 g/dL). Thirty-eight patients were referred for surgery, and eight were operated on, with one postoperative death. Six other patients died, five of whom had malignancies. The overall mortality of 6% reduced to 2% if those with malignancy were excluded. The 92 patients discharged had a median hospital stay of 15 days (range 2-30). CONCLUSIONS: Older people with acute UGIH have advanced upper gut pathology with preponderance of esophageal lesions. Classical symptoms seem lacking, but mortality can be decreased despite adverse comorbid factors. Lower thresholds for endoscopy are advocated in older adults, and comparative studies of UGIH symptoms with younger patients are required.

The similarity between tuftsin (Thr-Lys-Pro-Arg) receptors and tuftsin antibody: a case of induced molecular mimicry.

The characteristics of binding of tuftsin (Thr-Lys-Pro-Arg) and several of its synthetic analogues, to specific membrane receptors on rabbit polymorphonuclear granulocytes, were compared with the binding characteristics of rabbit specific antibody to tuftsin. [3H-Arg4]-tuftsin was used as the principal ligand. Six analogues were studied. Two of these, Thr-Lys-Pro and Ala-Lys-tuftsin-Glu-Ala3, showed no binding affinity either to receptor or antibody. Ala-Lys-tuftsin showed less binding than tuftsin to both acceptors. Three showed stronger binding than tuftsin. The order of binding among these was tuftsin ( [Glu]2-tuftsin ( [Pro-Pro3]-tuftsin (tuftsinyltuftsin. This same order of binding was found with both receptor and antibody.

Rifampicin-induced chromatid exchanges in Sarcoma-180 mouse ascites cells.

Sarcoma-180 ascites tumour-bearing male mice were injected i.p. with single dose of 0.5, 2.5, 5 mg/kg body wt. of rifampicin. Cells were sampled for mitotic chromosome analysis 4, 16 or 24 h after treatment. The maximal yield of chromatid-type aberrations induced was found 24 h after treatment with 5 mg/kg of rifampicin. More than 60% of the cells carried at least one chromatid exchange. The majority of these were exchanges derived from breaks in the centromeric heterochromatin.

Technique for the isolation of secondary phases in processed magnesite.

The study describes a new wet chemical technique, termed ANM, for the isolation of secondary phases in magnesite processed at a temperature of 1650 degrees C. The major MgO (periclase) phase in processed magnesite was preferentially extracted as ammonium nitrate magnesium double salt by ammonium nitrate in ethanol medium. The residues containing enriched secondary phases were identified by XRD.

Effects of glucose and fructose loading on glycogenesis in chicks infected with avian tuberculosis.

The chick was used as a rapid metabolic model to determine the fate of ingested fructose vs. glucose in noninfected chicks and in those subjected to the stress of avian tuberculosis. The chicks were crop-loaded with either a 72% fructose or glucose solution 21 and 28 days post TB inoculation and killed 2 and 4 hr after loading. In noninfected chicks, both sugars were rapidly converted to glycogen, and there was an interaction with time and the amount of glycogen formed from each sugar. Infection depressed glycogen formation from both fructose and glucose. While the total amount of glycogen formed from glucose could be directly correlated to increased liver size in the TB chicks loaded with glucose, in the chicks loaded with fructose less glycogen was formed even though liver size was increased as a result of the TB infection. The depression in glycogen formation was not related to the severity of the infection since the TB involvement was not the same in the two experiments conducted; but in both cases chicks loaded with fructose showed a greater reduction in the capacity of the liver to synthesize glycogen.

Giant cavernous hemangioma of liver.

An abscess forming in a giant cavernous hemangioma of the left lobe of the liver is reported. It was treated by lateral segmentectomy.