bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of nonresonant impurity gases in alkali vapor cells
Authors: Novikova I. , Matsko A. B. , Welch G. R.
Published: July 2002

We show that even small amounts of impurity gases significantly change the properties of the nonlinear Faraday effect in alkali vapor cells. These changes result from velocity-changing collisions. We propose a simple method of detection and measurement of the impurities based on this effect.
Different components of far-infrared photoresponse of quantum Hall detectors
Authors: Kalugin N. G. , Nachtwei G. , Vasilyev Yu. B. , Suchalkin S. D. , Eberl K.
Published: July 2002

We have performed time-resolved measurements of the far-infrared photoresponse of two-dimensional electron systems in the quantum Hall regime. The photoresponse consists of two equally important components: the longitudinal component, caused by the photoinduced change of the longitudinal resistance Rxx, and the transversal component, caused by the photoinduced Hall currents and by the photoinduced change of Rxy. Both these components are connected with two mechanisms of the photoresponse: a nonresonant bolometric, and a cyclotron-resonant contribution.
Adjustable responsivity for thermal infrared detectors
Authors: Song Woo-Bin , Talghader Joseph J.
Published: July 2002

With the recent interest in adaptive IR imaging, focal plane arrays are desired that can operate linearly over an enormous dynamic range. Unfortunately, large signals can cause thermal detectors to operate at temperatures significantly above their ambient resulting in intensity dependent performance or even device damage. In this letter, the responsivity of microbolometer devices is controlled using the detector and substrate as a simple electrostatic actuator. Microbolometers are demonstrated to switch between states that are over a factor of 50 apart in responsivity. The limits of the switching are theoretically separated by four to five orders of magnitude. In addition, intermediate values of responsivity can be obtained by designing devices in which the support beams snap down at lower voltage than the detector plate. Combining this idea with the pressure dependence of the thermal contact conductance, continuous thermal conductance tuning over a factor of 3 is demonstrated.
Electrical conductivity and thermopower of Cu–SiO2 nanogranular films
Authors: Chen W. , Lin J. J. , Zhang X. X. , Shin H. K. , Dyck J. S. , Uher C.
Published: July 2002

We have measured the thermopower S and electrical conductivity σ in a series of Cux(SiO2)1−x nanogranular films between 2 and 300 K with Cu volume fraction x varying from 0.43 up to 1.0. At low temperatures, disorder-enhanced electron–electron interaction effects dictate the behavior of σ. A crossover of the temperature dependence from σ∝T to σ∝T1/3 is observed as x is lowered and the metal–insulator transition is approached. S is small, shows linear temperature dependence, and is rather insensitive to the change of x. Effects of annealing are also discussed.
Laser-like mechanoluminescence in ZnMnTe-diluted magnetic semiconductor
Authors: Reddy D. Raja , Reddy B. K.
Published: July 2002

Laser-like mechanoluminescence is reported in the spintronic material ZnMnTe. The luminescence was also observed when the material was exposed to UV and x-rays. Photoluminescence spectra consisted of peaks at 386.5 and 648 nm, which may be attributed to band gap, and Mn2+ levels, respectively. Lattice contraction, sharpness of the x-ray diffraction peak, and the blueshift in the energy gap confirm the nanostructure of the material. A possible mechanism for lasing is also suggested.
Photovoltaic hybrid device with broad tunable spectral response achieved by organic/inorganic thin-film heteropairing
Authors: Schroeder R. , Ullrich B.
Published: July 2002

By means of laser deposition, spin casting and vacuum evaporation, optoelectronic hybrid devices were manufactured based upon the thin-film heteropairing of a perylene-derived molecule [di-isoquinoline perylene derivative (DQP)] and CdS. The photovoltaic characteristics of the devices are presented and discussed. We demonstrate that by exploitation of relatively high carrier mobilities in the CdS layer and the high photonic yield and deposition ease of the DQP film, efficient and technologically appealing optoelectronic devices are feasible. In addition, bias dependence of the spectral sensitivity demonstrates the versatility of the introduced device concept in light of photonic sensor applications.
Analysis of SiO2/Si(001) interface roughness for thin gate oxides by scanning tunneling microscopy
Authors: Gotoh Masahide , Sudoh Koichi , Itoh Hiroyasu , Kawamoto Kazunori , Iwasaki Hiroshi
Published: July 2002

We studied the interface roughnesses of SiO2/Si(001) for gate oxides of 8 and 15 nm thicknesses together with RCA-treated samples by using scanning tunneling microscopy (STM). By STM observation and scaling analysis we made clear that the interface roughnesses of thermal oxides/Si substrates were similar to each other and to that of the chemical oxide/Si substrate prior to thermal oxidation; the correlation length was 23–26 nm and the rms roughness at length scales larger than the correlation length was 0.28–0.29 nm. The results indicate that the interface roughnesses of the oxides are determined by the processes prior to the oxidations.
Formation of pnp bipolar structure by thermal donors in nitrogen-containing p-type Czochralski silicon wafers
Authors: Ma Xiangyang , Yu Xuegong , Fan Ruixin , Yang Deren
Published: July 2002

The carrier concentration profile in boron-doped p-type nitrogen-containing Czochralski silicon wafer subjected to a one-step high-temperature (1150 °C) annealing followed by a prolonged 450 °C annealing has been investigated by spreading resistance profile. It is found that the carrier concentration profile is characteristic of a pnp bipolar structure, while, that in the control wafer of p-type conventional Czochralki silicon subjected to the identical thermal treatment is just characteristic of a p-n junction. Moreover, it is suggested that only one-step annealing at high temperatures is an efficient method for intrinsic gettering of a nitrogen-containing Czochralski silicon wafer due to the outdiffusion of oxygen and nitrogen in the near-surface region and the nitrogen-enhanced oxygen precipitation in the bulk region.
Optical properties of Mn-doped CdS nanocrystals fabricated by sequential ion implantation
Authors: Kanemitsu Yoshihiko , Matsubara Hiroki , White C. W.
Published: July 2002

We have studied luminescence spectrum and dynamics of Mn-doped CdS nanocrystals fabricated by sequential Cd+, S+, and Mn+ ion implantation into Al2O3 matrices. The photoluminescence (PL) due to the Mn2+ intra-3d transition is clearly observed near 570 nm in Mn-doped CdS nanocrystals. The PL excitation spectrum of the Mn2+ luminescence in Mn-doped CdS nanocrystals is similar to the optical absorption spectrum and PL excitation spectrum of undoped CdS nanocrystals. Our spectroscopic data show that ion-beam synthesis is one of the methods of the fabrication of doped semiconductor nanocrystals. The luminescence mechanism of Mn-doped CdS nanocrystals will be discussed.
Light amplification and gain in polyfluorene waveguides
Authors: Heliotis George , Bradley Donal D. C. , Turnbull Graham A. , Samuel Ifor D. W.
Published: July 2002

We report a study of the properties of the semiconducting polymer poly(9,9-dioctylfluorene) (PFO) as a gain medium. We demonstrate amplification of blue light via amplified spontaneous emission (ASE) measurements on optically pumped PFO planar asymmetric waveguides. We show that the ASE wavelength can be tuned over a range of 20 nm by altering the supported waveguide modes. Gain/loss measurements at the peak ASE wavelength (466 nm) show that the waveguides can exhibit a large net gain of up to 74 cm−1 and have a very low loss coefficient ∼3 cm−1. These characteristics make PFO attractive as a high gain medium for short-wavelength lasers and optical amplifiers.
Highly efficient organic light-emitting diodes with a silole-based compound
Authors: Chen H. Y. , Lam W. Y. , Luo J. D. , Ho Y. L. , Tang B. Z. , Zhu D. B. , Wong M. , Kwok H. S.
Published: July 2002

Efficient light emission was obtained in a silole-based organic light-emitting diode. A high luminous current efficiency of 20 cd/A, corresponding to an external quantum efficiency of 8%, was achieved. The apparent violation of the upper theoretical limit of 5.5% for the external quantum efficiency of a singlet emitter is discussed. With a suitably designed cathode, a high power efficiency of ∼14 lm/W was obtained. A strong dependence of the power efficiency on the thickness of Alq3 layer is also observed and explained.
Formation of ZnO nanostructures by a simple way of thermal evaporation
Authors: Yao B. D. , Chan Y. F. , Wang N.
Published: July 2002

Mass production of ZnO nanowires, nanoribbons, and needle-like rods has been achieved by a simple method of thermal evaporation of ZnO powders mixed with graphite. Metallic catalysts, carrying gases, and vacuum conditions are not necessary. Temperature is the critical experimental parameter for the formation of different morphologies of ZnO nanostructures. Zn or Zn suboxide plays a crucial role for the nucleation of ZnO nanostructures. The as-prepared ZnO nanowires consist of single crystalline cores and thin amorphous shells. As determined by electron diffraction, the growth direction of ZnO nanowires is [001], which has no orientation relationship with the substrate. A strong room-temperature photoluminescence in ZnO nanostructures has been demonstrated.
Light up-conversion from near-infrared to blue using a photoresponsive organic light-emitting device
Authors: Chikamatsu Masayuki , Ichino Yoshiro , Takada Noriyuki , Yoshida Manabu , Kamata Toshihide , Yase Kiyoshi
Published: July 2002

A photoresponsive organic light-emitting device combining blue-emitting organic electroluminescent (EL) diode with titanyl phthalocyanine as a near-infrared (IR) sensitive layer was fabricated. By irradiating near-IR light to the device, blue emission occurred in the lower drive voltage (between 5 and 12 V). The result indicates that the device acts as a light switch and/or an up-converter from near-IR light (1.6 eV) to blue (2.6 eV). The EL response times of rise and decay using a near-IR light trigger were 260 and 330 μs, respectively. At a higher voltage (above 12 V), enhancement of blue emission was observed with near-IR light irradiation. The ON/OFF ratio reached a maximum of 103.
Electron energy-loss spectroscopy analysis of interface structure of yttrium oxide gate dielectrics on silicon
Authors: Niu D. , Ashcraft R. W. , Chen Z. , Stemmer S. , Parsons G. N.
Published: July 2002

Interface stability of high dielectric constant gate insulators on silicon is an important issue for advanced gate stack engineering. In this article, we analyze the silicon/dielectric interface structure for thin Y2O3 and Y silicate films deposited by chemical vapor deposition on clean and prenitrided Si(100) using high-resolution transmission electron microscopy, electron energy-loss spectroscopy, and x-ray photoelectron spectroscopy. The analysis shows the films to be stoichiometric Y2O3 on top and Y-silicate/SiO2 at the dielectric/Si interface. Prenitridation of the silicon surface impedes the reaction between the depositing film and the substrate, promoting a Si-free Y2O3 structure. Possible mechanisms leading to the observed Y2O3 and Y silicate structures are discussed.
Glycine residues in potassium channel-like selectivity filters determine potassium selectivity in four-loop-per-subunit HKT transporters from plants
Authors: Mäser Pascal , Hosoo Yoshihiro , Goshima Shinobu , Horie Tomoaki , Eckelman Brendan , Yamada Katsuyuki , Yoshida Kazuya , Bakker Evert P. , Shinmyo Atsuhiko , Oiki Shigetoshi , Schroeder Julian I. , Uozumi Nobuyuki
Published: July 2002

Plant HKT proteins comprise a family of cation transporters together with prokaryotic KtrB, TrkH, and KdpA transporter subunits and fungal Trk proteins. These transporters contain four loop domains in one polypeptide with a proposed distant homology to K
+
channel selectivity filters. Functional expression in yeast and
Xenopus
oocytes revealed that wheat HKT1 mediates Na
+
-coupled K
+
transport.
Arabidopsis
AtHKT1, however, transports only Na
+
in eukaryotic expression systems. To understand the molecular basis of this difference we constructed a series of AtHKT1/HKT1 chimeras and introduced point mutations to AtHKT1 and wheat HKT1 at positions predicted to be critical for K
+
selectivity. A single-point mutation, Ser-68 to glycine, was sufficient to restore K
+
permeability to AtHKT1. The reverse mutation in HKT1, Gly-91 to serine, abrogated K
+
permeability. This glycine in P-loop A of AtHKT1 and HKT1 can be modeled as the first glycine of the K
+
channel selectivity filter GYG motif. The importance of such filter glycines for K
+
selectivity was confirmed by interconversion of Ser-88 and Gly-88 in the rice paralogues OsHKT1 and OsHKT2. Surprisingly, all HKT homologues known from dicots have a serine at the filter position in P-loop A, suggesting that these proteins function mainly as Na
+
transporters in plants and that Na
+
/K
+
symport in HKT proteins is associated with a glycine in the filter residue. These data provide experimental evidence that the glycine residues in selectivity filters of HKT proteins are structurally related to those of K
+
channels.
Molecular characterization of meiotic recombination across the 140-kb multigenic
a1
-
sh2
interval of maize
Authors: Yao Hong , Zhou Qing , Li Jin , Smith Heather , Yandeau Marna , Nikolau Basil J. , Schnable Patrick S.
Published: July 2002

The 140-kb
a1-sh2
interval of the maize genome contains at least four genes (
a1
,
yz1
,
x1
, and
sh2
). Partial sequence analysis of two haplotypes has revealed many single nucleotide polymorphisms and InDel polymorphisms, including several large structural polymorphisms. The physical positions of 101 meiotic recombination breakpoints are not distributed uniformly across the interval and are instead concentrated within three recombination hot spots. Two of these recombination hot spots are genic (
a1
and
yz1
) and one is apparently nongenic. The
x1
gene is not a recombination hot spot. Thus, these results suggest that not all hot spots are genes and indicate that not all genes are hot spots. Two of the 101 recombination events arose by means of either noncrossover events involving conversion tract lengths of at least 17 kb or double-crossover events. Only one recombination breakpoint mapped to the ≈80-kb distal portion of the
a1-sh2
interval that contains large amounts of repetitive DNA including retrotransposons; in this region the ratio of genetic to physical distance is less than 0.5% of the genome's average. These results establish that the retrotransposon faction of the maize genome is relatively inert recombinationally.
Lysosomal destabilization in p53-induced apoptosis
Authors: Yuan Xi-Ming , Li Wei , Dalen Helge , Lotem Joseph , Kama Rachel , Sachs Leo , Brunk Ulf T.
Published: July 2002

The tumor suppressor wild-type p53 can induce apoptosis. M1-t-p53 myeloid leukemic cells have a temperature-sensitive p53 protein that changes its conformation to wild-type p53 after transfer from 37°C to 32°C. We have now found that these cells showed an early lysosomal rupture after transfer to 32°C. Mitochondrial damage, including decreased membrane potential and release of cytochrome
c,
and the appearance of apoptotic cells occurred later. Lysosomal rupture, mitochondrial damage, and apoptosis were all inhibited by the cytokine IL-6. Some other compounds can also inhibit apoptosis induced by p53. The protease inhibitor
N-
tosyl-
l
-phenylalanine chloromethyl ketone inhibited the decrease in mitochondrial membrane potential and cytochrome
c
release, the Ca
2+
-ATPase inhibitor thapsigargin inhibited only cytochrome
c
release, and the antioxidant butylated hydroxyanisole inhibited only the decrease in mitochondrial membrane potential. In contrast to IL-6, these other compounds that inhibited some of the later occurring mitochondrial damage did not inhibit the earlier p53-induced lysosomal damage. The results indicate that apoptosis is induced by p53 through a lysosomal-mitochondrial pathway that is initiated by lysosomal destabilization, and that this pathway can be dissected by using different apoptosis inhibitors. These findings on the induction of p53-induced lysosomal destabilization can also help to formulate new therapies for diseases with apoptotic disorders.
The etiology of white pox, a lethal disease of the Caribbean elkhorn coral,
Acropora palmata
Authors: Patterson Kathryn L. , Porter James W. , Ritchie Kim B. , Polson Shawn W. , Mueller Erich , Peters Esther C. , Santavy Deborah L. , Smith Garriet W.
Published: July 2002

Populations of the shallow-water Caribbean elkhorn coral,
Acropora palmata
, are being decimated by white pox disease, with losses of living cover in the Florida Keys typically in excess of 70%. The rate of tissue loss is rapid, averaging 2.5 cm
2
⋅day
−1
, and is greatest during periods of seasonally elevated temperature. In Florida, the spread of white pox fits the contagion model, with nearest neighbors most susceptible to infection. In this report, we identify a common fecal enterobacterium,
Serratia marcescens
, as the causal agent of white pox. This is the first time, to our knowledge, that a bacterial species associated with the human gut has been shown to be a marine invertebrate pathogen.
Genome expression analysis of
Anopheles gambiae
: Responses to injury, bacterial challenge, and malaria infection
Authors: Dimopoulos George , Christophides George K. , Meister Stephan , Schultz Jörg , White Kevin P. , Barillas-Mury Carolina , Kafatos Fotis C.
Published: July 2002

The complex gene expression responses of
Anopheles gambiae
to microbial and malaria challenges, injury, and oxidative stress (in the mosquito and/or a cultured cell line) were surveyed by using cDNA microarrays constructed from an EST-clone collection. The expression profiles were broadly subdivided into induced and down-regulated gene clusters. Gram
+
and Gram
−
bacteria and microbial elicitors up-regulated a diverse set of genes, many belonging to the immunity class, and the response to malaria partially overlapped with this response. Oxidative stress activated a distinctive set of genes, mainly implicated in oxidoreductive processes. Injury up- and down-regulated gene clusters also were distinctive, prominently implicating glycolysis-related genes and citric acid cycle/oxidative phosphorylation/redox-mitochondrial functions, respectively. Cross-comparison of
in vivo
and
in vitro
responses indicated the existence of tightly coregulated gene groups that may correspond to gene pathways.
Microsatellite evolution inferred from human– chimpanzee genomic sequence alignments
Authors: Webster Matthew T. , Smith Nick G. C. , Ellegren Hans
Published: July 2002

Most studies of microsatellite evolution utilize long, highly mutable loci, which are unrepresentative of the majority of simple repeats in the human genome. Here we use an unbiased sample of 2,467 microsatellite loci derived from alignments of 5.1 Mb of genomic sequence from human and chimpanzee to investigate the mutation process of tandemly repetitive DNA. The results indicate that the process of microsatellite evolution is highly heterogeneous, exhibiting differences between loci of different lengths and motif sizes and between species. We find a highly significant tendency for human dinucleotide repeats to be longer than their orthologues in chimpanzees, whereas the opposite trend is observed in mononucleotide repeat arrays. Furthermore, the rate of divergence between orthologues is significantly higher at longer loci, which also show significantly greater mutability per repeat number. These observations have important consequences for understanding the molecular mechanisms of microsatellite mutation and for the development of improved measures of genetic distance.
Loop–loop interaction of HIV-1 TAR RNA with N3′ → P5′ deoxyphosphoramidate aptamers inhibits
in vitro
Tat-mediated transcription
Authors: Darfeuille Fabien , Arzumanov Andrey , Gryaznov Sergei , Gait Michael J. , Di Primo Carmelo , Toulmé Jean-Jacques
Published: July 2002

A hairpin RNA aptamer has been identified by
in vitro
selection against the transactivation-responsive element (TAR) of HIV-1. A nuclease-resistant N3′ → P5′ phosphoramidate isosequential analog of this aptamer also folds as a hairpin and forms with TAR a loop–loop “kissing” complex with a binding constant in the low nanomolar range as demonstrated by electrophoretic mobility-shift assays and surface plasmon resonance experiments. The key structural determinants, which contribute to the stability of the RNA aptamer–TAR complex, loop complementarity and the GA residues closing the aptamer loop, remain crucial for the N3′ → P5′ aptamer–TAR complex. Moreover, the N3′ → P5′ phosphoramidate aptamer specifically interferes with the binding of a peptide derived from the transactivator protein (Tat) peptide to TAR and selectively inhibits the Tat-mediated transcription in an
in vitro
assay, which marks this nuclease-resistant aptamer as a relevant candidate for experiments in cells.
Contactless experiments on individual DNA molecules show no evidence for molecular wire behavior
Authors: Gómez-Navarro C. , Moreno-Herrero F. , de Pablo P. J. , Colchero J. , Gómez-Herrero J. , Baró A. M.
Published: July 2002

A fundamental requirement for a molecule to be considered a molecular wire (MW) is the ability to transport electrical charge with a reasonably low resistance. We have carried out two experiments that measure first, the charge transfer from an electrode to the molecule, and second, the dielectric response of the MW. The latter experiment requires no contacts to either end of the molecule. From our experiments we conclude that adsorbed individual DNA molecules have a resistivity similar to mica, glass, and silicon oxide substrates. Therefore adsorbed DNA is not a conductor, and it should not be considered as a viable candidate for MW applications. Parallel studies on other nanowires, including single-walled carbon nanotubes, showed conductivity as expected.
Important role of hypothalamic Y2 receptors in body weight regulation revealed in conditional knockout mice
Authors: Sainsbury Amanda , Schwarzer Christoph , Couzens Michelle , Fetissov Serguei , Furtinger Sabine , Jenkins Arthur , Cox Helen M. , Sperk Günther , Hökfelt Tomas , Herzog Herbert
Published: July 2002

Neuropeptide Y is implicated in energy homeostasis, and contributes to obesity when hypothalamic levels remain chronically elevated. To investigate the specific role of hypothalamic Y2 receptors in this process, we used a conditional Y2 knockout model, using the Cre-lox system and adenoviral delivery of Cre-recombinase. Hypothalamus-specific Y2-deleted mice showed a significant decrease in body weight and a significant increase in food intake that was associated with increased mRNA levels for the orexigenic NPY and AgRP, as well as the anorexic proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) in the arcuate nucleus. These hypothalamic changes persisted until at least 34 days after Y2 deletion, yet the effect on body weight and food intake subsided within this time. Plasma concentrations of pancreatic polypeptide and corticosterone were 3- to 5-fold increased in hypothalamus-specific Y2 knockout mice. Germ-line Y2 receptor knockout also produced a significant increase in plasma levels of pancreatic polypeptide. However, these mice differed from conditional knockout mice in that they showed a sustained reduction in body weight and adiposity associated with increased NPY and AgRP but decreased POMC and CART mRNA levels in the arcuate nucleus. The transience of the observed effects on food intake and body weight in the hypothalamus-specific Y2 knockout mice, and the difference of this model from germ-line Y2 knockout mice, underline the importance of conditional models of gene deletion, because developmental, secondary, or extrahypothalamic mechanisms may mask such effects in germ-line knockouts.
Probing solvent accessibility of amyloid fibrils by solution NMR spectroscopy
Authors: Ippel Johannes H. , Olofsson Anders , Schleucher Jürgen , Lundgren Erik , Wijmenga Sybren S.
Published: July 2002

Amyloid is the result of an anomalous protein and peptide aggregation, leading to the formation of insoluble fibril deposits. At present, 18 human diseases have been associated with amyloid deposits—e.g., Alzheimer's disease and Prion-transmissible Spongiform Encephalopathies. The molecular structure of amyloid is to a large extent unknown, because of lack of high-resolution structural information within the amyloid state. However, from other experimental data it has been established that amyloid fibrils predominantly consist of β-strands arranged perpendicular to the fibril axis. Identification of residues involved in these secondary structural elements is therefore of vital importance to rationally designing appropriate inhibitors. We have designed a hydrogen/deuterium exchange NMR experiment that can be applied on mature amyloid to enable identification of the residues located inside the fibril core. Using a highly amyloidogenic peptide, corresponding to residues 25–35 within the Alzheimer Aβ(1–43) peptide, we could establish that residues 28–35 constitute the amyloid core, with residues 31 and 32 being the most protected. In addition, quantitative values for the solvent accessibility for each involved residue could be obtained. Based on our data, two models of peptide assembly are proposed. The method provides a general way to identify the core of amyloid structures and thereby pinpoint areas suitable for design of inhibitors.
Apoptotic threshold is lowered by p53 transactivation of caspase-6
Authors: MacLachlan Timothy K. , El-Deiry Wafik S.
Published: July 2002

Little is known about how a cell's apoptotic threshold is controlled after exposure to chemotherapy, although the p53 tumor suppressor has been implicated. We identified executioner caspase-6 as a transcriptional target of p53. The mechanism involves DNA binding by p53 to the third intron of the caspase-6 gene and transactivation. A p53-dependent increase in procaspase-6 protein level allows for an increase in caspase-6 activity and caspase-6-specific Lamin A cleavage in response to Adriamycin exposure. Specific inhibition of caspase-6 blocks cell death in a manner that correlates with caspase-6 mRNA induction by p53 and enhances long-term survival in response to a p53-mediated apoptotic signal. Caspase-6 is an executioner caspase found directly regulated by p53, and the most downstream component of the death pathway controlled by p53. The induction of caspase-6 expression lowers the cell death threshold in response to apoptotic signals that activate caspase-6. Our results provide a potential mechanism of lowering the death threshold, which could be important for chemosensitization.
A possible evolutionary origin for the Mn
4
cluster of the photosynthetic water oxidation complex from natural MnO
2
precipitates in the early ocean
Authors: Sauer Kenneth , Yachandra Vittal K.
Published: July 2002

The photosynthetic water oxidation complex consists of a cluster of four Mn atoms bridged by O atoms, associated with Ca
2+
and Cl
−
, and incorporated into protein. The structure is similar in higher plants and algae, as well as in cyanobacteria of more ancient lineage, dating back more than 2.5 billion years ago on Earth. It has been proposed that the proto-enzyme derived from a component of a natural early marine manganese precipitate that contained a CaMn
4
O
9
cluster. A variety of MnO
2
minerals are found in nature. Three major classes are spinels, sheet-like layered structures, and three-dimensional networks that contain parallel tunnels. These relatively open structures readily incorporate cations (Na
+
, Li
+
, Mg
2+
, Ca
2+
, Ba
2+
, H
+
, and even Mn
2+
) and water. The minerals have different ratios of Mn(III) and Mn(IV) octahedrally coordinated to oxygens. Using x-ray spectroscopy we compare the chemical structures of Mn in the minerals with what is known about the arrangement in the water oxidation complex to define the parameters of a structural model for the photosynthetic catalytic site. This comparison provides for the structural model a set of candidate Mn
4
clusters—some previously proposed and considered and others entirely novel.
The systemin receptor SR160 from
Lycopersicon peruvianum
is a member of the LRR receptor kinase family
Authors: Scheer Justin M. , Ryan Clarence A.
Published: July 2002

The isolation to homogeneity of the 160-kDa systemin cell-surface receptor (SR160) from plasma membranes of suspension cultured cells of
Lycopersicon peruvianum
is reported. The purification procedure resulted in recovery of 13 μg of pure receptor protein, representing an 8,200-fold purification. Gel blot analyses using SR160-specific antibodies confirmed that a cross-reacting protein in the membranes of suspension-cultured cells comigrates with both the native and a deglycosylated form of the radiolabeled receptor. Internal amino acid sequences of the purified protein facilitated the isolation of a cDNA clone encoding the 160-kDa receptor. The identity of the encoded protein as SR160 was further confirmed by a comparison of its sequence with a mass spectral fingerprint of the SR160 protein. The deduced amino acid sequence of SR160 revealed that it is a member of the leucine-rich repeat (LRR) receptor kinase family, closely related to the brassinolide receptor kinase, BRI1.
Emergence of multiple genotypes of H5N1 avian influenza viruses in Hong Kong SAR
Authors: Guan Y. , Peiris J. S. M. , Lipatov A. S. , Ellis T. M. , Dyrting K. C. , Krauss S. , Zhang L. J. , Webster R. G. , Shortridge K. F.
Published: July 2002

Although A/Hong Kong/156/97 (H5N1/97)-like viruses associated with the “bird flu” incident in Hong Kong SAR have not been detected since the slaughter of poultry in 1997, its putative precursors continue to persist in the region. One of these, Goose/Guangdong/1/96 (H5N1 Gs/Gd)-like viruses, reassorted with other avian viruses to generate multiple genotypes of H5N1 viruses that crossed to chickens and other terrestrial poultry from its reservoir in geese. Whereas none of these recent reassortants had acquired the gene constellation of H5N1/97, these events provide insight into how such a virus may have been generated. The recent H5N1 reassortants readily infect and kill chicken and quail after experimental infection, and some were associated with significant mortality of chickens within the poultry retail markets in Hong Kong. Some genotypes are lethal for mice after intra-nasal inoculation and spread to the brain. On this occasion, the early detection of H5N1 viruses in the retail, live poultry markets led to preemptive intervention before the occurrence of human disease, but these newly emerging, highly pathogenic H5N1 viruses provide cause for pandemic concern.
Transcriptional collision between convergent genes in budding yeast
Authors: Prescott Elizabeth M. , Proudfoot Nick J.
Published: July 2002

Transcriptional interference between genes and the regulatory elements of simple eukaryotes such as
Saccharomyces cerevisiae
is an unavoidable consequence of their compressed genetic arrangement. We have shown previously that with the tandem arranged genes
GAL10
and
GAL7
, inefficient transcriptional termination of the upstream gene inhibits initiation of transcription on the downstream gene. We now show that transcriptional interference can occur also with
S. cerevisiae
RNA polymerase II genes arranged convergently. We demonstrate that when the
GAL10
and
GAL7
genes are rearranged in a convergent orientation, transcriptional initiation occurs at full levels. However, as soon as the two transcripts begin to overlap, elongation is restricted, resulting in a severe reduction in steady-state mRNA accumulation. This effect is observed only in cis arrangement, arguing against RNA-interference effects acting on the potential generation of antisense transcripts. These data reinforce the necessity of separating adjacent RNA polymerase II transcription units by efficient termination signals.
Alternate interactions define the binding of peptides to the MHC molecule IAb
Authors: Liu Xinqi , Dai Shaodong , Crawford Frances , Frugé Rachel , Marrack Philippa , Kappler John
Published: July 2002

We have solved the crystal structure of the MHCII molecule, IAb, containing an antigenic variant of the major IAb-binding peptide derived from the MHCII IEα chain. The four MHC pockets at p1, p4, p6, and p9 that usually bind peptide side chains are largely empty because of alanines in the peptide at these positions. The complex is nevertheless very stable, apparently because of unique alternate interactions between the IAband peptide. In particular, there are multiple additional hydrogen bonds between the N-terminal end of the peptide and the IAbα chain and an extensive hydrogen bond network involving an asparagine at p7 position of the peptide and the IAbβ chain. By using knowledge of the shape and size of the traditional side chain binding pockets and the additional possible interactions, an IAbpeptide-binding motif can be deduced that agrees well with the sequences of known IAb-binding peptides.
Adaptive immunity cooperates with liposomalall-trans-retinoic acid (ATRA) to facilitate long-term molecular remissions in mice with acute promyelocytic leukemia
Authors: Westervelt Peter , Pollock Jessica L. , Oldfather Kristie M. , Walter Matthew J. , Ma Margaret K. , Williams Anthony , DiPersio John F. , Ley Timothy J.
Published: July 2002

We previously developed a murine model of acute promyelocytic leukemia (APL) by using human cathepsin G gene regulatory elements to direct the expression of promyelocytic leukemia (PML)/retinoic acid receptor α (RARα) and RARα/PML fusion cDNAs to the early myeloid compartment of transgenic mice. To study the efficacy of noncytotoxic therapy in this animal model, cohorts of naive immunocompetent mice were inoculated with primary murine APL cells from a frozen tumor bank. Arsenic trioxide and liposomally encapsulatedall-trans-retinoic acid (Lipo ATRA), alone or in combination, were administered for 21 days by i.p. injection using doses that yielded plasma levels similar to those observed in human APL patients treated with these agents. Lipo ATRA was highly effective in inducing durable molecular remissions in immunocompetent mice [C57BL/6 × C3H F1(B6C3HF1)]; arsenic therapy was much less effective, and did not clearly synergize with Lipo ATRA to increase the remission rate in immunocompetent mice. The survival of Lipo ATRA-treated severe combined immunodeficient (SCID) animals (lacking functional T and B cells) was inferior to that of immunocompetent B6C3HF1 recipients (40% vs. 88% survival at 1 y,P< 0.001). These data suggest that adaptive immunity cooperates with pharmacologic therapy to induce or maintain remissions in murine APL. It also implies that immunosuppressive anti-leukemia therapies could paradoxically blunt effective anti-leukemia immune responses that are important for clearing small numbers of residual tumor cells after chemotherapy-mediated cytoreduction.
Urokinase–urokinase receptor interaction mediates an inhibitory signal for HIV-1 replication
Authors: Alfano Massimo , Sidenius Nicolai , Panzeri Barbara , Blasi Francesco , Poli Guido
Published: July 2002

Elevated levels of soluble urokinase-type plasminogen activator (uPA) receptor, CD87/u-PAR, predict survival in individuals infected with HIV-1. Here, we report that pro-uPA (or uPA) inhibits HIV-1 expression in U937-derived chronically infected promonocytic U1 cells stimulated with phorbol 12-myristate 13-acetate (PMA) or tumor necrosis factor-α (TNF-α). However, pro-uPA did not inhibit PMA or TNF-α-dependent activation of nuclear factor-kB or activation protein-1 in U1 cells. Cell-associated HIV protein synthesis also was not decreased by pro-uPA, although the release of virion-associated reverse transcriptase activity was substantially inhibited, suggesting a functional analogy between pro-uPA and the antiviral effects of IFNs. Indeed, cell disruption reversed the inhibitory effect of pro-uPA on activated U1 cells, and ultrastructural analysis confirmed that virions were preferentially retained within cell vacuoles in pro-uPA treated cells. Neither expression of endogenous IFNs nor activation of the IFN-inducible Janus kinase/signal transducer and activator of transcription pathway were induced by pro-uPA. Pro-uPA also inhibited acute HIV replication in monocyte-derived macrophages and activated peripheral blood mononuclear cells, although with great inter-donor variability. However, pro-uPA inhibited HIV replication in acutely infected promonocytic U937 cells and inex vivocultures of lymphoid tissue infectedin vitro. Because these effects occurred at concentrations substantially lower than those affecting thrombolysis, pro-uPA may represent a previously uncharacterized class of antiviral agents mimicking IFNs in their inhibitory effects on HIV expression and replication.
The genome-wide expression response to telomerase deletion in
Saccharomyces
cerevisiae
Authors: Nautiyal Shivani , DeRisi Joseph L. , Blackburn Elizabeth H.
Published: July 2002

Loss of the protective function of telomeres has previously been hypothesized to cause a DNA damage response. Here, we report a genome-wide expression response, the telomerase deletion response (TDR), that occurs when telomeres can no longer be maintained by telomerase. The TDR shares features with other DNA damage responses and the environmental stress response. Unexpectedly, another feature of the TDR is the up-regulation of energy production genes, accompanied by a proliferation of mitochondria. Finally, a discrete set of genes, the “telomerase deletion signature”, is uniquely up-regulated in the TDR but not under other conditions of stress and DNA damage that have been reported. The telomerase deletion signature genes define new candidates for involvement in cellular responses to altered telomere structure or function.
Rig is a novel Ras-related protein and potential neural tumor suppressor
Authors: Ellis Chad A. , Vos Michele D. , Howell Heather , Vallecorsa Teresa , Fults Daniel W. , Clark Geoffrey J.
Published: July 2002

The Ras superfamily consists of a large group of monomeric GTPases demonstrating homology to Ras oncoproteins. Although structurally similar, Ras-superfamily proteins are functionally diverse. Whereas some members exhibit oncogenic properties, others may serve as tumor suppressors. We have identified a novel Ras-related protein that suppresses cell growth and have designated it Rig (
R
as-related
i
nhibitor of cell
g
rowth). Overexpression of Rig inhibited Ras-mediated cellular transformation and activation of downstream signaling in NIH 3T3 cells.
rig
mRNA is expressed at high levels in normal cardiac and neural tissue. However, Rig protein expression is frequently lost or down-regulated in neural tumor-derived cell lines and primary human neural tumors. Moreover, expression of exogenous Rig in human astrocytoma cells suppressed growth. Rig has a C-terminal C
AAX
motif that codes for posttranslational modification by both farnesyl and geranylgeranyl isoprenoid lipids. Consequently, Rig may play a role in the cellular response to farnesyl transferase inhibitors. Rig bears 63% overall sequence homology to a recently described Ras-family member Noey2, a tumor suppressor in breast and ovarian tissue. Therefore, Rig and Noey2 may represent a new subfamily of Ras-like tumor suppressors.
Restricted islet-cell reactive T cell repertoire of early pancreatic islet infiltrates in NOD mice
Authors: Baker Felix J. , Lee Mark , Chien Yueh-hsiu , Davis Mark M.
Published: July 2002

The mechanisms responsible for initiating autoimmune diabetes remain obscure. Here, we describe a method for identifying both the α- and β-chains of the T cell receptor (TCR) from individual pancreatic islet-infiltrating T cells at the earliest stages of disease in nonobese diabetic mice (NOD). Analysis of the TCR repertoire of these early islet infiltrates reveals enrichment for a small subset of TCR sequences. Reconstitution of these TCRin vitrodemonstrates that these receptors confer reactivity to islet cells but not to the well characterized autoantigens, glutamic acid decarboxylase (GAD65) and insulin. Thus, autoimmune diabetes in NOD may be initiated by a limited number of antigens distinct from GAD65 and insulin.
Characterization of the expression of MHC proteins in human embryonic stem cells
Authors: Drukker Micha , Katz Gil , Urbach Achia , Schuldiner Maya , Markel Gal , Itskovitz-Eldor Joseph , Reubinoff Benjamin , Mandelboim Ofer , Benvenisty Nissim
Published: July 2002

Human embryonic stem (ES) cells are pluripotent cells that may be used in transplantation medicine. These cells can be induced to differentiate into cells from the three embryonic germ layers bothin vivoandin vitro. To determine whether human ES cells might be rejected after transplantation, we examined cell surface expression of the MHC proteins in these cells. Our results show very low expression levels of MHC class I (MHC-I) proteins on the surface of human ES cells that moderately increase onin vitroorin vivodifferentiation. A dramatic induction of MHC-I proteins was observed when the cells were treated with IFN-γ but not with IFN-α or -β. However, all three IFNs induced expression of MHC-I proteins in differentiated human ES cells. MHC-II proteins and HLA-G were not expressed on the surface of undifferentiated or differentiated cells. Ligands for natural killer cell receptors were either absent or expressed in very low levels in human ES cells and in their differentiated derivatives. In accordance, natural killer cytotoxic assays demonstrated only limited lysis of both undifferentiated and differentiated cells. To initiate a histocompatibility databank of human ES cells, we have isotyped several of the published ES cell lines for their human leukocyte antigens. In conclusion, our results demonstrate that human ES cells can express high levels of MHC-I proteins and thus may be rejected on transplantation.
Chimeric snRNA molecules carrying antisense sequences against the splice junctions of exon 51 of the dystrophin pre-mRNA induce exon skipping and restoration of a dystrophin synthesis in Δ48-50 DMD cells
Authors: De Angelis Fernanda Gabriella , Sthandier Olga , Berarducci Barbara , Toso Silvia , Galluzzi Giuliana , Ricci Enzo , Cossu Giulio , Bozzoni Irene
Published: July 2002

Deletions and point mutations in the dystrophin gene cause either the severe progressive myopathy Duchenne muscular dystrophy (DMD) or the milder Becker muscular dystrophy, depending on whether the translational reading frame is lost or maintained. Because internal in-frame deletions in the protein produce only mild myopathic symptoms, it should be possible, by preventing the inclusion of specific mutated exon(s) in the mature dystrophin mRNA, to restore a partially corrected phenotype. Such control has been previously accomplished by the use of synthetic oligonucleotides; nevertheless, a significant drawback to this approach is caused by the fact that oligonucleotides would require periodic administrations. To circumvent this problem, we have produced several constructs able to express
in vivo
, in a stable fashion, large amounts of chimeric RNAs containing antisense sequences. In this paper we show that antisense molecules against exon 51 splice junctions are able to direct skipping of this exon in the human DMD deletion 48–50 and to rescue dystrophin synthesis. We also show that the highest skipping activity was found when antisense constructs against the 5′ and 3′ splice sites are coexpressed in the same cell.
Modulating influence on HIV/AIDS by interactingRANTESgene variants
Authors: An Ping , Nelson George W. , Wang Lihua , Donfield Sharyne , Goedert James J. , Phair John , Vlahov David , Buchbinder Susan , Farrar William L. , Modi William , O'Brien Stephen J. , Winkler Cheryl A.
Published: July 2002

RANTES (regulated on activation normal T cell expressed and secreted), a ligand for the CC chemokine receptor 5, potently inhibits HIV-1 replicationin vitro. We tested the influence of fourRANTESsingle nucleotide polymorphism (SNP) variants and their haplotypes on HIV-1 infection and AIDS progression in five AIDS cohorts. Three SNPs in theRANTESgene region on chromosome 17 (403Ain the promoter,In1.1Cin the first intron, and3′222Cin the 3′ untranslated region) are associated with increased frequency of HIV-1 infection. The commonIn1.1CSNP allele is nested within an intronic regulatory sequence element that exhibits differential allele binding to nuclear proteins and a down-regulation of gene transcription. TheIn1.1Callele or haplotypes that includeIn1.1Cdisplay a strong dominant association with rapid progression to AIDS among HIV-1-infected individuals in African-American, European-American, and combined cohorts. The principalRANTESSNP genetic influence on AIDS progression derives from the down-regulatingRANTES In1.1Callele, although linkage disequilibrium with adjoiningRANTESSNPs including a weaker up-regulatingRANTESpromoter allele (−28G), can modify the observed epidemiological patterns. TheIn1.1C-bearing genotypes account for 37% of the attributable risk for rapid progression among African Americans and may also be an important influence on AIDS progression in Africa. The diminished transcription ofRANTESafforded by theIn1.1Cregulatory allele is consistent with increased HIV-1 spreadin vivo, leading to accelerated progression to AIDS.
The protofilament structure of insulin amyloid fibrils
Authors: Jiménez José L. , Nettleton Ewan J. , Bouchard Mario , Robinson Carol V. , Dobson Christopher M. , Saibil Helen R.
Published: July 2002

Under solution conditions where the native state is destabilized, the largely helical polypeptide hormone insulin readily aggregates to form amyloid fibrils with a characteristic cross-β structure. However, there is a lack of information relating the 4.8 Å β-strand repeat to the higher order assembly of amyloid fibrils. We have used cryo-electron microscopy (EM), combining single particle analysis and helical reconstruction, to characterize these fibrils and to study the three-dimensional (3D) arrangement of their component protofilaments. Low-resolution 3D structures of fibrils containing 2, 4, and 6 protofilaments reveal a characteristic, compact shape of the insulin protofilament. Considerations of protofilament packing indicate that the cross-β ribbon is composed of relatively flat β-sheets rather than being the highly twisted, β-coil structure previously suggested by analysis of globular protein folds. Comparison of the various fibril structures suggests that very small, local changes in β-sheet twist are important in establishing the long-range coiling of the protofilaments into fibrils of diverse morphology.