bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamical control of light propagation in nonlinear photonic crystals by applied electric fields
Authors: Xie Ping , Zhang Zhao-Qing
Published: January 2004

We propose that, by applying an electric field to a Kerr nonlinear photonic crystal, we can tune its photonic band gap and dynamically control the light propagation. The method is efficient and easy to implement in practice. The transmission behavior of the light caused by nonlinear effects induced by both the external electric field and the light is numerically studied in detail in a one-dimensional superlattice. The dynamical control of light propagation can also be made possible in a Pockels photonic crystal by applying an electric field.
Effect of uniaxial stress on the large-signal electromechanical properties of electrostrictive and piezoelectric lead magnesium niobate lead titanate ceramics
Authors: Viehland D. , Li Jie-Fang , McLaughlin E. , Powers J. , Janus R. , Robinson H.
Published: January 2004

The electromechanical performance characteristics of electrostrictive 0.9 Pb(Mg1/3Nb2/3)O3–0.1 PbTiO3 and piezoelectric 0.7 Pb(Mg1/3Nb2/3)O3–0.3 PbTiO3 ceramics have been investigated under uniaxial stress (σ). The results demonstrate that the large-signal electromechanical properties of electrostrictive ceramics are decreased with increasing σ, whereas those of the piezoelectric are increased but accompanied by significantly increased hysteretic losses.
Discharge efficiency in high-Xe-content plasma display panels
Authors: Hayashi Daiyu , Heusler Gero , Hagelaar Gerjan , Kroesen Gerrit
Published: January 2004

We study theoretically the overall output performance and the dominating reaction processes of the vacuum ultraviolet (UV) radiation production in high-Xe partial pressures in plasma display panels (PDPs) with Ne–Xe gas mixtures. A two-dimensional self-consistent fluid model is applied for the simulations of discharges and UV radiation in sustaining phases of PDPs. The UV intensity increases with the Xe partial pressure (PXe). The discharge efficiency also increases with PXe. The resonant radiation from Xe(3P1) dominates for 3.5%, while that from Xe2(3Σu+) becomes dominant over Xe(3P1) for 10%–30%. Remarkably for 30%, the intensity from Xe2(1Σu+) is even larger than that from Xe(3P1). It is found that for higher PXe, the UV radiation mainly consists of the excimer radiation from Xe2(1Σu+) and Xe2(3Σu+). Here, Xe(3P1) does not play a role itself as the UV radiator of the resonant radiation (147 nm), but as the precursor to Xe2(1Σu+), which results in the excimer radiation (173 nm).
Thermoelectric properties of binary Cd-Yb quasicrystals and Cd6Yb
Authors: Kuo Y. K. , Lai J. R. , Huang C. H. , Ku W. C. , Lue C. S. , Lin S. T.
Published: January 2004

The thermoelectric properties, including electrical resistivity (ρ), Seebeck coefficient (S), and thermal conductivity (κ) on binary icosahedral Cd-Yb quasicrystals and Cd6Yb are investigated. The Cd-Yb quasicrystals have a room-temperature (RT) resistivity value of about 200 (μΩ cm), however, the temperature-dependent resistivity is sensitive to a small composition change in these compounds. For all studied samples, Seebeck coefficients are positive and small (∼10 μV/K at RT). Upon cooling, S decreases quasilinearly, indicative of a metallic diffusion behavior, and then develops a broad phonon drag peak at around 40 K. The temperature characteristic of thermal conductivity κ of Cd-Yb quasicrystals shows a most peculiar feature in all measured thermoelectric properties. The RT κ value ∼6 (W/m K) of Cd-Yb quasicrystals is considerably larger than that of conventional ternary counterparts. Such an observation is attributed to the substantial electrical contribution κe (∼50%) to their total thermal conductivity, as deduced from the Wiedemann–Franz’s law, and larger lattice thermal conductivity κP due to less chemical disorder present in the binary Cd-Yb quasicrystalline structure. In addition κ decreases with decreasing temperature and shows a distinct maximum, a broad maximum, or a plateau at low temperatures, depending on the sample composition. The dimensionless thermoelectric figure of merit (ZT) for Cd-Yb quasicrystals is estimated to be small, on the order of 0.005 at RT.
Characteristics of multimode combined intense laser-induced electron acceleration and violent bunch compression
Authors: Huang Sh. J. , Tang Ch. X. , Wang P. X.
Published: January 2004

The interaction of low energy electrons with multimode combined intense laser beams in vacuum was studied by using three-dimensional test particle simulation. The process of interaction and the ponderomotive potential structures of some multimode combined intense laser beams are analyzed in detail. This article presents the detailed characteristics of the multimode combined intense laser-induced electron acceleration and violent bunch compression [Wang et al., Appl. Phys. Lett. 82, 2752 (2003)]. The properties of the output electron bunch are also investigated.
Structural and spectroscopic properties of rare-earth (Nd3+, Er3+, and Yb3+) doped transparent lead lanthanum zirconate titanate ceramics
Authors: de Camargo Andrea S. S. , de O. Nunes Luiz Antonio , Santos Ivair A. , Garcia Ducinei , Eiras José Antonio
Published: January 2004

This work presents the structural and spectroscopic characterization of transparent lead lanthanum zirconate titanate ceramics doped with Nd3+, Er3+, or Yb3+ ions. High optical quality samples presenting the perovskite structure were prepared through a mixed oxides method followed by conventional sintering or uniaxial hot pressing. Absorption and luminescence spectra were measured, and radiative emission parameters were calculated for Nd3+- and Er3+-doped samples. The results indicate the potential of these polycrystalline host–ion combinations for the construction of diode-pumped lasers in the near-infrared region.
Mechanical and thermal stresses in multilayered materials
Authors: Malzbender Jürgen
Published: January 2004

A general solution for elastic deformation of monolithic and multilayered materials due to external loads and moments, mismatch in thermal expansion, and temperature gradients is derived. Special consideration is given to materials with stress dependent stiffness or gradient in elastic modulus. The relationships can be used to determine the stiffness, thickness, thermal expansion coefficient, or thermal gradient. The fracture of a monolithic material with stress dependent stiffness and the temperature dependence of the elastic modulus and thickness are considered as well as the possibility to use the change in curvature in the case of delamination to determine the fracture energy.
Magnetic refrigeration: Single and multimaterial active magnetic regenerator experiments
Authors: Richard M.-A. , Rowe A. M. , Chahine R.
Published: January 2004

An investigation of active magnetic regenerators (AMRs) has been performed near room temperature using helium as a heat transfer fluid and a magnetic field of 2 T. To evaluate the impact of the operating conditions, the performance of two reciprocating 90 g gadolinium packed bed regenerators was mapped as a function of the fluid flux and cycle frequency. In addition, two multilayer regenerators of similar mass and dimensions, composed of a layer of gadolinium and a layer of a gadolinium–terbium alloy, were tested and compared to the performance of the Gd-only regenerators. The multilayer regenerators produced a larger temperature span and cooling power compared to the single material regenerators of equivalent mass and geometry (temperature spans of about 20 and 16 K, respectively). Theses results validate the concept of a multilayer AMR, provide useful data for magnetic refrigerator design, and provide better understanding of active magnetic refrigeration.
Ternary TiAlGe ohmic contacts for p-type 4H-SiC
Authors: Sakai T. , Nitta K. , Tsukimoto S. , Moriyama M. , Murakami Masanori
Published: January 2004

Reduction of annealing temperature to prepare low resistance ohmic contact materials for p-type 4H-SiC was achieved by adding Ge to the conventional TiAl contacts. Although the binary TiAl contact is required to anneal at temperature as high as 1000 °C to convert Schottky to ohmic behavior after deposition of the Ti and Al layers on the SiC substrate, the GeTiAl contacts provided the specific contact resistance of about 1×10−4 Ω cm2 by annealing at temperature as low as 600 °C. This low annealing temperature is desirable to reduce the gate leakage current of the SiC devices. The GeTiAl ohmic contacts were thermally stable during isothermal annealing at 400 °C subsequently after preparing the ohmic contacts by annealing at 600 °C, which is also required by the device packaging process.
Glass-forming ability and crystallization behavior of Ti–Cu–Ni–Sn–M (M=Zr, Mo, and Ta) metallic glasses
Authors: He G. , Eckert J. , Hagiwara M.
Published: January 2004

The kinetics of the glass transition and the crystallization behavior of Ti–Cu–Ni–Sn–M (M=Zr,Mo,Ta) glassy alloys were investigated by differential scanning calorimetry and x-ray diffraction. The glass-forming ability (GFA) of the glasses was analyzed in terms of the fragility concept and the width of the supercooled liquid region. The Ti-base glasses studied were found to have lower GFA than Zr, Pd, La, Fe, Mg-base bulk metallic glasses (BMGs), but to be comparative GFA to Ni- and Au-base BMGs. Higher Mo content or higher Ti–Ta content in the alloys lowers the GFA. The chemical complexity and multiphase crystallization requiring long-range atomic diffusion may contribute to the thermal stability of the supercooled liquid against crystallization. The products of crystallization of the glasses include bcc β-Ti(M) solid solution and Ti2Ni and Ti2Cu intermetallics.
Electron paramagnetic resonance parameters of Co2+ in GaP, InP, and GaAs semiconductors
Authors: Zheng Wen-Chen , Wu Shao-Yi , Tang Sheng , Zi Jian
Published: January 2004

High-order perturbation formulas for the electron paramagnetic resonance g factor for a 3d7 ion in cubic tetrahedral MX4 clusters are established from a cluster approach. In the formulas, not only the conventional contribution from the crystal-field (CF) mechanism, but also the contribution from charge-transfer (CT) (which is often omitted) are considered. Based on the formulas, the g-shifts Δg (=g−gs, where gs=2.0023) of Co2+ ions in III–V semiconductors GaP, InP, and GaAs are reasonably explained. It is found that the relative importance of the CT mechanism (characterized by ΔgCT/ΔgCF) increases with increasing covalency and hence with increasing atomic number of the ligand. Therefore, for 3dn ions in a strongly covalent crystal, the contributions to the g factor from both CF and CT mechanisms should be taken into account.
Dielectric loss study of oxygen vacancies and domain walls in Sr2Bi4−x/3Ti5−xVxO18 ceramics
Authors: Lu Wang-ping , Mao Xiang-yu , Chen Xiao-bing
Published: January 2004

An investigation on the ferroelectric and dielectric properties of vanadium-doped Sr2Bi4Ti5O18 ceramics was presented. The ferroelectricity of Sr2Bi4−x/3Ti5−xVxO18 samples (x=0, 0.003, 0.0048, 0.018, 0.048, and 0.096) was obviously improved by vanadium doping. The dielectric property measurement indicated that the Curie temperature was unaffected by vanadium doping, while it displayed a strong dependence of their dielectric loss on vanadium content. One dielectric loss peak around 230 °C related to oxygen vacancies was reduced with doping. Another peak which was just a few degrees below the Curie point and ascribed to viscous motion of domain walls declined drastically with the increase of vanadium content. Those results suggested that the substitution of a small amount of V5+ for Ti4+ reduced the concentration of oxygen vacancies significantly under the restriction of charge neutrality. This led to the weakening of domain pinning and the increasing of the mobility of domain walls, which would be responsible for the increase in 2Pr.
Comment on “Growth kinetics of oxides during furnace oxidation of silicon in N2O ambient” [J. Appl. Phys. 78, 2767 (1995)]
Authors: Morales-Acevedo Arturo
Published: January 2004

Bhat, Jia, and Kwong [J. Appl. Phys. 78, 2767 (1995)] proposed a model for explaining the growth kinetics of oxides obtained during thermal oxidation of silicon in N2O. They claimed that they were able to explain the growth rate for different temperatures and the nitrogen content within the silicon oxynitride. We show that Bhat’s model was erroneous, both in the proposal of the corresponding differential equations, and also in their solution. Therefore, all their analysis should be modified so that values for the diffusivities and reaction rates of oxygen and NO through the Si oxynitride can be determined by means of a correct model.
Structure and growth of metal on NiO(111) single crystal interfaces
Authors: Mocuta C. , Barbier A. , Renaud G. , Panabière M. , Bayle-Guillemaud P.
Published: January 2004

The structure, thermal stability, interfacial chemical composition, and growth parameters, derived from in situ grazing incidence x-ray diffraction (GIXD) and grazing incidence small angle x-ray scattering, ex situ atomic force microscopy, and transmission electron microscopy, of three ferromagnetic/antiferromagnetic metal/oxide interfaces [Co, Ni81Fe19 (permalloy) and Co70Fe30 on single crystalline NiO(111)] are reported. The samples were prepared in the 300–770 K temperature and 0–200 Å thickness ranges. The important role of Fe in the composition and creation of the interfacial compounds as well as in the film flatness is discussed. The strong influence of the NiO(111) single crystal in determining the crystalline structure of the metal layers is evidenced. The limitations of GIXD in the description of the growth morphology were investigated in detail and are discussed with respect to the substrate crystalline quality.
On a sheath between a plasma and a conducting surface
Authors: Alterkop B.
Published: January 2004

The influence of plasma inertia and temperature and wall polarity on the formation of a stationary charged sheath between the plasma and a conducting wall was considered. A criterion for stationary sheath existence for both negative and positive wall polarities was formulated and applied to several special cases. It was shown, in particular, that a sheath is not formed in a two-beam plasma with cold electrons and cold or warm supersonic ions. The formation of a discontinuity-like a shock wave at a thermal singularity was analyzed. Consideration of special cases showed that conditions for the steady sheath are compatible with the condition for shock wave formation (supersonic ions) only in the case of positive wall potential, hot electrons and warm ions, moving to the wall with velocity greater then the ion-sound velocity. The determined maximum wall positive potential at which no discontinuity forms is φc=[ZTe−Ti ln(1+(ZTe/Ti))]/2Ze, where Te is the electron temperature, and Ti and Ze are the ion temperature and charge.
A functional cellulose synthase from ascidian epidermis
Authors: Matthysse Ann G. , Deschet Karine , Williams Melanie , Marry Mazz , White Alan R. , Smith William C.
Published: January 2004

Among animals, urochordates (e.g., ascidians) are unique in their ability to biosynthesize cellulose. In ascidians cellulose is synthesized in the epidermis and incorporated into a protective coat know as the tunic. A putative cellulose synthase-like gene was first identified in the genome sequences of the ascidian
Ciona intestinalis
. We describe here a cellulose synthase gene from the ascidian
Ciona savignyi
that is expressed in the epidermis. The predicted
C. savignyi
cellulose synthase amino acid sequence showed conserved features found in all cellulose synthases, including plants, but was most similar to cellulose synthases from bacteria, fungi, and
Dictyostelium discoidium
. However, unlike other known cellulose synthases, the predicted
C. savignyi
polypeptide has a degenerate cellulase-like region near the carboxyl-terminal end. An expression construct carrying the
C. savignyi
cDNA was found to restore cellulose biosynthesis to a cellulose synthase (
CelA
) minus mutant of
Agrobacterium tumefaciens
, showing that the predicted protein has cellulose synthase activity. The lack of cellulose biosynthesis in all other groups of metazoans and the similarity of the
C. savignyi
cellulose synthase to enzymes from cellulose-producing organisms support the hypothesis that the urochordates acquired the cellulose biosynthetic pathway by horizontal transfer.
Molecular basis for the inhibition of G protein-coupled inward rectifier K+channels by protein kinase C
Authors: Mao Jinzhe , Wang Xueren , Chen Fuxue , Wang Runping , Rojas Asheebo , Shi Yun , Piao Hailan , Jiang Chun
Published: January 2004

G protein-coupled inward rectifier K+(GIRK) channels regulate cellular excitability and neurotransmission. The GIRK channels are activated by a number of inhibitory neurotransmitters through the G protein βγ subunit (Gβγ) after activation of G protein-coupled receptors and inhibited by several excitatory neurotransmitters through activation of phospholipase C. If the inhibition is produced by PKC, there should be PKC phosphorylation sites in GIRK channel proteins. To identify the PKC phosphorylation sites, we performed systematic mutagenesis analysis on GIRK4 and GIRK1 subunits expressed inXenopusoocytes. Our data showed that the heteromeric GIRK1/GIRK4 channels were inhibited by a PKC activator phorbol 12-myristate 13-acetate (PMA) through reduction of single channel open-state probability. Direct application of the catalytic subunit of PKC to excised patches had a similar inhibitory effect. This inhibition was greatly eliminated by mutation of Ser-185 in GIRK1 and Ser-191 in GIRK4 that remained G protein sensitive. The PKC-dependent phosphorylation seems to mediate the channel inhibition by the excitatory neurotransmitter substance P (SP) as specific PKC inhibitors and mutation of these PKC phosphorylation sites abolished the SP-induced inhibition of GIRK1/GIRK4 channels. Thus, these results indicate that the PKC-dependent phosphorylation underscores the inhibition of GIRK channels by SP, and Ser-185 in GIRK1 and Ser-191 in GIRK4 are the PKC phosphorylation sites.
Calcium influx through hyperpolarization-activated cation channels (
I
h
channels) contributes to activity-evoked neuronal secretion
Authors: Yu Xiao , Duan Kai-Lai , Shang Chun-Feng , Yu Han-Gang , Zhou Zhuan
Published: January 2004

The hyperpolarization-activated cation channels (
I
h
) play a distinct role in rhythmic activities in a variety of tissues, including neurons and cardiac cells. In the present study, we investigated whether Ca
2+
can permeate through the hyperpolarization-activated pacemaker channels (HCN) expressed in HEK293 cells and
I
h
channels in dorsal root ganglion (DRG) neurons. Using combined measurements of whole-cell currents and fura-2 Ca
2+
imaging, we found that there is a Ca
2+
influx in proportion to
I
h
induced by hyperpolarization in HEK293 cells. The
I
h
channel blockers Cs
+
and ZD7288 inhibit both HCN current and Ca
2+
influx. Measurements of the fractional Ca
2+
current showed that it constitutes 0.60 ± 0.02% of the net inward current through HCN4 at –120 mV. This fractional current is similar to that of the low Ca
2+
-permeable AMPA-R (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor) channels in Purkinje neurons. In DRG neurons, activation of
I
h
for 30 s also resulted in a Ca
2+
influx and an elevated action potential-induced secretion, as assayed by the increase in membrane capacitance. These results suggest a functional significance for
I
h
channels in modulating neuronal secretion by permitting Ca
2+
influx at negative membrane potentials.
Vertebrate ultraviolet visual pigments: Protonation of the retinylidene Schiff base and a counterion switch during photoactivation
Authors: Kusnetzow Ana Karin , Dukkipati Abhiram , Babu Kunnel R. , Ramos Lavoisier , Knox Barry E. , Birge Robert R.
Published: January 2004

For visual pigments, a covalent bond between the ligand (11-
cis
-retinal) and receptor (opsin) is crucial to spectral tuning and photoactivation. All photoreceptors have retinal bound via a Schiff base (SB) linkage, but only UV-sensitive cone pigments have this moiety
unprotonated
in the dark. We investigated the dynamics of mouse UV (MUV) photoactivation, focusing on SB protonation and the functional role of a highly conserved acidic residue (E108) in the third transmembrane helix. On illumination, wild-type MUV undergoes a series of conformational changes,
batho
→
lumi
→
meta I
, finally forming the active intermediate
meta II
. During the dark reactions, the SB becomes protonated transiently. In contrast, the MUV-E108Q mutant formed significantly less
batho
that did not decay through a protonated
lumi
. Rather, a transition to
meta I
occurred above ≈240 K, with a remarkable red shift (λ
max
≈ 520 nm) accompanying SB protonation. The MUV-E108Q
meta I
→
meta II
transition appeared normal but the MUV-E108Q
meta II
decay to opsin and free retinal was dramatically delayed, resulting in increased transducin activation. These results suggest that there are two proton donors during the activation of UV pigments, the primary counterion E108 necessary for protonation of the SB during
lumi
formation and a second one necessary for protonation of
meta I
. Inactivation of
meta II
in SWS1 cone pigments is regulated by the primary counterion. Computational studies suggest that UV pigments adopt a switch to a more distant counterion, E176, during the
lumi
to
meta I
transition. The findings with MUV are in close analogy to rhodopsin and provides further support for the importance of the counterion switch in the photoactivation of both rod and cone visual pigments.
Ly49Q, a member of the Ly49 family that is selectively expressed on myeloid lineage cells and involved in regulation of cytoskeletal architecture
Authors: Toyama-Sorimachi Noriko , Tsujimura Yusuke , Maruya Mikako , Onoda Atsuko , Kubota Toshiyuki , Koyasu Shigeo , Inaba Kayo , Karasuyama Hajime
Published: January 2004

Here, we identified and characterized a Ly49 family member, designated as Ly49Q. TheLy49qgene encodes a 273-aa protein with an immunoreceptor tyrosine-based inhibitory motif (ITIM) at the N terminus of its cytoplasmic domain. We show that the ITIM of Ly49Q can recruit SHP-2 and SHP-1 in a tyrosine phosphorylation-dependent manner. In contrast to other known members of the Ly49 family, Ly49Q was found not to be expressed on NK1.1+cells, but instead was detectable on virtually all Gr-1+cells, such as myeloid precursors in bone marrow. Monocytes/macrophages also expressed low levels of Ly49Q, and the expression was enhanced by the treatment of cells with IFN-γ. Treatment of activated macrophages with anti-Ly49Q mAb induced rapid formation of polarized actin structures, showing filopodia-like structure on one side and lamellipodial-like structure on the other side. A panel of proteins became tyrosine-phosphorylated in myeloid cells when treated with the mAb. Induction of the phosphorylation depends on the ITIM of Ly49Q. Thus, Ly49Q has unique features different from other known Ly49 family members and appears to be involved in regulation of cytoskeletal architecture of macrophages through ITIM-mediated signaling.
Increased soluble amyloid-β peptide and memory deficits in amyloid model mice overexpressing the low-density lipoprotein receptor-related protein
Authors: Zerbinatti Celina V. , Wozniak David F. , Cirrito John , Cam Judy A. , Osaka Hiroshi , Bales Kelly R. , Zhuo Min , Paul Steven M. , Holtzman David M. , Bu Guojun
Published: January 2004

Amyloid-β peptide (Aβ) is central to the pathogenesis of Alzheimer's disease, and the low-density lipoprotein receptor-related protein (LRP) has been shown to alter Aβ metabolism
in vitro
. Here, we show that overexpression of a functional LRP minireceptor in the brain of PDAPP mice results in age-dependent increase of soluble brain Aβ, with no changes in Aβ plaque burden. Importantly, soluble brain Aβ was found to be primarily in the form of monomers/dimers and to be highly correlated with deficits in spatial learning and memory. These results provide
in vivo
evidence that LRP may contribute to memory deficits typical of Alzheimer's disease by modulating the pool of small soluble forms of Aβ.
T cell repertoire scanning is promoted by dynamic dendritic cell behavior and random T cell motility in the lymph node
Authors: Miller Mark J. , Hejazi Arsalan S. , Wei Sindy H. , Cahalan Michael D. , Parker Ian
Published: January 2004

Dendritic cells (DCs) ingest antigens in peripheral tissues and migrate to lymph nodes where they present MHC class II-bound antigen to CD4
+
T cells. We used two-photon microscopy to image the single-cell dynamics of interactions between DCs and T cells within intact lymph nodes in the absence of relevant antigen. DCs were fluorescently labeled
in vivo
by cutaneous injection of alum adjuvant including carboxyfluorescein diacetate succinimidyl ester (CFSE). CFSE-positive DCs (CD11c
+
, CD11b
+
, and low-to-intermediate CD8
+
) were observed in draining lymph nodes 24–72 h later. Labeled DCs meandered slowly (2–3 μm·min
–1
) in the T cell zone near B cell follicles but vigorously extended long agile dendrites. Encounters between T cells and DCs arose as T cells moved autonomously along random paths. Moreover, T cells did not accumulate around DCs, and their relative velocities approaching and departing DCs were equivalent, implying that T cells are not attracted toward DCs by chemotactic gradients but rather encounter them by chance. T cell/DC contacts occurred primarily on dendrites at arm's length from the DC soma and typically lasted ≈3 min, enabling an individual DC to interact with up to 5,000 T cells per hour. We conclude that dynamic DC gesticulation and random T cell motility together enhance the stochastic scanning of the T cell repertoire, thereby enabling rapid initiation of the immune response.
A serine protease zymogen functions as a pattern-recognition receptor for lipopolysaccharides
Authors: Ariki Shigeru , Koori Kumiko , Osaki Tsukasa , Motoyama Kiyohito , Inamori Kei-ichiro , Kawabata Shun-ichiro
Published: January 2004

Bacterial lipopolysaccharide (LPS)-induced exocytosis of granular hemocytes is a key component of the horseshoe crab's innate immunity to infectious microorganisms; stimulation by LPS induces the secretion of various defense molecules from the granular hemocytes. Using a previously uncharacterized assay for exocytosis, we clearly show that hemocytes respond only to LPS and not to other pathogen-associated molecular patterns, such as β-1,3-glucans and peptidoglycans. Furthermore, we show that a granular protein called factor C, an LPS-recognizing serine protease zymogen that initiates the hemolymph coagulation cascade, also exists on the hemocyte surface as a biosensor for LPS. Our data demonstrate that the proteolytic activity of factor C is both necessary and sufficient to trigger exocytosis through a heterotrimeric GTP-binding protein-mediating signaling pathway. Exocytosis of hemocytes was not induced by thrombin, but it was induced by hexapeptides corresponding to the tethered ligands of protease-activated G protein-coupled receptors (PARs). This finding suggested the presence of a PAR-like receptor on the hemocyte surface. We conclude that the serine protease zymogen on the hemocyte surface functions as a pattern-recognition protein for LPS.
Selection of B lymphocytes in the periphery is determined by the functional capacity of the B cell antigen receptor
Authors: Wang Leo D. , Lopes Jared , Cooper A. Byron , Dang-Lawson May , Matsuuchi Linda , Clark Marcus R.
Published: January 2004

Within the B cell antigen receptor (BCR), the cytoplasmic tails of both Igα and Igβ are required for normal B cell development and maturation. To dissect the mechanisms by which each tail contributes to developmentin vivo, Igβ–/–mice were reconstituted with retroviruses encoding either wild-type Igβ, an Igβ molecule lacking a cytoplasmic tail (IgβΔC) or one in which the cytoplasmic tail was derived from Igα (IgβCα). All constructs rescued B cell development and generated immature B cell populations in the bone marrow with similar expression levels of both Igβ and membrane-bound IgM. In the periphery, receptor-surface density was inversely proportional to the number of Igα tails in the BCR. Although peripheral-surface-receptor levels differed, splenic B cells expressing either Igβ or IgβCαresponded similarly to stimulation through the BCR. Analysis of membrane-bound IgM and Igβ expression revealed that peripheral-receptor expression was primarily determined by positive selection between the bone marrow and peripheral immature B cell populations. These data indicate that B cells are selected into the periphery on the basis of a common level of antigen responsiveness.
Paired-pulse depression of unitary quantal amplitude at single hippocampal synapses
Authors: Chen Gong , Harata Nobutoshi C. , Tsien Richard W.
Published: January 2004

At central synapses, quantal size is generally regarded as fluctuating around a fixed mean with little change during short-term synaptic plasticity. We evoked quantal release by brief electric stimulation at single synapses visualized with FM 1–43 dye in hippocampal cultures. The majority of quantal events evoked at single synapses were monovesicular, based on examination of amplitude distribution of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-receptor-mediated responses. Consistent with previous findings, the quantal size did not change during paired-pulse facilitation (PPF), supporting the notion that the evoked events were monoquantal. However, during paired-pulse depression (PPD), there was a significant decrease in unitary quantal size, which was not due to postsynaptic receptor desensitization. This asymmetry of quantal modulation during PPF and PPD was demonstrated at the same single synapse at different extracellular calcium concentrations. Our results indicate that PPF can be fully accounted for by an increase of release probability, whereas PPD may be caused by decreases in both release probability and quantal size. One possible explanation is that the release of a quantum of neurotransmitter from synaptic vesicles is not invariant but subject to rapid calcium-dependent modulation during short-term synaptic plasticity.
The tethered configuration of the EGF receptor extracellular domain exerts only a limited control of receptor function
Authors: Mattoon Dawn , Klein Peter , Lemmon Mark A. , Lax Irit , Schlessinger Joseph
Published: January 2004

Quantitative epidermal growth factor (EGF)-binding experiments have shown that the EGF-receptor (EGFR) is displayed on the surface of intact cells in two forms, a minority of high-affinity and a majority of low-affinity EGFRs. On the basis of the three-dimensional structure of the extracellular ligand binding domain of the EGFR, it was proposed that the intramolecularly tethered and autoinhibited configuration corresponds to the low-affinity receptor, whereas the extended configuration accounts for the high-affinity EGFRs on intact cells. Here we test this model by analyzing the properties of EGFRs mutated in the specific regions responsible for receptor autoinhibition and dimerization, respectively. Our results show that mutagenic disruption of the autoinhibitory tether in EGFR results in a decrease in the dissociation rate of EGF without a detectable change in EGFR activation and signaling through EGFR even in response to stimulation with low concentrations of EGF. Mutagenic disruption of the dimerization arm, on the other hand, increased the rate of EGF dissociation and impaired EGFR activation and signaling via the EGFR. This study demonstrates that the extended configuration of EGFR does not account for the apparent high-affinity EGF-binding to EGFR on intact cells. Furthermore, the autoinhibition conferred by the tethered configuration of the extracellular ligand-binding domain provides only a limited control of EGFR function.
Insights into the molecular basis for fibroblast growth factor receptor autoinhibition and ligand-binding promiscuity
Authors: Olsen Shaun K. , Ibrahimi Omar A. , Raucci Angela , Zhang Fuming , Eliseenkova Anna V. , Yayon Avner , Basilico Claudio , Linhardt Robert J. , Schlessinger Joseph , Mohammadi Moosa
Published: January 2004

The prototypical fibroblast growth factor receptor (FGFR) extracellular domain consists of three Ig domains (D1–D3) of which the two membrane-proximal D2 and D3 domains and the interconnecting D2–D3 linker bear the determinants of ligand binding and specificity. In contrast, D1 and the D1–D2 linker are thought to play autoinhibitory roles in FGFR regulation. Here, we report the crystal structure of the three-Ig form of FGFR3c in complex with FGF1, an FGF that binds promiscuously to each of the seven principal FGFRs. In this structure, D1 and the D1–D2 linker are completely disordered, demonstrating that these regions are dispensable for FGF binding. Real-time binding experiments using surface plasmon resonance show that relative to two-Ig form, the three-Ig form of FGFR3c exhibits lower affinity for both FGF1 and heparin. Importantly, we demonstrate that this autoinhibition is mediated by intramolecular interactions of D1 and the D1–D2 linker with the minimal FGF and heparin-binding D2–D3 region. As in the FGF1–FGFR2c structure, but not the FGF1–FGFR1c structure, the alternatively spliced βC′–βE loop is ordered and interacts with FGF1 in the FGF1–FGFR3c structure. However, in contrast to the FGF1–FGFR2c structure in which the βC′–βE loop interacts with the β-trefoil core region of FGF1, in the FGF1–FGFR3c structure, this loop interacts extensively with the N-terminal region of FGF1, underscoring the importance of the FGF1 N terminus in conferring receptor-binding affinity and promiscuity. Importantly, comparison of the three FGF1–FGFR structures shows that the flexibility of the βC′–βE loop is a major determinant of ligand-binding specificity and promiscuity.
The presenilins turned inside out: Implications for their structures and functions
Authors: Dewji Nazneen N. , Valdez Dante , Singer S. J.
Published: January 2004

The presenilin (PS) proteins are polytopic integral membrane proteins that are critically involved in the development of Alzheimer's disease. The topography of the PS molecule in the endoplasmic reticulum membrane is widely accepted as exhibiting eight-hydrophobic-transmembrane (8-TM) helices. We have previously provided evidence, however, that the intact PS molecule is also present in the cell surface where it exhibits exclusively a 7-TM topography, which differs in significant structural features from the 8-TM model. This evidence, however, has been disparaged and generally rejected by researchers in Alzheimer's disease. The 7-TM model is definitively demonstrated in the present study for PS-1 at the surfaces of PS-1-transfected cells and for endogenous PS-1 at the surfaces of untransfected cells, by immunofluorescence studies using mAbs. These studies force substantial revision of current views of the structural and functional properties of the PS proteins.
Identifying gene regulatory elements by genome-wide recovery of DNase hypersensitive sites
Authors: Crawford Gregory E. , Holt Ingeborg E. , Mullikin James C. , Tai Denise ,   National Institutes of Health Intramural Sequencing Center‡, Green Eric D. , Wolfsberg Tyra G. , Collins Francis S.
Published: January 2004

Analysis of the human genome sequence has identified ≈25,000–30,000 protein-coding genes, but little is known about how most of these are regulated. Mapping DNase I hypersensitive (HS) sites has traditionally represented the gold-standard experimental method for identifying regulatory elements, but the labor-intensive nature of this technique has limited its application to only a small number of human genes. We have developed a protocol to generate a genome-wide library of gene regulatory sequences by cloning DNase HS sites. We generated a library of DNase HS sites from quiescent primary human CD4
+
T cells and analyzed ≈5,600 of the resulting clones. Compared to sequences from randomly generated
in silico
libraries, sequences from these clones were found to map more frequently to regions of the genome known to contain regulatory elements, such as regions upstream of genes, within CpG islands, and in sequences that align between mouse and human. These cloned sites also tend to map near genes that have detectable transcripts in CD4
+
T cells, demonstrating that transcriptionally active regions of the genome are being selected. Validation of putative regulatory elements was achieved by repeated recovery of the same sequence and real-time PCR. This cloning strategy, which can be scaled up and applied to any cell line or tissue, will be useful in identifying regulatory elements controlling global expression differences that delineate tissue types, stages of development, and disease susceptibility.
A subterranean mammal uses the magnetic compass for path integration
Authors: Kimchi Tali , Etienne Ariane S. , Terkel Joseph
Published: January 2004

Path integration allows animals to navigate without landmarks by continuously processing signals generated through locomotion. Insects such as bees and ants have evolved an accurate path integration system, assessing and coding rotations with the help of a general directional reference, the sun azimuth. In mammals, by contrast, this process can take place through purely idiothetic (mainly proprioceptive and vestibular) signals. However, without any stable external reference for measuring direction, path integration is highly affected by cumulative errors and thus has been considered so far as valid only for short-distance navigation. Here we show through two path integration experiments (homing and shortcut finding) that the blind mole rat assesses direction both through internal signals and by estimating its heading in relation to the earth's magnetic field. Further, it is shown that the greater the circumvolution and length of the traveled path, the more the animal relies on the geomagnetic field. This path integration system strongly reduces the accumulation of errors due to inaccuracies in the estimation of rotations and thus allows the mole rat to navigate efficiently in darkness, without the help of any landmark, over both short and long distances.
Germinal center-associated nuclear protein contributes to affinity maturation of B cell antigen receptor in T cell-dependent responses
Authors: Kuwahara Kazuhiko , Fujimura Satoru , Takahashi Yoshimasa , Nakagata Naomi , Takemori Toshitada , Aizawa Shinichi , Sakaguchi Nobuo
Published: January 2004

Acquired immunity depends on proliferation and differentiation of antigen (Ag)-specific B cells in germinal centers (GCs) of lymphoid follicles in response to T cell-dependent Ags. Here, we studied the function of GC-associated nuclear protein that is selectively up-regulated in GC-B cells. B cell-specificganp-deficient mice were compromised in affinity maturation of hapten-specific antibodies against T cell-dependent Ags with retarded development of GCs. B cell numbers and development, serum Ig levels, mitogen-induced B cell proliferationin vitro, and responses to T cell-independent Ag were nearly normal; however, the mutant B cells showed a decrease in anti-CD40-induced proliferation and an increased susceptibility to B cell apoptosisin vitroandin vivo. B cell-specificganp-deficient mice showed a decreased frequency of variable-region somatic mutations, especially of the high-affinity type (W33→ L) in the VH186.2 region against nitrophenyl-chicken gamma globulin, whereas the class switching was normal. We conclude that GC-associated nuclear protein is necessary for generation or maintenance of B cells with high-affinity B cell Ag receptors during the maturation in GCs.
Coregulator-dependent facilitation of chromatin occupancy by GATA-1
Authors: Pal Saumen , Cantor Alan B. , Johnson Kirby D. , Moran Tyler B. , Boyer Meghan E. , Orkin Stuart H. , Bresnick Emery H.
Published: January 2004

Coregulator recruitment by DNA-bound factors results in chromatin modification and protein-protein interactions, which regulate transcription. However, the mechanism by which the Friend of GATA (FOG) coregulator mediates GATA factor-dependent transcription is unknown. We showed previously that GATA-1 replaces GATA-2 at an upstream region of the
GATA
-
2
locus, and that this GATA switch represses
GATA
-
2
. Genetic complementation analysis in FOG-1-null hematopoietic precursors revealed that FOG-1 is not required for establishment or maintenance of the active
GATA
-
2
domain, but is critical for the GATA switch. Analysis of GATA factor binding to additional loci also revealed FOG-1-dependent GATA switches. Thus, FOG-1 facilitates chromatin occupancy by GATA-1 at sites bound by GATA-2. We propose that FOG-1 is a prototype of a new class of coregulators termed
c
hromatin
o
ccupancy
f
acilitators, which confer coregulation in certain contexts via enhancing trans-acting factor binding to chromatin
in vivo
.
Complementation of phytochrome chromophore-deficient
Arabidopsis
by expression of phycocyanobilin:ferredoxin oxidoreductase
Authors: Kami Chitose , Mukougawa Keiko , Muramoto Takuya , Yokota Akiho , Shinomura Tomoko , Lagarias J. Clark , Kohchi Takayuki
Published: January 2004

The covalently bound phytochromobilin (PϕB) prosthetic group is required for the diverse photoregulatory activities of all members of the phytochrome family in vascular plants, whereas by contrast, green algal and cyanobacterial phytochromes use the more reduced linear tetrapyrrole pigment phycocyanobilin (PCB). To assess the functional consequence of the substitution of PϕB with PCB in plants, the phytochrome chromophore-deficient
hy2
mutant of
Arabidopsis
was transformed with a constitutively expressed
pcyA
gene that encodes the cyanobacterial enzyme, PCB:ferredoxin oxidoreductase. Spectroscopic analyses of extracts from etiolated seedlings revealed that PcyA expression restored photoactive phytochrome to WT levels, albeit with blue-shifted absorption maxima, while also restoring light lability to phytochrome A. Photobiological measurements indicated that PcyA expression rescued phytochrome-mediated red high-irradiance responses, low-fluence red/far-red (FR) photoreversible responses, and very-low-fluence responses, thus confirming that PCB can functionally substitute for PϕB for these photoregulatory activities. Although PcyA expression failed to rescue phytochrome A-mediated FR high-irradiance responsivity to that of WT, our studies indicate that the FR high-irradiance response is fully functional in
pcyA
-expressing plants but shifted to shorter wavelengths, indicating that PCB can functionally complement this phytochrome-mediated response in vascular plants.
Direct interactions between Epstein–Barr virus leader protein LP and the EBNA2 acidic domain underlie coordinate transcriptional regulation
Authors: Peng Chih-Wen , Xue Yong , Zhao Bo , Johannsen Eric , Kieff Elliott , Harada Shizuko
Published: January 2004

The Epstein–Barr virus nuclear leader protein LP (EBNALP) and EBNA2 are expressed first in lymphocyte infection, coordinately regulate cell and viral gene transcription, and are critical for lymphocyte outgrowth into lymphoblastoid cell lines (LCLs). We have now found that EBNALP readily associated with EBNA2 or with the EBNA2 C-terminal acidic activation domain (E2AD) when both components were expressed by bacteria. In lymphoblasts, EBNALP and EBNA2 did not stably associate. However, EBNALP deleted for only 10 C-terminal amino acids stably associated with EBNA2 in lymphoblasts or with EBNA2 acidic activating domain from bacteria. The E2AD was essential for EBNALP coactivation of the latent membrane protein 1 promoter in lymphoblasts; EBNALP could coactivate with a deficient mutant EBNA2, EBNA2W
454
T, but not with EBNA2 deleted for E2AD. Moreover, EBNALP 31 amino acids (dW2Y1) with 24 C- or N-terminal amino acids was a specific and efficient affinity matrix for EBNA2 or EBNALP. Even an EBNALP 22-aa peptide, dW2, specifically bound EBNALP or EBNA2. These biochemical interactions between EBNALP and EBNA2 enable coordinated transcriptional regulation of cell and viral gene expression in lymphoblasts only when the interaction is unstable; deletion of the EBNALP C-terminal 10 aa stabilized association with EBNA2 and prevented coactivation. Because EBNALPd10 dominantly inhibited EBNALP coactivation with EBNA2, EBNALPd10 expression in LCLs may be useful in assessing the role of EBNALP coactivation in LCL growth or survival.
Evidence for complex, collective dynamics and emergent, distributed computation in plants
Authors: Peak David , West Jevin D. , Messinger Susanna M. , Mott Keith A.
Published: January 2004

It has been suggested that some biological processes are equivalent to computation, but quantitative evidence for that view is weak. Plants must solve the problem of adjusting stomatal apertures to allow sufficient CO
2
uptake for photosynthesis while preventing excessive water loss. Under some conditions, stomatal apertures become synchronized into patches that exhibit richly complicated dynamics, similar to behaviors found in cellular automata that perform computational tasks. Using sequences of chlorophyll fluorescence images from leaves of
Xanthium strumarium
L. (cocklebur), we quantified spatial and temporal correlations in stomatal dynamics. Our values are statistically indistinguishable from those of the same correlations found in the dynamics of automata that compute. These results are consistent with the proposition that a plant solves its optimal gas exchange problem through an emergent, distributed computation performed by its leaves.
Lipid–protein interactions: Biosynthetic assembly of CD1 with lipids in the endoplasmic reticulum is evolutionarily conserved
Authors: Park Jang-June , Kang Suk-Jo , De Silva A. Dharshan , Stanic Aleksandar K. , Casorati Giulia , Hachey David L. , Cresswell Peter , Joyce Sebastian
Published: January 2004

The CD1 family consists of lipid antigen-presenting molecules, which include group I CD1a, CD1b, and CD1c and group II CD1d proteins. Topologically, they resemble the classical peptide antigen-presenting MHC molecules except that the large, exclusively nonpolar and hydrophobic, antigen-binding groove of CD1 has evolved to present cellular and pathogen-derived lipid antigens to specific T lymphocytes. As an approach to understanding the biochemical basis of lipid antigen presentation by CD1 molecules, we have characterized the natural ligands associated with mouse CD1d1 as well as human CD1b and CD1d molecules. We found that both group I and II CD1 molecules assemble with cellular phosphatidylinositol (PI), which contains heterogeneous fatty acyl chains. Further, this assembly occurs within the endoplasmic reticulum. Because the structures of the antigen-binding grooves of CD1a and CD1c closely resemble those of CD1b and CD1d, we conclude that the assembly of CD1 molecules with PI in the endoplasmic reticulum is evolutionarily conserved. These findings suggest that PI plays a chaperone-like role in CD1 assembly, possibly to preserve the integrity of the antigen-binding groove until CD1 binds antigenic lipids in the endocytic pathway.