Glassy dynamics in the adaptive immune response prevents autoimmune disease

The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self-antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely, gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system's search for antibodies, a balance has evolved between binding affinity and specificity.     

IMP321 (sLAG-3), an immunopotentiator for T cell responses against a HBsAg antigen in healthy adults: a single blind randomised controlled phase I study

Background  

LAG-3 (CD223) is a natural high affinity ligand for MHC class II. The soluble form (sLAG-3) induces maturation of monocyte-derived dendritic cells in vitro and is used as a potent Th1-like immune enhancer with many antigens in animal models. To extend this observation to human, a proof of concept study was conducted with a clinical-grade sLAG-3, termed IMP321, coinjected with alum-non-absorbed recombinant hepatitis B surface antigen.     

Sequence space localization in the immune system response to vaccination and disease

We introduce a model of protein evolution to explain limitations in the immune system response to vaccination and disease. The phenomenon of original antigenic sin, wherein vaccination creates memory sequences that can increase susceptibility to future exposures to the same disease, is explained as stemming from localization of the immune system response in antibody sequence space. This localization is a result of the roughness in sequence space of the evolved antibody affinity constant for antigen and is observed for diseases with high year-to-year mutation rates, such as influenza.     

Interaction of biological and nonbiological surfaces. New opportunities for research and technologies using synchrotron radiation

The applicability of synchrotron radiation to implementation of medical ideas associated with introduction of nonbiological objects into a human body—implants, drug nanocapsules, and X-ray therapeutic means (metal nanoparticles and nanocrystalline phosphors and scintillators)—is considered. Synchrotron radiation presents new possibilities of analyzing the surface with a resolution comparable to the sizes of biological nanostructures involved in interactions such as chemical and biochemical modification of implant surfaces in vitro; activation of implant surface integration with biological tissue in a tissue culture (in vitro) and in vivo; biochemical modification of therapeutic nanoparticle surface in vitro; immunocamouflage by host proteins; attachment of “molecular targets”, i.e., antibodies, to target tissue to provide targeted delivery vehicles; and local activation of X-ray therapeutic drugs and drug nanocapsules in biological tissues. A functional block diagram of a medical technological station is given.     

A new ultrasonic method to detect chemical additives in branded milk

A new ultrasonic method — thermoacoustic analysis — is reported for the detection of the added chemical preservatives in branded milk. The nature of variation and shift in the thermal response of the acoustic parameters specific acoustic impedance, adiabatic compressibility and Rao’s specific sound velocity for different samples of branded milk as compared to the chemical added pure milk are explained as due to the presence of chemicals in these branded samples.     

An alternative definition of the electron propagator in the superoperator form and its relation to linear response theory in a coupled-cluster framework

In this paper it is shown that (i) there exists an alternative definition of the superoperator resolvent for calculation of difference energy satisfying linked cluster theorem for a coupled-cluster choice of the ground-state function which may even be approximate; (ii) the pole-structure of this propagator-like function in superoperator form is shown to contain information similar to that contained in the conventional propagator. (iii) It is demonstrated that suitable “Killer conditions” and completeness of the “operator manifold”—essential for understanding the pole-structure of the propagator—can be established both for an exact and an approximate ground state function in a coupled-cluster form. (iv) It is also demonstrated that difference energies calculated with these propagator-like functions are identical to those obtained from a linear response theory in a coupled-cluster form put forward recently by Mukherjeeet al and Monkhorst.     

Generating neutralizing antibodies,Th1 response and MHC non restricted immunogenicity of HIV-I <Emphasis Type="Underline">env</Emphasis> and <Emphasis Type="Underline">gag</Emphasis>peptides in liposomes and ISCOMs with in-built adjuvanticity

For enhancing immunogenicity and develop vaccine strategies using peptide based constructs against HIV-1, a chimeric peptide containing V3 loop and transmembrane sequence of gp41 with two glycine motifs as spacer was constructed. The V3-gp41, gp41 peptide and p17 and p24 peptides separately or in a cocktail were entrapped with or without MA729 as an immunoadjuvant in liposomes or ISCOMs. The immunogenicity, antigen induced T-cell proliferation and cytokine profiles of various formulations were studied in four different inbred strains of mice of H-2^d, H-2^b, H-2^k and H-2^q haplotypes, keeping alum as a control adjuvant. Both liposomes and ISCOM preparations elicited high titer and long lasting antibody response (60 days and above). When compared to the alum formulation, the liposomes co-entrapped with MA729 produced high antibody levels, comparable with that induced by ISCOMs. Peptide in alum, liposomes and ISCOMs enhanced both antigen specific IgG2a and IgG2b isotypes and high T-cell stimulation index. Peptide formulations also induced antibodies with high affinity and in vitro neutralizated the formation of HIV-1 syncytia. T-cell supernatants contained high levels of IFN-γ and IL-2. Thus formulation in these adjuvants induced a predominant Th1 like response with MA729 as a versatile novel delivery vehicle for stimulating the appropriate arm of the immune response that can selectively modulate MHC class I or MHC class II response. The above peptide can be of wide vaccination interest as a means to improve immune responses to several other HIV-1 antigens and may serve as candidates for vaccine development.     

Transient response of an open resonator in the time domain

In the present paper a time response of a quasi-optical open resonator when exciting it by a pulse signal with a radiofrequency filling has been investigated using an inverse Fourier transformation. The radiofrequency filling corresponds to millimeter wavelengths region. Fourier image of the time response of the resonator is calculated from a product of two frequency’s functions. One of these functions is the Fourier image of a pulse signal at the resonator input, and the second is a calculated or measured amplitude — phase characteristic of the resonator. When calculating the amplitude- phase characteristic of the resonator (a complex transfer coefficient) a plane — layered model of the resonator was used. Experimental investigation has been conducted in millimeter wavelengths with Fabry-Perot type open resonator. Amplitude- phase characteristic of the resonator were measured in “on passage“ regime in wide frequency band. It was shown that presence of weakly absorbing layer in the resonator leads to changing of the time response of the resonator. The obtained results can be used in the dielectric measurements, defectoscopy of stratiform materials, relaxometry, non-destructive control of materials and structures, etc.     

Microscopic calculations of charge-exchange nuclear modes

Microscopic calculations of nuclear states excited by means of charge-exchange reactions and involving spin and isospin degrees of freedom, in particular, of the Gamow—Teller and the spin—dipole resonances, are discussed. The framework is a fully self-consistent nonrelativistic spherical quasiparticle random-phase approximation constructed on top of the Hartree—Fock—Bardeen—Cooper—Schrieffer approach. Our results are compared with available experimental data, and a critical discussion is attempted. The text was submitted by the authors in English.     

Glow-discharge-pumped broadband ultraviolet lamp

The optical characteristics of a UV broadband lamp that was excited by a longitudinal glow discharge and operated on Kr—Br₂—I₂, Xe—Br₂—I₂, and Kr—Xe—Br₂—I₂ mixtures are investigated. The interelectrode spacing in the lamp is 10 cm, the inner diameter of a discharge tube being 14 mm. The current-voltage characteristics, the emission spectra of the plasma, and the dependence of the intensity of spectral lines (the amplitude of radiation bands) on the power that was pumped into the plasma based on mixtures of various compositions and pressures, as well as the radiation power in the spectral range from 200 to 390 nm, are studied. __________ Translated from Zhurnal Prikladnoi Spektroskopii, Vol. 72, No. 6, pp. 840–842, November–December, 2005.     

Silver and gold nanoparticle coated membranes applied to protein dot blots

Detection and identification of low abundance biomarker proteins is frequently based on various types of membrane-based devices. Lowering of the protein detection limits is vital in commercial applications such as lateral flow assays and in Western blots widely used in proteomics. These currently suffer from insufficient detection sensitivity and low retention for small 2–5 kDa proteins. In this study, we report the deposition of two types of metal nanoparticles: gold colloids (50–95 nm diameter) and silver fractals onto a range of commonly used types of membranes including polyvinylidene fluoride (PVDF). Due to strong affinity of proteins to noble metals, such modified membranes have the potential to effectively capture trace proteins preventing their loss. The membranes modified by metal particles were characterized optically and by SEM. The membrane performance in protein dot blots was evaluated using the protein—fluorophore conjugates Deep Purple-bovine serum albumin and fluorescein—human serum albumin. We found that the metal nanoparticles increase light extinction by metals, which is balanced by increased fluorescence, so that the effective fluorescence signal is unchanged. This feature combined with the capture of proteins by the nanoparticles embedded in the membrane increases the detection limit of membrane assays.     

Cosmic rays in the heliosphere

Summary This is a rapporteur paper for the XXIV International Cosmic-Ray Conference covering topics of anomalous cosmic rays, shock acceleration, modulation and transport theory, cosmic-ray gradients, corotating interaction regions, coronal-mass ejections, and solar neutrinos. Among the highlights of the meeting are —conclusive proof that most anomalous cosmic rays are singly charged,—undisputed detection of anomalous cosmic-ray hydrogen,—discovery of unexpectedly large anisotropies of pickup ions,—observation of pronounced solar rotational modulation of cosmic-ray fluxes to the highest heliolatitudes (∼80°) probed by the Ulysses spacecraft, and—new measurements of modulation effects sensitive to particle charge sign. Rapporteur talk given at the XXIV International Cosmic-Ray Conference, Rome, August 28–September 8, 1995.     

Watching it boil: Continuous observation for the quantum zeno effect

The quantum Zeno effect (QZE) is often associated with the ironic maxim, “a watched pot never boils”, although the notion of “watching” suggests a continuous activity at odds with the usual (pulsed measurement) presentation of the QZE. We show how continuous watching can provide the same halting of decay as the usual QZE, and, for incomplete hindrance, we provide a precise connection between the interval between projections and the response time of the continuous observer. Thus, watching closely, but not so closely as to halt the “boiling”, is equivalent to—gives the same degree of partial hindrance as—pulsed measurements with a particular pulsing rate. Our demonstration is accomplished by treating the apparatus for the continuous watching as a fully quantum object. This in turn allows us a second perspective on the QZE, in which it is the modified level structure of the combined system/apparatus Hamiltonian that slows the decay. This and other considerations favor the characterization “dominated time evolution” for the QZE.     

Immunostimulatory effects of three classes of CpG oligodeoxynucleotides on PBMC from HCV chronic carriers

Background  

Chronic hepatitis C virus (HCV) infection results from weak or absent T cell responses. Pegylated-interferon-alpha (IFN-α) and ribavirin, the standard of care for chronic HCV, have numerous immune effects but are not potent T cell activators. A potent immune activator such as TLR9 agonist CpG oligodeoxynucleotide (CpG) may complement current treatment approaches.     

Structure of zinc-borate low-melting glasses derived from IR spectroscopy data

The IR spectra of glasses of the ZnO—SrO—B₂O₃ system with constant additions of PbO, Al₂O₃, and Li₂O (20 mol. % in sum) were studied. It is established that on replacement of B₂O₃ by ZnO, the structure of the glasses is characterized by the presence of groupings with the bridge bonds B^III— O—B^III, B^III—O—B^IV, B^IV—O—B^IV and end groups B^III— O⁻; ZnO practically exerts no influence on the coordination transition [BO₃] → [BO₄]. At a high content of ZnO, zinc ions are present in both a six-and a four-coordinated state. __________ Translated from Zhurnal Prikladnoi Spektroskopii, Vol. 72, No. 6, pp. 778–781, November–December, 2005.     

A complete data base of kinematical data for early-type galaxies

Summary As a result of an exhaustive bibliographical search covering the period 1975–1988, a complete catalogue of kinematical data for early-type galaxies (ellipticals and lenticulars) has been compiled. The catalogue contains all data—both in tabular and in plotted form—appeared in specialized literature before December 1988 and includes central velocity dispersions, rotation curves, and velocity dispersion profiles for 846, 174 and 108 objects, respectively. The catalogue is also available on magnetic tape—made available to the astronomical community through the Strasbourg Data Center—and will be updated yearly. To speed up publication, the proofs were not sent to the authors and were supervised by the Scientific Committee.     

Antiviral activity of Engystol<Superscript>®</Superscript> and Gripp-Heel<Superscript>®</Superscript>: an in-vitro assessment

Background  

Infections with respiratory viruses can activate the innate immune response - an important host defence mechanism in the early stage of viral infection. Interferon (IFN) release, triggered by virus infection, is an important factor in establishing an antiviral state, where IFN activation occurs prior to the onset of the adaptive immune response.     

Tailoring the wetting response of silicon surfaces via fs laser structuring

Control over the wettability of solids and manufacturing of functional surfaces with special hydrophobic and self-cleaning properties has aroused great interest because of its significance for a vast range of applications in daily life, industry and agriculture. We report here a simple method for preparing stable superhydrophobic surfaces by irradiating silicon (Si) wafers with femtosecond (fs) laser pulses and subsequently coating them with chloroalkylsilane monolayers. It is possible, by varying the laser pulse fluence on the surface, to achieve control of the wetting properties through a systematic and reproducible variation of roughness at micro- and nano-scale which mimics both the topology of the “model” superhydrophobic surface—the natural lotus leaf—, as well as its wetting response. Water droplets can move along these irradiated superhydrophobic surfaces, under the action of small gravitational forces, and experience subsequent immobilization, induced by surface tension gradients. These results demonstrate the potential of manipulating liquid motion through selective laser patterning.     

Frequency response analysis of ionically conducting mixed system (1-x)CuI - xAg2MoO4 (0.15 ≤ x ≤ 0.55)

A systematic analysis of the electrical response of the mixed system (1-x)CuI — xAg₂MoO₄ (0.15≤x≤0.55) over the temperature range 297 – 447 K in the 20 Hz — 1 MHz frequency domain has been reported. Relaxation processes associated with individual compositions of this heterogeneous mixture of polycrystalline samples have been identified through a combined analysis of modulus and impedance spectral formalisms. The detailed analysis of these relaxation processes has indicated that AgI and Ag₂MoO₄ phases are the predominant sources of electric conduction in the case of samples in the composition region 0.33≤x≤0.55 whereas in those samples having x<0.33, the presence of Cu₂MoO₄ phase in the mixture is found to make a definite contribution to their effective electric conduction.