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Epidemiological studies indicate that fish consumption during pregnancy leads to improved neurodevelopment. This suggests that the beneficial nutrients in fish may offset the adverse effects of mercury in the case of the average fish meal. However, our previous risk/benefit model predicted a net neurodevelopmental risk for the majority of species analyzed. In this article the previous model is calibrated against fish benefit data and then compared to other fish risk/benefit models, including recent models from the World Health Organization and USFDA. Our calibrated model estimated greater benefit for low mercury species but greater risk for high mercury species than the other models. With respect to a commonly eaten high mercury fish, swordfish, the calibrated model yielded risks that are supportive of current fish advisories but, in contrast, the other models predicted net neurodevelopmental benefits. The calibrated model was used in a proposed 3 step framework for setting fish consumption adviso...

Fanconi's Anaemia is a rare autosomal recessive disease for which the incidence of head and neck cancer can be increased 700-fold1. We report a case of a 31-year old Caucasian male with FA who initially presented in July 2007 with oral squamous cell carcinoma for which he received radical surgery and radiotherapy. He was disease-free until August 2015 when he presented with an extremely aggressive recurrence.

It is widely believed that measurement of molecules in exhaled breath can provide a window into the metabolic state of the human body, detect the presence of cancer, monitor respiratory diseases, assess liver and kidney function, determine exposure to toxins, and possibly, even diagnose schizophrenia. Such conjectures are further supported by recent work performed by researchers at the Pine Street Foundation. Laser spectroscopic techniques, in particular, tunable laser absorption spectroscopy (TLAS), are candidate technologies for breath analysis applications. The paper presents the Breathmeter from Ekips Technologies. The Breathmeter is based on TLAS and consists of four primary components: 1) the laser source module, 2) sample gas cell, 3) optical detector, and 4) associated electronics hardware and software. The optical board layout of the breath meter system was shown. Its applications and future works were also discussed

The herpes simplex virus type 1 (HSV-1) protease and its substrate, the assembly protein ICP35, are involved in virion maturation. Both proteins are encoded by a single open reading frame but are translated independently from 3'-coterminal mRNAs of different sizes and are in frame. The herpesvirus shell assembles around an internal scaffold which is subsequently lost during packaging of the viral genome. The scaffold is composed of ICP35, which is the major component, and autoproteolytically processed forms of the viral protease containing sequences common to ICP35 (Nb). In the baculovirus system, HSV-1 intact capsids can be formed in the presence of the protease or ICP35, indicating that the protease may substitute for ICP35 (Thomsen et al., J. Virol. 68:2442-2457, 1994). This is further supported by the fact that ICP35, in contrast to the protease, is not absolutely essential for viral growth. The processed intermediate of the protease analogous to ICP35 is the 388-amino-acid (aa) protein, Na, which is an N-terminal 59-aa extension of the 329-aa ICP35. To directly examine whether Na can functionally substitute for ICP35 during viral replication, we first constructed a mutant virus, Na delta35, in which 35 aa from the N terminus of Na were deleted. Phenotypic analysis of the mutant showed that this deletion had no effect on protease function. The function of Na was further examined by construction of a plasmid expressing Na alone and testing its ability to complement the growth of the mutant Prb virus in the absence of ICP35. Our results demonstrate that Na can functionally substitute for ICP35 during viral replication.

The herpes simplex virus type 1 protease and its substrate, ICP35, are involved in the assembly of viral capsids. Both proteins are encoded by a single open reading frame from overlapping mRNAs. The protease is autoproteolytically processed at two sites. The protease cleaves itself at the C-terminal site (maturation site) and also cleaves ICP35 at an identical site, releasing a 25-amino-acid (aa) peptide from each protein. To determine whether these 25 aa play a role in capsid assembly, we constructed a mutant virus expressing only Prb, the protease without the C-terminal 25 aa. Phenotypic analysis of the Prb virus in the presence and absence of ICP35 shows the following: (i) Prb retains the functional activity of the wild-type protease which supports virus growth in the presence of ICP35; (ii) in contrast to the ICP35 null mutant delta ICP35 virus, the Prb virus fails to grow in the absence of ICP35; and (iii) trans-complementation experiments indicated that full-length ICP35 (ICP35 c,d), but not the cleaved form (ICP35 e,f), complements the growth of the Prb virus. The most striking phenotype of the Prb virus is that only unsealed aberrant capsid structures are observed by electron microscopy in mutant-infected Vero cells. Our results demonstrate that the growth of herpes simplex virus type 1 requires the C-terminal 25 aa of either the protease or its substrate, ICP35, and that the C-terminal 25 aa are involved in the formation of sealed capsids.

The herpes simplex virus type 1 (HSV-1) protease is cleaved at two autoprocessing sites during viral maturation, one of which shares amino acid identity with its substrate, ICP35. Similar autoprocessing sites have been observed within other members of the Herpesviridae. Introduction of point mutations within the autoprocessing sites of the HSV-1 protease indicated that specificity resides within the P4-P1' region of the cleavage sites.

The UL26 gene of herpes simplex virus type 1 (HSV-1) encodes a 635-amino-acid protease that cleaves itself and the HSV-1 assembly protein ICP35cd (F. Liu and B. Roizman, J. Virol. 65:5149-5156, 1991). We previously examined the HSV protease by using an Escherichia coli expression system (I. C. Deckman, M. Hagen, and P. J. McCann III, J. Virol. 66:7362-7367, 1992) and identified two autoproteolytic cleavage sites between residues 247 and 248 and residues 610 and 611 of UL26 (C. L. DiIanni, D. A. Drier, I. C. Deckman, P. J. McCann III, F. Liu, B. Roizman, R. J. Colonno, and M. G. Cordingley, J. Biol. Chem. 268:2048-2051, 1993). In this study, a series of C-terminal truncations of the UL26 open reading frame was tested for cleavage activity in E. coli. Our results delimit the catalytic domain of the protease to the N-terminal 247 amino acids of UL26 corresponding to No, the amino-terminal product of protease autoprocessing. Autoprocessing of the full-length protease was found to be unnecessary for catalysis, since elimination of either or both cleavage sites by site-directed mutagenesis fails to prevent cleavage of ICP35cd or an unaltered protease autoprocessing site. Catalytic activity of the 247-amino-acid protease domain was confirmed in vitro by using a glutathione-S-transferase fusion protein. The fusion protease was induced to high levels of expression, affinity purified, and used to cleave purified ICP35cd in vitro, indicating that no other proteins are required. By using a set of domain-specific antisera, all of the HSV-1 protease cleavage products predicted from studies in E. coli were identified in HSV-1-infected cells. At least two protease autoprocessing products, in addition to fully processed ICP35cd (ICP35ef), were associated with intermediate B capsids in the nucleus of infected cells, suggesting a key role for proteolytic maturation of the protease and ICP35cd in HSV-1 capsid assembly.

PbSe films were grown on (111)-oriented BaF2 substrates by using molecular beam epitaxy. High resolution x-ray diffraction characterization showed good crystalline quality of PbSe films. Both longitudinal optical phonon at 135 cm-1 and transverse optical phonon at 47.6 cm-1 were observed by Raman scattering measurements. The Raman tensor calculation demonstrates that both transverse-optical and longitudinal-optical (LO) phonons in PbSe crystal are Raman active on (111)-oriented surface. Furthermore, 2LO phonon at about 270 cm-1 and polaron at about 800 cm-1 in PbSe, were also observed. The observed Raman frequencies are in good agreement with theoretical calculations using point ion model.

Measurement of nitric oxide (NO) in the expired breath of crossbred calves received at a research facility was performed using tunable diode laser absorption spectroscopy. Exhaled NO (eNO) concentrations were measured using NO absorption lines at 1912.07 cm(-1) and employing background subtraction. The lower detection limit and measurement precision were determined to be approximately 330 parts in 10(12) per unit volume. A custom breath collection system was designed to collect lower airway breath of spontaneously breathing calves while in a restraint chute. Breath was collected and analyzed from calves upon arrival and periodically during a 42 day receiving period. There was a statistically significant relationship between eNO, severity of bovine respiratory disease (BRD) in terms of number of times treated, and average daily weight gain over the first 15 days postarrival. In addition, breathing patterns and exhaled CO2 showed a statistically significant relationship with BRD morbidity.

An absorption spectrometer equipped with a IV-VI semiconductor tunable mid-IR diode laser was used to make sensitive measurements of benzene (C(6)H(6)) gas in the 5.1-microm spectral range. Wavelength modulation coupled with second-harmonic detection achieved accurate real-time quantification of benzene concentrations down to a minimum detection limit of 1 ppmv with an integration time of 4 s. A variety of calibrated benzene-sensing measurements were made, including the determination of the benzene concentrations in vehicle exhaust and headspace vapors from unleaded gasoline and other liquids. Kinetic phenomena, including the monitoring of benzene evaporation and absorption/desorption by granulated activated carbon were observed with the instrument. Measurements were performed that allowed experimental determination of the activation energy for desorption of benzene from activated carbon, which was found to be 198 meV/molecule (19.0 kJ/mol).

The method of substrate phage display was used to select a preferred substrate from three monovalent display libraries using the HSV-1 protease. The display libraries consisted of four random amino acids, six random amino acids, and a biased library containing four amino acids from the P side of the HSV-1 maturation site followed by four random amino acids. A series of consensus peptides was synthesized based upon the results from these screens and tested in peptide cleavage assays. An eight amino acid consensus peptide (LVLASSSF) derived from the phage results was cleaved as efficiently as a 20-mer maturation site peptide. The selected amino acid sequences also allowed the design of a four amino acid paranitroanilide substrate for continuous assay of HSV-1 protease. Similar to HCMV protease, these results define P4 to P1 as a minimal substrate recognition domain for the HSV-1 protease and suggest that P4 to P1 is the minimal substrate domain which all herpesvirus proteases recognize.

Crack-free layers of PbSe were grown on Si (100) by a combination of liquid phase epitaxy (LPE) and molecular beam epitaxy (MBE) techniques. The PbSe layer was grown by LPE on Si (100) using a MBE-grown PbSe/BaF2/CaF2 buffer layer structure. Pb1−xSnxSe layers with tin contents in the liquid growth solution equal to 3%, 5%, 6%, 7%, and 10%, respectively, were also grown by LPE on Si (100) substrates using similar buffer layer structures. The LPE-grown PbSe and Pb1−xSnxSe layers were characterized by optical Nomarski microscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Optical Nomarski characterization of the layers revealed their excellent surface morphologies and good growth solution wipe-offs. FTIR transmission experimentsshowed that the absorption edge of the Pb1−xSnxSe layers shifted to lower energies with increasing tin contents. The PbSe epilayers were also lifted-off from the Si substrate by dissolving the MBE-grown BaF2 buffer layer. SEM micrographs of the cleaved edges revealed that the lifted-off layers formed structures suitable for laser fabrication.

In this paper, we study both the continuous model and the discrete model of the Quantum Hall Effect (QHE) on the hyperbolic plane. The Hall conductivity is identified as a geometric invariant associated to an imprimitivity algebra of observables. We define a twisted analogue of the Kasparov map, which enables us to use the pairing between $K$-theory and cyclic cohomology theory, to identify this geometric invariant with a topological index, thereby proving the integrality of the Hall conductivity in this case., Comment: AMS-LaTeX, 28 pages

The herpes simplex virus type 1 (HSV-1) protease (Pra) and related proteins are involved in the assembly of viral capsids and virion maturation. Pra is a serine protease, and the active-site residue has been mapped to amino acid (aa) 129 (Ser). This 635-aa protease, encoded by the UL26 gene, is autoproteolytically processed at two sites, the release (R) site between amino acid residues 247 and 248 and the maturation (M) site between residues 610 and 611. When the protease cleaves itself at both sites, it releases Nb, the catalytic domain (N0), and the C-terminal 25 aa. ICP35, a substrate of the HSV-1 protease, is the product of the UL26.5 gene. As it is translated from a Met codon within the UL26 gene, ICP35 cd are identical to the C-terminal 329-aa sequence of the protease and are trans cleaved at an identical C-terminal site to generate ICP35 e,f and a 25-aa peptide. Only fully processed Pra (N0 and Nb) and ICP35 (ICP35 e,f) are present in B capsids, which are believed to be precursors of mature virions. Using an R-site mutant A247S virus, we have recently shown that this mutant protease retains enzymatic activity but fails to support viral growth, suggesting that the release of N0 is required for viral replication. Here we report that another mutant protease, with an amino acid substitution (Ser to Cys) at the active site, can complement the A247S mutant but not a protease deletion mutant. Cell lines expressing the active-site mutant protease were isolated and shown to complement the A247S mutant at the levels of capsid assembly, DNA packaging, and viral growth. Therefore, the complementation between the R-site mutant and the active-site mutant reconstituted wild-type Pra function. One feature of this intragenic complementation is that following sedimentation of infected-cell lysates on sucrose gradients, both N-terminally unprocessed and processed proteases were isolated from the fractions where normal B capsids sediment, suggesting that proteolytic processing occurs inside capsids. Our results demonstrate that the HSV-1 protease has distinct functional domains and some of these functions can complement in trans.

Herpes simplex virus type-1 (HSV-1) encodes a protease responsible for proteolytic processing of the virus assembly protein, ICP35 (infected cell protein 35). The coding region of ICP35 is contained within the gene that encodes the protease, and ICP35 shares amino acid identity with the carboxyl-terminal 329 amino acids of the protease. The HSV-1 protease was expressed in Escherichia coli as a fusion protein containing a unique epitope and the protein A Fc binding domain at its carboxyl terminus. The fusion protease underwent autoproteolytic cleavage at two distinct sites. The size of the cleavage products containing the carboxyl-terminal epitope mapped one cleavage site near the carboxyl terminus of the protease corresponding to the proteolytic processing site of ICP35, and the second site proximal to the amino terminus consistent with previous data. The carboxyl-terminal autoproteolytic cleavage products were partially purified on an IgG affinity column by virtue of the protein A Fc binding domain and subjected to direct amino-terminal sequence analysis. Protein sequencing revealed that cleavage occurs between the Ala and Ser residues at amino acids 610/611 and 247/248 of the HSV-1 protease. The flanking sequences share homology with each other and are highly conserved in homologous proteases of other herpes viruses.

The UL26 gene of herpes simplex virus type 1 (HSV-1) encodes a protease which is responsible for the C-terminal cleavage of the nucleocapsid-associated proteins, ICP35 c and d, to their posttranslationally modified counterparts, ICP35 e and f. To further characterize the HSV-1 protease, the UL26 gene product was expressed in Escherichia coli. The expressed protease underwent autoproteolytic processing at two independent sites. The first site is shared with ICP35 and results in removal of 25 amino acids from the C terminus of the protease. The second unique site gives rise to protein species consistent with deletion of a 28-kDa fragment at the N terminus. A mutant protease, which showed no activity in a mammalian cell cotransfection assay (F. Liu and B. Roizman, Proc. Natl. Acad. Sci. USA 89:2076-2080, 1992), failed to exhibit autoproteolytic processing at either site when expressed in bacteria. The inactive mutant was able to serve as a substrate in a trans assay in which the substrate and protease were coexpressed in bacteria. This experiment demonstrated that the unique N-terminal processing was mediated exclusively by the HSV-1 protease. ICP35 c,d also served as a substrate in this assay and was correctly processed by HSV-1 protease in E. coli. This trans-cleavage assay will aid in the characterization of HSV-1 protease and assist in investigation of the role of proteolytic processing in the virus.

Experimental apparatus is described to detect EPR in solids using a low temperature version of the photo-acoustic effect involving second sound in superfluid helium. By chopping the microwave power to the sample second sound is generated and amplified by resonance in a chamber maintained at constant temperature. The process is analysed and is shown to provide the same depth profiling capability as the normal photo-acoustic effect. Some results are presented to provide illustration and comparison with other techniques.

Two quite different values of the g-factor of Co2+ in InP have been reported in the literature recently. Using both conventional and thermally detected EPR on several different samples, the authors have obtained a g-value of 2.191+or-0.001, which agrees with the value quoted by Lambert and co-workers (1982) and is consistent with that found in GaAs and GaP.

It is generally accepted that Cr-doped LEC GaAs has a higher resistivity than undoped semiinsulating material grown by the same technique. The principal aim of these measurements is to establish the compensation mechanism in LEC GaAs when both Cr and the native deep donor level EL2 are present. Using EPR mapping, the authors have measured the spatial distribution of the Cr2+ charge state in material which is known to be uniformly doped with Cr. The distribution of (Cr2+) is found to follow that of EL2 in undoped samples. It is concluded that for GaAs heavily doped with Cr the Fermi level is pinned at the Cr2+/Cr3+ acceptor level and that this level lies lower in the forbidden gap than the EL20/EL2+ donor level. The model is shown to explain the electrical characteristics of undoped and Cr-doped LEC GaAs ingots.

The herpes simplex virus type 1 UL12 gene product, alkaline nuclease (AN), appears to be involved in viral DNA processing and capsid egress from the nucleus (Shao, L., Rapp, L. M., and Weller, S. K., Virology 196, 146–162, 1993). Although the HSV-1 AN is not absolutely essential for viral replication in tissue culture, conservation of the AN gene in all herpesviruses suggests an important role in the life cycle of herpesviruses. The counterpart of HSV-1 AN for human cytomegalovirus (HCMV) is the UL98 gene product. To examine whether the HCMV AN could substitute for HSV-1 AN, we performed trans -complementation experiments using a HSV-1 amplicon plasmid carrying the HCMV UL98 gene. Our results indicate (i) HCMV AN can complement the growth of the HSV-1 AN deletion mutant UL12lacZ virus in trans; (ii) a new recombinant virus, UL12laZcUL98/99, appears to be generated by the integration of the HCMV UL98 gene into the HSV-1 UL12lacZ viral genome; (iii) in contrast to its parental HSV-1 UL12lacZ virus, capsids formed in UL12lacZUL98/99 -infected Vero cells were able to transport from the nucleus to the cytoplasm and mature into infectious viruses. Our results demonstrate a functional conservation of AN between HSV-1 and HCMV.