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We explore the abundances and depletion levels of elements important to dust composition in four Small Magellanic Cloud (SMC) sight lines observed with the Hubble Space Telescope. The apparent optical depth method is used to interpret the high-resolution ultraviolet absorption data toward AzV 18, AzV 456, Sk 108, and Sk 155; the latter two sight lines have been previously explored using component fitting. In contrast to previous studies, we find evidence that silicon is depleted in the SMC's interstellar medium (ISM). This makes it improbable that SMC-like extinction, i.e., no 2175 A bump and a steep far-ultraviolet rise, results from a lack of silicate grains in the SMC. Notable differences between our sight lines that have SMC-like and Milky Way-like extinction, AzV 18 and AzV 456, respectively, are that the former has a substantially larger gas-to-dust ratio and smaller fractional H2 abundance. Iron abundances and depletions in the SMC's ISM often diverge from the pattern shown by Si and Mg. This is evidence that Fe is not tied to the same grains as silicon, and therefore that most silicate grains are likely magnesium based. The presence of iron depletion in the SMC then suggests that this element is probably incorporated into grain types such as metals or oxides.

The Atlantic bottlenose dolphin (Tursiops truncatus), a marine mammal found off the Atlantic coast, has become the focus of considerable attention because of an increasing number of mortality events witnessed in this species over the last several years along the southeastern United States. Assessment of the impact of environmental stressors on bottlenose dolphins (BND) has been difficult because of the protected status of these marine mammals. The studies presented herein focused on establishing epidermal cell cultures and cell lines as tools for the in vitro evaluation of environmental stressors on BND skin. Epidermal cell cultures were established from skin samples obtained from Atlantic BND and subjected to karyotype analysis. These cultures were further characterized using immunohistochemical methods demonstrating expression of cytokeratins. By two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), we observed that the proteomic profile of BND skin tissue samples shared distinct similarities with that of skin-derived cultures. Epidermal cell cultures were transfected with a plasmid encoding the SV40 small t- and large T-antigens, as well as the neomycin-resistance gene. Five neomycin-resistant clones were isolated and expanded, and all of them proliferated at a faster rate than nontransfected BND epidermal cultures, which exhibited signs of senescence. Cell lysates prepared from two transfected clones were shown to express, by Western blot analysis, both SV40 tumor antigens. These experimental results are consistent with the concept that transfected clones expressing SV40 tumor antigens represent immortalized BND cell lines. Epidermal cell lines derived from Tursiops truncatuswill provide a unique tool for studying key features of the interaction occurring between dolphins and the environment in which they live at their most crucial interface: the skin. © 2005 Wiley-Liss, Inc.

Purpose: To provide a summary of the outcomes of two working conferences organized by the Centers for Disease Control and Prevention (CDC), to develop recommendations for practical, sustainable mechanisms to make quality control (QC) materials available to the genetic testing community.Methods: Participants were selected to include experts in genetic testing and molecular diagnostics from professional organizations, government agencies, industry, laboratories, academic institutions, cell repositories, and proficiency testing (PT)/external Quality Assessment (EQA) programs. Current efforts to develop QC materials for genetic tests were reviewed; key issues and areas of need were identified; and workgroups were formed to address each area of need and to formulate recommendations and next steps.Results: Recommendations were developed toward establishing a sustainable process to improve the availability of appropriate QC materials for genetic testing, with an emphasis on molecular genetic testing as an initial step.Conclusions: Improving the availability of appropriate QC materials is of critical importance for assuring the quality of genetic testing, enhancing performance evaluation and PT/EQA programs, and facilitating new test development. To meet the needs of the rapidly expanding capacity of genetic testing in clinical and public health settings, a comprehensive, coordinated program should be developed. A Genetic Testing Quality Control Materials Program has therefore been established by CDC in March 2005 to serve these needs.

We present an extinction analysis of nine reddened/comparison star pairs in the Large and Small Magellanic Clouds (LMC and SMC) based on Far-Ultraviolet Spectroscopic Explorer (FUSE) FUV observations. To date, just two LMC sight lines have probed dust grain composition and size distributions in the Magellanic Clouds using spectral data for wavelengths as short as 950 A. We supplement these two with data from four regions distinguished by their IR through UV extinction curves and grouped as LMCAvg, LMC2, SMC bar, and SMC wing. Despite the distinct characters of extinction in the Clouds and Milky Way, our results are generally analogous to those found for Galactic curves--namely, that the FUSE portions of each extinction curve are described reasonably well by Fitzpatrick & Massa curves fitted only to longer wavelength data and lack any dramatic new extinction features, and any deviations from the Cardelli, Clayton, & Mathis (CCM) formalism continue into FUV wavelengths. A maximum entropy method analysis of all of these curves suggests that LMCAvg and SMC wing sight lines, whose extinction parameters more closely resemble those for Galactic paths, require more silicon and/or carbon in dust than current abundance measurements would indicate are available. The requirements for LMC2 and SMC bar sight lines do not fully tax the available reservoirs, in part because large grains contribute less to the extinction in these directions. An intermediate product of this extinction analysis is the measurement of new H2 abundances in the Magellanic Clouds. Collectively considering Cloud sight lines that possess significant H2 column densities, E(B - V)/N(H img1.gif) ratios are reduced by significant factors relative to the Galactic mean, whereas the corresponding E(B - V)/N(H2) values more closely resemble their Galactic counterpart. These trends reflect the fact that among these sight lines f(H2) values are lower than those common in the Milky Way for paths with similar degrees of reddening.

Disclaimer: These standards and guidelines are designed primarily as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to this statement does not necessarily ensure a successful medical outcome. These standards and guidelines should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the clinical molecular geneticist should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. It may be prudent, however, to document in the laboratory record the rationale for any significant deviation from these standards and guidelines.

CD19 is a B cell-surface molecule that participates as an important regulatory signaling complex for antigen bound at the surface by Ig. Triggering of CD19 through its linkage with CD21 amplifies signals transduced through the Src family kinases and modulates B cell differentiation in response to antigen. This study examines the kinetics of antigen uptake and processing of antigen directly targeted to the CD19 protein on purified B cells. We have demonstrated that the antigen internalized within minutes through CD19 forms a cap at the B cell surface and can be found within lysosomes in the cytoplasm in 90 min. B cells acquiring antigen via CD19 express elevated levels of B7-1 and B7-2 co-stimulatory molecules. Moreover, antigen–anti-CD19 complexes administered intravenously bind B cells in vivo and activate antigen-specific T cells more efficiently than non-specific uptake and in a manner similar to antigen taken up through surface IgM on B cells. This work illustrates an important and previously unrecognized mechanism for targeting proteins to B lymphocytes for antigen presentation and activation of CD4 T cells.

We present extinction curves that include data down to far-ultraviolet wavelengths (FUV; 1050-1200 A) for nine Galactic sight lines. The FUV extinction was measured using data from the Far Ultraviolet Spectroscopic Explorer. The sight lines were chosen for their unusual extinction properties in the infrared through the ultraviolet; that they probe a wide range of dust environments is evidenced by the large spread in their measured ratios of total to selective extinction, RV = 2.43-3.81. We find that extrapolation of the Fitzpatrick & Massa relationship from the ultraviolet appears to be a good predictor of the FUV extinction behavior. We find that predictions of the FUV extinction based on the Cardelli, Clayton, & Mathis (CCM) dependence on RV give mixed results. For the seven extinction curves well represented by CCM in the infrared through ultraviolet (x < 8 mm-1), the FUV extinction is well predicted in three sight lines, overpredicted in two sight lines, and underpredicted in two sight lines. A maximum entropy method analysis using a simple three-component grain model shows that seven of the nine sight lines in the study require a larger fraction of grain materials to be in dust when FUV extinction is included in the models. Most of the added grain material is in the form of small (radii [?] 200 A) grains.

People with mental retardation have limited access to oral health care. Dental school administrators reported minimal training in U.S. dental schools for these patients. As a result, students and practitioners may not be prepared to provide needed services.

We present an exhaustive quantitative comparison of all the known extinction curves in the Small and Large Magellanic Clouds (SMC and LMC) with our understanding of the general behavior of Milky Way extinction curves. The RV-dependent CCM relationship of Cardelli, Clayton, and Mathis and the sample of extinction curves used to derive this relationship are used to describe the general behavior of Milky Way extinction curves. The ultraviolet portion of the SMC and LMC extinction curves are derived from archival IUE data, except for one new SMC extinction curve, which was measured using Hubble Space Telescope Space Telescope Imaging Spectrograph observations. The optical extinction curves are derived from new (for the SMC) and literature UBVRI photometry (for the LMC). The near-infrared extinction curves are calculated mainly from 2MASS photometry supplemented with DENIS and new JHK photometry. For each extinction curve, we give RV = A(V)/E(B - V) and N(H I) values that probe the same dust column as the extinction curve. We compare the properties of the SMC and LMC extinction curves with the CCM relationship three different ways: each curve by itself, the behavior of extinction at different wavelengths with RV, and the behavior of the extinction curve Fitzpatrick and Massa fit parameters with RV. As has been found previously, we find that a small number of LMC extinction curves are consistent with the CCM relationship, but the majority of the LMC and all the SMC curves do not follow the CCM relationship. For the first time, we find that the CCM relationship seems to form a bound on the properties of all the LMC and SMC extinction curves. This result strengthens the picture dust extinction curves exhibit of a continuum of properties between those found in the Milky Way and the SMC bar. Tentative evidence based on the behavior of the extinction curves with dust-to-gas ratio suggests that the continuum of dust extinction curves is possibly caused by the environmental stresses of nearby star formation activity.

The Galactic Legacy Infrared Mid-Plane Survey Extraordinaire (GLIMPSE), a Space Infrared Telescope Facility(SIRTF) Legacy Science Program, will be a fully sampled, confusion-limited infrared survey of 2/3 of the inner Galactic disk with a pixel resolution of ?1.?2 using the Infrared Array Camera at 3.6, 4.5, 5.8, and 8.0 ?m. The survey will cover Galactic latitudes |b|?1° and longitudes |l| = 10°-65° (both sides of the Galactic center). The survey area contains the outer ends of the Galactic bar, the Galactic molecular ring, and the inner spiral arms. The GLIMPSE team will process these data to produce a point-source catalog, a point-source data archive, and a set of mosaicked images. We summarize our observing strategy, give details of our data products, and summarize some of the principal science questions that will be addressed using GLIMPSE data. Up-to-date documentation, survey progress, and information on complementary data sets are available on the GLIMPSE Web site.

We have obtained new Hubble Space Telescope/Space Telescope Imaging Spectrograph spectra to search for structure in the ultraviolet interstellar extinction curve, with particular emphasis on a search for absorption features produced by polycyclic aromatic hydrocarbons (PAHs). The presence of these molecules in the interstellar medium has been postulated to explain the infrared emission features seen in the 3-13 mm spectra of numerous sources. Ultraviolet (UV) spectra are uniquely capable of identifying specific PAH molecules. We obtained high signal-to-noise ratio UV spectra of stars that are significantly more reddened than those observed in previous studies. These data put limits on the role of small (30-50 carbon atoms) PAHs in UV extinction and call for further observations to probe the role of larger PAHs. PAHs are of importance because of their ubiquity and high abundance inferred from the infrared data, and also because they may link the molecular and dust phases of the interstellar medium. A presence or absence of UV absorption bands due to PAHs could be a definitive test of this hypothesis. We should be able to detect a 20 A wide feature down to a 3 s limit of ~0.02 AV. No such absorption features are seen other than the well-known 2175 A bump.

We present two-dimensional radiation transfer models of class I protostars and show the effect of including more realistic geometries on the resulting spectral energy distributions and images. We begin with a rotationally flattened infalling envelope as our comparison model and add a flared disk and bipolar cavity. The disk affects the spectral energy distribution most strongly at edge-on inclinations, causing a broad dip at about 10 mm (independent of the silicate feature) due to high extinction and low scattering albedo in this wavelength region. The bipolar cavities allow more direct stellar+disk radiation to emerge into polar directions and more scattering radiation to emerge into all directions. The wavelength-integrated flux, often interpreted as luminosity, varies with viewing angle, with pole-on viewing angles seeing 2-4 times as much flux as edge-on, depending on geometry. Thus, observational estimates of luminosity should take into account the inclination of a source. The envelopes with cavities are significantly bluer in near-IR and mid-IR color-color plots than those without cavities. Using one-dimensional models to interpret Class I sources with bipolar cavities would lead to an underestimate of envelope mass and an overestimate of the implied evolutionary state. We compute images at near-, mid-, and far-IR wavelengths. We find that the mid-IR colors and images are sensitive to scattering albedo and that the flared disk shadows the midplane on large size scales at all wavelengths plotted. Finally, our models produce polarization spectra that can be used to diagnose dust properties, such as albedo variations due to grain growth. Our results of polarization across the 3.1 mm ice feature agree well with observations for ice mantles covering 5% of the radius of the grains.

Antimicrobial prophylaxis and highly active antiretroviral therapy have changed the epidemiology and impact of pulmonary infection in patients infected with the human immunodeficiency virus (HIV). However, pulmonary infection remains a significant contributor to the morbidity and mortality of such patients. Bacterial pneumonia and tuberculosis remain common lung infections in this setting, especially where appropriate prophylaxis is unavailable or when compliance with such therapy is poor. Pneumonia related to Pneumocystis cariniialso remains a significant problem, especially as a presenting illness in patients not yet known to be infected with HIV. Recrudescence of “treated” infection as a manifestation of the immune reconstitution syndrome may become more commonly encountered as more patients are treated with highly active therapy.

Previous studies have identified mutations in five ion channel genes as a cause of long QT syndrome, a heterogeneous disorder characterized by prolongation of the QT interval, multiform ventricular tachycardia (torsades de pointes), seizures, syncope, and sudden death. However, in these studies, the average age of initial symptoms is in the third decade of life or later, and few reports have described the genetic causes of long QT syndrome presenting in the prenatal or neonatal period. We used a candidate gene approach to identify the genetic cause of long QT syndrome in an infant whose initial manifestations were detected in utero. Direct bidirectional sequencing of long QT syndrome genes identified a previously unreported HERG missense mutation (R752Q). Three asymptomatic family members were heterozygous for R752Q, and the proband, who manifested ventricular tachycardia in utero, was homozygous. R752Q was not found in 100 normal unrelated chromosomes. Paternal DNA was unavailable for testing. Transient transfection of HERG generated robust IKr, but no current was observed for the mutant HERG. The HERG mutant, R752Q, is associated with a mild phenotype, inasmuch as family members with a heterozygous mutation appear unaffected. The homozygous mutation results in absence of functional IKr, causing a profound loss of HERG channel function, creating the equivalent of a “HERG knockout” and leading to a severe phenotype.

We present radiative transfer calculations showing the polarization effects of scattering and absorption by aligned grains. The grain model consists of a size distribution of oblate or spinning prolate particles with varying degrees of alignment. To develop an understanding of the radiative transfer effects, we begin with the simple case of a spherical envelope illuminated by a central source with constant grain alignment axis throughout the envelope. Nonaligned grains produce no net polarization in such envelopes, while aligned grains produce substantial linear and circular polarization. The linear polarization results from the competing effects of differential extinction and scattering. The polarization varies strongly with optical depth, with scattering dominating at low optical depth and differential extinction dominating at high optical depth. The net, or integrated, circular polarization from the envelopes is zero; however, the circular polarization across the resolved nebula is large, reaching +-50% in the "diagonal" regions of the nebula. Next we calculate axisymmetric models of protostellar envelopes, again with the simplifying case of constant grain alignment axis throughout the envelope. The polarization maps show differences from the case of nonaligned grains, especially in the disk midplane, where differential extinction of even the scattered light causes the polarization vectors to align perpendicular to the disk plane, in contrast to many observations. This suggests either that grains are not aligned in protostellar envelopes or that the magnetic field (the presumed alignment mechanism) is not aligned along the disk rotational axis throughout the envelope and disk. A definitive test of grain alignment could come from resolved circular polarization maps of protostars. Aligned grains produce large values of circular polarization across the cloud, up to +-25%-40% in the models presented here, whereas nonaligned grains produce maximum polarizations of less than 1%. In objects with aligned grains, analysis of linear and circular polarization maps can probe magnetic geometries.

Purpose: Folate insufficiency due to nutritional deficiency or folate processing gene mutations has been proposed as a trisomy 21 risk factor. This study examined the possibility that increased folic acid intake among women of childbearing age may decrease the prevalence of trisomy 21 and other aneuploidies.Methods: The prevalence of aneuploidies from 1990 through 1999 was compared with folic acid use in women of childbearing age in South Carolina.Results: Folic acid use and the prevalence of all aneuploidies significantly increased during this period.Conclusion: Increased folic acid utilization in South Carolina was not associated with decreased prevalence of trisomy 21 or other aneuploidies.

We investigate the observational signatures of a straightforward evolutionary scenario for protoplanetary disks, in which the disk mass of small ([?]50 mm) particles decreases homologously with time, but the disk structure and stellar parameters do not change. Our goal is to identify optimal infrared spectral indicators of the existence of disks, their structure, and mass evolution that may be tested with the upcoming SIRTF mission. We present simulated spectral energy distributions (SEDs) and colors over a wide range of masses, 10-8 M [?] Mdisk [?] 10-1 M. Our Monte Carlo radiative equilibrium techniques enable us to explore the wide range of optical depths of these disks and incorporate multiple, anisotropic dust scattering. The SED is most sensitive to disk mass in the far-IR and longer wavelengths, as is already known from millimeter and radio observations. As the disk mass decreases, the excess emission of the disk over the stellar photosphere diminishes more rapidly at the longest than at short wavelengths. At near-infrared wavelengths, the disk remains optically thick to stellar radiation over a wide range of disk masses, resulting in a slower decline in the SED in this spectral regime. Therefore, near-IR excesses (K-L) provide a robust means of detecting disks in star clusters down to Mdisk ~ 10-7 M, while the far-IR excess probes the disk mass, the caveat being that large inner-disk holes can decrease the near-IR disk emission. Various other disk parameters (outer radius, flaring, and dust size distribution) alter the SED quantitatively, but do not change our general conclusions on the evolution of SEDs and colors with the mass of small particles in the disk. Reducing the disk mass results in a clear progression in color-color diagrams, with low-mass disks displaying the bluest colors. We interpret color-color diagrams for Taurus-Auriga sources in the context of decreasing disk mass. Different viewing angles yield degeneracies in the color-mass relationship, but highly inclined disks are very faint and red and are readily identified in color-magnitude diagrams.

We present spectral energy distribution (SED) models for the edge-on classical T Tauri star HH 30 IRS that indicate that dust grains have grown to larger than 50 mm within its circumstellar disk. The disk geometry and inclination are known from previous modeling of multiwavelength Hubble Space Telescope images, and we use the SED (0.5 mm [?] l [?] 3 mm) to constrain the dust size distribution. Model spectra are shown for different circumstellar dust models: a standard interstellar medium (ISM) mixture and larger grain models. As compared to ISM grains, the larger dust grain models have a shallower wavelength-dependent opacity: smaller at short wavelengths and larger at long wavelengths. Models with the larger dust grains provide a good match to the observed SED of HH 30 IRS. Although the currently available SED is poorly sampled, we estimate L* [?] 0.2 L, Mdisk [?] 1.5 x 10-3 M, and a power law with exponential cutoff dust grain size distribution. This model provides a good fit to the currently available data, but mid- and far-IR observations are required to more tightly constrain the size distribution. The accretion luminosity in our models is Lacc [?] 0.2L*, corresponding to an accretion rate M [?] 4 x 10-9 M yr-1. Dust size distributions that are simple power-law extensions (i.e., no exponential cutoff) yield acceptable fits to the optical/near-IR but too much emission at millimeter wavelengths, and require larger disk masses up to Mdisk ~ 0.5 M. Such a simple size distribution would not be expected in an environment such as the disk of HH 30 IRS (i.e., where coagulation and accretion processes are occurring in addition to grain shattering), particularly over such a large range in grain sizes. Its ability to adequately characterize the grain populations, however, may be determined from more complete observational sampling of the SED in the mid- to far-IR.

Purpose: Autism is a chronic neurodevelopmental disorder characterized by deficits in reciprocal social interaction, language and communication, and by the presence of stereotypical behaviors. The disorder is a complex genetic trait with no known predisposing genes. We report the results of a pilot project to screen for aberrations in the gene-rich subtelomeric chromosomal regions of a cohort of children with autism.Methods: For our pilot project, we used a multiprobe system that includes probes for the subtelomeric regions of all human chromosomes. We assessed the subtelomeric regions of chromosomes from 10 children with a diagnosis of autism.Results: The screen identified one child with an apparent deletion of the subtelomeric region of chromosome 2q; nine children and pooled control samples yielded normal results. The deletion in our patient was confirmed with two other subtelomeric probes and a targeted cytogenetic study revealed a subtle difference in appearance for one chromosome 2 homologue.Conclusion: There have been several reports of children with dysmorphic features, autistic behaviors, and 2q deletions detectable with standard cytogenetic techniques. It may be that the distal region of chromosome 2q harbors a gene or genes that may predispose to autism.

We present Hubble Space Telescope near-infrared camera and multiobject spectrometer observations of the reflection nebulosity associated with the T Tauri star HH 30. The images show the scattered-light pattern characteristic of a highly inclined, optically thick disk with a prominent dust lane whose width decreases with increasing wavelength. The reflected nebulosity exhibits a lateral asymmetry in the upper lobe on the opposite side to that reported in previously published Wide Field Planetary Camera 2 images. The radiation transfer model that most closely reproduces the data has a flared accretion disk with dust grains larger than standard interstellar medium grains by a factor of approximately 2.1. A single hot spot on the stellar surface provides the necessary asymmetry to fit the images and is consistent with previous modeling of the light curve and images. Photometric analysis results in an estimated extinction of AV [?] 80; however, since the photometry measures only scattered light rather than direct stellar flux, this a lower limit. The radiative transfer models require an extinction of AV = 7900.

C3-tris-malonyl-C60-fullerene and D3-tris-malonyl-C60-fullerene derivatives inhibit citrulline and NO formation by all three nitric oxide synthase isoforms in a manner fully reversible by dilution. The inhibition of citrulline formation by C3-tris-malonyl-C60-fullerene occurs with IC50 values of 24, 17, and 123 μM for the neuronal, endothelial, and inducible nitric oxide synthase (NOS) isoforms, respectively. As measured at 100 μM l-arginine, neuronal NOS-catalyzed nitric oxide formation was inhibited 50% at a concentration of 25 μM C3-tris-malonyl-C60-fullerene. This inhibition was a multisite, positively cooperative inhibition with a Hill coefficient of 2.0. C3-tris-malonyl-C60-fullerene inhibited the arginine-independent NADPH-oxidase activity of nNOS with an IC50 value of 22 μM but had no effects on its cytochrome c reductase activity at concentrations as high as 300 μM. The inhibition of nNOS activity by C3-tris-malonyl-C60-fullerene reduced the maximal velocity of product formation but did not alter the EC50 value for activation by calmodulin. C3-tris-malonyl-C60-fullerene reduced the maximal velocity of citrulline formation by inducible NOS without altering the Km for l-arginine substrate or the EC50 value for tetrahydrobiopterin cofactor. As measured by sucrose density gradient centrifugation, fully inhibitory concentrations of C3-tris-malonyl-C60-fullerene did not produce a dissociation of nNOS dimers into monomers. These observations are consistent with the proposal that C3-tris-malonyl-C60-fullerene inhibits the inter-subunit transfer of electrons, presumably by a reversible distortion of the dimer interface.

Nωpropyl-l-arginine (NPA) and S-ethyl-N-[4-(trifluoromethyl)phenyl]isothiourea (TFMPITU) inhibit selectively the neuronal nitric oxide (NO) synthase (nNOS) isoform. In the presence of Ca2+ and calmodulin (CaM), NPA and TFMPITU produce a time- and concentration-dependent suppression of nNOS catalyzed NO formation. This suppression of activity occurs by a first order kinetic process as revealed from linear Kitz–Wilson plots but does not depend on catalytic turnover since it occurs in the absence of NADPH. Following full suppression of NO synthetic activity by either NPA or TFMPITU, NO synthesis can be restored slowly by excess arginine or by dilution, indicating that the effects of these agents are reversible. This behavior is consistent with a dissociation of NPA and TFMPITU from nNOS slowed by a conformational transition produced by Ca2+ CaM-binding. NPA and TFMPITU bind to nNOS rapidly producing a heme–substrate interaction as revealed by difference spectrophotometry. At physiological conditions (100 μM extracellular arginine), NPA and TFMPITU inhibit Ca2+-dependent NO formation by GH3 pituitary cells with IC50 values of 19 and 47 μM, respectively, but require millimolar concentrations to inhibit NO formation by cytokine-induced RAW 264.7 murine macrophages. The inhibition of NO formation by these agents in GH3 cells is rapidly reversible and not due to suppression of cellular arginine uptake.

Purpose: To correlate the X inactivation pattern, as determined by one or more molecular assays, with phenotype in individuals with structurally abnormal X chromosomes.Methods: We utilized methylation analysis of androgen receptor (AR) and Fragile X (FMR1) genes and expression studies of an XIST polymorphism to assess X inactivation patterns of 28 females with structurally abnormal X chromosomes. Individuals were placed in one of three categories: (1) completely nonrandom inactivation of one X chromosome, (2) preferential or skewed inactivation of one X chromosome, or (3) random inactivation of either X chromosome.Results: In 19 of 21 cases with complete (> 7%) skewing of X inactivation, the phenotype was either normal, consistent with a single gene disorder, or consistent with classical Turner syndrome; two cases with completely nonrandom X inactivation had unexplained mental retardation phenotypes. In contrast, six of seven cases that did not exhibit completely nonrandom X inactivation were phenotypically abnormal. Carriers of two balanced translocations, two duplicated Xs, one deleted X, and one 45,X/46,X,r(X) presented with mental retardation and/or multiple congenital anomalies.Conclusion: In patients with random or skewed X inactivation, the abnormal phenotype was hypothesized to be due to functional nullisomy or disomy of X-linked genes. Based on these results, we propose that X inactivation studies should be performed on all women with structurally abnormal X chromosomes. This should aid in the understanding of abnormal phenotypes in liveborn individuals with abnormal X chromosomes and may help to predict phenotypes for prenatally detected cases in the future.

Objective: To determine independent predictors for the development of hypercarbia, subcutaneous emphysema, pneumothorax, and pneumomediastinum during laparoscopy.

The vertical profiles of water vapor and its semi‐heavy hydrogen isotope HDO provided by instruments on ExoMars Trace Gas Orbiter constitute a unique new data set to understand the Martian water cycle including its isotopic composition. As water vapor undergoes hydrogen isotopic fractionation upon deposition (but not sublimation), the D/H isotopic ratio in water is a tracer of phase transitions, and a key quantity to understand the long‐term history of water on Mars. Here, we present 3D global simulations of D/H in water vapor and compare them to the vertically resolved observations of D/H and water ice clouds taken by NOMAD during the second half of Mars year 34. D/H is predicted to be constant with height up to the main cloud level, above which it drops because of strong fractionation, explaining the upper cut‐off in the NOMAD observations when HDO drops below detectability. During the global and regional dust storms of 2018/2019, we find that HDO ascends with H2O, and that the D/H ratio is constant and detectable up to larger heights. The simulations are within the provided observational uncertainties over wide ranges in season, latitude and height. Our work provides evidence that the variability of the D/H ratio in the lower and middle atmosphere of Mars is controlled by fractionation on water ice clouds, and thus modulated by diurnally and seasonally varying cloud formation. We find no evidence of other processes or reservoirs that would have a significant impact on the D/H ratio in water vapor. The isotopic composition of atmospheric water on Mars provides insights about the phase transitions in the water cycle, because the light (H2O) and semi‐heavy (HDO) form of water vapor deposit at different saturation pressures. Knowing the isotopic composition of atmospheric water also provides insights on the long‐term evolution of water on Mars. The NOMAD instrument on ExoMars Trace Gas Orbiter provided the first vertical profiles of the D/H ratio in water vapor on Mars. The data set shows a large variability with season and latitude. To understand this behavior, a general circulation model is required. We provide detailed simulations of the D/H ratio in Martian water vapor and compare them with the NOMAD observations. The model predicts that the D/H ratio is constant in the lower atmosphere and decreases across a layer of strong cloud formation that varies with season. During the global dust storm of 2018, this cloud layer was severely lifted. The simulations compare well to the observations, both out and in the dust storm, and explain their upper cut‐off by this predicted decrease in D/H. No other processes than cloud formation, nor special surface ice reservoirs with strongly different D/H values, were needed to reproduce the observations. Hydrogen fractionation by clouds in Mars water vapor is simulated and evaluated with NOMAD D/H observations in and out of dust stormsThe model D/H ratio is constant and drops when clouds form, explaining the upper cut‐off in the NOMAD profiles as HDO becomes undetectableNOMAD water ice observations provide evidence that fractionation by clouds is the main factor controlling the HDO distribution on Mars Hydrogen fractionation by clouds in Mars water vapor is simulated and evaluated with NOMAD D/H observations in and out of dust storms The model D/H ratio is constant and drops when clouds form, explaining the upper cut‐off in the NOMAD profiles as HDO becomes undetectable NOMAD water ice observations provide evidence that fractionation by clouds is the main factor controlling the HDO distribution on Mars

Estimates of abundance and occupancy are essential for wildlife management, particularly for species of conservation concern such as eastern spotted skunks Spilogale putorius. Most studies of eastern spotted skunks rely on limited evidence for best monitoring practices, and while many studies use attractants to increase detections, previous studies have not tested attractants against a control of no attractant to determine their effectiveness. We tested two common attractants (sardines and fatty acid tablets) and one uncommon attractant (wild boar carcasses) against a control of no attractant to determine if any attractant increased detections of eastern spotted skunks or changed their temporal activity. Based on our model, sardines and wild boar carcasses improved detections by three and eight times that of the control, respectively. Further, for every 100 trap nights, we detected eastern spotted skunks 10.67 times with wild boar carcasses, 1.02 times with sardines, 0.53 times with fatty acid tablets and 0.44 times with no attractant. Wild boar carcasses also substantially decreased latency to detection, with skunks detected two times faster than at other attractants and almost three times faster than at the control. Eastern spotted skunks were most active in the early morning before sunrise, and their temporal activity did not vary significantly by attractant. This study is the first to use an experimental framework to test attractants for eastern spotted skunks, and our results showed that choice of attractant matters. Large animal carcasses, although rarely used, may be most effective for detecting eastern spotted skunks, while fatty acid tablets were no different than the control, and we recommend against their use in future studies. Monitoring plans should incorporate our results as increasing detections is essential to understanding the abundance, range and demographics of eastern spotted skunks.

We present ∼1.5 Mars Years (MY) of ozone vertical profiles, covering LS= 163° in MY34 to LS= 320° in MY35, a period which includes the 2018 global dust storm. Since April 2018, the Ultraviolet and Visible Spectrometer channel of the Nadir and Occultation for Mars Discovery (NOMAD) instrument aboard the ExoMars Trace Gas Orbiter has observed the vertical, latitudinal and seasonal distributions of ozone. Around perihelion, the relative abundance of both ozone and water (from coincident NOMAD measurements) increases with decreasing altitude below ∼40 km. Around aphelion, localized decreases in ozone abundance exist between 25 and 35 km coincident with the location of modeled peak water abundances. High‐latitude (>±55°), high altitude (40–55 km) equinoctial ozone enhancements are observed in both hemispheres (LS∼350°–40°) and discussed in the companion article to this work (Khayat et al., 2021). The descending branch of the main Hadley cell shapes the observed ozone distribution at LS= 40°–60°, with the possible signature of a northern hemisphere thermally indirect cell identifiable from LS= 40°–80°. Morning terminator observations show elevated ozone abundances with respect to evening observations, with average ozone abundances between 20 and 40 km an order of magnitude higher at sunrise compared to sunset, attributed to diurnal photochemical partitioning along the line of sight between ozone and O or fluctuations in water abundance. The ozone retrievals presented here provide the most complete global description of Mars ozone vertical distributions to date as a function of season and latitude. We present over two years of new observations of the vertical distribution of ozone in the atmosphere of Mars. The ExoMars Trace Gas Orbiter spacecraft has been recording observations of the Martian atmosphere since 2018 to map the presence and changes in abundance of gases such as ozone by using the “Nadir and Occultation for Mars Discovery (NOMAD)” instrument. NOMAD continually observes the change in ozone abundance (among other gases) at different heights across much of the planet. These abundance profiles have revealed the presence of distinct layers of ozone enhancement at high altitudes in the atmosphere of Mars toward the polar regions and between spring and autumn in the southern hemisphere of Mars, discussed in detail in the companion article. We observe broad periods where often the abundance of ozone follows the abundance of water from ∼10 km altitude up to ∼50 km altitude, and other times when the two appear to be opposite in their variation with height. Our retrievals of ozone from NOMAD data provide the first coincident observations of ozone and water and provide previously unavailable information on the photochemistry of Mars. The annual Martian O3distribution has been measured at a vertical resolution up to 0.2 km and for the first time alongside H2O profilesO3and H2O show strong vertical anti‐correlation around aphelion as expected, contrasted with vertical correlation toward perihelionO3abundances between altitudes of 20–40 km are an order of magnitude higher at sunrise than at sunset between LS= 40°–50° The annual Martian O3distribution has been measured at a vertical resolution up to 0.2 km and for the first time alongside H2O profiles O3and H2O show strong vertical anti‐correlation around aphelion as expected, contrasted with vertical correlation toward perihelion O3abundances between altitudes of 20–40 km are an order of magnitude higher at sunrise than at sunset between LS= 40°–50°

Observations of Mars during 1996–1997 by the Hubble Space Telescope covered the entire spring season in the northern hemisphere of Mars, which was favorably positioned for viewing the north polar region. This paper reports observations of dust activity during this period. Local dust activity occurred near the edge of the subliming north polar cap during early spring; this included local dust clouds, similar to those seen by Viking near the edge of the south polar cap, and unusual, arc-shaped dust features that seem to represent a new type of dust phenomenon. These dust arcs may explain the Rima Tenuis rift, which has been occasionally seen by groundbased observers of Mars. Analysis of numerical simulations from a Mars general circulation model for the early northern spring season have provided insights into the plausible meteorological background at high latitudes in the vicinity of the retreating north polar cap. These Hubble observations extend the geographic and seasonal ranges during which local dust activity seems to be common on Mars. The combination of image analysis and model calculations support the hypothesis that these dust storms are the result of winds associated with fronts moving across the seasonal cap that lift dust exposed on the cap during CO2sublimation.

NG-Amino-l-arginine, N5-(1-iminoethyl)-l-ornithine, N6-(1-iminoethyl)-l-lysine, and aminoguanidine were studied for the mechanisms by which they produce suicidal inactivation of the neuronal nitric oxide synthase isoform (nNOS). All of the inactivators that were amino acid structural analogs targeted the heme residue at the nNOS active site and led to its destruction as evidenced by the time- and concentration-dependent loss of the nNOS heme fluorescence, which reflects the disruption of the protoporphyrin-conjugated structure. The loss of heme was exclusively associated with the dimeric population of the nNOS. This inactivator-mediated loss of the nNOS heme never reached more than 60%, suggesting that only half of the dimeric heme is involved in catalytic activation of mechanism-based inactivators studied. Aminoguanidine-induced nNOS inactivation produced covalent modification of the nNOS protein chain with a stoichiometry of 0.8 mol of aminoguanidine per mole of the nNOS monomer. Specific covalent modification by aminoguanidine was exclusively associated with the oxygenase domain of the nNOS. The mechanisms by which N6-(1-iminoethyl)-l-lysine and aminoguanidine inactivate the nNOS and iNOS do not differ between the isoforms. The selectivity of these inactivators toward the iNOS isoform is a reflection of their much lower partition ratios, which were determined to be 0.16 ± 0.1 for N6-(1-iminoethyl)-l-lysine and 12 ± 1.5 for aminoguanidine in case of the iNOS isoform while the same inactivators produced the partition ratios of 17 ± 2 and 206 ± 4, respectively, for the nNOS isoform.

We employed the Hubble Space Telescope (HST) Faint Object Spectrograph (FOS) to observe middle ultraviolet (220–330 nm) spectral scans of Mars for two periods during the 1996–1997 northern spring season. Analysis of these data yields quantitative measurements of atmospheric column opacities for aerosols and ozone over a wide range of latitudes (40°S–70°N) in two Mars seasons (solar longitudes,Lsof 10° and 61°). The most significant findings of the analysis are: (1) the global Mars atmosphere exhibited minimal aerosol loading during this season (variable opacities of 0.02–0.08 for clouds, or 0.05–0.2 for dust); (2) the low-to-mid latitude ozone abundance in the Mars atmosphere increased by roughly a factor of two (from 1.8 to 3.6 μm-atm) betweenLs=10° andLs=61°. These results support previous predictions (R. T. Clancy and H. Nair 1996,J. Geophys. Res.101, 12785–12790) and observations (R. T. Clancyet al.1996b,J. Geophys. Res.101, 12777–12783) of orbital (Ls) variations in Mars global ozone abundances, as driven by orbital variations in the global altitudes of water vapor saturation (R. T. Clancyet al.1996a,Icarus122, 36–62). They also support conclusions of very low dust levels in the Mars atmosphere around aphelion (Clancyet al.1996a), with upper limits for background dust opacities which are several times lower than described for this season by the Viking-based dusty model of the Mars climate (e.g.,τ<0.2, here; versus 0.6; D. S. Colburnet al.1989,Icarus79, 159–189). Also of interest is the observation of substantially reduced cloud opacities for the “aphelion cloud belt” in early northern spring (Ls∼ 60°) in 1997, versus 1995 or 1991.

We report initial results from Hubble Space Telescope (HST) images of Mars obtained at a near-IR wavelength of 1042 nm between February 1995 and June 1997. The images provide the highest spatial resolution global near-IR measurements of Mars obtained to date. The data have been calibrated to radiance factor (I/F) to an absolute accuracy of 2 to 5% (including new refinements to several HST calibration parameters) and now exist as a set of coregistered, map-projected images spanning a range of phase angles between 10° and 41°. The relatively high spatial resolution (20–30 km/pixel) global maps, when compared with Viking-era global albedo maps, reveal that substantial variations in Mars surface albedo patterns have occurred in the past 20 years. The most obvious changes include several classical dark regions that have become substantially brighter, and a few formerly bright regions that have darkened. The normal albedo of typical surface regions in the near-IR is derived from the multiple phase angle observations and is found to be bimodal with typical bright and dark values of 0.36 and 0.18, respectively. The surface near-IR phase coefficient ranges from 0.0 to 0.013 mag/deg, and there is no systematic correlation between phase coefficient and normal albedo. This observation is consistent with the diffusely scattering nature of the martian atmosphere even during times of low dust opacity. The data presented here may facilitate the planning and optimization of measurements to be obtained by the Mars Global Surveyor (MGS) Mars Orbiter Laser Altimeter (MOLA), which will begin mapping the planet in 1999. These HST data also provide a basis for comparison with future MOLA and Mars Orbiter Camera (MOC) data in searches for seasonal and interannual variations in surface and polar cap albedo.

A program of synoptic monitoring of Mars was carried out with the Hubble Space Telescope from August 8, 1994, through October 9, 1997, using the Wide Field Planetary Camera 2 (WFPC2). With the improved optics of the WFPC2 and the high angular resolution of the Planetary Camera (0.0442–0.0455 arcsec/pixel) we have been able to use these images to study the properties of the martian satellite Phobos. Phobos has been observed with the Planetary Camera from the ultraviolet (255 nm) to the near-infrared (1042 nm) in the phase range from 10.6° to 40.5°. Phase curves obtained with HST are consistent with results from a model (Simonelli et al. 1998, Icarus131, 52–77) using a global-average Hapke function and a normal albedo of 0.0689. The beginning of an opposition surge along with variations in surface reflectance across Phobos were observed by HST. Disk-integrated photometry encompassing the sub-Mars point suggests the detection of Marsshine at wavelengths longward of 502 nm. Possible weak spectral absorption features seen at 953 and 1042 nm hint at the existence of pyroxene on the surface. However, spectral comparison to different meteorite types resulted in finding no conclusive analogs to the surface reflectance spectrum of Phobos.

A series of substituted aminoguanidines and amino-substituted isothioureas have been examined as inhibitors of nitric oxide (NO) synthase (NOS) isoforms. Each of the agents produced a time- and concentration-dependent inactivation of the NO-forming activity of the affinity-purified NOS isoforms. These inactivations required exposure of NOS to the drug under conditions that supported catalysis, consistent with the proposal that they act as alternate substrate, mechanism-based inactivators. Of the aminoguanidines examined, 2-ethylaminoguanidine was the most efficient inactivator, exhibiting vs.iNOS an apparent KIvalue of 120 μM as measured at 100 μM arginine and a kinact maxvalue of 0.48 min−1and thus an apparent second-order rate constant for inactivation of 4.0 mM−1min−1. 2-Ethylaminoguanidine displayed a high isoform selectivity for the iNOS compared with the nNOS and eNOS isoforms. 2-Ethylaminoguanidine inactivated NO synthetic activity in cytokine-induced RAW 264.7 cells as measured at 100 μM extracellular arginine with an apparent KIvalue of 55 μM and a kinact maxvalue of 0.09 min−1. The inactivated RAW 264.7 cell NO synthetic capability was restored over a 3-hr period after drug removal to a value 60% of its pretreatment value. This recovery occurred despite the presence of cycloheximide sufficient to inhibit protein synthesis by >99%. 1-Amino-S-methylisothiourea by contrast with the aminoguanidines was identified as a mechanism-based inactivator selective for the nNOS isoform. In contrast to S-isopropylisothiourea, which was found to be both cell penetrant and reversible, 1-amino-S-methylisothiourea appeared cell impermeable and inhibited NOS enzyme “irreversibly.”

Infection is the major cause of morbidity and mortality in children receiving anticancer therapy. Children who have severe neutropenia (neutrophil count less than 100/ mm3) for longer than 2 weeks should receive oral antibiotic prophylaxis. At present, trimethoprim sulfame-thoxazole in combination with either nystatin or amphotericin B is the best regimen for reducing the incidence of serious infections. Trimethoprim sulfamethoxazole is very effective in the prevention of Pneumocystis cariniipncumonitis. Clinicans will have to balance the advantages and disadvantages of prophylaxis in patients who are at risk for P. cariniipneumonitis.

A Ca2+/calmodulin (CaM)-dependent multifunctional protein kinase has been isolated from Aspergillus nidulans and purified to homogeneity. Unlike any CaM-dependent multifunctional protein kinase described previously, the native enzyme from Aspergillus behaves as a monomer. The calculated molecular weight is 41,200. NaDodSO4/PAGE reveals a single protein band with an apparent Mr of 51,000. Two-dimensional isoelectric focusing/NaDodSO4/PAGE of the purified enzyme showed one major and one minor more acidic Coomassie blue-stained spot, both of which bind 125I-labeled calmodulin in a calcium-dependent manner. The kinase is autophosphorylated in a calcium- and CaM-dependent manner, yielding an increase in the amount and number of more acidic forms of the enzyme. The Aspergillus kinase catalyzes the Ca2+/CaM-dependent phosphorylation of known substrates of type II Ca2+/CaM-dependent protein kinases, including glycogen synthase, microtubule-associated protein 2, synapsin, tubulin, gizzard myosin light chain, and casein. Cross-reactivity between antiserum raised against native rat brain protein kinase II and 125I-labeled Aspergillus kinase has been detected. Two forms of CaM have been isolated from Aspergillus nidulans, both of which activate the Aspergillus kinase at lower concentrations than that required for activation by bovine brain CaM.

Adsorption of 12-(4-nitroanilino)dodecanethiol from ethanol and n-hexane onto polycrystalline gold substrates was studied in situ and in real time by second-harmonic generation. Depending on the fundamental wavelength used, the attachment of the thiol to the substrate or the behavior of the p-nitroaniline (pNA) endgroup can selectively be monitored. Striking solvent effects are shown for the process of film formation. The time scales on which changes related to the coverage and the orientation of the pNA moiety occur vary widely. In hexane the thiol coverage increases about four times faster than that in ethanol. The rearrangement of the pNA endgroups in ethanol occurs on a time scale that is larger by a factor of 2 to three compared to the adsorption. In contrast, hexane extends the process of reorientation by a factor of more than 30 relative to the time scale of adsorption. A qualitative model based on the differences in the solvent−thiol interactions is suggested.

The evidence from observation and theory is mounting that cosmic dust grains possess a fluffy and composite nature. The computational simplicity of using effective medium theory (EMT) with series solution cross sections to model such grains has lead some workers to disregard the validity criterion inherent in the various EMT mixing rules. Fortunately, the recent availability of robust electromagnetic scattering finite element codes allows one to explore the applicability of the various mixing rules through direct computation. Building on the methodology and results of a previous paper, we extend our calculations to the angular distribution of scattered light. We establish numerical and physical convergence properties for both solid and porous targets. The discrete dipole approximation (DDA) scattering properties are compared to those computed by the EMT/series solution technique in order to examine further the applicability of several mixing rules. For grains with vacuum inclusions in the Rayleigh limit, we show that the EMT/series solution approach is generally valid even for the particle phase functions, especially in the case of a polydispersion (size distribution) of particles. We also investigate the impact of inclusions that are clearly non-Rayleigh in nature and find that they can be significant and are not reproducible by the mixing rules considered. Possible ramifications of the results are explored through the simple example of radiation pressure in late-type stellar and brown dwarf environments.

A number of clinical reports have described children with a variety of congenital anomalies in association with uniparental disomy (upd) of chromosome 14, suggesting that at least some genes on chromosome 14 are subject to parent of origin, or imprinting, effects. However, little else is known about this putative imprinting of chromosome 14. Both maternal and paternal upd have been observed, but a consistent phenotype has only been suggested for the former. Here we report on a child with developmental delay, microcephaly, distinct facial findings, and who has a duplication of 14q24.3q31. The same cytogenetic abnormality was found in her phenotypically normal father. We hypothesize that this segment of chromosome 14 contains maternally silenced genes, and that this duplicated segment defines an imprinted region on chromosome 14. Alternatively, this cytogenetic duplication may be unrelated to the girl's phenotypic anomalies, and this duplication may contain genes that are not subject to dosage effect. Am. J. Med. Genet. 71:361–365, 1997. © 1997 Wiley-Liss, Inc.

Fluorescence in situ hybridization (FISH) using biotin labeled X- and Y-chromosome DNA probes was utilized in the analysis of 23 sex chromosome-derived markers. Specimens were obtained through prenatal diagnosis, because of a presumptive diagnosis of Ullrich-Turner syndrome, mental retardation, and minor anomalies or ambiguous genitalia; three were spontaneous abortuses. Twelve markers were derived from the X chromosome and eleven from the Y chromosome; this demonstrates successfully the value and necessity of FISH utilizing DNA probes in the identification of sex chromosome markers. Both fresh and older slides, some of which had been previously G-banded, were used in these determinations. We have also reviewed the literature on sex chromosome markers identified using FISH. Am. J. Med. Genet. 71:1–7, 1997. © 1997 Wiley-Liss, Inc.

Astro-2 has revealed a broad, weak spectral feature in the ultraviolet interstellar linear polarization for two lines of sight, confirming the original detection toward HD 197770 and adding HD 147933-4. These are the only two polarization features found in some 30 lines of sight now observed. Both features are centered close to 2175 Å, the position of the ubiquitous ultraviolet extinction bump. Two possibilities are considered for the source of the polarization feature: changes in the mass distribution of the aligned silicate grains responsible for the continuum polarization, and alignment of the small graphite grains responsible for the extinction bump. While the former approach meets with some success for the HD 197770 feature, it is not possible to produce a feature as clearly peaked as in HD 147933-4. The central wavenumbers and widths of both polarization features correspond closely to those of the corresponding extinction bump. Taken together, it seems the graphite grains are a more likely source of the polarization features. Both polarization features have amplitudes that are very small compared to the amount of excess extinction present in the 2175 Å bump, implying poor polarization efficiency. Many other lines of sight have been observed with sufficient signal-to-noise ratios such that features should have been clearly detected if the same polarization efficiency applied, and so real variations in the alignment or shape of the grains responsible seem to occur from one line of sight to another. The weak alignment might be caused by unusually low concentrations of paramagnetic impurities in rapidly spinning small grains.