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Meteoroids of sub‐milligram sizes burn up high in the Earth's atmosphere and cause streaks of plasma trails detectable by meteor radars. The altitude at which these trails, or meteors, form depends on a number of factors including atmospheric density and the astronomical source populations from which these meteoroids originate. A previous study has shown that the altitude of these meteors is affected by long‐term linear trends and the 11‐year solar cycle related to changes in our atmosphere. In this work, we examine how shorter diurnal and seasonal variations in the altitude distribution of meteors are dependent on the geographical location at which the measurements are performed. We use meteoroid altitude data from 18 independent meteor radar stations at a broad range of latitudes and investigate whether there are local time (LT) and seasonal variations in the altitude of the peak meteor height, defined as the majority detection altitude of all meteors within a certain period, which differ from those expected purely from the variation in the visibility of their astronomical source. We find a consistent LT and seasonal response for the Northern Hemisphere locations regardless of latitude. However, the Southern Hemisphere locations exhibit much greater LT and seasonal variation. In particular, we find a complex response in the four stations located within the Southern Andes region, which indicates that the strong dynamical atmospheric activity, such as the gravity waves prevalent here, disrupts, and masks the seasonality and dependence on the astronomical sources. Small meteoroids burn up high in the Earth's atmosphere producing trails of plasma detectable by ground‐based meteor radar instruments. The altitude at which these trails occur depends on a number of factors including atmospheric density and the astronomical source populations from which these meteoroids originate. Previous work demonstrated that the altitude at which the majority of these meteoroids burn up (termed “peak meteor altitude”) is affected by long‐term atmospheric changes, such as those related to greenhouse gas emissions and the 11‐year solar cycle. Here, we focus on shorter timescales and analyze meteoroid altitude data from 18 geographically diverse meteor radars to examine the local time (LT) and seasonal variation in the peak meteor altitudes on a latitude basis. We find a consistent LT and seasonal response among the six Northern Hemisphere meteor radar station locations irrespective of latitude. However, we find a more complex response among the 12 Southern Hemisphere stations with much greater LT and seasonal variation. In particular, we found a complex response in the four stations located within the Southern Andes region, a geographic region known for intense atmospheric gravity wave activity, which acts to mask and disrupt the seasonality and dependence on the astronomical sources. Local time (LT) and seasonal variations in the peak meteor height exist, which differ from those expected from astronomical variation aloneThere is a consistent LT and seasonal response in the Northern Hemisphere locations regardless of latitudeA complex response in the Andes region where a strong gravity wave component acts to mask seasonality and dependence on astronomical sources Local time (LT) and seasonal variations in the peak meteor height exist, which differ from those expected from astronomical variation alone There is a consistent LT and seasonal response in the Northern Hemisphere locations regardless of latitude A complex response in the Andes region where a strong gravity wave component acts to mask seasonality and dependence on astronomical sources

Observations by the Cloud Imaging and Particle Size (CIPS) instrument on the Aeronomy of Ice in the Mesosphere (AIM) satellite show an anomalous decline in Northern Hemisphere polar mesospheric clouds (PMCs) from 26 July to 6 August 2014. The decline is attributed to local warming associated with the quasi‐two‐day wave and interhemispheric coupling (IHC) triggered by planetary wave breaking in the Antarctic (winter) stratosphere. The results indicate that the IHC in 2014 occurred via a pathway that previous studies have not emphasized. Based on observations from the Aura Microwave Limb Sounder (MLS) and reanalyses from both the Modern‐Era Retrospective analysis for Research and Applications, Version 2 (MERRA‐2) and the Navy Global Environmental Model (NAVGEM), we argue that a strengthening of the summer easterly jet gave rise to enhanced meridional and vertical shear along its equatorward flank, which supported growth of the two‐day wave. The two‐day wave led to enhanced meridional mixing in northern midlatitudes and a weakening of the northern branch of the mesospheric residual circulation, reducing ascent and warming the polar summer mesopause. In 2014, the five‐day planetary wave modulated the response to IHC such that PMCs persisted in its cold phases even though zonal mean temperatures were too high to support PMCs, and were absent in the warm phases when zonal mean temperatures were low enough to support PMCs. Polar mesospheric cloud frequencies decline rapidly in July 2014 due to a two‐day wave‐driven warming of the mesopause regionWintertime planetary waves lead to anomalous temperatures at low latitudes, enhanced extratropical wind shear, and two‐day wave growthThe response of polar mesospheric clouds to the two‐day wave‐driven temperature increase is modulated by a large mesospheric five‐day wave

We examine wave components in a high‐altitude forecast‐assimilation system that arise from nonlinear interaction between the diurnal tide and the westward traveling quasi 2 day wave. The process yields a westward traveling “sum” wave with zonal wave number 4 and a period of 16 h, and an eastward traveling “difference” wave with zonal wave number 2 and a period of 2 days. While the eastward 2 day wave has been reported in satellite temperatures, the westward 16 h wave lies outside the Nyquist limits of resolution of twice daily local time satellite sampling. Hourly output from a high‐altitude forecast‐assimilation model is used to diagnose the nonlinear quadriad. A steady state primitive equation model forced by tide‐2 day wave advection is used to intepret the nonlinear wave products. The westward 16 h wave maximizes in the midlatitude winter mesosphere and behaves like an inertia‐gravity wave. The nonlinearly generated component of the eastward 2 day wave maximizes at high latitudes in the lower thermosphere, and only weakly penetrates to low latitudes. The 16 h and the eastward 2 day waves are of comparable amplitude and alias to the same apparent frequency when viewed from a satellite perspective. We have identified diurnal tide‐2 day wave interaction products in a global middle atmosphere data setWe have confirmed nonlinear interaction as a source using a numerical model with realistic background winds and temperaturesWe have compared the westward traveling 16 h wave with ground‐based radar wind measurements

There is currently an ambiguity in what controls polar mesospheric cloud (PMC) periodicities near 83 km altitude. This is primarily because satellite and ground‐based data sets cannot resolve global mesospheric temperature variability over the diurnal cycle. To address this limitation, we employ a global meteorological analysis and forecast system that assimilates mesospheric satellite data with two significant advances. The first is that we use output at a more rapid one hourly cadence, allowing for a quantitative description of diurnal (24 h), semidiurnal (12 h), and terdiurnal oscillations. The second is that the output drives a simple PMC parameterization which depends only on the local temperature, pressure, and water vapor concentrations. Our study focuses on results from July 2009 in the Northern Hemisphere and January 2008 in the Southern Hemisphere. We find that the 24 h migrating temperature tide as well as the 12 h and 24 h nonmigrating tides dominate northern PMC oscillations whereas the 12 h and 24 h nonmigrating tides dominate southern oscillations. Monthly averaged amplitudes for each of these components are generally 2–6 K with the larger amplitudes at lower PMC latitudes (50°). The 2 day and 5 day planetary waves also contribute in both hemispheres, with monthly averaged amplitudes from 1 to 3 K although these amplitudes can be as high as 4–6 K on some days. Over length scales of ~1000 km and timescales of ~1 week, we find that local temperature oscillations adequately describe midlatitude PMC observations. Solar temperature tides and the 2 day and 5 day planetary waves are quantified throughout the northern and southern PMC regionsThe impact of these periodicities on PMC frequency and ice water content are determinedPMC results are compared directly to two independent satellite data sets

The mesosphere/lower thermosphere (MLT, 80–100 km) region is an important boundary between Earth's atmosphere below and space above and may act as a sensitive indicator for anthropogenic climate change. Existing observational and modeling studies have shown the middle atmosphere and the MLT is cooling and contracting because of increasing greenhouse gas emissions. However, trend analyses are highly sensitive to the time periods covered, their length, and the measurement type and methodology used. We present for the first time the linear and 11‐year solar cycle responses in the meteor ablation altitude distributions observed by 12 meteor radars at different locations. Decreasing altitudes were seen at all latitudes (linear trends varying from −10.97 to −817.95 m dec−1), and a positive correlation with solar activity was seen for most locations. The divergence of responses at high latitudes indicates an important and complex interplay between atmospheric changes and dynamics at varying time scales. High up in our atmosphere lies the mesosphere/lower thermosphere region (80–100 km); an important transition zone between the atmosphere below and space above. Existing studies indicate that this region is changing (cooling and contracting) in response to increasing greenhouse gas emissions, quite unlike the net warming we see near the surface. However these trend studies are often highly sensitive to choice and length of time period covered, and the methodology and type of measurements used. Here we present for the first time a self‐consistent methodology applied to 12 different meteor radar station datasets located at a diverse range of latitudes. We looked at changes in the mean peak altitude of individual meteoroid detections, and found decreasing peak altitudes at all locations examined (linear trends varying from −10.97 to −817.95 m decade−1) consistent with a global cooling and contracting of the upper atmosphere. We also examined the response to the 11‐year solar cycle and found a positive correlation with solar activity (i.e., increased meteoroid peak altitudes during solar maximum, and vice versa) for low and mid‐latitude locations. However we found an anti‐correlation at high latitudes suggestive of an important and complex interplay between atmospheric changes and dynamics at varying time scales. Use of geographically diverse meteor radar peak detection altitudes to assess long‐term and 11‐year solar cycle (SC) trends in mesopause regionThe altitude of observed peak meteor height has decreased over time at all locations, regardless of latitude and data setPositive correlation at low‐ and mid‐latitude locations with the 11‐year SC, but more complex response at high‐latitudes Use of geographically diverse meteor radar peak detection altitudes to assess long‐term and 11‐year solar cycle (SC) trends in mesopause region The altitude of observed peak meteor height has decreased over time at all locations, regardless of latitude and data set Positive correlation at low‐ and mid‐latitude locations with the 11‐year SC, but more complex response at high‐latitudes

We present direct, global observations of longitudinally averaged CHAMP zonal winds gathered between 2003 and 2007. A diurnal variation dominates the global zonal wind. Westward flows are observed from the early morning through afternoon hours, while eastward flows peak in the evening. A semidiurnal harmonic is also present, with magnitudes that are approximately one third of the diurnal harmonic. The time mean wind indicates westward winds over much of the globe, with weak superrotation (+E, or eastward winds) that is symmetric about the equator during equinox, and confined to the winter hemisphere at solstice. Diurnal and time mean CHAMP winds agree fairly well with the Whole Atmosphere Model. Some differences are observed in the semidiurnal and higher‒order tidal winds, that underscore the challenges of modeling the sources, sinks, and mean wind effects upon tides between the surface and 400 km. Diurnal variation dominates the global zonal wind near 400 kmWeak superrotation at winter latitudes, and equinoctial low latitudesGood agreement with with WAM

An NCI-sponsored, phase II trial of N-(4-hydroxyphenyl)- retinamide (4-HPR) in patients with organ-confined prostate cancer in the period prior to radical prostatectomy was carried out. Thirty-seven men with the histologic diagnosis of prostate cancer planning to have radical prostatectomy entered the study after informed consent and were given 4-HPR (or matching placebo) as a single daily dose (two 100-mg capsules of 4-HPR or two capsules of placebo daily) for 3 weeks prior to surgery. Four men dropped out for unrelated reasons. Thirty-three men completed the study. At the time of surgery, repeat biopsies of the prostate were performed to study the effects of the drug on potential surrogate endpoint biomarkers (SEBs) of malignancy within the tissue. The panel of potential SEBs of malignancy include p53, cytomorphometric indices, ploidy, PNCA, erbB-2, erbB-3, EGF receptor, TGF-α tumor-associated glycoprotein-72, fatty acid synthetase and Lewis Y antigen. Twenty-three patients had matching pre- and posttherapy lesions and were considered informative. Results from the patients indicate significant differential expression of biomarkers in pretreatment specimens of uninvolved prostatic tissue (normal-appearing epithelia) prostatic intraepithelial neoplasia (PIN) and prostate cancer. The mean erbB-2 expression was 0.58 in uninvolved vs. 1.04 in PIN (p = 0.002); while the mean erbB-2 expression was 1.35 in prostate cancer (p = 0.0007, uninvolved vs. prostate cancer). A similar pattern of increased biomarker expression between uninvolved and PIN or prostate cancer tissues can be observed for EGF receptor (mean = 1.21, 1.87 and 1.76 for uninvolved, PIN and prostate cancer, respectively) and erbB-3 (mean = 0.81, 1.59 and 1.30 for uninvolved, PIN and prostate cancer, respectively). There were no statistically significant differences in biomarkers observed in the 4-HPR-treated patients when compared with placebo-treated control patients. There was a posttreatment up-regulation of biomarkers observed in both groups of patients. This observation is most likely explained by an effect due to the diagnostic sextant biopsy equally affecting both groups of patients. Results from this study do not demonstrate a chemoprevention effect of 4-HPR on tissue-based SEBs at the dose given.

Six patients with cutaneous metastases of malignant melanoma were treated with bacillus Calmette-Guérin (BCG). Rosette formation by sheep erythrocytes surrounding thymus-derived lymphocytes was studied by two methods (“active” and total rosette-forming cells) before and after therapy. Four patients showed good clinical response with regression of some or all skin nodules, and two did not respond. All four responders showed an increase in “active” rosette-forming cells; two also had increases in total rosette-forming cells. One nonresponder had an increase in “active” rosette-forming cells. It is proposed that BCG activates both nonspecific and specific thymus-derived cell populations. Traffic of thymus-derived cells may also occur after administration of BCG.

Cell and tissue growth is regulated through a complex interplay of stimulatory and inhibitory signals. We describe two biological actions of transforming growth factor beta 1 (TGF-beta 1) in primary cultures of rabbit uterine epithelial cells: (i) inhibition of cell proliferation and (ii) a concomitant increase in cells undergoing apoptosis (programmed cell death). It is proposed that proliferation and apoptosis together comprise normal cell growth regulation.

The effect of altered tubular sodium reabsorption on renin secretion (RSR) was examined under conditions in which other factors influencing renin release could be controlled or excluded. To do this, isolated canine kidneys were perfused at constant pressure with blood circulating from donor animals. Volume expansion or hemorrhage of the donor dogs produced large changes in the animal's blood pressure, renal function, sodium excretion (UNaV), and RSR, but were without effect on renal hemodynamics, UNaV, or RSR in the perfused kidney. Hemodilution without volume expansion, resulted in hypotension, decreased UNaV and increased RSR in the donor dogs, and increased UNaV and suppressed RSR in the perfused kidney. These effects of hemodilution in the perfused kidney were partially reversed when plasma protein concentration was restored to control levels with hyperoncotic albumin, and, overall, there was a significant inverse relationship between electrolyte excretion and RSR. These results provide new evidence for the hypothesis that the rate at which sodium is delivered to the macula densa is an important determinant of the rate of renin secretion.

We used site-directed mutagenesis to localize serologically defined (s) and CTL (c)-defined alloantigenic determinants to discrete amino acid sequences of a murine MHC class I antigen. Based on the prediction that amino acid position 63-73 of the H-2Dd antigen forms s-allodeterminants, the H-2Ld gene was mutated in a sequential fashion to replace codons for amino acid positions 63, 65, 66, 70, and 73 with those of the H-2Dd amino acids. Epitopes of the mutant antigens expressed in L-cells were examined by the binding of a series of mAbs specific for the H-2Dd antigen. The mutant antigen M66 had substitutions at residues 63, 65, and 66, and resulted in the acquisition of a number of H-2Dd-specific s-epitopes. Mutant M70 had an additional substitution at residue 70, which led to the gain of multiple additional H-2Dd s-epitopes. Together, more than half of all the relevant H-2Dd s-epitopes were mapped into amino acid position 63-70 of the H-2Dd molecule, which was expressed in the mutant H-2Ld gene. The final mutation at residue 73 (M73) caused no new epitope gains, rather, a few Dd s-epitopes acquired by the preceding mutations were lost. All of the H-2Ld-specific s-determinants were retained in the mutant molecules, as were H-2Dd s-determinants specific for the alpha-2 or alpha-3 domains. Changes of these residues affected c-determinants defined by CTL. Anti-H-2Dd CTL cultures and an anti-H-2Dd CTL clone recognized the mutant H-2Ld molecules, M66 and M70. Some CTL clones generated against the Q10d molecule, which has an identical sequence to H-2Dd between residues 61 and 73, failed to recognize native H-2Dd or Ld but did crossreact with mutant Ld. While bulk-cultured anti-H-2Ld CTL cultures reacted strongly against M73, bulk-cultured H-2Ld restricted anti-vesicular stomatitis virus CTL did not. Finally, at the clonal level two of three anti-H-2Ld CTL clones lost reactivity with some or all of these mutant molecules. From these results we conclude that a stretch of amino acids from position 63 to 70 of the alpha-1 domain controls major s- and c-antigenic sites on the H-2Dd antigen and c-sites on H-2Ld antigen.

A randomized concentration-controlled clinical trial (RCCCT) is an alternate experimental design to the standard dose-controlled study. In a RCCCT, patients are randomly assigned to predefined plasma or blood drug concentration ranges (low, medium, and high). With the caveat that concentration ranges are sufficiently separated, this design should enhance the ability to discover important concentration response relationships. FK-506, a potent and promising immunosuppressive agent for prevention and treatment of graft rejection, has shown significant clinical activity in some immune-mediated disorders. To implement the RCCCT design, a novel FK-506 intelligent dosing system (IDS) was used to guide all doses to prospectively achieve the target concentration range specified in the study protocol. Patients enrolled in these trials suffered from a variety of autoimmune disorders, including multiple sclerosis, primary biliary cirrhosis, psoriasis, autoimmune chronic active hepatitis, and nephrotic syndrome. We observed excellent predictive performance of the IDS for all patients. The accuracy (mean prediction error) of the IDS was −0.022 ng/ml and the precision (standard deviation of the prediction error) was 0.119 ng/ml. Thus, the IDS is both accurate and reproducible for autoimmune patients. We conclude that the RCCCT design, guided by an accurate and precise IDS, is an informative and cost-effective approach for evaluation of efficacy and safety of effective but highly toxic agents.

The Speech-Language Pathologist Stress Inventory (SLPSI) is a 48-item questionnaire adapted from the Teacher Stress Inventory (Fimian, 1988). Factor analyses of the responses of 626 speech-language pathologists revealed four stress source factors (Bureaucratic Restrictions, Time and Workload Management, Lack of Professional Supports, and Instructional Limitations) and two stress manifestation factors (Emotional-Fatigue Manifestations and Biobehavioral Manifestations). The internal consistency reliability of scales based on these factors ranged from .71 to .87, with .93 for the entire scale. Evidence for construct validity was found in moderate positive correlations between the scales of the SLPSI and the scales of the Maslach Burnout Inventory (MBI) (Maslach & Jackson, 1986). Stress and burnout subscale intercorrelations ranged from .10 to .82 (p<.01), and the correlation between stress strength and burnout frequency was .66 (p<.001).

Four recently developed adolescent language tests, the Fullerton Test for Adolescents (FLTA), the Test of Adolescent Language (TOAL), the Clinical Evaluation of Language Functions (CELF), and the Screening Test of Adolescent Language (STAL), were compared to determine: (a) whether they measured the same language skills (content) in the same way (procedures); and (b) whether students performed similarly on each of the tests. First, respective manuals were reviewed to compare selection of subtest content areas and subtest procedures. Then, each of the tests was administered according to standardized procedures to 30 unselected sixth-grade students. Despite apparent differences in test content and procedures, there was no significant difference in students' performance on three of the four tests, and correlations among test performance were moderate to high. A comparison of the pass/fail rates for overall performance on the tests, however, revealed a significant discrepancy between the proportions of students identified in need of further evaluation on the STAL (20%) and the proportion diagnosed as language impaired on the three diagnostic tests (60-73%). Clinical implications are discussed.

Crane scheduling problems are introduced together with a descriptive general model. In particular, crane scheduling problems with one operation per job are investigated when arrival patterns are static or dynamic and when the processing times are arbitrary.

The antibody response to the inulin [(In), beta-(2 leads to 1) fructosan] determinant of bacterial levan [(BL), a beta-(2 leads to 6) polyfructosan that contains beta-(2 leads to 1) branch points] requires the presence of the a haplotype of the Igh gene complex. BALB/c (Igh a) mice immunized with BL produce IgG anti-In antibodies of a single spectrotype by isoelectric focusing analysis. C57BL/6 mice, which possess the b haplotype of the Igh gene complex and which fail to produce anti-In antibodies, nevertheless possess a gene, spectrotype regulation gene 1 (Sr-1), that regulates the isoelectric focusing (IEF) pattern of anti-In antibodies in mice of the a haplotype. Thus, the IEF patterns of anti-In antibodies of (BALB/c x C57BL/6)F1 mice and of B.C8 mice (C57BL/Ka . Igh-Ca) are considerably more complex than those of BALB/c. Backcross analysis indicates that Sr-1 is not linked to the Igh complex, the major histocompatibility complex, or to the genes that code for coat color. Studies of the heterogeneity of anti-In antibodies in recombinant inbred lines and their progeny from matings to BALB/c and C.B20 (BALB/c . Igh-Cb) suggest the existence of other regulatory genes.

Idiotypes of inulin-binding myeloma proteins (InuBMP) were determined primarly by variable region light chains (VL) or by variable region heavy chains (VH) but needed both chains to be expressed. Recombinant molecules were used to show that individual idiotypes (IdI) of U61, E109, T957, and A4 InuBMP and cross-specific idiotypes (IdXB) of U61 were primarily determined by VL while cross-specific idiotype (IdXA) of A4 was determined mainly by VH. The assignment of genes controlling idiotypes to VH based on allotype linkage (e.g., IdXB) is dubious until the role of the L chain in determining that idiotype is assessed. IdXB has been shown to be a VL-VH marker which presumably is controlled by two unlinked genes. However IdXB can be used as a L chain marker in combinations of strains differing in their L chain genes but having the same permissive H chain genes. Conversely IdXB can be used as a H chain marker in strains having the same permissive L chain genes but differing in their H chain genes.

13 leven-binding myeloma proteins (LBMP) of BALB/c origin were classified into two groups with different binding specificities; one group of 11 proteins bound beta2 leads to 1 fructosans, a second group of two proteins bound fructosans probably of beta2 leads to 6 linkage. Anti-idiotypic sera prepared to 10 of the proteins in the appropriate strains of mice identified numerous idiotypic determinants. Each protein used for immunization had its own unique individual idiotypic specificities (IdI) and in addition most of the proteins carried two-nine cross-specific or shared idiotypes (IdX) that were found only among LBMP, and not found in 106 non-LBMP. Most of the IdX determinants and only four of the IdI determinants of the beta2 leads to 1 fructosan binding group were located in the antigen-binding site. The multiplicity of antigenic differences in this functionally related group of immunoglobulins reveals an unexpected degree of heterogeneity in V-regions that appears to be unrelated to binding.

Mice with the CBA/N defect are unresponsive to the hapten phosphorylcholine (PC) even when presented on a variety of immunogenic carriers. Since these mice have the variable region gene for PC, their inability to respond may reflect deletion or suppression of the line of B lymphocytes which is responsible for the anti-PC response.

Uteroglobin, the primary secretory protein of rabbit uterine epithelium, was localized by the direct immunoperoxidase method in uteri of control ovariectomized rabbits and of ovariectomized rabbits injected with progesterone or estradiol-17 ß.

The idiotype present on the Fab of a phosphorylcholine-binding IgA myeloma protein TEPC 15 (T15) of BALB/c origin was found in normal serum of BALB/c mice. Molecules carrying the T15 idiotype in normal serum could be adsorbed with Sepharose phosphorylcholine beads and R36A pneumococci. The T15 idiotype is absent in germ-free BALB/c but appears when the mice are conventionalized. A survey of normal sera of inbred strains for the T15 idiotype showed it to be present in BALB/c, 129, C57L, C58, and ST and absent or in low levels in CBA, C3H, C57BL/6, C57BL/Ka, C57BL/10, SJL, B10.D2, DBA/2, RIII, A, AL, AKR, NZB, and NH inbred strains of mice. The T15 idiotype is associated with some but not all strains carrying the IgCH allotypes found in BALB/c. Linkage of genes controlling the T15 idiotype in normal serum to the IgCH locus of BALB/c was demonstrated in F2 progeny of a BALB/c and C57BL cross, Bailey's recombinant inbred strains, C x BD, C x BE, C x BG, C x BH, C x BI, C x BJ, C x BK, and CB20 congenic strains. Among these strains, only those possessing the IgCH locus of BALB/c including the F2 progeny consisting of BALB/c homozygotes and BALB/c/C57BL heterozygotes and C x BG and C x BJ recombinants showed the T15 idiotype.

Two H-2-linked autosomal dominant immune response (Ir) genes Ir-IgG and Ir-IgA were demonstrated to be at separate loci. Ir-IgG controls the immune response to IgG (γ2a) myeloma proteins and Ir-IgA the immune response to IgA meyloma proteins. Both genes are associated with the H-2K region specificities of the H-2 chromosome, specifically Ir-IgG with H-2b and Ir-IgA with H-2a. Different recombinants derived from H-2a/H-2b crossovers were examined for their immune responsiveness to BALB/c IgG (γ2a) and IgA myeloma proteins. B10 (H-2b) parental type responded only to IgG; B10.A (H-2a) responded only to IgA. All the recombinants except for B10.A (4R) responded to either IgG or IgA. B10.A (4R), however, responded to both IgG and IgA. This indicated that the crossover event giving rise to B10.A (4R) occurred between the Ir-IgG and Ir-IgA loci.

Agglutinin responses to sheep erythrocytes and immunoglobulin heavy chain phenotypes determined in F1, F2, and backcross progeny of mice genetically selected for high and low antibody synthesis indicated that an immune response gene for sheep erythrocytes is linked to the immunoglobulin heavy chain allotype. Mice homozygous for the phenotype of the high line had significantly higher titers than mice homozygous for the phenotype of the low line. An association was also observed in some progeny of the backcross of the F1 generation with the low line. However, the control of the immune response was clearly multigenic since heterozygous mice of the same phenotype (2/3, 5) resulting from the two backcrosses (high and low) had very different immune responses. Immunoglobulin levels in the same progeny showed no linkage to the immunoglobulin allotype but a rather simple pattern of inheritance.

A randomized concentration-controlled clinical trial (RCCCT) is a trial design in which patients are randomized to predefined blood drug concentrations (low, medium, high). If the concentration ranges are sufficiently separated, this study design can reveal important blood concentration-response relations. Tacrolimus is a potent yet “infant” immunosuppressant for the treatment and prevention of graft rejection and has been shown to exhibit significant clinical activity in some immune-mediated disorders. A tacrolimus artificial intelligence modeling system (AIMS) was used to guide patient dosing to achieve target concentrations specified by the study protocols. In the Multiple Sclerosis study group, we were able to define a concentration range (0.3-0.7 ng/ml) that appeared to show efficacy and minimal tacrolimus toxicity. Patients randomized to the high zone (0.6-1.2 ng/ml) in the Primary Biliary Cirrhosis study group showed significant reduction (50%) in surrogate efficacy markers [aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT)] compared with patients in the low zone (0.1-0.6 ng/ml). Therefore the RCCCT allowed the detection and delineation of clinically significant concentration-response relations in an ethical and efficient manner.

Describes how the newly democratic masses in central Europe and the U.S.S.R.can't get enough of Hollywood on video. Popularity of VCRs; `Rambo', roc-n-roll, and porn; Success of video industry; Who set it all up; Unenforced laws.