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Immunological health has been challenging to characterize but could be defined as the absence of immune pathology. While shared features of some immune diseases and the concept of immunologic resilience based on age-independent adaptation to antigenic stimulation have been developed, general metrics of immune health and its utility for assessing clinically healthy individuals remain ill defined. Here we integrated transcriptomics, serum protein, peripheral immune cell frequency and clinical data from 228 patients with 22 monogenic conditions impacting key immunological pathways together with 42 age- and sex-matched healthy controls. Despite the high penetrance of monogenic lesions, differences between individuals in diverse immune parameters tended to dominate over those attributable to disease conditions or medication use. Unsupervised or supervised machine learning independently identified a score that distinguished healthy participants from patients with monogenic diseases, thus suggesting a quantitative immune health metric (IHM). In ten independent datasets, the IHM discriminated healthy from polygenic autoimmune and inflammatory disease states, marked aging in clinically healthy individuals, tracked disease activities and treatment responses in both immunological and nonimmunological diseases, and predicted age-dependent antibody responses to immunizations with different vaccines. This discriminatory power goes beyond that of the classical inflammatory biomarkers C-reactive protein and interleukin-6. Thus, deviations from health in diverse conditions, including aging, have shared systemic immune consequences, and we provide a web platform for calculating the IHM for other datasets, which could empower precision medicine.

Acute viral infections can have durable functional impacts on the immune system long after recovery, but how they affect homeostatic immune states and responses to future perturbations remain poorly understood1–4. Here we use systems immunology approaches, including longitudinal multimodal single-cell analysis (surface proteins, transcriptome and V(D)J sequences) to comparatively assess baseline immune statuses and responses to influenza vaccination in 33 healthy individuals after recovery from mild, non-hospitalized COVID-19 (mean, 151 days after diagnosis) and 40 age- and sex-matched control individuals who had never had COVID-19. At the baseline and independent of time after COVID-19, recoverees had elevated T cell activation signatures and lower expression of innate immune genes including Toll-like receptors in monocytes. Male individuals who had recovered from COVID-19 had coordinately higher innate, influenza-specific plasmablast, and antibody responses after vaccination compared with healthy male individuals and female individuals who had recovered from COVID-19, in part because male recoverees had monocytes with higher IL-15 responses early after vaccination coupled with elevated prevaccination frequencies of ‘virtual memory’-like CD8+T cells poised to produce more IFNγ after IL-15 stimulation. Moreover, the expression of the repressed innate immune genes in monocytes increased by day 1 to day 28 after vaccination in recoverees, therefore moving towards the prevaccination baseline of the healthy control individuals. By contrast, these genes decreased on day 1 and returned to the baseline by day 28 in the control individuals. Our study reveals sex-dimorphic effects of previous mild COVID-19 and suggests that viral infections in humans can establish new immunological set-points that affect future immune responses in an antigen-agnostic manner.

In this study, we used the NASA GEOS‐5 climate model to investigate the impact of snow darkening by deposition of light‐absorbing aerosols on the hydroclimate of Eurasia during boreal spring and summer. Two sets of 10‐member ensemble model integrations with prescribed sea surface temperature were carried out for 10 simulated years (2002–2011); one includes snow‐darkening effects (SDE) by light‐absorbing aerosols and one does not (NSDE). Differences between the two experiments in the hydroclimates over Eurasia were evaluated. Results show that SDE warming is most pronounced during the melting season due to strong snow‐albedo feedback in the vicinity of the retreating seasonal snowline. SDE spurs a wet‐first‐dry‐later modulation of the surface energy and water balances, characterized by an accelerated (days‐to‐weeks) snowmelt, accompanied by excessive runoff and a warming and wetting of the land (relative to NSDE) during the early melting season. The snowmelt is followed by a fast desiccation of the land during the late melting, and early warming season, and then a prolonged warmer and drier land, through the boreal summer. The prolonged warming is sustained by atmospheric conditions favorable for the development of atmospheric blocking, that is, higher middle‐to‐upper‐tropospheric geopotential height, lower relative humidity, reduced cloudiness, and enhanced atmospheric subsidence. Overall, SDE by light‐absorbing aerosols leads to a warmer and drier boreal summer hydroclimate, increasing the frequency of the top 5 and 1% extreme hot days (as defined by NSDE statistics) over western and northern Eurasia by approximately threefold and tenfold, respectively. Snow darkening by light‐absorbing aerosols spurs accelerated snowmelt, runoff, and warming of Eurasian land during boreal springLand drying persists through summer due to depleted supply of freshwater supply from accelerated snowmelt and increased evaporationAtmosphere‐land interaction exacerbates the hot and dry climate, enhancing the intensity and frequency of summertime extreme heating days

Light‐absorbing aerosols not only contribute to Earth's radiative balance but also influence regional climate by cooling the surface and warming the atmosphere. Following recent suggestions that organic aerosols (OAs) absorb substantial amount of solar radiation, we examine the role of light‐absorbing properties of OA on Asian summer monsoon rainfall redistribution using observational data and an atmospheric general circulation model experiment. Results suggest that the enhanced light absorption by OA in Southeast Asia and Northeast Asia is associated with the advance of the Indian summer monsoon in May and the southward shift of East Asian summer monsoon rainband in June. The rainfall redistribution in May is induced by elevated orographic effect with a warm‐core upper‐level anticyclone and surface warming of 1–2 °C over the Tibetan Plateau, whereas that of the East Asian summer monsoon in June is formed by stable conditions associated with surface cooling and atmospheric warming around 30°N. Impact of enhanced OA light absorption on Asian summer monsoon is examined using observations and an AGCM experimentOA light absorption acts to advance the Indian summer monsoon and shift East Asian summer monsoon rainband southwardThe effects of OA light absorption in aerosol‐monsoon interaction can be substantial and cannot be ignored

Viral warts – manifestations of cutaneous infection by human papilloma virus – can be a significant physical and emotional burden for patients when common treatments fail, particularly for individuals who are immunocompromised or with multiple lesions. Cidofovir, an antiviral agent typically used for the treatment of cytomegalovirus infection, has emerged as an alternative treatment option for viral warts when administered topically or intralesionally. In this review, we highlight the scientific rationale, published evidence, and practical clinical uses of intralesional cidofovir for the management of cutaneous warts as well as ongoing questions requiring further research and exploration of this emerging therapy for refractory verrucae.

The objectives of 7-SEAS/BASELInE (Seven SouthEast Asian Studies/Biomass-burning Aerosols & Stratocumulus Environment: Lifecycles & Interactions Experiment) campaigns in spring 2013–2015 were to synergize measurements from uniquely distributed ground-based networks (e.g., AERONET, MPLNET) and sophisticated platforms (e.g., SMARTLabs, regional contributing instruments), along with satellite observations/retrievals and regional atmospheric transport/chemical models to establish a critically needed database, and to advance our understanding of biomass-burning aerosols and trace gases in Southeast Asia (SEA). We present a satellite-surface perspective of 7-SEAS/BASELInE and highlight scientific findings concerning: (1) regional meteorology of moisture fields conducive to the production and maintenance of low-level stratiform clouds over land, (2) atmospheric composition in a biomass-burning environment, particularly tracers/markers to serve as important indicators for assessing the state and evolution of atmospheric constituents, (3) applications of remote sensing to air quality and impact on radiative energetics, examining the effect of diurnal variability of boundary-layer height on aerosol loading, (4) aerosol hygroscopicity and ground-based cloud radar measurements in aerosol-cloud processes by advanced cloud ensemble models, and (5) implications of air quality, in terms of toxicity of nanoparticles and trace gases, to human health. This volume is the third 7-SEAS special issue (after Atmospheric Research, vol. 122, 2013; and Atmospheric Environment, vol. 78, 2013) and includes 27 papers published, with emphasis on air quality and aerosol-cloud effects on the environment. BASELInE observations of stratiform clouds over SEA are unique, such clouds are embedded in a heavy aerosol-laden environment and feature characteristically greater stability over land than over ocean, with minimal radar surface clutter at a high vertical spatial resolution. To facilitate an improved understanding of regional aerosol-cloud effects, we envision that future BASELInE-likemeasurement/modeling needs fall into two categories: (1) efficient yet critical in-situprofiling of the boundary layer for validating remote-sensing/retrievals and for initializing regional transport/chemical and cloud ensemble models, and (2) fully utilizing the high observing frequencies of geostationary satellites for resolving the diurnal cycle of the boundary-layer height as it affects the loading of biomass-burning aerosols, air quality and radiative energetics.

We investigate changes in daily precipitation extremes using Tropical Rainfall Measuring Mission (TRMM) data (1998–2013), which coincides with the “global warming hiatus.” Results show a change in probability distribution functions of local precipitation events (LPEs) during this period consistent with previous global warming studies, indicating increasing contrast between wet and dry extremes, with more intense LPE, less moderate LPE, and more dry (no rain) days globally. Analyses for land and ocean separately reveal more complex and nuanced changes over land, characterized by a strong positive trend (+12.0% per decade, 99% confidence level (c.l.)) in frequency of extreme LPEs over the Northern Hemisphere extratropics during the wet season but a negative global trend (−6.6% per decade, 95% c.l.) during the dry season. A significant global drying trend (3.2% per decade, 99% c.l.) over land is also found during the dry season. Regions of pronounced increased dry events include western and central U.S., northeastern Asia, and Southern Europe/Mediterranean. TRMM data reveal more heavy rain, less moderate rain, and more dry days during 1998–2013Increase contrasts during 1998–2013 in extreme wet and dry conditions over land regionsGlobal precipitation changes persisted during “warming hiatus”

Using Modern‐Era Retrospective analysis for Research and Applications Version‐2 (MERRA‐2) re‐analyses, we have examined recent trends (2000–2019) in transport of surface carbonaceous aerosols (CAs), that is, organic carbon and black carbon, to the upper troposphere and lower stratosphere (UTLS) during the Asian summer monsoon (ASM). We find a significant increased concentration of UTLS CA, linked to a linear trend in an expansion of the Asian Summer Monsoon Anticyclone (ASMA). Over core monsoon latitudes (25°–35°N), the trends in UTLS CA are enabled by increased upward transport from surface sources via an intensified monsoon meridional circulation, with increased latent heating over the southern Tibetan Plateau and foothill regions, enhanced by feedback processes associated with radiative heating by UTLS CA. In the extra‐tropics, increased UTLS CA stems primarily from an extended source of increased wildfire emissions over eastern Siberia and northern Asia, coincident with a large‐scale anomalous anticyclone with enhanced surface warming and drying near (80°–120°E, 55°–70°N). Here, CAs are transported upward from the surface to the ULS, likely by increased pyro‐convection associated with enhanced wildfires, and enter the tropical UTLS via increased equatorward transport on the eastern flanks of anomalous upper‐level anticyclones, coupled to the expanded ASMA. Overall, the increasing UTLS CA trends associated with expansion of the ASMA are consistent with a hydrostatic expansion of a warming troposphere, reflected in a rise in the tropical tropopause and consequential dynamical adjustments of the ASM subtropical jetstream, modulating the climate of the greater ASM region. An interdecadal trend (2000–2019) in an expansion of the Asian Summer Monsoon Anticyclone (ASMA) is foundExpansion of the ASMA facilitates surface‐to‐upper troposphere and lower stratosphere transport of carbonaceous aerosols over the Asian monsoon regionsResults are consistent with a rise of the tropopause due to the hydrostatic thermal expansion of the troposphere in a warming climate An interdecadal trend (2000–2019) in an expansion of the Asian Summer Monsoon Anticyclone (ASMA) is found Expansion of the ASMA facilitates surface‐to‐upper troposphere and lower stratosphere transport of carbonaceous aerosols over the Asian monsoon regions Results are consistent with a rise of the tropopause due to the hydrostatic thermal expansion of the troposphere in a warming climate

Dust, black carbon (BC), and organic carbon (OC) aerosols, when deposited onto snow, are known to reduce the albedo of the snow (i.e., snow darkening effect (SDE)). Here using the NASA Goddard Earth Observing System Model, Version 5 (GEOS‐5) with aerosol tracers and a state‐of‐the‐art snow darkening module (GOddard SnoW Impurity Module: GOSWIM) for the land surface, we examine the role of SDE on climate in the boreal spring snowmelt season. SDE is found to produce significant surface warming (over 15 W m−2) over broad areas in midlatitudes, with dust being the most important contributor to the warming in central Asia and the western Himalayas and with BC having larger impact in the Europe, eastern Himalayas, East Asia, and North America. The contribution of OC to the warming is generally low but still significant mainly over southeastern Siberia, northeastern East Asia, and western Canada (~19% of the total solar visible absorption by these snow impurities). The simulations suggest that SDE strengthens the boreal spring water cycle in East Asia through water recycling and moisture advection from the ocean and contributes to the maintenance of dry conditions in parts of a region spanning Europe to central Asia, partially through feedback on the model's background climatology. Overall, our study suggests that the existence of SDE in the Earth system associated with dust, BC, and OC contributes significantly to enhanced surface warming over continents in northern hemisphere midlatitudes during boreal spring, raising the surface skin temperature by approximately 3–6 K near the snowline. NASA GEOS‐5/GOSWIM simulations on dust+BC+OC snow darkening effect (SDE)Impacts of the boreal spring SDE over land on climate were mainly analyzedThe SDE can enhance the regional dryness and water cycle during boreal spring

Light absorbing particles (LAP, e.g., black carbon, brown carbon, and dust) influence water and energy budgets of the atmosphere and snowpack in multiple ways. In addition to their effects associated with atmospheric heating by absorption of solar radiation and interactions with clouds, LAP in snow on land and ice can reduce the surface reflectance (a.k.a., surface darkening), which is likely to accelerate the snow aging process and further reduces snow albedo and increases the speed of snowpack melt. LAP in snow and ice (LAPSI) has been identified as one of major forcings affecting climate change, e.g. in the fourth and fifth assessment reports of IPCC. However, the uncertainty level in quantifying this effect remains very high. In this review paper, we document various technical methods of measuring LAPSI and review the progress made in measuring the LAPSI in Arctic, Tibetan Plateau and other mid-latitude regions. We also report the progress in modeling the mass concentrations, albedo reduction, radiative forcing, and climatic and hydrological impact of LAPSI at global and regional scales. Finally we identify some research needs for reducing the uncertainties in the impact of LAPSI on global and regional climate and the hydrological cycle.

The Society of Cardiovascular Anesthesiologists (SCA) introduced the FOCUS initiative (Flawless Operative Cardiovascular Unified Systems) in 2005 in response to the need for a rigorous scientific approach to improve quality and safety in the cardiovascular operating room (CVOR). The goal of the project, which is supported by the SCA Foundation, is to identify hazards and develop evidence-based protocols to improve cardiac surgery safety. A hazard is anything that has the potential to cause a preventable adverse event. Specifically, the strategic plan of FOCUS includes 3 goals: (1) identifying hazards in the CVOR, (2) prioritizing hazards and developing risk-reduction interventions, and (3) disseminating these interventions. Collectively, the FOCUS initiative, through the work of several groups composed of members from different disciplines such as clinical medicine, human factors engineering, industrial psychology, and organizational sociology, has identified and documented significant hazards occurring daily in our CVORs. Some examples of frequent occurrences that contribute to reduce the safety and quality of care provided to cardiac surgery patients include deficiencies in teamwork, poor OR design, incompatible technologies, and failure to adhere to best practices. Several projects are currently under way that are aimed at better understanding these hazards and developing interventions to mitigate them. The SCA, through the FOCUS initiative, has begun this journey of science-driven improvement in quality and safety. There is a long and arduous road ahead, but one we need to continue to travel.

OMiCC (OMics Compendia Commons) is a biologist-friendly web platform that facilitates data reuse and integration. Users can search over 40,000 publicly available gene expression studies, annotate and curate samples, and perform meta-analysis. Since the initial publication, we have incorporated RNA-seq datasets, compendia sharing, RESTful API support, and an additional meta-analysis method based on random effects. Here, we provide a step-by-step guide for using OMiCC.

ABSTRACTThe purpose of this randomized, multicenter, open-label study was to compare the continuous infusion of piperacillin-tazobactam with the standard intermittent infusion in 262 hospitalized patients with complicated intra-abdominal infections. Within 1 day of surgical intervention, eligible patients were randomized (1:1) to piperacillin-tazobactam 12 g/1.5 g administered continuously over 24 h or 3 g/0.375 g administered over 30 min intermittently every 6 h for 4 to 14 days. The demographics of the patients in the groups were similar, with a median APACHE II score of 7 and a median length of hospitalization of 7 days. Among 167 clinically evaluable patients, 86.4% and 88.4% of the patients treated with the continuous infusion and the intermittent infusion, respectively, were clinically cured or improved at the test-of-cure visit (P= 0.817). Bacteriological success was observed in 83.9% and 87.9% of patients (P= 0.597) in the two groups, respectively, and no differences in bacteriological response by pathogen were noted. Defervesence and white blood cell count normalization occurred in the majority of patients within 3 days and were similar between patients receiving the continuous infusion and those receiving the intermittent infusion. Drug-related adverse events were generally mild and were reported in similar numbers of patients in each arm of the trial. The results of this study support continuous infusion as a safe and reasonable alternate mode of administration of piperacillin-tazobactam for the treatment of complicated intra-abdominal infection.

ABSTRACTSkin and soft tissue infections (SSTIs) are a common cause of morbidity in both the community and the hospital. An SSTI is classified as complicated if the infection has spread to the deeper soft tissues, if surgical intervention is necessary, or if the patient has a comorbid condition hindering treatment response (e.g., diabetes mellitus or human immunodeficiency virus). The purpose of this study was to compare linezolid to vancomycin in the treatment of suspected or proven methicillin-resistant gram-positive complicated SSTIs (CSSTIs) requiring hospitalization. This was a randomized, open-label, comparator-controlled, multicenter, multinational study that included patients with suspected or proven methicillin-resistant Staphylococcus aureus(MRSA) infections that involved substantial areas of skin or deeper soft tissues, such as cellulitis, abscesses, infected ulcers, or burns (<10% of total body surface area). Patients were randomized (1:1) to receive linezolid (600 mg) every 12 h either intravenously (i.v.) or orally or vancomycin (1 g) every 12 h i.v. In the intent-to-treat population, 92.2% and 88.5% of patients treated with linezolid and vancomycin, respectively, were clinically cured at the test-of-cure (TOC) visit (P= 0.057). Linezolid outcomes (124/140 patients or 88.6%) were superior to vancomycin outcomes (97/145 patients or 66.9%) at the TOC visit for patients with MRSA infections (P< 0.001). Drug-related adverse events were reported in similar numbers in both the linezolid and the vancomycin arms of the trial. The results of this study demonstrate that linezolid therapy is well tolerated, equivalent to vancomycin in treating CSSTIs, and superior to vancomycin in the treatment of CSSTIs due to MRSA.

Abstract.: Peak bone density is an important determining factor of future osteoporosis risk. We previously identified a quantitative trait locus (QTL) that contributes significantly to high bone density on mouse chromosome 1 from a cross between C57BL/6J (B6) and CAST/EiJ (CAST) mouse strains. We then generated a congenic strain, B6.CAST-1T, in which the chromosomal fragment containing this QTL had been transferred from CAST to the B6 background. The congenic mice have a significantly higher bone density than the B6 mice. In this study we performed cDNA microarray analysis to evaluate the gene expression profile that might yield insights into the mechanisms controlling the high bone density by this QTL. This study led to several interesting observations. First, approximately 60% of 8,734 gene accessions on GEM I chips were expressed in the femur of B6 mice. The expression and function of two-thirds of these expressed genes and ESTs have not been documented previously. Second, expression levels of genes related to bone formation were lower in congenic than in B6 mice. These data are consistent with a low bone formation in the congenic mice, a possibility that is confirmed by reduced skeletal alkaline phosphatase activity in serum compared with B6 mice. Third, expression levels of genes that might have negative regulatory action on bone resorption were higher in congenic than in B6 mice. Together these findings suggest that the congenic mice might have a lower bone turnover rate than B6 mice and raise the possibility that the high bone density in the congenic mice could be due to reduced bone resorption rather than increased bone formation.

To determine if examination of respiratory secretions is useful in diagnosing Pneumocystis carinii pneumonia, smear preparations of expectorated sputum, tracheal aspirates, and transtracheal aspirates stained by the Gomori methenamine silver nitrate method were examined. Pneumocysts were observed more frequently in material obtained by transtracheal aspiration than in secretions obtained by the other methods. Transtracheal aspiration yielded material containing pneumocysts in 8 (13%) of 60 patients; each had pulmonary infiltrates and clinical courses consistent with P carinii pneumonia. Of 330 smear preparations examined from expectorated sputum, three patients had pneumocysts in their sputum and one had organisms in both transtracheal aspiration and expectorated sputum; all three had pneumonia. This study provides evidence that transtracheal aspiration is a useful initial step in the approach to the diagnosis of P carinii pneumonia.(JAMA 236:2399-2402, 1976)

Amikacin was used in 77 treatment courses at a dosage of ≥7.5 mg/kg every 8 h, and patients were monitored for ototoxicity by following serial audiograms, serum creatinine, and amikacin blood levels. Patients were leukopenic (58), were infected by gentamicin-resistant organisms (11), or had cystic fibrosis (8). Three patients developed tinnitus, but none had vertigo or nystagmus. Of 55 courses with pre- and post-treatment audiogram, 13 (24%) were associated with development of high-frequency hearing loss, which was usually bilateral. No patient had conversational hearing loss, and audiograms reverted to normal in three patients. Onset of cochlear damage occurred in one patient after therapy was stopped. The group with high-tone hearing loss, in comparison to the group without audiographic changes, received a larger mean total dose (24 versus 9.6 g), were treated for a longer duration (19 versus 9 days), and more frequently had previous aminoglycosides. Fifty-seven percent of patients with a “peak” serum level exceeding 32 μg/ml and 55% of patients with “trough” levels exceeding 10 μg/ml developed cochlear damage. There was no difference between the groups in age, body weight, previous cochlear damage, renal disease before or during therapy, or average daily dose. Both monitoring of blood levels and limiting duration of therapy may prevent amikacin ototoxicity.

To determine how progestins increase bone formation in vivo, the effects of the synthetic progestin norethindrone (NET), on aspects of bone formation in vitro were determined. NET at picomolar concentrations in vitro stimulated the proliferation of human TE85 osteosarcoma cells as assessed by the increase in [3H]thymidine incorporation into DNA and in cell number and also stimulated the release of osteocalcin in both the presence and absence of 10 nM 1,25‐(OH)2D3. NET increased cellular alkaline phosphatase specific activity (an index of osteoblastic differentiation), but at much higher concentrations, that is, nanomolar. These findings suggest that low concentrations of NET act directly on human TE85 osteosarcoma cells to stimulate their proliferation, differentiation, and cell activity. Furthermore, mitogenic doses of NET stimulated bone collagen synthesis both in a chicken calvarial organ culture assay (assessed by the incorporation and hydroxylation of [3H]proline) and in a human TE85 osteosarcoma cell culture assay (determined by the incorporation of [3H]proline into collagenase‐digestible proteins). In contrast, NET at 10−6‐10−12M had no apparent effect on the rate of basal or PTH‐stimulated release of 45Ca from prelabeled mouse calvariae in vitro. In summary, this study has demonstrated for the first time that picomolar NET acted directly on human TE85 osteosarcoma cells to increase (1) cell proliferation and differentiation, (2) osteoblastic activity (i.e., osteocalcin synthesis), and (3) bone collagen synthesis in vitro. The same doses of NET in vitro did not reduce the bone resorption rate under our assay conditions. In conclusion, these in vitro osteogenic activities of NET suggest that it may be a useful therapeutic agent to increase bone formation in patients with low bone mass.

An indexed sequential (IS) file allows both sequential and random retrieval of its records. When a large IS file is stored in a disk pack with one assembly that must seek different cylinders to retrieve records, the total seek times will become a primary concern for choosing file access methods. While sequential retrieval requires some additional time for sorting the input keys, it may gain considerable reduction in seek times as the access arm does not move in and out to access different records. Once a sorting (internal or external) algorithm is chosen, the time can be estimated as sorting techniques are well developed and documented. In this paper, the average total seek times for both sequential and random retrieval of the file are derived. The result can be used to facilitate a tradeoff study between the two retrieval methods for a particular application.

We recently reported that picomolar doses of norethindrone (NET), a synthetic analog of 19‐nortestosterone, significantly stimulated human TE85 osteosarcoma cell proliferation, differentiation, and activity in vitro. In the present study, we investigated the possibility that NET interacts with another osteogenic agent, i.e., fluoride, to stimulate human TE85 osteosarcoma cell proliferation, differentiation, and activities. Bone cell proliferation was measured by the stimulation in [3H]thymidine incorporation. Differentiation was monitored by the increase in alkaline phosphatase‐specific activity. Osteoblastic activity was assessed by the stimulations in collagen synthesis and in osteocalcin secretion (in the presence of 1 nM 1,25‐dihydroxyvitamin D3). When the human TE85 cells were incubated with mitogenic doses of NET and fluoride concurrently, the stimulatory effects of the two agents on these parameters exhibited no significant interaction. The enhancing effect of NET on the osteogenic effect of fluoride was not due to a shift of the fluoride dose response curve. Pretreatment with NET for 24 h followed by a treatment with a mitogenic dose (i.e., 100 μM) of fluoride for an additional 24 h significantly and synergistically potentiated the effects of fluoride on the [3H]thymidine incorporation, alkaline phosphatase‐specific activity, collagen synthesis, and osteocalcin secretion, compared with those with the subsequent vehicle (0.05% ethanol) treatments. In contrast, pretreatment with fluoride for 24 h before the addition of NET for 24 h did not produce significant synergistic stimulations in the test parameters. Pretreatment of TE85 cells with the same doses of dihydrotestosterone or progesterone prior to treatment with fluoride under the same conditions did not induce synergistic potentiation of fluoride in [3H]thymidine incorporation, suggesting that the synergistic interaction with fluoride is probably not a common property of anabolic sex steroids. In summary, we found that: (1) the osteogenic effects of fluoride and NET were additive when cells were treated with both agents concurrently; (2) a 24‐h pretreatment with picomolar doses of NET potentiated the osteogenic actions of fluoride in human TE85 osteosarcoma cells; and (3) pretreatment with NET produced a subsequent fluoride response that was synergistic. In conclusion, these findings led us to speculate that the osteogenic actions of NET and fluoride act through different mechanisms, and that NET at low doses has a permissive effect on the osteogenic effects of fluoride, and as such NET may be used in concert with fluoride to increase osteoblast proliferation, differentiation, and activity.

Zusammenfassung Bei der Berechnung von zweidimensionalen inkompressiblen Potentialströmungen um abgerundete und symmetrische Körper erhält man einen Annäherungswert für den Bereich nahe dem Staupunkt, indem man annimmt, dass die Strömungsart dieselbe ist wie die um einen Kreiszylinder.

ABSTRACTBacillus cereusis a rare cause of endocarditis, typically associated with intravenous drug abuse, rheumatic heart disease, prosthetic heart valves, pacemakers, or immunodeficiency. We present the first case of native valve Bacillus cereusendocarditis with no apparent risk factors. The patient had a fulminant course requiring emergent valve replacement.

Bacillus cereus is a rare cause of endocarditis, typically associated with intravenous drug abuse, rheumatic heart disease, prosthetic heart valves, pacemakers, or immunodeficiency. We present the first case of native valve Bacillus cereus endocarditis with no apparent risk factors. The patient had a fulminant course requiring emergent valve replacement.

ELECTRONIC MAIL AND MESSAGE HANDLING by Peter Vervest (London: Francis Pinter/ Westport, Conn.: Quorum Books, 1985-- L25/$35.00)THE INFORMATION TECHNOLOGY REVOLUTION edited by Tom Forester (London: Blackwell/ Cambridge: MIT Press, 1985---$14.95 paper, with hardback also available)AMERICAN UNIVERSITY PROGRAMS IN COMPUTER SCIENCE: THEIR RESOURCES, FACILITIES, AND COURSE OFFERING by William W. Lau (GGL Educational Press, Suite 606, 2555 East Chapman Ave., Fullerton, Ca. 92631-- $20.00)Latest from the prolific Harvard Program on Information Resources Policy (200 Aiken, Harvard University, Cambridge, Mass. 02138---price not given, paper)1985 TELECOMMUNICATIONS SOURCE BOOK (North American Telecommunications Association, 2000 M St. NW, Washington, D.C. 20036---$75.00, paper)

Zusammenfassung Es wird gezeigt, dass im Fall eines wirbelfreien zwei-dimensionalen Strömungsfeldes die eintretende Stromlinie den Winkel der von den Tangenten der abzweigenden Stromlinien gebildet wird, halbiert. Der Fall eines freien Staupunktes ist demnach nur als ein spezieller Fall des mehr allgemeinen und hier behandelten zu betrachten.

Cell-to-cell variation in gene expression and the propagation of such variation (PoV or “noise propagation”) from one gene to another in the gene network, as reflected by gene-gene correlation across single cells, are commonly observed in single-cell transcriptomic studies and can shape the phenotypic diversity of cell populations. While gene network “rewiring” is known to accompany cellular adaptation to different environments, how PoV changes between environments and its underlying regulatory mechanisms are less understood. Here, we systematically explored context-dependent PoV among genes in human macrophages, utilizing different cytokines as natural perturbations of multiple molecular parameters that may influence PoV. Our single-cell, epigenomic, computational, and stochastic simulation analyses reveal that environmental adaptation can tune PoV to potentially shape cellular heterogeneity by changing parameters such as the degree of phosphorylation and transcription factor-chromatin interactions. This quantitative tuning of PoV may be a widespread, yet underexplored, property of cellular adaptation to distinct environments.