bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the use of hydroxyethyl starch in granulocyte apheresis using Spectra Optia
Authors: Yoshihara Satoshi , Ikemoto Junko , Onomoto Hitomi , Sugiyama Hiroki , Okuda Noriko , Fukunaga Keiko , Yoshihara Kyoko , Kaida Katsuji , Ikegame Kazuhiro , Tamaki Hiroya , Okada Masaya , Osugi Yuko , Yamahara Kenichi , Higasa Satoshi , Fujimori Yoshihiro
Published: June 2021

Objectives

To determine the impact of the use of hydroxyethyl starch (HES) in granulocyte apheresis using Spectra Optia.

Background

Granulocyte transfusion (GT) is a therapeutic option for neutropenic patients with severe bacterial or fungal infections. Recent studies in emergency medicine have shown the potential risk of using HES, which is routinely used in granulocyte apheresis to increase yield by sedimenting red blood cells. We hypothesized that the use of a newer device (Spectra Optia) would spare the need for HES.

Methods

We retrospectively compared granulocyte apheresis with HES (HES group, n = 89) and without HES (non‐HES group, n = 36) using Spectra Optia.

Results

The granulocyte yield was significantly higher in the HES group (7.3 × 1010 vs. 2.0 × 10, p < 0.01) and was attributed to the difference in collection efficiency (36% vs. 7.7%, p < 0.01). The absolute neutrophil count on the following morning of GT was significantly higher in the HES group than in the non‐HES group (2460/μl vs. 505/μl, p < 0.01). There were no significant differences in the occurrence of adverse events between the HES and non‐HES groups. The renal function was unchanged in both groups after apheresis.

Conclusions

We demonstrated that the advantage of using HES remained unchanged in granulocyte apheresis using Spectra Optia.
Integration of Machine Learning and Computational Fluid Dynamics to Develop Turbulence Models for Improved Low-Pressure Turbine Wake Mixing Prediction
Authors: Akolekar Harshal D. , Zhao Yaomin , Sandberg Richard D. , Pacciani Roberto
Published: June 2021

This paper presents the development of accurate turbulence closures for low-pressure turbine (LPT) wake mixing prediction by integrating a machine-learning approach based on gene expression programming (GEP), with Reynolds-averaged Navier–Stokes (RANS)-based computational fluid dynamics (CFD). In order to further improve the performance and robustness of GEP-based data-driven closures, the fitness of models is evaluated by running RANS calculations in an integrated way, instead of an algebraic function. Using a canonical turbine wake with inlet conditions prescribed based on high-fidelity data of the T106A cascade, we demonstrate that the “CFD-driven” machine-learning approach produces physically correct non-linear turbulence closures, i.e., predict the right down-stream wake development and maintain an accurate peak wake loss throughout the domain. We then extend our analysis to full turbine blade cases and show that the model development is sensitive to the training region due to the presence of deterministic unsteadiness in the near-wake. Models developed including the near-wake have artificially large diffusion coefficients to over-compensate for the vortex shedding steady RANS cannot capture. In contrast, excluding the near-wake in the model development produces the correct physical model behavior, but predictive accuracy in the near-wake remains unsatisfactory. This can be remedied by using the physically consistent models in unsteady RANS. Overall, the “CFD-driven” models were found to be robust and capture the correct physical wake mixing behavior across different LPT operating conditions and airfoils such as T106C and PakB.
Sound speed gradients in mud
Authors: Holland Charles W.
Published: June 2021

Various methods have been used to estimate sound speed profiles in mud at the New England Mud Patch. Some of these methods show large sound speed gradients of order 10 s−1. New measurements of the seabed reflection coefficient exhibit an angle of intromission over three octaves in frequency; these data constrain the range of possible sound speed gradient values. The data indicate that sound speed gradients must be quite weak, i.e., much smaller than |10 s−1|. This conclusion is supported by core data which indicate nearly constant porosity in most of the mud layer.
Induction of suppressor T cells in delayed-type hypersensitivity to Mycobacterium bovis BCG in low-responder mice
Authors: Nakamura R M , Tokunaga T
Published: June 2021

The induction of delayed-type hypersensitivity to Mycobacterium bovis BCG was specifically inhibited by suppressor T cells in C3H/He, a strain of mice which is a low responder to BCG. The existence of these suppressor cells was confirmed by an adoptive transfer of spleen cells of BCG-injected mice into cyclophosphamide-treated recipients. The suppressor cells appeared in the spleens of the mice 2 to 7 days after intravenous BCG injection. They were sensitive to anti-theta serum and complement and did not adhere to Sephadex G-10. A pretreatment of the mice with cyclophosphamide eliminated the suppression of delayed-type hypersensitivity. These suppressor cells effectively inhibited the induction of delayed-type hypersensitivity to BCG, but showed only weak effect on the expression of it.
Analysis of the inhibitory effect of peritoneal macrophages on the spread of herpes simplex virus
Authors: Hayashi K , Kurata T , Morishima T , Nassery T
Published: June 2021

Peritoneal macrophages obtained from mice after an intraperitoneal injection of tryptose peptone inhibited the development of herpes simplex virus type 2 plaques in syngeneic mouse embryonic fibroblasts. In contrast, peritoneal macrophages, spleen cells, and thymocytes from untreated mice showed only a minimal inhibitory effect on the development of viral plaques. The effect was age dependent. Macrophages from 2 and 3-week-old mice showed weaker functions, requiring a larger number of cells for an equivalent reduction of plaques and virus yield than those from adult mice. When macrophages were treated with procaine, their phagocytic activity was completely abolished. However the procaine-treated macrophages still could inhibit the development of viral plaques. Peritoneal macrophages did not show any increased cytotoxicity against herpes simplex virus-infected cells; plaque inhibition might rather be attributable to their cytostatic effects on target cells.
Interaction of lipopolysaccharides with plasma high-density lipoprotein in rats
Authors: Freudenberg M A , Bøg-Hansen T C , Back U , Galanos C
Published: June 2021

The method of crossed immunoelectrophoresis was used to investigate early changes in plasma proteins of rats treated with lipopolysaccharide (LPS). Intravenous injection of a smooth (S)- and a rough (R)-form preparation led to alterations in the high-density lipoprotein (HDL) precipitation peak. The changes were dose dependent and characteristic for each LPS. The changes were identified as being due to the formation of a complex of LPS with HDL, the complex of the S-form LPS with HDL migrating slower and that of the R-form LPS with HDL migrating faster than free HDL. The fate of the complex was followed in the plasma of injected rats, and it was shown that the R-form LPS complex disappeared after several hours, whereas the S-form LPS complex was still partly present after 2 days. Plasma clearance studies, carried out with 14C-labeled LPS, revealed similar differences in the rate of elimination of the two LPSs. In both cases the time of clearance resembled that of the disappearance of LPS-HDL complex. These results may indicate that HDL represents a transport protein for LPS in plasma to organs of clearance or to other cellular targets.
Demonstration of cell envelope-bound exotoxin A in Pseudomonas aeruginosa
Authors: Fernandes P B , Cundy K R
Published: June 2021

The quantity of membrane-bound and extracellular exotoxin A in four strains of Pseudomonas aeruginosa was investigated. In strain PA-103, which is the prototype strain used for toxin production, all of the toxin was released into the growth medium and little toxin remained with the cell envelope. In a virulent strain from a clinical source, strain 119, exotoxin A was found in equal amounts in the growth medium and in the cell envelopes. An avirulent mutant of this strain, strain 119 (AP-), which was resistant to 800 microgram of polymyxin B per ml, had all the exotoxin A in a membrane-bound state and was unable to release exotoxin A into the growth medium. Thus, exotoxin A can be found in the membrane-bound form, in the extracellular form, or in both. The quantities of membrane-bound toxin and extracellular toxin vary with the strain P. aeruginosa. The polymyxin B-resistant mutant which is blocked in toxin release will be useful in studies of exotoxin A secretion.
Kinetics of peripheral blood leukocyte alterations in Thai children with dengue hemorrhagic fever
Authors: Wells R A , Scott R M , Pavanand K , Sathitsathein V , Cheamudon U , Macdermott R P
Published: June 2021

Peripheral leukocytes from 16 Thai children with dengue hemorrhagic fever were examined to determine the leukocyte composition on the day of presentation and on convalescent days 15 and 30. Mononuclear cells were isolated each time, and the concentrations of T, B, Fc receptor-bearing, and "null" cells were determined. On the day of hospitalization, in comparison to convalescent values, there was a significant increase in total lymphocytes, primarily due to concentrations of atypical lymphocytes. There was a significant loss of T cells with an increase in non-T, non-B, non-Fc receptor-bearing null cells. There were no changes in the concentrations of monocytes, B cells, or Fc receptor-bearing cells when acute and convalescent values were compared. During the convalescent period, a progressive increase in eosinophils was noted. Also, on day 15 but not on day 30 of the convalescent period, an increase was observed in the total leukocyte number due to an increase in granulocytes. There results indicate that in Thai children with dengue hemorrhagic fever, there are major shifts within several component cell subpopulations of the immune system.
Experimental Chagas' disease in complement-deficient mice and guinea pigs
Authors: Dalmasso A P , Jarvinen J A
Published: June 2021

The course of infection with trypomastigotes of Trypanosoma cruzi (House 510 strain) in mice and guinea pigs with genetic complement deficiencies was compared with that in normocomplementemic animals. Parasitemias in a mouse strain (B10.D2/old) genetically deficient in C5 and therefore unable to sustain lysis were similar to or lower than in a congenic normocomplementemic strain (B10.D2/new). The levels of C3 measured immunochemically were generally unaffected. There were no significant differences in mortality rates. These results indicate that, in mice, complement-mediated lysis does not play a significant role in the control of T. cruzi (House 510) infections. Studies were also performed in normocomplementemic guinea pigs and in guinea pigs genetically deficient in the fourth component of complement and thus unable to support functions mediated by the classical pathway of complement activation. No significant differences were noted between the two strains in the course of infection, persistence of subpatent infection, or rate of mortality, indicating that if the classical complement pathway plays a role in resistance to T. cruzi (House 510) in guinea pigs, this role must be a small one.
Local and systemic antibody response to oral administration of glucosyltransferase antigen complex
Authors: Smith D J , Taubman M A , Ebersole J L
Published: June 2021

The salivary and serum immune responses to orally administered glucosyltransferase antigen complex from Streptococcus mutants strain 6715 were investigated in hamsters. All enzyme-linked immunosorbent assay was used to measure the antibody quantity and isotype, and a [14C]glucosyl-labeled sucrose incorporation assay was used to measure functional inhibition of the enzyme. A total of 21 to 27 daily doses of antigen administered in hamster oral cavities elicited salivary immunoglobulin C and immunoglobulin A antibody responses and functional inhibitory activity. The salivary response increased throughout the immunization procedure, and the amount of salivary antibody was dependent upon the dose of antigen given. The salivary response to a second oral administration of antigen for 4 days showed some features of anamnesis. The response after a second antigen administration was detected sooner than the primary response, and somewhat higher levels of antibody and inhibitory activity were observed. Serum antibody (immunoglobulin G and immunoglobulin M) and functional inhibitory responses were also elicited by oral administration of the soluble enzyme antigen. These responses were lower than responses induced by local injections of antigen in complete Freund adjuvant. The ability to evoke a salivary immune response to the glucosyltransferase antigen complex may increase the potential of using this antigen in an effective caries vaccine.
Expression of Enzymic Activity by Exotoxin A from
Pseudomonas aeruginosa
Authors: Lory Stephen , Collier R. John
Published: June 2021

Exotoxin A from
Pseudomonas aeruginosa
is a single polypeptide chain (
M
r
, 66,000) containing little if any adenosine 5′-diphosphate ribosyltransferase or oxidized nicotinamide adenine dinucleotide glycohydrolase activity. These activities have been demonstrated in the reduced intact toxin and in a peptide (
M
r
, 26,000) isolated from culture fluids or toxin preparations after storage. In this report we describe methods for generating enzymically active fragments by cleaving the fully or partially reduced exotoxin by proteolytic or chemical methods. Incubation of reduced toxin with chymotrypsin in the presence of oxidized nicotinamide adenine dinucleotide yielded an enzymically active peptide (
M
r
, 26,000) similar to the fragment characterized previously. Chemical cleavage by treatment of the reduced molecule with CNBr or 2-nitro-5-thiocyanobenzoate yielded fragments (
M
r
, 50,000 and 30,000, respectively) with similar activities. Also both adenosine 5′-diphosphate ribosyltransferase and oxidized nicotinamide adenine dinucleotide glycohydrolase activities were maximally expressed by the intact exotoxin after reduction of only two of its four disulfide bridges. Kinetic constants for activated whole toxin were similar to those of fragment A of diphtheria toxin. It is evident that in the native toxin the catalytic center is buried or distorted and that alterations in the covalent structure permit the center to become exposed or assume an active configuration. It is unknown whether reduction, proteolytic processing, or both occur during the course of toxin action on whole cells.
Cytophilic and Opsonic Antibodies in Visceral Leishmaniasis in Mice
Authors: Herman Robert
Published: June 2021

Although acquired immunity to leishmaniasis is generally considered to be cell mediated, humoral factors may be partially responsible. The present study showed that antisera from C57BL/6J mice superinfected with
Leishmania donovani
contained cytophilic antibody and opsonins for both the amastigote and promastigote stages of the parasite. Macrophages treated with mouse hyperimmune serum in an in vitro macrophage culture system bound statistically significantly more parasites at 4°C (and subsequently phagocytized them at 37°C) than did macrophage cultures treated with control serum. The percentages of antibody-treated macrophages bearing and containing parasites were also significantly greater than the percentages of control serum-treated macrophages bearing and containing parasites, respectively. These differences persisted in cultures during a 9-day observation period when sera from mice killed 10 or 11 days after superinfection were used. However, when sera from mice killed 24 days after superinfection were tested with amastigotes, by day 9 the number of parasites and the percentage of cells parasitized in the culture decreased to control values or significantly below them. Thioglycolate-stimulated macrophages treated with hyperimmune serum bound more amastigotes at 4°C than did stimulated macrophages treated with control serum. Activated macrophages also demonstrated increased nonspecific binding of amastigotes. Treatment of macrophages with trypsin reduced both cytophilic antibody-specific and nonspecific binding of amastigotes. The demonstration of in vitro effects of anti-leishmanial antibody from superinfected mice might indicate a possible role for humoral antibody in immunity to leishmaniasis in mice.
Serological cross-reaction and cross-protection in guinea pigs infected with Rickettsia rickettsii and Rickettsia montana
Authors: Feng W C , Waner J L
Published: June 2021

Antisera produced in guinea pigs inoculated with Rickettsia rickettsii or Rickettsia montana were cross-reactive but sufficiently specific to identify the primary infecting agent. Guinea pigs immunized with R. montana were protected from fatal infection with R. rickettsii, although a few (25%) developed mild fever of short duration.
Phagocytosis of Borrelia recurrentis by blood polymorphonuclear leukocytes is enhanced by antibiotic treatment
Authors: Butler T , Aikawa M , Habte-Michael A , Wallace C
Published: June 2021

The removal of Borrelia spirochetes from the blood in relapsing fever was studied by examining patients' blood phagocytic cells with the Dieterle silver stain. Polymorphonuclear leukocytes ingested Borrelia at increased rates for several hours after antibiotic treatment, during which time the total numbers of circulating plasma spirochetes were decreasing. Incubation of infected blood at 37 degrees C for 2 h resulted in a progressive increase in phagocytosis. Addition of penicillin G and tetracycline to infected blood caused a further enhancement of phagocytosis. Electron microscopy of polymorphonuclear leukocytes revealed spirochetes in phagosomes. These results indicated that blood polymorphonuclear leukocytes have a prominent role in removing Borrelia from the plasma and suggested that antibiotics act by altering the surface of spirochetes to render them more susceptible to phagocytosis.
Enhancement of resistance to infections by endotoxin-induced serum factor from Mycobacterium bovis BCG-infected mice
Authors: Parant M A , Parant F J , Chedid L A
Published: June 2021

Necrosis of a variety of transplanted murine tumors can be induced by serum from Mycobacterium bovis BCG-treated mice challenged with a lethal dose of endotoxin. Results reported here show that the tumor necrosis serum (TNS) enhances resistance to infections, protecting mice against two types of challenges, either with Klebsiella pneumoniae or with the intracellular parasite Listeria monocytogenes. Moreover, TNS activity was demonstrated in animals which are refractory to lipopolysaccharide and very susceptible to infections, such as 8-day-old mice and adult C3H/He mice. Protection passively transferred by TNS was not related to antibodies, since it was not decreased by absorption with homologous organisms.
Modulation of immunoreactivity to periodontal disease-associated microorganisms during pregnancy
Authors: Lopatin D E , Kornman K S , Loesche W J
Published: June 2021

The lymphocyte blastogenic response to a panel of antigens and mitogens was assessed in a group of 20 women throughout their pregnancy. In addition, a group of five nonpregnant women was monitored simultaneously to identify variations in response to the same stimulants. The stimulants included orally associated bacterial antigens (Streptococcus sanguis, Actinomyces viscosus, Bacteroides asaccharolyticus, Bacteroides melaninogenicus subsp. intermedius, Bacteroides [Capnocytophaga] ochraceus, and Fusobacterium nucleatum) and non-orally associated-stimulants (streptokinase-streptodornase, tetanus toxoid, concanavalin A, phytohemagglutinin, and pokeweed mitogen). Intrinsic (cells cultured in male AB plasma) suppression of the lymphocyte response to these stimulants was observed to occur by the second trmester of pregnancy and was resolved after parturition. Additionally, an extrinsic (cells cultured in autologous plasma) suppression was also suggested to occur in a similar manner. There was no detectable enhancement of the blastogenic response to oral bacteria associated with elevated gingivitis, which is generally reported to occur during nonpregnancy gingivitis. We propose that concomitant immunosuppression occurs during the second trimester, which masks such enhancement.
Cross-linking analysis of the outer membrane proteins of Neisseria gonorrhoeae
Authors: Newhall W J , Sawyer W D , Haak R A
Published: June 2021

The organization of outer membrane proteins of Neisseria gonorrhoeae was investigated by using two-dimensional dodecyl sulfate-polyacrylamide gel electrophoresis and cross-linking agents. A naturally occurring protein aggregate, which may be composed of two proteins of 50,000 molecular weight, was detected in all strains. Treatment of whole cells with cross-linking agents yielded several additional complexes, suggesting that other proteins are arranged in the outer membrane as near neighbors. The principal outer membrane protein (molecular weight, 34,000) cross-linked (i) to itself to form a complex whch appeared to be trimeric, (ii) to the 28,000-molecular-weight outer membrane protein to form a bimolecular comlex, and (iii) to the 28,000-molecular-weight outer membrane protein in a 3:1 ratio. The formation of these complexes was independent of (i) colony type, (ii) colony opacity, (iii) pH during growth, and (iv) presence of markers for drug resistance or hypersensitivity.
Streptococcus mutans dextransucrase: effect of cerulenin on lipid synthesis and enzyme production
Authors: Leung W L , Harlander S K , Schachtele C F
Published: June 2021

The effect of the fatty acid synthesis inhibitor cerulenin on growth and dextransucrase (EC 2.4.1.5) production by Streptococcus mutans 6715 was analyzed. Growth was markedly inhibited by less than 1 microgram of the antibiotic per ml. Under conditions where cerulenin did not inhibit amino acid incorporation into protein but did block acetate metabolism into lipid, the production of extracellular dextransucrase was suppressed. Inhibition was not due to a direct effect of the antibiotic on the enzyme or the lack of release of enzyme from the bacterial cell surface. Gel column chromatography demonstrated that enzyme produced in the presence of cerulenin was highly aggregated, similar to the control enzyme. Although the addition of ysophosphatidylcholine to enzyme which had been synthesized in the presence of cerulenin stimulated glucan formation from sucrose, the increase was not greater than that produced with the control enzyme. The differential inhibition of dextransucrase production by cerulenin indicates that enzyme secretion requires the production of lipid and may reflect the mechanism by whch this enzyme is transported from the bacterial cell.
Activation of murine T-suppressor lymphocytes by group A streptococcal and staphylococcal pyurogenic exotoxins
Authors: Schlievert P M
Published: June 2021

The effect of group A streptococcal pyrogenic exotoxin (PE) type C and staphylococcal PE on the in vitro antibody response to sheep erythrocytes was studied in cultures of mouse spleen cells. Both exotoxins suppressed the day 4 direct plaque-forming cell response when added to the cultures. The maximum suppression was obtained with 1.0 or 0.1 ng of toxin per culture, and the suppressive effect was reversed by addition of gangliosides to the cultures at the same time as the exotoxins. Preincubation of T lymphocytes for 4 days with either exotoxin resulted in the generation of a suppressor cell population, which produced dose-dependent suppression of the direct plaque-forming cell response when added to fresh sheep eyrthrocyte-activated splenocytes. The suppression obtained was not reversed by gangliosides indicating toxin carry-over was not responsible for the effect. B cells, preincubated with exotoxin, failed to suppress the direct plaque-forming cell response of fresh erythrocyte-activated spleen cells.
Influence of type of oil and surfactant concentration on the efficacy of emulsified Mycobacterium bovis BCG cell walls to induce tumor regression in guinea pigs
Authors: Yarkoni E , Rapp H J
Published: June 2021

The influence of mineral ol, squalane, squalene, hexadecane, or peanut oil and of the concentration of Tween 80 on the immunotherapeutic capability of emulsified Mycobacterium bovis Bacillus Calmette-Guérin (BCG) cell walls was studied in guinea pigs, each with an established dermal transplant of a syngeneic hepatocarcinoma and tumor cells in the draining lymph node. Immunotherapy consisted of an intratumoral injection of emulsified cell walls. Conditions were established under which therapeutically effective emulsions could be made with mineral oil, squalane, squalene, or hexadecane. Emulsions made with peanut oil failed to cause tumor regression. Emulsions of squalene or hexadecane were effective substitutes for mineral oil as carriers of cell walls in the absence of added Tween or at a Tween concentration one-hundredth of that used to stabilize the mineral oil-containing emulsions. Cell wall emulsions made with squalane were therapeutically effective over the same range of Tween concentrations used to prepare emulsions containing mineral oil. Cell wall emulsions made without added Tween demonstrated effective antitumor activity even after autoclaving. Emulsions made with Tween separated after autoclaving. Emulsions of whole killed BCG were immunotherapeutically as active as those made with cell walls.
In vitro suppression of T-cell mitogenic response and tumor cell proliferation by spleen macrophages from normal chickens
Authors: Sharma J M
Published: June 2021

Adherent cells isolated from spleen of normal specific pathogen-free chickens inhibited mitogen-induced blastogenesis of autochthonous, syngeneic, or allogeneic lymphocytes. The adherent cells were also inhibitory to in vitro proliferation of cells of a rapidly dividing tumor line, MDCC-MSB-1, derived from a lymphoma induced by Marek's disease virus. The effector cell of suppression of both lymphoprolifrative functions appeared to be a macrophage because the suppressive activity of adherent cells could be abrogated by pretreatment with carrageenan but not with antisera specific to chicken T or B cells. The proportion of macrophages needed for effective suppression was substantially higher than the proportion of macrophages ordinarily present in spleen of normal, unstimulated chickens. This heretofore unrecognized suppressive capability of normal, presumably resting macrophages have been detected in certain infections.
Comparative in vitro imunotoxicology of acyclovir and other antiviral agents
Authors: Steele R W , Marmer D J , Keeney R E
Published: June 2021

In vitro lymphocyte blastogenic responses to the commonly employed mitogens phytohemagglutinin, pokeweed, and concanavalin A were evaluated when acyclovir, adenine arabinoside, cytosine arabinoside, and idoxuridine were added to the culture materials. Similarly, specific antigen-induced blastogenic responses, including herpes group antigens, and cytotoxicity and leukocyte inhibitory factor assays with herpes group viruses were determined in the presence and absence of antiviral agents. No depression of these cellular immmune responses by acyclovir or adenine arabinoside ws demonstrated. This was in contrast to the effects of cytosine arabinoside and idoxuridine, which severely inhibited blastogenic and cytotoxic responses but not leukocyte inhibitory factor production. Even at concentrations up to 20 microgram/ml, the antiviral agent acyclovir did not depress selected cellular immune responses that are important for successful elimination of invading herpes group viruses.
R-plasmic transfer from Serratia liquefaciens to Escherichia coli in vitro and in vivo in the digestive tract of gnotobiotic mice associated with human fecal flora
Authors: Duval-Iflah Y , Raibaud P , Tancrede C , Rousseau M
Published: June 2021

It was shown that a strain of Serratia liquefaciens harbors a conjugative R-plasmid responsible for reistance to the following 14 antibiotics: ampicillin, carbenicillin, cephalothin, butirosin, neomycin, paramomycin, kanamycin, lividomycin, gentamicin, tobramycin, streptomycin, tetracycline, sulfonamide, and chloramphenicol, which belong to five families, the beta-lactamines, the aminoglycosides, the tetracyclines, the sulfonamides, and the phenicols. Resistance to th 14 antibiotics was cotransferred by in vitro conjugation between S. liquefaciens and strains of Escherichia coli. Mating between S. liquefaciens and E. coli also occurred in vivo, in the digestive tract of axenic mice and gnotobiotic mice associated with the whole human fecal flora. It was also shown that mating between these two strains occurred even when the donor S. liquefaciens strain was only transient in the digestive tract of the gnotobiotic host animals. A dense population of Bacteroides (10(10) viable cells per g of fresh feces) did not hinder this mating. All the matings occurred in the absence of an antibiotic selection pressure, and the resulting transferred strain of E. coli did not have the same colonizing capacity as the recipient parental strain. However, during antibiotic administration to mice, and even after the end of the drug intake, the transconjugant became established in the dominant population and replaced the parental recipient strain.
Comparison of Online and Onsite Bioinformatics Instruction for a Fully Online Bioinformatics Master’s Program
Authors: Obom Kristina M. , Cummings Patrick J.
Published: June 2021

The completely online Master of Science in Bioinformatics program differs from the onsite program only in the mode of content delivery. Analysis of student satisfaction indicates no statistically significant difference between most online and onsite student responses, however, online and onsite students do differ significantly in their responses to a few questions on the course evaluation queries. Analysis of student exam performance using three assessments indicates that there was no significant difference in grades earned by students in online and onsite courses. These results suggest that our model for online bioinformatics education provides students with a rigorous course of study that is comparable to onsite course instruction and possibly provides a more rigorous course load and more opportunities for participation.
Effects of Temperature on the Meiotic Recombination Landscape of the Yeast
Saccharomyces cerevisiae
Authors: Zhang Ke , Wu Xue-Chang , Zheng Dao-Qiong , Petes Thomas D.
Published: June 2021

Although meiosis in warm-blooded organisms takes place in a narrow temperature range, meiosis in many organisms occurs over a wide variety of temperatures. We analyzed the properties of meiosis in the yeast
Saccharomyces cerevisiae
in cells sporulated at 14°C, 30°C, or 37°C. Using comparative-genomic-hybridization microarrays, we examined the distribution of Spo11-generated meiosis-specific double-stranded DNA breaks throughout the genome. Although there were between 300 and 400 regions of the genome with high levels of recombination (hot spots) observed at each temperature, only about 20% of these hot spots were found to have occurred independently of the temperature. In
S. cerevisiae
, regions near the telomeres and centromeres tend to have low levels of meiotic recombination. This tendency was observed in cells sporulated at 14°C and 30°C, but not at 37°C. Thus, the temperature of sporulation in yeast affects some global property of chromosome structure relevant to meiotic recombination. Using single-nucleotide polymorphism (SNP)-specific whole-genome microarrays, we also examined crossovers and their associated gene conversion events as well as gene conversion events that were unassociated with crossovers in all four spores of tetrads obtained by sporulation of diploids at 14°C, 30°C, or 37°C. Although tetrads from cells sporulated at 30°C had slightly (20%) more crossovers than those derived from cells sporulated at the other two temperatures, spore viability was good at all three temperatures. Thus, despite temperature-induced variation in the genetic maps, yeast cells produce viable haploid products at a wide variety of sporulation temperatures.

IMPORTANCE
In the yeast
Saccharomyces cerevisiae
, recombination is usually studied in cells that undergo meiosis at 25°C or 30°C. In a genome-wide analysis, we showed that the locations of genomic regions with high and low levels of meiotic recombination (hot spots and cold spots, respectively) differed dramatically in cells sporulated at 14°C, 30°C, and 37°C. Thus, in yeast, and likely in other non-warm-blooded organisms, genetic maps are strongly affected by the environment.
Strong and regulated expression of Escherichia coli beta-galactosidase in insect cells with a baculovirus vector
Authors: Pennock G D , Shoemaker C , Miller L K
Published: June 2021

The N-terminal region of the gene encoding polyhedrin, the major occlusion protein of the insect baculovirus Autographa californica nuclear polyhedrosis virus (AcNPV), has been fused to DNA encoding Escherichia coli beta-galactosidase. The fused gene was inserted into the AcNPV DNA genome by cotransfection of insect cells with recombinant plasmid DNA and wild-type AcNPV genomic DNA. Recombinant viruses were selected as blue plaques in the presence of a beta-galactosidase indicator, 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside. Studies of one such virus, L1GP-gal3, indicated that the synthesis of beta-galactosidase is temporally controlled beginning late (20 h) in infection after the release of infectious virus particles from the cell. By 48 h postinfection, a remarkably high level of expression is achieved. On the basis of these results, AcNPV should be a useful vector for the stable propagation and expression of passenger genes in a lepidopteran cell background. A generalized transplacement vector that facilitates the construction and selection of recombinant viruses carrying passenger genes under their own promoter control has also been developed.
Drosophila melanogaster has only one myosin alkali light-chain gene which encodes a protein with considerable amino acid sequence homology to chicken myosin alkali light chains
Authors: Falkenthal S , Parker V P , Mattox W W , Davidson N
Published: June 2021

A chimeric lambda DNA molecule containing the myosin alkali light-chain gene of Drosophila melanogaster was isolated. The encoded amino acid sequence was determined from the nucleic acid sequence of a cDNA homologous to the genomic clone. The identity of the encoded protein was established by two criteria: (i) sequence homology with the chicken alkali light-chain proteins and (ii) comparison of the two-dimensional gel electrophoretic pattern of the peptides synthesized by in vitro translation of hybrid-selected RNA to that of myosin alkali light-chain peptides extracted from Drosophila myofibrils. There is only one myosin alkali light-chain in D. melanogaster; its chromosomal location is region 98B . This gene is abundantly expressed during the development of larval as well as adult muscles. The Drosophila protein appears to contain one putative divalent cation-binding domain (an EF hand) as compared with the three EF hands present in chicken alkali light chains.
Studies of Spectral Broadening of the Lower Hybrid Wave Line in the Current-Drive Regimes and Ion Heating at the FT-2 Tokamak
Authors: Dyachenko V. V. , Altukhov A. B. , Gusakov E. Z. , Esipov L. A. , Konovalov A. N. , Lashkul S. I. , Stepanov A. Yu. , Shatalin S. V.
Published: June 2021

The experiments at the FT-2 tokamak are described that were focused on clearing up the role of the parametric decay instabilities in decreasing the generation efficiency of the non-inductive current excited by the electromagnetic waves in the lower hybrid frequency range. The most discussed instability of such kind is the decay of the pump wave into the daughter high-frequency waves and the low-frequency ion–acoustic quasi-modes. The studies performed have shown that, under conditions of the FT-2 experiment, the ion–acoustic instability has no decisive effect on the decrease in the efficiency of the lower hybrid current drive.
Reversal of ‘the dying’ diagnosis
Authors: Ali Maimoona , Goddard Andrew , Smith Eleanor
Published: June 2021

A 75-year-old woman was admitted with sepsis and treated with broad-spectrum antibiotics until examination of her lower limbs noted necrotising wounds. Surgical intervention was advised by the plastic surgeons; however, she was deemed unsuitable for intensive care. She underwent incision and drainage of the necrotic area and biopsies were taken. She deteriorated clinically and the decision was made for best supportive care and was therefore transferred to the inpatient palliative care unit for end-of-life care. However, she stabilised, and based on culture sensitivities, antibiotics were restarted. It was also noted that the patient had a 3-month history of loose stools, which had not been addressed previously. The biopsies were suggestive of pyoderma gangrenosum, prompting a dermatology review, and prednisolone and doxycycline were started. The wounds and her loose stools improved, and with ongoing rehabilitation, she made a full recovery. Referral to gastroenterology was made.
‘Diagnostic downshift’: clinical and system consequences of extrapolating secondary care testing tactics to primary care
Authors: Sajid Imran Mohammed , Frost Kathleen , Paul Ash K
Published: June 2021

Numerous drivers push specialist diagnostic approaches down to primary care (‘diagnostic downshift’), intuitively welcomed by clinicians and patients. However, primary care’s different population and processes result in under-recognised, unintended consequences. Testing performs poorer in primary care, with indication creep due to earlier, more undifferentiated presentation and reduced accuracy due to spectrum bias and the ‘false-positive paradox’. In low-prevalence settings, tests without near-100% specificity have their useful yield eclipsed by greater incidental or false-positive findings. Ensuing cascades and multiplier effects can generate clinician workload, patient anxiety, further low-value tests, referrals, treatments and a potentially nocebic population ‘disease’ burden of unclear benefit. Increased diagnostics earlier in pathways can burden patients and stretch general practice (GP) workloads, inducing downstream service utilisation and unintended ‘market failure’ effects. Evidence is tenuous for reducing secondary care referrals, providing patient reassurance or meaningfully improving clinical outcomes. Subsequently, inflated investment in per capita testing, at a lower level in a healthcare system, may deliver diminishing or even negative economic returns. Test cost poorly represents ‘value’, neglecting under-recognised downstream consequences, which must be balanced against therapeutic yield. With lower positive predictive values, more tests are required per true diagnosis and cost-effectiveness is rarely robust. With fixed secondary care capacity, novel primary care testing is an added cost pressure, rarely reducing hospital activity. GP testing strategies require real-world evaluation, in primary care populations, of all downstream consequences. Test formularies should be scrutinised in view of the setting of care, with interventions to focus rational testing towards those with higher pretest probabilities, while improving interpretation and communication of results.
Bridging the gap: aligning economic research with disease burden
Authors: Do Lauren A , Synnott Patricia G , Ma Siyu , Ollendorf Daniel A
Published: June 2021

Introduction

Cost-effectiveness analysis (CEA) is critical for identifying high-value interventions that address significant unmet need. This study examines whether CEA study volume is proportionate to the burden associated with 21 major disease categories.

Methods

We searched the Tufts Medical Center CEA and Global Health CEA Registries for studies published between 2010 and 2019 that measured cost per quality-adjusted life-year or cost per disability-adjusted life-year (DALY). Stratified by geographical region and country income level, the relationship between literature volume and disease burden (as measured by 2019 Global Burden of Disease estimates of population DALYs) was analysed using ordinary least squares linear regression. Additionally, the number of CEAs per intervention deemed ‘essential’ for universal health coverage by the Disease Control Priorities Network was assessed to evaluate how many interventions are supported by cost-effectiveness evidence.

Results

The results located below the regression line but with relatively high burden suggested disease areas that were ‘understudied’ compared with expected study volume. Understudied disease areas varied by region. Higher-income and upper-middle-income country (HUMIC) CEA volume for non-communicable diseases (eg, mental/behavioural disorders) was 100-fold higher than that in low-income and lower-middle-income countries (LLMICs). LLMIC study volume remained concentrated in HIV/AIDS as well as other communicable and neglected tropical diseases. Across 60 essential interventions, only 33 had any supporting CEA evidence, and only 21 had a decision context involving a low-income or middle-income country. With the exception of one intervention, available CEA evidence revealed the 21 interventions to be cost-effective, with base-case findings less than three times the GDP per capita.

Conclusion

Our analysis highlights disease areas that require significant policy attention. Research gaps for highly prevalent, lethal or disabling diseases, as well as essential interventions may be stifling potential efficiency gains. Large research disparities between HUMICs and LLMICs suggest funding opportunities for improving allocative efficiency in LLMIC health systems.
American Association for the Surgery of Trauma Prevention Committee review: Family Justice Centers—a not-so-novel, but unknown gem
Authors: Duncan Thomas K , Stewart Ronald , Joseph Kimberly , Kuhls Deborah A , Dechert Tracey , Taghavi Sharven , Bonne Stephanie , Matsushima Kazuhide
Published: June 2021

The American College of Surgeons Committee on Trauma requires that trauma centers demonstrate adequate financial support for an injury prevention program as part of the verification process. With the ongoing challenges that arise with important social determinants of health, trauma centers have the important task of navigating a patient through the complex process of obtaining services and tools for success. This summary from the American Association for the Surgery of Trauma Prevention Committee focuses on a model that has been present for several years, but has not been brought to full awareness in the trauma world. It highlights the importance of the Family Justice Center concept that brings a multitude of organizations under one roof, thus eliminating the hurdles encompassed by trauma patients, seeking life-changing resources necessary to mitigate the impact of both community violence exposure and intimate partner/domestic violence. It discusses the potential benefits of a partnership between trauma centers and Family Justice Centers and similar models. Finally, it also raises awareness of important programmatic evaluation research required in the arena of injury prevention targeting a population whose outcomes are difficult to measure.
Towards strategy evolution in pedestrian room evacuation
Authors: Guan Junbiao , Wang Kaihua , Yang Jianfang
Published: June 2021

Knowing how crowds behave is crucial to understanding pedestrian evacuation. In this work, we study strategy evolution in pedestrian room evacuation using a cellular automaton (CA) model with a spatial game. Agents play the game under certain conditions. While playing the game, they choose one of the three strategies (Patient strategy, Normal strategy and Impatient strategy) according to either fitness or imitation that leads to patient, normal or impatient behavior. Interactions among agents are reflected by the payoffs (related with friction cost) which may depend on agents’ surroundings. Simulation results show how evacuation conditions, agents’ individual actions, and friction cost affect strategy evolution in pedestrian room evacuation. It is found that cooperation exists both in emergency situation and relatively nonemergency situation, but appears more in the latter one. The imitation action has negative impacts either on the evolution of Normal strategy in relatively nonemergency situation or on the evolution of Patient strategy in emergency situation. In addition, uniform evolution phenomena are observed in the evacuation process, despite different composition of initial agents.
Age-dependent transcriptional alterations in cardiac endothelial cells
Authors: Emechebe Uchenna , Nelson Jonathan W. , Alkayed Nabil J. , Kaul Sanjiv , Adey Andrew C. , Barnes Anthony P.
Published: June 2021

Aging is a significant risk factor for cardiovascular disease. Despite the fact that endothelial cells play critical roles in cardiovascular function and disease, the molecular impact of aging on this cell population in many organ systems remains unknown. In this study, we sought to determine age-associated transcriptional alterations in cardiac endothelial cells. Highly enriched populations of endothelial cells (ECs) isolated from the heart, brain, and kidney of young (3 mo) and aged (24 mo) C57/BL6 mice were profiled for RNA expression via bulk RNA sequencing. Approximately 700 cardiac endothelial transcripts significantly differ by age. Gene set enrichment analysis indicated similar patterns for cellular pathway perturbations. Receptor-ligand comparisons indicated parallel alterations in age-affected circulating factors and cardiac endothelial-expressed receptors. Gene and pathway enrichment analyses show that age-related transcriptional response of cardiac endothelial cells is distinct from that of endothelial cells derived from the brain or kidney vascular bed. Furthermore, single-cell analysis identified nine distinct EC subtypes and shows that the Apelin Receptor-enriched subtype is reduced with age in mouse heart. Finally, we identify age-dysregulated genes in specific aged cardiac endothelial subtypes.
Optimization of Multiobjective Configuration of Multienergy Microgrid Based on HMM and Typical Scenarios: A Case Study of Smart Park
Authors: He Jianzong , Situ You , Su Junni , Zhang Xin , Li Mude
Published: June 2021

Decentralized regional multienergy system is one of the important development directions of energy and power systems, and researching on the optimization method of multienergy microgrid configuration could provide important support for the investment income guarantee and orderly development of regional multienergy systems. Based on a park-level multienergy microgrid, this paper proposed a multiobjective optimization model for a multienergy microgrid configuration based on the typical scenario set which was constructed by HMM. Besides, based on the actual historical data, the capacity configuration-oriented planning model and component configuration-oriented planning model were analysed and compared under different external environments. The results show that HMM has a good effect on the reduction and extraction of historical scenarios of the system. Compared with the traditional microgrid, the multienergy microgrid has better economic and emission reduction advantages. In addition, the capacity configuration-oriented planning model could reduce the investment cost by up to 62.4% compared with the component configuration-oriented planning model.