bluuebunny/crossref_metadata_2025 huggingface dataset:
Adoptive cell therapy using tumor‐infiltrating lymphocytes for melanoma refractory to immune‐checkpoint inhibitors
Authors: Hirai Ikuko , Funakoshi Takeru , Kamijuku Hajime , Fukuda Keitaro , Mori Mariko , Sakurai Masatoshi , Koda Yuya , Kato Jun , Mori Takehiko , Watanabe Naohide , Noji Shinobu , Yaguchi Tomonori , Iwata Takashi , Ohta Shigeki , Fujita Tomonobu , Tanosaki Ryuji , Handa Makoto , Okamoto Shinichiro , Amagai Masayuki , Kawakami Yutaka
Published: June 2021

To evaluate the feasibility of adoptive cell therapy (ACT) using ex vivo‐expanded tumor‐infiltrating lymphocytes (TILs) in Japanese patients with melanoma who failed immune‐checkpoint inhibitor therapy, an open‐label, single‐arm, pilot study was conducted. We investigated the immunological and genetic factors of the pretreatment tumor and expanded TILs that may be associated with the clinical response. The treatment protocol comprised preparation of TIL culture, lympho‐depleting non‐myeloablative preconditioning with cyclophosphamide and fludarabine, TIL infusion, and intravenous administration of low‐dose IL‐2. Three patients of clinical subtypes mucosal, superficial spreading, and acral melanoma underwent TIL‐ACT. Most severe adverse events, including fever and leukopenia, were manageable with the supportive regimen specified in the protocol, suggesting that the TIL‐ACT regimen is suitable for Japanese patients with melanoma. One patient showed a short‐term partial response, one relatively long‐stable disease, and one experienced disease progression. Whole‐exome and transcriptional sequencing of isolated tumor cells and immunohistochemical analyses before TIL‐ACT revealed various immunostimulatory factors, including a high tumor mutation burden and immune cell‐recruiting chemokines, as well as various immunosuppressive factors including TGF‐β, VEGF, Wnt/β‐catenin, and MAPK signaling and epithelial‐to‐mesenchymal transition, which might influence the efficacy of TIL‐ACT. Our results imply mechanisms for the antitumor effect of and resistance to TIL‐ACT. Further studies of immune‐resistant mechanisms of TIL‐ACT are warranted. This study is registered with the UMIN Clinical Trial Registry (UMIN 000011431).
From distraction to habituation: Ecological and behavioural responses of invasive fish to anthropogenic noise
Authors: Rojas Emilie , Thévenin Simon , Montes Gabriella , Boyer Nicolas , Médoc Vincent
Published: June 2021

Tolerance to human‐induced environmental stressors is known to contribute to the spread and success of invasive species but their response to anthropogenic noise has still to be explored. Anthropogenic noise might modulate the trophic impact of invasive species and their competitiveness against native species.

We used an ecological approach through the derivation of the functional response to test whether the strength of the trophic interaction between the invasive pumpkinseed sunfish andChaoboruslarvae was influenced by motorboat noise, with or without pre‐exposure.

Boat noise decreased maximum feeding rate in the fish that never experienced boat noise before, resulting in a lower functional response compared to the ambient noise condition. We hypothesised that fish were distracted and reallocated a part of their finite attention to this new acoustic stimulus at the expense of prey processing.

The distraction effect weakened with repeated exposure suggesting a habituation process. Although we cannot exclude persistent adjustments in behaviour, we did not find evidence for altered predation by fish pre‐exposed to boat noise.

Pumpkinseed sunfish did not exhibit clear symptoms of a behavioural stress response.Chaoborusmovements were more numerous under boat noise but this was unlikely to influence trophic interaction strength relative to fish behaviour. Local species might experience increased trophic competition if they are disturbed and do not habituate contrary to invasive species.
La participación de los agentes sociales en la gestión de la crisis de la COVID‐19: el diálogo social tripartito en España, Italia y Portugal
Authors: CANALDA CRIADO Sergio
Published: June 2021

Se aborda la participación de los agentes sociales en la gestión de la crisis de la COVID‐19 analizando las experiencias de diálogo social tripartito surgidas en España, Italia y Portugal. Se examinan las variables económicas y políticas que han podido favorecer la revitalización del tripartismo en estos tres países en comparación con la anterior crisis económica. En este sentido, la ausencia de políticas de austeridad y la asunción compartida de la responsabilidad por agentes sociales y gobiernos han impulsado la consecución de diferentes acuerdos que, aunque difieren en su contenido y alcance, evidencian un fortalecimiento del diálogo tripartito al máximo nivel.
Differential DNA methylation and mRNA transcription in gingival tissues in periodontal health and disease
Authors: Kim Hyunjin , Momen‐Heravi Fatemeh , Chen Steven , Hoffmann Per , Kebschull Moritz , Papapanou Panos N.
Published: June 2021

Aim

We investigated differential DNA methylation in gingival tissues in periodontal health, gingivitis, and periodontitis, and its association with differential mRNA expression.

Materials and methods

Gingival tissues were harvested from individuals and sites with clinically healthy and intact periodontium, gingivitis, and periodontitis. Samples were processed for differential DNA methylation and mRNA expression using the IlluminaEPIC (850 K) and the IlluminaHiSeq2000 platforms, respectively. Across the three phenotypes, we identified differentially methylated CpG sites and regions, differentially expressed genes (DEGs), and genes with concomitant differential methylation at their promoters and expression were identified. The findings were validated using our earlier databases using HG‐U133Plus2.0Affymetrix microarrays and Illumina (450 K) methylation arrays.

Results

We observed 43,631 differentially methylated positions (DMPs) between periodontitis and health, and 536 DMPs between gingivitis and health (FDR < 0.05). On the mRNA level, statistically significant DEGs were observed only between periodontitis and health (n = 126). Twelve DEGs between periodontitis and health (DCC, KCNA3, KCNA2, RIMS2, HOXB7, PNOC, IRX1, JSRP1, TBX1, OPCML, CECR1, SCN4B) were also differentially methylated between the two phenotypes. Spearman correlations between methylation and expression in the EPIC/mRNAseq dataset were largely replicated in the 450 K/Affymetrix datasets.

Conclusions

Concomitant study of DNA methylation and gene expression patterns may identify genes whose expression is epigenetically regulated in periodontitis.
A new way to produce odd‐allotetraploid lily (Lilium) through 2n gametes
Authors: Xiao Kongzhong , Cui Luomin , Wan Lin , Zhong Ju , Liu Yanmei , Sun Yanni , Zhou Shujun
Published: June 2021

Odd‐allotetraploid lily, such as ‘Honesty’ (LAAA), is a new type of allotetraploids. However, there has been no report on how to breed odd‐allotetraploid lily cultivars so far. According to their genomic composition, such as LAAA, we proposed LA × AAAA and LALA × AAAA would be two ways to breed them since LA lily could produce a small amount of 2n gametes and LALA could produce a large amount of normal 2x gametes. In the present study, an interploid cross, LA × AAAA, was made and its five seedlings were analysed using genomic in situ hybridization. Four of them were odd‐allotetraploid, one was near odd‐allotetraploid. Their intergenomic variations caused by 2n eggs increased the chance of selecting new cultivars. It was concluded that the interploid cross was a promising way to breed odd‐allotetraploid lilies with high genetic variations at chromosome levels.
Variation in persistency, postdrought recovery and root characteristics in a tall fescue germplasm under interactive effects of exogenously applied salicylic acid and water stress
Authors: Taleb Mohammad Hadi , Majidi Mohammad Mahdi , Mirmohammady Maibody Sayed Ali Mohammad , Pirnajmedin Fatemeh
Published: June 2021

This study was performed for a better understanding of genotypic responses of a germplasm of tall fescue to different prolonged drought stresses and exogenously applied salicylic acid (SA) in terms of drought tolerance, postdrought recovery, persistence and root‐related traits. Twenty‐one diverse tall fescue genotypes were evaluated under three irrigation treatments (IT) (normal, mild and intense drought stress) and the presence of two SA concentrations (0 and 1 mM) during 2015–2017. In the fourth year (2018), irrigation was withheld in all treatments for two months in summer (severe drought) and then plants were rewatered to investigate the effect of previous treatments on the mentioned traits. Results indicated that recovery after severe drought and persistence in tall fescue depends on previous environmental conditions with clear differences in genotypic responses. Foliar application of SA improved forage production, drought tolerance, postdrought recovery and most of the root traits, while it had a negative effect on persistence and root length. Associations amongst traits under different treatments and selection of superior genotypes will be discussed.
Institutional endowment, curse, and the impact of external political shock: The case of Macao
Authors: Chen Chaoqun , Zhou Yonghong
Published: June 2021

This study investigates the influence of external political shock under a special institutional endowment brought by a high degree of autonomy, taking Macao as an example. Macao monopolizes the gambling industry in China under the arrangement of “one country, two systems” and depends heavily on tourists from mainland China. To illustrate the problem under such an institutional endowment, this study estimates the impact of the decline in casino revenues caused by the 2014 anti‐corruption campaign in mainland China, by employing the difference‐in‐differences and synthetic control approaches. The results indicate that Macao experienced approximately 3 years of decline in the revenue growth of the gambling industry, which is nearly 231 billion MOP, under the political shock. Thus, an economy with institutional endowment may also face uncertainties caused by exogenous political shock. This paper contributes to the extension of the concept related to the tourism‐induced Dutch disease.
How we secured a COVID‐19 convalescent plasma procurement scheme in Japan
Authors: Terada Mari , Kutsuna Satoshi , Togano Tomiteru , Saito Sho , Kinoshita Noriko , Shimanishi Yumiko , Suzuki Tetsuya , Miyazato Yusuke , Inada Makoto , Nakamoto Takahito , Nomoto Hidetoshi , Ide Satoshi , Sato Mitsuhiro , Maeda Kenji , Matsunaga Akihiro , Satake Masahiro , Matsubayashi Keiji , Tsuno Hirokazu , Kojima Makiko , Kuramistu Madoka , Tezuka Kenta , Ikebe Emi , Okuma Kazu , Hamaguchi Isao , Shiratori Katsuyuki , Sato Motohiko , Kawakami Yuiko , Inaba Kumi , Igarashi Saori , Yamauchi Reina , Matsumura Mina , Ishimaru Keiko , Zhang Bijuan , Kuge Chika , Ishihara Maiko , Gouda Miho , Tanaka Keiko , Ishizaka Yukihito , Ohmagari Norio
Published: June 2021

Background

In order to tackle the COVID‐19 pandemic, a COVID‐19 convalescent plasma (CCP) procurement program was initiated in Japan in April 2020. The program was a collaboration between a government‐managed national hospital, an infectious disease research institute, and a blood banking organization. Each party assumed different responsibilities: recruitment, SARS‐CoV‐2 antibody profiling, and plasmapheresis; conduction of screening tests; and SARS‐CoV‐2 blood testing, respectively.

Methods

We adopted a two‐point screening approach before the collected CCP was labeled as a CCP product for investigational use, for which we mainly tested anti‐SARS‐CoV‐2 antibody eligibility and blood product eligibility. Anti‐SARS‐CoV‐2 spike protein titer was measured using enzyme‐linked immunosorbent assay, and the IC50 value was denoted as the neutralizing activity. Blood donor eligibility was extended beyond the normal blood donation guidelines to include a broader range of participants. After both eligibility criteria were confirmed, participants were asked to revisit the hospital for blood donation, which is a unique aspect of the Japanese CCP program, as most donations are taking place in normal blood donation venues in other countries. Some donors were re‐scheduled for repeat plasma donations. As public interest in anti‐SARS‐CoV‐2 antibodies increased, test results were given to the participants.

Results

As of September 17, 2020, our collection of CCP products was sufficient to treat more than 100 patients. As a result, projects for administration and distribution are also being conducted.

Conclusions

We successfully implemented a CCP procurement scheme with the goal to expand to other parts of the country to improve treatment options for COVID‐19.
Peru: From Exclusionary Constitutionalism to a Transformative One, Progress and Remaining Challenges
Authors: Huaita Marcela , Choccechanca Andrea
Published: June 2021

This article covers the evolution of key gender relations issues in Peruvian constitutions for almost a century, from 1931 to 2021. It analyses the path travelled from the exclusion of women as citizens to the achievement of parity in political participation; the transformation of the equality clause into one that has the possibility to incorporate discrimination based on sexual orientation as a prohibited category; as well as changes in the conception of maternity protection by the State, until one arrives at a provision that recognizes the right of people to decide individually about their reproductive choices. The article also reports on the participation of women in the struggle for these gains, their initiatives both in formal and informal spaces, as well as the demands of first and second wave feminist movements. All these points are organised through categories coined by Ruth Rubio Marín, to understand constitutionalism from a gender perspective: exclusionary, inclusive, participatory, and transformative constitutionalism.
Biochemical and structural basis of the passive mechanical properties of whole skeletal muscle
Authors: Lieber Richard L. , Binder‐Markey Benjamin I
Published: June 2021

Passive mechanical properties of whole skeletal muscle are not as well understood as active mechanical properties. Both the structural basis for passive mechanical properties and the properties themselves are challenging to determine because it is not clear which structures within skeletal muscle actually bear passive loads and there are not established standards by which to make mechanical measurements. Evidence suggests that titin bears the majority of the passive load within the single muscle cell. However, at larger scales, such as fascicles and muscles, there is emerging evidence that the extracellular matrix bears the major part of the load. Complicating the ability to quantify and compare across size scales, muscles and species, definitions of muscle passive properties such as stress, strain, modulus and stiffness can be made relative to many reference parameters. These uncertainties make a full understanding of whole muscle passive mechanical properties and modelling these properties very difficult. Future studies defining the specific load bearing structures and their composition and organization are required to fully understand passive mechanics of the whole muscle and develop therapies to treat disorders in which passive muscle properties are altered such as muscular dystrophy, traumatic laceration, and contracture due to upper motor neuron lesion as seen in spinal cord injury, stroke and cerebral palsy.

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Mo-Doped SnO2 Quantum Dots Dispersed Over Reduced Graphene Oxide Sheets as an Efficient Anode Material
Authors: Huang Yong-Cun , Brahma Sanjaya , Chang Chia-Chin , Huang Jow-Lay
Published: June 2021

We explore the effect of Mo doping over the large enhancement of electrochemical property of Mo-doped SnO2 quantum dots (3–5 nm) grown over rGO (reduced graphene oxide) sheets by a soft chemical process in ambient conditions. The composites were prepared over a range of Mo doping concentrations (0–10%) and 5% Mo doping had achieved the best energy storage characteristics. The capacity of the active material could reach ∼851 mAh g−1 (@ 78 mA g−1) in the beginning and that retained ∼89% (∼758 mAh g−1) with superior cyclic stability (100 cycles) and rate capability (506 mAh g−1 @ ∼1.5 A g−1). The addition of the reductant of 0.06 mol during the synthesis procedure led to further improvement of the capacity to ∼875 mAh g−1 (∼92% retention) and the rate capability (∼587 mAh g−1). These impressive results are ascribed to the distribution of Mo-doped SnO2 QDs, doping of Mo6+ at Sn4+ lattice sites providing more electrons for easy electrical transport, reduction of GO (graphene oxide) to rGO. Mo doping led to the decline in the charge transfer resistance (Rct) from 14.99 Ω for un-doped SnO2/rGO to 14.09 Ω (2.5%), 11.61 Ω (5%), and 11.4 Ω (10%) and promote the electrochemical property of the composite. A simple room-temperature synthesis process was used to produce Mo-doped SnO2/rGO nanocomposite and can be employed for the production of many other oxides and their composites for interesting applications.
Modeling the Creep of Nickel
Authors: Sandström Rolf , Zhang Jing
Published: June 2021

Many metals and alloys have a stress exponent for the creep rate that is considerably higher than the value of three that is typically predicted by creep recovery models. One example is pure Ni. Creep data from Norman and Duran that are analyzed in the paper give a stress exponent of about seven in the temperature range 0.3–0.55 of the melting point. It has recently been shown that the high creep exponent of Al and Cu in the power-law breakdown regime can be explained by the presence of strain-induced vacancies. By applying a creep recovery model that does not involve adjustable parameters, it is shown that strain-induced vacancies can also explain the high-stress exponent of pure nickel.
Analysis of the Bimaterial Interface Cracks Based on Configurational Forces
Authors: Liu Ran , Li Qun
Published: June 2021

In this paper, an innovative interface fracture criterion is proposed based on the concept of configurational forces in material space. In this criterion, the crack-tip configurational forces as the driving force are introduced to describe the interface crack evolution under mixed-mode loading conditions. And it assumes that the interface crack propagates due to the competition of resultant configurational forces with interface fracture toughness. The analytical expression of the configurational forces is obtained by differentiating the elastic strain energy density and conservative integral for interface cracks. And the relation of interface crack-tip configurational forces with classical complex intensity factors is obtained through strict mathematical deduction. The interface crack-tip configurational forces are evaluated for a classic interface crack problem covering a wide range of bimaterial oscillation indexes. The configurational forces-based interface fracture criterion is validated through series interface fracture experiments. The proposed criterion may provide a novel framework for the analysis of interface fracture under complex loading conditions.
Wind Power Deterministic Prediction and Uncertainty Quantification Based on Interval Estimation
Authors: Huang Hui , Jia Rong , Liang Jun , Dang Jian , Wang Zhengmian
Published: June 2021

With the increasing penetration of wind power into modern power systems, accurate forecast models play a crucial role in large-scale wind power consumption and power system stability. To improve the accuracy and reliability of ultrashort-term wind power prediction, a novel deterministic prediction model and uncertainty quantification with interval estimation were proposed in this study. In consideration of the dynamic characteristics of a generator and conditional dependence, the generator rotor speed and pitch angle were regarded as the indicators of the dynamic characteristics of the generator, and light gradient boosting machine (LGBM) with a Bayesian optimization method was explored to build the deterministic prediction model. Considering the conditional dependence between output power and forecast error, a fuzzy C-means clustering method was used to cluster forecast errors into different clusters, and the best error probability distribution was obtained by fitting the error histogram with nonparametric kernel density estimation. Prediction intervals at different confidence levels were calculated, and the error uncertainty was quantified. A case study was conducted to compare prediction accuracy and reliability by using the present and proposed methods. Results demonstrate that the LGBM deterministic prediction model combined with Bayesian optimization has better prediction accuracy and lower computational cost than the comparative models, specifically when the input features are high-dimensional big data. The nonparametric estimation method with conditional dependence is reliable for interval prediction. The proposed method has a certain reference value for wind turbines participating in frequency regulation and power control of power grid.
A Sense of History
Authors: Sinclair Bruce
Published: June 2021

The American Society of Mechanical Engineers reached the fiftieth anniversary of its founding in 1930. This kind of institutional milestone usually calls for special observance to celebrate an organization’s continuity and define its place in history. But besides the conventional impulses for that sort of exercise, the Society’s leaders were men with a taste for ceremony and a conviction that their profession deserved a prominent part in the story of human progress. ASME’s anniversary festivities thus promised to be rich in the self-congratulation customary on such occasions.
Technological Confidence during the Great Depression
Authors: Sinclair Bruce
Published: June 2021

To the men of the American Society of Mechanical Engineers, proof of the value of the organization lay in America’s remarkable technological triumphs. They could see the connection in several different ways. Most obviously, there were members famous for their accomplishments. George Westinghouse, for instance, ASME’s twenty-ninth president, reached the status of folk hero for his inventiveness and the giant industrial firm he created. There were others like him, such as George Babcock, Ambrose Swasey, and Charles Schwab, who, although not as well known, were held in great esteem in the mechanical community for their technical achievements and business enterprise.
Progress in Railway Mechanical Engineering 2019 – 2020 Survey – Locomotives
Authors: Mast Timothy
Published: June 2021

This survey reports on motive power developments for the previous year ending in August 2020. Invitations to collaborate were sent to several locomotive builders and railroads. The survey looks at the scope of new and rebuilt motive power during the past year. During this time, several Class 1 railroads have heavily adopted the rebuilding and modernization of existing motive power. The survey also looks at how the needs of the railroads are changing in terms of motive power both due to Precision Scheduled Railroading (PSR) and also due to the novel Coronavirus pandemic. Finally, this survey will conclude with a look back at the high horsepower race following the retirement of the EMD SD80MAC locomotives from Class 1 ownership.
An Experimental Study of the Influence of the Amount of Top-Of-Rail Friction Modifiers on Traction
Authors: Pan Yu , Radmehr Ahmad , Tajaddini Ali , Ahmadian Mehdi
Published: June 2021

This study presents an experimental study of the effect of Top-of-Rail Friction Modifiers (TORFM) in quantities ranging from a small to a large amount on the progression of wheel-rail wear, using the Virginia Tech-FRA (VT-FRA) roller rig. TORFM behaves as a third body layer in between the wheel and rail and is applied to reduce wheel and rail wear while preserving a stable traction condition. An added benefit of TORFM is that it is estimated that it can reduce fuel consumption by controlling friction, although we are not aware of any proven data in support of this. Although widely used by the U.S. Class I railroads, there exists no proven method for determining, qualitatively or quantitatively, how the amount of TORFM and rail/wheel wear are related. Simply put, would increasing TORFM amount by a factor of two reduce wheel/rail wear and damage by one-half? How would such doubling effect traction or the longevity of TORFM on the wheel/rail surface? In this study, the VT-FRA roller rig is used to perform a series of tests under highly controlled conditions to shed more light on answering these questions. A series of controlled experiments are designed and performed in order to investigate the potential factors that may influence the traction performance. The wheel surface profile is measured by a high-precision, 3D, laser profiler to measure the progression of wheel wear for the duration of the experiments. The results indicate that it takes as much longer time for the traction force (traction coefficient) to reach a condition that is the same as the unlubricated rail, when compared between lightly-, moderately-, and heavily-lubricated conditions. The results further indicate that wear generation is delayed significantly among all lubrication conditions — even, the lightly-lubricated — when compared with the unlubricated conditions. A further evaluation of the results and additional tests are needed to provide further insight into some of the preliminary results that we have observed thus far.
Develop a New Approach Measuring the Wheel/Rail Interaction Loads
Authors: Boronenko Yuriy , Rahimov Rustam , Lafta Waail Mahmod
Published: June 2021

Determine and control the impact of rolling stock on the railway track, one of the significant subjects of railway engineering, especially with heavy traffic and innovative freight cars with increased axle loads. Different methods utilized to measure the lateral impact of rolling stock on a railway based on the use of strain gauges installed on the rail differ in the location of strain gauges and the specifics of processing the received signals. The shortage of these methods that the lateral force arising from the wheel/rail interaction determined when the wheel position over the strain gauges sections. Therefore, continuous registration of details in the wheel/rail contact is impossible. Multiple passes of the test rolling stock along the measuring section are required to receive the right results.

In this article, a new method developed to continue recording the lateral forces of the wheel/rail interaction by measuring stresses in two sections of the rail on a significant part of the sleeper space. The railway track experiments approved this method’s ability to restore the lateral force of not more than 4% standard deviation along the measuring zone’s length and increased the volume of reliable statistical data obtained, improved the measurement accuracy, and reduced the time and cost.
Effect of Longitudinal Fastener Stiffness on Fastening System Loading - Initial Findings
Authors: Khachaturian Christian J. , Dersch Marcus S. , Edwards J. Riley , Trizotto Matheus
Published: June 2021

Over the past 20 years, there have been at least 10 derailments due to spike fatigue failures in North America. Researchers believe that fatigue failure is caused by a combination of lateral and longitudinal spike loading. The literature indicates the vertical load and fastener friction must be considered when estimating failure locations. Though the in-track vertical, lateral, and longitudinal fastener forces have been quantified at a location that has experienced spike failures, there is a need to account for additional fasteners and track locations. Fastening systems can affect track stiffness, thus, laboratory experimentation was performed to quantify stiffness of multiple fastening systems. This data was input into an analytical model which quantified the effect of stiffness on longitudinal fastener loading. The data indicate there is significant variance in fastening system stiffness within, and between, systems. However, this variation in fastener stiffness has a reduced effect on the load transferred to the fastening system. More work is needed to validate this in the lab or field given variability within a system could lead to stress concentrations that are not fully captured using the current idealized analytical method.
Viability of Mycobacterium leprae after multiplication in mice
Authors: Welch T M , Gelber R H , Murray L P , Ng H , O'Neill S M , Levy L
Published: June 2021

To measure the rate at which Mycobacterium leprae are killed in the course of the mouse footpad infection after the maximum of multiplication has been achieved, M. leprae were harvested shortly before and at intervals after multiplication had reached the level of 10(6) organisms per footpad, serially diluted, and inoculated into the footpads of passage mice. Beginning 1 year later, foot-by-foot harvests of M. leprae were performed from passage mice, and the proportion of viable organisms in the passage inocula was calculated by means of a most-probable-number calculation. In addition, the proportion of solidly staining M. leprae was measured in the passage inocula. The proportion of viable M. leprae in the passage inocula was found to decrease with the time after multiplication to 10(6) organisms per footpad of donor mice; the half-time of loss of viable M. leprae was 25 days. The proportion of solidly staining organisms appeared to be directly related to the proportion of viable organisms, as measured by mouse passage, and inversely proportional to the time after multiplication to 10(6) organisms per footpad.
Interaction of Mycoplasma gallisepticum with sialyl glycoproteins
Authors: Glasgow L R , Hill R L
Published: June 2021

The binding of several glycoproteins to freshly grown and harvested cells of Mycoplasma gallisepticum was examined. Only human glycophorin, the major sialoglycoprotein of the erythrocyte membrane, bound tightly as judged by direct binding assays with 125I-labeled glycoproteins. Neuraminidase-treated glycophorin did not bind, suggesting that binding is mediated through sialic acid groups. Although other sialoglycoproteins did not appear to bind M. gallisepticum by direct binding assays, some inhibited the binding of glycophorin. The best inhibitors had a mucin-like structure, with high molecular weights and high sialic acid contents. N-acetylneuraminic acid appeared to be the favored sialic acid structure for binding, but there was no strict specificity for its anomeric linkage. Neuraminidase activity could not be detected on the surface of M. gallisepticum, suggesting that this enzyme is not involved in the mechanism of adherence of sialoglycoproteins. Binding of sialoglycoproteins was time dependent, however, and markedly diminished with increasing ionic strength, but was largely unaffected between pH 4 and 9.
Correlation between measurements of the luminol-dependent chemiluminescence response and bacterial susceptibility to phagocytosis
Authors: Welch W D
Published: June 2021

The generation of chemiluminescence by phagocytosing leukocytes has been suggested to reflect concomitant microbicidal activity. Correlation between measurements of the chemiluminescence response and susceptibility of bacteria to phagocytosis, however, has not been studied. To examine and compare a range of responses in the two assays, four Escherichia coli serotypes were chosen as test organisms with degrees of susceptibilities to phagocytosis ranging from 0 to 100% bacteria killed. No complete correlation between peak, slope, or curve area integral measurements of the chemiluminescence response and bacterial susceptibility to phagocytosis were found, although a correlation between the two assays could be made after using specific opsonization procedures like the addition of antiserum to selected serotypes. Intrinsic differences present among the bacterial serotypes may be responsible for the observed lack of correlation between the two assays.
Aerosol stability and respiratory infectivity of japanese B encephalitis virus
Authors: Larson E W , Dominik J W , Slone T W
Published: June 2021

Experiments were conducted to examine the aerosol stability and respiratory infectivity of Japanese B encephalitis virus. At 75 degrees F (about 24 degrees C), survival of the virus as aerosol was inversely related to relative humidity. After correction for physical decay, the mean virus half-lives of the virus were 28, 38, and 62 min at relative humiditis of 80, 55, and 30%, respectively. Virus recoveries as aerosol at 4 min aftr dissemination generally exceeded the theoretical limit of 100%, based on the amount disseminated, to suggest that the process of dissemination operated to deagglomerate or release bound virus from the tissue cells in suspension. Swiss-ICR mice and golden Syrian hamsters were highly susceptible to lethal infections after respiratory challenge. Hartley strain guinea pigs and Fisher-Dunning rats, although infected, based on seroconversion observations, survived the infections. Deaths occurred in squirrel monkeys only after exposure to a high aerosol dose of virus (10(6.0) plaque-forming units). Studies of the virus concentration dynamics and histopathological findings in mouse tissues after aerosol challenge supported a hypothesis for direct transport of virus across the foramina of the cribriform plate to the tissues of the central nervous system to produce primary encephalitis.
Experimental otitis media after nasal inoculation of Streptococcus pneumoniae and influenza A virus in chinchillas
Authors: Giebink G S , Berzins I K , Marker S C , Schiffman G
Published: June 2021

Otitis media developed in 67% of chinchillas inoculated intranasally with type 7 Streptococcus pneumoniae and influenza A virus. Only 4% of chinchillas inoculated with influenza alone and 21% of chinchillas inoculated with S. pneumoniae alone developed otitis media. Among the chinchillas that developed otitis media after inoculation with both pneumococcus and influenza, 73% of the affected ears contained effusion, and 27% of the affected ears showed tympanic membrane inflammation without middle ear effusion obtained on paracentesis. Although a majority of the ears with effusion yielded S. pneumoniae on culture, one-third of the effusions were sterile for aerobic bacteria. This model resembles conditions accompanying otitis media in humans and suggests that respiratory viral infection contributes significantly to the pathogenesis of acute otitis media.
Suppression of antibody responses in humans infected with Trypanosoma cruzi
Authors: Cunningham D S , Grogl M , Kuhn R E
Published: June 2021

Peripheral blood leukocytes from patients serologically positive for Chagas' disease were examined for their ability to respond to heterologous antigens in vitro. It was found that mononuclear cells from chagasic patients had greatly reduced ability to respond to sheep erythrocytes (SRBC) as compared with peripheral blood mononuclear cells (PBMC) from control subjects. The reduction in anti-SRBC antibody activity was independent of antigen dose and was not a result of differences in antibody response kinetics. Depletion of plastic-adherent result of differences in antibody response kinetics. Depletion of plastic-adherent cells from the PBMC of patients did not affect the suppressed state of the nonadherent lymphocytes. No relationship was evident between the duration of Trypanosoma cruzi infection and the degree of humoral responsiveness.
Scanning electron microscopy of mycoplasmas adhering to erythrocytes
Authors: Razin S , Banai M , Gamliel H , Polliack A , Bredt W , Kahane I
Published: June 2021

The interaction of Mycoplasma pneumoniae and Mycoplasma gallisepticum with human erythrocytes (RBC) was studied by scanning electron microscopy. The tight nature of the attachment of the microorganisms to the RBC was indicated by the indentation of the RBC surface at the site of attachment of M. gallisepticum cells and by traction and resulting distortion in the shape of the RBC at the point of its attachment to M. pneumoniae filaments growing on glass or plastic. In many cases attachment took place via the tip of the filaments, the membrane of the parasite appearing to be fused with that of the RBC. The morphology of the mycoplasmas growing on cover slips conformed in general with previous descriptions obtained by scanning electron microscopy. Growth of M. pneumoniae on glass or plastic consisted of branching filaments spread on the inert surface and microcolonies made up of intertwining filaments projecting into the medium. The filaments had a bulbous swelling adjacent to a tapered tip end. A few filaments were shown to have a ropelike helical twist. M. gallisepticum grown on the cover slips of Leighton tubes had a peculiar fusiform or teardrop shape with blebs at one or both poles of the cells. Elongated filamentous forms and chains of coccobacillary bodies were observed as well.
Preparation and characterization of rabies virus hemagglutinin
Authors: Cox J H , Dietzschold B , Weiland F , Schneider L G
Published: June 2021

Rabies virus glycoprotein, released by treatment with Triton X-100, was isoelectrically focused in a sucrose gradient containing the nonionic detergent octylglucoside. Removal of the detergent by dialysis resulted in aggregates of variable size and shape. The hemagglutinating activity of this preparation was approximately sixfold higher than that of the intact virus. The protein with hemagglutinating activity and with a buoyant density of 1.237 consisted solely of polypeptide chains of the G-protein and contained 0.38% phospholipids and 16 ng of Triton X-100 per mg of protein. In the National Institutes of Health test the hemagglutinin conferred a significantly higher protective activity than detergent-associated glycoprotein and was as effective as an inactivated virus vaccine. However, after the application of a single dose of hemagglutinin, the onset of protection was delayed by approximately 7 days when compared with inactivated virus vaccine.
Exfoliative toxin plasmids of bacteriophage group 2 Staphylococcus aureus: sequence homology
Authors: Warren R L
Published: June 2021

The plasmid contents of seven exfoliative toxin-producing strains of phage group 2 Staphylococcus aureus were analyzed by agarose gel electrophoresis and deoxyribonucleic acid-deoxyribonucleic acid hybridization. All strains were found to contain a large plasmid with a molecular weight of 27 X 10(6) except for strain RW1005. A comparison of the restriction endonuclease cleavage products by agarose gel electrophoresis showed that the number and size distribution of the fragments of all these Tox plasmids were similar, except for pRW002, which appeared to contain two deletions. Deoxyribonucleic acid-deoxyribonucleic acid hybridization studies confirmed that these plasmids were related to a plasmid which carried the genes for exfoliative toxin B and bacteriocin R1 biosynthesis and that they shared some sequence homology with the penicillinase plasmid pI258 isolated from a phage group 3 S. aureus.
Evidence of species specificity in the cytocidal effects of Pasteurella haemolytica
Authors: Kaehler K L , Markham R J , Muscoplat C C , Johnson D W
Published: June 2021

Pasteurella haemolytica was found to have a cytotoxic effect on the peripheral blood mononuclear leukocytes of cattle, sheep, and goats, but no effect on the mononuclear leukocytes of swine, horses, or humans. In contrast, Escherichia coli caused marked cell death among mononuclear leukocytes of all species tested.
Comparison of In Vitro Lymphocyte Proliferations Induced by Cytomegalovirus-Infected Human Fibroblasts and Cell-Free Cytomegalovirus
Authors: Schirm Jurjen , Roenhorst Herwi W. , The T. Hauw
Published: June 2021

In vitro lymphocyte reactivity (LR) to cytomegalovirus (CMV)-infected human fetal fibroblasts (CMVFF) and cell-free CMV were measured by using lymphocytes from healthy donors. Lymphocytes from all seropositive donors were stimulated by CMVFF, whereas lymphocytes from negative donors were not. The optimal stimulator cell-to-lymphocyte ratio was in the range of 1:5 to 1:50, dependent on the virus dose used. LR to cell-free CMV was positive for 15 out of 18 seropositive donors and negative for 14 out of 16 seronegative donors. In most cases LR to CMVFF was considerably higher than LR to cell-free CMV. Within the CMV seropositive group there was no significant correlation between the LR to either CMVFF or cell-free CMV and the levels of antibodies to CMV early antigens or CMV late antigens. There was no strict correlation between LR to CMVFF and to cell-free CMV, especially not in tests with lymphocytes from two patients with CMV mononucleosis. Our data suggest that CMVFF and cell-free CMV are recognized (partly) by different subpopulations of CMV-specific memory lymphocytes. We conclude that the use of CMV-infected cells, in addition to cell-free CMV, in LR tests gives more reproducible and possibly also additional information about CMV-specific cellular immunity.
Effect of immunoglobulin G on the responsiveness of human neutrophils to soluble staphylococcal protein A-induced neutrophil migration inhibition factor from T-lymphocytes
Authors: Colburn K K , Wong L G , Ashman R F , Wistar R , Weisbart R H
Published: June 2021

Staphylococcal protein A is a bacterial cell wall product that binds human immunoglobulin G and thereby interferes with opsonization and phagocytosis of Staphylococcus aureus by neutrophils. Phagocytic cells are also responsive to various non-immunoglobulin lymphocyte mediators. We utilized the detection of a newly recognized mediator, a neutrophil migration inhibition factor from T-lymphocytes (NIF-T), to show that aggregates of staphylococcal protein A and immunoglobulins G could inhibit the responsiveness of neutrophils to NIF-T. That such aggregates may alter the responsiveness of neutrophils to lymphocyte mediators that amplify or modulate phagocytic functions may have important pathogenetic implications in staphylococcal infection.
Synthesis and biological assays of a peptide from a tuberculin-active protein
Authors: Savrda J
Published: June 2021

The heptapeptide Asn-Gly-Ser-Gln-Met-Arg-Leu, part of a tuberculin-active intracellular mycobacterial protein and described in the literature as having residual tuberculin activity, has been synthesized. Biological assays of the synthetic peptide showed it to be recognized as an antigen of mycobacterial origin by its ability to elicit an early allergic reaction in Mycobacterium bovis BCG-infected mice. The synthetic peptide was shown to be devoid of any tuberculin activity in BCG-infected mice and in skin tests on Mycobacterium tuberculosis-sensitized guinea pigs. Purified protein derivative, complex mixture of proteins of unknown composition which is excreted into the culture medium by M. tuberculosis and is in wide use as a tuberculin-active preparation, was shown to weakly cross-react in radioimmunoassays with the synthetic heptapeptide when 125I-labeled heptapeptide and an anti-heptapeptide antiserum were used.
Resolution of Basic Gonococcal Outer Membrane Proteins by Nonequilibrium pH Gradient Electrophoresis
Authors: Jones Robert B. , Jemison Patricia A. , Newhall Wilbert J. , Haak Richard A.
Published: June 2021

Outer membrane proteins from opaque and transparent colonial variants of strain F62 of
Neisseria gonorrhoeae
were analyzed by two-dimensional electrophoresis with isoelectric focusing in the first dimension and sodium dodecyl sulphate-polyacrylamide gel electrophoresis in the second. Most of the higher-molecular-weight proteins focused sharply in the acidic region of the gel. In contrast, the principal outer membrane protein, a 31,000-molecular-weight protein, and the opacity-associated proteins remained near the origin (at the basic end of the gel) without focusing. However, when the samples were loaded on the acidic end of an isoelectric focusing gel and subjected to nonequilibrium pH gradient electrophoresis, these proteins behaved as basic proteins. In addition, three distinct opacity-associated heat-modifiable proteins could be identified. No other differences in the protein composition of outer membranes from opaque and transparent variants were apparent. Amino acid analysis of the principal outer membrane protein indicated that its net positive charge may result from partial amidation of its acidic residues. The unexpected observation that the major surface proteins of the gonococcus are basic may have implications for intragonococcal adhesion and for gonococcal interactions with mammalian cells.
Resistance and Susceptibility of Mice to Bacterial Infection: Histopathology of Listeriosis in Resistant and Susceptible Strains
Authors: Mandel Thomas E. , Cheers Christina
Published: June 2021

C57BL/10 mice have previously been shown to be 100 times more resistant to intravenously injected
Listeria monocytogenes
than are BALB/c mice due to the action of a single gene,
Lr.
Differences in the histopathology of listeriosis in the two strains were sought. Of the tissues examined, only liver, spleen, blood, and thymus showed changes. In the liver,
Listeria
localized in Kupffer cells within 3 h of infection. By 24 h these cells became surrounded by neutrophilic polymorphonuclear leukocytes. After high doses of
Listeria
, the susceptible BALB/c mice showed many foci surrounded by few polymorphs, whereas in the resistant C57BL/10 mice there were relatively few foci surrounded by many polymorphs. By 4 days in sublethally infected mice the polymorphs in the liver of both strains were being replaced by monocytes and macrophages. Liver morphology returned to normal by 8 days postinfection. In the blood of both strains there was a rise in total lymphocyte numbers at 24 h, followed by a fall in T-lymphocytes and recovery at 5 days. C57BL/10 mice showed an early monocytic response in the blood, whereas BALB/c mice showed a polymorph leukocytosis. In the spleens of both C57BL/10 and BALB/c mice there was an early neutrophil response and red pulp hyperemia. This was followed by a dramatic lymphocyte depletion in the T-dependent periarteriolar regions in both strains beginning 2 days after infection. Absolute numbers of Thy-1
+
cells in spleen cell suspensions also fell to 10% of normal, recovering 6 to 8 days postinfection. Surface immunoglobulin-positive B-lymphocytes and Thy-1
−
, immunoglobulin-negative “null” cells rose in both strains at days 4 to 5, returning to normal levels on days 10 to 12. Whether the null cells represent lymphocytes or other cell types remains unresolved. Thymus atrophy was seen in the BALB/c mice but not in C57BL/10 mice.