Modular synthesis and modification of novel bifunctional dendrons

2019 ◽  
Vol 17 (11) ◽  
pp. 2906-2912
Author(s):  
Ludovico G. Tulli ◽  
Daniela Miranda ◽  
Cameron C. Lee ◽  
Yang Sullivan ◽  
Robert Grotzfeld ◽  
...  

The modular synthesis of two generations of highly branched bifunctional dendrons is reported. The first generation dendron–antibody conjugate is shown to selectively detect CD4+ T cells in the PBMC culture.

2019 ◽  
Author(s):  
Zac Wylde ◽  
Foteini Spagopoulou ◽  
Amy K Hooper ◽  
Alexei A Maklakov ◽  
Russell Bonduriansky

Individuals within populations vary enormously in mortality risk and longevity, but the causes of this variation remain poorly understood. A potentially important and phylogenetically widespread source of such variation is maternal age at breeding, which typically has negative effects on offspring longevity. Here, we show that paternal age can affect offspring longevity as strongly as maternal age does, and that breeding age effects can interact over two generations in both matrilines and patrilines. We manipulated maternal and paternal ages at breeding over two generations in the neriid fly Telostylinus angusticollis. To determine whether breeding age effects can be modulated by the environment, we also manipulated larval diet and male competitive environment in the first generation. We found separate and interactive effects of parental and grandparental ages at breeding on descendants’ mortality rate and lifespan in both matrilines and patrilines. These breeding age effects were not modulated by grandparental larval diet quality or competitive environment. Our findings suggest that variation in maternal and paternal ages at breeding could contribute substantially to intra-population variation in mortality and longevity.


2020 ◽  
Vol 54 (s41) ◽  
pp. 89-115
Author(s):  
Einat Gonen

Abstract This paper presents a diachronic study of Modern Hebrew agreement between numerals and their quantified nouns. This research is possible thanks to the discovery of two rare collections of recordings from the 1950s and 1960s, which document four generations of speakers and have become important sources of spoken Early Modern Hebrew. On the basis of these two corpora, I compare numeral agreement in the first two generations of speakers with present-day usage and analyze trends of change and conversation in Modern Hebrew. The study shows that the first generation of speakers (“Gen1”) largely acquired the gender distinction of cardinals. However, in contrast to other agreement issues that educated Gen1 speakers realized fully, numeral use showed variation and absence of agreement in a small set of cases. Moreover, some linguistic features of Gen1 Hebrew found in this study no longer characterize Present-Day Hebrew; among these features is prosodic conditioning, which led to a Gen1 tendency to use the feminine form of the numeral ‘four’ with masculine nouns more frequently than was the case with other numerals.


1986 ◽  
Vol 118 (4) ◽  
pp. 351-359 ◽  
Author(s):  
M.T. AliNiazee

AbstractSeasonal history, adult flight activity, and damage of the obliquebanded leafroller, Choristoneura rosaceana (Harris), on filbert were studied during a 7-year period between 1976 and 1984. Data from periodic field counts and moth catches in sex-attractant traps indicated two generations per year. The first-generation adult capture peak was generally higher than the second, except in 1978 when about an equal number of moths were trapped from both generations. A physiological time scale, using degree-days (DD), was devised for predicting emergence of obliquebanded leafroller adults. The first adults from overwintering larvae emerged at approximately 374 DD above a threshold of 10 °C starting 1 March. A total of 1172 DD were required between the first and the last adult emergence during the first generation and about 519 DD during the second generation. The obliquebanded leafroller causes both foliar and nut damage in filbert orchards of Oregon. Foliar damage was insignificant, but nut damage, caused exclusively by the first-generation larvae during June and early July, was highly destructive. Larval feeding on nuts caused staining and premature drop of infested nuts resulting in substantial yield reduction in heavily infested orchards.


2013 ◽  
Vol 47 (1) ◽  
pp. 438 ◽  
Author(s):  
I. Thabet ◽  
A. Kilias ◽  
A. Koroneos ◽  
S. Kamh

The study deals with the petrography of the granitoid rocks intruding the five (A to E) domes of Hafafit Culmination. The morphological characteristics of zircon crystals are also examined, in order to elucidate the genesis of zircon and their host Hafafit granitoids. The granitoid rocks are tonalites, granodiorites and quartz diorites, all exhibiting gneissic texture. The zircon crystals from all the rock types intruding each one of the domes are examined in detail for colour, inclusions, crystal length, crystal width, elongation ratio, crystal form and habit, degree of roundness and corrosion, and are distinguished in groups on the basis of the previous characteristics. Two generations of zircons have been recognized; the first generation with magmatic features and the second one with post magmatic features. The first generation of zircon is attributed to the subduction, magmatic and deformation events while the second generation of zircon is attributed to metamorphism.


2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A884-A884
Author(s):  
Li Peng ◽  
Lizhi Cao ◽  
Sujata Nerle ◽  
Robert LeBlanc ◽  
Abhishek Das ◽  
...  

BackgroundSialoglycans, a type of glycans with a terminal sialic acid, have emerged as a critical glyco-immune checkpoint that impairs antitumor response by inhibiting innate and adaptive immunity. Upregulation of sialoglycans on tumors has been observed for decades and correlates with poor clinical outcomes across many tumor types. We previously showed that targeted desialylation of tumors using a bifunctional sialidase x antibody molecule, consisting of sialidase and a tumor-associated antigen (TAA)-targeting antibody, has led to robust single-agent efficacy in mouse tumor models. In addition to tumor cells, most immune cells present substantially more abundant sialoglycans than non-hematological healthy cells, which may also contribute to immunosuppression. Therefore, we studied the impact of immune cell desialylation and evaluated the therapeutic potential of a newly developed sialidase-Fc fusion (Bi-Sialidase), which lacks a TAA-targeting moiety and consists of engineered human neuraminidase 2 (Neu2) and human IgG1 Fc region, in preclinical mouse tumor models.MethodsThe first generation Neu2 variant was further optimized to improve titers and stability to constructed Bi-Sialidase. Bi-Sialidase’s desialylation potency and impact on immune responses were studied in vitro using various human immune functional assays, including T-cell activation, allogeneic mixed lymphocyte reaction, antibody-dependent cellular cytotoxicity, macrophages polarization/activation, neutrophil activation, and peripheral blood mononuclear cell (PBMC) cytokine release assays. We evaluated its antitumor efficacy in mouse tumor models. Bi-Sialidase’s safety profile was characterized by conducting rat and non-human primate (NHP) toxicology studies.ResultsThe optimized Bi-Sialidase achieved a titer of 2.5 g/L from a 15-day fed-batch Chinese hamster ovary cell culture; in contrast, the wild-type and first-generation Neu2 had no production or a low titer (<0.1 g/L) under similar conditions, respectively. We demonstrated that Bi-Sialidase led to dose-dependent desialylation of immune cells and potentiated T-cell immunity, without impacting NK, macrophage, or neutrophil activation by desialylating immune cells. Activated and exhausted T cells upregulated surface sialoglycans and Bi-Sialidase-mediated desialylation reinvigorated exhausted-like T cells as measured by IFNg production. Bi-Sialidase treatment also enhanced DC priming and activation of naïve T cells by desialylating both T cells and DCs. Furthermore, Bi-Sialidase showed single-agent antitumor activity in multiple mouse tumor models, including MC38, CT26, A20, and B16F10. Importantly, Bi-Sialidase did not cause cytokine release in human PBMC assays and was tolerated to up to 100 mg/kg in rats and NHPs, demonstrating a wide safety margin.ConclusionsBi-Sialidase with an optimized Neu2 offers a novel immunomodulatory approach to enhancing T-cell immunity by desialylating immunosuppressive sialoglycans for cancer treatment.


2021 ◽  
Vol 29 ◽  
pp. 41-46
Author(s):  
V. A. Katsan ◽  
A.I. Potopalsky ◽  
B.O. Zadorozhnii

Aim. The investigation of the influence of the constituents of Izatison, DMSO and PEG400, on the oat growth and its grain productivity during 2 generations after the seed treatment became the aim of this study for the elucidation of mechanism of Izatison stimulant influence. Methods. The broad scale of the concentrations of the solvents composition in the proportion, to be as in Izatison, was used. The plants were grown in the field. The growth processes were evaluated by the stem height on the tubing stage. The grain productivity was characterized by the panicle length, the grains number in the panicle and of theirs weight. Results. The dependence of influence of the solvents composition on the stem growth from its concentration was detected in the first generation. In some variants the negative influence was revealed on the grains number in the panicle and on theirs weight. The stimulation of the growth regardless from the solvents concentration was observed in the second generation and the more pronounced negative effect on the grain productivity. Conclusions. The solvents DMSO and PEG400 are able to influence on the oat growth and its productivity, and that effect was manifested also in 2 generation after the seed treatment. Keywords: Izatison, DMSO, PEG400, oat growth and grain productivity.


2017 ◽  
Vol 9 (4) ◽  
pp. 1994-2003
Author(s):  
Hemant Sharma ◽  
Maha Singh Jaglan ◽  
S. S. Yadav

Biology of pink stem borer, Sesamia inferens (Walker) (Lepidoptera: Noctuidae) was conducted during 2015-16 in laboratories of CCS Haryana Agricultural University, Regional Research Station, Karnal on HQPM 1 (hybrid) and HKI 1128 (inbred) for two generations at room temperature. Results on biology of S. inferens in the first generation revealed that incubation period varied from 10-14 days on HQPM 1 and 11-15 days on HKI 1128. The larval duration lasted for 21-37 days on HQPM 1 and 24-39 days on HKI 1128. The adult longevity of male and female ranged from 6-7 days and 7-8 days on HQPM 1 and 5-7 days and 6-7 days on HKI 1128, respectively. The total life span ranged from 63-72 days for female and 45-58 days for male on HQPM 1 and 65-74 days for female and 49-62 days for male on HKI 1128, respectively in the first generation. The total life span in second generation ranged 94-107 days for female and 83-96 days for male on HQPM 1 and 98-112 days for female and 86-101 days for male on HKI 1128. The biology of an insect pest is a condition precedent to find out its management strategies. The biology of S. inferens on maize has not yet been studied in north western part of the country. Having regards to the fact that no systematic work on this aspect has been carried out, studies were conducted on biology of this pest for developing efficient pest management strategies.


2012 ◽  
Vol 23 (2) ◽  
pp. 65-76
Author(s):  
Willi Goetschel

This paper examines Rosenzweig?s philosophic project in the context of his time as a critical intervention in the discussion of the place of Jewish thought in the university and in society. If Hermann Cohen represented the first generation of Jewish philosophers claiming that participation in the university is constitutive for the institution?s claim to universalism, the second generation-represented by Martin Buber - was more diffident about the university and its openness. For Buber, literary modernism offered what the university would refuse. Disappointed about the failure of the recognition of the efforts of the previous two generations, Rosenzweig represents the third generation. He turns the situation into a creative response anchoring philosophy as a project that calls for a resolute move outside the university.


2021 ◽  
Author(s):  
Emily Rachel Awad

Rising levels of polybrominated diphenyl ethers (PBDEs) have been ovserved in the environment, humans, and animlas. Studies have shown that these compounds can elicit toxic effects in animals (e.g. neurotoxicity and thyroid toxicity). This research investigated the effects of BDE47 on the survival and reproduction of Daphnia magna over two generations. The impacts of water-borne exposure were compared to dietary exposure using the following treatments: dosed water (DW), dosed algae (DA) and dosed water and algae (DWA). In the first generation, significant impacts on reproduction were observed in daphnids in the DA and DWA treatments. In the second generation, no significant impacts on reproduction were observed indicating a recovery from maternal exposure. When second generation daphnids were exposed to BDE47, there was high mortality in the DWA treatment anad reduced reproduction in all dosed treatments. Dietary exposure to BDE47 had a more profound impact on daphnid reproduction than water exposure. In the second generation, dietary exposure affected both survival and reproduction and water exposure reduced reproduction, indicating that maternal exposure was a factor.


2021 ◽  
Vol 59 (6) ◽  
pp. 1693-1709
Author(s):  
Andrei Y. Barkov ◽  
Andrey A. Nikiforov ◽  
Vladimir N. Korolyuk ◽  
Larisa P. Barkova ◽  
Robert F. Martin

ABSTRACT The maximum value of Mg# [= 100Mg/(Mg + Fe2+ + Mn)] in chromium-bearing spinel-group minerals (Chr) in the Ultrabasic Core Zone (UCZ) of the Lyavaraka orthopyroxenite – harzburgite – dunite complex of the Serpentinite Belt in the Kola Peninsula is 54.5–67.5. Such highly magnesian compositions of spinel are associated with notable enrichments of ferric iron (Fe3+# 58–63). There are two generations of accessory Chr in the UCZ unit. The first generation occurs as inclusions in olivine that is not unusually magnesian (Mg# 90.3), and the second is closely associated with serpentine. The compositional series of Chr at Lyavaraka attains more aluminous compositions than was observed in nearby intrusive bodies. The anomalously high level of Mg in Chr, also manifest in ilmenite, is mainly a result of the high intrinsic fugacity of oxygen attained locally in the melt. A progressive buildup in H2O and increase in fO2 likely resulted from efficient vesiculation and selective loss of H2 from the Al-undepleted komatiitic magma crystallizing in a shallow setting. The chromian spinel forming in such a modified magma is virtually unzoned in Mn, and a minor quantity of Mn is also present in olivine and orthopyroxene. In contrast, zinc is strongly partitioned in the core of Chr, as it is relatively incompatible in the coexisting olivine and orthopyroxene at that stage. Zinc efficiently partitioned into the H2O-enriched melt, which crystallized as the pegmatitic orthopyroxenite near the contacts at Lyavaraka. A high potential of oxidation appears to be characteristic of all orthopyroxenite – harzburgite – dunite suites of the Serpentinite Belt formed from a primitive melt of komatiitic composition.


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