16 research outputs found
Immigrants’ housing in the housing market in Russia: from the results of sociological questionnaire
No full textThe study is based on the results of an original sociological survey conducted in 25 cities of Russia from June 2017 to March 2018 by the author. This paper focuses especially on labour immigrants from Central Asia, Ukraine, Belarus and Caucasus regions into Russia. This paper argues the following points; first, the correlation between the demographic movements and regional rental housing fee in Russia, second, the multi-layered structure and its informality of Russian housing market, finally, the relation between labour migrants’ housing condition and labour productivity. In the conclusion, the author points that the Russian housing market is segregated from this research results. Migrant’s housing deals are possibly the origin or bottom of the housing market. Their activity would move the regional housing rental market. However, some of their deals also seem to be invisible in the official housing statistics, that is to say, taking place in the informal housing market. This regards as one of characters, which Russian rental housing market has. It would be hurdle for foreign direct investor, which would invest into Russian market. In addition, the quality of immigrants’ housing condition is too low to support their labour productivity sustainably. We need to consider the improvement even for labour immigrants and the creation of more open housing market in Russia
Shin-gi-tai as a guiding principle in Kōdōkan jūdō : yet, another example of historical reinvention?
No full textJudo national governing bodies in recent years through slogans, posters, cartoons, and web site information have attempted to reignite their members’ appreciation for a judo morality constructed on Japanese bushido. Similarly, several judo federations actively promote ‘shin-gi-tai’ (mind-technique-body) as a guiding principle for rank promotions and conduct allegedly in association with Kano Jigoro’s philosophy. Using translation, critical and heuristic analysis of relevant original historical Japanese sources, it is the purpose of this paper to investigate the origin, etymology and justification of shin-gi-tai as a pre-existing principle in Kodokan judo. Our results show that shin-gi-tai was first used in judo by Michigami Haku while teaching in Shanghai in the 1940s. After his arrival in France in 1953, the concept was introduced and distributed within the Western judo world. However, Michigami was not the original author. It was on the island of Kyushu, from where Michigami hailed, that the term shin-gi-tai appears to have been first used in the Heiho shingitai oboegaki (Memorandum on military arts and mind-technique-body), a text authored by Toyoda Masanaga, an 18th century Niten ichi-ryu heiho swordsman influenced by Miyamoto Musashi. A similar term, shinkitai, later entered sumo through the Yoshida family, also active in Kyushu, who became responsible for the administration of sumo in the late Meiji period. Michigami as a young man had practiced both kendo and sumo. There is no link between Kano Jigoro and shin-gi-tai. While it is acceptable to use shin-gi-tai or any other legitimate meme in coaching athletes, asserting that it represents a fundamental principle that guides rank promotions and ethics in judo is nothing but historical reinvention that lacks any basis.Los órganos nacionales rectores del judo han intentado en los últimos años, a través de eslóganes, carteles, dibujos animados e informaciones en páginas web, reavivar entre sus miembros el aprecio por la moral judo, construida sobre el bushido japonés. Asimismo, algunas federaciones de judo promueven de forma activa el “shin-gi-tai” (mente-técnica-cuerpo) como principio guía para los ascensos de grado y la conducta del practicante, supuestamente en asociación con la filosofía de Kano Jigoro. Utilizando la traducción, el análisis crítico y heurístico de fuentes japonesas históricas, originales y relevantes, este trabajo tiene el propósito de investigar el origen, la etimología y la justificación del shin-gi-tai como principio preexistente en el judo Kodokan. Los resultados muestran que el shin-gi-tai fue utilizado por primera vez en el judo por Michigami Haku mientras enseñaba en Shanghái en la década de 1940. Tras su llegada a Francia en 1953, el concepto fue introducido y difundido en el judo occidental. Sin embargo, Michigami no fue el autor original. Fue en la isla de Kyushu, de donde procedía Michigami, donde el término shin-gi-tai parece haber sido utilizado por primera vez en el Heiho shingitai oboegaki (Memorándum sobre las artes militares y la mente-técnica-cuerpo), un texto cuyo autor fue Toyoda Masanaga, un espadachín heiho de la Niten ichi-ryu del siglo XVIII influenciado por Miyamoto Musashi. Un término similar, shinkitai, entró más tarde en el sumo a través de la familia Yoshida, también activa en Kyushu, que se hizo responsable de la administración del sumo a finales del periodo Meiji. Michigami, de joven, había practicado tanto el kendo como el sumo. No existe ningún vínculo entre Kano Jigoro y el shin-gi-tai. Si bien es aceptable usar el término o cualquier otro meme legítimo en el entrenamiento de atletas, afirmar que representa un principio fundamental que guía los ascensos de rango y la ética en el judo no es más que una reinvención histórica que carece de toda base.Os órgãos governamentais nacionais de judo nos últimos anos, por meio de slogans, pôsteres, desenhos animados e informações de sites, tentaram reacender a apreciação de seus membros por uma moralidade judo construída no bushido japonês. Do mesmo modo, várias federações de judo promovem ativamente o “shin-gi-tai” (mente-técnica-corpo) como princípio orientador das promoções de categoria e da conduta, alegadamente em associação com a filosofia de Kano Jigoro. Utilizando a tradução, a análise crítica e heurística de fontes históricas japonesas originais relevantes, o objetivo deste artigo é investigar a origem, a etimologia e a justificação do shin-gi-tai como um princípio pré-existente em Kodokan judo. Os nossos resultados mostram que o shin-gi-tai foi usado pela primeira vez no judo por Michigami Haku enquanto ensinava em Xangai na década de 1940. Após a sua chegada a França em 1953, o conceito foi introduzido e distribuído no judo ocidental. No entanto, Michigami não foi o autor original. Foi na ilha de Kyushu, de onde Michigami era originário, que o termo shin-gi-tai parece ter sido usado pela primeira vez no Heiho shingitai oboegaki (Memorando sobre artes militares e mente-técnica-corpo), um texto da autoria de Toyoda Masanaga, um espadachim heiho de Niten ichi-ryu do século XVIII influenciado por Miyamoto Musashi. Um termo semelhante, shinkitai, entrou mais tarde no sumo através da família Yoshida, também ativa em Kyushu, que se tornou responsável pela administração do sumo no final do período Meiji. Michigami, quando jovem, praticou tanto kendo quanto sumo. Não existe qualquer ligação entre o Kano Jigoro e o shin-gi-tai. Embora seja aceitável utilizar o shin-gi-tai ou qualquer outro meme legítimo no treino de atletas, afirmar que representa um princípio fundamental que orienta as promoções de categoria e a ética no judo não passa de uma reinvenção histórica sem qualquer fundamento.Judo national governing bodies in recent years through slogans, posters, cartoons, and web site information have attempted to reignite their members’ appreciation for a judo morality constructed on Japanese bushido. Similarly, several judo federations actively promote ‘shin-gi-tai’ (mind-technique-body) as a guiding principle for rank promotions and conduct allegedly in association with Kano Jigoro’s philosophy. Using translation, critical and heuristic analysis of relevant original historical Japanese sources, it is the purpose of this paper to investigate the origin, etymology and justification of shin-gi-tai as a pre-existing principle in Kodokan judo. Our results show that shin-gi-tai was first used in judo by Michigami Haku while teaching in Shanghai in the 1940s. After his arrival in France in 1953, the concept was introduced and distributed within the Western judo world. However, Michigami was not the original author. It was on the island of Kyushu, from where Michigami hailed, that the term shin-gi-tai appears to have been first used in the Heiho shingitai oboegaki (Memorandum on military arts and mind-technique-body), a text authored by Toyoda Masanaga, an 18th century Niten ichi-ryu heiho swordsman influenced by Miyamoto Musashi. A similar term, shinkitai, later entered sumo through the Yoshida family, also active in Kyushu, who became responsible for the administration of sumo in the late Meiji period. Michigami as a young man had practiced both kendo and sumo. There is no link between Kano Jigoro and shin-gi-tai. While it is acceptable to use shin-gi-tai or any other legitimate meme in coaching athletes, asserting that it represents a fundamental principle that guides rank promotions and ethics in judo is nothing but historical reinvention that lacks any basis.Los órganos nacionales rectores del judo han intentado en los últimos años, a través de eslóganes, carteles, dibujos animados e informaciones en páginas web, reavivar entre sus miembros el aprecio por la moral judo, construida sobre el bushido japonés. Asimismo, algunas federaciones de judo promueven de forma activa el “shin-gi-tai” (mente-técnica-cuerpo) como principio guía para los ascensos de grado y la conducta del practicante, supuestamente en asociación con la filosofía de Kano Jigoro. Utilizando la traducción, el análisis crítico y heurístico de fuentes japonesas históricas, originales y relevantes, este trabajo tiene el propósito de investigar el origen, la etimología y la justificación del shin-gi-tai como principio preexistente en el judo Kodokan. Los resultados muestran que el shin-gi-tai fue utilizado por primera vez en el judo por Michigami Haku mientras enseñaba en Shanghái en la década de 1940. Tras su llegada a Francia en 1953, el concepto fue introducido y difundido en el judo occidental. Sin embargo, Michigami no fue el autor original. Fue en la isla de Kyushu, de donde procedía Michigami, donde el término shin-gi-tai parece haber sido utilizado por primera vez en el Heiho shingitai oboegaki (Memorándum sobre las artes militares y la mente-técnica-cuerpo), un texto cuyo autor fue Toyoda Masanaga, un espadachín heiho de la Niten ichi-ryu del siglo XVIII influenciado por Miyamoto Musashi. Un término similar, shinkitai, entró más tarde en el sumo a través de la familia Yoshida, también activa en Kyushu, que se hizo responsable de la administración del sumo a finales del periodo Meiji. Michigami, de joven, había practicado tanto el kendo como el sumo. No existe ningún vínculo entre Kano Jigoro y el shin-gi-tai. Si bien es aceptable usar el término o cualquier otro meme legítimo en el entrenamiento de atletas, afirmar que representa un principio fundamental que guía los ascensos de rango y la ética en el judo no es más que una reinvención histórica que carece de toda base.Os órgãos governamentais nacionais de judo nos últimos anos, por meio de slogans, pôsteres, desenhos animados e informações de sites, tentaram reacender a apreciação de seus membros por uma moralidade judo construída no bushido japonês. Do mesmo modo, várias federações de judo promovem ativamente o “shin-gi-tai” (mente-técnica-corpo) como princípio orientador das promoções de categoria e da conduta, alegadamente em associação com a filosofia de Kano Jigoro. Utilizando a tradução, a análise crítica e heurística de fontes históricas japonesas originais relevantes, o objetivo deste artigo é investigar a origem, a etimologia e a justificação do shin-gi-tai como um princípio pré-existente em Kodokan judo. Os nossos resultados mostram que o shin-gi-tai foi usado pela primeira vez no judo por Michigami Haku enquanto ensinava em Xangai na década de 1940. Após a sua chegada a França em 1953, o conceito foi introduzido e distribuído no judo ocidental. No entanto, Michigami não foi o autor original. Foi na ilha de Kyushu, de onde Michigami era originário, que o termo shin-gi-tai parece ter sido usado pela primeira vez no Heiho shingitai oboegaki (Memorando sobre artes militares e mente-técnica-corpo), um texto da autoria de Toyoda Masanaga, um espadachim heiho de Niten ichi-ryu do século XVIII influenciado por Miyamoto Musashi. Um termo semelhante, shinkitai, entrou mais tarde no sumo através da família Yoshida, também ativa em Kyushu, que se tornou responsável pela administração do sumo no final do período Meiji. Michigami, quando jovem, praticou tanto kendo quanto sumo. Não existe qualquer ligação entre o Kano Jigoro e o shin-gi-tai. Embora seja aceitável utilizar o shin-gi-tai ou qualquer outro meme legítimo no treino de atletas, afirmar que representa um princípio fundamental que orienta as promoções de categoria e a ética no judo não passa de uma reinvenção histórica sem qualquer fundamento.A
T Cell-Association of Carboxy-Terminal Dendrimers with Different Bound Numbers of Phenylalanine and Their Application to Drug Delivery
No full textT cells play important roles in various immune reactions, and their activation is necessary for cancer immunotherapy. Previously, we showed that polyamidoamine (PAMAM) dendrimers modified with 1,2-cyclohexanedicarboxylic acid (CHex) and phenylalanine (Phe) underwent effective uptake by various immune cells, including T cells and their subsets. In this study, we synthesized various carboxy-terminal dendrimers modified with different bound numbers of Phe and investigated the association of these dendrimers with T cells to evaluate the influence of terminal Phe density. Carboxy-terminal dendrimers conjugating Phe at more than half of the termini exhibited a higher association with T cells and other immune cells. The carboxy-terminal Phe-modified dendrimers at 75% Phe density tended to exhibit the highest association with T cells and other immune cells, which was related to their association with liposomes. A model drug, protoporphyrin IX (PpIX), was encapsulated into carboxy-terminal Phe-modified dendrimers, which were then used for drug delivery into T cells. Our results suggest the carboxy-terminal Phe-modified dendrimers are useful for delivery into T cells
A "ligand-targeting" peptide-drug conjugate: Targeted intracellular drug delivery by VEGF-binding helix-loop-helix peptides via receptor-mediated endocytosis.
No full textAs a new alternative to antibody-drug conjugates, we generated "ligand-targeting" peptide-drug conjugates (PDCs), which utilize receptor-mediated endocytosis for targeted intracellular drug delivery. The PDC makes a complex with an extracellular ligand and then binds to the receptor on the cell surface to stimulate intracellular uptake via the endocytic pathway. A helix-loop-helix (HLH) peptide was designed as the drug carrier and randomized to give a conformationally constrained peptide library. The phage-displayed library was screened against vascular endothelial growth factor (VEGF) to yield the binding peptide M49, which exhibited strong binding affinity (KD = 0.87 nM). The confocal fluorescence microscopy revealed that peptide M49 formed a ternary complex with VEGF and its receptor, which was then internalized into human umbilical vein endothelial cells (HUVECs) via VEGF receptor-mediated endocytosis. The backbone-cyclized peptide M49K was conjugated with a drug, monomethyl auristatin E, to afford a PDC, which inhibited VEGF-induced HUVEC proliferation. HLH peptides and their PDCs have great potential as a new modality for targeted molecular therapy
Novel mutation in the ALPL gene with a dominant negative effect in a Japanese family
No full textIntroduction Hypophosphatasia (HPP) is caused by mutations in the ALPL gene encoding tissue nonspecific alkaline phosphatase (TNSALP) and inherited in either an autosomal recessive or autosomal dominant manner. It is characterized clinically by defective mineralization of bone, dental problems, and low serum ALP levels. In the current report, we demonstrate a novel mutation in the ALPL gene (c.244G > A p.Gly82Arg) in a Japanese family with low serum ALP levels. Materials and methods The ALPL gene analysis using hybridization capture-based next-generation sequencing was performed. The expression plasmids of the wild type and mutated TNSALP were introduced into COS-7 cells. The enzymatic activity of ALP in the cell lysates was measured using p-nitrophenylphosphate as a substrate. Results TNSALP with the novel ALPL mutation (c.244G > A p.Gly82Arg) completely lost its enzymatic activity and suppressed that of wild-type TNSALP, corroborating its dominant negative effect. The diagnosis of autosomal dominant HPP was confirmed in three members of the family. Conclusion Our approach would help to avoid the inappropriate use of bone resorption inhibitors for currently mis- or under-diagnosed HPP, given that the presence of further, yet undetected mutations of the ALPL gene are plausible
New Class of Drug Modalities: Directed Evolution of a De Novo Designed Helix–Loop–Helix Peptide to Bind VEGF for Tumor Growth Inhibition
No full textACS Chemical Biology. 2022, 17 (3), P.647-65
Effects of drug discontinuation after short-term daily alendronate administration on osteoblasts and osteocytes in mice
No full textIn order to determine whether osteoclastic bone resorption is restarted after withdrawn of bisphosphonates, we conducted histological examinations on murine osteoclasts, osteoblasts and osteocytes after discontinuation of a daily regimen of alendronate (ALN) with a dosage of 1 mg/kg/day for 10 days. After drug discontinuation, metaphyseal trabecular number and bone volume remained unaltered for the first 4 days. Osteoclast number did not increase, while the number of apoptotic osteoclasts was elevated. On the other hand, tissue non-specific alkaline phosphatase-immunoreactive area was markedly reduced after ALN discontinuation. In addition, osteocytes showed an atrophic profile with empty lacunar areas during and after ALN treatment. Interestingly, as early as 36 h after a single ALN injection, osteocytes show signs of atrophy despite the presence of active osteoblasts. Structured illumination microscopy system showed shortening of osteocytic cytoplasmic processes after drug cessation, suggesting a possible morphological and functional disconnection between osteocytes and osteoblasts. Taken together, it appears that osteoclastic bone resorption is not resumed after ALN discontinuation; also, osteoblasts and osteocytes hardly seem to recover once they are inactivated and atrophied by ALN. In summary, it seems that one must pay more attention to the responses of osteoblasts and osteocytes, rather focusing on the resuming of osteoclastic bone resorption after the ALN discontinuation
An Immune-Stimulatory Helix–Loop–Helix Peptide: Selective Inhibition of CTLA-4–B7 Interaction
No full textMolecular-targeting
peptides and mini-proteins are promising alternatives
to antibodies in a wide range of applications in bioscience and medicine.
We have developed a helix–loop–helix (HLH) peptide as
an alternative to antibodies to inhibit specific protein interactions.
Cytotoxic T lymphocyte antigen-4 (CTLA-4) downregulates immune responses
of cytotoxic T-cells by interaction with B7-1, a co-stimulatory molecule
expressed on antigen presenting cells (APCs). To induce immune stimulatory
activity, we used directed evolution methods to generate a HLH peptide
that binds to CTLA-4, inhibiting the CTLA-4–B7-1 interaction
and inducing immune stimulatory activity. Yeast-displayed libraries
of HLH peptides were constructed and screened against CTLA-4 and identified
the binding peptide Y-2, which exhibits a moderate affinity. The affinity
of Y-2 was improved by in vitro affinity maturation
to afford a stronger binder, ERY2-4. Peptide ERY2-4 specifically bound
to CTLA-4 with a KD of 196.8 ± 2.3
nM, comparable to the affinity of the CTLA-4–B7-1 interaction.
Furthermore, ERY2-4 inhibited the CTLA-4–B7-1 interaction with
an IC50 of 1.1 ± 0.03 μM and blocked the interaction
between CTLA-4 and dendritic cells (DCs) presenting B7 on their surface.
Importantly, ERY2-4 showed no cross-reactivity against CD28, suggesting
it does not suppress T-cell activation. Finally, in a mixed lymphocyte
reaction assay with DCs and T cells, ERY2-4 enhanced an allogeneic
lymphocyte response. Since CTLA-4 is a critical immune checkpoint
for restricting the cancer immune response, this inhibitory HLH peptide
represents a new class of drug candidates for immunotherapy
“Human and Mouse Cross-Reactive” Albumin-Binding Helix–Loop–Helix Peptide Tag for Prolonged Bioactivity of Therapeutic Proteins
No full textThe effectiveness
of protein and peptide pharmaceuticals depends
essentially on their intrinsic pharmacokinetics. Small-sized pharmaceuticals
in particular often suffer from short serum half-lives due to rapid
renal clearance. To improve the pharmacokinetics by association with
serum albumin (SA) in vivo, we generated an SA-binding
tag of a helix–loop–helix (HLH) peptide to be linked
with protein pharmaceuticals. For use in future preclinical studies,
screening of yeast-displayed HLH peptide libraries against human SA
(HSA) and mouse SA (MSA) was alternately repeated to give the SA-binding
peptide AY-VE, which exhibited cross-binding activities to HSA and
MSA with KD of 65 and 20 nM, respectively.
As a proof of concept, we site-specifically conjugated peptide AY-VE
with insulin to examine its bioactivity in vivo.
In mouse bioassay monitoring the blood glucose level, the AY-VE conjugate
was found to have a prolonged hypoglycemic effect for 12 h. The HLH
peptide tag is a general platform for extending the bioactivity of
therapeutic peptides or proteins
Generation of molecular-targeting helix-loop-helix peptides for inhibition of the interaction between cytotoxic T-lymphocyte-associated protein 4 and B7 in the dog
No full textJournal of Veterinary Medical Science. 2022, 84 (8), P.1101-110
