Course Of Circulation Research Articles

Targeting redox regulation and autophagy systems in cancer stem cells.

Cancer is a dysregulated cellular level pathological condition that results in tumor formation followed by metastasis. In the heterogeneous tumor architecture, cancer stem cells (CSCs) are essential to push forward the progression of tumors due to their strong pro-tumor properties such as stemness, self-renewal, plasticity, metastasis, and being poorly responsive to radiotherapy and chemotherapeutic agents. Cancer stem cells have the ability to withstand various stress pressures by modulating transcriptional and translational mechanisms, and adaptable metabolic changes. Owing to CSCs heterogeneity and plasticity, these cells display varied metabolic and redox profiles across different types of cancers. It has been established that there is a disparity in the levels of Reactive Oxygen Species (ROS) generated in CSCs vs Non-CSC and these differential levels are detected across different tumors. CSCs have unique metabolic demands and are known to change plasticity during metastasis by passing through the interchangeable epithelial and mesenchymal-like phenotypes. During the metastatic process, tumor cells undergo epithelial to mesenchymal transition (EMT) thus attaining invasive properties while leaving the primary tumor site, similarly during the course of circulation and extravasation at a distant organ, these cells regain their epithelial characteristics through Mesenchymal to Epithelial Transition (MET) to initiate micrometastasis. It has been evidenced that levels of Reactive Oxygen Species (ROS) and associated metabolic activities vary between the epithelial and mesenchymal states of CSCs. Similarly, the levels of oxidative and metabolic states were observed to get altered in CSCs post-drug treatments. As oxidative and metabolic changes guide the onset of autophagy in cells, its role in self-renewal, quiescence, proliferation and response to drug treatment is well established. This review will highlight the molecular mechanisms useful for expanding therapeutic strategies based on modulating redox regulation and autophagy activation to targets. Specifically, we will account for the mounting data that focus on the role of ROS generated by different metabolic pathways and autophagy regulation in eradicating stem-like cells hereafter referred to as cancer stem cells (CSCs).

Assessment of the Wear Resistance for Gearwheel Teeth in an Open Toothed Gear under the Conditions of a High Level of Dust

This paper presents a method for assessing wear resistance for open toothed gears that operate under the conditions of a high level of dust. The size of abrasive particles that occur in the air in a freely suspended state and adhere to the surface of toothed gears in the course of circulation has been determined. The wear rate of a gearwheel tooth is assessed taking the dust level and the size of abrasive particles; the geometrical, kinematic, and dynamic parameters that are characteristic of toothed gears; and the mechanical properties of gearwheel materials into account.

Injectable and Quadruple-Functional Hydrogel as an Alternative to Intravenous Delivery for Enhanced Tumor Targeting.

Intravenous (IV) route is the most commonly used drug-delivery approach. However, the targeting efficiency to tumor through IV delivery is usually less than 10%. To address this limitation, we report a new systemic delivery method utilizing injectable and quadruple-functional hydrogels to improve targeting efficiency through passive, active, and magnetic targeting, and hydrogel-controlled sustained release. The hydrogels consist of a folate/polyethylenimine-conjugated poly(organophosphazene) polymer, which encapsulates small interfering RNA (siRNA) and Au-Fe3O4 nanoparticles to form a nanocapsule (NC) structure by a simple mixing. The hydrogels are localized as a long-term "drug-release depot" after a single subcutaneous injection and sol-gel phase transition. NCs released from the hydrogels enter the circulatory systems and then target the tumor through enhanced permeability and retention/folate/magnetism triple-targeting, over the course of circulation, itself prolonged by the controlled release. In vivo experiments show that 12% of NCs are successfully delivered to the tumor, which is a considerable improvement compared to most results through IV delivery. The sustained targeting of gold to tumor enables two cycles of photothermal therapy, resulting in an enhanced silencing effect of siRNA and considerable reduction of tumor volume, which we are unable to achieve via simple intravenous injection.

Surplus Value Production and Realization in Marxian Theory – Applications to the U.S., 1990–2015

ABSTRACTMarx's Capital shows that surplus value can be produced in one industry, yet realized as profit (and possibly revenue) by other industries over the course of circulation. This paper highlights the separation between surplus value production and realization in Marx's work, and develops a new method for estimating surplus value production at the industry level to trace out transfers of surplus value across industries. The framework is based on the ‘New Interpretation’ and links money value added to surplus value production at the industry level. Data on value added by industry for the U.S. are used to estimate surplus value production by industry. The analysis allows comparison of surplus value production and realization in each industry. The pattern of differentials between surplus value creation and realization across industries sheds light on the processes of capitalist competition and points to a source of instability for capitalist economies.

Interdisciplinary connection between criminal law and pharmaceutical law in the course of circulation of narcotic substances for pharmaceutical provision of privileged categories of affected oncological patients.

Problem setting. Forensic and pharmaceutical researches indicate that «... in the structure of narcosis, the spectrum of chemical and pharmaceutical substances abused by drug addicts and criminals, has a clear-cut dynamics of constant recovery ...», which affects criminal and legal, medical and pharmaceutical, social and economic aspects related to life quality and expectancy of an individual and a patient. Therefore, the state policy aimed at protecting the rights and freedoms, life and health of patients and citizens ofUkraine.Recent research and publications analysis. V. Tatsiy notes that today in Ukraine there are not only numerous violations of human rights (guaranteed by the Universal Declaration of Human Rights, 1948), but also the lack of an effective mechanism for their renewal among state authorities and self-government, prosecutors, courts, law enforcement agencies, healthcare facilities and pharmacies. According to A. Hetman, V. Tatsiy, M. Panov, V. Golina, M. Shepitko and V. Timoschenko, the establishment of a systematic approach in interdisciplinary researches of the science of criminal law should be constantly the subject of both critical analysis and adjacent analysis (through the processes of their convergence, integration and harmonization) along with pharmaceutical law, criminalistics, criminology, forensic medicine, forensic pharmacy and forensic psychiatry. This is especially important during the implementation of the drug policy ofUkraine in counteracting of organized drug crimes, illegal circulation of narcotic substances to ensure the right of patients with malignant neoplasms to access to vital medicines in the system of preferential (free) provision with medicines of various classification and legal groups.Paper objective was to establish a multidisciplinary connection between criminal law and pharmaceutical law during in the course of circulation of narcotic substances for pharmaceutical provision of preferential categories of cancer patients affected by emergencies.Paper main body. Conducted a review of scientific literature on the study of the interdisciplinary connection of criminal law and pharmaceutical law in the course of the activity related to the circulation of narcotic substances for the pharmaceutical provision of preferential categories of cancer patients, affected by emergencies. Analyzed examples of forensic and pharmaceutical practice regarding the violation of the rights of oncological patients to obtain antineoplastic medicines for the sake of suffering.Conclusions of the research. The study of the interdisciplinary connection between criminal law and pharmaceutical law based on forensic and pharmaceutical practice during the circulation of narcotic substances for pharmaceutical provision of preferential categories of cancer patients, affected by emergencies, suggests that the disciplines also interact with the ecological, civil, labor, administrative, medical, pharmaceutical and other spheres, which, in turn, affect the legal relationship in the chain «doctor – cancer patient – pharmacist – lawyer» and are all in a pile of law enforcement in Ukraine.

Abstract 4601: Dissecting the spatial heterogeneity of circulating tumor cells reveals CCL5-Treg-mediated immune evasion in hepatocellular carcinoma

Abstract The prognosis of hepatocellular carcinoma (HCC) is closely linked to the occurrence of recurrent, metastatic disease. Metastasis has been proposed to be initiated by circulating tumor cells (CTCs); however, the transcriptomic plasticity and adaptive mechanisms of CTCs in systemic circulation are not well defined. Here, we established single-cell RNA-sequencing profiles of 113 CTCs isolated from four key vascular sites along the dissemination route in ten HCC patients. In our study, we found that single CTCs displayed profound spatial transcriptional heterogeneity within the circulatory system, which is associated with increased transcriptional activity, cell cycle progression, and chemokine-induced immune escape programs. In particular, CTCs dynamically drove chemokine (C-C motif) ligand 5 (CCL5) expression over the course of circulation. We demonstrated that increased CCL5 expression in turn recruited regulatory T cells to facilitate immune evasion and metastatic progression, as rigorously validated by our in vitro and in vivo models. Finally, we identified an inherently dormant CTC subset with an epithelial-mesenchymal transition and immune-evasive phenotype, and demonstrated its potential prognostic implications. Collectively, our results reveal the previously unappreciated spatial heterogeneity of CTCs, and define its role in diverse regulatory programs and cellular states. Our study offers new insight into metastatic mechanisms, highlighting the potential utility of anti-CTC therapeutic strategies. Citation Format: Liang Wu, Miaomiao Jiang, Yunfan Sun, Xinrong Yang, Yong Hou, Jia Fan, Shiping Liu. Dissecting the spatial heterogeneity of circulating tumor cells reveals CCL5-Treg-mediated immune evasion in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4601.

High speed lithium flow experiments for IFMIF target

Lithium flow was tested in a free surface test channel under pressurized or evacuated condition for the IFMIF target. The test channel, with a two-staged contraction nozzle designed after water test, was newly added to the Li loop facility in Osaka. Stable flow was obtained at the velocity of up to 13.8 m/s in 0.15 MPa, and up to 8.5 m/s at medium vacuum condition. In the course of circulation, wakes on free surface were begun to be observed due to small adhesives on the channel wall. These from the nozzle edge are considered to be prevented by keeping the edge clean. Those from the corners of the nozzle and sidewall were also observed. The shape was found to agree well with the theoretical prediction, Wake shape was estimated for IFMIF geometry, and it was indicated that the wakes emerge from the corners will not disturb the presently designed beam region.

Current and turbidity variations in the Western part of Suo-Nada, the Seto Inland sea, Japan: A hypothesis on the oxygen-deficient water mass formation

A hydrographic survey and a 25-hour stationary observation were carried out in the western part of Suo-Nada in the summer of 1998 to elucidate the formation mechanism of the oxygen-deficient water mass. A steep thermocline and halocline separated the upper layer water from the bottom water over the observational area except for near the Kanmon Strait. The bottom water, in comparison with the upper layer water, indicated lower temperature, higher salinity, lower dissolved oxygen, higher turbidity, and higher chlorophyll a. Turbidity in the upper layer water changed with semi-diurnal period while the bottom water turbidity showed a quarter-diurnal variation, though the M2 tidal current prevailed in both waters. From the turbidity distribution and the current variation, it is revealed that the turbidity in the upper layer water is controlled by the advection due to the M2 tidal current. On the other hand, the quarter-diurnal variation in the bottom water turbidity is caused by the resuspension of bottom sediments due to the M2 tidal current. The steep thermocline and halocline were maintained throughout the observation period in spite of the rather strong tidal currents. This implies an active intrusion of the low temperature and high salinity water from the east to the bottom of Suo-Nada. Based on the observational results, a hypothesis on the oxygen-deficient water mass formation was proposed; the periodical turbidity variation in the bottom water quickly modifies the oxygen-rich water in the east to the oxygen-deficient bottom water in Suo-Nada in a course of circulation.

A numerical experiment on the calculation of the tropical Atlantic circulation in 1982–1983, with the real wind considered

This paper discusses the results obtained through numerical modelling of the annual course of circulation and thermohaline field evolution in the tropical Atlantic under the impact of real wind forcing (from March 1982 to March 1983) and compares them with the calculation of seasonal variability induced by the climatic wind. Changes in the pattern of the equatorial currents and related temperature fields induced by the specific peculiarities in the wind field are analysed.

Blood Circulation in Insect Wings

Despite their inert appearance, the wings of insects are living appendages and are supplied with blood. This is true for definitive wings as well as for developing ones, and for modified wings such as tegmina, elytra, hemelytra, and halteres as for those that are specialized for flight. Typically the blood circulates only through the wing veins, but in some insects it escapes into the surrounding membrane in certain areas, and in highly modified forms it may be entirely unconfined. The course of circulation is basically the same in the wings of most insects. It flows outward from the body in the costo-medial veins, moves toward the posterior margins via cross-veins, and returns to the body through the cubito-anal veins and axillary cord. However, rhe precise route followed is highly variable concomitant with distinctive patterns of venation in different taxonomic groups and with wing structure. This is illustrated for a number of orders.

THE COURSE OF BLOOD CIRCULATION IN MATURE EMBRYOS OF THE COCKROACH BLABERUS GIGANTEUS (L.) (ORTHOPTERA:BLATTIDAE)

In mature embryos of B. giganteus the blood circulated vigorously through definite and often intricate pathways. Although the course through major sinuses depended upon the structure and location of organs and muscles and on the propulsive force of the heart, the direction of flow in the appendages and through the narrow spaces among the tissues was governed also by the aspirative force of adjacent major currents. The course of circulation is described in detail for each region of the body with special emphasis on that in the head. The structure and action of the frontal pulsatile organs is also described.

A Geograhpical Study of Rural Houses in Western Japan

i) In terms of geography, the rural house, especially its roof, is an important key to approach a settlement structure. The roof of a rural house differs from one area to another, as it reflects conditions as well as the specific way of living of the people of an area. It is possible to grasp the typical regional character in the type of roof and arrangement of rooms; also, the dynamic change of life in a rural area, such as pervasion of the use of roof-tiles and the rise and fall of silkworm culture, can be made clear through the roof-type and its change.The present writer chooses the whole Western Japan an object, examines the distribution of several roof-types, and courses of their circulation, and tries to make clear settlement structures as seen through the roofs.ii) Roofing material:More isolated mountain or island villages use more thatched or shingle roofs. Tiled roofs are widely used in industrialized areas; they show the tendency to spread from suburban areas into mountain areas with the development of urbanization and traffic. This tendency will grow stronger in future.Different roof-tiles are used between each area, reflecting local conditions: the tile-guard and the Iwami red tile in the snowy area of the northern parts (although not so wide spread as in the Tohoku and Hokuriku Districts); windbreaks in the seacoast area (especially in the Pacific Coast). Chinese red tiles in Okinawa are interesting as showing foreign influences.To a large extent, roofing material is conditioned by economic backgrounds.iii) Roof-types:Many types can be recognized: the U. and L. roofs, the conical roof and other varieties beside three fundamental types-the “irimoya” (gabled) roof, the “yosemune” (hipped) roof, the “kirizuma” (barge) roof.The “irimoya” roof is spread over the Kinki District north of the median dislocation line, eastern Chugoku, north-western Shikoku.The “yosemune” roof is widely adopted in the Kii Peninsular, western Chugoku, the Shikoku District, and the Kyushu District. It is especially much used along the Pacific Coast.The “kirizuma” roof is popular in the mountain areas of Tajima, Hyogo Pref., and the Yamato Basin. In Tajima, silkworm culture accounts for its popularity. In Yamato, the “kirizuma” style has developed into the so-called “yamatomune” roof.The U. type roof, a variety usually called “kudozukuri”, is centered at the Tsukushi Plain in the North Kyushu District. It is called “U” because it has two projections in the rear.The L. type roof, another variety with one projection in the rear of the house, is found in Kyushu (“kagiya”), in the Kochi Plain (“magariya”), and on the Tamba Plateau (“tsunoya”). Old families often adopt this roof-type.The “futamunezukuri” roof, where the main body of house and the kitchen are separated, is found in Kagoshima down to Nansei Islands. This roof-type is originated in the Micronesian and the Melanesian Islands.The conical roof is found in Okinoerabu and Yoron, the islands situated at the southernmost tip of Japan.iv) As shown here, roofs in Western Japan richly vary in type. They are further varied by the use of different ridge pressings (decorative). The distribution of these roof-types, remarkably correspond with distinctive areas. It further coincide with topographical districts.The mixture of two or more types as well as the transformation of a type is seen where two distributional areas meet. Social changes have at places resulted in changes of roof-type. Adaptation to climatic conditions has also contributed to improving the roof. At defiles and mountain passes, the course of circulation of each roof-type can be traced.

THE SALINE LAKES OF SASKATCHEWAN

Sixty lakes in central and southern Saskatchewan were investigated during the years 1938 to 1943. Most of these are saline and lie within the aspen parkland. A few freshwater lakes from the adjacent forest zone were included for comparison. Physical and chemical studies included observation of depth, temperature, dissolved oxygen, light penetration, and the mineral constituents of the water. The plankton was sampled with nets and traps, bottom organisms with an Ekman dredge, and the fish with gill nets and seines. In the first two years the survey covered all the main lakes in the southern part of the province. In the last three, more intensive studies were made in selected lakes.Most of the lakes have between 300 and 30,000 p.p.m. of total solids but Little Manitou Lake has 120,000 p.p.m. The salts are mostly sulphates of magnesium or sodium with little chlorides. Seasonal, annual, and long-term variations in salinity are discussed. Most of the lakes are shallow and only those of moderate depth show thermal stratification. High salinity affects the course of circulation. Light penetration is low in the shallow lakes but none is excessively turbid.The phytoplankton, dominated by the blue-green algae, is mostly composed of euryhaline species. Higher aquatic plants are widespread but absent from Little Manitou Lake. Cosmopolitan species of halophytes grow around the saline lakes. Rotifers are abundant with Pedalia and Brachionus dominant in the more saline water. The Entomostraca thrive in all salinities. The brine shrimp, Artemia salina, is found only in Little Manitou Lake. Chironomid larvae, amphipods, and mollusca dominate the bottom fauna. The relation of the quantity of bottom organisms to salinity is discussed.Twenty-six species of fish are found. Several species tolerate a salinity of 15,000 p.p.m. but only the nine-spined stickleback, Pungitius pungitius, occurs in 20,000 p.p.m. The saline lakes produce much game fish and about 5% of the commercial catch of the province. Fish planting and the results of three experiments in fish culture are recorded.These lakes may be classified as saline eutrophic. Salinity is the dominant influence and it is also an expression of the climatic and physiographic factors that were responsible for the formation of the lakes. The saline lakes of Saskatchewan are much like those in the steppes of western Siberia.

ACCESSORY HEARTS IN THE OYSTER, OSTREA GIGAS

In three species of Ostrea a pair of actively pulsating accessory hearts was observed in the lateral walls of the cloacal chamber. They appear to pump blood from the lacunae of the excretory organs into the large marginal arteries of the mantle lobes and into the gills.Counts of the rate of pulsation of heart and accessory hearts in O. gigas show that they act independently, the rate of pulsation of the accessories probably being determined by the rate at which they fill with blood. Only in this respect is their rate dependent upon the heart rate.The accessory hearts appear to be homologous to the gill hearts of cephalopods.The course of circulation, as influenced by the accessory hearts, is apparently as follows: blood from the ventricle passes through large arteries to the viscera, adductor muscle, and palps; the anterior aorta is directly continuous with the marginal arteries of the mantle; venous blood from viscera, palps, gills, and muscle passes to the excretory organs from which it is pumped by the accessory hearts into the marginal arteries of the mantle and to the gills; blood collected from the mantle returns directly to the auricles.Heart and accessories both pump blood into the marginal arteries, which therefore receive both venous and arterial, purified and unpurified blood.

On the Blood-Vase alar System of the Earthworm Pheretima, and the Course of the Circulation in Earthworms

ABSTRACT The typical arrangement of the blood-system in Phere-tima occurs in the region of the body behind the fourteenth segment, the first fourteen segments forming the cephalized region. The main longitudinal trunks are the same as in Lumbricus, except that the lateral neurals are absent as in Allolobophora. The dorsal vessel receives two pairs of dorso-intestinals and one pair of commissurals in each segment behind the cephalized region. The intestinal blood-plexus is both an external and an internal one, and three regions can easily be distinguished. The first is internal, and extends from the fourteenth to the twenty-sixth segment ; the second is both external and internal, is co existent with the typhlosole, and extends over the larger part of the gut ; and the third is only external, and is confined to the rectal or post-typhlosolar part of the gut (last twenty-three to twenty-six segments). The commissural vessel of Pheretima is a compound vessel, and represents both the ‘dorso-sous-nervien ’ of Lumbricus and theintestino-tegumentary of Megascolex. The capillaries of the integument are not like these of Lum-bricus but like these of Moniligaster, and there is a close ’parallelism ’ between an ‘artery ’and a ‘ vein ’in the body-wall, in which the two pass into each other through a number of capillary loops. There are four pairs of ‘hearts’ which connect the dorsal with the ventral vessel, and five pairs which supply blood directly to the various organs in the cephalized region. There are two pairs of non-contractile ‘anterior loops’ connecting the lateral oesophageals with the supra-intestinals, these loops being the counterpart of the connexions of the lateral oesophageals with the dorsal and the parietal in the tenth and twelfth segments respectively of Lumbricus. The subneural vessel is absent in the first fourteen segments, and is continuous with the lateral oesophageals of the anterior region. As regards the course of circulation of the blood, the chief fact is that the dorsal vessel is wholly ‘venous’ behind the ‘hearts’ and wholly ‘arterial ’ in the region of the ‘hearts ’ and in front (the whole of the cephalized region). The examination of valves and experiments by cutting and pinching the blood-vessels in Pheretima confirm the results of Johnstone for Lumbricus as regards the course of blood in dorso-intestinals and commissurals and make Bourne’s theory untenable. The ventral vessel is the arterial trunk throughout, while the venous function of the dorsal and subneural behind is taken up by the lateral oesophageals in the cephalized region. The thin-walled and non-contractile ‘loops’ of the tenth and eleventh segments must be distinguished from the thick walled and contractile ‘hearts’ of the other cephalized segments, the ‘loops ’ being the channels for conveying blood from the lateral oesophageals to the supra-intestinals.

IV. Experiments and observations on the various alloys, on the specific gravity, and on the comparative wear of gold. Being the substance of a report made to the Right Honourable the Lords of the Committee of Privy Council, appointed to take into consideration the state of the coins of this Kingdom, and the present establishment and constitution of his Majesty’s

The Lords of the Committee of his Majesty’s most honourable Privy Council, appointed by his Majesty, on the 10th of February, 1798, to take into consideration the state of the coins of this kingdom, having among other circumstances remarked the considerable loss which the gold coin appeared to have sustained by wear within certain periods, and being desirous to ascertain whether this loss was occasioned by any defect, either in the quality of the standard gold or in the figure or impression of the coins, were pleased to request that Henry Cavendish, Esq. F. R. S. and myself would examine, by such experiments as should be deemed requisite, whether any of these defects really existed. Two questions were to be principally decided, 1st. Whether very soft and ductile gold, or gold made as hard as is compatible with the process of coining, suffers the most by wear, under the various circumstances of friction to which coin is subjected in the course of circulation ?