bluuebunny/crossref_metadata_2025 huggingface dataset:
Pro-inflammatory cytokines induce cell death, inflammatory responses, and endoplasmic reticulum stress in human iPSC-derived beta cells
Authors: Demine Stéphane , Schiavo Andrea Alex , Marín-Cañas Sandra , Marchetti Piero , Cnop Miriam , Eizirik Decio L.
Published: January 2020

Background

Adult human pancreatic beta cells are the “gold standard” for studies on diabetes pathogenesis, but their use is limited by insufficient availability and variable quality. An important effort has recently taken place to differentiate beta cells from human induced pluripotent stem cells (iPSCs) and validate their use for diabetes research. We presently used a 7-stage protocol to generate beta cells from human iPSC and evaluated whether these cells are responsive to the pro-inflammatory cytokines (IFNγ, IL-1β, or IFNα) that play a role in type 1 diabetes.

Methods

The iPSC-derived islet-like cell clusters contained 40–50% beta and 10–15% alpha cells and expressed the receptors for IFNγ, IL-1β, or IFNα. Cells were exposed to either IFNγ (1000 U/mL) + IL-1β (50 U/mL) or IFNα alone (2000 U/mL) for 24/48 h. Apoptosis was quantified using Hoechst/propidium iodide staining or the RealTime Glo Apoptosis Kit (Promega). After treatment, CXCL10 secretion was quantified by ELISA. The expression of multiples genes (Ins, Gcg, Nkx2.2, Nkx6.1, Pdx1, Mafa, BiP, Chop, Atf3, CXCL10, CXCL9, CCL5, and HLA-ABC) was quantified by RT-qPCR. Phosphorylation state and total expression of STAT1/STAT2, as well as expression of PDL1 and of the ER chaperone BiP, were quantified by Western blotting. The co-localization of HLA-ABC or cleaved caspase-3 and Ins/Gcg expression was assessed by immunohistochemistry. The presence of HLA-ABC at the plasma membrane was measured by flow cytometry.

Results

IFNγ + IL-1β and IFNα induced apoptosis of the cells after 48 h of exposure. Cleaved caspase-3 co-localized mostly but not exclusively with Ins+ cells. Exposure to IFNγ + IL-1β induced a pro-inflammatory phenotype, including increased CXCL10, CXCL9, and CCL5 expression; CXCL10 secretion; and HLA-ABC expression. HLA overexpression was confirmed at the protein level by Western blotting and flow cytometry. Exposure to IFNγ + IL-1β (but not IFNα) also induced beta cell dedifferentiation and endoplasmic reticulum stress (increase in BiP, Chop, and Atf3 mRNA expression). Phosphorylation of STAT1 was stimulated already after 1 h by IFNγ + IL-1β and IFNα, while phosphorylation of STAT2 was only activated by IFNα at 1–4 h. PDL1 expression was increased by both IFNγ + IL-1β and IFNα.

Conclusions

Our data show that human iPSC-derived beta cells respond to pro-inflammatory cytokines IL-1β + IFNγ and IFNα, by activating the same pathogenic processes as adult human primary beta cells. These cells thus represent a valuable tool for future research on the pathogenesis of type 1 diabetes.
Preconditioning of mesenchymal stromal cells with low-intensity ultrasound: influence on chondrogenesis and directed SOX9 signaling pathways
Authors: Sahu Neety , Budhiraja Gaurav , Subramanian Anuradha
Published: January 2020

Background

Continuous low-intensity ultrasound (cLIUS) facilitates the chondrogenic differentiation of human mesenchymal stromal cells (MSCs) in the absence of exogenously added transforming growth factor-beta (TGFβ) by upregulating the expression of transcription factor SOX9, a master regulator of chondrogenesis. The present study evaluated the molecular events associated with the signaling pathways impacting SOX9 gene and protein expression under cLIUS.

Methods

Human bone marrow-derived MSCs were exposed to cLIUS stimulation at 14 kPa (5 MHz, 2.5 Vpp) for 5 min. The gene and protein expression of SOX9 was evaluated. The specificity ofSOX9upregulation under cLIUS was determined by treating the MSCs with small molecule inhibitors of select signaling molecules, followed by cLIUS treatment. Signaling events regulatingSOX9expression under cLIUS were analyzed by gene expression, immunofluorescence staining, and western blotting.

Results

cLIUS upregulated the gene expression ofSOX9and enhanced the nuclear localization of SOX9 protein when compared to non-cLIUS-stimulated control. cLIUS was noted to enhance the phosphorylation of the signaling molecule ERK1/2. Inhibition of MEK/ERK1/2 by PD98059 resulted in the effective abrogation of cLIUS-inducedSOX9expression, indicating that cLIUS-inducedSOX9upregulation was dependent on the phosphorylation of ERK1/2. Inhibition of integrin and TRPV4, the upstream cell-surface effectors of ERK1/2, did not inhibit the phosphorylation of ERK1/2 and therefore did not abrogate cLIUS-inducedSOX9expression, thereby suggesting the involvement of other mechanoreceptors. Consequently, the effect of cLIUS on the actin cytoskeleton, a mechanosensitive receptor regulatingSOX9, was evaluated. Diffused and disrupted actin fibers observed in MSCs under cLIUS closely resembled actin disruption by treatment with cytoskeletal drug Y27632, which is known to increase the gene expression ofSOX9. The upregulation ofSOX9under cLIUS was, therefore, related to cLIUS-induced actin reorganization.SOX9upregulation induced by actin reorganization was also found to be dependent on the phosphorylation of ERK1/2.

Conclusions

Collectively, preconditioning of MSCs by cLIUS resulted in the nuclear localization of SOX9, phosphorylation of ERK1/2 and disruption of actin filaments, and the expression ofSOX9was dependent on the phosphorylation of ERK1/2 under cLIUS.
Nonlinear conservation laws for the Schrödinger boundary value problems of second order
Authors: Ren Ming , Yun Shiwei , Li Zhenping
Published: January 2020

In this paper, we apply a reliable combination of maximum modulus method with respect to the Schrödinger operator and Phragmén–Lindelöf method to investigate nonlinear conservation laws for the Schrödinger boundary value problems of second order. As an application, we prove the global existence to the solution for the Cauchy problem of the semilinear Schrödinger equation. The results reveal that this method is effective and simple.
Correction to: Predictors of intracranial hemorrhage in adult patients on extracorporeal membrane oxygenation: an observational cohort study
Authors: Fletcher-Sandersjöö Alexander , Bartek Jiri , Thelin Eric Peter , Eriksson Anders , Elmi-Terander Adrian , Broman Mikael , Bellander Bo-Michael
Published: January 2020

In the original publication of this article [1], the first author’s name should be changed from Alexander Fletcher Sandersjöö to Alexander Fletcher-Sandersjöö. The family name of the author is Fletcher-Sandersjöö.
President's Page
Authors: Capello Maria Angela
Published: January 2020

I look forward to New Year's resolutions. They challenge me to shape the year ahead, hopefully as a better one than the last. For 2020, I included in my list specific step changes to reduce my own carbon footprint, and there is no better opportunity to discuss this than in the current issue of The Leading Edge, with its special section dedicated to carbon dioxide (CO2).
Memorial
Authors: Esmersoy Cengiz
Published: January 2020

Azra Tutuncu
The Prognostic Index Independently Predicts Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Resection
Authors: Gruber Elisabeth S. , Jomrich Gerd , Kaider Alexandra , Gnant Michael , Sahora Klaus , Schindl Martin
Published: January 2020

Background

Cancer-related inflammation is associated with tumour proliferation, maintenance and dissemination. It therefore impacts pancreatic cancer survival. The goal of this study was to examine the Prognostic Index (PI) as a prognostic biomarker for survival in patients with pancreatic ductal adenocarcinoma (PDAC). In addition, we explored factors known to interact with the immune and inflammation cascade that might interfere with the PI’s strength for prognostication.

Methods

Patients with PDAC undergoing resection were analysed retrospectively. The PI was calculated from preoperatively derived C-reactive protein levels and white blood count. Data were subject to correlation and survival analysis.

Results

Of 357 patients, 235 (65.8%) patients had a PI 0, 108 (30.3%) PI 1, and 14 (3.9%) PI 2. Median (quartiles) survival with a high PI (group 1 + 2) was 13.2 months (7.7–27.0), compared with 18.7 months (10.2–35.4) with a low PI (group 0; p = 0.012). The PI proved to be an independent prognostic factor for cancer-specific survival (p = 0.003) adjusted for conventional prognostic factors. Prognostic strength was influenced by the presence of a bile stent (p = 0.032).

Conclusions

The PI is a strong and solid independent prognostic tool for survival in patients with PDAC undergoing resection. Preoperative survey of inflammatory activity as provided by the use of a biomarker like the PI may help to identify those patients at risk of a poor prognosis.
An organized approach to imaging of benign cecal pathologies
Authors: Lewis Ariel , Mahendiran Shavitri , Hochsztein Jay , Alterman Daniel , Guelfguat Mark
Published: January 2020

Unique problems in cecal embryogenesis and cecal pathology can result in characteristic imaging findings. Familiarity with these findings and utilization of an organized approach help to define the cecum’s role in acute abdominal symptoms. Clinical symptoms associated with cecal diseases can be diverse and misleading. This pictorial essay should provide a framework for an understanding of anatomical, infectious, and inflammatory cecal diseases. Knowledge of a broad spectrum of cecal pathologies contributing to these disorders and their corresponding imaging findings can help a radiologist define the diagnosis and guide proper management.
Medicine and State Violence
Authors: Cuerda Esther
Published: January 2020

During the last decades, in different places and under different circumstances, some physicians and other health professionals have supported state violence. The Holocaust is a prime example for how doctors can cooperate with the state to plan, give ideological support to and implement violent policies. As a consequence of the Industrial Revolution, people gained access to health promotion and health protection, not as an achievement of the welfare state, but as a tool necessary to maintain healthy and more productive workers. Gradually, all social strata, employees and their relatives gained access to health coverage. Physicians as a group increased in number and changed the structure of their profession by establishing a symbiotic relationship with the state. Between the state and the medical class, different models of cooperation can be distinguished. In general, we can affirm that with the implementation of a public health system, greater interdependence among the state and the medical class was established. In the case of authoritarian or totalitarian regimes, the support of the medical class for violent policies depends on the degree of previous cooperation. National Socialist Germany and the Soviet Union are two striking examples of totalitarian states in which strong public health systems and subsequent close cooperation between the medical class and the state can be observed. In both countries, violent state policies were quickly accepted and integrated into medical practice. Practices such as forced sterilization, murder of patients or experimentation with prisoners were prevalent under National Socialism. The abuse of psychiatry as tool for exerting power was common in the Soviet Union. South American dictatorships constitute examples of totalitarian states with weak previous cooperation between the medical class and the state, as they did not have strong public health systems. In those countries, support for state violence can be found, such as participation of health care professionals in torture or abduction of babies, but cooperation was not as strong as in Nazi Germany or the Soviet Union. In other cases in which no strong previous relationship existed between medicine and the state, authoritarian regimes were not accompanied by medical support for violence, such as in the case of the Rwandan genocide or in Cambodia, where doctors were persecuted and murdered based on their membership of the bourgeois class.
The Rhetorical Biopower of Eugenics: Understanding the Influence of British Eugenics on the Nazi Program
Authors: Caleb Amanda M.
Published: January 2020

The relationship between the British and Nazi eugenics movements has been underexamined, largely because of the more obvious ties between the American and Nazi programs and the lack of a state-sponsored program in Britain. This article revisits this gap to reinsert the British eugenics movement into the historiography of the Nazi program by way of their shared rhetoric. To do this, I employ Foucault’s concepts of biopower and power/knowledge, arguing that biopower exists in rhetorical constructions of power and identity, which the eugenics movements employed at national and individual levels to garner support and participation, particularly from women. The article is not an exhaustive account of the rhetorical overlaps between the two movements, but rather serves as a model of how one might understand eugenics as a rhetoric of biopower.
Testing the Effectiveness of Interdisciplinary Curriculum-Based Multicultural Education on Tolerance and Critical Thinking Skill
Authors: Aslan Serkan , Aybek Birsel
Published: January 2020

This research aims to explore the effectiveness of interdisciplinary education program based on multicultural education on the tolerance value, attitude and critical thinking skills of the fourth grade primary school students. Single group pre-posttest design has been used in the study. The research has been carried out with 30 fourth-grade students, at a primary school located within the district of Karakocan in Elazig during the 2015-2016 academic year. Among the participants, 15 are females and 15 are males. The research has employed Tolerance Attitude Scale developed by Kaptan-Yarar, tolerance value and critical thinking story tests and scoring rubrics. Descriptive statistics and dependent samples t-test have been used during data analysis. Research results have revealed a statistically significant difference between critical thinking scoring rubric, tolerance value scoring rubric and tolerance attitude scale pretest-posttest scores in favor of posttest. Based on these results, it can be said that the interdisciplinary curriculum developed based on multicultural education improves students' critical thinking skills, tolerance value and attitudes.
Osteoblast differentiation of bone marrow stromal cells by femtosecond laser bone ablation
Authors: Zheng Jianqiao , Zhang Xinyue , Zhang Yaopeng , Yuan Fusong
Published: January 2020

This study examines the osteogenic effect of femtosecond laser bone
ablation on bone mesenchymal stromal cells (BMSCs). Three-week old
Sprague-Dawley (SD) rats were selected for experiments. Right tibias
were ablated by a 10-W femtosecond laser (treated group), whereas left
tibias were not subjected to laser ablation (control group). After
ablation, BMSCs of both tibias were cultured and purified separately.
Cell proliferation was then analyzed, as well as the expressions of
RNA and several proteins (alkaline phosphatase (ALP), runt-related
transcription factor 2 (RUNX2) and osteocalcin (OCN)). The results
suggest that femtosecond laser ablation promotes the differentiation
of BMSCs and up-regulates the expression of ALP, RUNX2, and OCN,
without affecting BMSC proliferation.
PAKAN ALTERNATIF PADA TRENGGILING JAWA (Manis javanica Desmarest, 1822) DI PENANGKARAN
Authors: Rianti Anita , Takandjandji Mariana
Published: January 2020

The use of alternative feed for Sunda pangolin in captivity is one way to cope with a shortage of feed. The aims of the research was to determine the impact of the use of alternative feed toward feed consumption and daily weight gain of pangolin in captivity. The research was conducted at Research Forest Dramaga, Bogor. The research material used by 4 individual pangolin consists of 2 males and 2 females with an average weight of 4.28 ± 0.22 kg. Research using 4x4 Latin Square Design, with 7 days of preliminary period and 14 days of data collection. The treatment applied were 4 alternative feeding i.e A= 50% kroto + 50% egg; B= 50% kroto + 50% tofu; C= 50% kroto + 20% egg + 30% tofu; D= 50% kroto + 18% egg + 26% tofu + 6% termites. The results showed that the effect of alternative feed not significantly (P<0.05) on feed consumption and body weight gain pangolin. Pangolin with treatment C consumed feed based on dry matter as much as 63.08 grams per day or 10.46% from body weight and the biggest weight gain 35.0 grams per individual per day.
THE DIVERSITY AND DISTRIBUTION OF TWO FAMILIES OF SUMATRAN LAND SNAIL (GASTROPODA: CAMAENIDAE AND CYCLOPHORIDAE)
Authors: Mujiono Nova , Priawandiputra Windra , Atmowidi Tri
Published: January 2020

The diversity of land snail in Sumatra, Indonesia was firstly studied by Bock (1881), followed by some comprehensive studies by Degner (1928), Van Benthem Jutting (1959), and recently by Marwoto (2016). This research aimed to update the data on diversity and distribution of those two families, documenting new information on their distribution, make historical records of species occurrence, list species occurrence from inside and outside the conservation area. We collected primary data from 274 numbers of museum collections and secondary data from 29 literatures. In total, 58 species of Camaenidae and 66 species of Cyclophoridae were known from Sumatra. Fourteen land snail species, seven from family Camaenidae and seven from family Cyclophoridae, were added to the previous list of land snail species in Sumatra. There were 30 land snail species with new distribution ranges.
THE IDENTITY OF EUPLOEA TULLIOLUS GOODENOUGHI CARPENTER, 1942, A CROW BUTTERFLY (LEPIDOPTERA: NYMPHALIDAE, DANAINAE) FROM PAPUA NEW GUINEA
Authors: Vane-Wright Richard Irwin
Published: January 2020

The nominal taxon Euploea tulliolus goodenoughi Carpenter, 1942, based on a unique crow butterfly collected on Goodenough Island in 1913, is shown to represent a small, aberrant female of the locally common Euploea leucostictos eustachius (Kirby, 1889). This new synonymy invalidates the only previous record of the Purple Crow, Euploea tulliolus (Fabricius, 1793), from the islands of Milne Bay Province, Papua New Guinea. However, two female Euploea tulliolus collected from islands in the Louisiade Archipelago during 2010 are reported here, constituting the first valid records of the Purple Crow from the Milne Bay islands.
Approach to the Post-Ablation Barrett's Esophagus Patient
Authors: Kahn Allon , Shaheen Nicholas J. , Iyer Prasad G.
Published: January 2020

Because of the rising incidence and lethality of esophageal adenocarcinoma, Barrett's esophagus (BE) is an increasingly important premalignant target for cancer prevention. BE-associated neoplasia can be safely and effectively treated with endoscopic eradication therapy (EET), incorporating tissue resection and ablation. Because EET has proliferated, managing patients after complete eradication of intestinal metaplasia has taken on increasing importance. Recurrence after complete eradication of intestinal metaplasia occurs in 8%–10% of the patients yearly, and the incidence may remain constant over time. Most recurrences occur at the gastroesophageal junction, whereas those in the tubular esophagus are endoscopically visible and distally located. A simplified biopsy protocol limited to the distal aspect of the BE segment, in addition to gastroesophageal junction sampling, may enhance efficiency and cost without significantly reducing recurrence detection. Similarly, research suggests that current surveillance intervals may be excessively frequent, failing to reflect the cancer risk reduction of EET. If validated, longer surveillance intervals could reduce the burden of resource-intensive endoscopic surveillance. Several important questions in post-EET management remain unanswered, including surveillance duration, the significance of gastric cardia intestinal metaplasia, and the role of advanced imaging and nonendoscopic sampling techniques in detecting recurrence. These merit further research to enhance quality of care and promote a more evidence-based approach.
Cannabinoids and Opioids in the Treatment of Inflammatory Bowel Diseases
Authors: Kienzl Melanie , Storr Martin , Schicho Rudolf
Published: January 2020

In traditional medicine, Cannabis sativa has been prescribed for a variety of diseases. Today, the plant is largely known for its recreational purpose, but it may find a way back to what it was originally known for: a herbal remedy. Most of the plant's ingredients, such as Δ9-tetrahydrocannabinol, cannabidiol, cannabigerol, and others, have demonstrated beneficial effects in preclinical models of intestinal inflammation. Endogenous cannabinoids (endocannabinoids) have shown a regulatory role in inflammation and mucosal permeability of the gastrointestinal tract where they likely interact with the gut microbiome. Anecdotal reports suggest that in humans, Cannabis exerts antinociceptive, anti-inflammatory, and antidiarrheal properties. Despite these reports, strong evidence on beneficial effects of Cannabis in human gastrointestinal diseases is lacking. Clinical trials with Cannabis in patients suffering from inflammatory bowel disease (IBD) have shown improvement in quality of life but failed to provide evidence for a reduction of inflammation markers. Within the endogenous opioid system, mu opioid receptors may be involved in anti-inflammation of the gut. Opioids are frequently used to treat abdominal pain in IBD; however, heavy opioid use in IBD is associated with opioid dependency and higher mortality. This review highlights latest advances in the potential treatment of IBD using Cannabis/cannabinoids or opioids.
“Singing Was More into My Blood, Than the Trumpet”
Authors: Hobson Vic
Published: January 2020

This chapter explores the reception history of Louis Armstrong’s singing and playing by musicians, writers, and critics. The present-day view of Armstrong whose singing and playing can be appreciated in equal measure, assumes that the two practices are not related and that Armstrong’s singing did not relate to the development of the jazz solo. This was not how Armstrong explained it. He explained in an interview that he knowingly interpreted the lines he sang in a quartet as lines he played on his instrument, using the example of “Sweet Adeline” (1903) This explains why Armstrong thought singing to be the nexus of his musicianship.
Gênese da Geografia Agrária no Brasil
Authors: Felício Munir Jorge
Published: January 2020

A geografia agrária estuda as formas de ocupação do território não isolando o olhar geográfico das demais abordagens como as históricas, sociais, econômicas e políticas. Como ciência ela evolui em função do aperfeiçoamento teórico-metodológico para interpretar, geograficamente o espaço, razão pela qual, acompanha as transformações do modo de produzir grão e carne, visando verificar as diferentes formas de analisar a agricultura. No decorrer das décadas de 1960-1970 a geografia agrária no Brasil iniciou sua própria trajetória ao produzir interpretações e desenvolver metodologia que lhe aparelhasse cada vez mais, proporcionando acompanhar as transformações no campo. No presente texto as duas partes que a compõe reuniu, na primeira, aspectos metodológicos da geografia agrária com as contribuições de Valverde (1964), Ceron e Diniz (1970), Keller (1973) e Oliveira (1977). Abordagens analíticas da geografia agrária constam, na segunda parte, contando com as discussões de Bernardes (1961), Andrade (1964), Guerra (1965) e Becker (1972).
(NON) HUMAN(IMAL) RIGHTS: DISMANTLING THE SEPARATENESS IN LAW AND POLICY
Authors: WILSON AMY P.
Published: January 2020

In 2016, the South African Constitutional Court recognised that the guaranteed human right to the environment, as contained in the Constitution, includes animal welfare. In its judgment, the court stated that the suffering of individual animals is correctly linked to conservation and that this “illustrates the extent to which showing respect and concern for individual animals reinforces broader environmental protections. Animal welfare and animal conservation together reflect two intertwined values”. Although the effect of the statement by the highest court in the land is yet to be fully realised, the court unambiguously demonstrated in its ruling the clear link between human rights and animal interests. These interests are not only to be interpreted in the broad sense relating to species-conservation, but rather the interests and welfare of individual animals.

Building on from this approach and the rationale provided by the court, this Paper looks to explore more broadly the interaction and linkages between human and animal rights and interests. More particularly, it attempts to illustrate how these concepts may reinforce and enrich one another and how this relationship may be better reflected in law and policy. It will argue that sophisticated democracies and movements require an integrational approach. By expanding the scope and interpretation of certain human rights to include animal interests; and through coordinated, targeted efforts – we ensure notion of justice is achieved, for all who require it.
Further structural studies of the lytic polysaccharide monooxygenase AoAA13 belonging to the starch-active AA13 family
Authors: Muderspach Sebastian J. , Tandrup Tobias , Frandsen Kristian E. H. , Santoni Gianluca , Poulsen Jens-Christian N. , Leggio Leila Lo
Published: January 2020

Lytic polysaccharide monooxygenases (LPMOs) are recently discovered copper enzymes that cleave recalcitrant polysaccharides by oxidation. The structure of an Aspergillus oryzae LPMO from the starch degrading family AA13 (AoAA13) has previously been determined from an orthorhombic crystal grown in the presence of copper, which is photoreduced in the structure. Here we describe how crystals reliably grown in presence of Zn can be Cu-loaded post crystallization. A partly photoreduced structure was obtained by severely limiting the X-ray dose, showing that this LPMO is much more prone to photoreduction than others. A serial synchrotron crystallography structure was also obtained, showing that this technique may be promising for further studies, to reduce even further photoreduction. We additionally present a triclinic structure of AoAA13, which has less occluded ligand binding site than the orthorhombic one. The availability of the triclinic crystals prompted new ligand binding studies, which lead us to the conclusion that small starch analogues do not bind to AoAA13 to an appreciable extent. A number of disordered conformations of the metal binding histidine brace have been encountered in this and other studies, and we have previously hypothesized that this disorder may be a consequence of loss of copper. We performed molecular dynamics in the absence of active site metal, and showed that the dynamics in solution differ somewhat from the disorder observed in the crystal, though the extent is equally dramatic.
Effects of Huaiqihuang Granules adjuvant therapy in children with primary nephrotic syndrome
Authors: Zhou Ping , Xiao Qiong , Chen Lan , Zou Zhi-Jie , Wang Yu-Qing , Zhu Lin , Yu Hai-Yan , Zhao Cheng-Guang , Wu Yu-Bin , Du Xuan-Yi
Published: January 2020

Objective

This study aims to observe the curative effect of Huaiqihuang Granules adjuvant therapy on primary nephrotic syndrome (PNS).

Methods

A total of 112 children with PNS were randomly divided into three groups, and changes in serum inflammatory cytokines, interleukin, lymphocyte subsets and immunoglobulin were observed.

Results

Before treatment, IL-18, TNF-α, CD8+ increased, while IL-10, CD4+, NK cells, IgA, IgG and Foxp3+Treg cells decreased. After Huaiqihuang Granules treatment, IL-18, TNF-α, CD8+ decreased, while IL-10, CD4+, NK cells, IgA, IgG and Foxp3+Treg cells increased.

Conclusion

Functions of cell immunity and humoral immunity in PNS patients before treatment were suppressed and disordered. Huaiqihuang granules can play a role in immunoregulation, with slight side reactions.
Immune negative regulator TIPE2 inhibits cervical squamous cancer progression through Erk1/2 signaling
Authors: Huang Li-Qiong , Zheng Bo , He Yi
Published: January 2020

Tumor necrosis factor (TNF)-α-induced protein-8-like 2, or TIPE2, is a newly found immune negative regulatory molecule. This study further investigated the role of TIPE2 on proliferation and invasion of cervical squamous cancer cells. Expression of TIPE2 was compared in cervical squamous cancer tissues and adjacent normal tissues by Western blot and immunohistochemistry (IHC). Cervical squamous cancer cell lines, SiHa and C33A, were transfected with recombinant plasmid encoding TIPE2 and tested for cytologic characteristics. The impact of TIPE2 on phosphorylation of extracellular signal-regulated kinase (Erk) signaling pathway was also tested by Western blot analysis of key factors. TIPE2 expression was higher in cervical cancer tissues than that in normal tissue. IHC score of tumor tissue was negatively associated with lymphatic metastasis. Over expression of TIPE2 effectively inhibited the proliferation of cervical cancer cells. Wound healing and transwell assay showed that over expression of TIPE2 suppressed cell migration and invasion in vitro. Meanwhile, phosphorylation of Erk1/2 and upstream mitogen-activated protein kinase kinase (MEK) 1/2 was reduced by TIPE2. TIPE2 is negatively related with development of cervical squamous cancer. TIPE2 is an inhibitory factor of proliferation and invasion of cervical squamous cancer cells, probably through inhibiting Erk signaling pathway.
Some transpose-free CG-like solvers for nonsymmetric ill-posed problems
Authors: Gazzola Silvia , Novati Paolo
Published: January 2020

This paper introduces and analyzes an original class of Krylov subspace methods that provide an efficient alternative to many well-known conjugate-gradient-like (CG-like) Krylov solvers for square nonsymmetric linear systems arising from discretizations of inverse ill-posed problems. The main idea underlying the new methods is to consider some rank-deficient approximations of the transpose of the system matrix, obtained by running the (transpose-free) Arnoldi algorithm, and then apply some Krylov solvers to a formally right-preconditioned system of equations. Theoretical insight is given, and many numerical tests show that the new solvers outperform classical Arnoldi-based or CG-like methods in a variety of situations.
Das Ende des Staatsstreichs
Authors: Heinemann Winfried
Published: January 2020

Vorspann

Der Staatsstreich, der am Abend des 20. Juli 1944 im Bendlerblock zusammenbrach, wurde nicht von Truppen des Berliner Wachbataillons niedergeschlagen, wie es dessen Kommandeur, der fanatische Nazi Major Otto Ernst Remer, und sein Adjutant Leutnant Hans Wilhelm Hagen, nach dem Krieg immer wieder dargestellt haben. Die ersten, die sich gegen Stauffenberg und dessen Mitverschwörer stellten, waren Offiziere aus dem Stab des Allgemeinen Heeresamts. Drei von ihnen, die Oberstleutnante Herber, von der Heyde und Pridun, wurden kurz darauf bevorzugt zum Oberst befördert; außer den Beförderungen von Remer und Hagen wurde im Wachbataillon kaum jemand belobigt. Nach außen hin aber zog das Regime es vor, den „Frontkämpfer“ und Eichenlaubträger Remer sowie den Reservisten aus dem Reichspropagandaministerium Hagen als die „Männer der Stunde“ herauszustellen, und nicht die Generalstabsoffiziere aus den Büros im Bendlerblock. Auch nach dem Krieg nutzten Remer und Hagen ihre Reputation für ihre rechtsradikalen Bestrebungen, während sich die eigentlichen Umsturzgegner aus dem Bendlerblock in bürgerliche Existenzen zurückzogen und von ihrer Rolle am 20. Juli möglichst wenig wissen wollten.
Der Generaloberst und die Historiker
Authors: Fröhlich Paul
Published: January 2020

Vorspann

In den 1950er und 1960er Jahren überschwemmte eine Fülle von zeitgeschichtlichen Memoiren, Editionen und Dokumentationen zum NS-Regime beziehungsweise zum Zweiten Weltkrieg den Markt. Wie zuletzt Magnus Brechtken für den Fall Albert Speer zeigte, (ent-)standen einiger dieser Werke unter dem geschichtspolitischen Einfluss der ehemaligen Akteure und dienten einer weit verbreiteten Exkulpationsmentalität. Im Lichte dieser aktuellen Forschungsthemen untersucht Paul Fröhlich die Publikationsgeschichte des Kriegstagebuchs von Franz Halder, Chef des Generalstabs des Heeres zwischen 1938 und 1942. Er zeigt den außerordentlichen Einfluss Halders und dessen Entlastungsnarrative auf die Praxis der zeitgeschichtlichen Forschung seit dem Ende der 1940er Jahre und stellt die Frage nach der Akteursnähe der damaligen Historiker.
СУЧАСНИЙ СТАН ТА ТЕНДЕНЦІЇ НЕБАНКІВСЬКОГО МІКРОКРЕДИТУВАННЯ В УКРАЇНІ
Authors: Shuplat O. M.
Published: January 2020

Мета дослідження – визначити проблеми та обґрунтувати шляхи розвитку сектору ринку небанківського мікрокредитування в Україні.У роботі застосовано сукупність методів наукового пізнання, серед яких методи наукової абстракції та логіко-діалектичний (у дослідженні змісту мікрокредитування); статистичний та графічний аналіз – для аналізу, порівняння і наочного відображення статистичних даних (у процесі дослідження сучасних тенденцій національного ринку мікрокредитування) та емпіричні методи досліджень.Уточнено сутнісні характеристики мікрокредитування та визначено його роль у споживчому кредитуванні. Виокремлено основні чинники, що негативно впливають на створення дієвого та якісного ринку небанківського мікрокредитування в Україні та запропоновано державні важелі щодо збільшення привабливості, прозорості та зниження ризиків ринку небанківського мікрокредитування. В свою чергу це позитивно впливатиме на розвиток економіки країни, соціальний добробут та приватну фінансову стабільність населення.У роботі на тему “Сучасний стан та тенденції небанківського мікрокредитування в Україні” обґрунтовано основні напрями регулювання небанківського мікрокредитування у споживчому кредитуванні суб’єктів господарювання в умовах соціально-економічної нестабільності. Це дозволить сформувати сприятливе нормативно-правове та інституційне забезпечення ринку небанківського мікрокредитування.
ВЛАСНІ ДОХОДИ БЮДЖЕТІВ ОБ’ЄДНАНИХ ТЕРИТОРІАЛЬНИХ ГРОМАД: СКЛАД, СТРУКТУРА ТА ТЕНДЕНЦІЇ
Authors: Shchur R.I. , Svirskyi V.S. , Plets I.I.
Published: January 2020

Стаття присвячена дослідженню з’ясування структури та виявлення тенденцій формування власних доходів бюджетів об’єднаних територіальних громад в умовах децентралізації. Розглянуто особливості формування власних доходів бюджетів об’єднаних територіальних громад, основними джерелами надходжень до яких у процесі проведення бюджетної децентралізації є: податок на доходи фізичних осіб, акцизний податок, плата за землю, єдиний податок та податок на нерухоме майно, відмінне від земельної ділянки. Аналіз надходжень власних доходів бюджетів об’єднаних територіальних громад протягом 2017-2018 рр. показав, що найбільшу питому вагу в загальній структурі джерел формування власних доходів об’єднаних територіальних громад становить податок на доходи фізичних осіб. Детальний аналіз формування власних доходів місцевих бюджетів показав, що в розрізі місцевих бюджетів у 2017-2018 рр. найвищим є темп зростання місцевих податків та зборів саме у місцевих бюджетах об’єднаних територіальних громад. Такі результати свідчать про зростання участі та зацікавленості органів місцевого самоврядування у збільшенні доходів бюджетів об’єднаних територіальних громад, реалізації заходів щодо пошуку резервів їх надходжень та підвищення ефективності фіскального адміністрування податків і зборів. Охарактеризовано ряд бюджетних новацій щодо доходів бюджетів об’єднаних територіальних громад: зарахування 3% рентної плати за користування надрами (видобування нафти, природного газу та газового конденсату), 100% єдиного податку, що сплачується платниками четвертої групи (сільгоспвиробниками), доходи бюджетів об’єднаних територіальних громад від затвердження Ліцензійних умов провадження господарської діяльності з випуску та проведення лотерей.Авторами обґрунтовано напрями розширення якісного й кількісного складу власних доходів бюджетів об’єднаних територіальних громад.
ТРАНСФОРМАЦІЯ ФІНАНСОВОГО ЗАБЕЗПЕЧЕННЯ ТРУДОВОГО ПОТЕНЦІАЛУ КРІЗЬ ПРИЗМУ РЕФОРМУВАННЯ СИСТЕМИ ОХОРОНИ ЗДОРОВ’Я
Authors: Tsizhma Yu.І. , Tsizhma O.A.
Published: January 2020

Стаття присвячена дослідженню стану фінансових ресурсів сфери охорони здоров’я та регенерації підходів фінансового забезпечення з метою розвитку трудового потенціалу. Здійснено узагальнення підходів фінансового забезпечення сфери охорони здоров’я з метою розвитку трудового потенціалу держави. Розглянуто необхідність реформування системи охорони здоров’я України, адже за показником витрат на охорону здоров’я наша держава посідає далеко не високе місце в загальному світовому рейтингу.Досліджено питання, що стосується частки суспільних ресурсів у фінансуванні охорони здоров’я в Україні.Проаналізовано бюджетну модель організації та фінансування охорони здоров’я, яка дісталася нашій державі у спадок і зараз трансформується в систему, котра поєднує суспільні та приватні джерела фінансування.Визначено, що докорінні зміни у підходах фінансування сфери охорони здоров’я перш за все повинні бути спрямовані на забезпечення гармонійного розвитку, високої працездатності і активного довголіття громадян, усунення факторів ризику для здоров’я громадян, покращення якісних характеристик життя населення, і як результат, збереження та відновлення трудового потенціалу країни.Зважаючи на те, що система охорони здоров’я будь-якої країни зазнає впливу багатьох соціально-економічних, політичних, культурно-історичних та інших чинників, визначено, що визначальними в них є витрати на охорону здоров’я у відсотках до ВВП, розмір реальних видатків на охорону здоров’я у розрахунку на душу населення, частка державних витрат у структурі загальних витрат на охорону здоров’я.Для успішного політичного, соціального та економічного розвитку трудового потенціалу здоров’я людини розглядається як головний чинник і результат та є складовою людського благополуччя..В результаті дослідження акцентовано увагу на необхідності виконання юридичного обов’язку держави щодо впровадження соціального медичного страхування, як гарантії реалізації прав громадян у сфері охорони здоров’я та медичної допомоги та продовження реформи первинної ланки надання медичної допомоги. Адже слід пам’ятати, що найбільших успіхів у вирішенні проблеми зміцнення здоров’я громадян досягли ті країни, які запровадили в системі охорони здоров’я механізм медичного страхування.Виокремлено підходи щодо покращення стану фінансового забезпечення системи охорони здоров’я у розрізі існуючих проблем.
НОРМАТИВНЕ РЕГУЛЮВАННЯ НАПРЯМІВ ФІНАНСОВОЇ ПІДТРИМКИ ТЕХНОЛОГІЧНОГО ОНОВЛЕННЯ ВИРОБНИЦТВА ТА МОДЕРНІЗАЦІЇ ДІЯЛЬНОСТІ СІЛЬСЬКОГОСПОДАРСЬКИХ ПДПРИЄМСТВ
Authors: Sas L.S. , Matkovskyi P.Ye.
Published: January 2020

Метою статті є визначення напрямів державної фінансової підтримки інноваційної діяльності, зокрема технологічного оновлення виробництва та модернізації діяльності сільськогосподарських підприємств, передбачених нормативними документами.У процесі дослідження використано методи аналізу, систематизації, групування, абстрагування з метою визначення нормативних документів щодо регулювання інноваційної діяльності суб’єктів господарювання, виокремлення та розгляду напрямів державної фінансової підтримки технологічного оновлення виробництва й модернізації діяльності сільськогосподарських підприємств.Інформаційну базу наукового дослідження склали наукові праці вітчизняних вчених-економістів та законодавчо-нормативні документи з питань регулювання інноваційної діяльності та фінансового забезпечення її здійснення.Обґрунтовано роль та місце державної фінансової підтримки у забезпеченні здійснення технологічного оновлення виробництва сільськогосподарських підприємств як складової їхнього інноваційного розвитку. Проведено аналіз нормативного забезпечення здійснення інноваційної діяльності. Виокремлено та розглянуто напрями фінансової підтримки технологічного оновлення і модернізації діяльності сільськогосподарських підприємств, зокрема щодо: бюджетної підтримки; створення необхідних умов для фінансування; пільгового кредитування; страхування інноваційної діяльності; створення спеціалізованих небанківських інноваційних фінансово-кредитних установ; пільгового оподаткування; фінансово-економічного забезпечення трансферу технологійНаукова новизна одержаних результатів полягає у визначенні та розкритті напрямів державної фінансової підтримки технологічного оновлення виробництва та модернізації діяльності сільськогосподарських підприємств.Одержані результати дослідження можуть бути використані при організації процесу технологічного оновлення виробництва та модернізації діяльності сільськогосподарських підприємств.
ЗАРУБІЖНИЙ ДОСВІД РЕГУЛЮВАННЯ ЗАЙНЯТОСТІ
Authors: Kaziuka N.P.
Published: January 2020

Статтю присвячено дослідженню зарубіжного досвіду регулювання зайнятості населення, підготовки та перепідготовки робочої сили у провідних країнах світу, забезпеченості працевлаштування трудових ресурсів. Виокремлено базові сценарії, моделі, методи подолання безробіття та бідності, ефективні способи зростання зайнятості для розгляду та вивчення можливостей реалізації в сучасних умовах функціонування вітчизняної економіки. Визначено фактори сприяння детінізації економіки та оптимальні шляхи реформування економіки для досягнень максимальних економічних показників.В статті виокремлено основні підходи до регулювання ринку праці, елементи розробки ефективної політики зайнятості США, Великобританії, Франції, Німеччини, Польщі, Японії та Китаю. На конкретних прикладах розглянуто досвід провідних країн світу в проведенні економічних реформ, розглянуто динаміку основних тенденції змін зайнятості населення.Розглянуто специфічні методи, програми та засоби боротьби з безробіттям, подолання кризи та бідності, підвищення рівня зайнятих, що успішно використовувались різними країнами на певному етапі розвитку. Визначено, що країни, які розвиваються характеризуються високим рівнем зайнятості в сільському господарстві, сфері послуг та низьким – в галузях матеріального виробництва. Вивчено обсяги зайнятості в тіньовій економіці провідних країн світу, роль державних органів у врегулюванні процесів, що відбуваються на ринку праці.В результаті вивчення світового досвіду формування ефективної системи зайнятості виокремлено наступні напрями формування продуктивної економіки регіону: зростання податкових відрахування до бюджетів різних рівнів завдяки підвищенню доходів населення та зростання обсягу виробництва наукомісткої продукції; створення додаткових робочих місць в усіх галузях економічної діяльності; скорочення чисельності екологічно шкідливих підприємств; вирішення існуючої екологічної проблеми на основі розробки та використання новітніх “зелених” технологій.
Lung Function of Adults Born at Very Low Birth Weight
Authors: Yang Jun , Kingsford Rachel A. , Horwood John , Epton Michael J. , Swanney Maureen P. , Stanton Josh , Darlow Brian A.
Published: January 2020

BACKGROUND:

Much remains unknown about the consequences of very low birth weight (VLBW) and bronchopulmonary dysplasia (BPD) on adult lungs. We hypothesized that VLBW adults would have impaired lung function compared with controls, and those with a history of BPD would have worse lung function than those without.

METHODS:

At age 26 to 30 years, 226 VLBW survivors of the New Zealand VLBW cohort and 100 term controls born in 1986 underwent lung function tests including spirometry, plethysmographic lung volumes, diffusing capacity of the lung for carbon monoxide, and single-breath nitrogen washout (SBN2).

RESULTS:

An obstructive spirometry pattern was identified in 35% VLBW subjects versus 14% controls, with the majority showing mild obstruction. Compared with controls, VLBW survivors demonstrated significantly lower forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC) ratio (FEV1/FVC), forced expiratory flow at 25% to 75% of FVC and higher residual volume (RV), RV/total lung capacity (TLC) ratio (RV/TLC), decreased diffusing capacity of the lung for carbon monoxide, and increased phase III slope for SBN2. The differences persisted after adjustment for sex and smoking status. Within the VLBW group, subjects with BPD showed significant reduction in FEV1, FEV1/FVC, and forced expiratory flow at 25% to 75% of FVC, and increase in RV, RV/TLC, and phase III slope for SBN2, versus subjects without. The differences remained after adjustment for confounders.

CONCLUSIONS:

Adult VLBW survivors showed a higher incidence of airflow obstruction, gas trapping, reduced gas exchange, and increased ventilatory inhomogeneity versus controls. The findings suggest pulmonary effects due to VLBW persist into adulthood, and BPD is a further insult on small airway function.
Impact of synthetic pesticides utilization on humans and the environment: an overview
Authors: Oaya C.S. , Malgwi A.M. , Degri M.M. , Samaila A.E.
Published: January 2020

Abstract. Pesticides are chemicals that kill or manage the population of pests. There are many different types of pesticides on the market today, but the most common are herbicides and insecticides, which kill or manage unwanted plants and insects. The benefits of pesticides include increased food production, increased profits for farmers and the prevention of diseases. Although pests consume or harm a large portion of agricultural crops, without the use of pesticides, it is likely that they would consume a higher percentage. More food is produced by farmers, thereby increasing profit. Pesticides also increase farm profits by helping the farmer save money on labor costs. Using pesticides reduces the amount of time required to manually remove weeds and pests from the fields. In addition to saving crops and livestock, pesticides have also had direct benefits to human health. It is estimated that since 1945, the use of pesticides has prevented the deaths of around seven million people by killing pests that carry or transmit diseases. Although there are benefits to the use of pesticides, there have also been many problems associated with their use. Pesticides do not always stay in the location where they are applied. They are mobile in the environment and often move through water, air and soil. The problem with pesticide mobility is that when they travel, the pesticides come in contact with other organisms and can cause harm. Pesticides have also been shown to disrupt the balance of an ecosystem. In many situations when a pesticide is used, it also kills non-pest organisms. This can drastically alter the natural balance of the ecosystem. By removing non-pest organisms, the environment can be changed to favor the pest. In addition to causing harm to wildlife, pesticides that travel from their original location are known to cause harm to humans. Human exposure to pesticides has caused poisonings, the development of cancer and the deaths of between 20000 and 40000 people worldwide each year. Another major problem associated with pesticide use is bioaccumulation and biological magnification. Bioaccumulation is when a substance builds up in the body because the body does not have the proper mechanisms to remove it. Many synthetic pesticides are not able to be broken down. Once they enter the body of an organism, they are permanently stored in the body tissue.