jimnoneill/paper-to-field-training huggingface dataset:
New patient-derived models of castrate-sensitive and castrate-resistant prostate cancer.

151 Background: There are fewer preclinical models of prostate cancer compared to other common tumours. New models that represent the diverse features of castrate-sensitive and castration-resistant prostate cancer (CRPC) are required for thorough preclinical testing of novel treatments. Therefore, the goal of the Melbourne Urological Research Alliance (MURAL) is to develop patient-derived xenografts (PDXs) spanning the clinical trajectory of prostate cancer. Methods: We grafted &gt;200 surgery, biopsy or rapid autopsy samples into testosterone-supplemented or castrated male NSG mice. Actively growing tumours were serially transplanted or grown as explants or organoids. PDXs were analysed using RNAseq, targeted genomic sequencing and histopathology review. Results: We previously reported 4 serially transplantable PDXs (Lawrence, et al., 2018, European Urology). Now we have established ~30 additional models spanning treatment naïve primary disease to CRPC. PDXs of CRPC were often from soft tissue metastases of patients who had failed docetaxel, cabazitaxel, enzalutamide, abiraterone and other contemporary treatments. Accordingly, they had diverse mechanisms of resistance, including AR mutations, genomic structural rearrangements, gene amplifications and expression of AR variants. In addition, several PDXs had AR-null phenotypes, including small cell prostate cancer. All PDXs closely reflected the genomic, transcriptomic and histopathological characteristics of the original patient tumours. As renewable sources of tissue, the PDXs could also be grown as ex vivo slice cultures and in vitro organoids, providing complementary models with different timescales and endpoints. Conclusions: We have developed a new collection of castrate-sensitive and castrate-resistant PDXs of prostate cancer, providing diverse tumours for preclinical testing of candidate treatments.

Topic: Prostate Cancer Treatment and Research
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Book No. 424 – T24S, R10E - Survey Showing Road R/W Location in Sections 26, 25 &amp; 36 - Mar. 1977

Map of Township 24S, Range 10E, subdivided for assessment purposes in Monterey County, California – Mar. 1976.

Topic: Spider Taxonomy and Behavior Studies
Subfield: Genetics
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
THE IMPACT OF HAJJ AND UMRAH ON ECONOMIC GROWTH IN SAUDI ARABIA

The objective of this research is to analyze the impact of Hajj and Umrah on the economic growth in the Kingdom of Saudi Arabia, in order to maximize the economic sectors’ returns in the light of the Kingdom’s vision objectives to diversify sources of income, launching the capabilities of non-oil sectors and stimulating economic growth. The descriptive analytical approach is adopted to analysis and interpret the research subject. The Econometrics approach is utilized in estimating the impact of Hajj and Umrah on the economic growth in the Kingdom during the period 1991-2017. In order to achieve the research objective, several tests were employed (Dickey–Fuller unit root test, Johansen cointegration test, Granger causality, and vector error correction model). The results indicate that there are no short-term integration relationships between the study variables. Meanwhile, a long-term integrated relationship is existed. There is a positive unidirectional relationship running from international tourists' spending to growth, and from economic growth to airline movement. Tourism employment adversely affects growth Economic level with a low level of significance. The researcher concludes that the number of domestic pilgrims and tourism investment have no significant relationship with the economic growth in the Kingdom, although this investment affects tourism expenditure, while influenced by employment size. In conclusion, the importance of the tourism sector and the need to pay attention to Hajj and Umrah from the economic perspective is recognized. This in order to promote development efforts and stimulate growth, especially if the public and private expenditure is rationalized and allocated efficiently and effectively. In addition, providing integrated services and attractive facilities, and the resettlement of industries and jobs that directly serve the travel and hospitality and those indirectly associated with them are required.
Keywords: Hajj, Umrah, Tourism, Economic Growth, Saudi Arabia.

Topic: Islamic Finance and Banking Studies
Subfield: Accounting
Field: Business, Management and Accounting
Domain: Social Sciences
Lanthanide-based molecular alloys with hydroxyterephthalate: a versatile system

Reactions in water between lanthanide chlorides and the di-sodium salt of 2-hydroxyterephthalic acid (H<sub>2</sub>hbdc) lead to six families of lanthanide-based coordination polymers depending on the lanthanide ion and the crystal growth method.

Topic: Metal-Organic Frameworks: Synthesis and Applications
Subfield: Inorganic Chemistry
Field: Chemistry
Domain: Physical Sciences
Observational determination of the adiabatic index in the quiet time plasma sheet

We show that in the quiet time (AE&lt;100nT) central plasma sheet the plasma density and temperature are, in general, anticorrelated. This indicates that the adiabatic index is less than 1 and that earthward converting plasma cools as it is compressed. We do not have a satisfactory explanation for this surprising result.

Topic: Magnetic confinement fusion research
Subfield: Nuclear and High Energy Physics
Field: Physics and Astronomy
Domain: Physical Sciences
Models of Demand for Capital in Agriculture of Kazakhstan

The financing of agricultural producers is one of the most acute problems along the entire scope of economic reforms in Kazakhstan. The issue is: What kind of financial sources could maintain the development of agricultural production? Internal sources such as profit, depreciation capital, and various reserve and insurance funds can not be considered as a key financial base. State financial support of agriculture in Kazakhstan (which plays a significant role in the most developed countries), is episodic in nature, small in size and typically does not reach the recipients. In these circumstances, a potential supplier of financial and investment resources could be a banking system and such non-banking credit institutions as credit cooperatives. In this study capital demand functions were used to analyze an influence of a number of factors on capital demand in agriculture. The results of simulations suggest the most significant factors are a rental price of capital and a price of production output. Major determinant of credit demand is collateral, that is, size of arable land possessed by the agricultural enterprise and a cost of equipment. Despite subsidized credit plays significant role existing corruption in this sphere decreases capital demand and investment opportunities for agricultural producers.

Topic: Agricultural risk and resilience
Subfield: Soil Science
Field: Agricultural and Biological Sciences
Domain: Life Sciences
Effect of random hydrodynamic inhomogeneities on low-frequency sound propagation loss in shallow water.

Low-frequency (100–500 Hz) sound propagation loss on the US Atlantic continental shelf and in the Barents Sea in the presence of stochastic surface waves, and for the US Atlantic shelf also in the presence of internal waves, is studied for the range of up to 150 km by means of numerical simulations. Surface waves simulations are carried out with Pierson–Neumann spectrum. Internal wave field realizations are modeled according to frequency spectrum of thermocline displacements that were recorded in Shallow Water’06 experiment. Qualitative difference between sound propagation loss behavior on the US Atlantic shelf and in the Barents Sea is demonstrated for summertime conditions even without random inhomogeneities. It is shown that whereas internal waves, on average, have a weak effect on propagation loss, surface waves result in its considerable increase in both areas under wintertime conditions with a wind speed of more than 9 m/s. [The authors wish to acknowledge and thank Dr. J. F. Lynch for discussing this work. The work was supported by the Russian Foundation for Basic Research Project 08-02-00283 and by the Civilian Research and Development Foundation Project No. REC 010.]

Topic: Underwater Acoustics Research
Subfield: Oceanography
Field: Earth and Planetary Sciences
Domain: Physical Sciences
Changes in the proteome of the cadmium-tolerant bacteria <i>Cupriavidus taiwanensis</i> KKU2500-3 in response to cadmium toxicity

Cupriavidus taiwanensis KKU2500-3 is a cadmium (Cd)-tolerant bacterial strain that was previously isolated from rice fields contaminated with high levels of Cd. In 500 μmol/L CdCl 2 , the KKU2500-3 strain grew slower and with a more prolonged lag-phase than when grown in the absence of Cd. A proteomic approach was used to characterize the protein expression in the Cd-tolerant bacteria C. taiwanensis KKU2500-3 during growth under Cd stress. When compared with the untreated cells, a total of 982 differentially expressed protein spots were observed in the CdCl 2 -treated cells, and 59 and 10 spots exhibited &gt;2- and &gt;4-fold changes, respectively. The level of up- and downregulation varied from 2.01- to 11.26-fold and from 2.01- to 5.34-fold, respectively. Of the 33 differentially expressed protein spots analyzed by MALDI TOF MS/MS, 19 spots were successfully identified, many of which were involved in stress responses. The most highly upregulated protein (+7.95-fold) identified was the chaperone GroEL, which indicated that this factor likely contributed to the bacterial survival and growth in response to Cd toxicity. Detection of the downregulated protein flagellin (–3.52-fold) was consistent with the less effective ATP-mediated and flagella-driven motility. The flagella-losing cells were also observed in the Cd-treated bacteria when analyzed by scanning electron microscopy. Thus, the Cd-stressed cells may downregulate pathways involving ATP utilization in favor of other mechanisms in response to Cd toxicity. When the KKU2500-3 strain was grown in the presence of Cd, H 2 S was not detected, suggesting a possible role of the sulfur in precipitation with Cd. Apart from a general response, no specific process could be determined using the present proteomic approach. However, the potential role of protein folding-mediated GroEL, flagella-mediated motility and CdS biotransformation in Cd toxicity response observed in this study as well as the extent of Cd-tolerant mechanisms using other methods could facilitate the future application of this strain in addressing Cd environmental contamination.

Topic: Chromium effects and bioremediation
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Antibiotics and UV Radiation Induce Competence for Natural Transformation in<i>Legionella pneumophila</i>

ABSTRACT Natural transformation by competence is a major mechanism of horizontal gene transfer in bacteria. Competence is defined as the genetically programmed physiological state that enables bacteria to actively take up DNA from the environment. The conditions that signal competence development are multiple and elusive, complicating the understanding of its evolutionary significance. We used expression of the competence gene comEA as a reporter of competence development and screened several hundred molecules for their ability to induce competence in the freshwater living pathogen Legionella pneumophila . We found that comEA expression is induced by chronic exposure to genotoxic molecules such as mitomycin C and antibiotics of the fluoroquinolone family. These results indicated that, in L. pneumophila , competence may be a response to genotoxic stress. Sunlight-emitted UV light represents a major source of genotoxic stress in the environment and we found that exposure to UV radiation effectively induces competence development. For the first time, we show that genetic exchanges by natural transformation occur within an UV-stressed population. Genotoxic stress induces the RecA-dependent SOS response in many bacteria. However, genetic and phenotypic evidence suggest that L. pneumophila lacks a prototypic SOS response and competence development in response to genotoxic stress is RecA independent. Our results strengthen the hypothesis that competence may have evolved as a DNA damage response in SOS-deficient bacteria. This parasexual response to DNA damage may have enabled L. pneumophila to acquire and propagate foreign genes, contributing to the emergence of this human pathogen.

Topic: Legionella and Acanthamoeba research
Subfield: Endocrinology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Spatial organization of RNA polymerase and its relationship with transcription in <i>Escherichia coli</i>

Recent studies have shown that RNA polymerase (RNAP) is organized into distinct clusters in Escherichia coli and Bacillus subtilis cells. Spatially organized molecular components in prokaryotic systems imply compartmentalization without the use of membranes, which may offer insights into unique functions and regulations. It has been proposed that the formation of RNAP clusters is driven by active ribosomal RNA (rRNA) transcription and that RNAP clusters function as factories for highly efficient transcription. In this work, we examined these hypotheses by investigating the spatial organization and transcription activity of RNAP in E. coli cells using quantitative superresolution imaging coupled with genetic and biochemical assays. We observed that RNAP formed distinct clusters that were engaged in active rRNA synthesis under a rich medium growth condition. Surprisingly, a large fraction of RNAP clusters persisted in the absence of high rRNA transcription activities or when the housekeeping σ 70 was sequestered, and was only significantly diminished when all RNA transcription was inhibited globally. In contrast, the cellular distribution of RNAP closely followed the morphology of the underlying nucleoid under all conditions tested irrespective of the corresponding transcription activity, and RNAP redistributed into dispersed, smaller clusters when the supercoiling state of the nucleoid was perturbed. These results suggest that RNAP was organized into active transcription centers under the rich medium growth condition; its spatial arrangement at the cellular level, however, was not dependent on rRNA synthesis activity and was likely organized by the underlying nucleoid.

Topic: RNA Research and Splicing
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Etyczność w przestrzennych działaniach innowacyjnych administracji publicznej

Changes in the management of the public administration are taking place in a very turbulent manner. The initial solutions for building a quality culture of the public organizations are supported by implementation of systems designed to combat corruption. Code of ethics for public officials and employees is getting better understood and the public officials themselves tend to constitute new ethics rules now. Additionally they have started to organize activities in order to eliminate unethical behavior. These innovative solutions of a spatial character are covering the entire country. This paper presents ethical problems, which cannot be solved by using only law regulations. It also presents an analysis of the implemented innovative measures like standards in public life, declarations on ethic, codes of ethics and ethics audits. These measures also include system solutions complaint with quality requirements.The most innovative solutions in the form of System of Counteracting Corruption Threats (System Przeciwdziałania Zagrożeniom Korupcyjnym), which contains 27 requirements, are well implemented in the public institutions because they have the same structure as the requirements of ISO 9001.

Topic: Polish Law and Legal System
Subfield: Political Science and International Relations
Field: Social Sciences
Domain: Social Sciences
Effect of nucleon exchange on projectile multifragmentation

Multifragmentation of quasiprojectiles was studied in reactions of 28 Si beam with 112 Sn and 124 Sn targets at projectile energies 30 and 50 MeV/nucleon. The quasiprojectile observables were reconstructed using isotopically identified charged particles with Zf ≤ 5 detected at forward angles. The nucleon exchange between projectile and target was investigated using isospin and excitation energy of reconstructed quasiprojectile. For events with total reconstructed charge equal to the charge of the beam ( Ztot = 14) the influence of beam energy and target isospin on neutron transfer was studied in detail. Simulations employing subsequently model of deep inelastic transfer, statistical model of multifragmentation and software replica of FAUST detector array were carried out. A concept of deep inelastic transfer provides good description of production of highly excited quasiprojectiles. The isospin and excitation energy of quasiprojectile were described with good overall agreement. The fragment multiplicity, charge and isospin were reproduced satisfactorily. The range of contributing impact parameters was determined using backtracing procedure. PACS numbers: 25.70.Mn, 25.70.Pq, 25.70.-z

Topic: Nuclear physics research studies
Subfield: Nuclear and High Energy Physics
Field: Physics and Astronomy
Domain: Physical Sciences
Q1VA, a Synthetic Chalcone, Induces Apoptosis and Decreases Invasion on Primary Culture of Human Glioblastoma

Glioblastoma (GBM) is the most commonly occurring type of primary tumor of the central nervous system (CNS) and is considered the worst type of glioma. Despite the current standard treatment for newly diagnosed GBM, which involves surgery followed by chemotherapy with temozolomide (TMZ) and radiation therapy, the average survival time for patients with GBM is only about 15 months. This is due to GBM’s tendency to recur, its high proliferative rates, its ability to evade apoptosis, and its ability to invade healthy tissue. Therefore, it is crucial to explore new treatment options for GBM. This study investigated the potential anticancer activities of a new series of synthetic chalcones, which are natural compounds found in the biosynthesis of flavonoids in plants. Primary cell culture of glioblastoma (GBM1) from surgical resection was used to evaluate the effects of synthetic chalcones on viability, cell death, reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), cell cycle, and invasion. One chalcone, Q1VA (at concentrations of 10, 50, and 100 μM for 24 h) induced cytotoxicity by increasing apoptosis levels and depolarizing the mitochondrial membrane, as evidenced by a TMRE assay. Further analysis using the molecular fluorescent probe H2DCFDA indicated that the increased levels of reactive oxygen species (ROS) might be linked to altered mitochondrial membrane potential and cell death. Furthermore, viable cells were observed to be delayed in the cell cycle, primarily in the M phase, and the invasion process was reduced. The findings of this study indicate that Q1VA is a potential adjuvant therapeutic agent for GBM due to its significant antitumor effects. If its safety and efficacy can be confirmed in animal models, Q1VA may be considered for clinical trials in humans. However, additional research is required to determine the optimal dosage, treatment schedule, and potential side effects of Q1VA.

Topic: Cancer therapeutics and mechanisms
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities

Surgical interposition of distal ileum into the proximal jejunum is a bariatric procedure that improves the metabolic syndrome. Changes in intestinal and hepatic physiology after ileal interposition (transposition) surgery (IIS) are not well understood. Our aim was to elucidate the adaptation of the interposed ileum, which we hypothesized, would lead to early bile acid reabsorption in the interposed ileum, thus short circuiting enterohepatic bile acid recycling to more proximal bowel segments. Rats with diet-induced obesity were randomized to IIS, with 10 cm of ileum repositioned distal to the duodenum, or sham surgery. A subgroup of sham rats was pair-fed to IIS rats. Physiological parameters were measured until 6 wk postsurgery. IIS rats ate less and lost more weight for the first 2 wk postsurgery. At study completion, body weights were not different, but IIS rats had reversed components of the metabolic syndrome. The interposed ileal segment adapted to a more jejunum-like villi length, mucosal surface area, and GATA4/ILBP mRNA. The interposed segment retained capacity for bile acid reabsorption and anorectic hormone secretion with the presence of ASBT and glucagon-like-peptide-1-positive cells in the villi. IIS rats had reduced primary bile acid levels in the proximal intestinal tract and higher primary bile acid levels in the serum, suggesting an early and efficient reabsorption of primary bile acids. IIS rats also had increased taurine and glycine-conjugated serum bile acids and reduced fecal bile acid loss. There was decreased hepatic Cyp27A1 mRNA with no changes in hepatic FXR, SHP, or NTCP expression. IIS protects against the metabolic syndrome through short-circuiting enterohepatic bile acid recycling. There is early reabsorption of primary bile acids despite selective “jejunization” of the interposed ileal segment. Changes in serum bile acids or bile acid enterohepatic recycling may mediate the metabolic benefits seen after bariatric surgery.

Topic: Clinical Nutrition and Gastroenterology
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Resolution and remission in schizophrenia: getting well and staying well

Summary Remission is a new research outcome indicating long-term wellness. Remission not only sets a standard for minimal severity of symptoms and signs (resolution); it also sets a standard for how long symptoms and signs need to remain at this minimal level (6 months). Individuals who achieve remission from schizophrenia have better subjective well-being and better functional outcomes than those who do not. Research suggests that remission can be achieved in 20–60% of people with schizophrenia. There is some evidence of the usefulness of remission as an outcome indicator for clinicians, service users and their carers. This article reviews the literature on remission in schizophrenia and asks whether it could be a useful clinical standard of well-being and a foundation for functional improvement and recovery.

Topic: Schizophrenia research and treatment
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences