Some Properties of the Basins of Attraction of the Newton’s Method for Simple Nonlinear Geodetic Systems

The research presented in this paper concerns the determination of the attraction basins of the Newton’s iterative method which was used to solve the non-linear systems of observational equations associated with the geodetic measurements. The authors considered simple observation systems corresponding to the intersections, or linear and angular resections, used in practice. The main goal was to investigate the properties of the sets of convergent in the initial points of the applied iterative method. An important issue regarding the possibility of automatic and quick selection of such points was also considered. Therefore, the answers to the questions regarding the geometric structure of the basins, their limitations, connectedness or self-similarity were sought. The research also concerned the iterative structures of the basins, i.e. maps of the number of iterations which are necessary to achieve the convergence of the Newton’s method. The determined basins were compared with the areas of convergence that result from theorems on the convergence of the Newton’s method, i.e. the conditions imposed on the eigenvalues and norms of the matrices of the studied iterative systems. One of the essential results of the research is the indication that the obtained basins of attraction contain areas resulting from the theoretical premises and their diameters can be comparable with the sizes of the analyzed geodetic structures. Consequently, in the analyzed cases it is possible to construct methods that enable quick selection of the initial starting points or automation of such selection. The paper also characterizes the global convergence mechanism of the Newton’s method for disconnected basins and, as a consequence, the non-local initial points, i.e. located far from the solution points.

Desiccation survival in Salmonella enterica, Escherichia coli and Enterococcus faecium related to initial cell concentration and cellular components

Salmonella enterica is well-known for its ability to survive and persist in low-moisture environments. Previous studies have indicated a link between the initial cell concentration and the population of Salmonella that survive upon desiccation and subsequent storage; however, how the initial cell concentration affects survival is unknown. This study examined the basis of this phenomena and whether it occurred in other microorganisms, specifically Shiga toxigenic Escherichia coli (STEC), and Enterococcus faecium . Salmonella, STEC, and E. faecium were grown as lawns on TSAYE and harvested using buffered peptone water (BPW). To determine recovery at different initial cell levels, cultures were diluted to 9, 7, and 5 log CFU/mL and applied to filters. Filters were dried for 24 h, then stored for 28 d at 25°C/33% RH. During storage, cells were recovered from filters using BPW and cultivated on TSAYE. Both Salmonella and E. coli , but not E. faecium , showed non-proportional recovery. Less viability remained with lower initial starting population after 24 h desiccation such that ≥10 log CFU/mL were recovered when 11 log CFU/mL was desiccated, but <3 log CFU/mL were recovered when 5 log CFU/mL was desiccated. Once dried, persistence did not appear affected by initial cell concentration. When dead cells (heat-treated) were added to the diluent, recovery of Salmonella was proportional with respect to the initial cell concentration. To further examine the response on desiccation, Salmonella was diluted in BPW containing one of 11 different test cell components related to quorum sensing or known to affect desiccation resistance to assess recovery and persistence. Of the 11 additions only cell debris fractions, cell-free extract, and peptidoglycan improved recovery of Salmonella . Desiccation survival appears related to cell wall components, however, the exact mechanism affecting survival remains unknown.

The trilogy of `love` beyond beauty, truth and drama

The initial starting point in directing and choreographic process in developing the `Love`trilogy: the core and heart of the idea behind creating a performative trilogy concerning the theme of love has been the reflecting studies of the performers involved in the creational process. These spectacular and performative sequences begin with `Savage/Love`- the first part of the trilogy desgined in 2019. Starting from the desire in exploring the unfamiliar professional aspects of dance-theater and contemporary dance techniques, the personal experiences of the performers become the leading sources of inspiration in the directing and choreographic process. The middle part of the trilogy will be shaped as a performative show entitled `August Rush`. The last and third part will organically become a performative solo- `In/UnLoved bodies`.

Genus-Specific Carbon Fixation Activity Measurements Reveal Distinct Responses to Oxygen Among Hydrothermal Vent Campylobacteria

Molecular surveys of low temperature deep-sea hydrothermal vent fluids have shown that Campylobacteria (prev. Epsilonproteobacteria ) often dominate the microbial community and that three genera - Arcobacter , Sulfurimonas and Sulfurovum - frequently coexist. In this study, we used replicated radiocarbon incubations of deep-sea hydrothermal fluids to investigate activity of each genus under three experimental conditions. To quantify genus-specific radiocarbon incorporation, we used newly designed oligonucleotide probes for Arcobacter , Sulfurimonas , and Sulfurovum to quantify their activity using catalyzed-reporter deposition fluorescence in-situ hybridization (CARD-FISH) combined with fluorescence-activated cell sorting. All three genera actively fixed CO 2 in short-term (∼ 20 h) incubations, but responded differently to the additions of nitrate and oxygen. Oxygen additions had the largest effect on community composition, and caused a pronounced shift in community composition at the amplicon sequence variant (ASV) level after only 20 h of incubation. The effect of oxygen on carbon fixation rates appeared to depend on the initial starting community. The presented results support the hypothesis that these chemoautotrophic genera possess functionally redundant core metabolic capabilities, but also reveal finer-scale differences in growth likely reflecting adaptation of physiologically-distinct phylotypes to varying oxygen concentrations in situ . Overall, our study provides new insights into how oxygen controls community composition and total chemoautotrophic activity, and underscores how quickly deep-sea vent microbial communities respond to disturbances. Importance: Sulfidic environments worldwide are often dominated by sulfur-oxidizing, carbon-fixing Campylobacteria . Environmental factors associated with this group's dominance are now understood, but far less is known about the ecology and physiology of members of subgroups of chemoautotrophic Campylobacteria . In this study, we used a novel method to differentiate the genus-specific chemoautotrophic activity of three subtypes of Campylobacteria. In combination with evidence from microscopic counts, chemical consumption/production during incubations, and DNA-based measurements, our data show that oxygen concentration affects both community composition and chemoautotrophic function in situ . These results help us better understand factors controlling microbial diversity at deep-sea hydrothermal vents, and provide first-order insights into the ecophysiological differences between these distinct microbial taxa.

CTNI-26. PHASE 2 STUDY OF DIANHYDROGALACTITOL (VAL-083) IN PATIENTS WITH MGMT-UNMETHYLATED, BEVACIZUMAB-NAÏVE GLIOBLASTOMA IN THE RECURRENT AND ADJUVANT SETTING

Current standard-of-care for glioblastoma (GBM) includes surgery followed by concurrent therapy with radiation and temozolomide (TMZ) followed by adjuvant TMZ. Almost all GBM patients experience recurrent/progressive disease despite upfront standard-of-care treatment, with a median survival of 3-9 months after recurrence. Unmethylated promoter for O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for TMZ-resistance and is correlated with poor patient prognosis. VAL-083 is a bi-functional DNA-targeting agent which rapidly induces interstrand DNA cross-links at N7-guanine inducing double-strand breaks causing cell death and acts independently of MGMT DNA repair. This trial is an open-label two-arm biomarker-driven phase 2 clinical trial in MGMT-unmethylated, bevacizumab-naïve GBM patients with either recurrent (Group 1) or newly diagnosed GBM requiring adjuvant therapy after chemo-irradiation with temozolomide (Group 2). Patients receive VAL-083 IV at 30 or 40 mg/m2/d on days 1, 2, and 3 of a 21-day cycle. The primary objective of this study is to determine the effect of VAL-083 on median overall survival (mOS) in MGMT-unmethylated recurrent GBM patients (Group 1); and progression-free survival (PFS) in newly diagnosed GBM patients requiring adjuvant therapy after chemo-irradiation with temozolomide (Group 2), compared to historical controls in both groups. Tumor response is assessed by MRI every 42 days, using RANO criteria. The initial starting dose in this study was 40 mg/m2/d on days 1, 2, and 3 of a 21-day cycle, which was subsequently reduced to 30 mg/m2/d to improve tolerance due to myelosuppression. As of May 2021, Group 1 (Recurrent GBM) is fully enrolled: 35 evaluable patients have received 40 mg/m2/d and 48 evaluable patients have received 30 mg/m2/d VAL-083. In the adjuvant setting (Group 2), 35 evaluable patients have been enrolled (30 mg/m2/day). Enrollment, safety data and efficacy updates will be presented at the meeting. Clinicaltrials.gov identifier: NCT02717962.

Physical-and-chemical calculations of safe mode of propane transportation

The key criteria used to assess fire-and-explosive hazard of any facility are: flash point, self-ignition temperature and minimum ignition energy. This article addresses how fire-and-explosive hazard criteria can be used to forecast emergency situations while transporting great quantities of flammable substance – propane, based upon ambient environment temperature. Calculations that were made have led to a conclusion that fire-and-explosive safety concentration mode for propane handling will be: lower concentration value is equal to 1.27 % or under than that value; upper concentration value is equal to 13.96 % or greater than that value. When selecting safe transportation and storage conditions for self-igniting combustible substances, great attention is given to relationship between environment, mass of substance transported and time-period to spontaneous ignition. For propane, the safe self-ignition temperature is deemed to be less than 360°C. Calculations for theoretical experiment regarding propane transportation were made based upon three critical temperature values: 1) 25 °C+10 °C - initial starting point when ambient temperature is 25 °C (roadway temperature is disregarded because ambient temperature is not high enough); 2) 60 °C+10 °C – point of arrival where ambient temperature is 60 °C; 3) 470 °C – propane self-ignition temperature. This helped us to figure out that propane can be stored and transported safely if the minimal electric ignition source is under 4*10−6 Joule.

Factors influencing procurement behaviour and decision-making: an exploratory qualitative study in a UK healthcare provider

Background In 2016 the UK Department of Health and Social Care published the results of a comprehensive review of efficiency in hospitals, identifying “unwarranted variation” in procurement (or purchasing) practices for materials, supplies and devices. Addressing this variation in materials and supplies procurement practice has been identified as particularly important for creating efficiencies in health service delivery. However, little is known about the behaviour and experiences of front-line individuals who make these procurement decisions, which has implications for the development of strategies to improve efficiency. The objective of this study is to improve understanding of the factors influencing procurement behaviour and decisions among requisitioners who use an internal electronic procurement portal for medical supplies and equipment, and identify areas where efficiency could be improved. Methods Qualitative semi-structured individual interview study, following approximately 70 h of exploratory observations on site. The study context was a large London National Health Service (NHS) healthcare provider (the Trust), where we focussed primarily on purchases managed by a large hospital. Participants were drawn from requisitioners from multiple directorates across the Trust (n = 15; of these n = 2 clinical staff members, n = 13 non-clinical). Results Four factors stood out in our analysis as directly affecting procurement decisions: (1) a high level of variation in electronic purchasing and inventory management procedures throughout the Trust, (ii) an inaccurate and cumbersome search facility on the internal electronic procurement platform, exacerbated by poor IT skills training and support (iii) an inefficient purchase approvals system and (iv) multiple working sites and cluttered environments. We observed that these factors led requisitioners to employ a variety of strategies or so-called ‘workarounds’ to overcome the challenges they encountered, including stockpiling, relying on internal and supplier relationships, by-passing procedures to save time, purchasing outside existing agreements to save cost, and (re) delegating purchasing responsibilities among requisitioner staff - which both addressed and created difficulties. Conclusions Working with the assumption that staff ‘workarounds’ indicate where main issues lie, we offer four possible explanations to why they occur: (a) to maintain services and prepare for future care requirements, (b) to save on costs for the organisation, (c) to develop skills and development in purchasing and (d) to break silos and work collaboratively. These four explanations help provide initial starting points for improving efficiencies in health supplies’ procurement processes.

High Crystal Number Densities From Mechanical Damage

Laboratory experiments investigating syn-eruptive crystallization are fundamental for interpreting crystal and vesicle textures in pyroclasts. Previous experiments have advanced our understanding by varying decompression and cooling pathways, volatile components, and melt composition. However, they have largely failed to produce the high crystal number densities seen in many cryptodome and dome samples. This is feasibly due to the relatively simple decompression pathways employed in experimental studies. In this study, we approach the problem by exploring non-linear decompression pathways. We present two series of experiments: (1) decompression from low initial starting pressure and (2) a compression-and-release step after the initial decompression. The purpose of each series was to simulate (1) decompression of magma that stalls during ascent and (2) pressure cycling that occurs in non-erupted magma during episodic explosive activity. The experiments were carried out on a synthetic rhyodacite (SiO2 = 69 wt%) held initially at 50 MPa and 885°C then decompressed at rates of 0.026 and 0.05 MPa s−1 to 10 MPa A subset of experiments was then subjected to a compression step to 110 MPa followed by near-instantaneous release back to 10 MPa. A substantial volume fraction of dendritic microlites (ϕxtl = 0.27–0.32, Na = 4.79 × 103 mm–2) formed during the initial hold at 50 MPa; additional crystallization during subsequent decompression to ≥ 10 MPa was minimal, as evidenced by only small increases in crystallinity (ϕxtl = 0.28–0.33) and comparable crystal number densities (4.11–7.81 × 103 mm–2). Samples that underwent recompression followed by a second decompression showed no increase in crystal volume fraction but did show extensive disruption of the initial dendritic, box-work microlite structures that produced high number densities (Na = 43.5–87.2 × 103 mm–2) of small individual crystals. The disruption was driven by a combination of rapid vesiculation, expansion and resulting shear along the capsule walls. From these results, we suggest that high crystal number densities may be a signature of rapid deformation occurring after magma stalling in the subsurface, perhaps related to pressure cycling and accompanying rapid changes in vesicularity during repeated small and shallow-sourced explosions. We compare our experiments to pyroclasts from shallow intrusions that preceded the 18 May 1980 eruption of Mount St Helens. These pyroclasts were erupted both prior to 18 May, during episodic precursory explosive activity, and by the 18 May initial lateral blast. The pattern of precursory activity indicates multiple episodes of pressurization (prior to explosive events) and rapid decompression (during explosive events) that we use to illustrate the significance of our experimental results.

Model-Free Approach for the Configurational Analysis of Marine Natural Products

The NMR-based configurational analysis of complex marine natural products is still not a routine task. Different NMR parameters are used for the assignment of the relative configuration: NOE/ROE, homo- and heteronuclear J couplings as well as anisotropic parameters. The combined distance geometry (DG) and distance bounds driven dynamics (DDD) method allows a model-free approach for the determination of the relative configuration that is invariant to the choice of an initial starting structure and does not rely on comparisons with (DFT) calculated structures. Here, we will discuss the configurational analysis of five complex marine natural products or synthetic derivatives thereof: the cis-palau’amine derivatives 1a and 1b, tetrabromostyloguanidine (1c), plakilactone H (2), and manzamine A (3). The certainty of configurational assignments is evaluated in view of the accuracy of the NOE/ROE data available. These case studies will show the prospective breadth of application of the DG/DDD method.

Cultures and cures: neurodiversity and brain organoids

Background Research with cerebral organoids is beginning to make significant progress in understanding the etiology of autism spectrum disorder (ASD). Brain organoid models can be grown from the cells of donors with ASD. Researchers can explore the genetic, developmental, and other factors that may give rise to the varieties of autism. Researchers could study all of these factors together with brain organoids grown from cells originating from ASD individuals. This makes brain organoids unique from other forms of ASD research. They are like a multi-tool, one with significant versatility for the scope of ASD research and clinical applications. There is hope that brain organoids could one day be used for precision medicine, like developing tailored ASD drug treatments. Main body Brain organoid researchers often incorporate the medical model of disability when researching the origins of ASD, especially when the research has the specific aim of potentially finding tailored clinical treatments for ASD individuals. The neurodiversity movement—a developmental disability movement and paradigm that understands autism as a form of natural human diversity—will potentially disagree with approaches or aims of cerebral organoid research on ASD. Neurodiversity advocates incorporate a social model of disability into their movement, which focuses more on the social, attitudinal, and environmental barriers rather than biophysical or psychological deficits. Therefore, a potential conflict may arise between these perspectives on how to proceed with cerebral organoid research regarding neurodevelopmental conditions, especially ASD. Conclusions Here, we present these perspectives and give at least three initial recommendations to achieve a more holistic and inclusive approach to cerebral organoid research on ASD. These three initial starting points can build bridges between researchers and the neurodiversity movement. First, neurodiverse individuals should be included as co-creators in both the scientific process and research communication. Second, clinicians and neurodiverse communities should have open and respectful communication. Finally, we suggest a continual reconceptualization of illness, impairment, disability, behavior, and person.