Genistein increases epidermal growth factor receptor signaling and promotes tumor progression in advanced human prostate cancer.

Genistein is an isoflavone found in soy, and its chemo-preventive and -therapeutic effects have been well established from in vitro studies. Recently, however, its therapeutic actions in vivo have been questioned due to contradictory reports from animal studies, which rely on rodent models or implantation of cell lines into animals. To clarify in vivo effects of genistein in advanced prostate cancer patients, we developed a patient-derived prostate cancer xenograft model, in which a clinical prostatectomy sample was grafted into immune deficient mice. Our results showed an increased lymph node (LN) and secondary organ metastases in genistein-treated mice compared to untreated controls. Interestingly, invasive malignant cells aggregated to form islands/micrometastasis only in the secondary organs of the genistein-treated groups, not in the untreated control group. To understand the underlying mechanism for metastatic progression, we examined cell proliferation and apoptosis on paraffin-sections. Immunohistological data show that tumors of genistein-treated groups have more proliferating and fewer apoptotic cancer cells than those of the untreated group. Our immunoblotting data suggest that increased proliferation and metastasis are linked to enhanced activities of tyrosine kinases, EGFR and its downstream Src, in genistein-treated groups. Despite the chemopreventive effects proposed by earlier in vitro studies, the cancer promoting effect of genistein observed here suggests the need for careful selection of patients and safer planning of clinical trials

Dokumentasjon av barns skapende prosesser: hvilke muligheter og utfordringer kan oppstå ved dokumentasjon av barns skapende prosesser?

I «Rammeplan for barnehagen- innhold og oppgaver» fra 2017 står det i kapittel 7 som omhandler barnehagen som pedagogisk virksomhet, blant annet om dokumentasjon. De skriver om hva hensikten med dokumentasjon er, og hvordan det kan synliggjøre om de oppgaver personalet gjør samsvarer og oppfyller kravene som er satt i barnehageloven og rammeplanen. Videre skriver de om de etiske sidene ved dokumentasjon av barn. «Barn har rett til vern om sin personlige integritet. Et etisk perspektiv skal derfor ligge til grunn ved dokumentasjon av barnegruppen og enkeltbarn» (Kunnskapsdepartementet, 2017, s. 39). Som barnehagelærer har man et ansvar om å oppfylle de krav som er nedfelt i styringsdokumentene, men hvordan opplever barna å bli tatt bilde av var noe av det jeg ønsket å utforske i tilknytning denne oppgaven. Ettersom denne oppgaven skal bygge på kunnskap knyttet til fordypningsemnet og pedagogikkfaget ble det naturlig å prøve ulike vinklinger med større vekt på fordypningsemnet mitt: musikk, drama og kunst og håndverk. Jeg ønsket å knytte det til kunst og håndverk ettersom det er et av de fagene jeg har følt meg trygg i på skolen og i barnehagen. I min tid som vikar og under praksisperiodene mine i barnehagen har jeg følt det naturlig å skape ulike uttrykk sammen med barna. Enten det er i form av tegning og maling, leire eller landart. Med dette i bakhodet under veiledning og selvstendig arbeid ble tema valgt, dokumentasjon av barns skapende prosesser. Å formulere problemstillingen min var en prosess som gikk over lengre tid. Dette var fordi jeg hadde et ønske om å utforske hvordan pedagogisk leder ivaretar barns personvern. Jeg visste ikke hva jeg la i begrepet personvern eller hvordan jeg skulle gå frem for å finne ut av dette. Det var først under veiledning at jeg ble stilt de riktige spørsmålene som gjorde at vi kom frem til det jeg egentlig var ute etter å utforske, dokumentasjon av barns skapende prosesser. Med et kritisk blikk har jeg opplevd at det stadig er de todimensjonale uttrykkene som bli dokumentert i barnehagen. Et eksempel på dette er da vi jobbet med stasjonsarbeid på en avdeling i barnehagen. Det som ble dokumentert av en medarbeider var de uttrykkene barna malte, disse ble tatt bilde av og hengt opp i barnehagens garderobe for foreldrene til å se. På en annen stasjon var det modelleire. Her lagde barna sine uttrykk, og når tiden var ute på den aktiviteten ble alle uttrykkene most sammen til en stor klump. Det var ingen som hverken tok bilde av det eller noen som tok vare på uttrykkene og for eksempel satte dem til utstilling. Hva vil dette gjøre med barna som ikke opplever tegningen sin som like fin, eller som opplever større mestring ved å bygge LEGO eller med modelleire? Det jeg ønsker å utforske er hvilke tanker pedagogisk leder har omkring dette, både muligheter og utfordringer. Med dette som inspirasjon utviklet jeg problemstillingen: Hvilke muligheter og utfordringer kan oppstå ved dokumentasjon av barns skapende prosesser?publishedVersionBHBAC391

A Linear Programming Model for Renewable Energy Aware Discrete Production Planning and Control

Industrial production in the EU, like other sectors of the economy, is obliged to stop producing greenhouse gas emissions by 2050. With its Green Deal, the European Union has already set the corresponding framework in 2019. To achieve Net Zero in the remaining time, while not endangering one's own competitiveness on a globalized market, a transformation of industrial value creation has to be started already today. In terms of energy supply, this means a comprehensive electrification of processes and a switch to fully renewable power generation. However, due to a growing share of renewable energy sources, increasing volatility can be observed in the European electricity market already. For companies, there are mainly two ways to deal with the accompanying increase in average electricity prices. The first is to reduce consumption by increasing efficiency, which naturally has its physical limits. Secondly, an increasing volatile electricity price makes it possible to take advantage of periods of relatively low prices. To do this, companies must identify their energy-intensive processes and design them in such a way as to enable these activities to be shifted in time. This article explains the necessary differentiation between labor-intensive and energy intensive processes. A general mathematical model for the holistic optimization of discrete industrial production is presented. With the help of this MILP model, it is simulated that a flexibilization of energy intensive processes with volatile energy prices can help to reduce costs and thus secure competitiveness while getting it in line with European climate goals. On the basis of real electricity market data, different production scenarios are compared, and it is investigated under which conditions the flexibilization of specific processes is worthwhile

Digital Twin Fidelity Requirements Model for Manufacturing

The Digital Twin (DT), including its sub-categories Digital Model (DM) and Digital Shadow (DS), is a promising concept in the context of Smart Manufacturing and Industry 4.0. With ongoing maturation of its fundamental technologies like Simulation, Internet of Things (IoT), Cyber-Physical Systems (CPS), Artificial Intelligence (AI) and Big Data, DT has experienced a substantial increase in scholarly publications and industrial applications. According to academia, DT is considered as an ultra-realistic, high-fidelity virtual model of a physical entity, mirroring all of its properties most accurately. Furthermore, the DT is capable of altering this physical entity based on virtual modifications. Fidelity thereby refers to the number of parameters, their accuracy and level of abstraction. In practice, it is questionable whether the highest fidelity is required to achieve desired benefits. A literary analysis of 77 recent DT application articles reveals that there is currently no structured method supporting scholars and practitioners by elaborating appropriate fidelity levels. Hence, this article proposes the Digital Twin Fidelity Requirements Model (DT-FRM) as a possible solution. It has been developed by using concepts from Design Science Research methodology. Based on an initial problem definition, DT-FRM guides through problem breakdown, identifying problem centric dependent target variables (1), deriving (2) and prioritizing underlying independent variables (3), and defining the required fidelity level for each variable (4). This way, DT-FRM enables its users to efficiently solve their initial problem while minimizing DT implementation and recurring costs. It is shown that assessing the appropriate level of DT fidelity is crucial to realize benefits and reduce implementation complexity in manufacturing

Steroidogenesis in peripheral and transition zones of human prostate cancer tissue

The peripheral zone (PZ) and transition zone (TZ) represent about 70% of the human prostate gland with each zone having differential ability to develop prostate cancer. Androgens and their receptor are the primary driving cause of prostate cancer growth and eventually castration-resistant prostate cancer (CRPC). De novo steroidogenesis has been identified as a key mechanism that develops during CRPC. Currently, there is very limited information available on human prostate tissue steroidogenesis. The purpose of the present study was to investigate steroid metabolism in human prostate cancer tissues with comparison between PZ and TZ. Human prostate cancer tumors were procured from the patients who underwent radical prostatectomy without any neoadjuvant therapy. Human prostate homogenates were used to quantify steroid levels intrinsically present in the tissues as well as formed after incubation with 2 µg/mL of 17-hydroxypregnenolone (17-OH-pregnenolone) or progesterone. A Waters Acquity ultraperformance liquid chromatography coupled to a Quattro Premier XE tandem quadrupole mass spectrometer using a C18 column was used to measure thirteen steroids from the classical and backdoor steroidogenesis pathways. The intrinsic prostate tissue steroid levels were similar between PZ and TZ with dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), pregnenolone and 17-OH-pregnenolone levels higher than the other steroids measured. Interestingly, 5-pregnan-3,20-dione, 5-pregnan-3-ol-20-one, and 5-pregnan-17-ol-3,20-dione formation was significantly higher in both the zones of prostate tissues, whereas, androstenedione, testosterone, DHT, and progesterone levels were significantly lower after 60 min incubation compared to the 0 min control incubations. The incubations with progesterone had a similar outcome with 5-pregnan-3,20-dione and 5-pregnan-3-ol-20-one levels were elevated and the levels of DHT were lower in both PZ and TZ tissues. The net changes in steroid formation after the incubation were more observable with 17-OH-pregnenolone than with progesterone. In our knowledge, this is the first report of comprehensive analyses of intrinsic prostate tissue steroids and precursor-driven steroid metabolism using a sensitive liquid chromatography-mass spectrometry assay. In summary, the PZ and TZ of human prostate exhibited similar steroidogenic ability with distinction in the manner each zone utilizes the steroid precursors to divert the activity towards backdoor pathway through a complex matrix of steroidogenic mechanisms

(3R,4R)-2,5-Dioxo-1-m-tolyl-3,4-diyl diacetate

In the enanti­omerically pure title compound, C15H15NO6, the five-membered ring displays a twist conformation with the local axis through the N atom. The acetyl groups are perpendicular to the ring [dihedral angles 80.3 (1) and 89.3 (1)°] and project to opposite sides. The packing is governed by two weak C—H⋯O inter­actions, forming layers of mol­ecules parallel to the ab plane

Application of electrostatic separation and differential scanning calorimetry for microplastic analysis in river sediments

A method with the potential for comprehensive microplastic monitoring in river sediments is presented in this study. We introduce a novel combination of electrostatic separation, density separation, and differential scanning calorimetry (DSC). Currently, microplastic analysis in sediments is limited in terms of sample masses, processing time, and analytical robustness. This work evaluated a method to process large sample masses efficiently and still obtain robust results. Four particulate matrices, including commercial sands and river sediments, were spiked with PCL, LD-PE, and PET microplastic particles (63–200 µm). Samples with a mass of 100 g and 1,000 g (sand only) contained 75 mg of each microplastic. After electrostatic separation, the mass of sand samples was reduced by 98%. Sediment samples showed a mass reduction of 70–78%. After density separation, the total mass reduction of sediment samples was above 99%. The increased concentration of total organic carbon seems to have the highest impact on mass reduction by electrostatic separation. Nevertheless, the recovery of microplastic was independent of the particulate matrix and was polymer-specific. In 100 g samples, the average recovery rates for PCL, LD-PE, and PET were 74 ± 9%, 93 ± 9%, and 120 ± 18%, respectively. The recoveries of microplastic from 1,000 g samples were 50 ± 8%, 114 ± 9%, and 82 ± 11%, respectively. In scale up experiments, high recoveries of all microplastics were observed with a decrease in standard deviation. Moreover, the biodegradable polymer PCL could be used as an internal standard to provide quality assurance of the process. This method can overcome the current limitations of routine microplastic analysis in particulate matrices. We conclude that this method can be applied for comprehensive microplastic monitoring in highly polluted sediments. More studies on electrostatic separation and polymer-specific recovery rates in complex matrices are proposed

Mikroplastik in sächsischen Gewässern: 2020 -2021

Mikroplastikgehalte in Gewässersedimenten wurden erfolgreich mit einem neuen Analysenverfahren bestimmt. Erfahrungen bei der Probenahme, Aufbereitung und Analytik werden beschrieben. Erste Ergebnisse für sächsische Gewässer sind aufgeführt. Die Studie richtet sich in erster Linie an ein interessiertes Fachpublikum aus dem Bereich der Gewässeranalytik. Die Ergebnisse sächsischer Gewässer sind auch für die allgemeine Öffentlichkeit von Interesse. Redaktionsschluss: 30.09.202

Measuring care of the elderly: psychometric testing and modification of the Time in Care instrument for measurement of care needs in nursing homes

<p>Abstract</p> <p>Background</p> <p>Aging entails not only a decrease in the ability to be active, but also a trend toward increased dependence to sustain basic life functions. An important aspect for appropriately elucidating the individual's care needs is the ability to measure them both simply and reliably. Since 2006 a new version of the Time in Care needs (TIC-n) instrument (19-item version) has been explored and used in one additional municipality with the same structure as the one described in an earlier study.</p> <p>Methods</p> <p>The TIC-n assessment was conducted on a total of 1282 care recipients. Factor analysis (principal component) was applied to explore the construct validity of the TIC-n. Cronbach's alpha was calculated to test reliability and for each of the items remaining in the instrument after factor analysis, an inter-rater comparison was carried out on all recipients in both municipalities. Independently of each other, a weighted Kappa (K_w) was calculated. Results. The mean of each weighted Kappa (K_w) for the dimensions in the two municipalities was 0.75 and 0.76, respectively. Factor analysis showed that all 19 items had a factor loading of ≥ 0.40. Three factors (General Care, Medical Care and Cognitive Care) were created.</p> <p>Conclusion</p> <p>The TIC-n instrument has now been tested for validity and reliability in two municipalities with satisfactory results. However, TIC-n can not yet be used as a golden standard, but it can be recommended for use of measurement of individual care needs in municipal elderly care.</p