Search

Artificial Intelligence (AI) has emerged as a promising tool for enhancing the efficiency, accuracy, and sustainability of water treatment systems. However, integrating AI into water treatment comes with its own set of challenges, and specific requirements must be met to fully utilize the potential of these techniques. This study delves into the complexities associated with implementing AI in waste water treatment (WWT) and the necessary prerequisites for developing effective AI-based solutions. The most commonly utilized AI techniques in WWT applications fall under the umbrella of supervised Machine Learning (ML). Supervised ML models serve as excellent tools (correlation coefficient >0,8) for modeling, predicting, and optimizing WWT processes. They have a wide range of applications, including data cleansing, system design, control optimization and predictive maintenance. ML models are particularly useful in optimizing process parameters with significant energy savings achievable (up to 30 % reported in literature). The main challenges for the implementation of such models in WWT are: quality data availability, efficient data management along the data chain and the choice of appropriate ML models. These challenges are highlighted with two concrete examples in the field of water reuse for microalgae cultivation and predictive maintenance of cooling towers. These examples showcase the diverse range of potential use cases for AI and machine learning, especially in wastewater applications.

•PRMT5 inhibition induces a FOXO1 driven, proapoptotic program in MCL.•Combination therapy with PRMT5 and BCL-2 inhibition is synergistic in preclinical MCL models, including those with ibrutinib resistance.

So far, only a minor proportion of businesses – across all economic sectors – has a business model designed to meet the complex requirements of the UN 2030 Agenda. The transformation to a more sustainable economy for the benefit of people and the planet, let alone honouring the principles of Humanistic Management, remains a Herculean task. This article presents family-run companies from the hospitality and tourism industry that have succeeded in aligning their corporate structures, products, and operations with Sustainable Development Goals of the UN 2030 Agenda, building the bridge to –and, in part, explicitly integrating –principles of Humanistic Management. A systemic approach serves as the conceptual-theoretical framework, providing a valuable basis for better understanding the role of individual companies in the complex overall system of the 2030 Agenda. Based on three case studies, presenting findings from expert interviews with selected managing directors or owners of family businesses, it becomes clear that this type of business is particularly well suited to successfully manage the multi-layered challenges of a transformation due to its inherent characteristics.

Aberrant activation of FGFR has been linked to the pathogenesis of many tumor types. Selective inhibition of FGFR has emerged as a promising approach for cancer treatment. Herein, we describe the discovery of compound 38(INCB054828, pemigatinib), a highly potent and selective inhibitor of FGFR1, FGFR2, and FGFR3 with excellent physiochemical properties and pharmacokinetic profiles. Pemigatinib has received accelerated approval from the U.S. Food and Drug Administration for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement. Additional clinical trials are ongoing to evaluate pemigatinib in patients with FGFR alterations.

ABSTRACTGermany’s traditional health resorts and spas have undergone far reaching transformation processes, triggered mainly by health care system reforms that started in the 1990s and resulted in significant cuts to the public funding of traditional restorative ‘Kur’ treatments in these destinations. Consequently, there has been a significant shift towards Germany’s so-called ‘second health care market’, which captures all privately funded health-related products and services. This paper provides an insight into these highly complex transformation processes using three Bavarian health resorts and spas (Bad Birnbach, Bad Füssing and Bad Griesbach) as case examples. Semi-structured interviews with experts from the three destinations offer insight into the structural transition towards the second health care market, including its manifold challenges and opportunities in an emerging health-leisure nexus.

Unter der Prämisse, dass das Humankapital ein entscheidender Faktor für die erneute Buchung einer Messe durch einen Aussteller ist, wurde im Januar 2018 eine Befragung von 129 Messeausstellern auf der Fachmesse Best of Events(BoE) durchgeführt. Ziel war die Identifikation des Einflusses von Humankapital (u. a. Kompetenzen der Mitarbeiter) des Messeveranstalters auf den Messeerfolg. Auf Basis einer multiplen Regression zeigt sich, dass das Humankapital des Messeveranstalters (u. a. Beratungsqualität, Fachkompetenz, Problemlösungsfähigkeit der Mitarbeiter) signifikant mit der Wiederbesuchsabsicht des Ausstellers, d. h. der Absicht der erneuten Buchung von Ausstellungsflächen auf der BoE korreliert. Die Studie legt daher nahe, dass gut ausgebildetes und kompetentes Personal für den Messeerfolg entscheidend ist. Dies gilt der Studie nach für die Planungsphase, jedoch überraschenderweise hat das Humankapital in der Durchführungsphase keinen signifikanten Einfluss auf die Wiederbesuchsabsicht des Ausstellers. Hieraus lässt sich als Handlungsempfehlung für Veranstalter ableiten, dass ein vorhandenes Budget eher vermehrt in die Planungsphase zu investieren ist, da sich dies positiv auf die Wiederbesuchsabsicht auswirkt.

Morocco and Jordan are among those destinations in the Arab world where the complex structures and processes of a neoliberal tourism policy can be examined quasi archetypically: to the extent that the policy largely considers the market as being the ultimate determinant for the exchange of tangible and intangible goods. Based on two case studies – the so-called Master Plan of Marrakesh(Morocco) and the Aqaba Special Economic Zone(Jordan) – this paper examines the conflicted effects of neoliberal penetration into tourism policy on these two destinations as well as on key stakeholders. Given the unilateral instrumentalization of individual freedom in terms of productivity, growth, and progress; it is evident that a neoliberal tourism policy does not justly serve those directly involved or the local communities, but instead, furthers the interests of Western industrialized nations.

The clinical use of first-generation phosphoinositide 3-kinase (PI3K)δinhibitors in B-cell malignancies is hampered by hepatotoxicity, requiring dose reduction, treatment interruption, and/or discontinuation of therapy. In addition, potential molecular mechanisms by which resistance to this class of drugs occurs have not been investigated. Parsaclisib (INCB050465) is a potent and selective next-generation PI3Kδinhibitor that differs in structure from first-generation PI3Kδinhibitors and has shown encouraging anti–B-cell tumor activity and reduced hepatotoxicity in phase 1/2 clinical studies. Here, we present preclinical data demonstrating parsaclisib as a potent inhibitor of PI3Kδwith over 1000-fold selectivity against other class 1 PI3K isozymes. Parsaclisib directly blocks PI3K signaling–mediated cell proliferation in B-cell lines in vitro and in vivo and indirectly controls tumor growth by lessening immunosuppression through regulatory T-cell inhibition in a syngeneic lymphoma model. Diffuse large B-cell lymphoma cell lines overexpressing MYC were insensitive to proliferation blockade via PI3Kδsignaling inhibition by parsaclisib, but their proliferative activities were reduced by suppression of MYCgene transcription. Molecular structure analysis of the first- and next-generation PI3Kδinhibitors combined with clinical observation suggests that hepatotoxicity seen with the first-generation inhibitors could result from a structure-related off-target effect. Parsaclisib is currently being evaluated in multiple phase 2 clinical trials as a therapy against various hematologic malignancies of B-cell origin (NCT03126019, NCT02998476, NCT03235544, NCT03144674, and NCT02018861).

Diversität respektive Diversity Management entwickelt sich angesichts bestimmter sozio-kultureller und ökonomischer Metaprozesse – insbesondere demographischer Wandel, Globalisierung sowie Individualisierung und Pluralisierung der Lebensstile – zu einem immer wichtigeren strategischen Erfolgsfaktor für Unternehmen. Nichtsdestotrotz steckt die wissenschaftliche Auseinandersetzung mit der entsprechenden Thematik im Tourismus- und Hospitalitysektor nach wie vor in den Anfängen. Im Rahmen einer qualitativ ausgerichteten Fallstudie anhand eines weltweit führenden Aviation-Konzerns – der Lufthansa Group – setzt sich der vorliegende Beitrag im Spannungsfeld von Tourismuswissenschaft und Diversitätsforschung mit den Konzepten Diversität und Diversity Management auseinander. In diesem Kontext lässt sich die explorative Studie in erster Linie von der Forschungsfrage leiten, wie eine zentrale stakeholder-Gruppe – Flugbegleiter – die auf dem Prinzip „Wertschöpfung durch Wertschätzung“ basierende Diversity-Strategie des Aviation-Konzerns wahrnimmt. Die mittels problemzentrierter Interviews generierten empirischen Ergebnisse erschließen einerseits vor dem Hintergrund divergierender konzeptioneller Verständnisansätze von Diversity Management das nach wie vor unterschätzte Potential dieses Managementkonzepts, andererseits sensibilisieren sie für potentielle Herausforderungen und Konflikte, die sich im Kontext personaler Heterogenität ergeben können.

El Doppler transcraneal (DTC) es una herramienta útil en la atención del paciente cerebrovascular. Sus resultados, además de ser dependientes del operador, pueden estar influenciados por variables fisiológicas y anatómicas, así como por la altura a la que se encuentra el sujeto estudiado.

La parálisis aislada del nervio oculomotor común (NOC) es una presentación clínica infrecuente del traumatismo craneoencefálico (TCE) leve. Escasas son las descripciones de casos en los que se ha podido demostrar el daño aislado del NOC por avulsión de las raíces con lesión axonal traumática y microhemorragia intraneural. Presentamos el caso de una paciente de 23 años que posterior a TCE leve inició con ptosis palpebral derecha, diplopía binocular y fotofobia. Al examen clínico se apreció una oftalmoparesia completa del III par craneal derecho, sin otras alteraciones. Los exámenes de neuroimagen no demostraron daño estructural compresivo sobre el NOC afectado. Se realizó resonancia magnética (RM) con ECO de gradiente y T1 contrastado. Demostrándose signos de hemorragia intraneural del NOC derecho, además de lesión axonal traumática desde su origen en el pedúnculo cerebral derecho hasta alcanzar la fisura orbitaria. Protocolos específicos de RM contribuyen a evidenciar lesiones aisladas del NOC.

Because both phosphatidylinositol 3-kinase δ (PI3Kδ) and Janus kinase (JAK)-signal transducer and activator of transcription pathways contribute to tumor cell proliferation and survival in B-cell malignancies, their simultaneous inhibition may provide synergistic treatment efficacy. This phase 1 dose-escalation/expansion study assessed the safety, efficacy, pharmacokinetics, and pharmacodynamics of INCB040093, a selective PI3Kδ inhibitor, as monotherapy or combined with itacitinib (formerly INCB039110), a selective JAK1 inhibitor, in adult patients with relapsed or refractory (R/R) B-cell lymphomas. Final results are reported. Overall, 114 patients were treated (monotherapy, n = 49; combination therapy, n = 72 [7 patients crossed over from monotherapy to combination]). INCB040093 100 mg twice daily (monotherapy) and INCB040093 100 mg twice daily + itacitinib 300 mg once daily (combination) were the recommended phase 2 doses. One dose-limiting toxicity (gastrointestinal bleed secondary to gastric diffuse large B-cell lymphoma [DLBCL] regression) occurred with monotherapy. The most common serious adverse events with monotherapy were pneumonia (n = 5) and pyrexia (n = 4), and with combination Pneumocystis jiroveci pneumonia (n = 5), pneumonia (unrelated to P jiroveci; n = 5), and pyrexia (n = 4). Grade 3 or higher transaminase elevations were less common with combination. INCB040093 was active across the B-cell lymphomas; 63% of patients (5/8) with follicular lymphoma responded to monotherapy. Adding itacitinib provided promising activity in select subtypes, with responses of 67% (14/21) in classic Hodgkin lymphoma (vs 29% [5/17] with monotherapy) and 31% (4/13) in nongerminal center B-cell-like DLBCL. INCB040093 with/without itacitinib was tolerated and active in this study, and is a promising treatment strategy for patients with select R/R B-cell lymphomas. This trial was registered at www.clinicaltrials.gov as #NCT01905813.

CDK9 is a master regulator of transcription that modulates transcription elongation via phosphorylation of RNA polymerase II. Short-term inhibition of CDK9 depletes short-lived transcripts and labile proteins such as MCL1, BFL1 and MYC to promote cancer cell death.

Phosphatidylinositol 3-kinase delta (PI3Kδ) is a critical signaling molecule in B cells and is considered a target for development of therapies against various B cell malignancies. INCB040093 is a novel PI3Kδsmall-molecule inhibitor and has demonstrated promising efficacy in patients with Hodgkin’s lymphoma in clinical studies. In this study, we disclose the chemical structure and the preclinical activity of the compound. In biochemical assays, INCB040093 potently inhibits the PI3Kδkinase, with 74- to >900-fold selectivity against other PI3K family members. In vitro and ex vivo studies using primary B cells, cell lines from B cell malignancies, and human whole blood show that INCB040093 inhibits PI3Kδ-mediated functions, including cell signaling and proliferation. INCB040093 has no significant effect on the growth of nonlymphoid cell lines and was less potent in assays that measure human T and natural killer cell proliferation and neutrophil and monocyte functions, suggesting that the impact of INCB040093 on the human immune system will likely be restricted to B cells. INCB040093 inhibits the production of macrophage-inflammatory protein-1β(MIP-1beta) and tumor necrosis factor-β(TNF-beta) from a B cell line, suggesting a potential effect on the tumor microenvironment. In vivo, INCB040093 demonstrates single-agent activity in inhibiting tumor growth and potentiates the antitumor growth effect of the clinically relevant chemotherapeutic agent, bendamustine, in the Pfeiffer cell xenograft model of non-Hodgkin’s lymphoma. INCB040093 has a favorable exposure profile in rats and an acceptable safety margin in rats and dogs. Taken together, data presented in this report support the potential utility of orally administered INCB040093 in the treatment of B cell malignancies.