From subscription revenue to intrinsic value: a company valuation of Okta Inc.

Okta, the largest independent identity-and-access-management platform, has seen its market value swing sharply amid rising interest rates and volatile software multiples. This work project derives Okta’s intrinsic equity value through an integrated operating model that feeds a discounted-cash flow model, peer trading multiples and precedent identity-software transactions, all rooted in detailed forecasts of revenue mix, margin expansion and capital intensity. Scenario-weighted DCF indicates US $124.60 per share; a growth-adjusted revenue multiple corroborates at US$114.02, yielding a blended estimate of US $120.37, which is about 8% above May 1, 2025 stock closing price

Partizipatives Forschen mit jungen Menschen zu Sexualität, Gewalt und Schutz in der (internationalen) Jugendarbeit: method(olog)ische Reflexionen

In diesem Beitrag reflektiere ich den partizipativen Forschungsstil im Verbundprojekt "SchutzNorm: Schutzkonzepte in der Kinder- und Jugendarbeit. Normalitätskonstruktionen von Sexualität und Gewalt unter Jugendlichen" (2018-2021) hinsichtlich methodologischer und methodischer Aspekte. Einleitend werden aktuelle deutschsprachige Debatten zum partizipativen Forschen dargelegt, mit theoretischen Perspektiven aus der Wissenssoziologie flankiert und mit Grundannahmen einer postkolonialen Pädagogik nach Paulo FREIRE verbunden. Sodann erfolgen methodologische Reflexionen zu den Beteiligungssituationen der partizipativen Jugendforschung "SchutzNorm" auf Verbundebene im Allgemeinen und zum Peer-Forschungsprozess in Forschungswerkstätten im Teilprojekt "Internationale Jugendarbeit" im Besonderen.In this article, I reflect on the participative research approach in the joint project "SchutzNorm: Protection Concepts in Child and Youth Work. Constructions of Normality of Sexuality and Violence Among Adolescents" (2018-2021), specifically regarding method(olog)ical issues. I present current German debates on participatory research, along with theoretical perspectives from the sociology of knowledge and connected with basic approaches of a postcolonial pedagogy according to Paulo FREIRE. First, I discuss participation situations in the project "SchutzNorm." Then I explore the peer research process in the sub-project "International Youth Work.

Queere Geflüchtete und die Diskursivierung des ‚Anderen‘ in Debatten um Sexarbeit, ‚Willkommenskultur‘ und Schutz

Unter Bezugnahme theoretischer Perspektiven zu postkolonialem Othering und diskursiven Grenzziehungen fragt dieser Beitrag nach den Un_Sichtbarmachungen und Ver-Anderungen von queeren Geflüchteten in Debatten um Sexarbeit, ‚Willkommenskultur‘ und Schutz. Anhand dieser drei Debatten werden diskursive Grenzziehungen entlang der Analysekategorie Un_Sichtbarmachungen unter besonderer Berücksichtigung der Verschränkung von Queerness und Migration/Flucht herausgearbeitet. Deutlich wird, inwiefern queere Geflüchtete im Kontext von Sexarbeit (strategisch) unsichtbar gemacht und auf eine vulnerable Position festgeschrieben werden sowie sexuell-geschlechtliche Selbstbestimmung weitreichend determiniert oder gar aberkannt ist

Calcium channels and pumps in cancer: changes and consequences

Increases in intracellular free Ca2+ play a major role in many cellular processes. The deregulation of Ca2+ signaling is a feature of a variety of diseases, and modulators of Ca2+ signaling are used to treat conditions as diverse as hypertension to pain. The Ca2+ signal also plays a role in processes important in cancer, such as proliferation and migration. Many studies in cancer have identified alterations in the expression of proteins involved in the movement of Ca2+ across the plasma membrane and subcellular organelles. In some cases, these Ca2+ channels or pumps are potential therapeutic targets for specific cancer subtypes or correlate with prognosis

The Multifaceted Neurotoxicity of Astrocytes in Ageing and Age-Related Neurodegenerative Diseases: A Translational Perspective.

In a healthy physiological context, astrocytes are multitasking cells contributing to central nervous system (CNS) homeostasis, defense, and immunity. In cell culture or rodent models of age-related neurodegenerative diseases (NDDs), such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), numerous studies have shown that astrocytes can adopt neurotoxic phenotypes that could enhance disease progression. Chronic inflammatory responses, oxidative stress, unbalanced phagocytosis, or alteration of their core physiological roles are the main manifestations of their detrimental states. However, if astrocytes are directly involved in brain deterioration by exerting neurotoxic functions in patients with NDDs is still controversial. The large spectrum of NDDs, with often overlapping pathologies, and the technical challenges associated with the study of human brain samples complexify the analysis of astrocyte involvement in specific neurodegenerative cascades. With this review, we aim to provide a translational overview about the multi-facets of astrocyte neurotoxicity ranging from in vitro findings over mouse and human cell-based studies to rodent NDDs research and finally evidence from patient-related research. We also discuss the role of ageing in astrocytes encompassing changes in physiology and response to pathologic stimuli and how this may prime detrimental responses in NDDs. To conclude, we discuss how potentially therapeutic strategies could be adopted to alleviate or reverse astrocytic toxicity and their potential to impact neurodegeneration and dementia progression in patients

3D Modelling of a Spatially Resolved Energy Metabolism in Physiological Astrocytic Morphology

Astrocytes, the most abundant cell in the central nervous system, have a star-shaped morphology and play a central role in brain homeostasis as metabolic mediators between neurons and blood vessels. Recent evidence put astrocytes therefore in the focus of neurodegeneration (ND), since in case of metabolic dysfunctions as e.g. observed in Alzheimer’s disease or Parkinson’s disease, they cannot provide neurons with sufficient amount of nutrients. Furthermore, progression of ND is often accompanied by changes in astrocytic morphology further indicating the essential role of astrocytes in the brain. Despite its importance, the complex astrocytic morphology is often neglected in modelling of metabolic reactions [1]. In this study, we propose a computational model that describes cellular metabolism through a reaction-diffusion system including two fundamental pieces of information: the intracellular spatial arrangement of the reaction sites and the real, complex geometries by using the previously developed method CutFEM([2][3]). Our findings show how intracellular spatial organisation and diffusion limitation as well as the physio- logical cell shape must be taken into account to go towards biological models that are closer to reality. In particular, the spatial distribution of mitochondria notably impacts the cellular ATP : ADP ratio, which is an indicator of the energetic state of the cell. Finally, we solve our system in a 3D human astrocytic morphology and study the different spatial arrangements of the reaction sites simulating physiological and dysfunctional behaviour. In this regard, we believe, that the proposed model is a useful instrument to gain insights into the role astrocytes play in neurodegeneration

Estrogen receptor beta expression in prostate adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>Prostate cancer is the most commonly diagnosed cancer in men and the second leading cause of cancer death in men. Estrogen induction of cell proliferation is a crucial step in carcinogenesis of gynecologic target tissues, and there are many studies recently done, showing that prostate cancer growth is also influenced by estrogen. The characterization of estrogen receptor beta (ER-b) brought new insight into the mechanisms underlying estrogen signalling. In the present study, we investigated the expression of estrogen receptor-b (ER-b) in human prostate cancer tissues.</p> <p>Methods</p> <p>We selected 52 paraffin-embedded blocks of prostate needle biopsies in a cross-sectional study to determine frequency and rate of ER-b expression in different grades of prostate adenocarcinoma according to Gleason grading system. Immunohistochemical staining of tissue sections by monoclonal anti ER-b antibody was performed using an Envision method visualising system.</p> <p>Results</p> <p>ER-b expression was seen in tumoral cells of prostatic carcinoma in all 29 cases with low and intermediate tumors (100%) and 19 of 23 cases with high grade tumor (83%). Mean rate of ER-b expression in low & intermediate grade cancers was 68.41% (SD = 25.63) whereas high grade cancers showed 49.48% rate of expression (SD = 28.79).</p> <p>Conclusions</p> <p>ER-b expression is reduced in high grade prostate cancers compared to low & intermediate grade ones (<it>P </it>value 0.027).</p

Orai1 contributes to the establishment of an apoptosis-resistant phenotype in prostate cancer cells

The molecular nature of calcium (Ca2+)-dependent mechanisms and the ion channels having a major role in the apoptosis of cancer cells remain a subject of debate. Here, we show that the recently identified Orai1 protein represents the major molecular component of endogenous store-operated Ca2+ entry (SOCE) in human prostate cancer (PCa) cells, and constitutes the principal source of Ca2+ influx used by the cell to trigger apoptosis. The downregulation of Orai1, and consequently SOCE, protects the cells from diverse apoptosis-inducing pathways, such as those induced by thapsigargin (Tg), tumor necrosis factor α, and cisplatin/oxaliplatin. The transfection of functional Orai1 mutants, such as R91W, a selectivity mutant, and L273S, a coiled-coil mutant, into the cells significantly decreased both SOCE and the rate of Tg-induced apoptosis. This suggests that the functional coupling of STIM1 to Orai1, as well as Orai1 Ca2+-selectivity as a channel, is required for its pro-apoptotic effects. We have also shown that the apoptosis resistance of androgen-independent PCa cells is associated with the downregulation of Orai1 expression as well as SOCE. Orai1 rescue, following Orai1 transfection of steroid-deprived cells, re-established the store-operated channel current and restored the normal rate of apoptosis. Thus, Orai1 has a pivotal role in the triggering of apoptosis, irrespective of apoptosis-inducing stimuli, and in the establishment of an apoptosis-resistant phenotype in PCa cells

Expression of TRPC6 channels in human epithelial breast cancer cells

<p>Abstract</p> <p>Background</p> <p>TRP channels have been shown to be involved in tumour generation and malignant growth. However, the expression of these channels in breast cancer remains unclear. Here we studied the expression and function of endogenous TRPC6 channels in a breast cancer cell line (MCF-7), a human breast cancer epithelial primary culture (hBCE) and in normal and tumour breast tissues.</p> <p>Methods</p> <p>Molecular (Western blot and RT-PCR), and immunohistochemical techniques were used to investigate TRPC6 expression. To investigate the channel activity in both MCF-7 cells and hBCE we used electrophysiological technique (whole cell patch clamp configuration).</p> <p>Results</p> <p>A non selective cationic current was activated by the oleoyl-2-acetyl-sn-glycerol (OAG) in both hBCE and MCF-7 cells. OAG-inward current was inhibited by 2-APB, SK&F 96365 and La³⁺. TRPC6, but not TRPC7, was expressed both in hBCE and in MCF-7 cells. TRPC3 was only expressed in hBCE. Clinically, TRPC6 mRNA and protein were elevated in breast carcinoma specimens in comparison to normal breast tissue. Furthermore, we found that the overexpression of TRPC6 protein levels were not correlated with tumour grades, estrogen receptor expression or lymph node positive tumours.</p> <p>Conclusion</p> <p>Our results indicate that TRPC6 channels are strongly expressed and functional in breast cancer epithelial cells. Moreover, the overexpression of these channels appears without any correlation with tumour grade, ER expression and lymph node metastasis. Our findings support the idea that TRPC6 may have a role in breast carcinogenesis.</p