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            <cerif:cfName>Differentiation of human and murine CD8+ T cells and their related functional properties</cerif:cfName>
            <cerif:cfDescr>&lt;p dir="ltr"&gt;CD8+ T cells are very important in clearing pathogen and providing long-term protective immunity. However, T cell responses to antigen are highly diverse, and the differentiation state of the T cells is one major determinant of this functional heterogeneity. Upon antigen encounter, antigen-specific CD8+ T cells clonally expand and contribute to pathogen clearance by eliminating infected cells. Following clearance, most antigen- experienced CD8+ T cells go through cell death while a small population persists as long-lived memory T cells. These cells are very important for a strong recall response upon re-encounter of the same pathogen. Understanding the molecular mechanisms underlying the functional and phenotypic diversity of T cells is critical for the development of effective vaccines and T cell-based therapies, as it enables the identification and selective induction of T cell subsets with optimal effector function, persistence, and protective capacity. This thesis aims to understand T cell differentiation and how T cell differentiation states relate to functional properties.&lt;/p&gt;&lt;p dir="ltr"&gt;By using high-dimensional approaches and studying T cell differentiation as a continuous process rather than discrete subsets, we identified the chemokine receptor CX3CR1 as a robust differentiation marker that captures the continuum of T cell differentiation in both human and mouse. We further demonstrated that CX3CR1 expression correlated with the functional properties of T cells, such as cytotoxic potential, cytokine production, and proliferative capacity, and reflects comparable functional states across species, thereby facilitating translation of findings across species. Moreover, by using CX3CR1 expression, we also unraveled mechanistic linkage between migratory behavior and homeostatic proliferation, which is necessary for the maintenance of memory T cell pool. Finally, in this thesis, we also identified micro-environmental factors that influence the induction and maintenance of CX3CR1 expression in memory CD8+ T cells in vitro, highlighting contexts in which CX3CR1 may be less reliable as a differentiation marker.&lt;/p&gt;&lt;h3 dir="ltr"&gt;List of scientific papers&lt;/h3&gt;&lt;p dir="ltr"&gt;I. Graded expression of the chemokine receptor CX3CR1 marks differentiation states of human and murine T cells and enables cross-species interpretation. Anthonie Johan Zwijnenburg, &lt;b&gt;Jyoti Pokharel&lt;/b&gt;, Renata Varnaitė, Wenning Zheng, Elena Hoffer, Iman Shryki, Natalia Ramirez Comet, Marcus Ehrström, Sara Gredmark-Russ, Liv Eidsmo and Carmen Gerlach. Immunity, 2023, 56(8), 1955-1974.e10. &lt;a href="https://doi.org/10.1016/j.immuni.2023.06.025" rel="noreferrer" target="_blank"&gt;https://doi.org/10.1016/j.immuni.2023.06.025&lt;/a&gt;&lt;/p&gt;&lt;p dir="ltr"&gt;II. The cellular microenvironment regulates CX3CR1 expression on CD8+ T cells and the maintenance of CX3CR1+ CD8+ T cells.&lt;b&gt; &lt;/b&gt;&lt;b&gt;Jyoti Pokharel&lt;/b&gt;*, Iman Shryki*, Anthonie Johan Zwijnenburg, Ioana Sandu, Laura Krumm, Christina Bekiari, Rebecka Heinbäck, Victor Avramov, Josefin Lysell, Liv Eidsmo, Helena Erlandsson Harris and Carmen Gerlach. *Equal contribution. European Journal of Immunology, 2024, 54(1):e2350658. &lt;a href="https://doi.org/10.1002/eji.202350658" rel="noreferrer" target="_blank"&gt;https://doi.org/10.1002/eji.202350658&lt;/a&gt;&lt;/p&gt;&lt;p dir="ltr"&gt;III. Preferential access to IL-15 rather than enhanced sensitivity underlies the superior self-renewal of CD8+ memory T cells with intermediate CX3CR1 expression levels.&lt;b&gt; &lt;/b&gt;&lt;b&gt;Jyoti Pokharel&lt;/b&gt;, Wenning Zheng, Anthonie J. Zwijnenburg, Christian Sommerauer, Qirong Lin, Ulrich H. von Andrian, Claudia Kutter, Jeff E. Mold, and Carmen Gerlach. [Manuscript]&lt;/p&gt;</cerif:cfDescr>
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high-energy-density
lithium-ion batteries (LIBs). Herein, we develop an attractive coconut-like
three-shell-structured Si/C composite with a Si content of 35 wt %,
i.e., thin-shelled hollow carbon@Si shell@carbon shell (h-C@Si@C).
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electrochemical performance is ascribed to the distinctive architecture
of h-C@Si@C: (i) The elastic inner carbon shell with cavities releases
the lithiation-induced stress through inward expansion, thereby preventing
the fracture of the outer carbon shell; (ii) the rigid outer carbon
shell enables the formation of a stable solid electrolyte interphase
during Si alloying/dealloying; (iii) the two sandwich-like  carbon
shells are conducive to the retention and electron contact of Si.
This study demonstrates an intriguing structural design of Si/C anodes
for advanced LIBs.</cerif:cfDescr>
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            <cerif:cfName>Tetrahydromethanopterin
as a Two-Carbon Carrier: Formation
of N&lt;sup&gt;5&lt;/sup&gt;‑Ethyl- and N&lt;sup&gt;5&lt;/sup&gt;,N&lt;sup&gt;10&lt;/sup&gt;-Ethylene-Tetrahydromethanopterin
in Methanothermobacter marburgensis</cerif:cfName>
            <cerif:cfDescr>Tetrahydromethanopterin (H&lt;sub&gt;4&lt;/sub&gt;MPT) is the main
carbon carrier
in methane metabolism, which allows the interconversion of a formyl
group into a methyl group. Although typically described as a single
carbon (C1) carrier, we identified and characterized &lt;i&gt;N&lt;/i&gt;&lt;sup&gt;5&lt;/sup&gt;-ethyltetrahydromethanopterin (&lt;i&gt;N&lt;/i&gt;&lt;sup&gt;5&lt;/sup&gt;-ethyl-H&lt;sub&gt;4&lt;/sub&gt;MPT) and &lt;i&gt;N&lt;/i&gt;&lt;sup&gt;5&lt;/sup&gt;,&lt;i&gt;N&lt;/i&gt;&lt;sup&gt;10&lt;/sup&gt;-(1,1-ethylene)tetrahydromethanopterin
(&lt;i&gt;N&lt;/i&gt;&lt;sup&gt;5&lt;/sup&gt;,&lt;i&gt;N&lt;/i&gt;&lt;sup&gt;10&lt;/sup&gt;-ethylene-H&lt;sub&gt;4&lt;/sub&gt;MPT) in the model methanogen &lt;i&gt;Methanothermobacter marburgensis&lt;/i&gt;. The chemical competence of H&lt;sub&gt;4&lt;/sub&gt;MPT to accept C2 moieties
was assayed through the study of the spontaneous formation of &lt;i&gt;N&lt;/i&gt;&lt;sup&gt;5&lt;/sup&gt;,&lt;i&gt;N&lt;/i&gt;&lt;sup&gt;10&lt;/sup&gt;-ethylene-H&lt;sub&gt;4&lt;/sub&gt;MPT by the condensation of acetaldehyde with H&lt;sub&gt;4&lt;/sub&gt;MPT under standard conditions. The rate constant for this reaction
was determined to be 1.53 ± 0.05 M&lt;sup&gt;–1&lt;/sup&gt; s&lt;sup&gt;–1&lt;/sup&gt;, and the equilibrium constant was determined to be
(8.8 ± 0.5) × 10&lt;sup&gt;3&lt;/sup&gt; M&lt;sup&gt;–1&lt;/sup&gt;, which
is ca. 35 times higher compared to the analogous reaction with the
more common carbon carrier tetrahydrofolate. Biochemical assays with &lt;i&gt;M. marburgensis&lt;/i&gt; cell lysate suggest that the observed formation
of &lt;i&gt;N&lt;/i&gt;&lt;sup&gt;5&lt;/sup&gt;-ethyl-H&lt;sub&gt;4&lt;/sub&gt;MPT relies on
the enzymatic reduction of &lt;i&gt;N&lt;/i&gt;&lt;sup&gt;5&lt;/sup&gt;,&lt;i&gt;N&lt;/i&gt;&lt;sup&gt;10&lt;/sup&gt;-ethylene-H&lt;sub&gt;4&lt;/sub&gt;MPT. These findings
illustrate the chemical competency of H&lt;sub&gt;4&lt;/sub&gt;MPT to promote
biocatalysis with two-carbon moieties and highlight that such reactions
might be compatible with established H&lt;sub&gt;4&lt;/sub&gt;MPT-mediated microbial
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            <cerif:cfDescr>&lt;p&gt;Reference genes (RGs) commonly serve as internal controls for normalization of gene expression data in quantitative real-time polymerase chain reaction (qPCR) analyses. To ensure accurate and reliable normalization and interpretation of the results, a systematic validation of RG stability under particular experimental conditions is essential. Our research group previously established a suitable in vitro model system for kohlrabi (Brassica oleracea var. gongylodes) growth and regeneration, encompassing four early developmental stages under varying cytokinin and sugar treatments. As the stability of potential RGs had not yet been evaluated for kohlrabi, we selected and tested suitable RGs for our specific experimental setup. A total of 15 candidate RGs were analyzed using the RefFinder online tool, which integrates four statistical algorithms (geNorm, NormFinder, BestKeeper, and the comparative ΔCt method) to generate a comprehensive stability ranking. TUA2, ACT7 and SAND were identified as the most stable RGs across all experimental subsets, while GAPB and GLUR3.2 exhibited the lowest stability. These findings were validated by qPCR analysis of selected sucrose-related target genes. Our results highlight the importance of context-specific RG validation and provide a valuable resource for gene expression studies in non-model horticultural crops such as kohlrabi.&lt;/p&gt;</cerif:cfDescr>
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            <cerif:cfName>Supplementary materials: Effects of cardiovascular single pill combinations compared with identical multi-pill therapies on healthcare cost and utilization in Germany</cerif:cfName>
            <cerif:cfDescr>&lt;p dir="ltr"&gt;&lt;b&gt;These are peer-reviewed supplementary materials for the article '&lt;/b&gt;&lt;b&gt;Effects of cardiovascular single pill &lt;/b&gt;&lt;b&gt;combinations compared with identical &lt;/b&gt;&lt;b&gt;multi-pill therapies on healthcare cost and &lt;/b&gt;&lt;b&gt;utilization in Germany&lt;/b&gt;&lt;b&gt;' published in the&lt;/b&gt;&lt;b&gt; &lt;/b&gt;&lt;b&gt;&lt;i&gt;Journal of Comparative Effectiveness Research&lt;/i&gt;&lt;/b&gt;&lt;b&gt;.&lt;/b&gt;&lt;/p&gt;&lt;ul&gt;&lt;li&gt;&lt;b&gt;Supplementary figure 1&lt;/b&gt;&lt;/li&gt;&lt;li&gt;&lt;b&gt;Supplementary figure 2&lt;/b&gt;&lt;/li&gt;&lt;li&gt;&lt;b&gt;Supplementary figure 3&lt;/b&gt;&lt;/li&gt;&lt;li&gt;&lt;b&gt;Supplementary table 1&lt;/b&gt;&lt;/li&gt;&lt;li&gt;&lt;b&gt;Supplementary table 2&lt;/b&gt;&lt;/li&gt;&lt;/ul&gt;&lt;p dir="ltr"&gt;&lt;b&gt;Aim:&lt;/b&gt; This study assessed whether a single pill combination (SPC) is associated with lower direct healthcare costs. &lt;b&gt;Materials &amp; methods:&lt;/b&gt; Anonymized claims data of patients ≥18 years treated with drugs for cardiovascular (CV)-related diseases either as a single pill combination or multi-pill combination (follow up to 1 year) were evaluated. After propensity score matching, 59,336 out of 1,369,840 patients were analyzed.&lt;b&gt; Results:&lt;/b&gt; In all cohorts, patients receiving a single pill combination had a lower frequency of general practitioner and specialist visits. The patients also had a significantly lower ratio of all-cause hospitalization days and number of CV-related prescriptions as well as all-cause prescriptions (with one exception) compared with those receiving a multi-pill combination. &lt;b&gt;Conclusion:&lt;/b&gt; Direct CV-related costs were significantly lower in four out of seven comparisons, with a trend toward lower costs in the other three comparisons.&lt;/p&gt;</cerif:cfDescr>
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            <cerif:cfName>Supplementary materials: Willingness to pay for a hypothetical malaria vaccine in Brazil: a cross-sectional study and the implications</cerif:cfName>
            <cerif:cfDescr>&lt;p dir="ltr"&gt;&lt;b&gt;These are peer-reviewed supplementary materials for the article '&lt;/b&gt;&lt;b&gt;Willingness to pay for a hypothetical &lt;/b&gt;&lt;b&gt;malaria vaccine in Brazil: a cross-sectional &lt;/b&gt;&lt;b&gt;study and the implications&lt;/b&gt;&lt;b&gt;' published in the&lt;/b&gt;&lt;b&gt; &lt;/b&gt;&lt;b&gt;&lt;i&gt;Journal of Comparative Effectiveness Research&lt;/i&gt;&lt;/b&gt;&lt;b&gt;.&lt;/b&gt;&lt;/p&gt;&lt;ul&gt;&lt;li&gt;&lt;b&gt;Previous knowledge about malaria&lt;/b&gt;&lt;/li&gt;&lt;li&gt;&lt;b&gt;Information about malaria&lt;/b&gt;&lt;/li&gt;&lt;li&gt;&lt;b&gt;Conference about context understanding&lt;/b&gt;&lt;/li&gt;&lt;li&gt;&lt;b&gt;Opinion research&lt;/b&gt;&lt;/li&gt;&lt;li&gt;&lt;b&gt;Clinical data&lt;/b&gt;&lt;/li&gt;&lt;li&gt;&lt;b&gt;Exclusive to interviewer&lt;/b&gt;&lt;/li&gt;&lt;/ul&gt;&lt;p dir="ltr"&gt;&lt;b&gt;Aim:&lt;/b&gt; Malaria is an infection caused by protozoa of genus Plasmodium, considered the one associated with increasingly large outbreaks. &lt;b&gt;Methods:&lt;/b&gt; A cross-sectional study was conducted with residents in the northern region of Brazil on the willingness to pay (WTP) for a hypothetical vaccine against malaria (effective protection of 80%). &lt;b&gt;Results: &lt;/b&gt;Of 616 people interviewed, most interviewees were female (61%) and were employed (97%). The median individual maximum WTP for a hypothetical malaria vaccine was US$11.90 (BRL 50). &lt;b&gt;Conclusion: &lt;/b&gt;The northern region of Brazil is one of the largest markets for a malaria vaccine due to its epidemiological relevance. Consequently, economic studies will be important to assist in the assessment of the potential price and value of new vaccines.&lt;/p&gt;</cerif:cfDescr>
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        <datestamp>2024-05-02T13:53:43Z</datestamp>
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            <cerif:cfName>Supplementary data: An economic evaluation of reducing colorectal cancer surveillance intensity</cerif:cfName>
            <cerif:cfDescr>&lt;p dir="ltr"&gt;&lt;b&gt;These are peer-reviewed supplementary materials for the article '&lt;/b&gt;&lt;b&gt;An economic evaluation of reducing &lt;/b&gt;&lt;b&gt;colorectal cancer surveillance intensity&lt;/b&gt;&lt;b&gt;' published in the&lt;/b&gt;&lt;b&gt; &lt;/b&gt;&lt;b&gt;&lt;i&gt;Journal of Comparative Effectiveness Research&lt;/i&gt;&lt;/b&gt;&lt;b&gt;.&lt;/b&gt;&lt;/p&gt;&lt;ul&gt;&lt;li&gt;&lt;b&gt;Table 1: &lt;/b&gt;Parameters Used in the Model&lt;/li&gt;&lt;li&gt;&lt;b&gt;Table 2: &lt;/b&gt;Distributions Used for Probabilistic Sensitivity Analysis&lt;/li&gt;&lt;/ul&gt;&lt;p dir="ltr"&gt;&lt;b&gt;Aim: &lt;/b&gt;Analyze the impact of national implementation of ‘low intensity’ post-treatment colorectal cancer surveillance compared with current practices. &lt;b&gt;Materials &amp; methods:&lt;/b&gt; Create a population-level Markov model to estimate impacts of expansion of low versus high intensity surveillance post-treatment on healthcare utilization, costs and caregiver time loss. &lt;b&gt;Results:&lt;/b&gt; Shifting to low intensity colorectal cancer surveillance would reduce patient burden by 301,830 h per patient annually over 5 years. Cost reductions over 5 years were US$43.5 million for Medicare and US$4.2 million for Medicaid. Total societal cost savings equaled US$104.2 million. Conclusion: National implementation of low intensity post-treatment colorectal cancer surveillance has the potential to significantly reduce burden and costs on patients and their caregivers with no added risks to health.&lt;/p&gt;</cerif:cfDescr>
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            <cerif:cfName>Identification
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Agents by Reducing Membrane Localization of ENO1 in Pancreatic Cancer
Cells</cerif:cfName>
            <cerif:cfDescr>The
hypoxic microenvironment of pancreatic cancer drives tumorigenesis,
invasion, multidrug resistance, and poor prognosis. Rakicidin A exhibits
hypoxia-selective cytotoxicity, while its stability, structure–activity
relationship (SAR), and molecular target remain unclear. Here, we
developed an efficient synthetic route to generate a library of 34
rakicidin A analogues. SAR analysis identified compound &lt;b&gt;10e&lt;/b&gt; as the most potent derivative. Target identification revealed that &lt;b&gt;10e&lt;/b&gt; covalently bound to Cys357 of enolase 1 (ENO1). Mechanistically, &lt;b&gt;10e&lt;/b&gt; disrupted ENO1 membrane translocation and its interaction
with c-MET, leading to suppression of the PI3K/AKT signaling pathway. &lt;i&gt;In vivo&lt;/i&gt; studies demonstrated that &lt;b&gt;10e&lt;/b&gt; significantly
inhibited tumor growth in pancreatic cancer xenograft models. This
work identifies &lt;b&gt;10e&lt;/b&gt; as a novel hypoxia-selective rakicidin
analogue targeting ENO1 and highlights inhibition of ENO1 membrane
localization as a promising strategy for hypoxia-directed pancreatic
cancer therapy.</cerif:cfDescr>
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        <identifier>oai:figshare.com:article/32124732</identifier>
        <datestamp>2026-04-29T00:00:00Z</datestamp>
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            <cerif:cfName>Preparation
and Regulation of Temperature-Sensitive
Organogel for Temperature-Controlled Information Displays and Smart
Temperature Labels</cerif:cfName>
            <cerif:cfDescr>Temperature-sensitive
gels are attractive in various fields, including
smart windows, information encryption, and actuators. Herein, we select
ethylene glycol as the solvent and prepare a poly(4-acryloylmorpholine)
(PACMO) organogel with UCST phase transition behavior via photopolymerization.
This temperature-sensitive organogel, with transition temperatures
adjustable between 10 and 62 °C, displays high temperature sensitivity,
a narrow transition window, and excellent cycling stability. The incorporation
of comonomers, cosolvents, and cross-linkers significantly affects
the transition behavior of the organogel through changing the transition
temperature or broadening the transition window from 2 to 25 °C.
Variable-temperature infrared spectroscopy and theory calculations
reveal that the ether bond of PACMO competes with the intermolecular
hydrogen bonds of ethylene glycol. As the temperature rises, the intermolecular
hydrogen-bond interaction between ethylene glycol molecules weakens,
while the hydrogen-bond interaction between the ether bond and ethylene
glycol strengthens, leading to changes in transparency of the organogel.
The applications of the organogel in the fields of temperature-controlled
information displays and smart temperature labels are demonstrated.
This design broadens the types of temperature-sensitive gel materials
to organogels, opening a pathway toward applications with multifunctional
optical requirements.</cerif:cfDescr>
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        <datestamp>2026-04-29T12:40:13Z</datestamp>
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            <cerif:cfName>Image 1_Resident T cell activation leads to human hair follicle immune privilege loss ex vivo, which is prevented by the DHODH inhibitor farudodstat: relevance for alopecia areata.pdf</cerif:cfName>
            <cerif:cfDescr>&lt;p&gt;The autoimmune hair loss disorder alopecia areata (AA), is characterized by immune privilege (IP) collapse of the hair follicle (HF) bulb resulting from a Th1-dependent inflammatory response. Although CD8&lt;sup&gt;+&lt;/sup&gt; T cells are recognized key drivers of the disease, it remains to be clarified whether the activation of HF resident T cells suffice to initiate IP loss and thus elicit the cascade of events leading to AA. Here, we utilized the human microdissected HF organ culture model to answer this question by activating intra- and peri-follicular HF resident T cells with αCD3/αCD28 antibodies. TCR stimulation indeed resulted in enhanced resident T cell proliferation, as indicated by significantly increased CD3&lt;sup&gt;+&lt;/sup&gt;Ki-67&lt;sup&gt;+&lt;/sup&gt; cells, and higher intrafollicular CD3&lt;sup&gt;+&lt;/sup&gt; T cell numbers. Furthermore, αCD3/αCD28 stimulation promoted key signs of HF IP collapse, by increasing bulbar MHC class I and II expression and elevating MHC class II&lt;sup&gt;+&lt;/sup&gt; cells numbers. We next sought to investigate whether T cell proliferation plays a central role in the TCR activation–dependent collapse of the bulb IP. To test this, we co-administered the DHODH inhibitor farudodstat 1 day prior and during the stimulation with αCD3/αCD28 in HF organ culture. Short-term treatment with farudodstat reduced the increase in T cell proliferation and significantly decreased the upregulated MHC class I and II expression induced by TCR stimulation with αCD3/αCD28. Our results show that stimulation of HF resident T cells via TCR engagement induces an AA–like phenotype in healthy human HFs ex vivo, characterized by T cell proliferation and subsequent IP collapse. DHODH inhibition with farudodstat only partially reduces T cell numbers but prevented HF IP collapse induction.&lt;/p&gt;</cerif:cfDescr>
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