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Publication Open Access Emergence of near-infrared photoluminescence via ZnS shell growth on the AgBiS2 nanocrystals(American Chemical Society, 2024) Department of Chemistry; Department of Electrical and Electronics Engineering; Önal, Asım; Kaya, Tarık Safa; Metin, Önder; Nizamoğlu, Sedat; Department of Chemistry; Department of Electrical and Electronics Engineering; Graduate School of Sciences and Engineering; College of Sciences; College of EngineeringAgBiS2 nanocrystals (NCs), composed of nontoxic, earth-abundant materials and exhibiting an exceptionally high absorption coefficient from visible to near-infrared (>105 cm(-1)), hold promise for photovoltaics but have lack of photoluminescence (PL) due to intrinsic nonradiative recombination and challenging shell growth. In this study, we reported a facile wet-chemical approach for the epitaxial growth of ZnS shell on AgBiS2 NCs, which triggered the observation of PL emission in the near-infrared (764 nm). Since high quality of the core is critical for epitaxial shell growth, we first obtained rock-salt structured AgBiS2 NCs with high crystallinity, nearly spherical shape and monodisperse size distribution (<6%) via a dual-ligand approach reacting Ag-Bi oleate with elemental sulfur in oleylamine. Next, a zincblende ZnS shell with a low-lattice mismatch of 4.9% was grown on as-prepared AgBiS2 NCs via a highly reactive zinc (Zn(acac)(2)) precursor that led to a higher photoluminescence quantum yield (PLQY) of 15.3%, in comparison with a relatively low reactivity precursor (Zn(ac)(2)) resulting in reduced PLQY. The emission from AgBiS2 NCs with ultrastrong absorption, facilitated by shell growth, can open up new possibilities in lighting, display, and bioimaging.Publication Open Access Multifunctional alginate-based hydrogel with reversible crosslinking for controlled therapeutics delivery(Elsevier, 2020) Ekinci, Duygu; N/A; Department of Chemical and Biological Engineering; Batool, Syeda Rubab; Nazeer, Muhammad Anwaar; Kızılel, Seda; Şahin, Afsun; PhD Student; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; College of Engineering; School of Medicine; N/A; N/A; 28376; 171267Glycan-based alginate hydrogels have great potential in creating new vehicles with responsive behavior and tunable properties for biomedicine. However, precise control and tunability in properties present major barrier for clinical translation of these materials. Here, we report the synthesis of pH responsive anthracene modified glycan-based hydrogels for selective release of therapeutic molecules. Hydrogels were crosslinked through simultaneous photopolymerization of vinyl groups and photodimerization of anthracene. Incorporation of anthracene into these gels leads to reversible control on crosslinking and transition between gel/sol states through dimerization/dedimerization of anthracene groups. Chemotherapeutic drug doxorubicin-loaded hydrogels were then tested in a cancer mimetic microenvironment where 85% of the drug was released from anthracene-conjugated hydrogels at pH 2 for 6 days. Control on gelation with anthracene incorporation was observed through alterations in modulus, where storage modulus was increased two-fold with anthracene conjugation during photopolymerization and photodimerization. Furthermore, cell survival analysis revealed that anthracene conjugation could selectively compromise cancer cell viability without inducing significant toxicity on healthy fibroblasts. This study combines light-induced control of crosslink density due to anthracene and pH-triggered therapeutics delivery with alginate. The approach would be applicable for systems where multiple control is required with high precision.Publication Open Access Preparation of Pt/Al2O3 and PtPd/Al2O3 catalysts by supercritical deposition and their performance for oxidation of nitric oxide and propene(Elsevier, 2020) Şanlı Yıldız, D.; Özener, B.; Hisar, G.; Rommel, S.; Aindow, M.; Department of Chemical and Biological Engineering; Güneş, Hande; Bozbağ, Selmi Erim; Erkey, Can; Researcher; Faculty Member; Department of Chemical and Biological Engineering; Koç University Tüpraş Energy Center (KUTEM) / Koç Üniversitesi Tüpraş Enerji Merkezi (KÜTEM); Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; 29633Pt/Al2O3 and bimetallic PtPd/Al2O3 catalysts were prepared via supercritical deposition method using supercritical carbon dioxide. The effects of Pt loading of Pt/Al2O3 and Pd addition to Pt/Al2O3 on particle size, particle size distribution (PSD) and activity for NO and C3H6 oxidation and C3H6-selective catalytic reduction (C3H6-SCR) were investigated. Pt/Al2O3 catalysts were prepared with Pt loadings of 0.6, 1.2 and 2.1 wt% and a bimetallic PtPd/Al2O3 catalyst was prepared with total metal loading of 1.4 wt% and Pt:Pd molar ratio of 1.3:1. A small fraction of the particles agglomerated after calcination at 550 °C. Around 98 % of the particles had an average particle size of ?1 nm. The rest of the particles were larger and average size of these larger particles was ?10 nm for monometallic catalysts and ?6.5 nm for PtPd/Al2O3. All catalysts were found to be active for NO and C3H6 oxidation and C3H6-SCR reactions. NO oxidation performance of 1.2 wt% Pt/Al2O3 catalyst was the highest. C3H6 oxidation activity increased with increasing metal content. Light-off temperature for C3H6 oxidation shifted to higher temperature in the presence of NO, suggesting competitive oxidation of C3H6 and NO. Concentration profiles indicated that C3H6-SCR started when C3H6 conversion by oxidation reached 50 %; C3H6 was consumed both by oxidation and C3H6-SCR at higher conversions.Publication Open Access Outcome of extended right lobe liver transplants(Wiley, 2021) Lozanovski, Vladimir J.; Unterrainer, Christian; Dohler, Bernd; Mehrabi, Arianeb; Süsal, Caner; Other; School of Medicine; Koç University Hospital; 351800Split-liver transplantation offers a solution to the organ shortage problem. However, the outcomes of extended right lobe liver transplantation (ERLT) and whether it is a suitable alternative to full-size liver transplantation (FSLT) remain controversial. We compared the outcomes of ERLT and FSLT in adult recipients of 43,409 first deceased donor liver transplantations using Cox regression. We also analyzed 612 ERLT and 1224 FSLT 1:2 matched cases to identify factors that affect ERLT outcome. The risk of graft loss was significantly higher following ERLT than following FSLT during the first posttransplantation year in the matched and unmatched collective (hazard ratio [HR], 1.39 and 1.27 and P = 0.01 and 0.006, respectively). Every additional hour of cold ischemia time (CIT) increased the risk of 1-year graft loss by 10% in the ERLT group compared with only 3% in the FSLT group (P = 0.003 and <0.001, respectively). Importantly, the outcome of ERLT and FSLT did not differ significantly if the CIT was below 10 hours (HR, 0.71; P = 0.22). One-year graft and patient survival were lower in high-risk ERLT recipients with a Model for End-Stage Liver Disease (MELD) score of ?20 (HR, 1.88; P = 0.03 and HR, 2.03; P = 0.02). In the male recipient–male donor combination, ERLT recipients had a higher risk of 1-year graft loss than FSLT recipients (HR, 2.44; P = 0.006). This was probably because of the significantly higher MELD score in ERLT recipients (P = 0.004). ERLT in adults is an adequate alternative to FSLT and offers an elegant solution to the problem of organ shortage as long as the cold storage is less than 10 hours and the recipient’s MELD score is <20.Publication Open Access Self-Help Plus for refugees and asylum seekers; study protocol for a series of individual participant data meta-analyses(Taylor _ Francis, 2021) Karyotaki, Eirini; Sijbrandij, Marit; Purgato, Marianna; Lakin, Daniel; Bailey, Della; Peckham, Emily; Uygun, Ersin; Tedeschi, Federico; Wancata, Johannes; Augustinavicius, Jura; Carswell, Ken; Valimaki, Maritta; van Ommeren, Mark; Koesters, Markus; Popa, Mariana; Leku, Marx Ronald; Anttila, Minna; Churchill, Rachel; White, Ross; Al-Hashimi, Sarah; Lantta, Tella; Au, Teresa; Klein, Thomas; Tol, Wietse A.; Cuijpers, Pim; Barbui, Corrado; Department of Psychology; Acartürk, Ceren; Faculty Member; Department of Psychology; College of Social Sciences and Humanities; 39271Background: refugees and asylum seekers face various stressors due to displacement and are especially vulnerable to common mental disorders. To effectively manage psychological distress in this population, innovative interventions are required. The World Health Organization (WHO) Self-Help Plus (SH+) intervention has shown promising outcomes in reducing symptoms of common mental disorders among refugees and asylum seekers. However, individual participant differences in response to SH+ remain largely unknown. The Individual Participant Data (IPD) meta-analysis synthesizes raw datasets of trials to provide cutting-edge evidence of outcomes that cannot be examined by conventional meta-analytic approaches. Objectives: this protocol outlines the methods of a series of IPD meta-analyses aimed at examining the effects and potential moderators of SH+ in (a) reducing depressive symptoms at post-intervention and (b) preventing the six-month cumulative incidence of mental disorders in refugees and asylum seekers. Method: RCTs on SH+ have been identified through WHO and all authors have agreed to share the datasets of the trials. The primary outcomes of the IPD meta-analyses are (a) reduction in depressive symptoms at post-intervention, and (b) prevention of six-month cumulative incidence of mental disorders. Secondary outcomes include post-traumatic stress disorder symptoms, well-being, functioning, quality of life, and twelve-month cumulative incidence of mental disorders. One-stage IPD meta-analyses will be performed using mixed-effects linear/logistic regression. Missing data will be handled by multiple imputation. Conclusions: these results will enrich current knowledge about the response to SH+ and will facilitate its targeted dissemination. The results of these IPD meta-analyses will be published in peer-reviewed journals.Publication Open Access The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation(Springer Nature, 2022) Carapito, Raphael; Aouadi, Ismail; Verniquet, Martin; Untrau, Meiggie; Pichot, Angelique; Beaudrey, Thomas; Bassand, Xavier; Meyer, Sebastien; Faucher, Loic; Posson, Juliane; Morlon, Aurore; Kotova, Irina; Delbos, Florent; Walencik, Alexandre; Aarnink, Alice; Kennel, Anne; Suberbielle, Caroline; Taupin, Jean-Luc; Matern, Benedict M.; Spierings, Eric; Congy-Jolivet, Nicolas; Essaydi, Arnaud; Perrin, Peggy; Blancher, Antoine; Charron, Dominique; Cereb, Nezih; Maumy-Bertrand, Myriam; Bertrand, Frederic; Garrigue, Valerie; Pernin, Vincent; Weekers, Laurent; Naesens, Maarten; Kamar, Nassim; Legendre, Christophe; Glotz, Denis; Caillard, Sophie; Ladriere, Marc; Giral, Magali; Anglicheau, Dany; Bahram, Seiamak; Süsal, Caner; Other; School of MedicineThe identity of histocompatibility loci, besides human leukocyte antigen (HLA), remains elusive. The major histocompatibility complex (MHC) class I MICA gene is a candidate histocompatibility locus. Here, we investigate its role in a French multicenter cohort of 1,356 kidney transplants. MICA mismatches were associated with decreased graft survival (hazard ratio (HR), 2.12; 95% confidence interval (CI): 1.45-3.11; P < 0.001). Both before and after transplantation anti-MICA donor-specific antibodies (DSA) were strongly associated with increased antibody-mediated rejection (ABMR) (HR, 3.79; 95% CI: 1.94-7.39; P < 0.001; HR, 9.92; 95% CI: 7.43-13.20; P < 0.001, respectively). This effect was synergetic with that of anti-HLA DSA before and after transplantation (HR, 25.68; 95% CI: 3.31-199.41; P = 0.002; HR, 82.67; 95% CI: 33.67-202.97; P < 0.001, respectively). De novo-developed anti-MICA DSA were the most harmful because they were also associated with reduced graft survival (HR, 1.29; 95% CI: 1.05-1.58; P = 0.014). Finally, the damaging effect of anti-MICA DSA on graft survival was confirmed in an independent cohort of 168 patients with ABMR (HR, 1.71; 95% CI: 1.02-2.86; P = 0.041). In conclusion, assessment of MICA matching and immunization for the identification of patients at high risk for transplant rejection and loss is warranted.Publication Open Access Atezolizumab, bevacizumab, and chemotherapy for newly diagnosed stage III or IV ovarian cancer: placebo-controlled randomized phase III trial (IMagyn050/GOG 3015/ENGOT-OV39)(Wolters Kluwer, 2021) Moore, K. N.; Bookman, M.; Sehouli, J.; Miller, A.; Anderson, C.; Scambia, G.; Myers, T.; Robison, K.; Mäenpää, J.; Willmott, L.; Colombo, N.; Thomes-Pepin, J.; Liontos, M.; Gold, M. A.; Garcia, Y.; Sharma, S. K.; Darus, C. J.; Aghajanian, C.; Okamoto, A.; Wu, X.; Safin, R.; Wu, F.; Molinero, L.; Maiya, V.; Khor, V. K.; Lin, Y. G.; Pignata, S.; Taşkıran, Çağatay; Faculty Member; School of Medicine; 134190Purpose: to evaluate the addition of the humanized monoclonal antiprogrammed death ligand-1 (PD-L1) antibody, atezolizumab, to platinum-based chemotherapy and bevacizumab in newly diagnosed stage III or IV ovarian cancer (OC). Methods: this multicenter placebo-controlled double-blind randomized phase III trial (ClinicalTrials.gov identifier: NCT03038100) enrolled patients with newly diagnosed untreated International Federation of Gynecology and Obstetrics (FIGO) stage III or IV OC who either had undergone primary cytoreductive surgery with macroscopic residual disease or were planned to receive neoadjuvant chemotherapy and interval surgery. Patients were stratified by FIGO stage, Eastern Cooperative Oncology Group performance status, tumor immune cell PD-L1 staining, and treatment strategy and randomly assigned 1:1 to receive 3-weekly cycles of atezolizumab 1,200 mg or placebo (day 1, cycles 1-22), with paclitaxel plus carboplatin (day 1, cycles 1-6) plus bevacizumab 15 mg/kg (day 1, cycles 2-22), omitting perioperative bevacizumab in neoadjuvant patients. The co-primary end points were investigator-assessed progression-free survival and overall survival in the intention-to-treat and PD-L1-positive populations. Results: between March 8, 2017, and March 26, 2019, 1,301 patients were enrolled. The median progression-free survival was 19.5 versus 18.4 months with atezolizumab versus placebo, respectively (hazard ratio, 0.92; 95% CI, 0.79 to 1.07; stratified log-rank P = .28), in the intention-to-treat population and 20.8 versus 18.5 months, respectively (hazard ratio, 0.80; 95% CI, 0.65 to 0.99; P = .038), in the PD-L1-positive population. The interim (immature) overall survival results showed no significant benefit from atezolizumab. The most common grade 3 or 4 adverse events were neutropenia (21% with atezolizumab v 21% with placebo), hypertension (18% v 20%, respectively), and anemia (12% v 12%). Conclusion: current evidence does not support the use of immune checkpoint inhibitors in newly diagnosed OC. Insight from this trial should inform further evaluation of immunotherapy in OC.Publication Open Access R-SPONDIN2(+) mesenchymal cells form the bud tip progenitor niche during human lung development(Elsevier, 2022) Hein, Renee F. C.; Wu, Joshua H.; Holloway, Emily M.; Frum, Tristan; Conchola, Ansley S.; Tsai, Yu-Hwai; Wu, Angeline; Fine, Alexis S.; Miller, Alyssa J.; Szenker-Ravi, Emmanuelle; Yan, Kelley S.; Kuo, Calvin J.; Glass, Ian; Frum, Tristan; Glass, Ian; Spence, Jason R.; Reversade, Bruno; Faculty Member; School of MedicineThe human respiratory epithelium is derived from a progenitor cell in the distal buds of the developing lung. These ""bud tip progenitors'' are regulated by reciprocal signaling with surrounding mesenchyme; however, mesenchymal heterogeneity and function in the developing human lung are poorly understood. We interrogated single-cell RNA sequencing data from multiple human lung specimens and identified a mesenchymal cell population present during development that is highly enriched for expression of theWNT agonist RSPO2, and we found that the adjacent bud tip progenitors are enriched for the RSPO2 receptor LGR5. Functional experiments using organoid models, explant cultures, and FACS-isolated RSPO2(+) mesenchyme show that RSPO2 is a critical niche cue that potentiates WNT signaling in bud tip progenitors to support their maintenance and multipotency.Publication Open Access Ground-state cooling of mechanical resonatorsby quantum reservoir engineering(Springer Nature, 2021) Department of Physics; Müstecaplıoğlu, Özgür Esat; Naseem, Muhammad Tahir; Faculty Member; Department of Physics; College of Sciences; Graduate School of Sciences and Engineering; 1674; N/ACooling a mechanical oscillator to its ground state underpins many applications ranging from ultra-precise sensing to quantum information processing. The authors propose a new scheme that addresses the problem of the simultaneous cooling of many mechanical resonators with nearby frequencies. Ground-state cooling of multiple mechanical resonators becomes vital to employ them in various applications ranging from ultra-precise sensing to quantum information processing. Here we propose a scheme for simultaneous cooling of multiple degenerate or near-degenerate mechanical resonators to their quantum ground-state, which is otherwise a challenging goal to achieve. As opposed to standard laser cooling schemes where coherence renders the motion of a resonator to its ground-state, we consider an incoherent thermal source to achieve the same aim. The underlying physical mechanism of cooling is explained by investigating a direct connection between the laser sideband cooling and ""cooling by heating"". Our advantageous scheme of cooling enabled by quantum reservoir engineering can be realized in various setups, employing parametric coupling of a cooling agent with the target systems. We also discuss using non-thermal baths to simulate ultra-high temperature thermal baths for cooling.Publication Open Access Extensive androgen receptor enhancer heterogeneity in primary prostate cancers underlies transcriptional diversity and metastatic potential(Nature Portfolio, 2022) Kneppers, J.; Severson, T.M.; Siefert, J.C.; Schol, P.; Joosten, S.E.P.; Yu, I.P.L.; Huang, C.F.; Morova, T.; Giambartolomei, C.; Seo, J.H.; Baca, S.C.; Carneiro, I.; Emberly, E.; Pasaniuc, B.; Jerónimo, C.; Henrique, R.; Freedman, M.L.; Wessels, L.F.A.; Bergman, A.M.; Zwart, W.; N/A; Lack, Nathan Alan; Altıntaş, Umut Berkay; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Sciences and Engineering; 120842; N/AAndrogen receptor (AR) drives prostate cancer (PCa) development and progression. AR chromatin binding profiles are highly plastic and form recurrent programmatic changes that differentiate disease stages, subtypes and patient outcomes. While prior studies focused on concordance between patient subgroups, inter-tumor heterogeneity of AR enhancer selectivity remains unexplored. Here we report high levels of AR chromatin binding heterogeneity in human primary prostate tumors, that overlap with heterogeneity observed in healthy prostate epithelium. Such heterogeneity has functional consequences, as somatic mutations converge on commonly-shared AR sites in primary over metastatic tissues. In contrast, less-frequently shared AR sites associate strongly with AR-driven gene expression, while such heterogeneous AR enhancer usage also distinguishes patients’ outcome. These findings indicate that epigenetic heterogeneity in primary disease is directly informative for risk of biochemical relapse. Cumulatively, our results illustrate a high level of AR enhancer heterogeneity in primary PCa driving differential expression and clinical impact.