bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapamycin induces apoptosis in monocyte- and CD34-derived dendritic cells but not in monocytes and macrophages
Authors: Woltman Andrea M. , de Fijter Johan W. , Kamerling Sylvia W. A. , van der Kooij Sandra W. , Paul Leendert C. , Daha Mohamed R. , van Kooten Cees 
Published: July 2002

AbstractRapamycin (Rapa), a recently introduced immunosuppressive drug, seems to be effective in preventing acute allograft rejection. Although its antiproliferative effect on T lymphocytes has been investigated extensively, its effect on the initiators of the immune response, the dendritic cells (DCs), is not known. Therefore, the effect of Rapa on monocyte- (mo-DCs) and CD34+-derived DCs in vitro but also on other myeloid cell types, including monocytes and macrophages, was examined. The present study shows that Rapa does not affect phenotypic differentiation and CD40L-induced maturation of mo-DCs. However, Rapa dramatically reduced cell recovery (40%-50%). Relatively low concentrations of Rapa (10−9 M) induced apoptosis in both mo-DCs and CD34+-derived DCs, as visualized by phosphatidylserine exposure, nuclear condensation and fragmentation, and DNA degradation. In contrast, Rapa did not affect freshly isolated monocytes, macrophages, or myeloid cell lines. The sensitivity to Rapa-induced apoptosis was acquired from day 2 onward of mo-DC differentiation. Rapa exerts its apoptotic effect via a reversible binding to the cytosolic receptor protein FKBP-12, as demonstrated in competition experiments with FK506, which is structurally related to Rapa. Partial inhibition of Rapa-induced apoptosis was obtained by addition of ZVAD-fmk, which implies caspase-dependent and caspase-independent processes. The fact that Rapa exerts a specific effect on DCs but not on monocytes and macrophages might contribute to the unique actions of Rapa in the prevention of allograft rejection and other immune responses.
The TEL/PDGFβR fusion in chronic myelomonocytic leukemia signals through STAT5-dependent and STAT5-independent pathways
Authors: Sternberg David W. , Tomasson Michael H. , Carroll Martin , Curley David P. , Barker George , Caprio Michael , Wilbanks Alyson , Kazlauskas Andrius , Gilliland D. Gary 
Published: July 2002

AbstractThe TEL/PDGFβR gene, which encodes a fusion protein containing the ETS-family member TEL fused to the protein-tyrosine kinase domain of the platelet-derived growth factor receptor-β (PDGFβR), confers interleukin 3 (IL-3)–independent growth on Ba/F3 hematopoietic cells. TEL/PDGFβR mutants have been generated that contain tyrosine-to-phenylalanine (Tyr→Phe) substitutions at phosphorylation sites present in the native PDGFβR to assess the role of these sites in cell transformation by TEL/PDGFβR. Similar to previous findings in a murine bone marrow transplantation model, full transformation of Ba/F3 cells to IL-3–independent survival and proliferation required the TEL/PDGFβR juxtamembrane and carboxy terminal phosphorylation sites. In contrast to previous reports concerning comparable mutants in the native PDGFβR, each of the TEL/PDGFβR mutants is fully active as a protein-tyrosine kinase. Expression of the TEL/PDGFβR fusion protein causes hyperphosphorylation and activation of signal transducer and activator of transcription (STAT5), and this activation of STAT5 requires the juxtamembrane Tyr579 and Tyr581 in the TEL/PDGFβR fusion. Hyperphosphosphorylation of phospholipase Cγ (PLCγ) and the p85 subunit of phosphatidylinositol 3-kinase (PI3K) requires the carboxy terminal tyrosine residues of TEL/PDGFβR. Thus, full transformation of Ba/F3 cells by TEL/PDGFβR requires engagement of PI3K and PLCγ and activation of STAT5. Taken together with the growth properties of cells transformed by the TEL/PDGFβR variants, these findings indicate that a minimal combination of these signaling intermediates contributes to hematopoietic transformation by the wild-type TEL/PDGFβR fusion.
De novo methylation of an embryonic globin gene during normal development is strand specific and spreads from the proximal transcribed region
Authors: Singal Rakesh , vanWert Jane M. 
Published: July 2002

AbstractThe recently discovered de novo methyltransferases DNMT3a and DNMT3b have been shown to be critical to embryonic development. However, at a single gene level, little is known about how the methylation pattern is established during development. The avian embryonic ρ-globin gene promoter is completely unmethylated in 4-day-old chicken embryonic erythroid cells, where it is expressed at a high level, and completely methylated in adult erythroid cells, where it is silent. The methylation pattern of the ρ-globin gene promoter, proximal transcribed region, and distal transcribed region on both DNA strands was examined during development in chicken erythroid cells. It was found that de novo methylation targets the CpG-dense proximal transcribed region on the coding (top) strand initially, followed by spreading into the 3′ region and into the promoter region. Methylation of the template (bottom) strand lags behind that of the coding strand, and complete methylation of both strands occurs only after the gene has been silenced. The results of the study indicate that establishment of the de novo methylation pattern involves strand-specificity and methylation spreading.
Altered apoptosis pathways in mantle cell lymphoma detected by oligonucleotide microarray
Authors: Hofmann Wolf-K. , de Vos Sven , Tsukasaki Kunihiro , Wachsman William , Pinkus Geraldine S. , Said Jonathan W. , Koeffler H. Phillip 
Published: July 2002

AbstractAn imbalance between cellular apoptosis and survival may be critical for the pathogenesis of lymphoma. Therefore, the gene expression pattern in lymph node preparations from patients with mantle cell lymphoma (MCL) was compared to the pattern in nonmalignant hyperplastic lymph nodes (HLs). Oligonucleotide microarray analysis was performed comparing 5 MCLs to 4 HLs using high-density microarrays. The expression data were analyzed using Genespring software. For confirmation, the expression of selected genes was analyzed by real-time polymerase chain reaction using the RNA extracted from 16 MCL and 12 HL samples. The focus was on 42 genes that were at least 3-fold down-regulated in MCL; in addition to the B-cell leukemia 2 (BCL2) system other apoptotic pathways were altered in MCL. The FAS-associated via death domain (FADD) gene that acts downstream of the FAS cascade as a key gene to induce apoptosis was more than 10-fold down-regulated in MCL. Furthermore, the death-associated protein 6(DAXX) gene, the caspase 2 (CASP2) gene, and the RIPK1 domain containing adapter with death domain(RAIDD) gene, which are key genes in other proapoptotic pathways, were also decreased in the MCL samples. The suggestion is made that in addition to the known overexpression of cyclin D1, which drives entry into the cell cycle, disturbances of pathways associated with apoptosis contribute to the development of MCL.
HTLV-1 p12I protein enhances STAT5 activation and decreases the interleukin-2 requirement for proliferation of primary human peripheral blood mononuclear cells
Authors: Nicot Christophe , Mulloy James C. , Ferrari Maria G. , Johnson Julie M. , Fu Kaisong , Fukumoto Risaku , Trovato Raffaella , Fullen Jake , Leonard Warren J. , Franchini Genoveffa 
Published: July 2002

Abstract
The p12I protein, encoded by the pX open reading frame I of the human T-lymphotropic virus type 1 (HTLV-1), is a hydrophobic protein that localizes to the endoplasmic reticulum and the Golgi. Although p12I contains 4 minimal proline-rich, src homology 3–binding motifs (PXXP), a characteristic commonly found in proteins involved in signaling pathways, it has not been known whether p12I has a role in modulating intracellular signaling pathways. This study demonstrated that p12I binds to the cytoplasmic domain of the interleukin-2 receptor (IL-2R) β chain that is involved in the recruitment of the Jak1 and Jak3 kinases. As a result of this interaction, p12I increases signal transducers and activators of transcription 5 (STAT5) DNA binding and transcriptional activity and this effect depends on the presence of both IL-2R β and γc chains and Jak3. Transduction of primary human peripheral blood mononuclear cells (PBMCs) with a human immunodeficiency virus type 1–based retroviral vector expressing p12I also resulted in increased STAT5 phosphorylation and DNA binding. However, p12I could increase proliferation of human PBMCs only after stimulation of T-cell receptors by treatment of cells with low concentrations of αCD3 and αCD28 antibodies. In addition, the proliferative advantage of p12I-transduced PBMCs was evident mainly at low concentrations of IL-2. Together, these data indicate that p12I may confer a proliferative advantage on HTLV-1–infected cells in the presence of suboptimal antigen stimulation and that this event may account for the clonal proliferation of infected T cells in vivo.
Human hematopoiesis in murine embryos after injecting human cord blood–derived hematopoietic stem cells into murine blastocysts
Authors: Harder Friedrich , Henschler Reinhard , Junghahn Ilse , Lamers Marinus C. , Müller Albrecht M. 
Published: July 2002

Abstract
At different developmental stages, candidate human hematopoietic stem cells (HSCs) are present within the CD34+ CD38− population. By means of xenotransplantation, such CD34+CD38− cells were recently shown to engraft the hematopoietic system of fetal sheep and nonobese diabetic severe combined immunodeficient adult mice. Here it is demonstrated that, after their injection into murine blastocysts, human cord blood (CB)–derived CD34+and CD34+ CD38− cells repopulate the hematopoietic tissues of nonimmunocompromised murine embryos and that human donor contribution can persist to adulthood. It is further observed that human hematopoietic progenitor cells are present in murine hematopoietic tissues of midgestational chimeric embryos and that progeny of the injected human HSCs activate erythroid-specific gene expression. Thus, the early murine embryo provides a suitable environment for the survival and differentiation of human CB CD34+ CD38− cells.
CEACAM1 Expression in Cutaneous Malignant Melanoma Predicts the Development of Metastatic Disease
Authors: Thies Anka , Moll Ingrid , Berger Jürgen , Wagener Christoph , Brümmer Jens , Schulze Hans-Joachim , Brunner Georg , Schumacher Udo 
Published: July 2002

PURPOSE: The cell adhesion molecule CEACAM1 is involved in intercellular adhesion and subsequent signal transduction events in a number of epithelia. CEACAM1 downregulation has been demonstrated in colorectal and prostate carcinomas. This study sought to analyze whether its expression in malignant melanoma is associated with metastasis.PATIENTS AND METHODS: CEACAM1 expression was immunohistochemically evaluated in 100 primary cutaneous malignant melanomas and correlated with metastasis in a 10-year follow-up. Furthermore, CEACAM1 expression was analyzed in metastatic lesions (11 distant metastases and six sentinel lymph node metastases). Univariate Kaplan-Meier analysis and multivariate Cox proportional hazard regression analysis adjusted for standard prognostic indicators were performed to assess the prognostic relevance of CEACAM1 expression.RESULTS: A total of 28 of 40 patients with CEACAM1-positive primary melanomas developed metastatic disease, compared with only six of 60 patients with CEACAM1-negative melanomas. Often, the strongest CEACAM1 expression was observed at the invading front. In addition, CEACAM1 expression was preserved in the metastatic lesions. Kaplan-Meier analysis revealed a highly significant association between CEACAM1 expression and metastasis (P < .0001); multivariate Cox regression analysis, including CEACAM1 expression status adjusted for tumor thickness, presence of ulceration, and mitotic rate, confirmed that CEACAM1 is an independent factor for the risk of metastasis and demonstrated that the predictive value of CEACAM1 expression is superior to that of tumor thickness.CONCLUSION: Expression of the cell adhesion molecule CEACAM1 in the primary tumors in melanoma patients is associated with the subsequent development of metastatic disease. This raises the possibility of a functional role for this cell adhesion molecule in the metastatic spread it indicates.
Excellent Disease Control and Survival in Patients With Advanced Nasopharyngeal Cancer Treated With Chemoradiation
Authors: Rischin Danny , Corry June , Smith Jennifer , Stewart Josephine , Hughes Peter , Peters Lester 
Published: July 2002

PURPOSE: To determine the efficacy and safety of epirubicin, cisplatin, and infusional fluorouracil (5-FU) chemotherapy followed by radiation with concurrent cisplatin in patients with locally and/or regionally advanced nasopharyngeal cancer. PATIENTS AND METHODS: Thirty-five patients were treated with three cycles of induction chemotherapy with epirubicin 50 mg/m2 and cisplatin 75 mg/m2 combined with continuous-infusion 5-FU 200 mg/m2 daily for 9 weeks, followed by concurrent chemoradiation of 60 Gy in 2-Gy fractions with cisplatin 20 mg/m2 daily for 5 days in weeks 1 and 6. RESULTS: Median age was 43 years, 74% had World Health Organization type III histology, and 91% had stage IV disease (International Union Against Cancer, ed 4). All patients received three cycles of induction chemotherapy, and 97% completed chemoradiation. The estimated 4-year progression-free survival rate was 81% (95% CI, 59% to 93%), and the estimated 4-year overall survival rate was 90% (95% CI, 74% to 97%). Only two patients have had a locoregional relapse by the close-out date despite the use of only 60 Gy. Induction chemotherapy was well tolerated, with 11% grade 3 or 4 stomatitis, 26% grade 3 vomiting, and no episodes of febrile neutropenia. Acute toxicities of chemoradiation were as follows: 23% grade 3 or 4 vomiting, 6% febrile neutropenia, 31% grade 3 mucositis, and 23% grade 3 skin toxicity. The most prevalent grade 3 late effects were xerostomia and hearing loss. CONCLUSION: This regimen was well tolerated, can be delivered as planned, and has resulted in excellent locoregional disease control and survival in patients with locally advanced nasopharyngeal cancer.
Supply and Geographic Distribution of Geriatric Physicians and Geriatric Nurse Practitioners
Authors: Xue Ying , Poghosyan Lusine , Lin Qinyun 
Published: November 2024

ImportanceThe rapidly growing population of older adults and their concomitant high prevalence of chronic health conditions require an increased supply in the specialized geriatric workforce to meet increasing health care demands. Understanding trends and geographic disparities in the supply of the geriatric workforce is essential for developing effective policies.ObjectivesTo examine temporal and geographic trends in the supply of geriatric physicians (GMDs) and geriatric nurse practitioners (GNPs) from 2010 to 2020 and to assess potential disparities between metropolitan and nonmetropolitan counties.Design, Setting, and ParticipantsThis repeated cross-sectional study used annual county-level data from 2010 to 2020, encompassing all counties in the 50 US states and Washington, DC. Statistical analysis was performed from June 2023 to March 2024.Main Outcomes and MeasuresThe primary outcomes were the numbers of GMDs, GNPs, and the combined number of GMDs and GNPs per 100 000 older adults. The secondary outcome included the proportion of counties with or without any GMDs or GNPs.ResultsFrom 2010 to 2020, the national per capita supply of GMDs decreased by 12.7%, from 13.4 per 100 000 older adults in 2010 to 11.7 per 100 000 older adults in 2020, while GNPs increased by 125.0%, from 4.4 per 100 000 older adults in 2010 to 9.9 per 100 000 older adults in 2020. The combined GMD and GNP workforce increased by 21.3%, from 17.8 per 100 000 older adults in 2010 to 21.6 per 100 000 older adults in 2020. The distributions of older adults, GMDs, and GNPs closely resembled the distribution of metropolitan and nonmetropolitan counties, with GMDs and GNPs highly concentrated in metropolitan counties where the number of older adults was greatest. Throughout the study period, 63.9% of counties (2008 of 3142 in 2010-2019; 2009 of 3143 in 2020), predominantly small and nonmetropolitan counties, had no GMDs or GNPs, which was associated with the disparities between metropolitan and nonmetropolitan counties.Conclusions and RelevanceThis repeated cross-sectional study found that from 2010 to 2020, the overall national supply of GMDs and GNPs kept pace with the growth of the older population, largely due to the rapid growth in the number of GNPs. However, significant geographic disparities persisted, particularly in small and nonmetropolitan counties. Future efforts should focus on increasing the availability of GMDs and GNPs in underserved small and nonmetropolitan counties to ensure equitable access to geriatric care.
Production and Forming of Deposition‐Welded Hybrid Multimaterial Shafts
Authors: Merkel Paulina , Budde Laura , Biester Kai , Faqiri Yusuf , Prasanthan Vannila , Herrmann Paul , Kriwall Mareile , Schwarz Nick , Hermsdorf Jörg , Stonis Malte , Breidenstein Bernd , Hassel Thomas , Overmeyer Ludger , Behrens Bernd‐Arno 
Published: November 2024

The combination of several materials in one component can contribute to increased performance. Herein, three types of hybrid components are manufactured using two cladding processes and one joining process. The resulting workpieces are then formed and tested to determine the potential of the different material combinations. Two types of workpieces are produced to investigate multilayer claddings made of different materials, which serve to positively adjust the residual stress. The workpieces are tested using microstructural images and hardness measurements to characterize the microstructure and properties of the intermediate layers. In addition, residual stress measurements are carried out to determine the residual stress ratios. Compressive residual stresses are present in the subsurface of the welded and subsequently formed layer, which will improve the service life in case of rolling load conditions. The third type of workpiece is a combination of aluminum alloy and steel with a cladding layer that combines the performance of the cladding material in the bearing seat with the weight reduction of the aluminum alloy. Scanning Electron Microscopy (SEM) measurements are used to determine whether the application of the cladding has an influence on the intermetallic phase seam in the joining zone of aluminum alloy and steel.
Design Rules for 3D Printing‐Assisted Pressure Sensor Manufacturing: Achieving Broad Pressure Range Linearity
Authors: Baek Jinwook , Zhang Yuxuan , Qin Fei , Fu Xingyu , Kim Min‐Seok , Song Han‐Wook , Oh Jung‐Hyun , Kim Garam , Lee Sunghwan 
Published: November 2024

AbstractRecent advancements in 3D printing technology have expanded its application to manufacturing pressure sensors. By harnessing the cost‐effectiveness, streamlined processes, and design flexibility of 3D printing, sensor fabrication can be customized to meet specific performance needs. Thus far, 3D printing in pressure sensor development has been primarily limited to creating molds for transferring patterns onto flexible substrates, restricting both material selection and sensor performance. To fully unlock the potential of 3D printing in advanced pressure sensor fabrication, it is crucial to establish effective design rules focused on enhancing the figure of merit performance. This study introduces a universal design strategy aimed at maintaining high sensitivity across a wide pressure range—a challenging feat, as sensitivity significantly decreases at higher pressures. Our approach centers on engineering the deformability of 3D‐printed structures, achieving a linear increase in contact area between sensor patterns and electrodes without reaching saturation. Sensors designed with high elongation and low stiffness exhibit consistent sensitivity of 162.5 kPa⁻¹ across a broad pressure range (0.05–300 kPa). Mechanistic investigations through finite element analysis confirm that engineered deformability is key to achieving this enhanced linear response, offering robust sensing capabilities for demanding applications such as deep‐sea and space exploration.
Picosecond Operation of Optoelectronic Hybrid Phase Change Memory Based on Si‐Doped Sb Films
Authors: Liu Qianchen , Wei Tao , Zheng Yonghui , Xuan Chuantao , Sun Lihao , Hu Jing , Cheng Miao , Liu Qianqian , Wang Ruirui , Li Wanfei , Cheng Yan , Liu Bo 
Published: November 2024

AbstractPhase‐change random access memory is anticipated to break the bottleneck of the “storage wall” due to its advantages in simultaneous data storage and in‐memory computing. However, operation speed constrains its application scenarios. Antimony (Sb) thin film has ultrafast phase change speeds, low power consumption, and a straightforward chemical composition. In this study, silicon (Si) doping is employed to enhance the stability of pure Sb while achieving both ultrafast operational speeds and superior thermal stability concurrently. By utilizing optoelectronic hybrid phase change memory, the SET and RESET operation speeds can reach as fast as 26 and 13 ps, respectively, when using Si‐doped Sb films. The absence of the Si─Sb bond results in simple cubic nuclei within the amorphous film, which is posited as the structural basis for the high operational speed. These novel insights into ultrafast speed and phase mechanisms are poised to have valuable evidence for future high‐speed memory designs.
Polymeric Charge‐Transporting Materials for Inverted Perovskite Solar Cells
Authors: Hu Xiaodong , Wang Lingyuan , Luo Siwei , Yan He , Chen Shangshang 
Published: November 2024

AbstractInverted perovskite solar cells (PSCs) hold exceptional promise as next‐generation photovoltaic technology, where both perovskite absorbers and charge‐transporting materials (CTMs) play critical roles in cell performance. In recent years, polymeric CTMs have played an important role in developing efficient, stable, and large‐area inverted PSCs due to their unique properties of high conductivity, tunable structures, and mechanical flexibility. This review provides a comprehensive overview of polymeric CTMs used in inverted PSCs, encompassing polymeric hole transport materials (HTMs) and electron transport materials (ETMs). the relationship between their molecular structures, modification strategies are systematically summarized and analyzed for adjusting energy levels, and improving charge extraction, enabling a deep understanding of these widely used materials. The review also explores effective strategies for designing even more efficient polymeric CTMs. Finally, an outlook is proposed on the exciting research of novel polymeric CTMs, paving the way for their commercialized applications in PSCs.
PbSe Thermoelectrics: Efficient Candidates for Power Generation and Cooling
Authors: Liu Shibo , Qin Bingchao , Zhao Li‐Dong 
Published: November 2024

AbstractThermoelectric materials enable efficient and clean conversion between heat and electricity, offering significant application prospects in waste heat recovery and solid‐state cooling. Lead selenide (PbSe) is a more abundant and cost‐effective alternative to PbTe with promising potential for mid‐temperature applications. However, things have changed very recently with the discovery of the traditional power generator PbSe being rather competitive as a thermoelectric cooler, opening new avenues for investigating this compound. This review aims to comb how the research achievements and promising performance of PbSe have shifted from medium to near‐room temperatures, by comprehensively discussing various strategies to enhance the thermoelectric efficiency at different temperature ranges. Subsequently, it is reviewed how these advances in materials have triggered deep investigations on constructing high‐efficiency power generation and cooling devices based on PbSe. Finally, a personal summary and outlook are presented on how to fully exploit the high‐ranged thermoelectric performance of PbSe materials and manufacture high‐efficiency power generators and coolers, thus promoting practical applications in the future.