Permissive Status Research Articles

Revised HLA-DP TCE-Core Permissiveness Model Better Defines Relapse Risk and Survival following Haploidentical Transplant

The presence of an HLA-DPB1 nonpermissive mismatch (NPMM) by the TCE-3 model has been associated with improved survival following haploidentical donor transplantation (HIDT) using post-transplantation cyclophosphamide (PTCy). With the development of a revised model (TCE-Core) that further separates TCE-3 "group 3" alleles into "core" (C) and "noncore" (NC) alleles, a formerly permissive mismatch (PMM) resulting from group 3 alleles in both donor and recipient is now considered a C-NPMM if 1 or more of those alleles is NC. We aimed to study the additional effect of HLA-DPB1 C-NPMM according to the TCE-Core algorithm, as well as the directional vector of the mismatch, on outcomes following HIDT. To this end, we analyzed 242 consecutive HIDT recipients with acute leukemia or myelodysplastic syndrome who underwent transplantation between 2005 and 2021 (median age, 51 years; range, 19 to 80 years). The median follow-up was 62 months (range, 23 to 199 months). Of the 136 HIDTs classified as PMM by TCE-3, 73 were reclassified as a C-NPMM by the TCE-Core algorithm, of which 36 were in the graft-versus host (GVH) vector (37 were host-versus-graft [HVG] only). Given comparable survival between conventional NPMM and C-NPMM, GVH/bidirectional were analyzed together (nonpermissive). HVG-only C-NPMM were combined with HLA-DPB1-matched and PMM (permissive) because of similar outcomes. The presence of a TCE-Core-defined nonpermissive HLA-DP mismatch resulted in superior 5-year overall survival (OS) (66% versus 47%) and disease-free survival (DFS) (60% versus 43%). Compared to the conventional TCE-3 algorithm, TCE-Core identified a higher percentage of nonpermissive transplants (38% versus 23%) and better discriminated outcomes between nonpermissive and permissive status, with a larger difference in survival outcomes using TCE-Core compared to TCE-3 (OS Δ, 18.3% versus 12.7%; DFS Δ, 16.5% versus 8.5%). In multivariable analysis (MVA), a nonpermissive TCE-Core mismatch led to improved OS (hazard ratio [HR], .54; P = .003) and DFS (HR, .62; P = .013), largely due to decreased relapse risk (HR, .63; P = .049). In contrast, nonrelapse mortality (NRM) and graft-versus-host disease (GVHD) outcomes were not significantly impacted. In summary, the presence of nonpermissive TCE-Core HLA-DP mismatch strongly predicts survival following PTCy-based HIDT, owing to a reduction in relapse risk without a corresponding increase in GVHD or NRM. As a donor selection tool, TCE-Core appears to better discriminate HIDT outcomes while at the same time identifying a larger percentage of the potential donor pool.

Enhancing Permit Status Checking for the Integrated Public Service Information and Reporting System Application

The district government of Sanggau already has a public service mall (MPP), which is used by all agencies as a place of service. SIPADU (Integrated Public Service Information and Reporting System) is the name of this application, which has various features to meet the needs of MPPs (Public Service Mall). Currently, users of the SIPADU application find it difficult to check the status of permissions. Users must first complete the authentication procedure in order to obtain the desired permission status. This research was conducted to implement a solution to make it easier for users to check the status of the submitted licensing by building a web-based system that will search for the data without requiring login authentication. The analytical methods used include Literature Study and Interview. The design method used is the waterfall method with 6 stages of the process, namely Planning, Analysis, Design, Implementation, Testing, and Verification. The result of this system is a website that can check the status of the permit being submitted. The results of the User Interface evaluation are following the provisions of the Eight Golden Rules method and the results of the evaluation of system testing using the BlackBox testing method with the results showing 100% no errors occur so that it is very suitable for use by users. This study applies the Web Scraping method using PHP scripts and using the Apache Web Server to obtain all licensing data using authentication data provided by PT Media Visual Group so that all users of the SIPADU application can track licensing.

ARRANGEMENT OF ROAD PASS PERMISSION WITH LOGARITHMIC METHOD IN GAS STATION PROCESSED RECONSTRUCTION ISLANDS

In terms of showing the details of the zoning islands within themselves, the zoning plans show different places under the application roof as additions, locations and revisions in a scale of 1/1000. In the zoning plan of 1000, some zoning islands are processed as gas station areas according to the condition of the road networks. The most critical problem in the processed gas station areas is to determine which way to enter and exit the gas station. In other words, it is the job of editing the road pass permission status. Especially in our country, this situation can be realized with the opinion of two different institutions. In this way, it is determined how many meters of road pass permission will be taken from the side of the municipality or highways, from the route under its own road dominance, from the wide part of the road and taking into account various parameters such as this. As a method, when the legal regulation with a certain upper and lower limit is considered as an exponential logarithmic function, this process can be done by determining the floor and ceiling in the logarithmic interval from bottom to top.

Cyber-physical system based on image recognition to improve traffic flow: A case study

Vehicular traffic in metropolitan areas turns congested along either paths or periods. As a case study, we have considered a mass transport system with a bus fleet that rides over exclusive lanes across streets and avenues in an urban area that does not allow
 the circulation of lightweight vehicles, cargo, and motorcycles. This traffic flow becomes congested due to the absence of restriction policies based on criteria. Moreover, the exclusive lanes are at ground level, decreasing lanes for other vehicles. The main objective of this proposal consists of controlling the access to the exclusive lanes by a cyber-physical system following authorization conditions, verifying the permission status of a vehicle by the accurate recognition of license plates to reduce traffic congestion. Therefore, in the case of invading an exclusive lane without permission, the vehicle owner gets a notification of the fine with the respective evidence.

English

The amount of scientific researches is increasing steadily. In today's information age, parallel to technological advances, scientific research keeps pace with innovation and development. Recent research in social and humanities sheds light on many innovative approaches and guides. In this study, answers were sought with the help of the document analysis model for answering the What is the distribution of postgraduate studies on string in Turkey between 1993 and 2019 in terms of years, institute types, permission status, and university variables? problem statement. With the research, it was intended to determine the frequency and percentage rates of postgraduate studies carried out under the name of Stringed instruments in the National Thesis Centre of Higher Education Institution between 1993 and 2019, to obtain answers to How are the distributions by the university? How are the distributions by years? How are the distributions by postgraduate thesis type? and How is the distribution of the theses made according to the access status? questions. Key words: String instruments, string research, string graduate studies, music research, graduate music theses.

A SCREENING STUDY ABOUT DOCTORATE AND PROFICIENCY IN ARTS THESIS IN THE FIELD OF INTERIOR ARCHITECTURE

In this study, aimed to investigate the doctorate and proficiency in arts thesis which was done in the field of interior architecture in Turkey. First stage, in the context of this purpose, doctorate and proficiency in arts thesis in the field of interior architecture which accessible from YÖK National Thesis Center were analyzed according to permission status, the types, the years, the university and the institute. In the second stage, the content of the thesis studies (methods, data collection tools and subjects) were evaluted by classifying the according to the information of the thesis (type, year, university and institute). Descriptive survey model was chosen as the method of study. The findings obtained from the analysis are important in terms of revealing the status and trends of the field of interior architecture.

Maternal SENP7 programs meiosis architecture and embryo survival in mouse

Understanding the mechanisms underlying abnormal egg production and pregnancy loss is significant for human fertility. SENP7, a SUMO poly-chain editing enzyme, has been regarded as a mitotic regulator of heterochromatin integrity and DNA repair. Herein, we report the roles of SENP7 in mammalian reproductive scenario. Mouse oocytes deficient in SENP7 experienced meiotic arrest at prophase I and metaphase I stages, causing a substantial decrease of mature eggs. Hyperaceylation and hypomethylation of histone H3 and up-regulation of Cdc14B/C accompanied by down-regulation of CyclinB1 and CyclinB2 were further recognized as contributors to defective M-phase entry and spindle assembly in oocytes. The spindle assembly checkpoint activated by defective spindle morphogenesis, which was also caused by mislocalization and ubiquitylation-mediated proteasomal degradation of γ-tubulin, blocked oocytes at meiosis I stage. SENP7-depleted embryos exhibited severely defective maternal-zygotic transition and progressive degeneration, resulting in nearly no blastocyst production. The disrupted epigenetic landscape on histone H3 restricted Rad51C loading onto DNA lesions due to elevated HP1α euchromatic deposition, and reduced DNA 5hmC challenged the permissive status for zygotic DNA repair, which induce embryo death. Our study pinpoints SENP7 as a novel determinant in epigenetic programming and major pathways that govern oocyte and embryo development programs in mammals.

수지형 체외식 초음파 프로브의 성능 평가 가이드라인 개발

세계적인 인구 고령화와 생활수준의 향상에 따른 국민들의 건강에 대한 관심이 커지면서 최근 전자의료기기의 시장도 증대되고 있다. 수지형체외식초음파프로브는 허가 신청 건수가 높은 다빈도 허가 심사 대상 의료기기이며 최근 병원 등의 임상분야에서 그 활용도가 높다. 하지만, 수지형체외식초음파프로브의 성능 평가를 위한 국내 기준은 명확하게 마련되지 않은 실정이고, 허가심사 및 품질평가 등을 위한 가이드라인 조차 마련되어 있지 않다. 따라서 본 연구에서는 수지형체외식초음파프로브의 특성, 허가 및 시장현황을 조사하고, 관련 국내 외 규격을 검토하여 성능평가 시험항목, 기준 및 방법을 도출하였으며, 시험검증을 통하여 최종적으로 국제조화되고 국내 실정에 적합한 성능 평가 가이드라인을 마련하였다. 향후 본 연구결과를 의료기기 관련 업체에서 활용함으로써 수지형체 외식초음파프로브의 품질 및 성능 향상을 도모하고, 허가를 위한 심사 평가의 일관성을 확보할 수 있을 것으로 기대된다. The electrical medical device market have been expanded since the public interest in healthy living that has deepened together with the global health trend of the aging population. The external hand-held ultrasonic probe is a frequently approved medical device and it is commonly used in the clinical field. However, there is no obvious standard or a guideline in Korea on regarding evaluation of performance of such external hand-held ultrasonic probe for approval and quality management. In this study, local and foreign reference standards were reviewed to propose performance test standards and methods after conducting characteristic of probe, market, and permission status. In addition, such proposed test items were validated to develop a draft guideline that is internationally harmonized for performance evaluation. This study is expected not only improve the quality and performance of the external hand-held ultrasonic probe but also contribute to securing consistency of permission and evaluation works for approval.

Prognostic Impact of Physiological B-Cell Precursors (hematogones) in the Bone Marrow As Determined by Immunophenotyping in the Post-Transplant Period in Patients with AML

AbstractAbstract 1406▪▪This icon denotes a clinically relevant abstractAiming to improve post-transplant monitoring strategies for patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), approaches to monitor the minimal residual disease load are at present limited to distinct genetic subgroups, e.g. NPM1mut AML. In the conservative treatment setting, increased levels of physiologic B-cell precursors (>0.01% CD10+/CD19+ cells; “hematogones”) as determined by multiparameter flow cytometry (MFC) in the bone marrow (BM) were suggested to be favorable in AML pts (Chantepie et al., Blood, 2011). We investigated whether the prognostic impact of physiologic B-cell precursors can be confirmed in pts with myeloid malignancies in the transplant context.We quantified CD10+/CD19+ B-cell precursors by MFC in the post-transplant period in 76 pts with AML/MDS who received allogeneic hematopoietic stem cell transplantation (HSCT) at Hamburg University, and performed correlation with survival (41 m/35 f; 18–71 yrs; de novo AML: n=51; s-/t-AML: n=11; MDS: n=13). The majority (n=84, 73%) received reduced intensity conditioning (RIC), mainly based on the FLAMSA regimen. Hematogones were evaluated by MFC on days +30 (d30) and +100 (d100) post-HSCT including the following antibody panel: CD19+, CD10+, CD34+, TdT+.Median levels of CD10+/CD19+ cells were 0,06% on day 30 (mean, 0.25%; range, 0–2.4%) and 1.55% on day 100 (mean, 2.13%; range, 0–12.4%). OS from HSCT did not differ on the basis of the CD10+/CD19+ cells measured on d30 (mean±SD=61±6 weeks, for CD10+/CD19+ cells below the mean of 0.25% vs 74±13 weeks for CD10+/CD19+ cells above the mean, RR=0.73, p=0.685). Estimated 1-year-OS±SE was 63±10% for CD10+/CD19+ cells below the mean of 0.25% versus 71±17% for CD10+/CD19+ cells above the mean, respectively. EFS did not show a significant difference, either. Mean CD10+/CD19+ cells on day 100 associated positively with 1-year-OS. In the group below the mean CD10+/CD19+ cells of 2.13%, 1-year-OS±SE was estimated to be 69±9% (median±SEM=89±10 weeks) which was worse when compared to the group above the mean with a 1-year-OS±SE of 83±15% (median±SEM=96±8 weeks; RR=0.124, p=0.046). The effect of low versus high CD10+/CD19+ cells measured at day 100 on EFS was even more pronounced. 1-year-EFS was significantly worse with 60±10% in the group with lower CD10+CD19+ counts on day 100 versus 95±4% in the group with higher counts (RR=0.095, 95%CI=0.012–0.728, p=0.024).In univariate analysis, disease stage, remission status pre-HSCT, cytogenetic risk group and cGVHD had significant influence on OS and/or EFS. By multivariate analysis, CD10+/CD19+ cells on day 100 remained significantly associated with improved EFS (RR=0.998, p=0.001) but significance of the association with OS was lost (RR=0.145, p=0.07). Other factors significantly associated with superior OS and EFS were occurrence of cGVHD (OS: RR=0.997, p=0.049, EFS: RR=0.996, p=0.001), and low/intermediate cytogenetic risk group (OS: RR=0.995, p=0.005, EFS: RR=0.997, p=0.03).To the best of our knowledge, an association of CD10+/CD19+ cells measured by MFC with survival has not been performed after HSCT in pts with AML and MDS. Our study is the first one showing a favorable prognostic impact of increased CD10+/CD19+ cells 100 days after HSCT. It seems that the level of physiological precursors contributes to the prognostic parameters in patients with myeloid malignancies undergoing HSCT. In more detail, a proportion of more than 2.13% of hematogones at day 100 was associated with improved OS and EFS. The association remained positive in multivariate Cox regression analysis, when other parameters such as pre-transplant permission status, disease stage and cGvHD were included. In conclusion, the hematogones level at day 100 seems to be an independent prognostic parameter which should be further evaluated in pts with myeloid malignancies undergoing HSCT. Considering the experience needed for the determination of leukemia associated immunophenotypes by MFC, or the lack of molecular markers suitable for MRD monitoring in many AML and MDS patients, the introduction of hematogones measurement at defined time points may contribute to the identification of high-risk patients in the transplant context. Disclosures:Bacher:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership.

STAT1 signaling is required for optimal Th1 cell differentiation in mice

Although IFN-γ alone does not prime type I T helper cell (Th1) differentiation, the loss of IFN-γ signaling leads to impaired Th1 phenotype: IFN-γ receptor-deficient (Ifngr −/−) Th1 cells fail to permanently repress IL-4 expression. They can differentiate into IL-4-producing cells under Th2-inducing conditions. These observations suggest that IFN-γ signaling plays a critical role in silencing Il4 gene in Th1 cells and stabilizing Th1 phenotype. IFN-γ signaling has been further shown to inhibit IL-4 expression by inhibiting STAT6 phosphorylation. This work aims to study the mechanism by which STAT1, the downstream molecule that transduces IFN-γ signaling, may mediate suppression of IL-4 expression in Th1 cells. The results show that STAT1-deficient naive CD4+ T cells express a reduced level of IFN-γ as well as an elevated level of IL-4. These cells exhibit bias to differentiate into Th2 cells under unpolarized conditions. Under Th1-inducing conditions, STAT1-deficient naive CD4+ T cells show impaired Th1 differentiation: Stat1 −/− Th1 cells express reduced levels of IFN-γ and T-bet. These cells also fail to repress the expression of IL-4 and GATA-3 and retain STAT6 signaling. More importantly, Stat1 −/− Th1 cells can be effectively induced to differentiate into IL-4-producing cells under Th2-inducing conditions. Ectopic expression of T-bet in Stat1 −/− Th1 cells dramatically represses their ability to do so and drastically restores IFN-γ expression, suggesting that STAT1 may inhibit IL-4 expression through T-bet. Finally, histone H3 acetylation (H3AC) and histone H3 K4 dimethylation (H3K4dim) were observed in two enhancer regions of Il4 gene locus in Stat1 −/− Th1 cells, suggesting a permissive status of Il4 gene locus in these cells. Thus, this study reveals new mechanisms by which STAT1 signaling may mediate repression of Il4 gene in Th1 cells: upregulating T-bet that subsequently represses GATA3 and IL-4 expression, antagonizing STAT6 signaling, and inhibiting epigenetic modifications in Il4 gene locus.

Epigenetic patterns of the retinoic acid receptor β2 promoter in retinoic acid-resistant thyroid cancer cells

Treatment with retinoic acid (RA) is effective to restore radioactive iodine uptake in metastases of a small fraction of thyroid cancer patients. In order to find predictive markers of response, we took advantage of two thyroid cancer cell lines, FTC133 and FTC238, with low RA-receptor (RAR)beta expression but differing in their response to RA. We report that in both cell lines, RA signalling pathways are functional, as transactivation of an exogenous RARbeta2 promoter is effective in the presence of pharmacological concentrations of all-trans RA, and enhanced in RA-resistant FTC238 cells after ectopical expression of RARbeta, suggesting a defective endogenous RARbeta2 promoter in these cells. Further analyses show that whereas the RARbeta2 promoter is in an unmethylated permissive status in both FTC133 and FTC238 cells, it failed to be associated with acetylated forms of histones H3 or H4 in FTC238 cells upon RA treatment. Incubation with a histone deacetylase inhibitor, alone or in combination with RA, restored histone acetylation levels and reactivated RARbeta and differentiation marker Na+/I- symporter gene expression. Thus, histone modification patterns may explain RA-refractoriness in differentiated thyroid cancer patients and suggest a potential benefit of combined transcriptional and differentiation therapies.

Expression and regulation of 17β-hydroxysteroid dehydrogenase 7 in the rabbit

We cloned partial cDNA sequences of rabbit 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1) and 17β-HSD7. We analyzed the tissue distribution of 17ß-HSD7 as well as the expression in corpus luteum and endometrium during pseudopregnancy. The obtained cDNA sequence of 17β-HSD7 coded for all functional regions of the protein and showed 86 and 81% similarity to human and rodent sequences, respectively. The partial sequence of rabbit 17β-HSD1 was 76 and 82% similar to rodent and human sequences. By Northern analysis 17β-HSD7 expression was predominantly found in reproductive organs like ovary, oviduct, endometrium, placenta and mammary gland. Substantial expression was also apparent in the heart, stomach and cerebellum. The 17β-HSD1 could be detected in placenta by reverse transcriptase-polymerase chain reaction (RT-PCR), so far. During rabbit pseudopregnancy 17β-HSD7 expression was found to be regulated in corpus luteum as well as in endometrium. In the corpus luteum, strongest expression occurred from d10 to d14 of pseudopregnancy (p. hCG) and was downregulated on d16 p. hCG. In endometrium strongest expression of 17β-HSD7 was found on d6 p. hCG, when the endometrium was differentiated to its implantation permissive status.

Effects of host endocrine gland removal on the permissive status of laboratory rodents to infection by Schistosoma mansoni

Knopf P. M. and Soliman M. 1980. Effects of host endocrine gland removal on the permissive status of laboratory rodents to infection by Schistosoma mansoni. International Journal for Parasitology, 10: 197–204. The capacity of Schistosoma mansoni to complete its life cycle was compared in CD-1 mice (permissive hosts) and Sprague-Dawley rats (nonpermissive hosts) from which the pituitary gland had been removed prior to infection with cercariae. Except for a modest decrease in egg burden, none of the parameters of worm life cycle assessed were affected in hypophysectomized mice. In contrast, all these parameters were affected in hypophysectomized rats, e.g. onset of adult worm elimination was delayed, worm development improved, oviposition increased and miracidia developed. Effects of removal from rats of the thyroid/parathyroid glands on the parasite life cycle were similar to hypophysectomy; adrenalectomy or gonadectomy were without affect. Differences between thyroidectomized and thymectomized rats are discussed. It is concluded that host hormones contribute to the nonpermissive status of rats to Schistosoma mansoni infections.