bluuebunny/crossref_metadata_2025 huggingface dataset:
SISTEM INFORMASI ADMINISTRASI DESA DI KANTOR DESA SUMBERSEKAR
Authors: Susilowati Meme , Chandra Dicky
Published: February 2021

Kantor Desa Sumbersekar merupakan kantor desa yang terletak di daerah Dau, Malang. Kantor desa inibergerak pada bidang pelayanan masyarakat, seperti : Membuat Kartu Tanda Penduduk (KTP), membuatKartu Keluarga (KK), dan membuat surat keterangan sesuai dengan keinginan warga, namun seiringberjalannya waktu Kantor Desa Sumbersekar mencetak surat dalam jumlah yang banyak, sehinggamenyulitkan proses perekapan surat serta No. Kop surat yang masih direkap secara manual. Sehinggamenyulitkan staf kantor desa untuk mencari No. Kop surat yang akan digunakan karena jumlah suratyang juga terhitung sangat banyak dan harus mencarinya di buku rekapan. Proses pembuatan surat jugamasih menggunakan Microsoft Word, meskipun itu menggunakan teknologi komputer tetapi itu masihsangat menyulitkan karena menyetikan isi surat tersebut secara manual dan juga tehitung sangat banyak.Proses pelaporan operasional tahunan maupun bulanan juga masih dilakukan secara manual. Sehinggastaf desa juga harus merekap menghitung jumlah surat yang keluar, surat yang gagal diterbitkan. Olehkarena itu, diperlukan sebuah sistem informasi administrasi desa yang dapat membantu pencatatannomor surat, membantu pembuatan surat, perekapan surat, pembuata KTP maupun KK, serta sebuahfitur pelaporan yang lengkap sehingga memudahkan kinerja dari kantor desa tersebut sendiri.
ANALISIS KESENJANGAN TERHADAP PENERAPAN SISTEM MANAJEMEN MUTU ISO 9001:2015 PADA CV. TIRTA MANGKOK MERAH
Authors: Crismanto Yoan , , ST., MprocgMgnt Sunday Noya
Published: February 2021

CV. Tirta Mangkok Merah adalah sebuah perusahaan yang bergerak di bidang industri air mineral. Masalah yang dihadapi adalah tidak maksimalnya penerapan sistem manajemen mutu. Hal tersebut terjadi karena kurangnya sosialisasi yang dilakukan oleh perushaan, sehingga mengakibatkan karyawan tidak dapat memahami prosedur-prosedur yang sesuai dengan sistem manajemen mutu yang ada.Oleh sebab itu, untuk mengatasi permasalahan mengenai penerapan sistem manajemen mutu ISO 9001:2015 di perusahaan, maka akan diindentifikasi mengenai permasalahan apa saja yang menyebabkan penerapan tidak dapat berjalan secara penuh. Kemudian faktor-fator tersebut akan dianalisis dengan menggunakan metode Gap Analysis dan Fault Tree Analysis (FTA).Berdasarkan hasil analisis yang telah dilakukan dengan menggunakan dua metode yaitu Gap Analysis dan FTA, maka diketahui bahwa perusahaan telah dapat meningkatkan presentase penerapan Sistem Manajemen Mutu ISO 9001:2015 berdasarkan range presentase peniliaian sebesar 73%-97% dari sebelumnya sebesar 58%-90%.
SISTEM INFORMASI LAYANAN PEMINJAMAN FASILITAS IT (IT HELP-DESK MANAGEMENT SYSTEM)
Authors: Kurniawan Yudhi , Wiranti Frasiska
Published: February 2021

Universitas Ma Chung merupakan salah satu perguruan tinggi swasta di Kota Malang. Dalam rangka memenuhi kebutuhan seluruh sivitas akademik, Universitas Ma Chung menyediakan beberapa fasilitas mulai dari barang IT, layanan perbaikan fasilitas IT dan layanan mahasiswa. Hingga saat ini, Universitas Ma Chung masih menggunakan cara manual dengan menggunakan Ms, Excel untuk mencatat permohonan peminjaman barang IT, perbaikan dan permohonan layanan. Selain itu, pengguna yang akan melakukan peminjaman juga harus membuat surat pinjaman dan kemudian diberikan kepada kepala divisi. Pengguna juga tidak dapat mengetahui apakah barang yang akan dipinjam masih ada pada tanggal yang diajukan atau tidak. Jika tidak, maka calon pengguna harus membuat ulang surat peminjaman fasilitas. Berdasarkan latar belakang, terdapat tiga masalah utama dalam proses layanan. Pertama, permohonan peminjaman fasilitas IT, permohonan perbaikan dan permohonan layanan IS/IT serta penjadwalan masih dilakukan dengan cara manual. Kedua, keluar masuk fasilitas Universitas yang dipinjam tidak dapat dipantau secara realtime. Ketiga, tidak adanya grafik laporan yang menunjukkan berapa banyak fasilitas Universitas yang dipinjam. Pengembangan sistem dilakukan dengan metode Three Major Phase yang dibagi dalam tiga fase utama, yaitu analisis, desain, dan implementasi. Sistem ini diharapkan dapat membantu Universitas Ma Chung untuk memantau perkembangan alur bisnis peminjaman, perbaikan dan layanan IS/IT. Hasil akhir yang didapat adalah laporan keluar masuk barang universitas serta jadwal peminjaman, perbaikan dan layanan.
PERILAKU NON PLAYER CHARACTER (NPC) PADA GAME FPS “ZOMBIE COLONIAL WARS” MENGGUNAKAN FINITE STATE MACHINE (FSM)
Authors: Astuti Yulia Windi , Yunus Amak , Ahsan Moh.
Published: February 2021

Penerapan kecerdasan buatan (AI) dalam sebuah game merupakan salah satu inovasi teknologi. Variasi game salah satunya adalah First Person Shooter (FPS). Kecerdasan buatan yang dikembangkan untuk merancang perilaku Non Player Character (NPC) dimana NPC dapat berperilaku secara bertahap dan berurutan sesuai state. Oleh sebab itu dikembangkan dengan menerapkan metode Finite State Machine (FSM) pada game “Zombie Colonial Wars”. Penerapan metode Finite State Machine (FSM) dalam game Zombie Colonial Wars berfungsi untuk melihat variasi respon perilaku pada NPC sesuai interaksi yang dilakukan oleh player. Hasil dari penelitian ini adalah game zombie colonial wars menghasilkan sebuah kecerdasan buatan pada perilaku NPC dengan mengimplementasikan metode finite state machine sehingga musuh dapat berperilaku berdasarkan interaksi yang telah dilakukan oleh player.
SOFTWARE REQUIREMENT SPECIFICATION SISTEM INFORMASI MANAJEMEN DAN GEOGRAFIS PEMETAAN SUMBER DAYA AIR
Authors: Kurniawan Yudhi , Lucky TI Paulus
Published: February 2021

Informasi Visual pada beberapa tahun ini menjadi trend dikalangan pengembang sistem visualisasi informasi dalam bentuk multimedia menjadi hal yang sudah tidak asing lagi bagi dunia teknologi informasi khususnya di bidang elektronik marketing, visual bukan hanya bisa dilihat dalam bentuk gambar bergerak 3 dimensi melainkan informasi yang mengandung unsur geografis dan keruangan juga merupaka visualisasi informasi yang cukup relevan digunakan untuk sebuah perencanaan, dengan melakukan mapping dan memetakan letak serta posisi bagi seorang eksekutif pada tataran pemerintahan merupakan salah satu tools yang sangat berguna, karena dengan memetakan suatu informasi maka dapat diketahui sebaran pola dan analisa ruang untuk pengambilan keputusan. Begitupun juga dengan Sumber Daya Air di mana pemetaan letak dan posisi serta pengelolaannya menjadi mutlak dibutuhkan untuk menjamin ketersediaan air bagi masyarakat, identifikasi dan inventarisasi sumber daya air didukung dengan validitas data penanggung jawab pada kelompok hippam serta monitoring pemeliharaan terhadap aset atau komponen pada infrastruktur dan kelengkapan sumber daya air perlu direncanakan dalam setiap anggaran belanja dan tentunya juga memperhatikan pemerataan pembangunan dengan tujuan untuk menjamin hajat hidup masyarakat. Dengan Sistem Informasi Manajemen Dan Geografis Pemetaan Sumber Daya Air menjadi sebuah early warning system bagi aktifitas pengelolaan dan manajemen Sumber Daya Air identifikasi awal dan dokumentasi kebutuhan peranglat lunak menjadi standar pengembangan Sistem Informasi dalam skala enterprise sesuai dengan standar IEEE 830-1998.
Fluid Dynamics of Condensation Process with Direct Contact in Desuperheaters
Authors: Rahman Towsibur , Islam Shubho MD. Ariful
Published: February 2021

Due to the global warming and environmental implications, the focus of household heating has shifted from fossil fuels towards environmentally friendly and renewable sources. Desuperheaters have been found an attractive option as a domestic provision for the warm water; they used steam induced direct contact condensation (DCC) as the major means to warm the water. The present study has been an attempt to investigate the hydrodynamics in the Desuperheater vessel experimentally, when the pressurized pulsating steam was injected into the vessel, where, the steam jet interacted co-currently with the slow-moving water. Visual flow visualization provided an overall flow picture that showed a circulation region when the pulsating steam was injected into the slow co-currently moving water and the peaked vorticity corresponded to the steam injection duration varying from 10-60 seconds. An array of 7 Hot Film Anemometers (HFA) was traversed axially and radially to determine the velocity fluctuations at 0 – 20 cm from the steam's nozzle exit. Vertical structures were obtained that corresponded to the entrainment of the steam with the surrounding concurrently moving water. The circulation regions were thus exhibited in relation to the steam's injection durations as well as the downstream axial distance of 2 cm and 15 cm from the nozzle exit, which showed that the core local circulation at 2 cm, lost 75-79% of its circulation at 15 cm downstream of the nozzle exit.
Nurses’ roles in palliative care: An Islamic perspective
Authors: Suprayitno Edy , Setiawan Iwan
Published: February 2021

Palliative care is an important approach for nurses to improve the quality of life of patients holistically and mitigate suffering among the patients in critical condition and near to death. This article provides an Islamic perspective about nurses’ roles in palliative care, which can be applied worldwide, especially in Muslim-majority countries. Understanding Islamic beliefs will help nurses provide professional and culturally sensitive nursing care. In its principle, Islam always respects the process of life until death comes. So, the application of Islamic values in palliative care will make the patients accept their ill condition completely, keep being close to Allah SWT (God), and die peacefully. The concepts of illness, death, early action on the dead, and palliative care application in nursing are explained in this article to open up new ideas rather than provide definitive answers. We hope that this perspective will highlight healthcare policymakers the need to integrate Islamic values in nursing practice.
Renal Sympathetic Denervation: From acute renal nerve stimulation induced hemodynamic changes to long-term clinical perspectives
Authors:   , Hoogerwaard Anna Francina
Published: February 2021

Worldwide there are many people with hypertension. However, the treatment of high blood pressure is not optimal and in many patients the blood pressure remains too high despite drug therapy. A potential new treatment for hypertension is renal sympathetic denervation (RDN); hereby the sympathetic nerves surrounding the renal arteries are denervated. The first results were promising regarding blood pressure reduction, but the first randomized sham-controlled studies showed disappointing results. Currently, the RDN procedure is under investigation to improve the procedure and select the appropriate hypertension patient category. In this thesis renal nerve stimulation (RNS) before and after renal denervation has been applied to improve the procedure. RNS was used both before and after RDN. Before RDN, RNS causes a rise in blood pressure, this effect is no longer present after RDN. This thesis describes the acute RNS-induced hemodynamic effects and changes in heart rate variability before and after RDN. In addition, we showed that patients who had no RNS-induced blood pressure increase after RDN had much better blood pressure lowering at follow-up compared to the patients who still had RNS-induced blood pressure rise. RNS may thus potentially be used to determine whether the denervation is complete. In addition, we describe in the thesis the possible future applications of RDN in other cardiovascular diseases characterized by sympathetic overdrive. Further research into the exact role of renal nerve stimulation during RDN is necessary, but this thesis has provided insight into the possible underlying mechanism of both RDN and RNS.
Natural Vascular Scaffolding Treatment Promotes Outward Remodeling During Arteriovenous Fistula Development in Rats
Authors: Shiu Yan-Ting , He Yuxia , Tey Jason C. S. , Knysheva Marina , Anderson Blake , Kauser Katalin
Published: February 2021

Following creation, an arteriovenous fistula (AVF) must mature (i.e., enlarge lumen to allow high blood flow) before being used for hemodialysis. AVF maturation failure rates are high, and currently, there are no effective therapy to treat this problem. The maturation process is likely affected by the integrity of the vascular extracellular matrix (ECM). Natural Vascular Scaffolding (NVS) Therapy is a new technology that interlinks collagen and elastin via photoactivation of a locally delivered small molecule (4-amino-1,8-naphtalamide). We hypothesized that NVS Therapy may improve AVF remodeling by preserving ECM integrity. AVFs were created in Wistar male rats by connecting the femoral vein (end) to femoral artery (side) in the same limb. Immediately after blood flow was restored to dilate the femoral vein by arterial pressure, a 10 μl-drop of the NVS compound (2 mg/ml) was placed on the anastomosis perivascularly. Following 5-min incubation, the NVS treated area was exposed to 1-min illumination by 450-nm light. The control group received 10 μl-drop of phosphate buffered saline (PBS) and the same light activation. The skin was closed, and rats were euthanized 4 weeks (n = 6–9 per group) post-AVF creation for histology, morphometry, immunohistochemistry (IHC), and multiphoton microscopy for second-harmonic-generation evaluation of collagen fibers. The vascular thickness was similar in both groups. The AVF vein’s open lumen area and % open lumen area in NVS-treated rats were significantly larger than in PBS-treated rats (4.2-fold p = 0.014 and 2-fold p = 0.009, respectively). The inflammatory markers IL-6 and MMP-9 in the AVF walls were significantly decreased in the NVS group than the PBS group. Collagen fibers in the vascular wall trended toward perpendicular alignment to the lumen circumference in the NVS-treated AVFs, with more defined shape but less area than in the PBS-treated AVFs. These results indicate that the NVS Therapy exerted changes in collagen, which may influence AVF maturation. Rats tolerated the NVS treatment well, and the lack of cell death by the treatment was confirmed in cell culture experiments. These results suggest that NVS treatment is safe and may have therapeutic potential by facilitating lumen expansion to enhanced AVF maturation in patients.
Cyber Physical Defense Framework for Distributed Smart Grid Applications
Authors: Sinha Ayush , Mohandas Manasi , Pandey Pankaj , Vyas O. P.
Published: February 2021

Cyber-Physical Systems (CPS) is the amalgamation of highly sophisticated sensors with physical spaces. These close conjunctions of sensors with communication infrastructure intrinsically linking to society’s Critical Infrastructures (C.I.) are being witnessed more often in the context of Smart Grid (SG). As a backbone of C.I., Smart Grid demonstrates ability to precisely monitor large scale energy systems and designed in order to achieve complex local and global objectives. Being capable of performing such sophisticated operation it also bears the vulnerability of being exposed for cyber-physical co-ordinated attack that may lead to catastrophic effect. Many researchers have analyze the different stages of cyber-physical co-ordinated attacks like attack detection, prevention, impact analysis and recovery plans but there exist a research gap to address all the issues under single framework. Through this paper, we propose a novel Cyber Physical Defense Framework (CPDF) based on National Institute of Standards and Technology (NIST) guidelines to address the cyber attack on SG. Our work addresses the pre and post attack scenario, attack vector formulation through hierarchical PetriNet modeling and recovery mechanism. We have performed experiment for Distributed Denial of Service (DDoS) and False Data Injection attack (FDI) to validate our framework effectiveness and established the efficacy of proposed model. In the end, we have presented a case study of FDI attack detection using machine learning technique on IEEE 9-bus and 14-bus system.
Repositioning Drugs to the Mitochondrial Fusion Protein 2 by Three-Tunnel Deep Neural Network for Alzheimer's Disease
Authors: Wang Xun , Zhong Yue , Ding Mao
Published: February 2021

Alzheimer's disease (AD) is a common neurodegenerative dementia in the elderly. Although there is no effective drug to treat AD, proteins associated with AD have been discovered in related studies. One of the proteins is mitochondrial fusion protein 2 (Mfn2), and its regulation presumably be related to AD. However, there is no specific drug for Mfn2 regulation. In this study, a three-tunnel deep neural network (3-Tunnel DNN) model is constructed and trained on the extended Davis dataset. In the prediction of drug-target binding affinity values, the accuracy of the model is up to 88.82% and the loss value is 0.172. By ranking the binding affinity values of 1,063 approved drugs and small molecular compounds in the DrugBank database, the top 15 drug molecules are recommended by the 3-Tunnel DNN model. After removing molecular weight <200 and topical drugs, a total of 11 drug molecules are selected for literature mining. The results show that six drugs have effect on AD, which are reported in references. Meanwhile, molecular docking experiments are implemented on the 11 drugs. The results show that all of the 11 drug molecules could dock with Mfn2 successfully, and 5 of them have great binding effect.
Comprehensive Analysis of CD4+ T Cell Responses to CMV pp65 Antigen Restricted by Single HLA-DR, -DQ, and -DP Allotype Within an Individual
Authors: Hyun You-Seok , Jo Hyeong-A , Lee Yong-Hun , Kim Sun-Mi , Baek In-Cheol , Sohn Hyun-Jung , Cho Hyun-Il , Kim Tai-Gyu
Published: February 2021

Within an individual, six different HLA class II heterodimers are expressed co-dominantly by two alleles of HLA-DR, -DQ, and -DP loci. However, it remained unclear which HLA allotypes were used in T cell responses to a given antigen. For the measurement of the CD4+ T cell responses restricted by a single HLA allotype, we established a panel of artificial antigen-presenting cells (aAPCs) expressing each single HLA allele of 20 HLA-DRB1, 16 HLA-DQ, and 13 HLA-DP alleles. CD4+ T cell responses to cytomegalovirus (CMV) pp65 restricted by single HLA class II allotype defined in 45 healthy donors. The average magnitude of CD4+ T cell responses by HLA-DR allotypes was higher than HLA-DQ and HLA-DP allotypes. CD4+ T cell responses by DRA*01:01/DRB1*04:06, DQA1*01:02/DQB1*06:02, DPA1*02:02/DPB1*05:01 were higher among the other alleles in each HLA-DR, -DQ, and -DP locus. Interestingly, the frequencies of HLA-DR alleles and the positivity of specific allotypes showed an inverse correlation. One allotype within individuals is dominantly used in CD4+ T cell response in 49% of donors, and two allotypes showed that in 7% of donors, and any positive response was detected in 44% of donors. Even if one individual had several dominant alleles, CD4+ T cell responses tended to be restricted by only one of them. Furthermore, CD8+ and CD4+ T cell responses by HLA class I and class II were correlated. Our results demonstrate that the CD4+ T cell preferentially use a few dominant HLA class II allotypes within individuals, similar to CD8+ T cell response to CMV pp65.
Engineered IgG1-Fc Molecules Define Valency Control of Cell Surface Fcγ Receptor Inhibition and Activation in Endosomes
Authors: Bailey Elizabeth M. , Choudhury Amit , Vuppula Harika , Ortiz Daniel F. , Schaeck John , Manning Anthony M. , Bosques Carlos J. , Hoppe Adam D.
Published: February 2021

The inhibition of Fcγ receptors (FcγR) is an attractive strategy for treating diseases driven by IgG immune complexes (IC). Previously, we demonstrated that an engineered tri-valent arrangement of IgG1 Fc domains (SIF1) potently inhibited FcγR activation by IC, whereas a penta-valent Fc molecule (PentX) activated FcγR, potentially mimicking ICs and leading to Syk phosphorylation. Thus, a precise balance exists between the number of engaged FcγRs for inhibition versus activation. Here, we demonstrate that Fc valency differentially controls FcγR activation and inhibition within distinct subcellular compartments. Large Fc multimer clusters consisting of 5-50 Fc domains predominately recruited Syk-mScarlet to patches on the plasma membrane, whereas PentX exclusively recruited Syk-mScarlet to endosomes in human monocytic cell line (THP-1 cells). In contrast, SIF1, similar to monomeric Fc, spent longer periods docked to FcγRs on the plasma membrane and did not accumulate and recruit Syk-mScarlet within large endosomes. Single particle tracking (SPT) of fluorescent engineered Fc molecules and Syk-mScarlet at the plasma membrane imaged by total internal reflection fluorescence microscopy (SPT-TIRF), revealed that Syk-mScarlet sampled the plasma membrane was not recruited to FcγR docked with any of the engineered Fc molecules at the plasma membrane. Furthermore, the motions of FcγRs docked with recombinant Fc (rFc), SIF1 or PentX, displayed similar motions with D ~ 0.15 μm2/s, indicating that SIF1 and PentX did not induce reorganization or microclustering of FcγRs beyond the ligating valency. Multicolor SPT-TIRF and brightness analysis of docked rFc, SIF1 and PentX also indicated that FcγRs were not pre-assembled into clusters. Taken together, activation on the plasma membrane requires assembly of more than 5 FcγRs. Unlike rFc or SIF1, PentX accumulated Syk-mScarlet on endosomes indicating that the threshold for FcγR activation on endosomes is lower than on the plasma membrane. We conclude that the inhibitory effects of SIF1 are mediated by stabilizing a ligated and inactive FcγR on the plasma membrane. Thus, FcγR inhibition can be achieved by low valency ligation with SIF1 that behaves similarly to FcγR docked with monomeric IgG.
Modified Adenovirus Prime-Protein Boost Clade C HIV Vaccine Strategy Results in Reduced Viral DNA in Blood and Tissues Following Tier 2 SHIV Challenge
Authors: Malherbe Delphine C. , Vang Lo , Mendy Jason , Barnette Philip T. , Spencer David A. , Reed Jason , Kareko Bettie W. , Sather D. Noah , Pandey Shilpi , Wibmer Constantinos K. , Robins Harlan , Fuller Deborah H. , Park Byung , Lakhashe Samir K. , Wilson James M. , Axthelm Michael K. , Ruprecht Ruth M. , Moore Penny L. , Sacha Jonah B. , Hessell Ann J. , Alexander Jeff , Haigwood Nancy L.
Published: February 2021

Designing immunogens and improving delivery methods eliciting protective immunity is a paramount goal of HIV vaccine development. A comparative vaccine challenge study was performed in rhesus macaques using clade C HIV Envelope (Env) and SIV Gag antigens. One group was vaccinated using co-immunization with DNA Gag and Env expression plasmids cloned from a single timepoint and trimeric Env gp140 glycoprotein from one of these clones (DNA+Protein). The other group was a prime-boost regimen composed of two replicating simian (SAd7) adenovirus-vectored vaccines expressing Gag and one Env clone from the same timepoint as the DNA+Protein group paired with the same Env gp140 trimer (SAd7+Protein). The env genes were isolated from a single pre-peak neutralization timepoint approximately 1 year post infection in CAP257, an individual with a high degree of neutralization breadth. Both DNA+Protein and SAd7+Protein vaccine strategies elicited significant Env-specific T cell responses, lesser Gag-specific responses, and moderate frequencies of Env-specific TFH cells. Both vaccine modalities readily elicited systemic and mucosal Env-specific IgG but not IgA. There was a higher frequency and magnitude of ADCC activity in the SAd7+Protein than the DNA+Protein arm. All macaques developed moderate Tier 1 heterologous neutralizing antibodies, while neutralization of Tier 1B or Tier 2 viruses was sporadic and found primarily in macaques in the SAd7+Protein group. Neither vaccine approach provided significant protection from viral acquisition against repeated titered mucosal challenges with a heterologous Tier 2 clade C SHIV. However, lymphoid and gut tissues collected at necropsy showed that animals in both vaccine groups each had significantly lower copies of viral DNA in individual tissues compared to levels in controls. In the SAd7+Protein-vaccinated macaques, total and peak PBMC viral DNA were significantly lower compared with controls. Taken together, this heterologous Tier 2 SHIV challenge study shows that combination vaccination with SAd7+Protein was superior to combination DNA+Protein in reducing viral seeding in tissues in the absence of protection from infection, thus emphasizing the priming role of replication-competent SAd7 vector. Despite the absence of correlates of protection, because antibody responses were significantly higher in this vaccine group, we hypothesize that vaccine-elicited antibodies contribute to limiting tissue viral seeding.
T Cells Actively Infiltrate the White Matter of the Aging Monkey Brain in Relation to Increased Microglial Reactivity and Cognitive Decline
Authors: Batterman Katelyn V. , Cabrera Payton E. , Moore Tara L. , Rosene Douglas L.
Published: February 2021

Normal aging is characterized by declines in processing speed, learning, memory, and executive function even in the absence of neurodegenerative diseases such as Alzheimer's Disease (AD). In normal aging monkeys and humans, neuronal loss does not account for cognitive impairment. Instead, loss of white matter volume and an accumulation of myelin sheath pathology begins in middle age and is associated with cognitive decline. It is unknown what causes this myelin pathology, but it likely involves increased neuroinflammation in white matter and failures in oligodendrocyte function (maturation and repair). In frontal white matter tracts vulnerable to myelin damage, microglia become chronically reactive and secrete harmful pro-inflammatory cytokines. Despite being in a phagocytic state, these microglia are ineffective at phagocytosing accruing myelin debris, which directly inhibits myelin sheath repair. Here, we asked whether reported age-related increases in pro-inflammatory markers were accompanied by an adaptive immune response involving T cells. We quantified T cells with immunohistochemistry in the brains of 34 cognitively characterized monkeys and found an age-related increase in perivascular T cells that surround CNS vasculature. We found a surprising age-related increase in T cells that infiltrate the white matter parenchyma. In the cingulum bundle the percentage of these parenchymal T cells increased with age relative to those in the perivascular space. In contrast, infiltrating T cells were rarely found in surrounding gray matter regions. We assessed whether T cell infiltration correlated with fibrinogen extravasation from the vasculature as a measure of BBB leakiness and found no correlation, suggesting that T cell infiltration is not a result of passive extravasation. Importantly, the density of T cells in the cingulum bundle correlated with microglial reactivity and with cognitive impairment. This is the first demonstration that T cell infiltration of white matter is associated with cognitive decline in the normal aging monkey.
A Low-Pressure, N2/CO2 Atmosphere Is Suitable for Cyanobacterium-Based Life-Support Systems on Mars
Authors: Verseux Cyprien , Heinicke Christiane , Ramalho Tiago P. , Determann Jonathan , Duckhorn Malte , Smagin Michael , Avila Marc
Published: February 2021

The leading space agencies aim for crewed missions to Mars in the coming decades. Among the associated challenges is the need to provide astronauts with life-support consumables and, for a Mars exploration program to be sustainable, most of those consumables should be generated on site. Research is being done to achieve this using cyanobacteria: fed from Mars's regolith and atmosphere, they would serve as a basis for biological life-support systems that rely on local materials. Efficiency will largely depend on cyanobacteria's behavior under artificial atmospheres: a compromise is needed between conditions that would be desirable from a purely engineering and logistical standpoint (by being close to conditions found on the Martian surface) and conditions that optimize cyanobacterial productivity. To help identify this compromise, we developed a low-pressure photobioreactor, dubbed Atmos, that can provide tightly regulated atmospheric conditions to nine cultivation chambers. We used it to study the effects of a 96% N2, 4% CO2 gas mixture at a total pressure of 100 hPa on Anabaena sp. PCC 7938. We showed that those atmospheric conditions (referred to as MDA-1) can support the vigorous autotrophic, diazotrophic growth of cyanobacteria. We found that MDA-1 did not prevent Anabaena sp. from using an analog of Martian regolith (MGS-1) as a nutrient source. Finally, we demonstrated that cyanobacterial biomass grown under MDA-1 could be used for feeding secondary consumers (here, the heterotrophic bacterium E. coli W). Taken as a whole, our results suggest that a mixture of gases extracted from the Martian atmosphere, brought to approximately one tenth of Earth's pressure at sea level, would be suitable for photobioreactor modules of cyanobacterium-based life-support systems. This finding could greatly enhance the viability of such systems on Mars.
Clinical Study of Correlation for the Intestinal and Pharyngeal Microbiota in the Premature Neonates
Authors: Yang Sen , Qiao Lina , Shi Jing , Xie Liang , Liu Yang , Xiong Ying , Liu Hanmin
Published: February 2021

Objective:There are mutual influences between intestine and lung, that propose a concept of the gut-lung axis, but the mechanism is still unclear. Microbial colonization in early life plays an important role in regulating intestinal and lung function. In order to explore the characteristics of early microbiota on the gut-lung axis, we studied the correlation between intestinal and pharyngeal microbiota on day 1 and day 28 after birth in premature neonates.

Methods:Thirteen neonates born at 26–32 weeks gestational age (GA) hospitalized at the neonatal intensive care unit (NICU) of the West China Second Hospital of Sichuan University were enrolled in this study. Stool samples and pharyngeal swabs samples were collected from each neonate on the first day (T1) and the 28th day (T28) after birth. Total bacterial DNA was extracted and sequenced using the Illumina MiSeq Sequencing System based on the V3–V4 hyper-variable regions of the 16S rRNA gene. Based on the sequencing results, the composition of the intestinal and pharyngeal microbiota was compared and analyzed.

Results:At T1, the difference in microbial composition between intestine and pharynx was not statistically significant. The intestinal microbiota was mainly composed ofUnidentified Enterobacteriaceae, Ralstonia, Streptococcus, Fusobacterium, Ureaplasma, etc. The pharyngeal microbiota was mainly composed ofUreaplasma, Bacteroides, Fusobacterium, etc.UreaplasmaandFusobacteriumwere detected in both intestine and pharynx. At T28, there was a significant difference in microbial composition between intestine and pharynx (p< 0.001). The intestinal microbiota was mainly composed ofUnidentified Clostridiales, Klebsiella, Unidentified Enterobacteriaceae, Enterobacter, Streptococcus, etc. Pharyngeal microbiota was mainly composed ofStreptococcus, Rothia, etc.Streptococcuswas detected in both intestine and pharynx.

Conclusions:The intestine and pharynx of premature neonates have a unique microbial composition, and share some common microbiota. Whether these microbiotas play a role in the mechanism of gut-lung crosstalk needs further study.
Transcriptome-Based Co-Expression of BRD4 and PD-1/PD-L1 Predicts Poor Overall Survival in Patients With Acute Myeloid Leukemia
Authors: Chen Cunte , Xu Ling , Gao Rili , Wang Shunqing , Zhang Yuping , Wang Caixia , Zeng Chengwu , Li Yangqiu
Published: February 2021

Positive response to PD-1/PD-L1 blockades was observed in the treatment of solid tumors. However, the clinical response to PD-1/PD-L1 blockade varied in patients with acute myeloid leukemia (AML). It is thought that there are factors other than PD-1 and PD-L1 that may affect the effect of immunotherapy. This study explored the impact of transcriptome-based co-expression of bromodomain containing 4 (BRD4) and PD-1/PD-L1 on the overall survival (OS) of patients with AML, in order to understand whether BRD4 would affect the effect of PD-1/PD-L1 blockades. Bone marrow samples from 59 AML patients in our clinical center and data of 176 patients from the Cancer Genome Atlas (TCGA) database were used for OS analysis and validation. It was found that increased expression of BRD4 was associated with poor OS in AML patients. Moreover, co-expression of BRD4 with PD-1 or PD-L1 was related to poor OS. The co-expression of BRD4 and PD-L1 was better than BRD4 and PD-1 for OS prediction. Furthermore, co-expression of BRD4 and PD-L1 was positively correlated with high tumor mutation burden, which contributed to poor OS in AML patients. Additionally, the co-expression of BRD4 and PD-L1 was associated with poor OS in non-acute promyelocytic leukemia patients with intermediate/high risk or under 60 years. Our results suggest that transcriptome-based co-expression of BRD4 and PD-L1 is a predictor for poor OS in AML patients, which might provide novel insight into designing combinational targeted therapy for AML.
Shear Wave Dispersion as a Potential Biomarker for Cervical Remodeling During Pregnancy: Evidence From a Non-Human Primate Model
Authors: Torres Abel , Palmeri Mark L. , Feltovich Helen , Hall Timothy J. , Rosado-Mendez Ivan M.
Published: February 2021

Shear wave dispersion (variation of phase velocity with frequency) occurs in tissues with layered and anisotropic microstructure and viscous components, such as the uterine cervix. This phenomenon, mostly overlooked in previous applications of cervical Shear Wave Elasticity Imaging (SWEI) for preterm birth risk assessment, is expected to change drastically during pregnancy due to cervical remodeling. Here we demonstrate the potential of SWEI-based descriptors of dispersion as potential biomarkers for cervical remodeling during pregnancy. First, we performed a simulation-based pre-selection of two SWEI-based dispersion descriptors: the ratioRof group velocities computed with particle-velocity and particle-displacement, and the slopeSof the phase velocity vs. frequency. The pre-selection consisted of comparing the contrast-to-noise ratio (CNR) of dispersion descriptors in materials with different degrees of dispersion with respect to a low-dispersive medium. Shear waves induced in these media by SWEI were simulated with a finite-element model of Zener viscoelastic solids. The pre-selection also considered two denoising strategies to improve CNR: a low-pass filter with automatic frequency cutoff determination, and singular value decomposition of shear wave displacements. After pre-selection, the descriptor-denoising combination that produced the largest CNR was applied to SWEI cervix data from 18 pregnant Rhesus macaques acquired at weeks 10 (mid-pregnancy stage) and 23 (late pregnancy stage) of the 24.5-weeks full pregnancy. A maximum likelihood linear mixed-effects model (LME) was used to evaluate the dependence of the dispersion descriptor on pregnancy stage, maternal age, parity and other experimental factors. The pre-selection study showed that descriptorScombined with singular value decomposition produced a CNR 11.6 times larger than the other descriptor and denoising strategy combinations. In the Non-Human Primates (NHP) study, the LME model showed that descriptor S significantly decreased from mid to late pregnancy (−0.37±0.07 m/s-kHz per week,p<0.00001) with respect to the base value of 15.5±1.9 m/s-kHz. This change was more significant than changes in other SWEI features such as the group velocity previously reported. Also, S varied significantly between the anterior and posterior portions of the cervix (p=0.02) and with maternal age (p=0.008). Given the potential of shear wave dispersion to track cervical remodeling, we will extend its application to ongoing longitudinal human studies.
An Integrated Approach of QTL Mapping and Genome-Wide Association Analysis Identifies Candidate Genes for Phytophthora Blight Resistance in Sesame (Sesamum indicum L.)
Authors: Asekova Sovetgul , Oh Eunyoung , Kulkarni Krishnanand P. , Siddique Muhammad Irfan , Lee Myoung Hee , Kim Jung In , Lee Jeong-Dong , Kim Minsu , Oh Ki-Won , Ha Tae-Joung , Kim Sung-Up , Cho Kwang-Soo
Published: February 2021

Phytophthora blight (PB) caused byPhytophthora nicotianaeis a highly destructive disease in sesame (Sesamum indicumL.). In this study, we used linkage mapping and genome-wide association study (GWAS) to identify quantitative trait loci (QTL) and candidate genes associated with PB resistance. The QTL mapping in 90 RILs of the Goenbaek × Osan cross using genotyping-by-sequencing detected significant QTLs for PB resistance on chromosome 10, explaining 12.79%–13.34% of phenotypic variation. Association of this locus to PB resistance was also revealed through bulked segregant analysis in second RIL population (Goenbaek × Milsung cross) comprising 188 RILs. The GWAS of 87 sesame accessions evaluated against threeP. nicotianaeisolates identified 29 SNPs on chromosome 10 significantly associated with PB resistance. These SNPs were located within a 0.79 Mb region, which co-located with the QTL intervals identified in RIL populations, and hence scanned for identifying candidate genes. This region contained several defense-related candidateRgenes, five of which were selected for quantitative expression analysis. One of these genes,SIN_1019016was found to show significantly higher expression in the resistant parent compared to that in the susceptible parents and selected RILs. Paired-end sequencing of the geneSIN_1019016in parental cultivars revealed two synonymous SNPs between Goenbaek and Osan in exon 2 of coding DNA sequence. These results suggestedSIN_1019016as one of the candidate gene conferring PB resistance in sesame. The findings from this study will be useful in the marker-assisted selection as well as the functional analysis of PB resistance candidate gene(s) in sesame.
The Diverse Roles of FLOWERING LOCUS C in Annual and Perennial Brassicaceae Species
Authors: Soppe Wim J. J. , Viñegra de la Torre Natanael , Albani Maria C.
Published: February 2021

Most temperate species require prolonged exposure to winter chilling temperatures to flower in the spring. In the Brassicaceae, the MADS box transcription factor FLOWERING LOCUS C (FLC) is a major regulator of flowering in response to prolonged cold exposure, a process called vernalization. Winter annualArabidopsis thalianaaccessions initiate flowering in the spring due to the stable silencing ofFLCby vernalization. The role of FLC has also been explored in perennials within the Brassicaceae family, such asArabis alpina.The flowering pattern inA. alpinadiffers from the one inA. thaliana.A. alpinaplants initiate flower buds during vernalization but only flower after subsequent exposure to growth-promoting conditions. Here we discuss the role of FLC in annual and perennial Brassicaceae species. We show that, besides its conserved role in flowering, FLC has acquired additional functions that contribute to vegetative and seed traits.PERPETUAL FLOWERING 1(PEP1), theA. alpina FLCortholog, contributes to the perennial growth habit. We discuss that PEP1 directly and indirectly, regulates traits such as the duration of the flowering episode, polycarpic growth habit and shoot architecture. We suggest that these additional roles ofPEP1are facilitated by (1) the ability ofA. alpinaplants to form flower buds during long-term cold exposure, (2) age-related differences between meristems, which enable that not all meristems initiate flowering during cold exposure, and (3) differences between meristems in stable silencing ofPEP1after long-term cold, which ensure thatPEP1expression levels will remain low after vernalization only in meristems that commit to flowering during cold exposure. These features result in spatiotemporal seasonal changes ofPEP1expression during theA. alpinalife cycle that contribute to the perennial growth habit. FLC and PEP1 have also been shown to influence the timing of another developmental transition in the plant, seed germination, by influencing seed dormancy and longevity. This suggests that during evolution,FLCand its orthologs adopted both similar and divergent roles to regulate life history traits. Spatiotemporal changes ofFLCtranscript accumulation drive developmental decisions and contribute to life history evolution.
From Data to Causes III: Bayesian Priors for General Cross-Lagged Panel Models (GCLM)
Authors: Zyphur Michael J. , Hamaker Ellen L. , Tay Louis , Voelkle Manuel , Preacher Kristopher J. , Zhang Zhen , Allison Paul D. , Pierides Dean C. , Koval Peter , Diener Edward F.
Published: February 2021

This article describes some potential uses of Bayesian estimation for time-series and panel data models by incorporating information from prior probabilities (i.e., priors) in addition to observed data. Drawing on econometrics and other literatures we illustrate the use of informative “shrinkage” or “small variance” priors (including so-called “Minnesota priors”) while extending prior work on the general cross-lagged panel model (GCLM). Using a panel dataset of national income and subjective well-being (SWB) we describe three key benefits of these priors. First, they shrink parameter estimates toward zero or toward each other for time-varying parameters, which lends additional support for an income → SWB effect that is not supported with maximum likelihood (ML). This is useful because, second, these priors increase model parsimony and the stability of estimates (keeping them within more reasonable bounds) and thus improve out-of-sample predictions and interpretability, which means estimated effect should also be more trustworthy than under ML. Third, these priors allow estimating otherwise under-identified models under ML, allowing higher-order lagged effects and time-varying parameters that are otherwise impossible to estimate using observed data alone. In conclusion we note some of the responsibilities that come with the use of priors which, departing from typical commentaries on their scientific applications, we describe as involving reflection on how best to apply modeling tools to address matters of worldly concern.
Music Therapy for Depression Enhanced With Listening Homework and Slow Paced Breathing: A Randomised Controlled Trial
Authors: Erkkilä Jaakko , Brabant Olivier , Hartmann Martin , Mavrolampados Anastasios , Ala-Ruona Esa , Snape Nerdinga , Saarikallio Suvi , Gold Christian
Published: February 2021

Introduction: There is evidence from earlier trials for the efficacy of music therapy in the treatment of depression among working-age people. Starting therapy sessions with relaxation and revisiting therapeutic themes outside therapy have been deemed promising for outcome enhancement. However, previous music therapy trials have not investigated this issue.

Objective: To investigate the efficacy of two enhancers, resonance frequency breathing (RFB) and listening homework (LH), when combined with an established music therapy model (trial registration number ISRCTN11618310).

Methods: In a 2 × 2 factorial randomised controlled trial, working-age individuals with depression were allocated into groups based on four conditions derived from either the presence or absence of two enhancers (RFB and LH). All received music therapy over 6 weeks. Outcomes were observed at 6 weeks and 6 months. The primary outcome was the Montgomery Åsberg Depression Rating Scale (MADRS) score.

Results: There was a significant overall effect of treatment for the primary outcome favouring the breathing group (d = 0.50, 95% CI 0.07 to 0.93, p = 0.02). The effect was larger after adjustment for potential confounders (d = 0.62, 95% CI 0.16 to 1.08, p = 0.009). Treatment effects for secondary outcomes, including anxiety (anxiety scale of Hospital Anxiety and Depression Scale) and quality of life (RAND-36), were also significant, favouring the breathing group. The homework enhancer did not reach significant treatment effects.

Conclusion: We found that the addition of RFB to a music therapy intervention resulted in enhanced therapeutic outcome for clients with depression.
Creating or Destructing Value in Use? Handling Cognitive Impairments in Co-Creation with Serious and Chronically Ill Users
Authors: Skarli Jim Broch
Published: February 2021

Theoretically based on public service logic (PSL), this article addresses how users’ cognitive impairments can affect co-creation processes and value outcomes in a public sector environment, and how the service providers can handle this issue. It directs attention to value creation in the context of vulnerable and unwilling service users and contributes to understanding how cognitive gaps between public health care services and users inhibit value co-creation. Based on qualitative interview data, findings substantiate that cognitive impairments reduce the users’ health literacy and therefore affect both their ability and willingness to participate in co-creation. The study recognizes that there is a built-in asymmetry between the involved actors and that failing to reduce this asymmetry through adequate facilitation by the service providers, can result in co-destruction of value in use. It is acknowledged that the users might not be cognitively able to determine whether they actually come better or worse off in the end. Therefore, it is suggested that the service provider might need to play a larger role in determining what is positive or negative value in use. Hence, this article adds to PSL by clearly emphasizing the key role played by public service organizations (PSOs) in facilitating the value creation process, which takes place during service delivery.
The Click Production of Captive Yangtze Finless Porpoises (Neophocaena asiaeorientalis asiaorientalis) Is Influenced by Social and Environmental Factors
Authors: Serres Agathe , Xu Chen , Hao Yujiang , Wang Ding
Published: February 2021

Yangtze finless porpoises use high-frequency clicks to navigate, forage, and communicate. The way in which click production may vary depending on social or environmental context has never been investigated. A group of five captive Yangtze finless porpoises was monitored for one year, and 107 h of audio recordings was collected under different conditions. Using a MATLAB-generated interface, we extracted click density (i.e., number of clicks per minute) from these recordings and analyzed its variation depending on the context. As expected, click density increased as the number of animals present increased. The click density did not exhibit diurnal variations but did have seasonal variations, with click density being highest in summer and fall. Yangtze finless porpoises produced more clicks when socially separated than when not (136% more), during training/feeding sessions than outside of such sessions (312% more), when enrichment was provided (265% more on average), and when noisy events occurred rather than when no unusual event occurred (22% more). The click density decreased when many visitors were present in the facility (up to 35% less). These results show that Yangtze finless porpoises modulate their click production depending on the context and suggest that their echolocation activity and their emotional state may be linked to these changes. Such context-dependent variations also indicate the potential usefulness of monitoring acoustical activity as part of a welfare assessment tool in this species. Additionally, the click density variation found in captivity could be useful for understanding click rate variations of wild populations that are hardly visible.