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Ultra-high-strength steel (UHSS) structures are exposed to corrosive environments during service, and hydrogen-assisted cracking (HAC) may occur owing to stress corrosion cracking and hydrogen embrittlement. In this study, the HAC threshold stress intensity factor and fatigue life of UHSS steel were evaluated by applying stress in a corrosive environment to prevent structural fracture. For specimen with semicircular slits by electric discharge machining, fatigue limit was obtained by static fatigue test under corrosive environment. The fatigue limit of the crack specimen was evaluated by the fatigue limit of the experiment and HAC threshold stress intensity factor, and comparative evaluation was performed. On the surface of cracks, grain boundaries were embrittled by corrosion, and grains were clearly observed. Meanwhile, cracks in the surface direction propagated slightly, unlike cracks in the depth direction. The static fatigue limit of UHSS (SKD11:HV670) was determined to be 400 MPa, and the fatigue limit of the crack specimen could be evaluated. The experimental results agreed well with the evaluation results.

Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea.An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph+ CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response.During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients).This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph+ CML in routine clinical practice settings.

We previously demonstrated that interferon γ (IFN-γ) derived from donor T cells co-opts the indoleamine 2,3-dioxygenase 1 (IDO1) → aryl hydrocarbon receptor (AHR) axis to suppress idiopathic pneumonia syndrome (IPS). Here we report that the dysregulated expression of AP-1 family genes in Ahr−/− lung epithelial cells exacerbated IPS in allogeneic bone marrow transplantation settings. AHR repressed transcription of Jund by preventing STAT1 from binding to its promoter. As a consequence, decreased interleukin-6 impaired the differentiation of CD4+ T cells toward Th17 cells. IFN-γ– and IDO1-independent induction of Ahr expression indicated that the AHR agonist might be a better therapeutic target for IPS than the IDO1 activator. We developed a novel synthetic AHR agonist (referred to here as PB502) that potently inhibits Jund expression. PB502 was highly effective at inducing AHR activation and ameliorating IPS. Notably, PB502 was by far superior to the endogenous AHR ligand, L-kynurenine, in promoting the differentiation of both mouse and human FoxP3+ regulatory CD4+ T cells. Our results suggest that the IDO1-AHR axis in lung epithelial cells is associated with IPS repression. A specific AHR agonist may exhibit therapeutic activity against inflammatory and autoimmune diseases by promoting regulatory T-cell differentiation.

Due to several issues, standard treatments are not recommended for asymptomatic patients with moderate immune thrombocytopenia (ITP). Since platelet responses are reported in some patients with Helicobacter pylori (H. pylori)-positive ITP after eradication, we conducted a multicenter, phase 3 study to evaluate the safety and efficacy of recently established sequential eradication for these patients having moderate thrombocytopenia. Persistent or chronic ITP patients with platelet count (30 × 10

Ampullary adenoma is a rare premalignant lesion, but its incidence is increasing. Endoscopic papillectomy has become the first treatment of choice for ampullary adenomas due to its safety and effectiveness, thereby replacing surgical resection. However, recurrence rates and adverse events after endoscopic papillectomy were reported in up to 30% of cases.To review the long-term outcomes of endoscopic papillectomy and investigate the factors that affect these outcomes.We retrospectively analyzed the data of patients who underwent endoscopic papillectomy for ampullary adenoma at five tertiary hospitals between 2013 and 2020. We evaluated clinical outcomes and their risk factors. The definitions of outcomes were as follow: (1) curative resection: complete endoscopic resection without recurrence; (2) endoscopic success: treatment of ampullary adenoma with endoscopy without surgical intervention; (3) early recurrence: reconfirmed adenoma at the first endoscopic surveillance; and (4) late recurrence: reconfirmed adenoma after the first endoscopic surveillance.A total of 106 patients were included for analysis. Of the included patients, 81 (76.4%) underwent curative resection, 99 (93.4%) had endoscopic success, showing that most patients with non-curative resection were successfully managed with endoscopy. Sixteen patients (15.1%) had piecemeal resection, 22 patients (20.8%) had shown positive/uncertain resection margin, 11 patients (16.1%) had an early recurrence, 13 patients (10.4%) had a late recurrence, and 6 patients (5.7%) had a re-recurrence. In multivariate analysis, a positive/uncertain margin [Odds ratio (OR) = 4.023,Endoscopic papillectomy is a safe and effective treatment for ampullary adenomas. Careful selection and follow-up of patients is mandatory, particularly in cases with positive/uncertain margin and piecemeal resection.

This paper proposes a novel method to impart intelligence to metal parts using additive manufacturing. A sensor-embedded metal bracket is prototyped via a metal powder bed fusion process to recognise partial screw loosening or total screw missing or identify the source of vibration with the assistance of artificial intelligence (AI). The digital metal bracket can recognise subtle changes in the screw fixation state with 90% accuracy and identify unknown sources of vibration with 84% accuracy. The von Mises stress distribution in the prototyped metal bracket is evaluated using a finite element analysis, which is learned by AI to match the real-time deformation analysis of the metal bracket in augmented reality. The proposed prototype can contribute to hyper-connectivity for developing next-generation metal-based mechanical components. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) [grant Nos. 2021M2D2A1A01050059 and 2021R1F1A1046079].

There are various methods for treating advanced hepatocellular carcinoma with portal vein invasion, such as systemic chemotherapy, transarterial chemoembolization, transarterial radioembolization, and concurrent chemoradiotherapy. These methods have similar clinical efficacy but are designed with a palliative aim. Herein, we report a case that experienced complete remission through “associating liver partition and portal vein ligation for staged hepatectomy (ALPPS)” after concurrent chemoradiotherapy and hepatic artery infusion chemotherapy. In this patient, concurrent chemoradiotherapy and hepatic artery infusion chemotherapy induced substantial tumor shrinkage, and hypertrophy of the nontumor liver was sufficiently induced by portal vein ligation (stage 1 surgery) followed by curative resection (stage 2 surgery). Using this approach, long-term survival with no evidence of recurrence was achieved at 16 months. Therefore, the optimal use of ALPPS requires sufficient consideration in cases of significant hepatocellular carcinoma shrinkage for curative purposes.

Vertebrates utilize the mannose 6-phosphate (M6P) recognition system to deliver lysosomal hydrolases to lysosomes. Key to this pathway is GlcNAc-1-phosphotransferase (PTase) that selectively adds GlcNAc-P to mannose residues of the hydrolases. Human PTase is an α2β2γ2 heterohexamer with a catalytic core and several peripheral domains that recognize and bind substrates. Here we report a cryo-EM structure of the catalytic core of human PTase and identification of a hockey-stick-like motif that controls the activation of the enzyme. Movement of this motif out of the catalytic pocket is associated with a rearrangement of part of the peripheral domains that unblocks hydrolase glycan access to the catalytic site, thereby activating PTase. We propose that PTase fluctuates between inactive and active states in solution, and the selective substrate binding of a lysosomal hydrolase through its protein binding determinant to PTase locks the enzyme in the active state to permit glycan phosphorylation. This mechanism would help ensure that only N-linked glycans of lysosomal enzymes are phosphorylated.

Objective Dual trigger is used to induce final oocyte maturation during the process of controlled ovarian hyperstimulation, yet yielding controversial results. Also, there are yet no data regarding the effect of the dosage of the dual trigger on clinical outcomes. Based on the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria, this study aimed to determine the clinical difference of a single bolus versus two boluses of gonadotropin-releasing hormone agonist (GnRHa) in POSEIDON group IV patients using dual trigger.Methods We screened a total of 1,256 patients who underwent in vitro fertilization (IVF) cycles who met the POSEIDON group IV criteria. Six hundred and twenty-nine patients received one bolus of GnRHa, and 627 patients were given two boluses. All patients received the same dose of recombinant human chorionic gonadotropin during the dual trigger cycle.Results Metaphase II oocyte retrieval rate, fertilization rate and clinical pregnancy rate did not differ between the two groups. However, a lower percentage of at least one top-quality embryo transfer (34.3% vs. 26.0%, P=0.001) in the two bolus-GnRHa group was noted.Conclusion A double bolus of GnRHa did not show superior clinical results compared to a single bolus of GnRHa in the dual trigger IVF cycle. Therefore, GnRHa doses for use should be decided based on individual clinical situations considering cost-effectiveness and patient compliance, but further investigation will be needed.

We systematically reviewed the short-term effects of hippotherapy and therapeutic horseback riding (THR) on lower-limb muscle spasticity in children with cerebral palsy (CP).PubMed, EMBASE, Cochrane Library, and Google Scholar databases were searched for relevant quantitative studies. Treatment effects were coded using the Ashworth scale (AS) or modified Ashworth scale (MAS) in pre- and posttreatment evaluations. Of the 73 studies identified initially, 7 met the inclusion criteria.Treatment was associated with positive effects on lower-limb muscle spasticity, as supported by the AS or MAS scores. However, repeated trials did not show a statistically significant difference from a single trial (Q = 2.95, P = .086).Hippotherapy and THR can be used to treat lower-limb muscle spasticity in children with CP. However, repeated sessions did not show a better effect in reducing spasticity.This is the first meta-analysis to confirm that hippotherapy or THR can reduce lower-limb muscle spasticity in children with CP in the short term, but long-term effects on function still require further studies.

Acute pancreatitis can range from a mild, self-limiting disease that requires no more than supportive care to severe disease with life-threatening complications. Therefore, to provide a framework for clinicians to manage acute pancreatitis and to improve national health care, the Korean Pancreatobiliary Association (KPBA) established the first Korean guideline for the management of acute pancreatitis in 2013. However, many challenging issues exist, which sometimes lead to differences in practice between clinicians. Taking together the recent dramatic changes of latest knowledge and evidence newly obtained, the committee of the KPBA decided to perform an extensive revision of the guidelines. These revised guidelines were developed by using mainly Delphi methods, and the main topics of these guidelines fall under the following topics: 1) diagnosis, 2) severity assessment, 3) initial treatment, nutritional support, and convalescent treatment, 4) the treatment of local complication and necrotizing pancreatitis. The specific recommendations are presented with the quality of evidence and classification of recommendations.

Background: Long-term outcomes of live kidney donors remain controversial, although this information is crucial for selecting potential donors. Thus, this study compared the long-term risk of all-cause mortality between live kidney donors and healthy non-donors.Methods: We performed a retrospective cohort study including donors from seven tertiary hospitals in South Korea. Persons who underwent voluntary health screening were included as controls. We created a matched control group considering age, sex, era, body mass index, baseline hypertension, diabetes, estimated glomerular filtration rate, and dipstick albuminuria. The study outcome was progression to end-stage kidney disease (ESKD), and all-cause mortality as identified in the linked claims database. Results: We screened 1,878 kidney donors and 78,115 health screening examinees from 2003 to 2016. After matching, 1,701 persons remained in each group. The median age of the matched study subjects was 44 years, and 46.6% were male. Among the study subjects, 2.7% and 16.6% had underlying diabetes and hypertension, respectively. There were no ESKD events in the matched donor and control groups. There were 24 (1.4%) and 12 mortality cases (0.7%) in the matched donor and control groups, respectively. In the age-sex adjusted model, the risk for all-cause mortality was significantly higher in the donor group than in the control group. However, the significance was not retained after socioeconomic status was included as a covariate (adjusted hazard ratio, 1.82; 95% confidence interval, 0.87–3.80). Conclusion: All-cause mortality was similar in live kidney donors and matched non-donor healthy controls with similar health status and socioeconomic status in the Korean population.

The liquid filling machine is used in packaging fields such as food, chemistry, and oil industries. In particular, the machines are used to package products in drums after manufacturing products in hazardous chemical factories. Existing filling machine allows the operator to directly inject the product and set the injection capacity only to the standard drum. In this paper, we propose position tracking algorithm with a vision sensor that can track the inlet location of various types of drums. Hough transform detection method is used to search for objects in images from the vision sensor. The proposed algorithm can calculate the position of the injection hole after extracting the feature points so that it is possible to inject the product by automatically moving the injection nozzle. Therefore, it expected that the developed algorithm for the automatic liquid filling machine will give more production and save a lot of manpower for packaging industry.

In this letter, a threshold switching (TS) selector with Ag doping-based nano-polycrystalline ZnO switching layer (SL) having (002) preferred orientation has been manifested, without incorporating an active Ag metal layer, using a facile co-sputtering deposition technique. The TS selectors with extremely controlled doping of ~0.14 at. % Ag concentration showed remarkable electroforming (EF)-free selection behavior such as gigantic selectivity (~1011), extreme-low off-current (~10 fA), high on-current density (~1.6 MA/cm2), ultra-steep switching slope (~0.8 mV/decade), satisfactory endurance (>106), fast switch-on speed (~38 ns) and relaxation speed (~64 ns), and high device yield (~90%). Furthermore, selector devices showed reproducible selection behavior with stable threshold voltage (Vth) having merely 8% variances.

Nanoplastics (NPs) are emerging environmental pollutants and are a significant concern for human health. The small size of NPs allows them to accumulate within and adversely affect various tissues by penetrating the gastrointestinal barrier. However, most toxicity studies on NPs have been based on commercial polystyrene nanoparticles. Among plastics, polypropylene (PP) is one of the most widely used, and it is continuously micronized in the environment. Although PP has high potential for forming NPs by weathering, little is known about the biological effects of polypropylene nanoplastics (PPNPs) due to a lack of particle models. Here, we present a simple and high-yield method for PPNP production by nonsolvent-induced phase separation. The synthesized PPNPs were spherical in shape, with an average diameter of 562.15 ± 118.47 nm and a high yield of over 84%. These PPNPs were fluorescently labeled by the combined swelling-diffusion method to study their biodistribution after exposure to developing zebrafish embryos (ZFEs). We found that the fluorescent PPNPs were internalized by ingestion, distributed in the intestine of developing ZFEs, and eventually excreted. This study will aid evaluations of the potential risks of environmentally relevant plastics at the nanoscale.

The present paper intensively studies various properties of certain topologies on the set of integers $ {\mathbb Z} $ (resp. $ {\mathbb Z}^n $) which are either homeomorphic or not homeomorphic to the typical Khalimsky line topology (resp. $ n $-dimensional Khalimsky topology). This finding plays a crucial role in addressing some problems which remain open in the field of digital topology.

Supplementary Methods, Supplementary Figure Legends, Supplementary Table

Kaplan-Meier estimated progression-free survival (PFS) in the intention-to-treat population

Major molecular response by 12 months, by Sokal risk group. bid, twice daily; MMR, major molecular response (defined as BCR-ABL1 transcript level {less than or equal to}0.1% [MR3.0]); qd, daily.

Purpose: Radotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) approved in Korea for chronic phase chronic myeloid leukemia (CML-CP) in patients newly diagnosed or with insufficient response to other TKIs. This study was conducted to evaluate the efficacy and safety of radotinib as first-line therapy for CML-CP.Experimental Design: This multinational, open-label study assigned patients (1:1:1) to one of two twice-daily radotinib doses, or imatinib daily. The primary endpoint was major molecular response (MMR) by 12 months.Results: Two hundred forty-one patients were randomized to receive radotinib 300 mg (n = 79) or 400 mg twice-daily (n = 81), or imatinib 400 mg daily (n = 81). MMR rates by 12 months were higher in patients receiving radotinib 300 mg (52%) or radotinib 400 mg twice-daily (46%) versus imatinib (30%; P = 0.0044 and P = 0.0342, respectively). Complete cytogenetic response (CCyR) rates by 12 months were higher for radotinib 300 mg (91%) versus imatinib (77%; P = 0.0120). Early molecular response at 3 months occurred in 86% and 87% of patients receiving radotinib 300 mg and radotinib 400 mg, respectively, and 71% of those receiving imatinib. By 12 months, no patients had progression to accelerated phase or blast crisis. Most adverse events were manageable with dose reduction.Conclusions: Radotinib demonstrated superiority over imatinib in CCyR and MMR in patients newly diagnosed with Philadelphia chromosome–positive CML-CP. This trial was registered at www.clinicaltrials.gov as NCT01511289. Clin Cancer Res; 23(23); 7180–8. ©2017 AACR.

Achievement of MMR by 12 months according to 3-month EMR (< 10% of BCR-ABL1IS). (c) Radotinib 300 mg bid (n = 79 patients with evaluable molecular data at 3 months).

Supplementary Table 1 from Erythropoietin Induces Lymph Node Lymphangiogenesis and Lymph Node Tumor Metastasis

BackgroundA chemotherapy of rituximab, fludarabine and cyclophosphamide (R-FC) has been accepted as a promising frontline chemotherapy in selected patients with chronic lymphocytic leukemia (CLL). Although R-FC regimen is a relatively dose-dense regimen and neutropenia incidence is more than 50%, primary prophylactic pegfilgrastim was not fully recommended in the clinical field. Therefore, the study evaluated the prophylactic effectiveness of pegfilgrastim to reduce the incidence of febrile neutropenia associated with R-FC of patients with CLL.Patients and methodsA single-arm, multicenter, prospective phase II study was designed to assess the efficacy of prophylactic pegfilgrastim. Thirty-four CLL patients were enrolled and analyzed for neutropenia and other related factors, and comparative analysis was performed with historical cohort.ResultsCompared with our historical cohort, incidence of grade 3-4 neutropenia and febrile neutropenia was remarkably reduced during any cycle of chemotherapy (14.7% vs. 48.2% of study cohort vs. historical cohort during C1, 5.9% vs. 65.8% during C2, 12.9% vs. 80.6% during C3, 10% vs. 84.6% during C4, 3.4% vs. 83.6% during C5, and 10.7% vs. 85.7% during C6, p ConclusionPrimary prophylactic pegfilgrastim is effective in the prevention of neutropenia/febrile neutropenia, and infection-related mortality during R-FC regimen in patients with CLL.

We are concerned with weak solutions of elliptic equations involving measurable nonlinearities with Orlicz growth to address what would be the weakest regularity condition on the associated nonlinearity for the Calderón–Zygmund theory. We prove that the gradient of weak solution is as integrable as the nonhomogeneous term under the assumption that the nonlinearity is only measurable in one of the variables while it has a small BMO assumption in the other variables. To this end, we develop a nonlinear Moser-type iteration argument for such a homogeneous reference problem with one variable–dependent nonlinearity under Orlicz growth to establish $W^{1,q}$–regularity for every $q>1$. Our results open a new path into the comprehensive understanding of the problem with nonstandard growth in the literature of optimal regularity theory in highly nonlinear elliptic and parabolic equations.

Chlamydomonas reinhardtii is a eukaryotic, unicellular photosynthetic organism and a potential algal platform for producing biomass and recombinant proteins for industrial use. Ionizing radiation is a potent genotoxic and mutagenic agent used for algal mutation breeding that induces various DNA damage and repair responses. In this study, however, we explored the counterintuitive bioeffects of ionizing radiation, such as X- and γ-rays, and its potential as an elicitor to facilitate batch or fed-batch cultivation of Chlamydomonas cells. A certain dose range of X- and γ-rays was shown to stimulate the growth and metabolite production of Chlamydomonas cells. X- or γ-irradiation with relatively low doses below 10 Gy substantially increased chlorophyll, protein, starch, and lipid content as well as growth and photosynthetic activity in Chlamydomonas cells without inducing apoptotic cell death. Transcriptome analysis demonstrated the radiation-induced changes in DNA damage response (DDR) and various metabolic pathways with the dose-dependent expression of some DDR genes, such as CrRPA30, CrFEN1, CrKU, CrRAD51, CrOASTL2, CrGST2, and CrRPA70A. However, the overall transcriptomic changes were not causally associated with growth stimulation and/or enhanced metabolic activities. Nevertheless, the radiation-induced growth stimulation was strongly enhanced by repetitive X-irradiation and/or subsequent cultivation with an inorganic carbon source, i.e., NaHCO3, but was significantly inhibited by treatment of ascorbic acid, a scavenger of reactive oxygen species (ROS). The optimal dose range of X-irradiation for growth stimulation differed by genotype and radiation sensitivity. Here, we suggest that ionizing radiation within a certain dose range determined by genotype-dependent radiation sensitivity could induce growth stimulation and enhance metabolic activities, including photosynthesis, chlorophyll, protein, starch, and lipid synthesis in Chlamydomonas cells via ROS signaling. The counterintuitive benefits of a genotoxic and abiotic stress factor, i.e., ionizing radiation, in a unicellular algal organism, i.e., Chlamydomonas, may be explained by epigenetic stress memory or priming effects associated with ROS-mediated metabolic remodeling.

Background Optimal sizing for phakic intraocular lens (EVO-ICL with KS-AquaPort) implantation plays an important role in preventing postoperative complications. We aimed to formulate optimal lens sizing using ocular biometric parameters measured with a Heidelberg anterior segment optical coherence tomography (AS-OCT) device. Methods We retrospectively analyzed 892 eyes of 471 healthy subjects treated with an intraocular collamer lens (ICL) and assigned them to either the development (80%) or validation (20%) set. We built vault prediction models using the development set via classic linear regression methods as well as partial least squares and least absolute shrinkage and selection operator (LASSO) regression techniques. We evaluated prediction abilities based on the Bayesian information criterion (BIC) to select the best prediction model. The performance was measured using Pearson’s correlation coefficient and the mean squared error (MAE) between the achieved and predicted results. Results Measurements of aqueous depth (AQD), anterior chamber volume, anterior chamber angle (ACA) distance, spur-to-spur distance, crystalline lens thickness (LT), and white-to-white distance from ANTERION were highly associated with the ICL vault. The LASSO model using the AQD, ACA distance, and LT showed the best BIC results for postoperative ICL vault prediction. In the validation dataset, the LASSO model showed the strongest correlation (r = 0.582, P Conclusion This is the first study to develop a postoperative ICL vault prediction and lens-sizing model based on the ANTERION. As the measurements from ANTERION and other AS-OCT devices are not interchangeable, ANTERION may be used for optimal ICL sizing using our formula. Because our model was developed based on the East Asian population, further studies are needed to explore the role of this prediction model in different populations.

The majority of the vitamin D that is present in the blood binds to vitamin D binding protein (VDBP) and circulates in the form of a complex (VDBP-Complex). Knowing the level of vitamin D in the body is crucial for vitamin D-related treatments so that the right dosage of vitamin D can be given. In other words, it is essential to distinguish between the protein VDBP and the complex form bound to vitamin D. As a novel way for the detection of VDBP-Complex, a more effective phage display methodology was applied in this study along with the addition of two approaches. In order to screen a sequence specific to the target only, the pre-binding method and after-binding method were performed. VDBP-Complex was directly coated on the petri dishes. In order to select phages that specifically bind to the VDBP-Complex, random phages were attached, and selected by 7 times of biopanning. Individual DNA sequences were analyzed for each biopanning to find specific peptide sequences for VDBP-Complex. The affinity of binding phages was verified by ELISA assay using an anti-M13 antibody. The phage having a sequence of SFTKTSTFTWRD (called as M3) has shown the highest binding affinity to VDBP-Complex. As a result of the removal test of VDBP-Complex using magnetic beads conjugated with M3 peptide, it was confirmed that significant decrease of VDBP-Complex. The unique characteristic of the M3 sequence was confirmed through a sequence-modified peptide (SFT motif). That is, it is expected that the M3 peptide may be used to determine the vitamin D levels in the blood.

A linear–shaped small organic molecule (E)-4-(5-(3,5-dimethoxy-styryl)thiophen-2-yl)-7-(5″-hexyl-[2,2′:5′,2″-terthiophen]-5-yl)benzo[c][1,2,5]thiadiazole (MBTR) comprising a benzothiadiazole (BTD) acceptor linked with the terminal donors bithiophene and dimethoxy vinylbenzene through a π-bridge thiophene was synthesized and analyzed. The MBTR efficiently tuned the thermal, absorption, and emission characteristics to enhance the molecular packing and aggregation behaviors in the solid state. The obtained optical bandgap of 1.86 eV and low-lying highest occupied molecular orbital (HOMO) level of −5.42 eV efficiently lowered the energy losses in the fabricated devices, thereby achieving enhanced photovoltaic performances. The optimized MBTR:PC71BM (1:2.5 w/w%) fullerene-based devices showed a maximum power conversion efficiency (PCE) of 7.05%, with an open-circuit voltage (VOC) of 0.943 V, short-circuit current density (JSC) of 12.63 mA/cm2, and fill factor (FF) of 59.2%. With the addition of 3% 1,8-diiodooctane (DIO), the PCE improved to 8.76% with a high VOC of 1.02 V, JSC of 13.78 mA/cm2, and FF of 62.3%, which are associated with improved charge transport at the donor/acceptor interfaces owing to the fibrous active layer morphology and favorable phase separation. These results demonstrate that the introduction of suitable donor/acceptor groups in molecular design and device engineering is an effective approach to enhancing the photovoltaic performances of organic solar cells.

Venadaparib (VEN), a next-generation inhibitor of poly (ADP-ribose) polymerases, is under development for oral use in patients having cancers with deoxyribonucleic acid repair defects. The objective of this study was to develop and validate a sensitive and robust analytical method for quantifying VEN in a small volume of plasma samples from rats and dogs, and to assess the feasibility of the assay for application in pharmacokinetic/toxicokinetic studies. Plasma samples were subjected to deproteination, and an aliquot was injected into an LC–MS/MS system. VEN and imipramine were analyzed in the positive ion mode and quantified by monitoring the transition at m/z 407.2 → 70.0 for VEN and 281.2 → 86.1 for imipramine. The lower and upper limits of the assay were determined to be 1 and 1000 ng/mL, respectively, with acceptable linearity (r2 > 0.995). Validation parameters, such as accuracy, precision, dilution, recovery, matrix effect, and stability, were within acceptable ranges. This method was adequately applied to the characterization of pharmacokinetics of VEN in rats and dogs at the oral dose of 30 and 0.5 mg/kg, respectively. These findings suggest that the validated assay is applicable to the kinetic studies of VEN with a small volume of plasma samples from the animals.

Hardware-based neural networks (NNs) can provide a significant breakthrough in artificial intelligence applications due to their ability to extract features from unstructured data and learn from them. However, realizing complex NN models remains challenging because different tasks, such as feature extraction and classification, should be performed at different memory elements and arrays. This further increases the required number of memory arrays and chip size. Here, we propose a three-dimensional ferroelectric NAND (3D FeNAND) array for the area-efficient hardware implementation of NNs. Vector-matrix multiplication is successfully demonstrated using the integrated 3D FeNAND arrays, and excellent pattern classification is achieved. By allocating each array of vertical layers in 3D FeNAND as the hidden layer of NN, each layer can be used to perform different tasks, and the classification of color-mixed patterns is achieved. This work provides a practical strategy to realize high-performance and highly efficient NN systems by stacking computation components vertically.