Miracle-dz/UniFAR-FTUs huggingface dataset:
THE JOURNAL OF HISTOCHEMISTRY AND CYTOCHEMISTRY

Conditions for the biochemical and flow cytometric assay of 7-bromo-3-hydroxy-2-naphtho-o-anisidine phosphatase and /1-n-glucurothdase activities in Chinese hamster ovary cells were studied. In the biochemical assays, the pH optimum for the phosphatase activity was pH 4.6 with a Km of 1O M; the pH optimum for fJ-D-glucuronidase activity was pH 5.0 with a Km of 2 x iO M. For intact cells the derived constants were 3 to 10 times higher. The rate of hydrolysis of both substrates was also examined by flow cytometry. Cellular fluorescence increased linearly for only about 15 mm. Diffusion of the fluorescent product probably caused nonlinearity of the fluorescence increase and was demonstrated by mixing cells incubated with substrate with those that had not been incubated. After 15 mm, cells that had not been exposed previously to product or substrate contained the fluorescent product. Cells fractionated into size classes by centrifugal elutriation also were analyzed by flow cytometry for $-D-glucuronidase activity. The activity increased linearly with the increase in cell size corresponding to the progression from G1 through S and into G2-M phases of the cell cycle.
THE JOURNAL OF HISTOCHEMISTRY AND CYTOCHEMISTRY

The application of a new preparation method for demonstrating the activities of hydrolytic and oxidative enzymes in Candida albicans is reported. The problem of inadequate penetration of fixatives into yeast cells has been solved by sectioning solidified pellets of the cells in the presence of glutaraldehyde, a procedure that yields a fairly well preserved ultrastructure and sufficient enzyme activities. The subcellular distribution of most specific and nonspecific phosphatases and of peroxidases is at variance with that found in mammalian cells. The activities toward $-glycerophosphate, p-nitrophenylphosphate, adenosine triphosphate, adenosine monophosphate, thiamine pyrophosphate and glucose 6-phosphate are almost exclusively confined to the central vacuolar apparatus. Oxidative and peroxidative activities are demonstrated only in mitochondria. Specific marker enzymes for endoplasmic reticulum, plasmalemma, Golgi apparatus and peroxisomes in C. albicans are not found. The possible function of the various subcellular organelles in relation to their enzymatic content is discussed.
Hematological convergence between Mesozoic marine reptiles (Sauropterygia) and extant aquatic amniotes elucidates diving adaptations in plesiosaurs

Plesiosaurs are a prominent group of Mesozoic marine reptiles, belonging to the more inclusive clades Pistosauroidea and Sauropterygia. In the Middle Triassic, the early pistosauroid ancestors of plesiosaurs left their ancestral coastal habitats and increasingly adapted to a life in the open ocean. This ecological shift was accompanied by profound changes in locomotion, sensory ecology and metabolism. However, investigations of physiological adaptations on the cellular level related to the pelagic lifestyle are lacking so far. Using vascular canal diameter, derived from osteohistological thin-sections, we show that inferred red blood cell size significantly increases in pistosauroids compared to more basal sauropterygians. This change appears to have occurred in conjunction with the dispersal to open marine environments, with cell size remaining consistently large in plesiosaurs. Enlarged red blood cells likely represent an adaptation of plesiosaurs repeated deep dives in the pelagic habitat and mirror conditions found in extant marine mammals and birds. Our results emphasize physiological aspects of adaptive convergence among fossil and extant marine amniotes and add to our current understanding of plesiosaur evolution.
Low expression or hypermethylation of PLK2 might predict favorable prognosis for patients with glioblastoma multiforme

Background As the most aggressive brain tumor, patients with glioblastoma multiforme (GBM) have a poor prognosis. Our purpose was to explore prognostic value of Polo-like kinase 2 (PLK2) in GBM, a member of the PLKs family. Methods The expression profile of PLK2 in GBM was obtained from The Cancer Genome Atlas database. The PLK2 expression in GBM was tested. Kaplan–Meier curves were generated to assess the association between PLK2 expression and overall survival (OS) in patients with GBM. Furthermore, to assess its prognostic significance in patients with primary GBM, we constructed univariate and multivariate Cox regression models. The association between PLK2 expression and its methylation was then performed. Differentially expressed genes correlated with PLK2 were identified by Pearson test and functional enrichment analysis was performed. Results Overall survival results showed that low PLK2 expression had a favorable prognosis of patients with GBM (P-value = 0.0022). Furthermore, PLK2 (HR = 0.449, 95% CI [0.243–0.830], P-value = 0.011) was positively associated with OS by multivariate Cox regression analysis. In cluster 5, DNA methylated PLK2 had the lowest expression, which implied that PLK2 expression might be affected by its DNA methylation status in GBM. PLK2 in CpG island methylation phenotype (G-CIMP) had lower expression than non G-CIMP group (P = 0.0077). Regression analysis showed that PLK2 expression was negatively correlated with its DNA methylation (P = 0.0062, Pearson r = −0.3855). Among all differentially expressed genes of GBM, CYGB (r = 0.5551; P < 0.0001), ISLR2 (r = 0.5126; P < 0.0001), RPP25 (r = 0.5333; P < 0.0001) and SOX2 (r = −0.4838; P < 0.0001) were strongly correlated with PLK2. Functional enrichment analysis results showed that these genes were enriched several biological processes or pathways that were associated with GBM. Conclusion Polo-like kinase 2 expression is regulated by DNA methylation in GBM, and its low expression or hypermethylation could be considered to predict a favorable prognosis for patients with GBM.
Bibliographic revision of Mesacanthion Filipjev, 1927 (Nematoda: Thoracostomopsidae) with description of a new species from Jeju Island, South Korea

A new species of the genus Mesacanthion Filipjev, 1927 was discovered during a survey of natural beaches of Jeju Island in South Korea. The new species Mesacanthion jejuensis sp. nov. shares general morphology of the genus such as the outer labial and cephalic setae being situated at the middle of cephalic capsule, well-developed mandibles with two columns united by a curved bar, and three equally sized and shaped teeth shorter than the mandibles. The new species belongs to a group of Mesacanthion species in which spicules are shorter than two anal body diameters. The new species is most closely related to M. pannosum, first discovered in Puget Sound, Washington, in terms of having enlarged cervical setae flap at the end of cephalic capsule, spicules which are shorter than 2 anal body diameter, both supplementary organ and gubernaculum. It can be distinguished from M. pannosum by its stronger inner labial setae, longer outer labial setae, and difference in the index value of b and c’. Along with the description of Mesacanthion jejuensis sp. nov., the genus Mesacanthion Filipjev, 1927 is bibliographically reviewed and revised. Including the new species, a total of 48 species are described within the genus; 39 which are valid; eight which are considered to be species inquirenda due to misplacement of genus and poor description; one which is considered nomen nudum. An updated diagnosis of the genus is provided along with a compiled tabular key comparing different diagnostic morphological characters of all valid species, as well as a pictorial key consisting of 21 species with spicules shorter than two anal body diameters.
Engineering formal systems in constructive type theory

This thesis presents a practical methodology for formalizing the meta-theory of formal systems with binders and coinductive relations in constructive type theory. While constructive type theory offers support for reasoning about formal systems built out of inductive definitions, support for syntax with binders and coinductive relations is lacking. We provide this support. We implement syntax with binders using well-scoped de Bruijn terms and parallel substitutions. We solve substitution lemmas automatically using the rewriting theory of the σ-calculus. We present the Autosubst library to automate our approach in the proof assistant Coq. Our approach to coinductive relations is based on an inductive tower construction, which is a type-theoretic form of transfinite induction. The tower construction allows us to reduce coinduction to induction. This leads to a symmetric treatment of induction and coinduction and allows us to give a novel construction of the companion of a monotone function on a complete lattice. We demonstrate our methods with a series of case studies. In particular, we present a proof of type preservation for CCω, a proof of weak and strong normalization for System F, a proof that systems of weakly guarded equations have unique solutions in CCS, and a compiler verification for a compiler from a non-deterministic language into a deterministic language. All technical results in the thesis are formalized in Coq.
Radio map estimation with neural networks and active learning for indoor localization

Accurate estimation of the radio frequency maps is key in practical indoor localization, but this requires dense sampling of the electromagnetic ﬁeld, which is also known as ﬁngerprinting. To decrease the time-consuming ﬁngerprinting process, we both aim to estimate probabilistic radio frequency maps (RM) using artiﬁcial neural networks (ANN), and automatically pick the most informative ﬁngerprint positions following an active learning strategy based on uncertainty sampling, aided by Gaussian Processes (GP). Once we have an estimate of the RM of the environment, the problem can be formulated as a tracking problem with a Hidden Markov Model (HMM), and the RM can be used as the observation densities of the HMM. The trajectories of sequential positions are approximated with a sequential Monte Carlo ﬁlter. The results indicate that ﬁngerprint measurements can be reduced by 30% in return of 8.1% decrease in the localization performance.
THIN Si BASED FUEL CELL WITH POROUS Pt LAYER FORMED ON A Si SUBSTRATE

Improved performance of our Si based fuel cell was demonstrated. Recently, we discovered that porous Pt can be obtained by immersing porous Si into a Pt plating bath containing HF. The porous Si is prepared on a Si chip by anodization in a HF electrolyte. In the plating bath, it is supposed that Pt replaces Si and the porous Pt layer is obtained. Using the porous Pt as a catalyst layer, we proposed a monolithic Si based fuel cell electrode. Although power generation was demonstrated with a prototype cell using the Si based electrodes, studies about the porous Pt formation were quite insufficient and the porous Pt formation was still instable. Various porous Pt formation tests were carried out and more stable conditions were found. Using those conditions, prototype cells were built and peak output of 82mW/cm was obtained.
INHIBITORY IMMUNOGLOBULIN POLYPEPTIDES TO HUMAN PDGF BETA RECEPTOR

Continuation of application No. 09/419,076, filed on Oct. 15, 1999, now abandoned, which is a continua tion of application No. 09/003,810, filed on Jan. 7, 1998, which is a continuation of application No. 08/258,283, filed on Jun. 10, 1994, now Pat. No. 5,817,310, which is a continuation-in-part of appli cation No. 08/253,440, filed on Jun. 7, 1994, now abandoned, which is a continuation of application No. 07/801,795, filed on Dec. 2, 1991, now abandoned.
Resolving noise–control conflict by gene duplication

Gene duplication promotes adaptive evolution in two principle ways: allowing one duplicate to evolve a new function and resolving adaptive conflicts by splitting ancestral functions between the duplicates. In an apparent departure from both scenarios, low-expressing transcription factor (TF) duplicates commonly regulate similar sets of genes and act in overlapping conditions. To examine for possible benefits of such apparently redundant duplicates, we examined the budding yeast duplicated stress regulators Msn2 and Msn4. We show that Msn2,4 indeed function as one unit, inducing the same set of target genes in overlapping conditions, yet this two-factor composition allows its expression to be both environmental-responsive and with low-noise, thereby resolving an adaptive conflict that inherently limits expression of single genes. Our study exemplified a new model for evolution by gene duplication whereby duplicates provide adaptive benefit through cooperation, rather than functional divergence: attaining two-factor dynamics with beneficial properties that cannot be achieved by a single gene.
Relaxation Dynamics of Hydrated Thymine, Thymidine, and Thymidine Monophosphate Probed by Liquid Jet Time-Resolved Photoelectron Spectroscopy.

The relaxation dynamics of thymine and its derivatives thymidine and thymidine monophosphate are studied using time-resolved photoelectron spectroscopy applied to a water microjet. Two absorption bands are studied, the first is a bright ππ* state which is populated using tunable-ultraviolet light in the range of 4.74 - 5.17 eV and probed using a 6.20 eV probe pulse. By reversing the order of these pulses, a band containing multiple ππ* states is populated by the 6.20 eV pulse and the lower energy pulse serves as the probe. The lower lying ππ* state is found to decay in ~400 fs in both thymine and thymidine independent of pump photon energy while thymidine monophosphate decays vary from 670 - 840 fs with some pump energy dependence. The application of a computational QM/MM scheme at the XMS-CASPT2//CASSCF/AMBER level of theory suggests that conformational differences existing between thymidine and thymidine monophosphate in solution accounts for this difference. The higher lying ππ* band is found to decay in ~600 fs in all three cases, but is only able to be characterized when using the 5.17 eV probe pulse. Notably, no long-lived signal from an nπ* state can be identified in either experiment on any of the three molecules.
Comparison of warfarin versus antiplatelet therapy after surgical bioprosthetic aortic valve replacement

Objectives To compare effectiveness of warfarin and antiplatelet exposure regarding both thrombotic and bleeding events, following surgical aortic valve replacement with a biological prosthesis(bioSAVR). Methods The study included all patients in Sweden undergoing a bioSAVR during 2008–2014 who were alive at discharge from the index hospital stay. Exposure was analysed and defined as postdischarge dispension of any antithrombotic pharmaceutical, updated at each following dispensions and categorised as single antiplatelet (SAPT), warfarin, warfarin combined with SAPT, dual antiplatelet (DAPT) or no antithrombotic treatment. Exposure to SAPT was used as comparator. Outcome events were all-cause mortality, ischaemic stroke, haemorrhagic stroke, any thromboembolism and major bleedings. We continuously updated adjustments for comorbidities with any indication for antithrombotic treatment by Cox regression analysis. Results We identified 9539 patients with bioSAVR (36.8% women) at median age of 73 years with a mean follow-up of 3.13 years. As compared with SAPT, warfarin alone was associated with a lower incidence of ischaemic stroke (HR 0.49, 95% CI 0.35 to 0.70) and any thromboembolism (HR 0.75, 95% CI 0.60 to 0.94) but with no difference in mortality (HR 0.94, 95% CI 0.78 to 1.13). The incidence of haemorrhagic stroke (HR 1.94, 95% CI 1.07 to 3.51) and major bleeding (HR 1.67, 95% CI 1.30 to 2.15) was higher during warfarin exposure. As compared with SAPT, DAPT was not associated with any difference in ischaemic stroke or any thromboembolism. Risk-benefit analyses demonstrated that 2.7 (95% CI 1.0 to 11.9) of the ischaemic stroke cases could potentially be avoided per every haemorrhagic stroke caused by warfarin exposure instead of SAPT during the first year. Conclusion In patients discharged after bioSAVR, warfarin exposure as compared with SAPT exposure was associated with lower long-term risk of ischaemic stroke and thromboembolic events, and with a higher incidence of bleeding events but with similar mortality.
Association of magnesium consumption with type 2 diabetes and glucose metabolism: A systematic review and pooled study with trial sequential analysis

Prevention of type 2 diabetes (T2D) with diet or diet supplementation is challenging. This article aims to draw conclusive associations between magnesium intake and T2D incidence and evaluate the effect of magnesium supplementation on glucose metabolism. Databases were searched for related articles from inception to May 15, 2019. Prospective cohort studies investigating the relevant relationship as well as randomized controlled trials (RCTs) assessing the effect of magnesium supplementation were eligible. We conducted trial sequential analysis (TSA) to prove the sufficiency of the current evidence. Twenty‐six publications involving 35 cohorts were included in the analysis. Compared to the lowest magnesium intake, the highest level was associated with a 22% lower risk for T2D; the risk was reduced by 6% for each 100 mg increment in daily magnesium intake. Additional analysis of 26 RCTs (1168 participants) was performed, revealing that magnesium supplementation significantly reduced the fasting plasma glucose (FPG) level (SMD, −0.32 [95% CI, −0.59 to −0.05], 2‐hour oral glucose tolerance test (2‐h OGTT) result (SMD, −0.30 [−0.58 to −0.02]), fasting insulin level (SMD, −0.17 [−0.30 to −0.04]), homeostatic model assessment‐insulin resistance (HOMA‐IR) score (SMD, −0.41 [−0.71 to −0.11]), triglyceride (TG) level, systolic blood pressure (SBP) and diastolic blood pressure (DBP). TSA showed an inverse association, with most benefits of magnesium supplementation on glucose metabolism being stable. In conclusion, magnesium intake has an inverse dose‐response association with T2D incidence, and supplementation appears to be advisable in terms of glucose parameters in T2D/high‐risk individuals.
Fragmentation and thresholds in hydrological flow‐based ecosystem services

Abstract Loss and fragmentation of natural land cover due to expansion of agricultural areas is a global issue. These changes alter the configuration and composition of the landscape, particularly affecting those ecosystem services (benefits people receive from ecosystems) that depend on interactions between landscape components. Hydrological mitigation describes the bundle of ecosystem services provided by landscape features such as woodland that interrupt the flow of runoff to rivers. These services include sediment retention, nutrient retention and mitigation of overland water flow. The position of woodland in the landscape and the landscape topography are both important for hydrological mitigation. Therefore, it is crucial to consider landscape configuration and flow pathways in a spatially explicit manner when examining the impacts of fragmentation. Here we test the effects of landscape configuration using a large number (>7,000) of virtual landscape configurations. We created virtual landscapes of woodland patches within grassland, superimposed onto real topography and stream networks. Woodland patches were generated with user‐defined combinations of patch number and total woodland area, placed randomly in the landscape. The Ecosystem Service model used hydrological routing to map the “mitigated area” upslope of each woodland patch. We found that more fragmented woodland mitigated a greater proportion of the catchment. Larger woodland area also increased mitigation, however, this increase was nonlinear, with a threshold at 50% coverage, above which there was a decline in service provision. This nonlinearity suggests that the benefit of any additional woodland depends on two factors: the level of fragmentation and the existing area of woodland. Edge density (total edge of patches divided by area of catchment) was the best single metric in predicting mitigated area. Distance from woodland to stream was not a significant predictor of mitigation, suggesting that agri‐environment schemes planting riparian woodland should consider additional controls such as the amount of fragmentation in the landscape. These findings highlight the potential benefits of fragmentation to hydrological mitigation services. However, benefits for hydrological services must be balanced against any negative effects of fragmentation or habitat loss on biodiversity and other services.
Clinic-Level Factors Associated with Retention in Care among People Living with HIV in a Multi-Site United States Cohort, 2010-2016.

BACKGROUND Retention in care (RIC) leads to reduced HIV transmission and mortality. Few studies have investigated the availability of clinic services and RIC among people living with HIV (PLWH) in the United States (US). We conducted a multi-site retrospective cohort study to identify clinic services associated with RIC from 2010-2016 in the US. METHODS PLWH with ≥1 attended HIV primary care visit from 2010-2016 at seven sites in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) were included. Clinic-level factors evaluated via site survey included patients per provider/trainee, peer navigation, RIC posters/brochures, laboratory test timing, flexible scheduling, appointment reminder methods, and stigma support services. RIC was defined as ≥2 encounters per year, ≥90 days apart, observed until death, administrative censoring (December 31, 2016), or loss to follow-up (censoring at first 12-month interval without a visit if there were no future visits). Poisson regression with robust error variance, clustered by site and adjusted for calendar year, age, sex, race/ethnicity, and HIV transmission risk factor, estimated risk ratios (RR) and 95% confidence intervals (CI) for RIC. RESULTS Among 21,046 PLWH contributing 103,348 person-years, 67% of person-years were retained. Availability of text appointment reminders (RR:1.13; 95% CI:1.03-1.24) and stigma support services (RR:1.11; 95% CI:1.04-1.19) were associated with better RIC. Disparities persisted with respect to age, sex, and race after accounting for clinic-level factors. CONCLUSION Availability of text appointment reminders and stigma support services was associated with higher rates of RIC indicating that these may be feasible and effective approaches for improving RIC.
CGRP Signaling via CALCRL Increases Chemotherapy Resistance and Stem Cell Properties in Acute Myeloid Leukemia

The neuropeptide CGRP, acting through the G-protein coupled receptor CALCRL and its coreceptor RAMP1, plays a key role in migraines, which has led to the clinical development of several inhibitory compounds. Recently, high CALCRL expression has been shown to be associated with a poor prognosis in acute myeloid leukemia (AML). We investigate, therefore, the functional role of the CGRP-CALCRL axis in AML. To this end, in silico analyses, human AML cell lines, primary patient samples, and a C57BL/6-based mouse model of AML are used. We find that CALCRL is up-regulated at relapse of AML, in leukemic stem cells (LSCs) versus bulk leukemic cells, and in LSCs versus normal hematopoietic stem cells. CGRP protects receptor-positive AML cell lines and primary AML samples from apoptosis induced by cytostatic drugs used in AML therapy, and this effect is inhibited by specific antagonists. Furthermore, the CGRP antagonist olcegepant increases differentiation and reduces the leukemic burden as well as key stem cell properties in a mouse model of AML. These data provide a basis for further investigations into a possible role of CGRP-CALCRL inhibition in the therapy of AML.