Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Blood Glucose Self-Monitoring Errors on Glucose Variability, Risk for Hypoglycemia, and Average Glucose Control in Type 1 Diabetes: An In Silico Study

Background: Clinical trials assessing the impact of errors in self-monitoring of blood glucose (SMBG) on the quality of glycemic control in diabetes are inherently difficult to execute. Consequently, the objectives of this study were to employ realistic computer simulation based on a validated model of the human metabolic system and to provide potentially valuable information about the relationships among SMBG errors, risk for hypoglycemia, glucose variability, and long-term glycemic control. Methods: Sixteen thousand computer simulation trials were conducted using 100 simulated adults with type 1 diabetes. Each simulated subject was used in four simulation experiments aiming to assess the impact of SMBG errors on detection of hypoglycemia (experiment 1), risk for hypoglycemia (experiment 2), glucose variability (experiment 3), and long-term average glucose control, i.e., estimated hemoglobin A1c (HbA1c)(experiment 4). Each experiment was repeated 10 times at each of four increasing levels of SMBG errors: 5, 10, 15, and 20% deviation from the true blood glucose value. Results: When the permitted SMBG error increased from 0 to 5–10% to 15–20%—the current level allowed by International Organization for Standardization 15197—(1) the probability for missing blood glucose readings of 60 mg/dl increased from 0 to 0–1% to 3.5–10%; (2) the incidence of hypoglycemia, defined as reference blood glucose ≤70 mg/dl, changed from 0 to 0–0% to 0.1–5.5%; (3) glucose variability increased as well, as indicated by control variability grid analysis; and (4) the incidence of hypoglycemia increased from 15.0 to 15.2–18.8% to 22–25.6%. When compensating for this increase, glycemic control deteriorated with HbA1c increasing gradually from 7.00 to 7.01–7.12% to 7.26–7.40%. Conclusions: A number of parameters of glycemic control deteriorated substantially with the increase of permitted SMBG errors, as revealed by a series of computer simulations (e.g., in silico) experiments. A threshold effect apparent between 10 and 15% permitted SMBG error for most parameters, except for HbA1c, which appeared to be increasing relatively linearly with increasing SMBG error above 10%.
The heritability of otitis media: a twin and triplet study.

CONTEXT Anatomical, physiological, and epidemiological data indicate that there may be a significant genetic component to prolonged time with and recurrent episodes of otitis media in children. OBJECTIVE To determine the genetic component of time with and episodes of middle ear effusion and acute otitis media (AOM) during the first 2 years of life. DESIGN Prospective twin and triplet cohort study with enrollment from 1982 through 1995. SETTING Otitis Media Research Center in the ear, nose, and throat clinic of Children's Hospital of Pittsburgh, Pittsburgh, Pa. PATIENTS A total of 168 healthy same-sex twin and 7 triplet sets were recruited within the first 2 months of life; zygosity results were available for 140 sets; 138 (99%) of these were followed up for 1 year and 126 (90%) for 2 years. MAIN OUTCOME MEASURES Proportion of time with middle ear effusion, episodes of middle ear effusion, and episodes of AOM by zygosity status. RESULTS At the 2-year end point, the estimate of heritability of time with middle ear effusion was 0.73 (P<.001). The estimates of discordance for 3 or more episodes of middle ear effusion were 0.04 for monozygotic twins and 0.37 for dizygotic twins (P = .01). The estimate of discordance of an episode of AOM in monozygotic twins was 0.04 compared with 0.49 in dizygotic twins (P = .005). CONCLUSIONS Our study suggests there is a strong genetic component to the amount of time with middle ear effusion and episodes of middle ear effusion and AOM in children.
Optimum design of a miniaturized multilayer SIW diplexer using orthogonal-mode resonator

The optimum design of a miniaturized multilayer SIW diplexer in the X-band is presented using the orthogonal mode square resonator, which replaces the conventional T-junctions connecting the lower and upper frequency channels. The placement of metallic posts in the SIW excites two degenerate orthogonal modes. The two mode channel frequencies are adjusted by the displacement of positions of posts. The magnetic couplings between the middle SIW layer and the upper and lower ones are achieved by perpendicular rectangular apertures, where each one excites one of the orthogonal modes. Consequently, the isolation between the output ports is maximized. The ports are made by tapered microstrip lines. The proposed structure leads to substantial miniaturization of the SIW diplexer. A prototype model is fabricated and measured to verify its proposed structure and design procedure.
How and why do plant nuclei move in response to light?

We recently found that nuclei take different intracellular positions depending upon dark and light conditions in Arabidopsis thaliana leaf cells. Under dark conditions, nuclei in both epidermal and mesophyll cells are distributed baso-centrally within the cell (dark position). Under light conditions, in contrast, nuclei are distributed along the anticlinal walls (light position). Nuclear re-positioning from the dark to light positions is induced specifically by blue light at >50 μmol m-2 s-1 in a reversible manner. Using analysis of mutant plants, it was demonstrated that the response is mediated by the blue-light photoreceptor phototropin2. Intriguingly, phototropin2 also seems to play an important role in the proper positioning of nuclei and chloroplasts under dark conditions. Light-dependent nuclear positioning is one of the organelle movements regulated by phototropin2. However, the mechanisms of organelle motility, physiological significance, and generality of the phenomenon are poorly understood. In this addendum, we discussed how and why nuclei move depending on light, together with future perspectives.
Effectiveness of intraocular pressure-lowering medication determined by washout.

IMPORTANCE While medication efficacy is well documented in clinical trials, less is known of medication effectiveness in real-world clinical settings. OBJECTIVE To assess the effectiveness of intraocular pressure (IOP)-lowering medications in patients with open-angle glaucoma. DESIGN, SETTING, AND PARTICIPANTS Prospective, multicenter, interventional cohort from the prerandomization phase of a randomized clinical trial at multiple ophthalmology clinics. A total of 603 patients (603 eyes) with primary open-angle glaucoma who were using up to 3 glaucoma medications were included. INTERVENTIONS One IOP measurement was made while the patient was using his or her usual medications to lower IOP (ON IOP). Eligible participants underwent washout of all IOP-lowering drops, and the diurnal IOP was measured 2 to 4 weeks later (OFF IOP). MAIN OUTCOMES AND MEASURES Difference between OFF IOP and ON IOP. The hypothesis was formulated after data collection. RESULTS The mean (SD) ON IOPs for participants using 0 (n = 102), 1 (n = 272), 2 (n = 147), or 3 (n = 82) medications were 24.2 (3.2), 17.5 (3.2), 17.2 (3.1), and 17.2 (3.1) mm Hg, respectively. Patients not using medication had a mean (SD) IOP decrease of 0.2 (2.8) mm Hg at the OFF visit. Patients using 1, 2, and 3 medications had mean (SD) IOP increases of 5.4 (3.0), 6.9 (3.3), and 9.0 (3.8) mm Hg, respectively, at the OFF visit. The percentages of patients with less than a 25% increase in IOP were 38%, 21%, and 13% for those using 1, 2, and 3 medications, respectively. CONCLUSIONS AND RELEVANCE Discontinuation of 1, 2, and 3 medications was associated with a clinically significant increase in IOP, although with smaller effects for the second and third medications compared with the first medication. A substantial proportion of patients showed only small changes in IOP after medication washout, suggesting either that they were not using the medication effectively or that the medication itself, although used properly, was not lowering the IOP. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01085357.
Ubiquitination of Human T-Cell Leukemia Virus Type 1 Tax Modulates Its Activity

ABSTRACT Human T-cell leukemia virus type 1 (HTLV-1) encodes a 40-kDa Tax phosphoprotein. Tax is a transcriptional activator which modulates expression of the viral long terminal repeat and transcription of many cellular genes. Because Tax is a critical HTLV-1 factor which mediates viral transformation of T cells during the genesis of adult T-cell leukemia, it is important to understand the processes which can activate or inactivate Tax function. Here, we report that ubiquitination of Tax is a posttranscriptional mechanism which regulates Tax function. We show that ubiquitination does not target Tax for degradation by the proteasome. Rather, ubiquitin addition modifies Tax in a proteasome-independent manner from an active to a less-active transcriptional form.
Generating Fixed-Length Representation From Minutiae Using Kernel Methods for Fingerprint Authentication

The ISO/IEC 19794-2-compliant fingerprint minutiae template is an unordered and variable-sized point set data. Such a characteristic leads to a restriction for the applications that can only operate on fixed-length binary data, such as cryptographic applications and certain biometric cryptosystems (e.g., fuzzy commitment). In this paper, we propose a generic point-to-string conversion framework for fingerprint minutia based on kernel learning methods to generate discriminative fixed length binary strings, which enables rapid matching. The proposed framework consists of four stages: (1) minutiae descriptor extraction; (2) a kernel transformation method that is composed of kernel principal component analysis or kernelized locality-sensitive hashing for fixed length vector generation; (3) a dynamic feature binarization; and (4) matching. The promising experimental results on six datasets from fingerprint verification competition (FVC)2002 and FVC2004 justify the feasibility of the proposed framework in terms of matching accuracy, efficiency, and template randomness.
Decolorization of anthraquinone Vat Blue 4 by the free cells of an autochthonous bacterium, Bacillus subtilis.

Uncontaminated soil, Vat Blue 4 contaminated soil and Vat Blue 4 effluent were screened for heterotrophic bacterial population and the bacterial density were found to be 19.3 x 10(4) Colony Forming Units (CFU)/gm, 5.5 x 10(4) CFU/gm and 1.1 x 10(4) CFU/ml respectively. Student's 't' test analysis affirmed that significant variation prevailed between the three set of 't' tests conducted (P<0.001 to 0.002). The heterotrophic bacterial population of dye contaminated soil comprised of 32.5% of Pseudomonas spp. followed by 27.5% of Bacillus spp. , 15.0% of Aeromonas spp. , 12.5% of Micrococcus spp. and 12.5% of Achromobacter spp. The optimum inoculums load, pH and temperature were found to be 5% (10 x 10(4) counts), 10 and 35 degrees C respectively. Free cells of B. subtilis decolorized Vat Blue 4 up to 92.30% after 24 hours of treatment. Total Dissolved Solids (TDS), Biological Oxygen Demand (BOD(5)) and Chemical Oxygen Demand (COD) were reduced up to 50.00, 79.60 and 75.40% respectively.
Thrombotic complications in essential thrombocythemia with relatively low platelet counts

Essential thrombocythemia (ET) is often associated with thrombotic and hemorrhagic complications, mostly at platelet counts exceeding 600 × 109/L. There are, however, a few reports of such complications in ET at considerably lower platelet levels and the therapeutic approach to affected patients with relatively low platelet counts is still controversial. In the present study, the first to directly address the issue of hemostatic manifestations at relatively low platelet counts, we have determined the lowest platelet counts associated with such manifestations in 56 consecutive ET patients. Clinical manifestations related to ET were recorded in 46 (82%) patients. Of the symptomatic patients, 32 (70%) had symptoms at platelet counts lower than 600 × 109/L, 23 (50%) at counts lower than 500 × 109/L, 10 (22%) at counts lower than 400 × 109/L, and 6 patients (13%) at platelet counts as low as 300–350 × 109/L. Severe complications occurred at platelet counts lower than 600 × 109/L in 10 patients (22%), lower than 500 × 109/L in 7 (15%), and at lower than 400 × 109/L in 2 (4%). Thrombotic neurologic symptoms were the most common (31 patients, 67%), followed by peripheral vascular symptoms (17 patients, 37%); hemorrhagic complications were relatively rare (3 patients, 7%). In most cases, cessation or improvement of clinical manifestations was observed only after further reduction in platelet counts. In conclusion, thrombotic manifestations, including severe ones, are not uncommon in ET at relatively low platelet counts. We recommend that symptomatic patients with relatively low platelet counts be treated and the platelet counts further reduced well into the lower normal range. Am. J. Hematol. 56:168–172, 1997. © 1997 Wiley‐Liss, Inc.
Noxious heat‐induced CGRP release from rat sciatic nerve axons in vitro

Noxious heat may act as an endogenous activator of the ionotropic capsaicin receptor (VR1) and of its recently found homologue VRL1, expressed in rat dorsal root ganglion cells and present along their nerve fibres. We have previously reported that capsaicin induces receptor‐mediated and Ca++‐dependent calcitonin gene‐related peptide (CGRP) release from axons of the isolated rat sciatic nerve. Here we extended the investigation to noxious heat stimulation and the transduction mechanisms involved. Heat stimulation augmented the CGRP release from desheathed sciatic nerves in a log–linear manner with a Q10 of ≈ 15 and a threshold between 40 and 42 °C. The increases were 1.75‐fold at 42 °C, 3.8‐fold at 45 °C and 29.1‐fold at 52 °C; in Ca++‐free solution these heat responses were abolished or reduced by 71 and 92%, respectively. Capsazepine (10 µm) and Ruthenium Red (1 µm) used as capsaicin receptor/channel antagonists did not significantly inhibit the heat‐induced release. Pretreatment of the nerves with capsaicin (100 µm for 30 min) caused complete desensitization to 1 µm capsaicin, but a significant heat response remained, indicating that heat sensitivity is not restricted to capsaicin‐sensitive fibres. The sciatic nerve axons responded to heat, potassium and capsaicin stimulation with a Ca++‐dependent CGRP release. Blockade of the capsaicin receptor/channels had little effect on the heat‐induced neuropeptide release. We conclude therefore that other heat‐activated ion channels than VR1 and VRL1 in capsaicin‐sensitive and ‐insensitive nerve fibres may cause excitation, axonal Ca++ influx and subsequent CGRP release.
DEF-1/ASAP1 Is a GTPase-activating Protein (GAP) for ARF1 That Enhances Cell Motility through a GAP-dependent Mechanism*

DEF-1/ASAP1 is an ADP-ribosylation factor GTPase-activating protein (ARF GAP) that localizes to focal adhesions and is involved in cytoskeletal regulation. In this paper, we use a cell-based ARF GAP assay to demonstrate that DEF-1 functions as a GAP for ARF1 and not ARF6 in vivo. This degree of substrate preference was unique to DEF-1, as other ARF GAP proteins, ACAP1, ACAP2, and ARFGAP1, were able to function on both ARF1 and ARF6. Since transient overexpression of DEF-1 has been shown to interfere with focal adhesion formation and platelet-derived growth factor-induced membrane ruffling, we investigated whether NIH 3T3 cells stably expressing DEF-1 have altered cell motility. Here we report that ectopic DEF-1 enhances cell migration toward PDGF as well as IGF-1. This chemotactic effect appears to result from a general increase in cell motility, as DEF-1-expressing cells also exhibit enhanced levels of basal and chemokinetic motility. The increase in cell motility is dependent on DEF-1 GAP activity, since a DEF-1 mutant lacking the GAP domain failed to stimulate motility. This suggests that DEF-1 alters cell motility through the deactivation of ARF1. In contrast, the inhibition of cell spreading by DEF-1 was not dependent on GAP activity, indicating that spreading and motility are altered by DEF-1 through different pathways.
Subcellular sites for bacterial protein export

Most bacterial proteins destined to leave the cytoplasm are exported to extracellular compartments or imported into the cytoplasmic membrane via the highly conserved SecA‐YEG pathway. In the present studies, the subcellular distributions of core components of this pathway, SecA and SecY, and of the secretory protein pre‐AmyQ, were analysed using green fluorescent protein fusions, immunostaining and/or immunogold labelling techniques. It is shown that SecA, SecY and (pre‐)AmyQ are located at specific sites near and/or in the cytoplasmic membrane of Bacillus subtilis. The localization patterns of these proteins suggest that the Sec machinery is organized in spiral‐like structures along the cell, with most of the translocases organized in specific clusters along these structures. However, this localization appears to be independent of the helicoidal structures formed by the actin‐like cytoskeletal proteins, MreB or Mbl. Interestingly, the specific localization of SecA is dynamic, and depends on active translation. Moreover, reducing the phosphatidylglycerol phospholipids content in the bacterial membrane results in delocalization of SecA, suggesting the involvement of membrane phospholipids in the localization process. These data show for the first time that, in contrast to the recently reported uni‐ExPortal site in the coccoïd Streptococcus pyogenes, multiple sites dedicated to protein export are present in the cytoplasmic membrane of rod‐shaped B. subtilis.
Erythrocyte C3d and C4d for monitoring disease activity in systemic lupus erythematosus.

OBJECTIVE Disease activity in systemic lupus erythematosus (SLE) is typically monitored by measuring serum C3 and C4. However, these proteins have limited utility as lupus biomarkers, because they are substrates rather than products of complement activation. The aim of this study was to evaluate the utility of measuring the erythrocyte-bound complement activation products, erythrocyte-bound C3d (E-C3d) and E-C4d, compared with that of serum C3 and C4 for monitoring disease activity in patients with SLE. METHODS The levels of E-C3d and E-C4d were measured by flow cytometry in 157 patients with SLE, 290 patients with other diseases, and 256 healthy individuals. The patients with SLE were followed up longitudinally. Disease activity was measured at each visit, using the validated Systemic Lupus Activity Measure (SLAM) and the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). RESULTS At baseline, patients with SLE had higher median levels of E-C3d and E-C4d (P < 0.0001) in addition to higher within-patient and between-patient variability in both E-C3d and E-C4d when compared with the 2 non-SLE groups. In a longitudinal analysis of patients with SLE, E-C3d, E-C4d, serum C3, and anti-double-stranded DNA (anti-dsDNA) antibodies were each significantly associated with the SLAM and SELENA-SLEDAI. In a multivariable analysis, E-C4d remained significantly associated with these SLE activity measures after adjusting for serum C3, C4, and anti-dsDNA antibodies; however, E-C3d was associated with the SLAM but not with the SELENA-SLEDAI. CONCLUSION Determining the levels of the erythrocyte-bound complement activation products, especially E-C4d, is an informative measure of SLE disease activity as compared with assessing serum C4 levels and should be considered for monitoring disease activity in patients with SLE.
Evaluation of the effects of hydrophilic organic solvents on CYP3A-mediated drug-drug interaction in vitro

This study evaluated the effects of the commonly used hydrophilic organic solvents, acetonitrile, methanol, ethanol, 1-propanol, dimethyl sulfoxide (DMSO), N,N-dimethylformamide, polyethylene glycol and propylene glycol, on CYP3A in pooled human liver microsomes, using testosterone and midazolam as substrates. Furthermore, we examined the modulation effect of organic solvents on CYP3A inhibition by ketoconazole. Testosterone 6b-hydroxylation activity was potently inhibited in the presence of DMSO and 1-propanol in a concentration-dependent manner. Midazolam 1'-hydroxylation activity, however, was weakly inhibited only by 1% of DMSO, the highest concentration used in this study. Moreover, the potency of ketoconazole to inhibit CYP3A activities was variable, depending on the organic solvent used as a dissolving solvent for ketoconazole. Our data indicate that each organic solvent had an effect on CYP3A4 activity, evaluated by both substrates with different magnitudes. Furthermore, it was shown that the effects of organic solvents on CYP3A activity are substrate-dependent. The present study also shows that methanol had little effect on either substrate.
Past and projected trends of body mass index and weight status in South Australia: 2003 to 2019

Objective: Functional data analysis (FDA) is a forecasting approach that, to date, has not been applied to obesity, and that may provide more accurate forecasting analysis to manage uncertainty in public health. This paper uses FDA to provide projections of Body Mass Index (BMI), overweight and obesity in an Australian population through to 2019.
On Uncoordinated Service Placement in Edge-Clouds

Edge computing has emerged as a new paradigm to bring cloud applications closer to users for increased performance. ISPs have the opportunity to deploy private edge-clouds in their infrastructure to generate additional revenue by providing ultra-low latency applications to local users. We envision a rapid increase in the number of such applications for “edge” networks in the near future with virtual/augmented reality (VR/AR), networked gaming, wearable cognitive assistance, autonomous driving and IoT analytics having already been proposed for edge- clouds instead of the central clouds to improve performance. This raises new challenges as the complexity of the resource allocation problem for multiple services with latency deadlines (i.e., which service to place at which node of the edge-cloud in order to satisfy the latency constraints) becomes significant. In this paper, we propose a set of practical, uncoordinated strategies for service placement in edge-clouds. Through extensive simulations using both synthetic and real-world trace data, we demonstrate that uncoordinated strategies can perform comparatively well with the optimal placement solution, which satisfies the maximum amount of user requests.
Acquired activated protein C resistance in sarcoma patients

Acquired activated protein C resistance (aAPCR) is seen more frequently in solid and hematological cancer patients. We aimed to investigate the presence of aAPCR and the frequency of clinically detectable thrombosis in sarcoma patients. Normalized activated protein C sensitivity ratio (nAPCSR), factor V Leiden (FVL) mutation, factor V (FV) levels and factor VIII (FVIII) levels were prospectively measured in 52 patients and in 52 healthy controls. Clinically detectable thrombosis was present in one patient (1.92%). Compared with healthy controls (106%), the sarcoma patients had significantly lower values of the nAPCSR at pre (87.25%) and post (94.35%) treatment period (P < 0.0001). aAPCR was found as 4.2, 13 and 0%, respectively. The post-treatment FV levels (178.1 U/dl) were significantly (P < 0.001) higher than the pretreatment levels (147.5 U/dl). Inverse correlation was found between post-treatment FV levels and nAPCSR values (r = −0.38, P < 0.02). We found out a slightly increased frequency of venous thromboembolism in sarcoma patients. As an original finding which has not been reported previously in the literature, we also found out a decrease in the nAPCSR, persisting even after treatment. Thirdly, we found out that the significantly higher rate of aAPCR at the time of diagnosis totally disappeared after treatment.