Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of a carbohydrate‐binding site in physarum haemagglutinin I

Carbohydrate‐binding peptides from trypsin‐digests of Physarum lectins (haemagglutinins I and II) were isolated by affinity column chromatography. The amino acid sequence of the peptlde fragment from haemagglutinin I was determined to be 48TVHQSWY54. A similar amino acid sequence was found in the peptide fragment from haemagglutinin II, in which alignment of valine, histidine, tryptophan and tyrosine was identical. Deletion of the heptapeptide sequence (TVHQSWY) by site‐directed mutation abolished the haemagglutinating activity. The replacement of Trp53 by alanine resulted in a complete loss of the haemagglutinating activity, suggesting that the tryptophan residue in the heptapeptide sequence is essential for carbohydrate binding.
Evaluating the Safety and Efficacy of Glucommander®, a Computer-based Insulin Infusion Method, in Management of Diabetic Ketoacidosis in Children, and Comparing its Clinical Performance with Manually Titrated Insulin Infusion

The Glucommander is a computer-based system for directing intravenous insulin infusion. Using a physician-selected glucose target range and a weight-based multiplier, it recommends an insulin infusion rate and interval to next glucose measurement. We evaluated the safety and efficacy of this system by conducting a retrospective chart review of 65 new-onset or existing type 1 diabetic children, admitted with diabetic ketoacidosis (DKA), managed with the Glucommander. We compared outcomes with 22 patients managed using manually titrated infusion. Time to glycemic control and correction of acidosis, number of insulin units used per kilogram per hour, and length of pediatric intensive care unit (PICU) and total hospital stay were analyzed using measures of central tendency. Children managed with Glucommander achieved equally rapid glycemic control and correction of acidosis, used less intravenous insulin, and spent less time in both PICU and hospital overall, compared to those managed with manual insulin infusion.
Central chemoreceptors and sympathetic vasomotor outflow

The present study explores how elevations in brain P CO 2 increase the sympathetic nerve discharge (SND). SND, phrenic nerve discharge (PND) and putative sympathoexcitatory vasomotor neurons of the rostral ventrolateral medulla (RVLM) were recorded in anaesthetized sino‐aortic denervated and vagotomized rats. Hypercapnia (end‐expiratory CO2 from 5% to 10%) increased SND (97 ± 6%) and the activity of RVLM neurons (67 ± 4%). Injection of kynurenic acid (Kyn, ionotropic glutamate receptor antagonist) into RVLM or the retrotrapezoid nucleus (RTN) eliminated or reduced PND, respectively, but did not change the effect of CO2 on SND. Bilateral injection of Kyn or muscimol into the rostral ventral respiratory group (rVRG‐pre‐Bötzinger region, also called CVLM) eliminated PND while increasing the stimulatory effect of CO2 on SND. Muscimol injection into commissural part of the solitary tract nucleus (commNTS) had no effect on PND or SND activation by CO2. As expected, injection of Kyn into RVLM or muscimol into commNTS virtually blocked the effect of carotid body stimulation on SND in rats with intact carotid sinus nerves. In conclusion, CO2 increases SND by activating RVLM sympathoexcitatory neurons. The relevant central chemoreceptors are probably located within or close to RVLM and not in the NTS or in the rVRG‐pre‐Bötzinger/CVLM region. RVLM sympathoexcitatory neurons may be intrinsically pH‐sensitive and/or receive excitatory synaptic inputs from RTN chemoreceptors. Activation of the central respiratory network reduces the overall sympathetic response to CO2, presumably by activating barosensitive CVLM neurons and inhibiting RTN chemoreceptors.
Key role for myeloid cells: Phase II results of anti‐GD2 antibody 3F8 plus granulocyte‐macrophage colony‐stimulating factor for chemoresistant osteomedullary neuroblastoma

Anti‐GD2 murine antibody 3F8 plus subcutaneously (sc) administered granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) was used against primary refractory neuroblastoma in metastatic osteomedullary sites. Large study size and long follow‐up allowed assessment of prognostic factors in a multivariate analysis not reported with other anti‐GD2 antibodies. In a phase II trial, 79 patients without prior progressive disease were treated for persistent osteomedullary neuroblastoma documented by histology and/or metaiodobenzyl‐guanidine (MIBG) scan. In the absence of human antimouse antibody, 3F8 + scGM‐CSF cycles were repeated up to 24 months. Minimal residual disease (MRD) in bone marrow was measured by quantitative reverse transcription‐polymerase chain reaction pre‐enrollment and post‐cycle #2, before initiation of 13‐cis‐retinoic acid. Study endpoints were: (i) progression‐free survival (PFS) compared with the predecessor trial of 3F8 plus intravenously administered (iv) GM‐CSF (26 patients) and (ii) impact of MRD on PFS. Using all 105 patients from the two consecutive 3F8 + GM‐CSF trials, prognostic factors were analyzed by multivariate Cox regression model. Complete response rates to 3F8 + scGM‐CSF were 87% by histology and 38% by MIBG. Five‐year PFS was 24 ± 6%, which was significantly superior to 11 ± 7% with 3F8 + ivGM‐CSF (p = 0.002). In the multivariate analysis, significantly better PFS was associated with R/R or H/R FCGR2A polymorphism, sc route of GM‐CSF and early MRD response. MYCN amplification was not prognostic. Complement consumption was similar with either route of GM‐CSF. Toxicities were manageable, allowing outpatient treatment. 3F8 + scGM‐CSF is highly active against chemoresistant osteomedullary neuroblastoma. MRD response may be an indicator of tumor sensitivity to anti‐GD2 immunotherapy. Correlative studies highlight the antineoplastic potency of myeloid effectors.
Proline-directed and Non-proline-directed Phosphorylation of PHF-tau (*)

To gain insight into the abnormal phosphorylation of PHF-tau, we have determined the phosphorylation sites by identifying phosphopeptides by means of ion spray mass spectrometry followed by sequencing of ethanethiol-modified peptides. Nineteen sites have been identified; all but Ser-262 are localized to the amino- and carboxyl-terminal flanking regions of the microtubule-binding domain. Eleven sites correspond to fetal type sites. Unexpectedly, 10 are non-proline-directed, whereas the others are proline-directed. Thus, the abnormal phosphorylation of PHF-tau can be considered to consist of fetal type phosphorylation and additional proline-directed and non-proline-directed phosphorylation. This non-fetal type phosphorylation may provide PHF-tau with the unusual characteristics.
Effect of natural fibres on the mechanical properties of thermoplastic starch

Abstract This paper presents the results covering the mechanical properties of thermoplastic potato starch granules with flax, cellulose fibre, and pine bark addition. A modified single screw extrusion-cooker TS-45 with L/D = 18 and an additional cooling section of the barrel was used as the processing unit. The establishment influence of the fibre addition, as well as the extrusion-cooker screw speed, on the mechanical properties of the thermoplastic starch granules was the main objective of the investigation. The maximum force during compression to 50% of the sample diameter, elastic modulus, and compression strength were evaluated. Significant differences were noted depending on the amount of fibre used, while only an insignificant influence of screw speed on the mechanical properties of the granulate was reported. An increased amount of fibres lowered the maximum force as well as the elastic modulus and compression strength of the thermoplastic starch granulates.
Anomalous transport in the crowded world of biological cells

A ubiquitous observation in cell biology is that the diffusive motion of macromolecules and organelles is anomalous, and a description simply based on the conventional diffusion equation with diffusion constants measured in dilute solution fails. This is commonly attributed to macromolecular crowding in the interior of cells and in cellular membranes, summarizing their densely packed and heterogeneous structures. The most familiar phenomenon is a sublinear, power-law increase of the mean-square displacement (MSD) as a function of the lag time, but there are other manifestations like strongly reduced and time-dependent diffusion coefficients, persistent correlations in time, non-Gaussian distributions of spatial displacements, heterogeneous diffusion and a fraction of immobile particles. After a general introduction to the statistical description of slow, anomalous transport, we summarize some widely used theoretical models: Gaussian models like fractional Brownian motion and Langevin equations for visco-elastic media, the continuous-time random walk model, and the Lorentz model describing obstructed transport in a heterogeneous environment. Particular emphasis is put on the spatio-temporal properties of the transport in terms of two-point correlation functions, dynamic scaling behaviour, and how the models are distinguished by their propagators even if the MSDs are identical. Then, we review the theory underlying commonly applied experimental techniques in the presence of anomalous transport like single-particle tracking, fluorescence correlation spectroscopy (FCS) and fluorescence recovery after photobleaching (FRAP). We report on the large body of recent experimental evidence for anomalous transport in crowded biological media: in cyto- and nucleoplasm as well as in cellular membranes, complemented by in vitro experiments where a variety of model systems mimic physiological crowding conditions. Finally, computer simulations are discussed which play an important role in testing the theoretical models and corroborating the experimental findings. The review is completed by a synthesis of the theoretical and experimental progress identifying open questions for future investigation.
Microtubule network asymmetry in motile cells: Role of Golgi-derived array

Cell migration requires polarization of the cell into the leading edge and the trailing edge. Microtubules (MTs) are indispensable for polarized cell migration in the majority of cell types. To support cell polarity, MT network has to be functionally and structurally asymmetric. How is this asymmetry achieved? In interphase cells, MTs form a dynamic system radiating from a centrosome-based MT-organizing center (MTOC) to the cell edges. Symmetry of this radial array can be broken according to four general principles. Asymmetry occurs due to differential modulation of MT dynamics, relocation of existing MTs within a cell, adding an asymmetric nucleation site, and/or repositioning of a symmetric nucleation site to one side of a cell. Combinations of these asymmetry regulation principles result in a variety of asymmetric MT networks typical for diverse motile cell types. Importantly, an asymmetric MT array is formed at a non-conventional MT nucleation site, the Golgi. Here, we emphasize the contribution of this array to the asymmetry of MT network.
A retrospective clinicopathological study of 131 cases with endometrial cancers--is it possible to define the role of retroperitoneal lymphadenectomy in low-resource settings?

AIM The study objectives were evaluation of clinicopathological characteristics, correlations between the preoperative and postoperative tumor grades, and their implications on lymph node metastasis. MATERIALS AND METHODS We conducted a retrospective descriptive study of 131 cases of endometrial cancer examined and treated at a tertiary regional cancer institute between the years 2003 and 2009. We reviewed the oncology database as well as the clinical records and surgico-pathological registry of all these patients. Statistical Methods Used: All the summary measure computation and Chi-square test for comparing more than one proportion was done in spreadsheet (Excel). RESULTS The multiparity association with endometrial cancer was commonly seen 113/131 (86.2%). Twelve (9.7%) patients preoperatively diagnosed as Grade 1 tumors upgraded to Grade 3 changes in postoperative specimens and six of these 12 patients (50%) had lymph node metastasis. A total of 14/131 (10.6%) cases had lymph nodes metastasis. CONCLUSIONS There is a poor correlation between the preoperative and the postoperative tumor grades. Routine pelvic lymphadenectomy may be a valuable method in low-risk cases and para-aortic lymphadenectomy may be limited to high-risk endometrial cancers.
The synthetic retinoid AGN 193109 but not retinoic acid elevates CYP1A1 levels in mouse embryos and Hepa-1c1c7 cells.

The synthetic retinoid AGN 193109 is a potent pan retinoic acid receptor (RAR) antagonist. Treatment of pregnant mice with a single oral 1 mg/kg dose of this antagonist on day 8 postcoitum results in severe craniofacial (median cleft face or frontonasal deficiency) and eye malformations in virtually all exposed fetuses. Using differential display analysis, we have determined that CYP1A1 mRNA levels are elevated in mouse embryos 6 h following treatment with AGN 193109. Similarly, an elevation in CYP1A1 mRNA levels, protein levels, and aryl hydrocarbon hydoxylase activity occurs in Hepa-1c1c7 cells, with the maximal elevation observed when the cells were treated with 10(-5) M AGN 193109 for 4 to 8 h. Elevation in CYP1A1 mRNA levels in mouse embryos and Hepa-1c1c7 cells does not occur upon treatment with the natural retinoid, all-trans-retinoic acid. Finally, elevation in CYP1A1 mRNA levels was not observed when mutant Hepa-1c1c7 cells, which are defective in either the aryl hydrocarbon receptor (AhR) or aryl hydrocarbon receptor nuclear translocator (ARNT), were treated with AGN 193109. This suggests that the AhR/ARNT pathway and not the RAR/RXR pathway is mediating the elevation of CYP1A1 mRNA levels by AGN 193109, at least in the Hepa-1c1c7 cells. This is the first example of a retinoid that displays the abililty to regulate both the RAR/RXR and AhR/ARNT transcriptional regulatory pathways.
A novel nucleotide incorporation activity implicated in the editing of mitochondrial transfer RNAs in Acanthamoeba castellanii.

In Acanthamoeba castellanii, most of the mtDNA-encoded tRNAs are edited by a process that replaces one or more of the first three nucleotides at their 5' ends. As a result, base pairing potential is restored at acceptor stem positions (1:72, 2:71, and/or 3:70, in standard tRNA nomenclature) that are mismatched according to the corresponding tRNA gene sequence. Here we describe a novel nucleotide incorporation activity, partially purified from A. castellanii mitochondria, that has properties implicating it in mitochondrial tRNA editing in this organism. This activity is able to replace nucleotides at the first three positions of a tRNA (positions 1, 2, and 3), matching the newly incorporated residues through canonical base pairing to the respective partner nucleotide in the 3' half of the acceptor stem. Labeling experiments with natural (Escherichia coli tRNATyr) and synthetic (run-off transcripts corresponding to A. castellanii mitochondrial tRNALeu1) substrates suggest that the nucleotide incorporation activity consists of at least two components, a 5' exonuclease or endonuclease and a template-directed 3'-to-5' nucleotidyltransferase. The nucleotidyltransferase component displays an ATP requirement and generates 5' pppN. termini in vitro. The development of an accurate and efficient in vitro system opens the way for detailed studies of the biochemical properties of this novel activity and its relationship to mitochondrial tRNA editing in A. castellanii. In addition, the system will allow delineation of the structural features in a tRNA that identify it as a substrate for the labeling activity.
Inhibition of cellular alpha DNA polymerase and herpes simplex virus-induced DNA polymerases by the triphosphate of BW759U

The triphosphate form of the acyclovir analog BW759U (9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine) inhibited the DNA polymerases (EC 2.7.7.7) from several strains of herpes simplex virus type 1. Two acyclovir triphosphate-resistant DNA polymerases were as sensitive to BW759U-triphosphate as were the DNA polymerases induced by wild-type viruses (Ki = 0.05 to 0.1 microM). The Ki value for cellular alpha DNA polymerase was 35- to 50-fold greater than those for the DNA polymerases induced by the various herpes simplex virus strains investigated. Incubation of Vero cells infected by the KOS strain of herpes simplex virus type 1 with the acyclovir analog resulted in the formation of substantial quantities of (9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine) triphosphate.
Damage inhibition during frozen storage of horse mackerel (Trachurus trachurus) fillets by a previous plant extract treatment

We investigated the effect of a commercial plant extract, Rosmol-P (RP) on the stability of fish during frozen storage. Horse mackerel (Trachurus trachurus) fillets were soaked in water (water control) and 2 RP concentrations (RP-1 = 0.333%; RP-2 = 1.333%) and compared with untreated fillets (blank control). Fluorescence detection and thiobarbitoric acid index showed a lower oxidation development for both RP treatments than for both controls, especially in the case of the highest concentration (RP-2). The decrease in ghitathione peroxidase activity was found to be shower in the case of the RP-2 treatment. The sensory analysis showed an increased shelf-life according to the sequence blank control < water control < RP-1, RP-2.
Identification of p21-Activated Kinase Specificity Determinants in Budding Yeast: a Single Amino Acid Substitution Imparts Ste20 Specificity to Cla4

ABSTRACT Two closely related p21-activated kinases from Saccharomyces cerevisiae, Ste20 and Cla4, interact with and are regulated by Cdc42, a small Rho-like GTPase. These kinases are argued to perform a common essential function, based on the observation that the single mutants are viable whereas the double mutant is inviable. Despite having a common upstream regulator and at least one common function, these molecules also have many distinct cellular signaling roles. Ste20 signals upstream of several mitogen-activated protein kinase cascades (e.g., pheromone response, filamentous growth, and high osmolarity), and Cla4 signals during budding and cytokinesis. In order to investigate how these kinases are directed to distinct functions, we sought to identify specificity determinants within Ste20 and Cla4. To this end, we constructed both chimeric fusions and point mutants and tested their ability to perform unique and shared cellular roles. Specificity determinants for both kinases were mapped to the C-terminal kinase domains. Remarkably, the substitution of a single amino acid, threonine 818, from Ste20 into an otherwise wild-type Cla4, Cla4D772T, conferred the ability to perform many Ste20-specific functions.
Costs and Utilization of End-stage Glaucoma Patients Receiving Visual Rehabilitation Care: A US Multisite Retrospective Study

PurposeGlaucoma is a prevalent ophthalmologic disease and leading cause of blindness. A retrospective analysis was conducted to evaluate resources and costs for end-stage glaucoma patients receiving visual rehabilitation care (VRC). Materials and MethodsA chart review was conducted in 3 United States VRC centers. Charts of patients with primary open-angle glaucoma as the primary cause of vision loss (1998 to 2003) were selected, yielding 81 records. Data were collected from patient-level billing and reimbursement records (ophthalmologist/optometrist visits, glaucoma medications, procedures, and specialized low-vision and glaucoma-related services). Visual rehabilitation services included utilization of low-vision devices, assessment of daily functioning, orientation and mobility training, and patient counseling. ResultsMean age at baseline was 72.7 years [standard deviation (SD)=17.2, range: 29 to 95]. Of those with known sex (n=77), 55.8% were women. Medicare was the payer type for most patients (59.3%), whereas 20% had Medicaid. Mean number of visits was 7.1 (SD=6.1) in year 1 and 3.7 (SD=4.2) in year 2, for an annual mean of 5.4 (SD=5.0) visits overall. Total mean cost per patient in year 1 was greater than year 2 [$2170 (SD=$2252) vs. $1202 (SD=$1080), respectively]; of the total 2-year costs, 15% were VRC, 37% ophthalmology care, and 48% pharmacy. Analysis of nonpharmacy costs revealed that VRC accounted for 28% and ophthalmology for 72%. ConclusionsEnd-stage glaucoma is associated with appreciable resource utilization and costs, because of both vision rehabilitation and ophthalmology care. Advanced primary open-angle glaucoma has a substantial cost-of-illness, warranting improved management in early stages of disease.
An in-depth numerical investigation into packaging design of multi-finger GaInP/GaAs collector-up HBTs

A novel finite-element modeling approach is developed to design thermal-via packaging configurations of collector-up heterojunction bipolar transistors (C-up HBTs) in high-power amplifiers (HPAs). The thermal interaction between HBT fingers has been examined based on the temperature distribution phenomena in multifinger C-up HBTs. The results reveal that the overall compactness of thermal-via configuration can be further improved more than 33%.
Safe Policy Improvement with Baseline Bootstrapping

A common goal in Reinforcement Learning is to derive a good strategy given a limited batch of data. In this paper, we adopt the safe policy improvement (SPI) approach: we compute a target policy guaranteed to perform at least as well as a given baseline policy. Our SPI strategy, inspired by the knows-what-it-knows paradigms, consists in bootstrapping the target policy with the baseline policy when it does not know. We develop two computationally efficient bootstrapping algorithms, a value-based and a policy-based, both accompanied with theoretical SPI bounds. Three algorithm variants are proposed. We empirically show the literature algorithms limits on a small stochastic gridworld problem, and then demonstrate that our five algorithms not only improve the worst case scenarios, but also the mean performance.
Estimating Parameters in Optimal Control Problems

In nature, there are many processes that are assumed to run optimally, for example, human motion or, in particular, human gait. In this paper, we consider models of such processes, which can be described by optimal control problems. These models are characterized by quantities that are not known and cannot be measured (examples are system parameters or the constitution of the optimality criterion). Our goal is to determine these unknown quantities from measurement data, which is equivalent to solving a parameter estimation problem based on an optimal control model. We investigate two approaches for finding the solution of this hierarchical optimization problem; both follow the idea of replacing the underlying optimal control problem by its optimality conditions. The first approach is based on Pontryagin's maximum principle, whereas the second approach uses direct multiple shooting and the corresponding Karush--Kuhn--Tucker conditions. Both approaches pose numerical challenges that are discussed in this pa.