cssi/SciSciGPT-SciSciNet huggingface dataset:
Outcomes in patients with severe COVID-19 disease treated with tocilizumab: a case-controlled study.

Background COVID-19 is an ongoing threat to society. Patients who develop the most severe forms of the disease have high mortality. The interleukin-6 inhibitor tocilizumab has the potential to improve outcomes in these patients by preventing the development of cytokine release storm. Aims To evaluate the outcomes of patients with severe COVID-19 disease treated with the interleukin-6 inhibitor tocilizumab. Methods We conducted a retrospective, case-control, single-center study in patients with severe to critical COVID-19 disease treated with tocilizumab. Disease severity was defined based on the amount of oxygen supplementation required. The primary endpoint was the overall mortality. Secondary endpoints were mortality in non-intubated patients and mortality in intubated patients. Results A total of 193 patients were included in the study. Ninety-six patients received tocilizumab, while 97 served as the control group. The mean age was 60 years. Patients over 65 years represented 43% of the population. More patients in the tocilizumab group reported fever, cough and shortness of breath (83%, 80% and 96% vs. 73%, 69% and 71%, respectively). There was a non-statistically significant lower mortality in the treatment group (52% vs. 62.1%, P = 0.09). When excluding intubated patients, there was statistically significant lower mortality in patients treated with tocilizumab (6% vs. 27%, P = 0.024). Bacteremia was more common in the control group (24% vs. 13%, P = 0.43), while fungemia was similar for both (3% vs. 4%, P = 0.72). Conclusion Our study showed a non-statistically significant lower mortality in patients with severe to critical COVID-19 disease who received tocilizumab. When intubated patients were excluded, the use of tocilizumab was associated with lower mortality.
Historically unprecedented Northern Gulf of Mexico hurricane activity from 650 to 1250 CE

Hurricane Michael (2018) was the first Category 5 storm on record to make landfall on the Florida panhandle since at least 1851 CE (Common Era), and it resulted in the loss of 59 lives and $25 billion in damages across the southeastern U.S. This event placed a spotlight on recent intense (exceeding Category 4 or 5 on the Saffir-Simpson Hurricane Wind Scale) hurricane landfalls, prompting questions about the natural range in variability of hurricane activity that the instrumental record is too short to address. Of particular interest is determining whether the frequency of recent intense hurricane landfalls in the northern Gulf of Mexico (GOM) is within or outside the natural range of intense hurricane activity prior to 1851 CE. In this study, we identify intense hurricane landfalls in northwest Florida during the past 2000 years based on coarse anomaly event detection from two coastal lacustrine sediment archives. We identified a historically unprecedented period of heightened storm activity common to four Florida panhandle localities from 650 to 1250 CE and a shift to a relatively quiescent storm climate in the GOM spanning the past six centuries. Our study provides long-term context for events like Hurricane Michael and suggests that the observational period 1851 CE to present may underrepresent the natural range in landfalling hurricane activity.
Throwing Event Detection using Acceleration Magnitude collected with Wrist-Worn Sensors

Recent advancements to reduce rates of injury and pain related to pitching include the release of “Pitch Smart” guidelines that specify the number of pitches per day and required rest recommendations for youth and high school baseball players. However, monitoring pitch counts for adherence to these guidelines requires significant human resources for tracking individuals throughout training and games. The availability of low-cost tools that can monitor and report pitch count and cumulative loads have the potential to improve adherence to pitch count guidelines, reduce the burden of monitoring on coaching staff, and reduce the chances of injury. In this work, acceleration datasets collected using a wrist-worn sensor during throwing events are explored as a method to identify throwing events. The detection algorithm, using a 18g threshold and 3 second window, identified 100% of the 161 pitching events from 8 participants, with only 1 false-positive. This supports that using acceleration datasets from wrist-worn sensors may be an effective method to identify and count throwing & pitching events.
Deployment of a New CRRT/PIRRT Device during the COVID-19 Pandemic Emergency: Organizational Challenges and Implementation Results.

Introduction The coronavirus disease 2019 (COVID-19) pandemic led to increased demand nationwide for dialysis equipment, including supplies and machines. To meet the demand in our institution, our surge plan included rapid mobilization of a novel continuous renal replacement treatment (CRRT) machine named SAMI. The SAMI is a push-pull filtration enhanced dialysis machine that can conjugate extremely high single-pass solute removal efficiency with very precise fluid balance control. Material and methods Machine assembly was conducted on-site by local biomedical engineers with remote assistance by the vendor. One 3-h virtual training session of 3 dialysis nurses was conducted before SAMI deployment. The SAMI was deployed in prolonged intermittent replacement therapy (PIRRT) mode to maximize patients covered per machine per day. Live on-demand vendor support was provided to troubleshoot any issues for the first few cases. After 4 weeks of the SAMI implementation, data on treatments with the SAMI were collected, and a questionnaire was provided to the nurse trainees to assess device usability. Results On-site installation of the SAMI was accomplished with remote assistance. Delivery of remote training was successfully achieved. 23 PIRRT treatments were conducted in 10 patients. 7/10 of patients had CO-VID-19. The median PIRRT dose was 50 mL/kg/h (IQR [interquartile range] 44 - 62 mL/kg/h), and duration of the treatment was 8 h (IQR 6.3 - 8 h). Solute control was adequate. The user response was favorable to the set of usability questions involving user interface, on-screen instructions, machine setup, troubleshooting, and the ease of moving the machine. Conclusion Assembly of the SAMI and training of nurses remotely are possible when access to vendor employees is restricted during states of emergency. The successful deployment of the SAMI in our institution during the pandemic with only 3-h virtual training supports that operating the SAMI is simple and safe.
Quantitative dual-energy imaging in the presence of metal implants using locally constrained model-based decomposition

Purpose: To mitigate effects of metal artifacts in Dual-Energy (DE) CT imaging, we introduce a constrained optimization algorithm to enable simultaneous reconstruction-decomposition of three materials: two tissues-of-interest and the metal. Methods: The volume conservation principle and nonnegativity of volume fractions were incorporated as a pair of linear constraints into the Model-Based Material Decomposition (MBMD) algorithm. This enabled solving for three unknown material concentrations from DE projection data. A primal-dual Ordered Subsets Predictor-Corrector Interior-Point (OSPCIP) algorithm was derived to perform the optimization in the proposed constrained-MBMD (CMBMD). To improve computational efficiency and monotonicity of CMBMD, we investigated an approach where the constraint was applied locally onto a small region containing the metal (identified from a preliminary reconstruction) during initial iterations, followed by final iterations with the constraint applied globally. Validation studies involved simulations and test bench experiments to assess the quantitative accuracy of bone concentration measurements in the presence of fracture fixation hardware. In all studies, DE data was acquired using a kVp-switching protocol with the 60 kVp low-energy beam and the 140 kVp high-energy beam. The system geometry emulated the extremity Cone-Beam CT (CBCT). Simulation studies included: i) a cylindrical phantom (80 mm diameter) with a 30 mm long Ti screw and an insert of varying cortical bone concentrations (3 – 13%), and ii) a realistic tibia phantom created from patient CBCT data with Ti fixation hardware of increasing complexity. The test bench experiment involved a 100 mm diameter water bath containing four Ca inserts (6.5 – 39.1% bone concentration) and a Ti plate. Results: CMBMD substantially reduced artifacts in DE decompositions in the presence of metal. The sequentially localglobal constraint strategy resulted in more monotonic convergence than using a global constraint for all iterations. In the simulation studies, CMBMD achieved quantitative accuracy within ~12% of nominal bone concentration in areas adjacent to metal, and within ~5% in areas further away from the metal, compared to ~80% error for the two-material MBMD. In the test bench study, CMBMD generated ~40% reduction in the error of bone concentration estimates compared to MBMD for nominal insert concentrations of <250 mg/mL, and ~12% reduction for concentrations <250 mg/mL. Conclusion: Proposed CMBMD enables accurate DE decomposition in the presence of metal implants by incorporating the metal as an additional base material. Proposed method will be particularly useful in quantitative orthopedic imaging, which is often challenged by metal fracture fixation and joint replacement hardware.
Xylooligosaccharides production by crude and partially purified xylanase from Aureobasidium pullulans: Biochemical and thermodynamic properties of the enzymes and their application in xylan hydrolysis

Abstract In this study, crude and partially purified xylanase from Aureobasidium pullulans CCT 1261 were characterized and applied in beechwood xylan hydrolysis to obtain xylooligosaccharides (XOS). Fractional precipitation (0–30 %/30–60 %) with ammonium sulfate allowed partial purification of xylanases in 6.8-fold and recovery of 69.4 %. Both extracts exhibited optimum activity at 50 °C and pH 4.5, and greater stability at 40 °C within the studied range. The thermostability parameters (kd, t1/2, ΔH*, ΔG*, ΔS*) of the extracts indicated the enzyme denaturation by the increment in temperature from 40 °C to 60 °C; its process was endothermic and led to protein unfolding in a more random structure. Crude xylanase showed a lower value of the Michaelis-Menten constant (25 mg/mL) than the partially purified enzyme (50 mg/mL). In hydrolysis reactions, total XOS contents (7.7 mg/mL and 7.9 mg/mL) and XOS yields (25.7 % and 26.5 %) were equal statistically using the crude or partially purified extracts, differing only in the amount of xylose released. The hydrolysates were mainly composed of potential prebiotics, i.e., xylobiose (50.9 % and 53.8 %) and xylotriose (30.9 % and 32.8 %). Based on these results, the use of crude and partially purified xylanase from A. pullulans showed a promising perspective for xylan hydrolysis to produce XOS.
RECOMB 2020 Special Issue

After initial reviews, articles were opened to discussion among the PC reviewers and PC chair before final decisions were made This volume contains the first half of a selected subset of articles that appeared in the 24th Annual International Conference on Research in Computational Molecular Biology (RECOMB) Ten extended proceedings articles and two software articles were ultimately accepted for this two-volume special issue, in addition to one extended proceedings article carried over from a prior RECOMB [Extracted from the article] Copyright of Journal of Computational Biology is the property of Mary Ann Liebert, Inc and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )
Rational combination of an immune checkpoint inhibitor with CSF1R inhibitor–loaded nanoparticle enhances anticancer efficacy

Since the advent of immune checkpoint inhibitors, rapid strides have been made in the realm of cancer immunotherapy. Of the abundance of infiltrating immune cells in the tumor microenvironment (TME), macrophages contribute a significant portion and make up to 50% of the tumor mass. In addition to this, the relative plasticity of macrophages makes it an attractive target to modulate macrophage functions to initiate an anti-tumor response. However, many challenges hinder this strategy. Macrophage colony-stimulating factor (MCSF) secreted by cancer cells binds to the colony-stimulating factor receptor present on macrophages and negatively influences macrophage functions. MCSF, along with a cocktail of immunosuppressive cytokines present in the TME, polarizes macrophages to an immunosuppressive pro-tumorigenic M2-like phenotype. M2-like macrophages dampen tumor response and are known to be associated with increased tumor progression and metastasis. Indeed, clinical interventions aimed to reprogram macrophage response from an M2-like tumor aiding phenotype to an M1-like tumor-killing phenotype using small-molecule inhibitors of the CSF1R axis have gathered much attention in the recent past. However, poor response and systemic toxicities observed in these therapies necessitate alternative therapeutic strategies. Furthermore, another key signaling pathway that has been recently implicated in aiding the CSF1R signaling in TAMs is the PDL1 signaling axis. Hence, in this study, we designed a self-assembled lipid nanoparticle system encompassing a potent small-molecule inhibitor of the CSF1R signaling axis, while the surface of the nanoparticle was tethered with anti-PDL1 mAb. The purpose of this is twofold; the nanoparticles can deliver the cargo in a targeted manner to PDL1 expressing M2-like macrophages while simultaneously blocking the receptor. The resulting nanoparticle system termed α-PDL1-CSF-LNP showed enhanced repolarization of M2 like macrophages in vitro while also upregulating the phagocytic index. Furthermore, suboptimal dose administration of α-PDL1-CSF-LNP in an aggressive melanoma mouse model resulted in superior anti-tumor efficacy with minimal toxicities. These results were validated by ex vivo mechanistic analysis showing that TAMs have successfully been repolarized to a predominantly M1-like phenotype. This, along with increased tumor infiltration of CD8+ T cells, worked in synergy to provide an effective anti-tumor strategy.
Indications for ERCP

Endoscopic retrograde cholangiopancreatography (ERCP) has evolved from being a purely diagnostic modality at its birth, more than 40 years ago, to become a predominantly therapeutic procedure today. We have witnessed significant advances in both diagnostic and therapeutic utilities of this procedure. With these advances, however, we have seen an unfortunate increase in numbers and types of complications and the resultant medico-legal sequelae. It is essential that the endoscopist have a thorough understanding of the indications, risks, and complications involved in performing this range of procedures.
Size of Nest Cavities Selected by Swarms of Africanized Honeybees in Venezuela

SummaryMost feral swarms of Africanized honeybees (Apis mellifera, South American ecotype) in Venezuela selected cavities with a volume of 80 litres as nest sites when presented with a choice of 10, 20, 40 and 80 litres. Agonistic behaviour between scout bees inspecting nest boxes was common, indicating that nest cavities were a limited resource for this population of feral honeybees.
Behavior Therapy for Childhood Tic Disorders

Abstract Tic disorders are neurodevelopmental conditions characterized by repetitive movements and vocalizations, often beginning during childhood and peaking in adolescence. Contextual factors influence tic expression, and specific somatosensory urges preceding tics have been identified. As such, behavioral methods, based on the operant and respondent learning principles, have been developed to manage tics. While psychopharmacological treatments are most commonly used, they carry significant limitations (e.g., side effects and unsatisfactory response). Behavior therapy has been demonstrated as effective for treating tic disorders. Moreover, translational research in behavior analysis has built a comprehensive psychotherapy that provides learning-based skills for managing tics. This chapter will provide a brief description of tic disorders, followed by discussion of the neurobehavioral model for tics, effective behavioral techniques and their empirical support, comprehensive behavioral treatment packages, and directions for future research.
Hybrid Lossless-Lossy Compression of Industrial Radiographs

Image data compression provides a means for efficient storage and transmission of digitized industrial radiographs and can result in significant cost savings when the amount of data involved is large. Image compression methods are generally classified into two categories: lossless and lossy. In lossless compression, the image data are compressed in such a way that exact reconstruction of the original images is possible. But, the compression factors obtained are generally low and image dependent i.e., they cannot be fixed. In lossy compression, some amount of distortion is introduced in the reconstructed images. The compression factors are however larger and can be fixed irrespective of the activity levels of the images.
Protecting the Treasure: An Assessment of State Court Rules and Policies for Access to Online Civil Court Records

State courts throughout the United States are rapidly implementing e-filing for civil court documents. Public access to these online records furthers the long-standing common law right of citizens to review court records. At the same time, online access exposes a wealth of personal information contained in these records. During the last decade state courts struggled to develop and implement rules and policies for public access as courts anticipated a transition from print to electronic records. Now, as e-fling becomes more prevalent, state courts must consider whether current rules and policies regarding public access to electronic court records are adequate to provide privacy protection. This article discusses the ongoing development of courts rules and policies for public access to electronic court records. It assesses common approaches for providing and limiting access, and determines that these approaches do not adequately address privacy concerns. It recommends that courts adopt the alternative approach of the Florida courts. That approach required changes throughout the filing system to minimize the inclusion of personal information in court documents. Courts must rethink the nature and purpose of court filings and how the content of those filings furthers the resolution of disputes.
In Vivo Regulatory Phosphorylation of Soybean Nodule Phosphoenolpyruvate Carboxylase

In this report we provide evidence that cytosolic phosphoenolpyruvate carboxylase (PEPC) in soybean (Glycine max L.) root nodules is regulated in vivo by a seryl-phosphorylation cycle, as with the C4, Crassulacean acid metabolism, and C3 leaf isoforms. Pretreatment of parent plants by stem girdling for 5 or 14 h caused a significant decrease in the apparent phosphorylation state of nodule PEPC, as indicated by the 50% inhibition constant (L-malate) and specific activity values assayed at suboptimal conditions, whereas short-term darkness alone was without effect. However, extended (26 h) darkness led to the formation of a relatively dephosphorylated nodule PEPC, an effect that was reversed by illuminating the darkened plants for 3 h. This reversal of the apparent phosphorylation state in the light was prevented by concomitant stem girdling. In contrast, the optimal activity of nodule PEPC and its protein level showed little or no change in all pretreated plants. These results suggest that the phosphorylation state of PEPC in soybean root nodules is possibly modulated by photosynthate transported recently from the shoots. In situ [32P]orthophosphate labeling, immunoprecipitation, and phosphoamino acid analyses confirmed directly that PEPC in detached intact soybean nodules is phosphorylated on a serine residue(s).
Intergenerational Justice By Axel Gosseries and Lukas H. Meyer

The editors of this 14 chapter volume have gathered together theoretical and pragmatic writings of philosophers on intergenerational justice and its implications, especially the long-term consequen...
Teaching ASIC design with FPGAs

The University of Southern Colorado has developed a VLSI design program that has been used in several courses and design projects. ASICs employing field programmable gate array (FPGA) technologies are used for implementation of the resulting designs. Designs of a 4-b computer, a microcode CPU, and a floating point coprocessor are discussed. FPGA reprogrammability and fast turn-around times have proven ideal for the educational environment. >
Schedule-induced attack on a pictorial target in feral pigeons (Columba livia)

Two of three feral pigeons exhibited schedule-induced attack on a colored photograph of a conspecific during exposure to a fixed-time food schedule. The rate and pattern of attack were comparable to that observed with domesticated pigeons. Schedule-induced attack against a conspecific target image is not confined to domesticated birds.
Substrate curvature due to thin film mismatch strain in the nonlinear deformation range

The physical system considered is a thin film bonded to the surface of an initially flat circular substrate, in the case when a residual stress exists due to an incompatible mismatch strain in the film. The magnitude of the mismatch strain is often inferred from a measurement of the curvature it induces in the substrate. This discussion is focused on the limit of the linear range of the relationship between the mismatch strain and the substrate curvature, on the degree to which the substrate curvature becomes spatially nonuniform in the range of geometrically nonlinear deformation, and on the bifurcation of deformation mode from axial symmetry to asymmetry with increasing mismatch strain. Results are obtained on the basis of both simple models and more detailed finite element simulations.
Ticket-based reliable routing in VANET

One of the notoriously difficult problems in vehicular ad-hoc networks is to ensure that established paths do not break before the end of data transmission. This is a difficult problem because the network topology is changing constantly and the routing links are inherently unstable. Inspired by ticket based probing, we propose a scheme to selects a stable routing path in vehicular network environment. On the basis of stability preference, an optimal path (low-cost, low-delay and high-stability) is considered. Our algorithms consider not only the efficiency of path searching but also the balance of stability, delay, and cost metrics to find the optimal routing path. Several possible paths are searched at the same time. The path selection is based on three types of control packets probing routing paths satisfying stability, delay and cost requirements. Extensive simulations show that the proposed algorithm can tolerate the constantly-changing topology in vehicular ad-hoc networks.
Elliptic filter design using arithmetic-geometric mean

A simple direct algorithm for computation of elliptic functions for use in designing elliptic filters is offered. Compromise approximations to common filter specifications are not required. Precision is limited only by the accuracy of the processor and its square root, sine and arcsine routines. A scientific pocket calculator is adequate for all computations.
Laboratory study on the sliding resistance of level ice and rubble on sand

Abstract An experimental set-up was constructed to study the friction behaviour of level ice and ice rubble on different seabeds at large scale and realistic stress levels. This paper presents the results of loading on a sand seabed. The tests were performed with a 4 m 2 footprint with vertical stress levels up to 17 kPa. The ice was moved horizontally a distance of about 120 mm with displacement rates from 0.003 to 0.342 mm/s. Four position transducers measured vertical displacements. A total of 47 tests were conducted with level ice and another 24 with ice rubble. Friction coefficients of 0.47 and 0.39 for peak and steady shear stresses, respectively, were obtained with level ice. Those produced with ice rubble were 0.65 and 0.62 for the peak and steady shear resistance, respectively, which represents an increase of about 50% in shear resistance compared with level ice. Shear failure is believed to have occurred at the ice–sediment interface, although the sand's internal friction may have been fully mobilized by the ice rubble. Sediment freeze-up caused a substantial increase in sliding resistance. During this process, the failure plane is believed to have migrated downward and laterally along the freezing front, into the sand bed, with a concurrent increase in shear resistance up to levels comparable to the sand's internal friction. Sand compaction may have contributed also in increasing sliding resistance. These results may be useful for the design of spray ice pads and to assess the stability of grounded ice features.
Research on Heat Transfer during LFEC Processing by In Situ Temperature Measurement

Low-frequency electromagnetic casting (LFEC) processing could improve not only the metallurgical quality of magnesium billet including refining grain size, reducing regional microstructural difference and lightening segregation, but also its surface quality due to the effect of applied electromagnetic field according to the results by microstructure observation and the numerical simulation. In this research in-situ temperature measurement was carried out in LFEC processing in order to investigate heat transfer behavior of billet during solidification. The effects of the electromagnetic conditions (frequency and the intensity) together with the casting temperature on the sump and the mushy zone were investigated in detail. The results indicate that all the casting conditions affect the temperature field of magnesium billet markedly during solidification. Electromagnetic field could decrease not only the sump depth but also the difference of regional temperature field along the solidification direction leading to much more uniform cooling rate.
Continuous Families of Embedded Solitons in the Third-Order Nonlinear Schrödinger Equation

The nonlinear Schrodinger equation with a third-order dispersive term is considered. Infinite families of embedded solitons, parameterized by the propagation velocity, are found through a gauge transformation. By applying this transformation, an embedded soliton can acquire any velocity above a certain threshold value. It is also shown that these families of embedded solitons are linearly stable, but nonlinearly semi-stable.
The role of submarine hydrothermal systems in the synthesis of amino acids.

There is little consensus regarding the plausibility of organic synthesis in submarine hydrothermal systems (SHSs) and its possible relevance to the origin of life. The primary reason for the persistence of this debate is that most experimental high temperature and high-pressure organic synthesis studies have neglected important geochemical constraints with respect to source material composition. We report here the results of experiments exploring the potential for amino acid synthesis at high temperature from synthetic seawater solutions of varying composition. The synthesis of amino acids was examined as a function of temperature, heating time, starting material composition and concentration. Using very favorable reactant conditions (high concentrations of reactive, reduced species), small amounts of a limited set of amino acids are generated at moderate temperature conditions (∼125-175°C) over short heating times of a few days, but even these products are significantly decomposed after exposure times of approximately 1 week. The high concentration dependence observed for these synthetic reactions are demonstrated by the fact that a 10-fold drop in concentration results in orders of magnitude lower yields of amino acids. There may be other synthetic mechanisms not studied herein that merit investigation, but the results are likely to be similar. We conclude that although amino acids can be generated from simple likely environmentally available precursors under SHS conditions, the equilibrium at high temperatures characteristic of SHSs favors net amino acid degradation rather than synthesis, and that synthesis at lower temperatures may be more favorable.
Progress report on the CAC manpower and educational planning model

Economic planning has recently begun to focus on a new dimension: that of anticipating the manpower, educational and skill requirements likely to result from different patterns of economic and social development. The U. S. record in this area thus far has not been encouraging, and the present difficulties faced by job seekers in many fields of engineering and natural sciences-and in a number of other professional disciplines-attest to the failure of educational and manpower planning in this nation in the late 1950's and the 1960's. This paper discusses a large-scale manpower and educational planning model presently being developed at the Center for Advanced Computation (CAC) of the University of Illinois. This model is unique in several respects: it utillzes a number of detailed data sets available from the Federal government which have not previously been integrated in a coherent manner, it is a user oriented system which allows it to be employed by persons unfamiliar with economic modeling or computer software, and it can accept inputs and deliver outputs nationwide via ARPANET facilities. A brief overview of the system is presented, the results of several empirical analyses conducted with components of the model are discussed, and the prospects for continued implementation and development of this type of system are indicated.
Energy consumption modelling and benchmarking in continuous galvanising lines

The pot hardware in continuous galvanising lines is prone to failure and needs to be replaced quite frequently which results in considerable loss of production time and high energy consumption. Galvanizing Energy Profiler and Decision Support Systems (GEPDSS) was developed to consider major energy consuming equipment in a typical hot dip continuous line which tracks the current production and energy consumption for up to three different processes. It can simulate a scenario to identify energy, cost, and productivity benefits obtained from energy savings measures and can evaluate the economic desirability of investment in new and improved pot hardware.
Bead injection for biomolecular assays: Affinity chromatography enhanced by bead injection spectroscopy

Selective capture of target biomolecules by ligands immobilized on a solid support is a cornerstone of two seemingly unrelated techniques: micro-Affinity Chromatography (microAC) and micro-Bead Injection Spectroscopy (microBIS). This work shows, for the first time, how these techniques can be carried out using the same instrument and how the data obtained this way complement each other, yielding complete information on retention and elution of target biomolecules. Biomolecular association and dissociation were investigated by microAC and microBIS, using computer-controlled programmable flow and the same instrument for automated bead transport, packing of a micro-column, assay of the analyte, and bead disposal. The absorbance of the analyte was monitored within the fiber optic flow cell configured either for monitoring directly on the beads or post-column after elution. The separation, binding, and elution of immunoglobulins (human IgG, rabbit IgG, and horse IgG) on protein G-coated Sepharose beads were studied as model systems. The limit of detection of the microAC technique was determined to be 5 ng microL(-1) IgG, and that of the microBIS technique was 50 ng microL(-1) IgG.
The lysosome among targets of metformin: new anti-inflammatory uses for an old drug?

Background: Rheumatoid arthritis and type-2 diabetes exhibit progressive co-morbidity. Chloroquine (CQ) reportedly improves both. CQ inhibits lysosomal function in cultured cells at supra-therapeutic concentration; however, this is doubted as target mechanism. Some anti-diabetic biguanides are metal-interactive lysosomal inhibitors; and all bind Zn2+.Objectives: i) To bioassay the potency of CQ using 3H-leucine release from perfused myocardial tissue. ii) To determine whether metformin (MET) is CQ-mimetic, and interactive with Zn2+.Results: Therapeutic CQ concentration (0.1 – 0.5 μM) clearly does cause lysosomal inhibition although delayed and submaximal. MET alone (10 μM) caused sub-maximal inhibition. Supra-physiological extracellular Zn2+ (5 – 50 μM) alone increased tissue Zn2+ content, and inhibited lysosomal proteolysis. Physiological equivalent Zn2+ (approximately 1 μM) had no effect. MET (≤ 25 μM) and Zn2+ (≤ 1 μM) exhibited astounding 10 – 100 fold anti-lysosomal synergy. Cathepsin B was 50% inhib...
Agent-based modeling of alveolar type II cyst formation in vitro

We present an agent-based model of cultured alveolar type II (AT II) cells and early simulation results that provide new mechanistic insights into generative principles that may underpin alveolar morphogenesis in 3D cell cultures. The AT II cell-mimetic analogue comprises discrete components that represent cells and basic parts composing cell cultures. Cells are represented as quasi-autonomous agents that act based on a set of operating principles articulated as axioms and decision logic. By adhering strictly to those principles, cell agents self-organize and develop into multi-cell structures that resemble alveolar-like cysts in vitro. While it is premature to assign a specific biological mapping to the in silico operating principles, the findings enforce the idea that complex morphogenetic phenomena are a consequence of adherence to a small set of epigenetic principles. We expect more advanced adaptations will help elucidate basic principles and mechanisms underlying alveolar development and regeneration.
Peroxisome Proliferator-activated Receptor γ (PPARγ) and Its Target Genes Are Downstream Effectors of FoxO1 Protein in Islet β-Cells MECHANISM OF β-CELL COMPENSATION AND FAILURE

The molecular mechanisms and signaling pathways that drive islet β-cell compensation and failure are not fully resolved. We have used in vitro and in vivo systems to show that FoxO1, an integrator of metabolic stimuli, inhibits PPARγ expression in β-cells, thus transcription of its target genes (Pdx1, glucose-dependent insulinotropic polypeptide (GIP) receptor, and pyruvate carboxylase) that are important regulators of β-cell function, survival, and compensation. FoxO1 inhibition of target gene transcription is normally relieved when upstream activation induces its translocation from the nucleus to the cytoplasm. Attesting to the central importance of this pathway, islet expression of PPARγ and its target genes was enhanced in nondiabetic insulin-resistant rats and markedly reduced with diabetes induction. Insight into the impaired PPARγ signaling with hyperglycemia was obtained with confocal microscopy of pancreas sections that showed an intense nuclear FoxO1 immunostaining pattern in the β-cells of diabetic rats in contrast to the nuclear and cytoplasmic FoxO1 in nondiabetic rats. These findings suggest a FoxO1/PPARγ-mediated network acting as a core component of β-cell adaptation to metabolic stress, with failure of this response from impaired FoxO1 activation causing or exacerbating diabetes.
Study of envelope proteins in E. coli cet and recA mutants by SDS acrylamide gel electrophoresis.

Disc-electrophoresis of E. coli envelope proteins on SDS acrylamide gels reproducibly revealed up to 50 distinct polypeptide bands. Corresponding molecular weights ranged from 105,000 to 20,000 daltons or less. Major bands corresponded to molecular weights of 73,000, 48,000, 36,000 and 30,000 with the latter constituting up to 20% of the total envelope protein depending upon the method of isolation. Minimum levels of detection using stained gels equaled 0.25 μg protein or 1% of total sample analyzed; for a polypeptide of molecular weight 40,000 daltons this was calculated to be equivalent to 1,200 molecules per cell envelope. In envelopes from a cetB− mutant strain (refractory to colicin E2), an additional band, constituting up to 5% of the total envelope protein was present. The molecular weight of this protein, which was maximally present in wild type envelopes in only trace amounts, is 44,000 daltons, indicating a cellular concentration of approximately 6 × 103 molecules per envelope. This new band was not affected by heating envelope preparations to 100° prior to electrophoresis, but was largely eliminated by washing isolated envelopes in low ionic strength buffer, or by pre-incubating cells with trypsin prior to preparation of envelopes. Treatment of isolated envelopes with Triton X-100, which preferentially releases inner membrane proteins from the envelope (18), resulted in the extraction of a preponderance of the high molecular weight polypeptides, including the 44,000 dalton protein from envelopes of the mutant. The major polypeptides of the envelope and the low molecular weight components were not extracted by Triton X-100. The properties of the 44,000 dalton protein indicated that it is relatively loosely associated with the surface envelope and may be exposed on the external surface of the cytoplasmic membrane. Possible explanations for the appearance of this protein in mutant strains and its relationship to the inability of these to respond, specifically to surface bound colicin E2, will be discussed. Extensive analysis of envelopes from recA− mutants was also carried out and revealed an unusual amount of variation in polypeptide profiles obtained from different preparations. However, no consistent quantitative or qualitative difference between recA and rec+ strains was obtained. In recA, cetB double mutants, the increased level of the 44,000 dalton polypeptide was identical to that found in the rec+, cetB mutant.
Merlin and the ERM proteins--regulators of receptor distribution and signaling at the cell cortex

Recent studies highlight the importance of the distribution of membrane receptors in controlling receptor output and in contributing to complex biological processes. The cortical cytoskeleton is known to affect membrane protein distribution but the molecular basis of this is largely unknown. Here, we discuss the functions of Merlin and the ERM proteins both in linking membrane proteins to the underlying cortical cytoskeleton and in controlling the distribution of and signaling from membrane receptors. We also propose a model that could account for the intricacies of Merlin function across model organisms.
Dark Matter: The Leptonic Connection

Abstract Recent observations of high-energy positrons and electrons by the PAMELA and ATIC experiments may be an indication of the annihilation of dark matter into leptons and not quarks. This leptonic connection was foreseen already some years ago in two different models of radiative neutrino mass. We discuss here the generic interactions ( ν η 0 − l η + ) χ and l c ζ − χ c which allow this to happen, where χ and/or χ c are fermionic dark-matter candidates. We point out in particular the importance of χ χ → l + l − γ to both positron and gamma-ray signals within this framework.
Generational differences in work values and attitudes among frontline and service contact employees

Abstract Utilizing data collected from frontline and service contact employees, this study identifies employees’ work values for a hospitality business, and then examines differences among employees belonging to different generations. Through an exploratory factor analysis, seven dimensions of employees’ work values are identified. Results of a series of one-way ANOVA tests reveal significant differences among three generation of employees’ work values. Managerial implications and recommended strategies to manage those differences to create and maintain a work environment that foster leadership, motivation, communication and generational synergy are discussed.
Gender, generations, and nations: An experiment in Hmong American discourse and sociophonetics

Abstract This study of Hmong discourse provides new perspectives on language, gender, and age by researching an underrepresented community. The experiment tested how 33 Hmong people in St. Paul, Minnesota would respond to the same young female Hmong interviewer. The recordings show that older men often style-shifted into an acoustically distinctive “authoritative voice,” whereas women and younger men did not use this speech style. For Hmong Americans, then, “doing gender” also involves “doing generations.” In moment-by-moment discourse choices, older men use the “authoritative voice” to construct social hierarchy and traditions, admonish youth, and practice other aspects of Hmong American nationhood. In feminist terms of gender and nation, young Hmong American women are a locus of cultural tension: conservative “cultural reproducers/border guards” but also progressive agents of change.
EDITORIAL COMMENT: GUEST COMMENTARY READING DIFFICULTIES‐THE ECONOMISTS' PARADIGM

The stimulus for this paper came from a talk presented by Dr. Lance Gentile at the Chancellor's Scholars’ Breakfast at the University of North Carolina at Asheville. These breakfasts are held regularly as a means of presenting the scholarly work of one academic to a diverse group of peers in an informal setting, and thus provide an interdisciplinary setting for the presentation of research that epitomises the liberal arts tradition. Dr. Gentile's talk was on “Stress and Reading Difficulties,” and during the course of his presentation, as I tried to come to grips with the methodology of another field, it became apparent that the economists’ paradigm was eminently appropriate for application to this area, in both a normative and prescriptive manner. After all, as an educator in a particular area (i.e., Economics) this paradigm had served me well for the past ten years, and there seemed no reason why it could not be transferred from learning in one area to learning in another, in particular the learning of r...
From Distal to Proximal: Routine Educational Data Monitoring in School-Based Mental Health.

Research and practice in school-based mental health (SBMH) typically include educational variables only as distal outcomes, resulting from improvements in mental health symptoms rather than directly from mental health intervention. Although sometimes appropriate, this approach also has the potential to inhibit the integration of mental health and schools. This paper applies an existing model of data-driven decision-making (Daleiden, E., & Chorpita, B.F. (2005). From data to wisdom: Quality improvement strategies supporting large-scale implementation of evidence based services. Child and Adolescent Psychiatric Clinics of North America, 14, 329–349) to detail how SBMH can better integrate routine monitoring of school and academic outcomes into four evidence bases: general services research evidence, case histories, local aggregate and causal mechanisms. The importance of developing new consultation protocols specific to data-driven decision-making in SBMH as well as supportive infrastructure (e.g. measureme...
The Effects of Surface Layers on Spin-Wave Spectra in YIG Films

Experimental spin-wave spectra for thin magnetic (YIG) films have been matched by computations in which the surface boundary conditions were provided by thin surface layers with magnetic properties different from the bulk. In the case of annealed films, a diffusion layer between the film and its non-magnetic substrate (GGG) is assumed to result from the thermal annealing. Thislayer is shown to produce a surface anisotropy field similar to the tensorial field postulated by Yu, Turk, and Wigen. This model accurately predicts the experimental spin-wave spectra for all angular orientations of the applied field and qualitatively predicts the temperature dependence of the critical angle, the angle at which only the uniform mode is excited. Expressions for the resonance field and the critical angle are derived. The properties of the surface layers are discussed and the model is compared with experimental data from annealed and unannealed YIG films. Experimentelle Spinwellen-Spektren von dunnen magnetischen (YIG) Schichten werden durch Rechnungen angepas, bei denen die Oberflachengrenzbedingungen durch dunne Oberflachenschichten geliefert werden, deren magnetische Eigenschaften sich von denen des Volumens unterscheiden. Im Falle getemperter Schichten wird angenommen, das eine Diffusionsschicht zwischen der Schicht und ihrer nichtmagnetischen Unterlage (GGG) durch die Temperung entsteht. Es wird gezeigt, das diese Schicht ein Oberflachenanisotropiefeld hervormft, das dem von Yu, Turk und Wigen postulierten Tensorfeld ahnlichist. Dieses Modell sagt korrekt die experimentellen Spinwellen-Spektren fur alle Winkelorientierungen des angelegten Feldes voraus und bestimmt qualitativ die Temperaturabhan- gigkeit des kritischen Winkels, des Winkels, bei dem nur die gleichformige Mode angeregtist. Ausdrucke fur das Resonanzfeld und den kritischen Winkel werden abgeleitet. Die Eigenschaften der Oberflachenschicht werden diskutiert und das Modell wird mit experimentellen Werten von getemperten und ungetemperten YIG-Schichten verglichen.
Lewis Carroll's Formal Logic

Charles L. Dodgson's reputation as a significant figure in nineteenth-century logic was firmly established when the philosopher and historian of philosophy William Warren Bartley, III published Dodgson's ‘lost’ book of logic, Part II of Symbolic Logic, in 1977. Bartley's commentary and annotations confirm that Dodgson was a superb technical innovator. In this paper, I closely examine Dodgson's methods and their evolution in the two parts of Symbolic Logic to clarify and justify Bartley's claims. Then, using more recent publications and unpublished letters, I argue that Dodgson approached the elimination problem in class logic differently than his contemporaries, and in doing so, anticipated several important concepts and techniques in automated deductive reasoning. These materials also provide additional insight into his reasons for writing this book.
6T SRAM and 3T DRAM data retention and remanence characterization in 65nm bulk CMOS

While SRAM and DRAM are often assumed to have very small data retention times (bits are lost immediately at power-down) and no data remanence (stored bits leave no traces even after a prolonged storage period), under some conditions these assumptions do not hold. Both retention and remanence have been exploited by malicious attackers to compromise system data and encryption keys in secure systems. To precisely measure retention and remanence in SRAM and DRAM, we implemented specially instrumented 6T SRAM and 3T DRAM test structures in 65nm bulk CMOS and tested them from −40°C to 85°C and under accelerated aging conditions. Results show that the 50% retention time (i.e., half the bits retained data) is 44 ms for the 6T SRAM and 3.8 ms for the 3T DRAM at −40°C. Further, the data remanence effects were exploited to predict stored bits with over 82% accuracy for 22% of a 4kb SRAM array.
Transcatheter embolization of a ruptured superior gluteal artery aneurysm: case report and review of the literature.

PURPOSE To report the successful coil embolization of a true gluteal artery aneurysm and review therapeutic options for this rare condition. METHODS AND RESULTS A ruptured superior gluteal artery aneurysm in a symptomatic 80-year-old man was successfully thrombosed by embolization using a combination of Gianturco coils and helical platinum microcoils. Six-month computed tomography demonstrated persistent thrombosis of the aneurysm and resolution of the perivascular blood. CONCLUSIONS This report offers support for the use of catheter-based techniques as an alternative to standard surgical repair of gluteal artery aneurysms.