cssi/SciSciGPT-SciSciNet huggingface dataset:
Inhibition of the catalytic function of activation-induced cytidine deaminase promotes apoptosis of germinal center B cells in BXD2 mice.

Objective To determine whether functional suppression of the catalytic domain of activation-induced cytidine deaminase (AID) can suppress the hyperreactive germinal center (GC) responses in BXD2 mice. Methods We generated transgenic BXD2 mice expressing a dominant-negative (DN) form of Aicda at the somatic hypermutation site (BXD2-Aicda-DN–transgenic mice). Real-time quantitative reverse transcriptase–polymerase chain reaction was used to determine the expression of Aicda and DNA damage/repair genes. Enzyme-linked immunosorbent assay was used to measure serum levels of autoantibodies and immune complexes (ICs). Development of GCs and antibody-containing ICs as well as numbers of proliferative and apoptotic cells were determined using flow cytometry and/or immunohistochemical analyses. Development of arthritis and kidney disease was evaluated histologically in 6–8-month-old mice. Results Suppression of the somatic hypermutation function of AID resulted in a significant decrease in autoantibody production without affecting the expression of DNA damage–related genes in GC B cells of BXD2-Aicda-DN–transgenic mice. There was decreased proliferation, increased apoptosis, increased expression of caspase 9 messenger RNA in GC B cells, and lower numbers of GCs in the spleens of BXD2-Aicda-DN–transgenic mice. Decreased GC response was associated with lower levels of IgG-containing ICs. Anti-IgM– and anti-CD40 plus anti-Ig–induced B cell proliferative responses were decreased in BXD2-Aicda-DN–transgenic mice. Conclusion Inhibition of the AID somatic hypermutation function in BXD2 mice suppressed development of spontaneous GCs, generation of autoantibody-producing B cells, and autoimmunity in BXD2 mice. Suppression of AID catalytic function to limit selection-based survival of GC B cells could become a novel therapy for the treatment of autoimmune disease.
Natural category discrimination in chimpanzees ( Pan troglodytes ) at three levels of abstraction

Two adult chimpanzees were presented with a series of natural category discrimination tasks on a touch screen computer, in which the discriminations varied in degree of abstraction. At the concrete level, discriminations could be made on the basis of single perceptual features, but at the more abstract level, categories were more inclusive, containing exemplars with variant perceptual features. For instance, at the most abstract level, the chimpanzees were required to select images of animals rather than nonanimals, and exemplars within both categories were perceptually diverse. One chimpanzee showed positive transfer at each level of abstraction but required more sessions to reach criterion as the discriminations became more abstract. The other chimpanzee failed to demonstrate consistent significant acquisition of a concept. The results indicate that unlike other apes and black bears, tested previously, chimpanzees found the most abstract discriminations the most difficult to acquire. Analyses of the features of pictures that yielded high or low accuracy revealed no significant differences on several key features, suggesting that the presence of facial features, eyes, or specific coloration did not control responding. In addition, the chimpanzees performed more accurately with photos judged as less typical exemplars of the category by human raters. However, responses to pictures of particular species suggest that chimpanzees may rely on perceptual similarity to familiar exemplars when acquiring experimenter-defined natural categories.
Scape: supporting stereoscopic collaboration in augmented and projective environments

Our collaborative augmented reality system for multiple users simultaneously creates outside-in workbench views and inside-out life-size walkthrough views, bridging the virtual and augmented reality paradigms. Here we introduce a collaborative infrastructure - stereoscopic collaboration in augmented and projective environments(Scape). Scape seamlessly merges the paradigm of virtual reality with that of augmented reality in a single system and provides multimodality interface devices and unique widget interfaces to facilitate collaborative work in 3D environments. A custom-designed cross-platform application-programming interface (API) allows high and medium-level controls over the Scape workspace to enable augmented interaction and collaboration.
Effects of clomiphene on various biochemical reactions in the mouse testis in vitro.

Abstract Clomiphene(2 × 10−4 M) was found to inhibit mouse testis protein and RNA synthesis in vitro. The inhibition of protein synthesis was not principally the result of altered membrane transport since clomiphene had relatively little effect on the accumulation of a-aminoisobutyric acid-3-14C in testis. The inhibitory effect of clomiphene on protein synthesis could be reversed by the addition of glucose. The drug was found to partially reduce the oxidation of d -Glucose-U-14C to 14CO2 and to significantly reduce protein labeling from d -Glucose-U-14C.
Segment-sliding implementation of a shift-variant z-slope correction algorithm for multislice volumetric CT

This paper presents a modification of the z-slope algorithm introduced in the accompanying paper 'An algorithm to correct for z-detector gain variations in multislice volumetric CT.' The x-expansion coefficients found by SVD are plugged into the equation describing the final estimate of the error vector. It is then found that the algorithm can be expressed in vector form as a matrix equation relating the final error estimate to the initial error estimate, where the final error vector estimate e is subtracted from the projection data for correction. In this form, the matrix coefficients, but not the size, are dependent on the correction order. Also, the final correction matrix MXF (size Nchan by N, where Nchan is the number of channels corrected) is calculated channel-by- channel, by evaluating MX as above for a segment of N channels (with N odd), and extracting the central row to define the corresponding row of MXF. The segment of N channels is then slid by one channel, and the process is iterated till completion of MXF. Although the number of calculations required to obtain the correction matrix is greatly increased, as MXF depends only on the detector cell gains, these calculations can be performed off-line in calibrations. The scan data-dependent calculations are greatly streamlined.
Repeated hospital encounters for asthma in children and exposure to traffic-related air pollution near the home

Background Aggregate hospital encounters for asthma (admissions or emergency department visits) have been associated with daily regional air pollution. There are fewer data on relationships between repeated hospital encounters and traffic-related air pollution near the home. Objective To estimate the association of local traffic–generated air pollution with repeated hospital encounters for asthma in children. Methods Hospital records for 2,768 children aged 0 to 18 years (697 of whom had ≥2 encounters) were obtained for a catchment area of 2 hospitals in northern Orange County, California. Residential addresses were geocoded. A line source dispersion model was used to estimate individual seasonal exposures to local traffic–generated pollutants (nitrogen oxides and carbon monoxide) longitudinally beginning with the first hospital encounter. Recurrent proportional hazards analysis was used to estimate risk of exposure to air pollution adjusting for sex, age, health insurance, census-derived poverty, race/ethnicity, residence distance to hospital, and season. The adjustment variables and census-derived median household income were tested for effect modification. Results Adjusted hazard ratios for interquartile range increases in nitrogen oxides (4.00 ppb) and carbon monoxide (0.056 ppm) were 1.10 (95% confidence interval, 1.03–1.16) and 1.07 (1.01–1.14), respectively. Associations were strongest for girls and infants but were not significantly different from other groups. Stronger associations in children from higher-income block groups ( P Conclusions Associations for repeated hospital encounters suggest that locally generated air pollution near the home affects asthma severity in children. Risk may begin during infancy and continue in later childhood, when asthma diagnoses are clearer.
Stochastic perturbation of Kerr law optical solitons

The soliton perturbation theory is used to study and analyze the stochastic perturbation of optical solitons, due to Kerr law nonlinearity, in addition to deterministic perturbations of optical solitons that is governed by the nonlinear Schrodinger’s equation. The Langevin equations are derived and analyzed. The deterministic perturbations that are considered here are of both Hamiltonian as well as of non-Hamiltonian type.
Fluorescent pigment and pentane production by lipid peroxidation in honey bees, Apis mellifera.

Abstract The concentration of fluorescent pigment associated with the oxidation of polyunsaturated lipids is significantly higher in old worker bees than in newly emerged worker adults. Pentane and hexane are produced by bees, presumably by decomposition of lipid hydroperoxides formed by peroxidation of membrane lipids. Protection against lipid peroxidation by vitamin E and glutathione peroxidase appears to be minimal in bees.
Lymphocyte 5′-nucleotidase deficiency in hypogammaglobulinemia: Clinical characteristics

Abstract Twelve patients with congenital agammaglobulinemia, 2 of 10 patients with selective IgA deficiency, and 4 of 15 patients with common variable immunodeficiency have reduced 5′-nucleotidase activity on lymphocyte plasma membranes. In congenital agammaglobulinemia and common variable immunodeficiency, enzyme-deficient patients have an early onset of immune dysfunction, low levels or an absence of circulating B-lymphocytes, and a positive family history of similar immunodeficiency. The enzyme deficiency involves peripheral E-rosette-forming lymphocytes, suggesting an abnormality of T-lymphocytes in these diseases. No systemic disorder of purine nucleotide degradation to uric acid is detectable in the enzyme-deficient patients. No direct relationship between 5′-nucleotidase activity and in vitro production of IgG is evident, since inhibition of the enzyme did not decrease IgG synthesis. At present the data do not allow a distinction between two hypotheses to explain the role of 5′-nucleotidase in hypogamma-globulinemia, that is, whether 5′-nucleotidase deficiency causes the immune dysfunction or is simply a marker for an intrinsic lymphocyte abnormality. However, this enzyme deficiency may provide a useful means of classifying disorders of immunoglobulin synthesis.
Traumatic Birth Injury

After completing this article, readers should be able to: 1. Describe the delivery conditions that increase the risk for birth trauma. 2. Explain why subgaleal hemorrhage can be a medical emergency. 3. Delineate the common presenting findings of traumatic intracranial bleeding. 4. Describe the risk factors for brachial plexus palsy. 5. Differentiate facial nerve palsy from congenital palsies and hypoplasia of the depressor anguli oris muscle. Birth injuries are sustained during the labor and delivery process. They can be divided into those due to physical trauma during the birth process (traumatic birth injury) and those due to lack of oxygen (hypoxic-ischemic injury). These types of injuries can occur separately or in combination. This review focuses on the diagnosis and management of traumatic birth injuries. Traumatic injuries often are the result of a discrepancy between the size or position of the fetus in relation to the birth canal or an unusually rigid pelvis that has not adapted to the size of the fetal head. The reported rate of birth trauma from a 7-year review published in 1990 was 3.2%. Some injuries are avoidable, and with improvements in obstetric care, the frequency of birth injury as a cause for perinatal mortality has decreased over the past 25 years. Predisposing factors for traumatic birth injury are listed in Table 1. Macrosomic fetuses, including those from poorly controlled diabetic pregnancies, represent a particularly high-risk group for birth injury. However, predicting which macrosomic infants will be injured during the birth process is difficult. Injuries also are more frequent with instrumented vaginal deliveries. Use of forceps has been associated with facial nerve and brachial plexus injuries, skull and facial fractures, and intracranial hemorrhages. Ocular injuries, including fracture of the base of the orbit, intraorbital hemorrhage, corneal laceration, and breaks in Descemet’s membrane with corneal opacification, as well as dislocated nasal …
Inverse Scattering Approach to Improving Pattern Recognition

The Helmholtz machine provides what may be the best existing model for how the mammalian brain recognizes patterns. Based on the observation that the "wake-sleep" algorithm for training a Helmholtz machine is similar to the problem of finding the potential for a multi-channel Schrodinger equation, we propose that the construction of a Schrodinger potential using inverse scattering methods can serve as a model for how the mammalian brain learns to extract essential information from sensory data. In particular, inverse scattering theory provides a conceptual framework for imagining how one might use EEG and MEG observations of brain-waves together with sensory feedback to improve human learning and pattern recognition. Longer term, implementation of inverse scattering algorithms on a digital or optical computer could be a step towards mimicking the seamless information fusion of the mammalian brain.
Development of a regional climate model of the western Arctic

Abstract An Arctic region climate system model has been developed to simulate coupled interactions among the atmosphere, sea ice, ocean, and land surface of the western Arctic. The atmospheric formulation is based upon the NCAR regional climate model RegCM2, and includes the NCAR Community Climate Model Version 2 radiation scheme and the Biosphere–Atmosphere Transfer Scheme. The dynamic–thermodynamic sea ice model includes the Hibler–Flato cavitating fluid formulation and the Parkinson–Washington thermodynamic scheme linked to a mixed-layer ocean. Arctic winter and summer simulations have been performed at a 63 km resolution, driven at the boundaries by analyses compiled at the European Centre for Medium-Range Weather Forecasts. While the general spatial patterns are consistent with observations, the model shows biases when the results are examined in detail. These biases appear to be consequences in part of the lack of parameterizations of ice dynamics and the ice phase in atmospheric moist processes in ...
Regulation of lipid stores and metabolism by lipophagy

Intracellular lipids are stored in lipid droplets (LDs) and metabolized by cytoplasmic neutral hydrolases to supply lipids for cell use. Recently, an alternative pathway of lipid metabolism through the lysosomal degradative pathway of autophagy has been described and termed lipophagy. In this form of lipid metabolism, LD triglycerides (TGs) and cholesterol are taken up by autophagosomes and delivered to lysosomes for degradation by acidic hydrolases. Free fatty acids generated by lipophagy from the breakdown of TGs fuel cellular rates of mitochondrial β-oxidation. Lipophagy therefore functions to regulate intracellular lipid stores, cellular levels of free lipids such as fatty acids and energy homeostasis. The amount of lipid metabolized by lipophagy varies in response to the extracellular supply of nutrients. The ability of the cell to alter the amount of lipid targeted for autophagic degradation depending on nutritional status demonstrates that this process is selective. Intracellular lipids themselves regulate levels of autophagy by unclear mechanisms. Impaired lipophagy can lead to excessive tissue lipid accumulation such as hepatic steatosis, alter hypothalamic neuropeptide release to affect body mass, block cellular transdifferentiation and sensitize cells to death stimuli. Future studies will likely identify additional mechanisms by which lipophagy regulates cellular physiology, making this pathway a potential therapeutic target in a variety of diseases.
Acute Dyspnea and a New Murmur in a Team Physician

A 61-year-old physician for a professional sports team experienced transient palpitations and dyspnea while playing in an over-50 basketball scrimmage. He had been physically active for many years, had no known cardiopulmonary disorders, and had never been told of a heart murmur. He had not been febrile, nor had he experienced any chest pain. There was no history of recent dental work.
From Reimagining to Repositioning Accountability

This article contributes to reimagining a ‘new generation’ of accountability. It draws on country studies and a workshop organised by ActionAid International. The studies highlight the need for further clarifying roles between development actors, the importance of allowing sufficient time for organisational and relational changes and strengthened accountability, the continuing significance of meaningful participation and the need to recognise power in accountability relationships and practices. The author proposes making accountability a central driver in a development actor's theory of change, which would give the organisation a resilient spine as well as flexibility and manoeuvrability. A new relationship between accountability and monitoring and evaluation is also proposed. Such a conceptualisation of accountability provides the clarity and simplicity needed to leapfrog the myriad initiatives created in response to donor pressures for accountability and the measurement focus that currently grips the development sector.
Audiometric measurements by electroencephalography.

Abstract The EEG pattern in children in secobarbital sleep showed responses to the presentation of tones generated by an audiometer. These responses consisted of an on effect (usually a K formation), a continuous effect, and off effect and a delayed reaction (arousal). Any intensity of tone was considered to be above threshold when it evoked a positive EEG response 50 per cent or more of the time. The thresholds so determined in 22 selected cases agreed with those obtained by standard audiometry to within plus or minus 18 db. Variations in response occurred with depth of sleep, quantity and type of sedative, pattern of stimulation presented, changes in the experimental procedure in the midst of the testing, as well as unknown factors presumably involving the child and mechanisms of sleep. The discussion suggested that these EEG responses were associated with some simple arousing system in the central nervous system because they were diffuse, not influenced by age from 3 months to 27 years and capable of being duplicated by other sensory modalities. These thresholds have great clinical usefulness if combined with all other information and not made the sole basis for clinical judgement. They extend the measurement of auditory profiles into those infants and handicapped children who do not communicate.
Initial laparoscopic appendectomy versus initial nonoperative management and interval appendectomy for perforated appendicitis with abscess: a prospective, randomized trial.

Introduction: Perforated appendicitis is a common condition in children, which, in a small number of patients, may be complicated by a well-formed abscess. Initial nonoperative management with percutaneous drainage/aspiration of the abscess followed by intravenous antibiotics usually allows for an uneventful interval appendectomy. Although this strategy has become well accepted, there are no published data comparing initial nonoperative management (drainage/interval appendectomy) to appendectomy upon presentation with an abscess. Therefore, we conducted a randomized trial comparing these 2 management strategies. Methods: After internal review board approval (#06 11-164), children who presented with a well-defined abdominal abscess by computed tomographic imaging were randomized on admission to laparoscopic appendectomy or intravenous antibiotics with percutaneous drainage of the abscess (when possible), followedby intervallaparoscopicappendectomyapproximately10weeks later. Thiswasa pilot studywith a samplesizeof40,whichwasbasedonourrecentvolumeofpatientspresentingwithappendicitisandabscess. Results: On presentation, there were no differences between the 2 groups regarding age, weight, body mass index, sex distribution, temperature, leukocyte count, number of abscesses, or greatest 2-dimensional area of abscess in the axial view. Regarding outcomes, there were no differences in length of total hospitalization, recurrent abscess rates, or overall charges. There was a trend toward a longer operating time in patients undergoing initial appendectomy (61 minutes versus 42 minutes mean, P = .06). Conclusions: Although initial laparoscopic appendectomy trends toward a requiring longer operative time, there seems to be no advantages between these strategies in terms of total hospitalization, recurrent abscess rate, or total charges.
The potential application of risk assessment to the Breakthrough Propulsion Physics Project

In May of 2001, researchers at the NASA Glenn Research center in Cleveland Ohio began exploring the possibility of applying risk assessment to a frontier propulsion project called Breakthrough Propulsion Physics (BPP). The goals of BPP are the drastic reduction or elimination of propellant mass, the attainment of hyper-fast space travel (approaching or exceeding) the speed of light, and new methods for onboard energy conversion. The BPP challenges transcend mere engineering and forces a re-examination of the fundamental physics from which technology is developed. BPP is at a maturity level of emerging science. The challenge is formidable: to apply risk assessment to a project that will not have conceptual designs for a long time to come. However, we suggest that it still makes a great deal of sense to think about the risks associated with various paths of research. In particular, it is suggested that there are a number of potential areas where risk assessment can be applied even when a project is at the maturity level of emerging science. It is believed that with the concepts and tools of risk assessment, more is possible than assessing potential reliability and maintainability. There is more to the story than the obvious need for greater reliability. We are proposing that risk assessment tools can be applied to guide research success.
A Grouped Threshold Approach for Scene Identification in AVHRR Imagery

The authors propose a grouped threshold method for scene identification in Advanced Very High Resolution Radiometer imagery that may contain clouds, fire, smoke, or snow. The philosophy of the approach is to build modules that contain groups of spectral threshold tests that are applied concurrently, not sequentially, to each pixel in an image. The purpose of each group of tests is to identify uniquely a specific class in the image, such as smoke. A strength of this approach is that insight into the limits used in the threshold tests may be gained through the use of radiative transfer theory. Methodology and examples are provided for two different scenes, one containing clouds, forest fires, and smoke; and the other containing clouds over snow in the central United States. For both scenes, a limited amount of supporting information is provided by surface observers.
Endoscopic versus microscopic pituitary surgery

In recent years, endoscopic approaches to the pituitary and skull base are being used with increasing frequency for pituitary tumours and other tumours originating in the anterior skull base. Ammirati and colleagues report the results of their meta-analysis comparing the results of the short-term outcome of pituitary surgery performed using a purely endoscopic approach versus a microscopic approach.1 They included comparison of mortality, extent of tumour removal and complications (cerebrospinal fluid leak, meningitis, vascular complications, visual complications, diabetes insipidus, hypopituitarism and cranial nerve injury) in their analysis. They conclude that the only significant difference with these two approaches is that the incidence of vascular injury was increased with endoscopic surgery. The …
Separation of heteromeric potassium channel Kcv towards probing subunit composition-regulated ion permeation and gating

The chlorella virus-encoded Kcv can form a homo-tetrameric potassium channel in lipid membranes. This miniature peptide can be synthesized in vitro, and the tetramer purified from the SDS–polyacrylamide gel retains the K+ channel functionality. Combining this capability with the mass-tagging method, we propose a simple, straightforward approach that can generically manipulate individual subunits in the tetramer, thereby enabling the detection of contribution from individual subunits to the channel functions. Using this approach, we showed that the structural change in the selectivity filter from only one subunit is sufficient to cause permanent channel inactivation (“all-or-none” mechanism), whereas the mutation near the extracellular entrance additively modifies the ion permeation with the number of mutant subunits in the tetramer (“additive” mechanism).
Replacing a PID controller by a lat-lead compensator for a robot-a frequency-response approach

Because of their simplicity, PD (Proportional-derivative) or PID (proportional-integral-derivative) controllers are widely used with various robot control strategies. For dynamic control of robots, this algorithm can be shown to lead to unsatisfactory tradeoffs between static accuracy, system stability, and insensitivity to disturbances. These tradeoffs become more serious as the sampling rate decreases. By deriving a more realistic discrete-time system model and using frequency-response analysis, a lag-lead compensator is designed and implemented. Both theoretical analysis and real tests are given for the comparisons of the PD or PID controller and the lag-lead compensator. Replacing PD or PID controllers by lag-lead compensators results in a small increase of offline design and tuning effort and online computational load, but the improvements in robot performance are significant. >
Ca2+ inhibition of type III adenylyl cyclase in vivo

Type III adenylyl cyclase is stimulated by β-adrenergic agonists and glucagon in vitro and in vivo, but not by Ca2+ and calmodulin. However, the enzyme is stimulated by Ca2+ and calmodulin in vitro when it is concomitantly activated by the guanyl nucleotide stimulatory protein Gs (Choi, E. J., Xia, Z., and Storm, D. R. (1992a) Biochemistry 31, 6492-6498). Here, we examined regulation of type III adenylyl cyclase by Gs-coupled receptors and intracellular Ca2+in vivo. Surprisingly, intracellular Ca2+ inhibited hormone-stimulated type III adenylyl cyclase activity. Submicromolar concentrations of intracellular free Ca2+, which stimulated type I adenylyl cyclase, inhibited glucagon- or isoproterenol-stimulated type III adenylyl cyclase. Inhibition of type III adenylyl cyclase by intracellular Ca2+ was not mediated by Gi, cAMP-dependent protein kinase, or protein kinase C. However, an inhibitor of CaM kinases antagonized Ca2+ inhibition of the enzyme, and coexpression of constitutively activated CaM kinase II completely inhibited isoproterenol-stimulated type III adenylyl cyclase activity. We propose that Ca2+ inhibition of type III adenylyl cyclase may serve as a regulatory mechanism to attenuate hormone-stimulated cAMP levels in some tissues.
Convex methods in actuator placement

A new formulation of the actuator placement problem is presented. This formulation considers capital cost in the objective function and highlights the importance of magnitude limits on both input and output signals through variance bounding constraints on each. Thus, the proposed optimization problem is aimed at finding the set of minimum cost actuator arrays such that there exists a linear feedback for which all closed-loop signals will satisfy their magnitude limits. The original formulation of this problem results in a Mixed Integer Nonlinear Program (MINLP). However, through an LMI based transformation we exactly convert the problem into a computationally advantageous Mixed Integer Convex Program (MICP). Finally, the design method is applied to an example of actuator placement in a non-isothermal tubular reactor.
Emit® ETS® plus ethyl alcohol assay for the determination of ethanol in human serum and urine

We evaluated the enzymatic Emit ETS Plus Ethyl Alcohol Assay (Emit) intended for the quantitative analysis of ethanol in human urine, serum, and plasma. The assay had been designed for use with the new Syva ETS Plus analyzer. The assay had a linear range up to 6.5 g/L and a low detection limit of 0.1 g/L. Assay within-run precision in serum with ethanol added to 0.25, 0.40, 1.00, 3.00, and 5.00 g/L yielded CVs (n = 32) of 6.1, 5.8, 3.7, 3.5, and 4.5%, respectively. Within-run precision of the assay using with ethanol added to 0.25, 0.40, 1.00, 3.00, and 5.00 g/L yielded CVs (n = 32) of 4.9, 5.0, 4.3, 3.3, and 5.0%, respectively. Between-run precision of aqueous controls yielded 0.41 +/- 0.02 g/L ethanol (target value, 0.40 g/L), CV = 4.5% (n = 31) and 3.05 +/- 0.06 g/L ethanol (target value, 3.00 g/L) CV = 2.1% (n = 31). Absolute recovery of the assay with 0.40 to 6.00 g/L ethanol added to serum and urine yielded mean recovery values of 105.5 and 101.5%, respectively. Results of the analysis of patient serum and urine specimens for ethanol by the Emit assay correlated well with those obtained by other methods. The Emit assay was found to be rapid, precise, and accurate for the determination of ethanol in clinical specimens. It was also found to be free of interferences from small molecular weight alcohols, aldehydes, ketones, and glycols. The Emit assay's linear range of up to 6.50 g/L ethanol was a major advantage over the ADx and aca assays; these assays were only linear to 3.00 g/L.
Design and engineering of intracellular-metabolite-sensing/regulation gene circuits in Saccharomyces cerevisiae

The development of high-throughput phenotyping tools is lagging far behind the rapid advances of genotype generation methods. To bridge this gap, we report a new strategy for design, construction, and fine-tuning of intracellular-metabolite-sensing/regulation gene circuits by repurposing bacterial transcription factors and eukaryotic promoters. As proof of concept, we systematically investigated the design and engineering of bacterial repressor-based xylose-sensing/regulation gene circuits in Saccharomyces cerevisiae. We demonstrated that numerous properties, such as induction ratio and dose–response curve, can be fine-tuned at three different nodes, including repressor expression level, operator position, and operator sequence. By applying these gene circuits, we developed a cell sorting based, rapid and robust high-throughput screening method for xylose transporter engineering and obtained a sugar transporter HXT14 mutant with 6.5-fold improvement in xylose transportation capacity. This strategy should be generally applicable and highly useful for evolutionary engineering of proteins, pathways, and genomes in S. cerevisiae. Biotechnol. Bioeng. 2016;113: 206–215. © 2015 Wiley Periodicals, Inc.
Polycyclic Aromatic Triptycenes: Oxygen Substitution Cyclization Strategies

The cyclization and planarization of polycyclic aromatic hydrocarbons with concomitant oxygen substitution was achieved through acid catalyzed transetherification and oxygen-radical reactions. The triptycene scaffold enforces proximity of the alcohol and arene reacting partners and confers significant rigidity to the resulting π-system, expanding the tool set of iptycenes for materials applications.
Hybrid Cooperative Reconnaissance Without Communication

The cooperative reconnaissance performance of two ve- hicles in an uncertain environment while minimizing communication is investigated. Instead of direct communication, information between vehicles is transferred using mode perturbation signatures based on Gold codes. The behavior of the observed vehicle is modelled as a hybrid system with a finite number of operating modes defined by the vehicle’s dynamics and a perturbation signature. The second vehicle estimates the operating mode of the first vehicle in order to collaborate in collecting information. The performance of the system is gauged using two metrics: 1) by the length of time required for the two vehicles to collect a certain level of information, and 2) by the amount of information collected in a time interval. The follower decides whether cooperation is advantageous by evaluating one of the performance metrics. Monte Carlo simulations of the system are compared to a decentralized system in which there is no cooperation and a centralized system with full communication.
Metabolic influences of fiber size in aerobic and anaerobic locomotor muscles of the blue crab, Callinectes sapidus.

Diameters of some white locomotor muscle fibers in the adult blue crab, Callinectes sapidus, exceed 500 microm whereas juvenile white fibers are 190 g were examined with transmission electron microscopy to determine the density of mitochondria and subdivision diameters. Across all size classes, there was a constant mitochondrial fractional area (25% of the total subdivision area) and subdivision size (mean diameter of 36.5+/-2.7 microm). Thus, blue crab dark levator fibers are unusual in having metabolic functional units (subdivisions) that do not increase in size during development while the contractile functional units (fibers) grow hypertrophically. The body mass scaling of post-contractile lactate dynamics was monitored during recovery from anaerobic, burst exercise in white and dark muscle, and in hemolymph. There were no differences among size classes in lactate accumulation during exercise in either muscle. However, in white fibers from large crabs, lactate continued to increase after exercise, and lactate removal from tissues required a much longer period of time relative to smaller crabs. Differences in lactate removal among size classes were less pronounced in dark fibers, and post-contractile lactate accumulation was significantly higher in white than in dark fibers from large animals. These data suggest that the large white fibers invoke anaerobic metabolism following contraction to accelerate certain phases of metabolic recovery that otherwise would be overly slow. This implies that, in addition to the typical mass-specific decrease in oxidative capacity that accompanies increases in animal mass, aerobic metabolic processes become increasingly limited by surface area to volume and intracellular diffusion constraints in developing white muscle fibers.
Depletion of Glycolytic Intermediates Plays a Key Role in Glucose-Phosphate Stress in Escherichia coli

In bacteria like Escherichia coli, the accumulation of glucose-6-phosphate (G6P) or its analogs such as α-methyl glucoside-6-phosphate (αMG6P) results in stress that appears in the form of growth inhibition. The small RNA SgrS is an essential part of the response that helps E. coli combat glucose-phosphate stress; the growth of sgrS mutants during stress caused by αMG is significantly impaired. The cause of this stress is not currently known but may be due to either toxicity of accumulated sugar-phosphates or to depletion of metabolic intermediates. Here, we present evidence that glucose-phosphate stress results from depletion of glycolytic intermediates. Addition of glycolytic compounds like G6P and fructose-6-phosphate rescues the αMG growth defect of an sgrS mutant. These intermediates also markedly decrease induction of the stress response in both wild-type and sgrS strains grown with αMG, implying that cells grown with these intermediates experience less stress. Moreover, αMG transport assays confirm that G6P relieves stress even when αMG is taken up by the cell, strongly suggesting that accumulated αMG6P per se does not cause stress. We also report that addition of pyruvate during stress has a novel lethal effect on the sgrS mutant, resulting in cell lysis. The phosphoenolpyruvate (PEP) synthetase PpsA, which converts pyruvate to PEP, can confer resistance to pyruvate-induced lysis when ppsA is ectopically expressed in the sgrS mutant. Taken as a whole, these results provide the strongest evidence thus far that depletion of glycolytic intermediates is at the metabolic root of glucose-phosphate stress.
Pretreatment of cellulosic wastes to increase enzyme reactivity

The enzymatic hydrolysis of cellulose to glucose is generally a slow reaction. Different pretreatments, such as ball milling to a -200 mesh or swelling in 1 to 2 percent NaOH are reported to increase the reactivity considerably. In this work a fiber fraction from cattle manure was treated in an autoclave for 5 to 30 min at temperatures ranging from 130 to 200/sup 0/C. The reactivity of the cellulose, measured by incubating samples with a commercial cellulase preparation for one hour at 50/sup 0/C and pH 4.8, was increased by a factor of 4 to 6 compared to NaOH treatment and 10 to 20 compared to untreated fiber. The increased reaction rate is probably mostly due to an increase in cellulose availability to enzymatic attack, as structural hemicellulose is hydrolyzed and removed during the treatment. Sugars, produced by hemicellulosis hydrolysis, will react further to give caramelization products. These side reactions were shown to be suppressed by short treatment times. The treated fiber could support growth of a mixed culture of Trichoderma viride and Candida utilis only after washing, indicating the formation of water soluble inhibitory products during treatment. The treatment with high-temperature steam can probably be used also with othermore » cellulosic materials to increase reactivity. This may be an attractive way to prepare low-valued wastes such as manure fibers, straw, stalks, or corn cobs for fermentation processes to increase the protein content or for use directly as ruminant animal feed.« less
Team collectivist culture: A remedy for creating team effectiveness

This article provides a review of literature on collective orientation and effective teams by theoretically elucidating the relationship between these two constructs. The relationship between these two constructs is found by identifying the elements that go into creating an effective team, which are also found in a collectivist orientation. As those elements are identified, a model encompassing “team collectivist” corporate culture is proposed. The model depicts the development of team collectivist corporate culture, including members' attitudes, behaviors, and characteristics that reflect collectivist orientation that would aid in the development of effective teams, thus increasing performance and productivity within the organization. The model seeks to provide the Human Resource Development (HRD) professional with a tool that will (a) enable them to predict whether or not certain individuals have the potential to be an effective team player, (b) enable the organization to be proactive in building effective teams, and (c) allow team managers to diagnose and provide solutions to dysfunctional teams.
Proteomic-Based Approach for the Identification of Tumor Markers Associated with Hepatocellular Carcinoma

There is increasing evidence for an immune response to cancer in humans, demonstrated in part by the identification of autoantibodies to tumor antigens. The identification of panels of tumor antigens that elicit a humoral response may have utility in cancer screening, diagnosis or in establishing prognosis. Several approaches are currently available for the identification of tumor antigens. We have used a proteomic-based approach for the identification of tumor antigens that induce an antibody response which we have applied to hepatocellular carcinoma, a major type of cancer worldwide. Two-dimensional gel electrophoresis allows simultaneous separation of several thousand individual proteins from tumor tissue or tumor cell lines. Proteins eliciting a humoral response in HCC were identified by 2-D Western blotting using sera from patients with hepatocellular carcinoma, followed by mass spectrometry analysis and database search. The common occurrence of autoantibodies to specific proteins may have utility for HCC screening and diagnosis.
Variants of the CD36 gene and metabolic syndrome in Boston Puerto Rican adults

Abstract Objective Puerto Ricans experience a high prevalence of several chronic conditions, including metabolic syndrome. Genetic variants of the CD36 gene have been associated with metabolic syndrome. We aimed to determine the association between 6 single nucleotide polymorphisms (SNPs) for CD36 and metabolic syndrome and its components in Puerto Ricans (45–75 year) living in the Greater Boston area. Methods Associations between each SNP, metabolic syndrome and its components were examined using multivariate logistic regression models. Haplotype trend regression analysis was used to determine associations between haplotypes and metabolic syndrome. Results For two SNPs of CD36 (rs1049673 and rs3211931), homozygous subjects of the minor allele (G and T, respectively) were associated with a higher likelihood of metabolic syndrome (odds ratio (OR) (95% confidence interval (CI)): 1.89 (1.0, 3.5) and 1.77 (1.0, 3.1), respectively) relative to carriers of the major allele. Although CD36 haplotypes were not significantly associated with metabolic syndrome overall (global significance, P =0.23), one haplotype (G-C-C vs. C-C-C (reference haplotype)) was marginally associated ( P =0.049). Conclusion SNPs of CD36 were associated with metabolic syndrome in Puerto Ricans. Prospective studies should further explore the role of CD36 variants in the development of this condition.
Telephone triage of influenza-like illness during pandemic 2009 H1N1 in an obstetric population

We sought to determine the safety and efficiency of a telephone-based triage system for influenza-like illness, during the 2009 pandemic, at our institution. A triage system was implemented that involved initial telephone screening by a provider who determined whether outpatient telephone-based care or assessment in a centralized evaluation unit was needed. Those who received outpatient care were empirically treated. Those seen in the evaluation unit were assessed for inpatient admission. Of the 230 women who were evaluated, 41% were treated as outpatients and 59% were seen in the evaluation unit. Of those treated as outpatients, 9% were eventually seen in the evaluation unit and only 4% were ultimately admitted, with a maximum hospitalization of 4 days. Of the 135 patients initially seen in the evaluation unit, 32% were admitted and 44% had a positive polymerase chain reaction for respiratory pathogens. This triage system improved efficiency of resource utilization without incurring apparent influenza-like illness morbidity.
Strategies for Cardiovascular Risk Assessment and Prevention Over the Life Course Progress Amid Imperfections

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality worldwide, including in the United States. Fortunately, the major risk factors contributing to the development of atherosclerotic CVD have been detailed in epidemiological studies, and randomized clinical trials have demonstrated the benefits of lowering elevated levels of risk factors. Yet, one of the most challenging questions in clinical medicine remains: if and when to treat and how best to treat individuals with ≥1 CVD risk factors. Article see p 384 A few concepts have helped us in identifying strategies to answer the question posed above. First, CVD risk develops over the entire life course as a result of the combined influences of lifestyle-related factors, environmental triggers, and genetic susceptibility. Second, clinically overt CVD usually is antedated by the presence of ≥1 risk factors and subclinical atherosclerosis. Such a time course of evolution provides us with a window of opportunity for prevention/intervention. The long latency of CVD means that preventive approaches also may vary over the life course. Third, CVD prevention is best thought of as a combination of “population-based” prevention, primary prevention in high-risk individuals, and secondary prevention in those with established clinical CVD.1 The exact proportion allocated to each of these 3 approaches varies, depending on the mean absolute CVD risk (and its distribution) in a given community and the healthcare resources available at hand. Fourth, with regard to the “high-risk individuals” approach, rates of CVD vary among people with identical levels of any particular risk factor based on the levels of other risk factors, emphasizing the multifactorial origin of CVD. Therefore, combining information about levels of different CVD risk factors in an individual using 1 or more risk prediction algorithms is the best approach for assessing the likelihood that he or she will experience a CVD …
Tapping Into Motivations for Drinking Among Youth: Normative Beliefs About Alcohol Use Among Underage Drinkers in the United States

Social norms affect human behavior, and underage drinking is no exception. Using the theory of normative social behavior, this study tested the proposition that the association between perceptions about the prevalence of drinking (descriptive norms) and underage drinking is strengthened when perceived pressures to conform (injunctive norms) and beliefs about the benefits of drinking (outcome expectations) are high. This proposition was tested on a nationally representative sample of underage drinkers ages 13–20 (N = 1,031) in relation to their alcohol consumption, expanding on research with college-age youth. On average, males and females reported drinking 23 and 18 drinks per month, respectively. The main effect of descriptive norms (β = .10, p < .01) on alcohol consumption was modified by interactions with injunctive norms (β = .11, p < .01), benefit to self (β = .12, p < .001), and benefit to others (β = .10, p < .01). Underage drinkers are most vulnerable to excessive drinking if they believe that mos...
Learning to Behave by Reading

In this talk, I will address the problem of grounding linguistic analysis in control applications, such as game playing and robot navigation. We assume access to natural language documents that describe the desired behavior of a control algorithm (e.g., game strategy guides). Our goal is to demonstrate that knowledge automatically extracted from such documents can dramatically improve performance of the target application. First, I will present a reinforcement learning algorithm for learning to map natural language instructions to executable actions. This technique has enabled automation of tasks that until now have required human participation --- for example, automatically configuring software by consulting how-to guides. Next, I will present a Monte-Carlo search algorithm for game playing that incorporates information from game strategy guides. In this framework, the task of text interpretation is formulated as a probabilistic model that is trained based on feedback from Monte-Carlo search. When applied to the Civilization strategy game, a language-empowered player outperforms its traditional counterpart by a significant margin.