cssi/SciSciGPT-SciSciNet huggingface dataset:
Efavirenz Outperforms Boosted Atazanavir among Treatment-Naive HIV-1-Infected Persons in Routine Clinical Care

Background:Effectiveness of antiretroviral therapy (ART) in a routine clinical care may result different from the clinical trials. We assessed the virologic outcomes in treatment-naive persons who received either efavirenz (EFV) or atazanavir/ritonavir (ATV/r) with a backbone of tenofovir/emtricitabine (TDF/FTC) as their combination ART (cART).Methods:This was a retrospective cohort study conducted at the Washington University HIV Outpatient Clinic from January 2004 to June 2009. Predictors of virologic suppression (HIV RNA level <400 copies/mL) by week 48 were assessed by multivariate Cox proportional hazards regression models.Results:Of 324 persons, 221(68%) received EFV and 103 (32%) received ATV/r. Persons on EFV had 1.4-fold increased likelihood of virologic suppression (95% confidence interval, 1.0-1.8) when compared to ATV/r after adjustment with primary drug resistance, pre-cART opportunistic infection, HIV RNA levels, and timing to start cART.Conclusions:In routine clinical care settings, EFV ha...
The l-Isoaspartyl Protein Repair Methyltransferase Enhances Survival of Aging Escherichia coli Subjected to Secondary Environmental Stresses

Like its homologs throughout the biological world, the L-isoaspartyl protein repair methyltransferase of Escherichia coli, encoded by the pcm gene, can convert abnormal L-isoaspartyl residues in proteins (which form spontaneously from asparaginyl or aspartyl residues) to normal aspartyl residues. Mutations in pcm were reported to greatly reduce survival in stationary phase and when cells were subjected to heat or osmotic stresses (C. Li and S. Clarke, Proc. Natl. Acad. Sci. USA 89:9885‐9889, 1992). However, we subsequently demonstrated that those strains had a secondary mutation in rpoS, which encodes a stationary-phase-specific sigma factor (J. E. Visick and S. Clarke, J. Bacteriol. 179:4158‐4163, 1997). We now show that the rpoS mutation, resulting in a 90% decrease in HPII catalase activity, can account for the previously observed phenotypes. We further demonstrate that a new pcm mutant lacks these phenotypes. Interestingly, the newly constructed pcm mutant, when maintained in stationary phase for extended periods, is susceptible to environmental stresses, including exposure to methanol, oxygen radical generation by paraquat, high salt concentrations, and repeated heating to 42°C. The pcm mutation also results in a competitive disadvantage in stationary-phase cells. All of these phenotypes can be complemented by a functional pcm gene integrated elsewhere in the chromosome. These data suggest that protein denaturation and isoaspartyl formation may act synergistically to the detriment of aging E. coli and that the repair methyltransferase can play a role in limiting the accumulation of the potentially disruptive isoaspartyl residues in vivo.
Smooth, Low-Resistance, Pinhole-Free, Conformal Ruthenium Films by Pulsed Chemical Vapor Deposition

Ruthenium (Ru) metal has many unique properties. It has a relatively high work function, its oxide, RuO2, is conductive, and it is compatible with many high-κ dielectric oxides, such as SrTiO3 1 and TiO2. 2 Hence, Ru is being considered for electrodes in dynamic random access memories (DRAM) 2 and gate metal in metal-oxidesemiconductor-field-effect (MOSFET) transistors. 3 Ru can also be used as a seed layer for electrodeposition of copper interconnects. 4 Many chemical processes use ruthenium as a catalyst. 5 Preparing thin Ru films with good properties, such as high density, low resistivity, and pinhole-free smooth surfaces, has raised much interest in industry recently. Vapor deposition is a promising approach to obtain thin Ru films with high quality and uniform thickness even inside narrow features. Several Ru compounds have been studied as precursors for atomic layer deposition (ALD) and chemical vapor deposition (CVD). But many of them, such as Ru(Cp)2, 6 Ru(EtCp)2, 4 Ru(thd)3, 7,8 bis(2,4-dimethylpentadienyl)ruthenium, 9 and bis(2,6, 6-trimethyl-cyclohexadienyl)ruthenium, 10 need to react with O2 in order to deposit Ru films. This may cause some unwanted oxidation of conductive substrates, such as titanium nitride in DRAM electrodes or tantalum nitride diffusion barriers in microelectronic interconnects. Recently, several Ru cyclooctatetraene precursors were reported to deposit Ru films with H2 in a reducing ambient, 11 however, the reported resistivity of deposited Ru films is quite high, 11 which may be due to a high-level carbon impurity from the precursors or to a low film density. Gordon and coworkers have synthesized an amidinate Ru precursor, bis(N,N � -di-tert-butylacetamidinato)ruthenium(II) dicarbonyl, which can react with NH3 to produce Ru films by ALD 12,13 and also in a non-oxidizing ambient. 13 However, the best film properties were obtained by including small amounts of oxygen in the ALD process. 14 ALD is a very slow process, so we investigated the use of this precursor in chemical vapor deposition (CVD) conditions. In this paper, we used this amidinate precursor to deposit thin Ru films with a pulsed CVD method. We were able to obtain dense, low resistive, pure and conformal Ru films with smooth and pinhole-free surfaces. We further examined the conformality of Ru films deposited inside narrow holes, in which the films showed good step coverage.
Mid-Career Burnout in Generalist and Specialist Physicians

ASTUDY OF US PHYSICIANS SHOWED that physicians in 1997 were less satisfied in every aspect of their professional life than those asked similar questions in 1986. They were dissatisfied with the time they have with individual patients and their lack of incentives for high-quality care. Similarly, a 1998 study revealed that two thirds of Canadian physicians have a workload they consider too heavy, and more than half stated their family and personal lives have suffered because they chose medicine as a profession. Dissatisfaction has been documented in several diverse physician groups, including primary care, surgery, infectious disease specialists, and anesthesiologists. The leaders of medical school departments are exposed to similar pressures. These recent articles highlight the growing discontent of physicians with the increasing complexities of the practice of medicine. Burnout, a term that has moved from colloquial speech into the social and psychological vernacular, describes this phenomenon. There is a growing awareness within medicine that physicians and other health care professionals are at risk for burnout, which threatens the sustainability of the health care enterprise. Preventing burnout by promoting the wellbeing of physicians has been the focus of several recent initiatives. The Western Journal of Medicine devoted its entire January 2001 issue to offer guidance in living positive and healthy lives. In addition, the Joint Commission on Accreditation of Healthcare Organizations has mandated that as of January 1, 2001, all hospitals have a process to address physician well-being, separate from disciplinary processes. We review the definition of burnout and its sources; examine the interaction of physician personality factors and the unique stressors they encounter in the workplace and at home; and highlight current resources for preventing burnout and promoting wellbeing in physicians and within their organizations.
Inducing agrammatic profiles in normals: Evidence for the selective vulnerability of morphology under cognitive resource limitation

The selective vulnerability of morphology in agrammatic aphasia is often interpreted as evidence that closedclass items reside in a particular part of the brain (i.e., Broca's area); thus, damage to a part of the language processor maps onto behavior in a transparent fashion. We propose that the selective vulnerability of grammatical morphemes in receptive processing may be the result of decrements in overall processing capacity, and not the result of a selective lesion. We demonstrate agrammatic profiles in healthy adults who have their processing capacity diminished by engaging in a secondary task during testing. Our results suggest that this selective profile does not necessarily indicate the existence of a distinct subsystem specialized for the implicated aspects of syntax, but rather may be due to the vulnerability of these forms in the face of global resource diminution, at least in grammaticality judgment.
Reversible and irreversible emittance growth

Emittance growth in bunched charged particle beams in linear accelerators is considered in the case of a Hamiltonian system where nonlinear and time-dependent forces are dominant. Emittance growth is divided into two classes: reversible and irreversible depending on the corresponding entropy change. We consider the case where the measurement resolution is important. We show that a generalized free-energy function acts as a driver for phase-space evolution and emittance growth.
Dialing Back Abuse on Phone Verified Accounts

In the past decade the increase of for-profit cybercrime has given rise to an entire underground ecosystem supporting large-scale abuse, a facet of which encompasses the bulk registration of fraudulent accounts. In this paper, we present a 10 month logitudinal study of the underlying technical and financial capabilities of criminals who register phone verified accounts (PVA). To carry out our study, we purchase 4,695 Google PVA as well as acquire a random sample of 300,000 Google PVA through a collaboration with Google. We find that miscreants rampantly abuse free VOIP services to circumvent the intended cost of acquiring phone numbers, in effect undermining phone verification. Combined with short lived phone numbers from India and Indonesia that we suspect are tied to human verification farms, this confluence of factors correlates with a market-wide price drop of 30--40% for Google PVA until Google penalized verifications from frequently abused carriers. We distill our findings into a set of recommendations for any services performing phone verification as well as highlight open challenges related to PVA abuse moving forward.
Suitability and use of the 15N-isotope dilution method to estimate nitrogen fixation by actinorhizal shrubs

Nitrogen fixation rates were estimated by the 15 N-isotope dilution method for Ceanothus velutinus and Purshia tridentata in the understory of central Oregon ponderosa pine forests. Field rates were measured in small pole-, large pole-, and sawtimbersized pine stands using two shrubs (Arctostaphylos patula, Ribes cereum) and one graminoid (Carex rossii) as non-fixing reference species. Shrub cover ranged from 23 to 59% for Ceanothus and from 9 to 15% for Purshia. Foliage samples were collected monthly following two applications of 15 N ammonium sulfate (5 kg N ha ˇ1 at 10 atom% 15 N) to compare N uptake patterns and determine the fraction of N derived from fixation (Ndff). Several violations of the underlying assumption of the isotope dilution method that N fixing and reference plants have access to similar pools of soil 15 N were identified. These included non-uniform distribution of 15 N in the soil profile and dissimilarities in rooting volumes, N uptake patterns, and plant ages between the reference and N fixing plants. Despite these compromises, there were only minor differences in percentage of Ndff when calculated independently using each reference species. Low 15 N uptake by Ceanothus and Purshia evidently negated the requirement that N fixing and reference plants have comparable spatial and temporal access to soil 15 N. Both Ceanothus and Purshia were highly effective, obtaining more than 80% of their N from fixation regardless of pine stand, shrub cover, or shrub age. Annual N fixation by Ceanothus ranged from 4 to 15 kg ha ˇ1 year ˇ1 . This rate is lower than previously reported for Ceanothus in other ecosystems in the western United States, yet is sufficient to replace N losses from disturbances such as prescribed fire. Purshia fixed considerably less N, ca. 1 kg ha ˇ1 year ˇ1 , roughly equivalent to the rate of atmospheric
Adaptive Control of the Uncertain Duffing Oscillator

An adaptive feedback controller is developed based on rigorous Lyapunov argument for an uncertain chaotic Duffing oscillator, in which the three key system parameters are essentially unknown. The proposed method can be easily extended to handle some other chaotic dynamical systems with mild modifications. Simulation results are included to verify the control theory and controller design method.
Compositional software reuse with case-based reasoning

Case-based reasoning can be applied to software reuse. The approach presented goes beyond furnishing a library of potentially reusable modules and provides a tool that supports the process of reusing software. It uses case-based reasoning to add flexibility and adaptability to the compositional model of reuse. The authors describe the structure of the case base, emphasizing the case acquisition process during which high level functional information is associated with its components. The system performs advanced data-flow analysis of source code to guide acquisition of the functional specification of a library of software modules. The system then decomposes a user's problem, retrieves matching cases, and adapts and assembles their code. The data-flow of the result is again analyzed to produce test cases which can be used to evaluate the success of case-based reasoning. >
Drug-related pneumonitis during mammalian target of rapamycin inhibitor therapy in patients with neuroendocrine tumors: a radiographic pattern-based approach.

Abstract Purpose The purpose of this study was to investigate the incidence of drug-related pneumonitis during mammalian target of rapamycin (mTOR) inhibitor therapy in patients with neuroendocrine tumours (NET) and characterise radiographic patterns of pneumonitis. Methods Sixty-six patients (39 males, 27 females, age: 22–79 years) with advanced NET treated with mTOR inhibitor, everolimus, were retrospectively studied. Chest computed tomography scans during therapy were reviewed for abnormalities suspicious for drug-related pneumonitis by an independent review of two radiologists. Extent, distributions, and specific findings were evaluated in cases positive for pneumonitis. Radiographic patterns of pneumonitis were classified using the American Thoracic Society/European Respiratory Society classification of interstitial pneumonia. Results Drug-related pneumonitis was radiographically detected in 14 patients (21%). Time from the initiation of therapy to pneumonitis was within 6 months of therapy in 10 patients (71%), while it ranged from 1.0 to 27.7 months. Pneumonitis was more common in patients who had never smoked (p = 0.03). Lower lungs were more extensively involved than upper and middle lungs. Peripheral and lower distributions were most common (n = 8), followed by peripheral and multifocal distributions (n = 3). Ground glass and reticular opacities were present in all cases, with consolidation in eight cases. The radiographic pattern of pneumonitis was classified as cryptogenic organising pneumonia (COP) pattern in eight patients, non-specific interstitial pneumonia (NSIP) pattern in five, and hypersensitivity pneumonitis pattern in one patient. Conclusion Drug-related pneumonitis was noted in 21% of the advanced NET patients treated with everolimus. Radiographic pattern of pneumonitis was most commonly COP pattern, followed by NSIP pattern.
Stress concentrations around multiple windows in a high-pressure vessel

A pressure vessel with four radial windows was designed in which to conduct equation-of-state experiments at pressures up to 1 GPa (145,000 psi). To determine the relative safety of the vessel, the stress distribution in the cylindrical sidewalls, particularly the stress concentration near the window openings, was studied. Conventional analysis was used for the initial evaluation but was found to give somewhat higher stress values than were actually present. Better determinations of the stress distribution were obtained by photoelastic analysis of a model of the pressurevessel linear and by proof tests with strain gages of the actual liner and the assembled pressure vessel. Apparently, the tapered sapphire windows, loaded in compression by the internal pressure in the vessel, modify the stress distribution sufficiently to allow operation at higher pressures than otherwise would be attainable. Design features of the pressure vessel are presented, together with a synoptic stress analysis, a photoelastic analysis, and results of the strain-gage studies.
A serum volume test for the hemorrhagic diathesis in jaundice

Abstract 1.1. The problem of the hemorrhagic diathesis in jaundice is still unsolved. 2.2. Only the prothrombin deficiency theory, the liver damage theory and the defective clot theory are now tenable. These theories are briefly reviewed. 3.3. The defective clot theory is examined in the light of our personal observations, which corroborate the observations of others, and an explanation for it is advanced. 4.4. The tests now in use for predicting the hemorrhagic tendency in jaundice are reviewed, and it is pointed out that they are generally either unreliable or impractical. 5.5. The serum volume test is described and is advocated as a simple and reliable test of the bleeding tendency. Illustrative cases are adduced. 6.6. The preoperative preparation of jaundiced patients is discussed. 7.7. The low incidence of hemorrhage in jaundice in this community is commented upon.
Smart server: Concepts and applications: Research Articles

The Internet has become a critical tool for information and communication that has reached much of the developed world. It is comprised of numerous components, of which the World Wide Web (WWW) is the largest and fastest growing. Efficient functionality of the WWW depends on a multitude of web servers in operation throughout the world. A web server, in and of itself, is frequently inefficient. We propose several concepts—all of which involve the assimilation of computational intelligence into a web server—that will ultimately improve its performance. A web server would then become a “smart” server that will learn during its operation and subsequently adapt its components and behavior to optimize many of its functions and modes of operation. Furthermore, it will be more secure, robust, and reliable via a hierarchical security system. A smart server will ultimately be more efficient, thus providing an enhanced experience for the multitude of people making use of the WWW every day. © 2007 Wiley Periodicals, Inc. Int J Int Syst 22: 1139–1154, 2007.
Commentary: Social contracts for open access of healthcare information

For the great benefits of our being—our life, health, and reason—we look upon ourselves. Seneca the Elder (c. 55 B.C.E. – c. 39 C.E.)In healthcare, clear communication is critical. Misinformation m...
Application of the Intervention Mapping Framework to Develop an Integrated Twenty-first Century Core Curriculum-Part Three: Curriculum Implementation and Evaluation.

Public health professionals have been challenged to radically reform public health training to meet evolving demands of 21st century public health. Such a transformation requires a system thinking approach with an interdisciplinary focus on problem solving, leadership, management and teamwork, technology and information, budgeting and finance, and communication. This paper presents processes for implementing and evaluating a revised public health curriculum and outlines lessons learned from this initiative. To date, more than 200 students have participated in the initial pilot testing of this program. A rigorous process and outcome evaluation plan was developed and employed. Results from the evaluation were used to enhance the resulting curriculum. Specifically, all instructional materials were evaluated by both the students who received the materials and the faculty who presented the materials. As each successive pilot is delivered, both enrollment and faculty involvement has increased. Through this process, the value of committed faculty, the importance of engaging learners in the evaluation of an education program, and the need to implement curriculum that has been carefully evaluated and evidence-informed in nature has emerged. We credit our successful transformation of the MPH core to the challenge provided by the Framing the Future task force, the commitment of our COPH leadership, the engagement of our faculty, and the time we allowed for the process to unfold. Ultimately, we believe this transformed curriculum will result in better trained public health professionals, interdisciplinary practitioners who can see public health challenges in new and different ways.
Ethics, Leadership, and Ethical Leadership

This chapter engages recent studies in ethical leadership, mainly from their foundation and the working definition and construct of ethical leadership. Ethical leadership is weak in its foundation, but consistently deployed for statistical analysis, especially in light of ethical leadership scale developed by Brown, Trevino, and Harrison (2005). The lack of theological foundation is noted as a weakness and opportunity for deeper reflection, both for people of religious interest and for leadership theory.
A Stress Response that Monitors and Regulates mRNA Structure Is Central to Cold Shock Adaptation

Summary Temperature influences the structural and functional properties of cellular components, necessitating stress responses to restore homeostasis following temperature shift. Whereas the circuitry controlling the heat shock response is well understood, that controlling the E. coli cold shock adaptation program is not. We found that during the growth arrest phase (acclimation) that follows shift to low temperature, protein synthesis increases, and open reading frame (ORF)-wide mRNA secondary structure decreases. To identify the regulatory system controlling this process, we screened for players required for increased translation. We identified a two-member mRNA surveillance system that enables recovery of translation during acclimation: RNase R assures appropriate mRNA degradation and the Csps dynamically adjust mRNA secondary structure to globally modulate protein expression level. An autoregulatory switch in which Csps tune their own expression to cellular demand enables dynamic control of global translation. The universality of Csps in bacteria suggests broad utilization of this control mechanism.
Elevating the Profession of Navigation

Although it took some time for navigation to be recognized as an actual profession, once oncology nurse navigation became more established and recognized through the development and implementation of the AONN+ organization, it now is recognized as a specialty that oncology nurses can choose to aspire to. Patient (lay) navigation is a profession as well; however, the credentialing and certification process is quite different. For the purpose of this chapter’s discussion, the primary focus will be on oncology nurse navigation and how ONNs can climb a career ladder of their own creation and choosing while simultaneously elevating the profession of navigation globally. Key elements to successfully achieving career goals associated or starting with navigation require various skills; these include critical thinking, problem-solving, ethics, team building, leadership skills, professional development, and others. The value of certification will also be discussed. Today the only national organization devoted to the profession of navigation for nurse navigators as well as patient navigators is the Academy of Oncology Nurse & Patient Navigators (AONN+). This organization is continuously striving to have navigators recognized as valuable members of an oncology multidisciplinary team. What the membership’s goals and needs are is what the organization works to provide on a continuous basis. It provides mentorship for those navigators needing support as they expand their knowledge and experiences, educates and keeps its membership abreast of the newest information and quality improvement results, and provides information on research outcomes focused on navigation. It also provides education about changes in treatment modalities for different types of cancer, updates in clinical standards as they occur, the ability to measure one’s own performance through the use of evidence-based quality metrics, strategic information about the world and economics of oncology care, and opportunities to network with others so no one spends time reinventing the wheel.
Thermodynamic and NMR Assessment of Ligand Cooperativity and Intersubunit Communication in Symmetric Dimers: Application to Thymidylate Synthase

Thymidylate synthase (TS) is a homodimeric enzyme with evidence for negative regulation of one protomer while the other protomer acts on substrate, so called half-the-sites reactivity. The mechanisms by which multisubunit allosteric proteins communicate between protomers is not well understood, and the simplicity of dimeric systems has advantages for observing conformational and dynamic processes that functionally connect distance-separated active sites. This review considers progress in overcoming the inherent challenges of accurate thermodynamic and atomic-resolution characterization of interprotomer communication mechanisms in symmetric protein dimers, with TS used as an example. Isothermal titration calorimetry (ITC) is used to measure ligand binding cooperativity, even in cases where the two binding enthalpies are similar, and NMR spectroscopy is used to detect site-specific changes occurring in the two protomers. The NMR approach makes use of mixed-labeled dimers, enabling protomer-specific detection of signals in the singly ligated state. The rich informational content of the NMR signals from the singly ligated state, relative to the apo and saturated states, requires new considerations that do not arise in simple cases of 1:1 protein-ligand interactions.
Heats of Immersion of Hydroxyapatities in Water

Heats of immersion have been reported for many polar solids of metal oxides and silicates both in polar and nonpolar liquids. These heats have been determined as a function of outgassing temperatures, specific surface areas, and particle size. Usually they are made on the “bare” sample only. However, with most of the hydrophilic metal oxide surfaces, it is not always known whether the surface was “bare” (i.e. completely dehydroxylated) or had some residual hydroxyl groups still on the surface. How “bare” the surface was, would depend greatly upon the outgassing temperature and pressure at which the sample was prepared. Although the heats measured were relatively insensitive to these factors for a nonpolar liquid such as hexane on silica, titanium dioxide, or alumina1, for a polar molecule such as water on these solids, large and complex changes have been observed . Wade and Hackerman, et al. measured heats of immersion for water on TiO2 3, SiO2 4,5, and on Al2O3 6,7 as a function of the outgassing temperature and specific surface area. Whalen8 and Kiselev, et al.9,10 measured heats of immersion of different silica gel preparations and quartz.
Continuum Formulations of Conservation Laws

The theme for this chapter is captured by a quote from Herbert Callen’s book (Callen 1960) on thermodynamics. Callen introduces the conservation of energy and the concept of internal energy in the following paragraph: “The development of the principle of conservation of energy has been one of the most significant achievements in the evolution of physics. The present form of the principle was not discovered in one magnificent stroke of insight but has been slowly and laboriously developed over two and a half centuries. The first recognition of a conservation principle, by Leibnitz in 1693, referred only to the sum of the kinetic energy ((1/2)mv2) and the potential energy (mgh) of a simple mechanical mass point in the terrestrial gravitational field. As additional types of systems were considered, the established form of the conservation principle repeatedly failed, but in each case it was found possible to revive it by the addition of a new mathematical term - a “new kind of energy.” Thus consideration of charged systems necessitated the addition of the Coulomb interaction energy (Q1Q2/r) and eventually of the energy of the electromagnetic field. In 1905 Einstein extended the principle to the relativistic region, adding such terms as the relativistic rest-mass energy. In the 1930’s Enrico Fermi postulated the existence of a new particle, called the neutrino, solely for the purpose of retaining the energy conservation principle in nuclear reactions. Contemporary research in nuclear physics seeks the form of interaction between nucleons within a nucleus in order that the conservation principle may be formulated explicitly at the subnuclear level. Despite the fact that unsolved problems of this type remain, the energy conservation principle is now accepted as one of the most fundamental, general, and significant principles of physical theory.”
Impact of health care system on physicians' discontent.

This study was designed to investigate the impact of physicians' perceptions of the health care system on their discontent with their profession. By using a random digit dialing technique, a structured telephone interview was conducted with 401 generalist physicians (343 men, 56 women) who were practicing medicine at least for five years and were younger than 65 years. Physicians' willingness to choose medicine again was correlated with their perceptions of different aspects of the health care system. Of the total participants, 288 (72 percent) indicated that they would choose medicine again, 91 (23 percent) would not choose medicine, and 22 (5 percent) were not sure. Results of the stepwise logistic regression showed that after adjustment for physicians' gender and age, those who would not choose medicine again were more than twice as likely as other physicians who would choose medicine to believe that the health care environment will deteriorate more in the future (odds ratio = 2.1, p < .01), were less than half as likely to believe that physicians nowadays share more responsibilities with other health care professionals (odds ratio = .42, p < .01), and were less than half as likely to confirm that patients understand their health insurance better than before (odds ratio = .46, p < .01). Findings suggest that physicians' discontent can be predicted by their negative perceptions of the health care environment. Findings have implications for improving the quality of professional and personal life of the physician, thus improving the quality of care and satisfaction of the patient.
CBLB Constrains Inactivated Vaccine–Induced CD8+ T Cell Responses and Immunity against Lethal Fungal Pneumonia

Fungal infections in CD4+ T cell immunocompromised patients have risen sharply in recent years. Although vaccines offer a rational avenue to prevent infections, there are no licensed fungal vaccines available. Inactivated vaccines are safer but less efficacious and require adjuvants that may undesirably bias toward poor protective immune responses. We hypothesized that reducing the TCR signaling threshold could potentiate antifungal CD8+ T cell responses and immunity to inactivated vaccine in the absence of CD4+ T cells. In this study, we show that CBLB, a negative regulator of TCR signaling, suppresses CD8+ T cells in response to inactivated fungal vaccination in a mouse model of CD4+ T cell lymphopenia. Conversely, Cblb deficiency enhanced both the type 1 (e.g., IFN-γ) and type 17 (IL-17A) CD8+ T cell responses to inactivated fungal vaccines and augmented vaccine immunity to lethal fungal pneumonia. Furthermore, we show that immunization with live or inactivated vaccine yeast did not cause detectable pathologic condition in Cblb-/- mice. Augmented CD8+ T cell responses in the absence of CBLB also did not lead to terminal differentiation or adversely affect the expression of transcription factors T-bet, Eomes, and RORγt. Additionally, our adoptive transfer experiments showed that CBLB impedes the effector CD8+ T cell responses in a cell-intrinsic manner. Finally, we showed that ablation of Cblb overcomes the requirement of HIF-1α for expansion of CD8+ T cells upon vaccination. Thus, adjuvants that target CBLB may augment inactivated vaccines and immunity against systemic fungal infections in vulnerable patients.
Interactiles: 3D Printed Tactile Interfaces to Enhance Mobile Touchscreen Accessibility

The absence of tactile cues such as keys and buttons makes touchscreens difficult to navigate for people with visual impairments. Increasing tactile feedback and tangible interaction on touchscreens can improve their accessibility. However, prior solutions have either required hardware customization or provided limited functionality with static overlays. Prior investigation of tactile solutions for large touchscreens also may not address the challenges on mobile devices. We therefore present Interactiles, a low cost, portable, and unpowered system that enhances tactile interaction on Android touchscreen phones. Interactiles consists of 3D-printed hardware interfaces and software that maps interaction with that hardware to manipulation of a mobile app. The system is compatible with the built-in screen reader without requiring modification of existing mobile apps. We describe the design and implementation of Interactiles, and we evaluate its improvement in task performance and the user experience it enables with people who are blind or have low vision.
A Convergence Result for Regularized Actor-Critic Methods

In this paper, we present a probability one convergence proof, under suitable conditions, of a certain class of actor-critic algorithms for finding approximate solutions to entropy-regularized MDPs using the machinery of stochastic approximation. To obtain this overall result, we prove the convergence of policy evaluation with general regularizers when using linear approximation architectures and show convergence of entropy-regularized policy improvement.
Data-based Aggregate Model of Refrigerators for Electric Power Grid Services

Electrical power system stability under high penetration of intermittent renewable energy generation, such as wind and solar energy, has become a high concern. It is unpredictable and hard to control due to little inertial behavior characteristic to these generation resources. To help mitigate possibly undesirable frequency excursions, demand-side frequency control presents an emerging solution. By observing the frequency deviation, devices could switch operating modes for a short time to rebalance generation. To analyze device level control algorithms, aggregate models for their behavior are needed. Refrigerators are household devices that could help with load modulation. This paper uses real measured data to analyze the refrigerator behavior, learn about its operating mode and power consumption ranges. A Markov chain process is proposed to model the transition of a refrigerator population from one operating mode to another, such that the overall load is modulated according to the control input. The Markov-chain model can be used to design control so that the overall load is modulated according to the control input.
Phosphate solubilizing bacteria stimulate wheat rhizosphere and endosphere biological nitrogen fixation by improving phosphorus content

Phosphate (P) availability often limits biological nitrogen fixation (BNF) by diazotrophic bacteria. In soil, only 0.1% of the total P is available for plant uptake. P solubilizing bacteria can convert insoluble P to plant-available soluble P (ionic P and low molecular-weight organic P). However, limited information is available about the effects of synergistic application of diazotrophic bacteria and P solubilizing bacteria on the nitrogenase activity of rhizosphere and nifH expression of endosphere. In this study, we investigated the effects of co-inoculation with a diazotrophic bacterium (Paenibacillus beijingensis BJ-18) and a P-solubilizing bacterium (Paenibacillus sp. B1) on wheat growth, plant and soil total N, plant total P, soil available P, soil nitrogenase activity and the relative expression of nifH in plant tissues. Co-inoculation significantly increased plant biomass (length, fresh and dry weight) and plant N content (root: 27%, shoot: 30%) and P content (root: 63%, shoot: 30%). Co-inoculation also significantly increased soil total N (12%), available P (9%) and nitrogenase activity (69%) compared to P. beijingensis BJ-18 inoculation alone. Quantitative real-time PCR analysis showed co-inoculation doubled expression of nifH genes in shoots and roots. Soil nitrogenase activity and nifH expression within plant tissues correlated with P content of soil and plant tissues, which suggests solubilization of P by Paenibacillus sp. B1 increased N fixation in soils and the endosphere. In conclusion, P solubilizing bacteria generally improved soil available P and plant P uptake, and considerably stimulated BNF in the rhizosphere and endosphere of wheat seedlings.
Atomic-precision engineering of metal nanoclusters

Ultrasmall metal nanoparticles (below 2.2 nm core diameter) start to show discrete electronic energy levels due to strong quantum confinement effects and thus behave much like molecules. The size and structure dependent quantization induces a plethora of new phenomena, including multi-band optical absorption, enhanced luminescence, single-electron magnetism, and catalytic reactivity. The exploration of such new properties is largely built on the success in unveiling the crystallographic structures of atomically precise nanoclusters (typically protected by ligands, formulated as MnLmq, where M = metal, L = Ligand, and q = charge). Correlation between the atomic structures of nanoclusters and their properties has further enabled atomic-precision engineering toward materials design. In this frontier article, we illustrate several aspects of the precise engineering of gold nanoclusters, such as the single-atom size augmenting, single-atom dislodging and doping, precise surface modification, and single-electron control for magnetism. Such precise engineering involves the nanocluster's geometric structure, surface chemistry, and electronic properties, and future endeavors will lead to new materials design rules for structure-function correlations and largely boost the applications of metal nanoclusters in optics, catalysis, magnetism, and other fields. Following the illustrations of atomic-precision engineering, we have also put forth some perspectives. We hope this frontier article will stimulate research interest in atomic-level engineering of nanoclusters.
Purpose-first Programming: A Programming Learning Approach for Learners who Care Most About What Code Achieves

Becoming "a programmer" is associated with gaining a deep understanding of programming language semantics. However, as more people learn to program for more reasons than creating software, their learning needs differ. In particular, end-user programmers and conversational programmers often care about code's purpose, but don't wish to engage with the low-level details of precisely how code executes. I propose the creation of scaffolding that allows these learners to interact with code in an authentic way, highlighting code's purpose while providing support that avoids the need for low-level tracing knowledge. This scaffolding builds on theories of programming plans.
The United States of America: Unfounded Fears of Press Subsidies

One of the central assumptions of US political discourse is that state-funded media subsidies are deeply antithetical to American values, and democratic practice generally. This assumption is rarely challenged, though a good deal of historical evidence gives us reason to doubt it. Not only are various media subsidies firmly established in American traditions, but the historical record shows that both in the USA and across the globe, press subsidies are compatible with democratic self-governance. Still, misconceptions about subsidies abound in the USA and continue to impede rational debates about an important policy option—an option that might be the last remaining systemic alternative to the failing model of ad revenue-supported journalism. The following chapter provides a brief overview of past and present American press subsidies. Drawing from historical and international research, the chapter sketches a political economic rationale for subsidizing media and concludes with some suggestions for future policy trajectories.
Letter to the Editor: Proof of the HRT Conjecture for Almost Every (1,3) Configuration

We prove that for almost every (1,3) configuration, there is no linear dependence between the associated time-frequency translates of any $$f\in L^2(\mathbb {R})\backslash \{0\}$$ .
Incidental Findings in CT and MR Angiography for Preoperative Planning in DIEP Flap Breast Reconstruction.

Background Autologous breast reconstruction with deep inferior epigastric perforator flaps is considered a standard of care in the treatment after mastectomy, yet vascular anatomy is highly variable and perforator selection remains challenging. The use of preoperative imaging can influence surgical planning and assist intraoperative decision-making. However, this imaging can inevitably uncover incidental findings. The purpose of this study was to analyze incidental findings, evaluate correlation with patient factors, and examine effects on overall care. Methods A retrospective review was performed on 350 consecutive patients who received magnetic resonance angiography (MRA) or computed tomographic angiography (CTA) as a preoperative evaluation for deep inferior epigastric perforator flap breast reconstructions done between August 2015 and June 2019. Radiology reports were analyzed for incidental findings. Patient charts were reviewed for patient history, genetic history, cancer treatment, and type of reconstruction. Results Of the 350 patients meeting the criteria, 56.9% were noted to have incidental findings on preoperative imaging, 12.9% received additional imaging, and 4.0% underwent additional interventions. There was no difference in the percentage of patients with incidental findings between immediate and delayed reconstructions or between CTA and MRA. Five patients were found to have malignancies. Conclusions Preoperative CTA and MRA is a valuable tool to optimize outcomes and efficiency in breast reconstruction with abdominal perforator flaps. However, this imaging can also be beneficial to the overall wellness of the patient. With the high prevalence of incidental findings on preoperative imaging, it is important to counsel patients and adjust surgical plans, if necessary.
Acetyl-CoA Synthetase 2: A Critical Linkage in Obesity-Induced Tumorigenesis in Myeloma

Summary Obesity is often linked to malignancies including multiple myeloma, and the underlying mechanisms remain elusive. Here we showed that acetyl-CoA synthetase 2 (ACSS2) may be an important linker in obesity-related myeloma. ACSS2 is overexpressed in myeloma cells derived from obese patients and contributes to myeloma progression. We identified adipocyte-secreted angiotensin II as a direct cause of adiposity in increased ACSS2 expression. ACSS2 interacts with oncoprotein interferon regulatory factor 4 (IRF4), and enhances IRF4 stability and IRF4-mediated gene transcription through activation of acetylation. The importance of ACSS2 overexpression in myeloma is confirmed by the finding that an inhibitor of ACSS2 reduces myeloma growth both in vitro and in a diet-induced obese mouse model. Our findings demonstrate a key impact for obesity-induced ACSS2 on the progression of myeloma. Given the central role of ACSS2 in many tumors, this mechanism could be important to other obesity-related malignancies.
How do you stop the books being cooked? A management-control perspective on financial accounting standard setting and the section 404 requirements of the Sarbanes-Oxley Act

The recent series of corporate scandals has resulted in an unprecedented crisis in accounting. Investors have lost faith in financial statements on the assumption that ‘cooking the books’ has become a routine practice in corporate America. Restoring the credibility of financial reporting is clearly an urgent priority, as indicated by the passage of the Sarbanes–Oxley Act, which mandates that chief executive officers personally certify the accuracy of their firms' financial statements. The approach being contemplated by the accounting profession itself is a shift away from the rules-based approach to financial accounting standards used by US Generally Accepted Accounting Principles towards the principles-based approach of International Accounting Standards. Both these initiatives draw attention to the fact that accounting standards are only useful and effective if they are actually implemented by firms in the way the standard setter intended. In other words, the need to ensure implementation of accounting standards by managers who have an incentive to beat analysts' earnings forecasts means that accounting standards have a management-control component. In this paper the authors put forward an ex. post perspective on accounting-standard implementation that places the problem clearly within the domain of control theory. That in turn implies that, to ensure compliance by management, standard setters can make use of the powerful tools that control theory provides — the four levers of control: belief, boundary, diagnostic and interactive control systems. The authors' control perspective provides new insights into accounting standard setting, including the need for both belief and boundary controls rather than reliance on one alone. Of even greater potential significance is the implication this management-control perspective has for the Sarbanes–Oxley Act's section 404 requirement for management and auditor assurance on the effectiveness of a firm's internal controls over financial reporting. A management-control perspective can provide a much-needed framework within which the COSO (The Committee of Sponsoring Organizations of the Treadway Commission) standards can be applied, avoiding an excessive focus on the existence and documentation of controls and increasing their efficacy.
Parent-EMBRACE: An Adaptive Dialogic Reading Intervention

Dialogic reading is a practice where adults and children engage in a dialogue as they read together to improve children’s language strategies and comprehension. These dialogues are often initiated by parent questioning behaviors, but parents do not always engage in this behavior spontaneously. In this paper, we describe an adaptive intervention for dialogic reading, Parent-EMBRACE, built into an iPad application that uses an embodied cognition approach and is designed specifically for Latino dual language learners in the US. The intervention: 1) Models parent question asking, 2) Provides parents with on-demand hints on questions that can be asked at particular moments during the story, 3) Prompts parents to ask questions at appropriate times, 4) Includes a dashboard that presents parents with data on their question-asking behaviors, 5) Provides all support in both English and Spanish. We discuss the implications of this intervention as an intelligent tutoring system for parent-child interactions, plans to extend and evaluate the system.
A Journey of Transforming to an Online Government Documents Collection

As a selective depository library in Tennessee for decades, the Paul Meek Library has received and housed publications of the Government Printing Office (GPO) in a variety of formats as part of the...