cssi/SciSciGPT-SciSciNet huggingface dataset:
Assessing the Efficiency of Polymeric Excipients by Atomistic Molecular Dynamics Simulations

We have performed all-atom molecular dynamics simulations of aqueous solutions of model oligomers of hydroxypropyl methylcellulose (HPMC) and hydroxypropyl methylcellulose acetate succinate (HPMCAS) excipients interacting with a representative poorly soluble active pharmaceutical ingredient (API), phenytoin. Simulations reveal formation of excipient-API complexes for some of the oligomers, which results in a reduction of API aggregation. API aggregation and diffusivity decreased with an increase in excipient content. Excipients form a "gel-like" phase spanning the simulation box beyond ∼10 wt %; API diffusivity within this gel phase is much smaller than API diffusivity without excipient, and decreases exponentially, by 5 orders of magnitude, with increased polymer concentration. Substantial differences are observed with variations in methyl, hydroxypropyl, acetate, and succinate substitution levels in the model oligomers and with the deprotonation state of succinate groups, with strongest interactions with hydrophobic phenytoin observed in the case of acetate substitution. These are used to develop quantitative measures of excipient-API interactions and excipient efficiency in the inhibition of API aggregation. We also find that for model oligomers based on Methocel E (manufactured by Dow Pharma & Food Solutions) chemistry, oligomers of length 10 monomers and simulation boxes of size 7 nm give results similar to those for longer oligomers and bigger boxes. The quantitative measures developed in this study are expected to prove useful as computational screening tools in excipient design.
Restoration of normal implantation rates in mouse embryos with a hatching impairment by use of a new method of assisted hatching

Objective To use a newly developed mouse model for embryos with a hatching defect to develop improved methods of assisted hatching. Design We had previously demonstrated that mouse embryos with reduced cell numbers, when resident within an intact zona, exhibit a hatching deficiency, and we used these " hatching-defective" embryos to demonstrate that hatching is mediated predominantly, if not entirely, by lysis of the zona pellucida. In the present study, the hatching-defective embryos were implanted into pseudopregnant females to determine if implantation rates were reduced. In addition, to compensate for reduced zona lysin production, the zonae of some embryos were circumferentially thinned with acid Tyrode's solution. The implantation rates and developmental potential of hatching-defective embryos subjected to zona thinning were compared with those of the hatching-defective embryos implanted without zona thinning. Setting University-based basic research laboratory. Results When hatching-defective embryos, created by destruction of 1 4 of the blastomeres at the four-cell stage, were implanted into pseudopregnant female mice, no pregnancies were established, and no implantation sites could be identified after transfer of 41 embryos. However, when hatching-defective embryos were subjected to zona thinning before ET, a normal rate of implantation was observed (18 implantation events of 49 embryos transferred). Fetuses appeared morphologically normal. The difference in implantation rates between hatching-defective embryos subjected to zona thinning and those not treated by zona thinning was highly significant by χ 2 analysis. Conclusion Failure of embryos with cell numbers reduced by micromanipulation to implant and restoration of normal implantation and development after circumferential zona thinning demonstrates that the developmental defect of the manipulated embryos is confined to hatching, and thus, that this procedure establishes a useful model for defective hatching. High rates of implantation after circumferential thinning of the zona shows that this procedure of assisted hatching is highly effective. These findings have important implications for use of assisted hatching in human IVF because the assisted hatching procedure is safe and effective and increases the efficiency of the normal hatching mechanism. Thus, the procedure may be useful in a wide variety of circumstances for which assisted hatching by zona opening has been found to be ineffective.
Aquinas and ontotheology again

ABSTRACTA number of contemporary authors have argued that Aquinas’s understanding of God is ontotheological. In this paper, I consider the charge as it is formulated by Kevin Hart in his influential book The Trespass of the Sign: Deconstruction, Theology, and Philosophy. Hart claims that three features of Aquinas’s approach to the divine make it ontotheological, namely that it (1) privileges positive theology over negative theology, (2) regards God as the ‘highest value’, and (3) takes God to be the essence of beings. I argue that these features are either not to be found in Aquinas’s thinking about God or that Hart misunderstands them.
Ethics Education in the MPA Curriculum: What Difference Does It Make?

This study of 203 public administrators from across the United States, each of whom holds a master's degree in public administration, addresses the effects of ethics education upon professional behavior. Survey respondents were grouped on the basis of whether or not they had in their MPA program a semester-long class that focused solely or primarily on ethics. Those who reported having had this formal ethics education recognized ethical conflict as distinct from other conflicts significantly more often than those who did not.They were also significantly more likely to refuse to engage in unethical behavior, even when directed to do so by a superior, than were those reporting no formal ethics education. Implications for further research are outlined.
Counting, Recurrences, and Trees

Section 3.1 introduces a number of principles useful in counting complicated sets of objects. These principles include the rule of sum, the rule of product, and the pigeonhole principle. The section also introduces permutations and combinations, and the binomial theorem. Section 3.2 extends the formal study of trees, which were briefly encountered in Chapter 2, and explores ways of counting and computing based on recurrence relations. The final section has a different flavor but is still devoted to counting — this time to counting the number of steps taken by an algorithm to process data. It thus introduces the reader to the important topic of “analysis of algorithms” which enables us to compare the efficiency of different approaches to solve a given problem.
Evaluating outcomes of pancreatic cancer patients with cacehxia.

e15208 Background: Although cachexia is a common complication in pancreatic cancer patients and a risk factor for poor outcomes, physicians do not necessarily diagnose and treat it. In a nationally...
An analysis of indirect water withdrawal and consumption due to electricity and workers in automotive manufacturing facilities

AbstractWater is a key resource for all life. Recent droughts have also exemplified the importance for manufacturers to understand their impact on water resources. While most manufacturers typically know the amount of water they use in their facilities, they have little knowledge about the indirect effects they have on water resources. In this paper, the indirect impact from the automakers’ electricity use and work force on water resources is examined. Water withdrawal and consumption from electricity use by hypothetical but representative facilities around the world is quantified and analysed. Water withdrawal by the workers is also quantified and analysed. The results indicate that the water withdrawal and consumption by the workforce and caused by the use of electricity is larger than the direct water use and consumption in the facilities themselves.
Modified Random Sequential Adsorption Model for Understanding Kinetics of Proteins Adsorption at a Liquid–Solid Interface

In this Article, we experimentally measure the adsorption kinetics of human serum albumin (HSA) on a hydrophobic hexadecanethiolated gold surface. We use micromachined quartz crystal resonators with fundamental frequency of 83 MHz to accomplish these measurements in real time. In this work, we focus on two key results: (i) asymptotic behavior of the sensor responses upon HSA adsorption and (ii) the jamming limit of adsorbed layer formed by both single-injection and multi-injection experiments with the same value of final concentration. We develop a new interface-depletion modified random sequential adsorption (RSA) model to elucidate the adsorption kinetics and the transport properties of the protein molecules. Analysis of the experimentally measured data shows that the results can be explained on the basis of the exponentially depleting interfacial layer RSA model. To better understand the origin of the formation of the interfacial depletion region where the supply of protein molecules is dramatically re...
Efficacy of Tramadol Extended-Release for Opioid Withdrawal: A Randomized Clinical Trial.

Importance Opioid use disorder (OUD) is a significant public health problem. Supervised withdrawal (ie, detoxification) from opioids using clonidine or buprenorphine hydrochloride is a widely used treatment. Objective To evaluate whether tramadol hydrochloride extended-release (ER), an approved analgesic with opioid and nonopioid mechanisms of action and low abuse potential, is effective for use in supervised withdrawal settings. Design, Setting, and Participants A randomized clinical trial was conducted in a residential research setting with 103 participants with OUD. Participants’ treatment was stabilized with morphine, 30 mg, administered subcutaneously 4 times daily. A 7-day taper using clonidine (n = 36), tramadol ER (n = 36), or buprenorphine (n = 31) was then instituted, and patients were crossed-over to double-blind placebo during a post-taper period. The study was conducted from October 25, 2010, to June 23, 2015. Main Outcomes and Measures Retention, withdrawal symptom management, concomitant medication utilization, and naltrexone induction. Results were analyzed over time and using area under the curve for the intention-to-treat and completer groups. Results Of the 103 participants, 88 (85.4%) were men and 43 (41.7%) were white; mean (SD) age was 28.9 (10.4) years. Buprenorphine participants (28 [90.3%]) were significantly more likely to be retained at the end of the taper compared with clonidine participants (22 [66.1%]); tramadol ER retention was intermediate and did not differ significantly from that of the other groups (26 [72.2%]; χ 2 = 8.5, P = .01). Time-course analyses of withdrawal revealed significant effects of phase (taper, post taper) for the Clinical Opiate Withdrawal Scale (COWS) score (taper mean, 5.19 [SE, .26]; post-taper mean, 3.97 [SE, .23]; F 2,170 = 3.6, P = .03) and Subjective Opiate Withdrawal Scale (SOWS) score (taper mean,8.81 [SE, .40]; post-taper mean, 4.14 [SE, .30]; F 2,170 = 15.7, P F 2,159 = 17.7, P P P = .03), but not buprenorphine (taper mean, 6.4; post-taper mean, 7.4). Use of concomitant medication increased significantly ( F 2,159 = 30.7, P P P = .003) groups and from stabilization to post taper in the buprenorphine group (stabilization mean, 0.46 [SE, .05] post-taper mean, 1.17 [SE, .09]; P = .006), suggesting higher withdrawal for those groups during those periods. Naltrexone initiation was voluntary and the percentage of participants choosing naltrexone therapy within the clonidine (8 [22.2%]), tramadol ER (71 [9.4%]), or buprenorphine (3 [9.7%]) groups did not differ significantly (χ 2 = 2.5, P = .29). Conclusions and Relevance The results of this trial suggest that tramadol ER is more effective than clonidine and comparable to buprenorphine in reducing opioid withdrawal symptoms during a residential tapering program. Data support further examination of tramadol ER as a method to manage opioid withdrawal symptoms. Trial Registration Clinicaltrials.gov Identifier:NCT01188421
Nonrigid Registration of Hyperspectral and Color Images with Vastly Different Spatial and Spectral Resolutions for Spectral Unmixing and Pansharpening

In this paper, we propose a framework to register images with very large scale differences by utilizing the point spread function (PSF), and apply it to register hyperspectral and hi-resolution color images. The algorithm minimizes a least-squares (LSQ) objective function with an incorporated spectral response function (SRF), a nonrigid freeform deformation applied on the hyperspectral image and a rigid transformation on the color image. The optimization problem is solved by updating the two transformations and the two physical functions in an alternating fashion. We executed the framework on a simulated Pavia University dataset and a real Salton Sea dataset, by comparing the proposed algorithm with its rigid variation, and two mutual information-based algorithms. The results indicate that the LSQ freeform version has the best performance for the nonrigid simulation and real datasets, with less than 0.15 pixel error given 1 pixel nonrigid distortion in the hyperspectral domain.
Interfacial Hydration Dynamics in Cationic Micelles Using 2D-IR and NMR

Using the thiocyanate anion as a vibrational probe chromophore in conjunction with infrared and NMR spectroscopy, we find that SCN- strongly associates with the cationic head group of dodecyltrimethylammonium bromide (DTAB) micelles, both in normal-phase and reverse micelles. In competition with chloride and iodide ions, we find no evidence for displacement of thiocyanate, in accord with the chaotropicity of the Hofmeister ordering, while lending support to a direct interaction picture of its origin. Ultrafast 2D-IR spectroscopy of the SCN- probe in a range of DTAB micelle sizes (w0 = 4 to w0 = 12) shows little if any size dependence on the time scale for spectral diffusion, which is found to be ∼3.5 times slower than in bulk water (both D2O and H2O). Normal-phase micelles studied with 2D-IR exhibit essentially the same spectral dynamics as do reverse micelles, indicating a lack of sensitivity to interfacial curvature. Combined with 1H NMR chemical shift perturbations, we conclude that the SCN- ions tightly associate with the head groups and are partially buried. The 3-4-fold slowdown in spectral diffusion is consistent with the excluded volume model for interfacial perturbation to hydrogen bond reorientation dynamics. On the basis of these observations and comparisons to previous studies of zwitterionic interfaces probed with phosphate transitions, we conclude that the SCN- spectral dynamics in both reverse- and normal-phase micelles is largely dominated by hydration contributions, and offers a promising probe of interfacial hydration at cationic interfaces. Addition of competitive anions alters neither the IR spectra nor the ultrafast dynamics, indicating that SCN- is robustly associated with the head groups.
Advances in Film Cooling Heat Transfer

Abstract Advances in cooling technologies have enabled turbine designers to push the turbine entry temperature to temperatures as high as 1700°C which are well beyond the material limit of the turbine components. Efficient use of the cooling air is a key goal of the turbine designer. Overall cooling effectiveness has increased to values as high as 0.6 in recent advanced cooling designs. In this chapter, the state of the art in film cooling is reviewed, and key advances in this field are discussed. The ideal configuration in film cooling is a slot where a two-dimensional coolant film is initially injected. Key aspects of the slot cooling are presented particularly in light of advanced manufacturing techniques that enable double-walled airfoils with pin fins and slots. The primary focus in the literature and in industrial practice has been on discrete hole cooling due to manufacturing and structural constraints. The role of injection angles, blowing and momentum ratio, density ratio, freestream turbulence, surface curvature, and pressure gradient on the film cooling behavior is explored in this chapter. Various cooling hole designs and their performance are summarized. While the majority of the studies discussed are based on flat plate film cooling studies, the literature on film cooling in full vane passages is also presented to highlight the key effects of the various parameters.
Collective Creation and ‘Historical Imagination’: Mabou Mines’s Devised Adaptations of History

This chapter explores the American avant-garde company Mabou Mines’s distinctive approach to devising and adaptation as a mode for reimagining women and events of the past in two productions: Dead End Kids and Belen: A Book of Hours. Here, Mabou Mines changes identifiable historical source material to challenge accepted notions of history, confronting audiences with new perspectives on people and events of the past and undermining the authority of traditional master narratives. Dead End Kids and Belen are history plays that establish an interrogative relationship with the past, though each production establishes a distinct methodology particular to its perspective on the history it investigates. The approach, as Peter Weiss described his documentary drama, frankly ‘partisan’.
A 2.56mm 2 718GOPS configurable spiking convolutional sparse coding processor in 40nm CMOS

A configurable neuro-inspired inference processor is designed as an array of neurons each operating in an independent clock domain. The processor implements a recurrent network using efficient sparse convolutions with zero-patch skipping for feedforward operations, and sparse spike-driven reconstruction for feedback operations. A globally asynchronous locally synchronous structure enables scalable design and load balancing to achieve 22% reduction in power. Fabricated in 40nm CMOS, the 2.56mm2 inference processor integrates 48 neurons, a hub and an OpenRISC processor. The chip achieves 718GOPS at 380MHz, and demonstrates applications in feature extraction from images and depth extraction from stereo images.
Estimation of thermocapillary force during laser trapping of confined microbubbles in a liquid

A theoretical model is introduced to determine the thermocapillary force acting on a microbubble, which adheres to the wall of a container filled with a liquid, during trapping using a focused continuous-wave (CW) laser beam. The model is developed by considering all possible forces acting on the microbubble, which also includes the optical force, the viscous force, and the friction force. The thermocapillary force, estimated from the relative velocity of the trapped microbubble with respect to the container, compares favorably with theoretical predictions based on the temperature gradient induced by the focused laser beam. The proposed experiment can be also used to determine the contact angle and/or the coefficient of friction of the microbubble at the microbubble–container interface. Our results should be useful in the design of efficient systems using microbubbles for drug delivery and water treatment systems.
Functional Glycomics Analysis: Challenges and Methodologies

Abstract Glycans are a ubiquitous class of biological molecules responsible for modulating a diverse array of physiological processes including development, immune recognition, and host–pathogen interaction. Elucidating structure–function relationships has been challenging due to the structural complexity of glycans and the dominant role of multivalency in their biological interactions. Therefore, a glycomics approach—defined as an integrated, systems-level study of glycans—is necessary to elucidate the structure–function relationships. In this chapter, we review the fundamental glycomics tools used for structural elucidation and functional analysis across multiple levels, emphasizing integration across these axes. We conclude with a case study of influenza A virus hemagglutinin interaction with sialylated glycan receptors to demonstrate a robust structure–function paradigm that is born out of a glycomics approach.
Moral Motivation and Sports

Largely neglected by moral psychologists, sports offer a special window into human motivation. Ryan and Deci (2007) note that “sport and exercise epitomize motivation” because of the “exertion, energy, focus, and … discipline” they typically demand.
Assessing Suicidal and NonSuicidal Self-Injury via In-Depth Interview or Self-Report: Balancing Assessment Effort and Results.

Objective Both suicide and nonsuicidal self-injury (NSSI) represent major public health concerns, and effective assessment, management, and treatment requires assessment tools that can simultaneously be quick and accurate. This study compared the validity of a self-report measure of suicide attempts and NSSI acts with a gold standard in depth interview. Method Ninety women answered questions about their suicidal behavior history using both a self-report assessment and in-depth interview. Results The plurality of patients over estimated their suicidal acts using the self-report measure when compared to the gold standard interview. Conclusion Self-report assessments may not be an accurate method of retrieving information about suicide.
Evaluating Job Satisfaction of Latino/a Journalists in Multimedia Newsrooms: A Comparative Examination Between 2010 and 2017

This study provides an assessment of the current working conditions of Latino/a journalists employed at Latino-oriented news media outlets as well as those employed at legacy companies and evaluate...
Exploring human-robot trust during teaming in a real-world testbed

Project Aquaticus is a human-robot teaming competition on the water involving autonomous surface vehicles and human operated motorized kayaks. Teams composed of both humans and robots share the same physical environment to play capture the flag. In this paper, we present results from seven competitions of our half-court (one participant versus one robot) game. We found that participants indicated more trust in more aggressive behaviors from robots.
Ultrasonography and X-Ray guided drain placement to evacuate a pneumopericardium/pneumomediastinum in a 1-day-old infant

Ultrasonographic (US) guided procedures have wide range of application in the abdomen and pelvis, however their role is somewhat limited in the chest due to complete reflection of the ultrasound beam by the air in the lungs, preventing the direct imaging of the tissues deep to the air-sound interface. Most of the chest procedures, other than the exception of thoracentesis, rely on the use of CT (computed tomography) scan. The disadvantages of using CT scan is the cost, lack of portability, and most importantly the radiation involved, particularly in case of infants and children, whose tissues are more radiosensitive than the adults. Identification of air by Ultrasonography can help direct needles and wires, to accomplish procedures which may otherwise need CT. A 1-day-old infant with respiratory distress syndrome (RDS) on a ventilator, developed an expanding symptomatic pneumopericardium/pneumomediastinum. The patient was too unstable to leave the neonatal intensive care unit (NICU), so a pericardial/mediastinal drain was placed under ultrasonographic and radiographic guidance. This case, highlights a method for bedside treatment of pneumopericardium/pneumomediastinum in an unstable neonate. This procedure may be equally effective in older children and adults.
Strengthening Humanistic Management

Humanistic management is emerging as a response to the economistic paradigm prevalent in today’s business schools, corporations, and society. There are many compelling reasons why the economistic paradigm is becoming obsolete, and even dangerous, for business if it is to become an agent of world benefit. The purpose of this article is not to explain these reasons but rather to situate the transition to humanistic management in the context of multiple worldviews. We propose an historical sequence of worldviews each with its own paradigmatic assumptions about what it means to be human and the nature of the world. We draw on converging insights between new science and ancient spiritual traditions to outline an emerging quantum worldview. We further submit that integrating elements of the quantum worldview into humanistic management strengthens it in ways that are essential to humankind’s ability to shift to full-spectrum flourishing, defined as a world in which people and all life thrive now and across future generations.
NaBaR(BO3)2 (R = Dy, Ho, Er and Tm): structurally perfect triangular lattice materials with two rare earth layers

We report the crystal growth of NaBaR(BO3)2 (R = Dy, Ho, Er and Tm) by the flux method. In the rhombohedral crystal structures, [RO6] octahedra and planar [BO3] units connect by bridging O atoms, forming triangular layers in the ab plane that are evenly spaced along c. Two perfectly triangular rare earth layers of identical dimension are found. Anisotropic magnetic susceptibility is observed for all; NaBaEr(BO3)2 is nearly isotropic while NaBaTm(BO3)2 is the most anisotropic. Heat capacity measurements reveal no long-range magnetic ordering down to 0.35 K for R = Dy or Er, while the Ho material displays a significant entropy loss. All the magnetic entropy appears to be absent in the Tm case by low temperature, suggesting that a singlet ground state may have formed.
Embryonic Cells Redistribute SUMO1 upon Forced SUMO1 Overexpression

Conjugation of small ubiquitin-like modifiers (SUMOs) to substrate proteins is a posttranslational protein modification that affects a diverse range of physiological processes. Global inhibition of SUMO conjugation in mice results in embryonic lethality, reflecting the importance of the SUMO pathways for embryonic development. Here, we demonstrated that SUMO1 overexpression was not well tolerated in murine embryonic carcinoma and embryonic stem (ES) cells and that only a few clones were recovered after transduction with vectors delivering SUMO1 expression constructs. Differentiated NIH/3T3 cells overexpress SUMO1 without deleterious effects and maintain high levels of both conjugated and free forms of SUMO1. The few embryonic cells surviving after forced overexpression retained all their SUMO1 in the form of a few high-molecular-weight conjugates and maintained undetectable levels of free SUMO1. The absence of free SUMO in embryonic cells was seen specifically upon overexpression of SUMO1, but not SUMO2. Moreover, blocking SUMO1 conjugation to endogenous substrates by C-terminal mutations of SUMO1 or by overexpression of a SUMO1 substrate "sponge" or by overexpression of the deSUMOylating enzyme SUMO-specific peptidase 1 (SENP1) dramatically restored free SUMO1 overexpression. The data suggest that overexpression of SUMO1 protein leading to an excess accumulation of critical SUMO1-conjugated substrates is not tolerated in embryonic cells. Surviving embryonic cells exhibit SUMO1 conjugation to allowed substrates but a complete absence of free SUMO1.IMPORTANCE Embryonic stem (ES) cells exhibit unusual transcriptional, proteomic, and signal response profiles, reflecting their unusual needs for rapid differentiation and replication. The work reported here demonstrated that mouse embryonic cell lines did not tolerate the overexpression of SUMO1, the small ubiquitin-like modifier protein that is covalently attached to many substrates to alter their intracellular localization and functionality. Forced SUMO1 overexpression is toxic to ES cells, and surviving cell populations adapt by dramatically reducing the levels of free SUMO1. Such a response is not seen in differentiated cells or with SUMO2 or with nonconjugatable SUMO1 mutants or in the presence of a SUMO1 "sponge" substrate that accepts the modification. The findings suggest that excess SUMO1 modification of specific substrates is not tolerated by embryonic cells and highlight a distinctive need for these cells to control the levels of SUMO1 available for conjugation.
Effect of Different Blanket Weights on Surface Temperature of Horses in Cold Climates

Abstract The objective of this study was to examine changes in surface temperature of blanketed horses during cold weather. Four mature stock-type horses were used in a 4 × 4 Latin square design. Treatments included 3 different blanket weights (based on g of fiberfill): light weight (LW; 0 g), medium weight (MW; 200 g), heavy weight (HW; 400 g), and a nonblanketed control (CON). Thermographic images were obtained from a standardized lumbar location before blanketing and immediately after cold exposure. During cold exposure, horses were outside with ad libitum access to grass hay and water for 1 hour. Mean temperature was −23°C with a wind chill of −32°C. After 1 hour, horses were brought inside (15°C) and lumbar images immediately recorded. A 30-minute equilibration period was allowed between each sampling period. Analysis of variance was computed using the general linear model procedure of SAS with statistical significance declared at P values ≤ 0.05. There was an overall treatment effect (P = .02) for lumbar temperatures after horses were outside for 1 hour with temperatures measuring 22.3°C, 26.8°C, 30.3°C, and 31.5°C for CON, LW, MW, and HW, respectively. Lumbar temperature was warmer (P ≤ .009) for HW and MW compared with CON and tended to be warmer (P = .10) in LW compared with CON. Change in lumbar temperature decreased significantly (P ≤ .01) in CON compared with all other treatments. In conclusion, wearing a blanket can increase lumbar surface temperature during cold weather with the degree of warmth influenced by blanket weight.
Chemistry on Quantum Computers with Virtual Quantum Subspace Expansion.

Author(s): Urbanek, Miroslav; Camps, Daan; Van Beeumen, Roel; Jong, Wibe A de | Abstract: Several novel methods for performing calculations relevant to quantum chemistry on quantum computers have been proposed but not yet explored experimentally. Virtual quantum subspace expansion [T. Takeshita et al., Phys. Rev. X 10, 011004 (2020)] is one such algorithm developed for modeling complex molecules using their full orbital space and without the need for additional quantum resources. We implement this method on the IBM Q platform and calculate the potential energy curves of the hydrogen and lithium dimers using only two qubits and simple classical post-processing. A comparable level of accuracy would require twenty qubits with previous approaches. We also develop an approach to minimize the impact of experimental noise on the stability of a generalized eigenvalue problem that is a crucial component of the algorithm. Our results demonstrate that virtual quantum subspace expansion works well in practice.
The Evolving Role of Calcineurin Inhibitors in Treating Lupus Nephritis

The overall kidney survival among lupus nephritis patients has improved with currently used induction immunosuppression regimens of corticosteroids and either cyclophosphamide or mycophenolate mofetil; however, there still remains a significant number of lupus nephritis patients who do not achieve remission with these regimens. Investigators have looked at other immunosuppressive regimens for lupus nephritis, and there has been interest in the use of calcineurin inhibitors in this regard. Calcineurin inhibitors are potentially an attractive option because of their established ability to inhibit T cell function, attenuate proteinuria through non-immunologic means, and their safety in pregnancy and lactation. In this review, we discuss the findings and limitations of selected trials that evaluated the use of calcineurin inhibitors in the treatment of lupus nephritis, either with corticosteroids alone or as a component of multitarget therapy when combined with mycophenolate mofetil. There may be a role for calcineurin inhibitors among patients with heavy proteinuria, as well as younger patients with refractory lupus nephritis. The multitarget therapy trials reveal higher rates of remission compared with mycophenolate mofetil alone and cyclophosphamide; however, some trials highlight the possibility of more infectious adverse events. We discuss the need for further study of calcineurin inhibitors in more diverse patient populations and the need for trials with longer follow-up with "hard" endpoints beyond proteinuria reduction, such as worsening CKD or repeat protocol biopsies, given the calcineurin inhibitors ability to reduce proteinuria non-immunologically and thus increased rate of relapse when the drug is tapered. While there may indeed be a space for calcineurin inhibitors to help increase remission rates in lupus nephritis patients, more work is needed to help address the questions the studies available to date have yet to answer.
A lower bound for parallel submodular minimization

In this paper, we study submodular function minimization in the adaptive complexity model. Seminal work by Gr'otschel, Lovasz, and Schrijver shows that with oracle access to a function f, the problem of submodular minimization can be solved exactly with poly(n) queries to f. A long line of work has since then been dedicated to the acceleration of submodular minimization. In particular, recent work obtains a (strongly) polynomial time algorithm with O(n 3) query complexity. A natural way to accelerate computation is via parallelization, though very little is known about the extent to which submodular minimization can be parallelized. A natural measure for the parallel runtime of a black-box optimization algorithm is its adaptivity, as recently introduced in the context of submodular maximization. Informally, the adaptivity of an algorithm is the number of sequential rounds it makes when each round can execute polynomially-many function evaluations in parallel. In the past two years there have been breakthroughs in the study of adaptivity for both submodular maximization and convex minimization, in particular an exponential improvement in the parallel running time of submodular maximization was obtained with a O(logn)-adaptive algorithm. Whether submodular minimization can enjoy, thanks to parallelization, the same dramatic speedups as submodular maximization is unknown. To date, we do not know of any polynomial time algorithm for solving submodular minimization whose adaptivity is subquadratic in n. We initiate the study of the adaptivity of submodular function minimization by giving the first non-trivial lower bound for the parallel runtime of submodular minimization. We show that there is no o(logn/loglogn)-adaptive algorithm with poly(n) queries which solves the problem of submodular minimization. This is the first adaptivity lower bound for unconstrained submodular optimization (whether for maximization or minimization) and the analysis relies on a novel and intricate construction of submodular functions.
Unidirectional Injection-Locked Brillouin Laser in Silicon

We demonstrate injection-locked operation of a silicon-based Brillouin laser for the first time. The unique spatio-temporal inter-modal Brillouin dynamics enable nonreciprocal control and low-phase-noise operation within a monolithically integrated system.
Early Childhood Educators’ Perceptions of Inclusion for Children with Autism Spectrum Disorder

Children with autism spectrum disorders (ASD) are being increasingly included in early childhood settings. As such early childhood teachers need pre-service training to support their knowledge of ASD and preparation to implement evidence-based practices. Mentor teachers and administrators of pre-service clinical sites play an important role in this pre-service training. As such we conducted an explanatory sequential mixed method study to understand how pre-service early childhood teachers’ knowledge of ASD, attitudes towards inclusion of children with ASD, perceptions of challenging behaviors, and familiarity with intervention practices was influenced by the amount of coursework completed, number of field experiences, and mentor teacher/administrator perspectives. The study included surveys and follow up interviews with a subset of survey participants. Findings provide important insights into the pre-service preparation of early childhood teachers to support the inclusion of children with ASD including the importance of mentor teachers’ and administrators’ attitudes towards inclusion, the need to educate pre-service teachers about evidence-based practices, and provide clinical placements that are inclusive of children with ASD. Limitations, practical implications, and recommendations for future research are discussed.
Inferred Clades of Transposable Elements in Drosophila Suggest Co-evolution with piRNAs

Abstract Transposable elements (TEs) are self-replicating “genetic parasites” ubiquitous to eukaryotic genomes. In addition to conflict between TEs and their host genomes, TEs of the same family are in competition with each other. They compete for the same genomic niches while experiencing the same regime of copy-number selection. This suggests that competition among TEs may favor the emergence of new variants that can outcompete their brethren. To investigate the sequence evolution of TEs, we developed a method to infer clades: collections of TEs that share SNP variants and represent distinct TE family lineages. We applied this method to a panel of 85 Drosophila melanogaster genomes and found that the genetic variation of several TE families shows significant population structure that arises from the population-specific expansions of single clades. We used population genetic theory to classify these clades into younger versus older clades and found that younger clades are associated with a greater abundance of sense and antisense piRNAs per copy than older ones. Further, we find that the abundance of younger, but not older clades, is positively correlated with antisense piRNA production, suggesting a general pattern where hosts preferentially produce antisense piRNAs from recently active TE variants. Together these findings suggest a co-evolution of TEs and hosts, where new TE variants arise by mutation, then increase in copy number, and the host then responds by producing antisense piRNAs which may be used to silence these emerging variants.
Some remarks on $$W^{s,p}$$ W s , p interior elliptic regularity estimates

With the help of certain inequalities which we have established for multiplication in Sobolev–Slobodeckij spaces, we will give a simple proof of a version of elliptic estimate for elliptic operators that belong to a certain general class of operators denoted by $$D^{e,q}_m$$ . This version of elliptic estimate is not restricted to second order operators and the coefficients are not assumed to be smooth. Our proof is tailored to accommodate fractional Sobolev spaces and our methods are elementary in nature in the sense that they do not directly appeal to the theory of pseudo-differential operators or Littlewood–Paley theory. The elliptic estimate whose proof is presented in this paper has applications in the existence theory of several important PDEs that appear in the study of Einstein constraint equations in general relativity.
Author’s Reply: Negligence and Normative Import

In this paper we attempt to reply to the thoughtful comments made on our book, Responsible Brains, by a stellar group of scholars. Our reply focuses on two topics discussed in the commenting papers: first, the issue of responsibility for negligent behavior; and second, the broad claim that facts about brain function are normatively inert. In response to worries that our theory lacks normative implications, we will concentrate on an area where our theory has clear relevance to law and legal policy: juvenile responsibility.
Finite Mixture Models, a Flexible Alternative to Standard Modeling Techniques for Extrapolated Mean Survival Times Needed for Cost-Effectiveness Analyses.

Abstract Objectives To compare finite mixture models with common survival models with respect to how well they fit heterogenous data used to estimate mean survival times required for cost-effectiveness analysis. Methods Publicly available overall survival (OS) and progression-free survival (PFS) curves were digitized to produce nonproprietary data. Regression models based on the following distributions were fit to the data: Weibull, lognormal, log-logistic, generalized F, generalized gamma, Gompertz, mixture of 2 Weibulls, and mixture of 3 Weibulls. A second set of analyses was performed based on data in which patients who had not experienced an event by 30 months were censored. Model performance was compared based on the Akaike information criterion (AIC). Results For PFS, the 3-Weibull mixture (AIC = 479.94) and 2-Weibull mixture (AIC = 488.24) models outperformed other models by more than 40 points and produced the most accurate estimates of mean survival times. For OS, the AIC values for all models were similar (all within 4 points). The means for the mixture 3-Weibulls mixture model (17.60 months) and the 2-Weibull mixture model (17.59 months) were the closest to the Kaplan-Meier mean estimate of (17.58 months). The results and conclusions from the censored analysis of PFS were similar to the uncensored PFS analysis. On the basis of extrapolated mean OS, all models produced estimates within 10% of the Kaplan-Meier mean survival time. Conclusions Finite mixture models offer a flexible modeling approach that has benefits over standard parametric models when analyzing heterogenous data for estimating survival times needed for cost-effectiveness analysis.
Localization of the ubiquitin ligase Dma1 to the fission yeast contractile ring is modulated by phosphorylation

The timing of cytokinesis relative to other mitotic events in the fission yeast Schizosaccharomyces pombe is controlled by the septation initiation network (SIN). During a mitotic checkpoint, the SIN is inhibited by the E3 ubiquitin ligase Dma1 to prevent chromosome mis-segregation. Dma1 dynamically localizes to spindle pole bodies (SPBs) and the contractile ring (CR) during mitosis, though its role at the CR is unknown. Here, we examined whether Dma1 phosphorylation affects its localization or function. We found that preventing Dma1 phosphorylation by substituting the six phosphosites with alanines diminished its CR localization but did not affect its mitotic checkpoint function. These studies reinforce the conclusion that Dma1 localization to the SPB is key to its role in the mitotic checkpoint.
Subacute and Chronic Type A Aortic Dissection

The management of subacute and chronic aortic dissection should be treated according to non-dissected aortic disease, with the Class I to IV type of tear influencing management based on extent of dissection. It is important to consider extent of dilation of the aorta, brain protection, and comorbidities. Definitive operations for dilated aortas with subacute or chronic dissection may include aortic valve reimplantation and root replacement, ascending aorta tube graft, or tricuspid valve repair with ascending arch or separate tube graft replacement. An elephant trunk procedure may need to be performed for more extensive dissections.
The folk theorem in repeated games with private monitoring

We show that the folk theorem generically holds for N -player repeated games with private monitoring when each players number of signals is su¢ ciently large. Neither cheap talk communication nor public randomization is necessary. Journal of Economic Literature Classi cation Numbers: C72, C73, D82
Estimation of size–transition matrices with and without molt probability for Alaska golden king crab using tag–recapture data

Size-structured population dynamics models are used for stock assessments of hard to age invertebrate species, such as crabs, and size–transition matrices play an important role in modeling growth in those models. Crabs grow by molting and then incrementing in size. Therefore, the size–transition matrix should ideally contain sub-models for the probability of molt and the growth increment. Size–transition matrices were estimated in an integrated model setting, which included tagging data. Various models, including those that explicitly model molt probability and that include the molt implicitly in the size–transition model, were applied to data for golden king crab (Lithodes aequispinus) in the eastern Aleutian Islands region. Several diagnostic statistics (e.g., covariance matrix, likelihood, AIC, mean growth increment metric, sensitivity of estimates of mature male biomass, and the fits to the tag recapture, catch-per-unit effort, and length frequency data) were used to investigate the implications of the way growth was modeled. Overall, the fit of the integrated model that included the molt probability sub-model was better than that of the model that did not include this sub-model. However, the trends in key stock assessment outputs did not differ markedly between approaches for modeling growth even though the estimates of the size–transition matrices differed.
An Elementary Overview of the Selection of Materials for Service in Oxygen-enriched Environments

The process for selecting materials for use in oxygen or oxygen-enriched environments is one that continues to be investigated by many industries due to the importance to those industries of oxygen systems. There are several excellent resources available to assist oxygen systems design engineers and end-users, with the most comprehensive being ASTM MNL-36, Safe Use of Oxygen and Oxygen Systems: Handbook for Design, Operation and Maintenance, 2nd Edition. ASTM also makes available several standards for oxygen systems. However, the ASTM publications are extremely detailed, and typically designed for professionals who already possess a working knowledge of oxygen systems. No notable resource exists, whether an ASTM or other organizational publication, which can be used to educate engineers or technicians who have no prior knowledge of the nuances of oxygen system design and safety. This paper will fill the void for information needed by organizations that design or operate oxygen systems. The information in this paper is not new information, but is a concise and easily understood summary of selecting materials for oxygen systems. This paper will serve well as an employee s first introduction to oxygen system materials selection, and probably the employee s first introduction to ASTM.
The Genetic Basis of Natural Variation in Drosophila melanogaster

Publisher Summary This chapter reviews that the description of genetic variation in natural populations has reached a point of immediate promise. Straightforward methods have been developed and used to describe genetic variations in terms of allelic differences and of polygenic differences. At both levels, the successful solution of restricted problems has led to a broader understanding of general questions. The identification of electrophoretic enzyme variations with phenodeviants can be regarded as an imminent and major step. It discusses that genetics has always had the unusual property, even for a biological subject, of associating factors at two distant levels of organization, like genes and morphologica1 traits. The genetic structure of an individual is often known in impressive detail, in terms of linkage groups and the like, although the causal pathways to the phenotype soon disappear in a tangle. Development involves a great deal more than genes. The chapter also explores that so far, polygenes have only been associated in this same sense with phenotypic traits.
Schaefer, Jacob: A Brief History of the Combination of Cross Polarization and Magic Angle Spinning

The sections in this article are 1 Background 2 The 1972 Asilomar Experimental NMR Conference 3 Stejskal's First Rotors 4 Combination Spinning Experiments 5 The First CP MAS Experiments 6 Putting Spin on a Billiard Ball 7 Close Encounters with Reviewers 8 The Hand Diagram 9 Waugh's Explanation 10 Retrospective 11 Biographical Sketch
Adaptation of population sizes by competing subpopulations

We present a competition scheme which dynamically allocates the number of trials given to different search strategies. The competition scheme changes the sizes of the subgroups, but also the size of the whole population. The competition scheme is able to combine the strengths of individual search strategies in a synergetic way. This claim is demonstrated by numerical experiments with two difficult functions to be optimized.