cssi/SciSciGPT-SciSciNet huggingface dataset:
Generation of polyclonal rabbit antisera to mouse melanoma associated antigens using gene gun immunization.

Abstract Lymphocytes from patients with melanoma have been used to clone melanoma associated antigens which are, for the most part, nonmutated melanocyte tissue differentiation antigens. To establish a mouse model for the use of these `self' antigens as targets for anti-tumor immune responses, we have employed the mouse homologues of the human melanoma antigens Tyrosinase, Tyrosinase Related Protein-1 (TRP-1), gp100, and MART-1. We sought to generate antisera against these proteins for use in the construction of experimental recombinant and synthetic anti-cancer vaccines, and for use in biologic studies. Using genes cloned from the B16 mouse melanoma or from murine melanocytes, we immunized rabbits with plasmid DNAs coated onto microscopic gold beads that were then delivered using a hand-held, helium-driven `gene gun'. This strategy enabled us to generate polyclonal rabbit sera containing antibodies that specifically recognized each antigen, as measured by immunostaining of vaccinia virus infected cells. The sera that we generated specifically for TRP-1, gp100, and MART-1 recognized extracts of the spontaneous murine melanoma, B16. The identities of the recognized proteins was confirmed by Western blot analysis. The titers and specificities of these antisera were determined using ELISA. Interestingly, serum samples generated against murine MART-1 and gp100 developed antibodies that were cross-reactive with the corresponding human homologues. Recognition of human gp100 and murine Tyrosinase appeared to be dependent upon conformational epitopes since specificity was lost upon denaturation of the antigens. These antisera may be useful in the detection, purification and characterization of the mouse homologues of recently cloned human tumor associated antigens and may enable the establishment of an animal model of the immune consequences of vaccination against `self' antigens.
Complete vesiculation of Golgi membranes and inhibition of protein transport by a novel sea sponge metabolite, ilimaquinone

We have identified a novel natural metabolite, ilimaquinone (IQ), from sea sponges that causes Golgi membranes to break down completely in vivo into small vesicular structures (called vesiculated Golgi membranes [VGMs]). Under these conditions, transport of newly synthesized proteins from endoplasmic reticulum (ER) to the cis-Golgi-derived VGMs is unaffected; however, further transport along the secretory pathway is blocked. Upon removal of the drug, VGMs reassemble rapidly into a Golgi complex, and protein transport is restored. By employing a cell-free system that reconstitutes vesicular transport between successive Golgi cisternae, we provide evidence that the inhibition of protein transport by IQ is specifically due to an inhibition of transport vesicle formation. In addition, like brefeldin A (BFA), IQ treatment prevents the association of beta-COP and ADP-ribosylation factor to the Golgi membranes; however, unlike BFA treatment, there is no retrograde transport of Golgi enzymes into ER.
Direct Use of the High Impedance Surface as an Antenna Without Dipole on Top

High impedance surfaces (HISs) have been proposed and used as substrate for dipoles for realizing low-profile antennas. Here, we show that HISs can be used directly as low-profile antennas with a single feed point, without any dipole on top. The structure is made of only two metallic layers, the patterned surface and the ground plane below, at a subwavelength distance. We analyze two possible feeding mechanisms of an HIS made of dogbone-shaped conductors, though the ideas proposed here can be applied also to other HIS structures. We show that broadside gain of the order of 7-11 dBi can be obtained. We also explain that radiation of the HIS is in part related to a TM-like leaky wave with attenuation constant that is not as small in contrast to other standard high-gain leaky-wave antennas.
The Seasonal Cycle of Wind Stress Curl in Subtropical Eastern Boundary Current Regions

Abstract Historical surface marine wind reports have been processed to define characteristic seasonal distributions of wind-stress curl over the four major eastern boundary current regions of the World Ocean (i.e., the California, Canary, Benguela, and Peru/Humboldt systems) on smaller scales than previously available. Interregional comparisons show that these “classical” coastal upwelling systems are characterized by cyclonic wind-stress curl near the continental boundaries and anticyclonic curl offshore, in association with predominantly equatorward (upwelling favorable) alongshore wind stress. The cross-shore profile of alongshore stress typically has an offshore maximum located some 200 to 300 km from the coast. The decay of the wind stress toward the coast defines a region of cyclonic wind-stress curl, where coastal upwelling is enhanced by curl-induced oceanic upwelling (Ekman pumping). During summer in the respective hemispheres, the region of cyclonic curl expands poleward in each boundary current...
Disposal of Hydrofracking Waste Fluid by Injection into Subsurface Aquifers Triggers Earthquake Swarm in Central Arkansas with Potential for Damaging Earthquake

Only a handful of the thousands of waste disposal wells across the United States have been linked to induced or triggered earthquakes. Still, two well-documented cases—Rocky Mountain Arsenal, Colorado, in the 1960s (Healy et al. 1968) and Paradox Valley, Colorado, in the 1990s (Ake et al. 2005)— demonstrate that fluid injection into the subsurface can trigger earthquakes. The largest event at Rocky Mountain Arsenal was M 5.2, and the largest event at Paradox Valley was M 4.3. The U.S. Environmental Protection Agency provides Underground Injection Control (UIC) regulations administered by the states to protect underground sources of drinking water. However, the UIC does not limit the proximity of waste disposal wells to active seismic zones or to critical facilities ( e.g. , hospitals, schools, or nuclear power plants) based on the potential to induce or trigger earthquakes. Over the last several years, hydraulic fracturing (hydrofracking), a technique used to enhance natural gas recovery, has become widely used in north-central Arkansas (Figure 1). Wastewater, a byproduct of the hydrofracking process, is being injected under pressure into subsurface rocks at eight waste disposal wells (Table 1) in the study area. Since the first waste disposal well became operational in April 2009, the study area has experienced an increase in the rate of magnitude ≥ 2.5 earthquakes, with one in 2007, two in 2008, 10 in 2009, 54 in 2010, and 157 in 2011. The study area has a long history of seismic activity including earthquake swarms in the early 1980s (Chiu et al. 1984) and 2001 (Rabak et al. 2010), so the current earthquake-rate increase may simply reflect another peak in a natural cycle. However, 98% of the recent earthquakes occurred within 6 km of one of three waste disposal wells after the start of injection at those wells. This close spatial and …
Optimization of Angular Position and Location Accuracy in Robots

The use of robots in manufacturing requires a high degree of accuracy in holding a work-piece at a certain position relative to the machine tool. A robot with an extra degree of freedom can bring a workpiece to a predetermined position in infinite ways, as measured by the rotation of its different linkages. This study shows that it is possible to optimize the movement of these linkages, so as to maximize accuracy of angular position and location of the workpiece.
Effects of herbivory on the reproductive effort of 4 prairie perennials.

Background: Herbivory can affect every aspect of a plant's life. Damaged individuals may show decreased survivorship and reproductive output. Additionally, specific plant species (legumes) and tissues (flowers) are often selectively targeted by herbivores, like deer. These types of herbivory influence a plant's growth and abundance. The objective of this study was to identify the effects of leaf and meristem removal (simulated herbivory within an exclosure) on fruit and flower production in four species (Rhus glabra, Rosa arkansana, Lathyrus venosus, and Phlox pilosa) which are known targets of deer herbivory. Results: Lathyrus never flowered or went to seed, so we were unable to detect any treatment effects. Leaf removal did not affect flower number in the other three species. However, Phlox, Rosa, and Rhus all showed significant negative correlations between seed mass and leaf removal. Meristem removal had a more negative effect than leaf removal on flower number in Phlox and on both flower number and seed mass in Rosa. Conclusions: Meristem removal caused a greater response than defoliation alone in both Phlox and Rosa, which suggests that meristem loss has a greater effect on reproduction. The combination of leaf and meristem removal as well as recruitment limitation by deer, which selectively browse for these species, is likely to be one factor contributing to their low abundance in prairies.
Long-period acoustic and seismic measurements and ocean floor currents

Pressure fluctuations caused by a strong ocean floor current are evident during most of an eighty-day-long record of very-low-frequency acoustic ambient noise measured by an instrument on the seafloor in the western Atlantic in the framework of the HEBBLE (High Energy Benthic Boundary Layer Experiment). The differential pressure gauges on the instrument produce useful measurements over a wide frequency band extending from 0.0005 to 16 Hz. The spectrum of current-induced pressure fluctuations is red with a power-law dependence on frequency with an exponent of -1.5. Turbulence in the ocean floor boundary layer is the source of these pressure fluctuations rather than the effects of flow around the transducers. This record of boundary-layer pressure fluctuations is used to predict the effect of seafloor currents on long-period seismograph measurements from the seafloor and from under the seafloor in boreholes. >
Powering Up Dark Silicon: Mitigating the Limitation of Power Delivery via Dynamic Pin Switching

The end of Dennard scaling has led to a large amount of inactive or significantly underclocked transistors on modern chip multiprocessors in order to comply with the power budget and prevent the processors from overheating. This so-called dark silicon is one of the most critical constraints that will hinder the scaling with Moore’s Law in future. While advanced cooling techniques, such as liquid cooling, can effectively decrease the chip temperature and alleviate the power constraints, the peak performance, determined by the maximum number of transistors, which are allowed to switch simultaneously, is still confined by the amount of power pins on the chip package. In this paper, we propose a novel mechanism to power up the dark silicon by dynamically switching a portion of I/O pins to power pins when off-chip communications are less frequent. By enabling extra cores or increasing processor frequency, the proposed strategy can significantly boost the performance compared with the traditional designs.
Association Between Treatment at a High-Volume Facility and Improved Survival for Radiation-Treated Men With High-Risk Prostate Cancer.

Purpose Although the association between higher hospital volume and improved outcomes has been well-documented in surgery, there is little data about whether this effect exists for radiation-treated patients. We investigated whether treatment at a radiation facility that treats a high volume of prostate cancer patients is associated with improved survival for men with high-risk prostate cancer. Methods and Materials We used the National Cancer Database (NCDB) to identity patients diagnosed with prostate cancer from 2004 to 2006. The radiation case volume (RCV) of each hospital was based on its number of radiation-treated prostate cancer patients. We used propensity-score based analysis to compare the overall survival (OS) of high-risk prostate cancer patients in high versus low RCV hospitals. Primary endpoint is overall survival. Covariates adjusted for were tumor characteristics, sociodemographic factors, radiation type, and use of androgen deprivation therapy (ADT). Results A total of 19,565 radiation-treated high-risk patients were identified. Median follow-up was 81.0 months (range: 1-108 months). When RCV was coded as a continuous variable, each increment of 100 radiation-managed patients was associated with improved OS (adjusted hazard ratio [AHR]: 0.97; 95% confidence interval [CI]: 0.95-0.98; P P =.0005; AHR: 0.91, 95% CI: 0.86-0.96, P =.0005). This association remained significant when RCV was dichotomized at 75th (37 patients/year), 90th (60 patients/year), and 95th (84 patients/year) percentiles but not the 50th (19 patients/year). Conclusions Our results suggest that treatment at centers with higher prostate cancer radiation case volume is associated with improved OS for radiation-treated men with high-risk prostate cancer.
Efficacy of Angiotensin-Converting Enzyme Inhibitors and Angiotensin-Receptor Blockers in Coronary Artery Disease without Heart Failure in the Modern Statin Era: a Meta-Analysis of Randomized-Controlled Trials.

Purpose Current practice guidelines support the use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARBs) in patients with coronary artery disease (CAD) without heart failure (HF). However, a number of cited trials were performed prior to the era of prevalent statin use. Our objective was to evaluate the effectiveness of ACEi and ARBs in reducing cardiovascular events as well as the impact of statin therapy.
Contribution of Military Organization and Leadership Factors in Perpetuating Generational Cycle of Preventable Wartime Mental Health Crises: Part One

This is the first of a two-part series of the contribution of organizational and leadership factors in perpetuating a generational cycle of preventable wartime behavioral health crises. The current study includes a comprehensive review of government-initiated studies on the policies, leadership, and organizational structure of military mental healthcare. Among other things, the paper reports on the persistent, serious inadequacies within the U.S. Department of Defense including fragmentation, gross inefficiencies, inadequate coordination, lack of leadership accountability and responsibility both within and across military mental health across all branches. It is hypothesized that these problems have led to past and present wartime crises and are linked to ignoring documented lessons learned. These lessons point to the need for an integrated, coordinated organizational structure with a clear chain-of-command and accountable leadership. Such leadership, it is argued, will ensure adequate planning, preparation, and implementation to meet military mental health needs. While first-order changes have been made over the years through several incremental system corrections that have been tried, second-order (structural and systemic) change is necessary to “fix” the system. The latter section of the paper calls for and describes a complete reorganization of military mental health to improve mental healthcare for military populations.
Method for decision making in virtual library teams

Purpose – The purpose of this paper is to demonstrate an action process method including coordination, monitoring, and backup response, to improve collaborative decision making in online library work teams. Design/methodology/approach – The method was tested using a single factor experimental design where some groups used an action process intervention developed by the researcher, while others used team designated ad hoc process. Participants comprised 26 four person teams. The experiment was performed in a distributed environment where teams used Google chat communication, and a shared Google document to organize, clarify, and evaluate information. Decision performance was measured in two ways. Decision accuracy was measured by the selection of a correct choice from four alternatives. Decision quality was measured by shift in suitability ratings from participants’ individual choice to the correct answer after team discussion. Findings – Teams using an action process method based on monitoring, coordinati...
Bringing Scholarship to the Classroom: Strategies for promoting research through teaching

An issue all academics grapple with is how to strike the desired balance between research and teaching. This balance is heavily influenced by the type of institution where one seeks employment. At liberal arts colleges, excellence is expected in the classroom and a premium is put on faculty student interaction. The expectation, however, is to be teacher-scholar, not simply teacher. And indeed, the desire of most professors at liberal arts colleges is to remain active in their field. With limited time and large teaching demands, the challenge becomes one of continuously making progress on one’s research agenda. When asked to consider how to connect scholarship and teaching on the “Bringing Scholarship to the Classroom: Japan Studies” panel at the ASIANetwork conference in March 2008, I realized I had developed several strategies to link my research and teaching. What I also realized was that all these strategies were influenced by the fact that I was a junior professor vying for tenure. That is, my motivation for connecting scholarship and teaching was largely instrumental. In addition to being able to speak more passionately about topics we research and therefore engage students more fully, I would argue that finding ways to incorporate one’s research in as many classes as possible is a way to better tackle the dual role of teacher-scholar. Connecting research and teaching can accelerate one’s research agenda simply by preventing the liberal arts professor from being torn in too many different directions.
Proximal bicarbonate absorption independent of Na+-H+ exchange: effect of bicarbonate load.

To study proximal tubule bicarbonate absorption that is not due to the neutral Na+-H+ antiporter, mid to late proximal convolutions of the rat kidney were microperfused in vivo with a sodium-free choline solution containing 10(-3) M amiloride. The average sodium concentration resulting from sodium influx was 12 mM. At such low intraluminal [Na+], 10(-3) M amiloride should have inhibited the Na+-H+ antiporter by greater than 95%. When 25 mM HCO3- was in the perfusion fluid, measured total CO2 absorption was 100 pmol.mm-1.min-1. When luminal [HCO3-] was raised to 50 mM, and blood [HCO3-] was also raised to approximately 50 mM to avoid a transepithelial HCO3- concentration gradient, total CO2 absorption increased to greater than 300 pmol.mm-1.min-1. Thus raising intraluminal HCO3- concentration caused a marked increase in total CO2 absorption even though intraluminal [Na+] was low and amiloride was present. Control perfusions containing 140 mM Na+ yielded total CO2 absorption that was approximately 100 pmol.mm-1.min-1 higher than with the respective sodium-free perfusion solutions. In additional experiments, either DCCD or NEM was added to sodium-free perfusion solutions to inhibit H+-ATPase. These inhibitors reduced Na+-H+ independent total CO2 absorption markedly. Our observations suggest that under physiological acid-base conditions, sodium-independent H+ secretion can account for approximately 50% of total HCO3- absorption in mid to late proximal convolutions. This mechanism is stimulated by an increase in ambient HCO(-3) concentration to a degree that might account for the load-dependency of proximal HCO(-3) absorption in these segments of the proximal tubule.(ABSTRACT TRUNCATED AT 250 WORDS)
Pulmonary Embolism Presenting as Abdominal Pain: An Atypical Presentation of a Common Diagnosis

Pulmonary embolism (PE) is a frequent diagnosis made in the emergency department and can present in many different ways. Abdominal pain is an unusual presenting symptom for PE. It is essential to maintain a high degree of suspicion in these patients, as a delay in diagnosis can be devastating for the patient and confers a high risk of mortality if left untreated. Here, we report the case of a 53-year-old male who presented to the emergency department with worsening right upper quadrant abdominal pain with fevers. Initial imaging was benign, although lab work showed worsening leukocytosis and bilirubin. Abdominal pathology seemed most likely, but the team kept PE on the differential. Further imaging revealed acute pulmonary embolus in the segmental branch of the right lower lobe extending distally into subsegmental branches. The patient was started on anticoagulation and improved drastically. This case highlights the necessity of keeping a broad differential and maintaining a systematic approach when dealing with nonspecific complaints. Furthermore, a discussion on the pathophysiology on why PE can present atypically as abdominal pain, as well as fevers, is reviewed. Using this information can hopefully lead to a subtle diagnosis of PE in the future and lead to a life-saving diagnosis.
Mapping Educational Policy Borrowing and Lending

Portnoi provides an overview of educational policy borrowing and lending, highlighting the political nature of these processes. The policy borrowing and lending continuum, with coercive lending on one side and voluntary transfer on the other, provides a useful way for considering the influences and purposes involved in policy borrowing. When intentionally borrowing policies, countries often undertake ‘quick fix’ or symbolic reforms for political reasons such as an upcoming election. In other cases, countries enact policies to comply with international mandates and conventions. Lending countries also have political motivations because they gain cache as ‘star’ systems that others wish to emulate. Global governance organizations also play a significant role, especially through the diffusion of ‘best practice’ reforms.
The role of integrated modeling and simulation in disaster preparedness and emergency preparedness and response: The SUMMIT platform

The Department of Homeland Security, Science and Technology Directorate (DHS S&T), in partnership with the Federal Emergency Management Agency (FEMA), and in collaboration with Sandia National Laboratories, has developed the Standard Unified Modeling, Mapping, and Integration Toolkit (SUMMIT) as a geo-agile platform that enables users to discover and reuse models, integrate them quickly and economically, and apply them in analyses to improve the planning and execution of large and small exercises, planning efforts, and eventually response operations. The SUMMIT technology is innovative and promises to reduce the exercise cycle time by more than an order of magnitude. SUMMIT has been deployed to support National Level Exercises, regional exercises, and international exercises in Sweden, revolutionizing how exercises are designed and conducted. SUMMIT is now in the transition stage, from DHS S&T to the FEMA National Exercise and Simulation Center (NESC), where it will become available to the emergency management community. It will support the National Preparedness System[1] and integrate with the NESC Technology Platform in support of local, state, regional and national level exercises.
The combination of gallium nitrate, rituximab and dexamethasone is effective and safe as a salvage regimen for diffuse large B-cell lymphoma

17510 Background: More than 56,000 new cases of non-Hodgkin’s lymphoma (NHL) will be diagnosed this year in the United States. As our aging patient population develops worsening performance status ...
Mega Sporting Events and Air Pollution: The Case of the Super Bowl

In attempt to improve local economy, local officials often seek to host major sporting events. While previous studies have examined the economic costs and benefits of such events, some prospective externality costs related to changes in ambient air quality have not yet been included in those evaluations. This study focuses on the possible changes of Particulate Matter (PM10) and air quality during the Super Bowl. Particulate Matter are suspended particles which are present in the air, these particles when inhaled can lead to negative health effects. Statistical models are estimated using daily data from EPA’s Air Quality System which measures particle pollution (PM10) as well as air quality (AQI). Estimates using PM10 measurements and AQI reveal similar outcomes, although the Air Quality Index model has a better fit. Significantly higher levels of pollution are observed on Super Bowl Sunday while accounting for a variety of confounding factors. The concentration of pollution varies by distance from the stadium hosting the event, it would be beneficial for future research to have more active monitoring stations on the day of mega-events such as the Super Bowl in order to increase the ability to analyses and understand the environmental consequences of hosting the event.
Management of acute thermal injury

Thermal injury is a common cause of trauma that results in significant costs to both the individual and to society. The mechanism of injury whether it is flash or flame burns, scald injury, or electrical burn provides important prognostic information, and is critical information in the management of this patient population. Although outcomes and survival have improved over time as a result of proper resuscitation and immediate transfer to tertiary care centers when appropriate, providers must be careful to recognize infectious complications, specifically wound infections and pneumonia promptly so that antibiotic therapy can be initiated. In this process, appropriate fluid administration, supportive care, and wound management in the critical care setting are vital to improving the overall recovery and quality of life of patients with burns.
Characteristics of a Mild Traumatic Brain Injury Sample Recruited Using Amazon's Mechanical Turk

Abstract Background Several barriers exist in the recruitment of individuals with a history of mild traumatic brain injury (mTBI). The current study is the first to examine whether crowdsourcing, which has been used in other clinical populations, is useful in the recruitment of those with mTBI. Objective To examine whether Amazon's Mechanical Turk (MTurk), an online crowdsourcing platform, is a useful tool in the recruitment of individuals with a history of mTBI and to examine the injury and psychological characteristics of individuals who report a history of mTBI. Design Retrospective, cross-sectional study. Setting Online. Participants A total of 468 MTurk workers (215 who reported mTBI history on the screener, 253 who did not). Methods Comparison of MTurk participants ("workers") who report a history of mTBI on a one-item screener and/or a more comprehensive mTBI assessment tool (ie, the Ohio State University Traumatic Brain Injury Identification Method [OSU TBI-ID]) with workers who do not report mTBI history. Main Outcome Measures Prevalence rates of mTBI in the MTurk sample (one-item screener and/or OSU TBI-ID), associations between self-reported mTBI with history of psychological disorders and current psychological symptoms (ie, selected Patient-Reported Outcomes Measurement Information System scales). Results Of workers who reported a history of mTBI on the screener, 169 (79%) met mTBI criteria on the OSU TBI-ID. Compared with those who denied history of mTBI on both the screener and OSU TBI-ID, workers who reported a history of mTBI on both measures were more likely to have a history of diagnosed depression ( P = .008), anxiety ( P = .007) or attention deficit-hyperactivity disorder ( P = .04), and were more likely to currently experience cognitive ( P = .01) and sleep disorder symptoms ( P = .003). Conclusions Workers recruited via MTurk with history of mTBI show similar rates of psychological disorder history and current symptoms to samples recruited via noncrowdsourcing methods in previous studies. MTurk may be a useful recruitment tool in the mTBI population and should be used in future studies of outcomes after mTBI. Level of Evidence III
A Vermont Woman Meets the Anti-Slavery Movement: Eliza Marsh and her “Book of Sentiments”

Though she was an ordinary person, not a leader or organizer, Eliza Marsh's life shows the importance of rural women to abolitionism, and suggests this female contribution was undervalued, as men, ...
Gradient-based inverse risk-sensitive reinforcement learning

We address the problem of inverse reinforcement learning in Markov decision processes where the agent is risksensitive. In particular, we model risk-sensitivity in a reinforcement learning framework by making use of models of human decision-making having their origins in behavioral psychology and economics. We propose a gradient-based inverse reinforcement learning algorithm that minimizes a loss function defined on the observed behavior. We demonstrate the performance of the proposed technique on two examples, the first of which is the canonical Grid World example and the second of which is an MDP modeling passengers' decisions regarding ride-sharing. In the latter, we use pricing and travel time data from a ride-sharing company to construct the transition probabilities and rewards of the MDP.
Abstract A083: A phase Ib study of the combination of MLN0128 (dual TORC1/2 inhibitor) and MLN8237 (Aurora A inhibitor, alisertib) in patients with advanced solid tumors

Background: MLN0128 is an oral inhibitor of mTOR kinase and mTORC1/2 signaling. Alisertib is an oral inhibitor of Aurora A kinase. Senescence and upregulation of genes in the PI3K/AKT/mTor pathway have been observed in triple-negative breast cancer (TNBC) patient-derived xenograft models treated with alisertib, with greater tumor growth inhibition demonstrated in combination with MLN0128 as compared to each agent alone. An investigator-initiated trial was developed to evaluate the combination of MLN0128 and alisertib in patients with advanced solid tumors, followed by an expansion cohort in metastatic TNBC and other selected cancers. The goals of this ongoing study are to evaluate safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of the combination. Results of dose escalation are presented here. Methods: Patients with advanced solid tumors refractory to standard therapy were treated orally at escalating doses with the combination of MLN0128 daily on a continuous schedule and alisertib twice daily (BID) on days 1-7 of a 21-day cycle. Dose escalation was conducted according to a standard 3+3 design. Key eligibility criteria included HgbA1c max was 24.7 (± 13.6) ng/mL for MLN0128 and 1049 (±363) ng/mL for alisertib at combination MTD doses. MLN0128 AUC was 128.2 (±72.7) ng/mLxhr and alisertib AUC 0-8 was 6119 (±2331) ng/mlxhr at these doses. Conclusions: MLN0128 2mg daily on a continuous schedule and alisertib 30mg BID days 1-7 of a 21-day cycle is the MTD of the drug combination. An expansion cohort in patients with TNBC and other selected cancers is currently enrolling at this dose. Functional imaging and serial tumor biopsies are being integrated into this cohort to assess the pharmacodynamic interactions of the combination. Citation Format: S. Lindsey Davis, Elaine T. Lam, Bradley R. Corr, Cindy L. O9Bryant, Ashley Glode, Nichole Adler, Todd M. Pitts, John J. Tentler, Anna Capasso, Kyrie Dailey, Natalie J. Serkova, Colin D. Weekes, Daniel L. Gustafson, Christopher H. Lieu, Wells A. Messersmith, Stephen Leong, S. Gail Eckhardt, Jennifer R. Diamond. A phase Ib study of the combination of MLN0128 (dual TORC1/2 inhibitor) and MLN8237 (Aurora A inhibitor, alisertib) in patients with advanced solid tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A083.
The pharmacokinetics and analgesic effects of extended-release buprenorphine administered subcutaneously in healthy dogs.

Buprenorphine is a partial μ agonist opioid used for analgesia in dogs. An extended-release formulation (ER-buprenorphine) has been shown to provide effective analgesia for 72 hr in rats and mice. Six healthy mongrel dogs were enrolled in a randomized, blinded crossover design to describe and compare the pharmacokinetics and pharmacodynamics of ER-buprenorphine administered subcutaneous at 0.2 mg/kg (ER-B) and commercially available buprenorphine for injection intravenously at 0.02 mg/kg (IV-B). After drug administration, serial blood samples were collected to measure plasma buprenorphine concentrations using liquid chromatography/mass spectrometry detection. Heart rate, respiratory rate, body temperature, sedation score, and thermal threshold latency were recorded throughout the study. Median (range) terminal half-life, time to maximum concentration, and maximum plasma concentration of ER-buprenorphine were 12.74 hr (10.43-18.84 hr), 8 hr (4-36 hr), and 5.00 ng/ml (4.29-10.98 ng/ml), respectively. Mild bradycardia, hypothermia, and inappetence were noted in both groups. Thermal threshold latency was significantly prolonged compared to baseline up to 12 hr and up to 72 hr in IV-B and ER-B, respectively. These results showed that ER-buprenorphine administered at a dose of 0.2 mg/kg resulted in prolonged and sustained plasma concentrations and antinociceptive effects up to 72 hr after drug administration.
The Cotherapy Situation as a Model for Group Therapist Training: Its Pitfalls and Pratfalls

Training programs in group therapy have recently been using the cotherapy model as a setting in which to teach group therapy techniques. The purpose is not necessarily to prepare the student for cotherapy but to introduce group therapy as a tool.
Epilepsy in children with cerebral palsy

Cerebral palsy (CP) is often associated with epilepsy. We sought to determine the frequency with which epilepsy is associated with CP and to define the relationship in terms of gender, etiology, pathophysiology, and topographical parameters. This was a retrospective analysis of children with CP treated at the University Clinical Centre of Kosova (UCCK) in Prishtina, over a 5-year period, 2000-2005. A total of 154 children (aged 7-15 years) with CP, treated at the UCCK were enrolled. CP was associated with epilepsy in 63 cases (40.9%), 29 (46.0%) of which had spastic quadriparetic CP; 17 (27.0%), diplegic CP; and 15 (23.8%), hemiparetic CP. For the quadriparetic children, there was no significant difference in the number associated with epilepsy between the genders (female, 45.2%; male, 46.9%). Epilepsy was frequently associated with CP, with the spastic quadriparetic group being most affected. There was no large difference in the number associated with epilepsy between the right and left hemiparetic CP cases. Tonic-clonic epilepsy was more frequently associated with hemiparetic CP, whereas partial-type epilepsy was more often associated with quadriparetic CP.
Simultaneous extraction of mRNA and microRNA from whole blood stabilized in tempus tubes

Studies of mRNA and miRNA expression profiling increasingly use stabilized whole blood. Commercial RNA extraction kits do not provide information about the simultaneous recovery of both mRNA and miRNA. This study evaluated yield, quality, integrity and representation of mRNA and miRNA from whole blood stabilized in Tempus tubes using three RNA extraction kits; two filter-based (Tempus and Norgen) and one bead-based (MagMax; manual vs. semi-automated, and with and without DNase treatment). All RNA extraction kits and methods resulted in similar yields of mRNA (total RNA yield, quality, integrity and representation) whereas there were differences in yields of miRNA. MagMax, either manual or semi-automated, with or without DNase treatment, yielded 1.6–2.2-fold more miRNA than Tempus and Norgen kits. In addition, MagMax and Norgen methods gave greater than 12-fold more and 3.3-fold less enrichment of specific miRNA targets, respectively, in comparison to Tempus extraction reagents. This study identified MagMax kit for simultaneous recovery of both mRNA and miRNA from whole blood collected in Tempus tubes.
Do good stories make for good policy

�� First-person narrative accounts have long been a staple of policy debates. Reform advocates understand that policy wonks and academics may be persuaded with a regression analysis, but that the general public and legislators are more likely to be moved by a compelling story. Because of their simplicity and transparency, narratives can crystallize and mobilize public opinion, and force an issue to the top of the policy agenda. Personal stories are accordingly employed as a matter of routine by journalists, legislators, and advocates for every conceivable cause. Indeed, on Capitol Hill, the standard practice was described by the Los Angeles Times as “when studies don’t sway, bring on the victims” (Lawrence 1990). Health care policy is routinely influenced by stories. Stories about patients being refused treatment by emergency rooms led to a federal prohibition of patient-dumping. Stories about bad outcomes after rapid postpartum discharges led to a federal prohibition on “drive-through deliveries.” Stories about various forms of misconduct by managed care organizations have fueled the drive to enact a federal patients’ bill of rights and spurred most of the states to enact such legislation. Stories about senior citizens who travel to Canada and Mexico to buy prescription drugs have prompted some politicians to propose price controls and others to support a Medicare prescription drug benefit. Stories may be effective in mobilizing support for a policy, but it is quite a different question whether sound policies will result. When atypical or incomplete stories are used as the basis for public policy, “reform”
Adenomatous polyposis coli (APC) protein causes hypersensitivity of mouse embryonic fibroblast cell lines to DNA-alkylating agent methylmethane sulfonate through base excision repair pathway

1961 The role of adenomatous polyposis coli (APC) has been implicated in various cellular functions including cell migration, cell-cell adhesion, cell cycle control, chromosomal segregation and apoptosis. Mutations in APC gene impair these functions and render cells susceptible to tumorigenesis. Recently, we discovered a novel role of APC in DNA base excision repair (BER) and showed that APC interacts with DNA polymerase β (pol-β) and flap endonuclease 1 (Fen-1) and interferes long-patch (LP)-BER by blocking strand-displacement synthesis. Many times, the chemotherapeutic drugs induce DNA-alkylation damage, which is primarily repaired by the BER pathway. Thus, the efficacy of such drugs can be increased by APC resulting in the blockage of LP-BER. In the present study, we tested this hypothesis by using isogenic wild-type and pol-β-knockout mouse embryonic fibroblast cell lines in which the APC gene was knocked down by the SiRNA technique and treated with methylmethane sulfonate (MMS). The MEF-APC+/+/polβ-/- cells were hypersensitive to MMS treatment compared to the MEF-APC+/+/polβ+/+ cells. However, once the APC gene was knocked down, these cells became more resistant to MMS treatment, suggesting that the MMS-induced hypersensitivity was associated with APC. We then determined whether the hypersensitivity of MEF-APC+/+/polβ-/- and MEF-APC+/+/polβ+/+ cell lines were due to decreased pol-β-independent and pol-β-dependent LP-BER pathways, respectively. The results of in vivo and in vitro LP-BER assays supported our findings. Further, APC-mediated hypersensitivity to MMS treatment was correlated with increased apoptosis of APC+/+/polβ-/- and MEF-APC+/+/polβ+/+ as compared to APC-/-/polβ-/- and MEF-APC-/-/polβ+/+ cells. These results suggest that an increased level of APC can increase the efficacy of DNA-alkylating drugs used as a curative therapy. Supported by NCI-NIH (CA-097031 and CA-100247) to SN.
More on Veils: Reply to Levitt and Mueller

I thank Justin Levitt and Derek Mueller for their thoughtful replies to my article, which have helped me (at least) to understand my own position better. I also thank the Florida Law Review for giving me the opportunity to briefly respond to them. I can't (and probably couldn't) give detailed or persuasive answers to their questions; instead, I want to flag some issues that they bring up, and which deserve fuller consideration than I was able to give in my article.
Adolescent microglia play a role in executive function in male mice exposed to perinatal high fat diet

In humans, excessive gestational weight gain during pregnancy is associated with an increased risk for executive function deficits in the offspring. Our previous work has confirmed this finding in mice, as offspring from dams fed a 60% high fat (HF) diet during breeding, gestation, and lactation demonstrate impulsive-like behavior in the 5 choice serial reaction time task (5CSRTT). Because the prefrontal cortex (PFC), which plays a key role in executive function, undergoes substantial postnatal adolescent pruning and microglia are actively involved in synaptic refinement, we hypothesized that microglia may play a role in mediating changes in brain development after maternal HF diet, with a specific focus on microglial activity during adolescence. Therefore, we treated male and female offspring from HF or control diet (CD) dams with PLX3397-formulated diet (PLX) to ablate microglia during postnatal days 23-45. After PLX removal and microglial repopulation, adult mice underwent testing to evaluate executive function. Adolescent PLX treatment did increase the control male dropout rate in learning the basic FR1 task, but otherwise had a minimal effect on behavior in control offspring. In males, HF offspring learned faster and performed better on a simple operant task (fixed ratio 1) without an effect of PLX. However, in HF offspring this increase in FR1 responding was associated with more impulsive errors in the 5CSRTT while PLX eliminated this association and decreased impulsive errors specifically in HF offspring. This suggests that adolescent PLX treatment improves executive function and particularly impulsive behavior in adult male HF offspring, without an overall effect of perinatal diet. In females, maternal HF diet impaired reversal learning but PLX had no effect on performance. We then measured gene expression in adult male PFC, nucleus accumbens (NAC), and amygdala (AMG), examining targets related to synaptic function, reward, and inflammation. Maternal HF diet increased PFC synaptophysin and AMG psd95 expression. PFC synaptophysin expression was correlated with more impulsive errors in the 5CSRTT in the HF offspring only and PLX treatment eliminated this correlation. These data suggest that adolescent microglia may play a critical role in mediating executive function after perinatal high fat diet in males.
Innate and adaptive immune responses in Parkinson's disease

Parkinson's disease (PD) has classically been defined as a movement disorder, in which motor symptoms are explained by the aggregation of alpha-synuclein (α-syn) and subsequent death of dopaminergic neurons of the substantia nigra pars compacta (SNpc). More recently, the multisystem effects of the disease have been investigated, with the immune system being implicated in a number of these processes in the brain, the blood, and the gut. In this review, we highlight the dysfunctional immune system found in both human PD and animal models of the disease, and discuss how genetic risk factors and risk modifiers are associated with pro-inflammatory immune responses. Finally, we emphasize evidence that the immune response drives the pathogenesis and progression of PD, and discuss key questions that remain to be investigated in order to identify immunomodulatory therapies in PD.
Assessing Cannabis Demand: A Comprehensive Review of the Marijuana Purchase Task

The marijuana purchase task (MPT) is a behavioral economic measure of individualized cannabis value (i.e., demand). The MPT follows purchase tasks for other substances (e.g., alcohol, tobacco), though presents with unique caveats due to its mixed illicit status, non-uniform units of purchase and use, and substantial within substance variability in strain, potency, and quality. As the regulatory climate surrounding purchase and use of cannabis continues to evolve in the USA and globally, rigorous assessment of cannabis use and value are of the utmost importance. This study represents the first comprehensive review of investigations utilizing the MPT. Searches through PubMed and Web of Science databases by two independent coders identified 15 empirical articles referencing the use of an MPT and were published through the year 2019. Articles were coded for demographic and procedural characteristics, structural characteristics of the MPT itself, data analytic characteristics, and relationships with cannabis-related outcomes. Rigorous assessment of demand for cannabis is essential with respect to the broad public health issues surrounding cannabis legalization. We have synthesized the research presented herein and comment on vital considerations for subsequent MPT work, including recommendations for a unified approach to using the MPT in subsequent research.
Implicit bias, officer wellness, and police training

Abstract As part of the Department of Justice funded National Initiative for Building Community Trust and Justice, I worked in the field alongside police officer trainers to develop and implement anti-bias officer trainings, with the objective to translate the science of bias into a language that resonated for officers. My commitment to reflexivity, adaptability, and the co-production of knowledge were critical to deploying anti-bias training to help officers better understand how their safety is directly tied to the safety of the most marginalized communities they police. This chapter draws on my experiences in the field delivering anti-bias trainings, foregrounding reflections from officers about the ways in which implicit biases interfere with officers’ most frequently listed professional priorities: going home safely and protecting the communities they serve.
Moving on from Genre Analysis: An update and tasks for the transitional student

Abstract The author first discusses the evolution of two major concepts in Genre Analysis, “genre”, particularly as it relates to purpose and text prototypicality, and “task”, particularly as it relates to context. Then, she draws from evolving understandings of these concepts, the work of Swales and Feak, 2012a , Swales and Feak, 2012b and of Rhetorical Genre Studies scholars ( Bawarshi and Reiff, 2010 , Prior, 2001 ), to describe pre-writing tasks completed by transitional bilingual (Spanish/English) secondary school students as they prepared responses to prompts for a college application essay, The Personal Statement, a challenging, seemingly anomalous, genre.
Increasing ground-layer plant taxonomic diversity masks declining phylogenetic diversity along a silvicultural disturbance gradient

Most plant diversity in temperate deciduous forests is found in the ground layer, but nearly all studies comparing plant community assembly using taxonomic, trait, and phylogenetic diversity indice...
Black TiO 2 on Nanoporous Substrates for Improved Solar Vapor Generation

We report a black TiO 2 on nanoporous anodic alumina oxide (AAO) architecture for improved solar vapor generation. The efficiency reached 85.3% under one sun illumination, corresponding to a vapor generation rate of 1.29 kg/(m2·h).