cssi/SciSciGPT-SciSciNet huggingface dataset:
Coordinating Self-Renewal and Proliferation via MLL1-HOX Pathways and Beyond

Abstract SCI-28 Epigenetic regulation of gene expression plays a central role in normal hematopoietic stem cell (HSC) maintenance and leukemogenesis. The histone methyltransferase, MLL1, is essential for the maintenance of HSCs and is a common target of chromosomal translocations that result in acute leukemia. To discover genetic networks regulated by MLL1 in HSCs, we identified genes that were acutely deregulated upon Mll1 loss in HSCs, using a conditional knockout approach and lineage-negative, c-Kit+, Sca-1+, CD48-negative (LSK/CD48neg) cells. The majority of genes that changed were proliferation-associated genes, upregulated in Mll1−/− LSK/CD48neg cells. This reflected the fact that Mll1-deficient HSCs exhibit increased proliferation in vivo, a phenotype previously documented using the Mx1-cre inducible model. To determine whether the increased proliferation was cell-intrinsic, we performed single cell proliferation studies in serum-free medium containing SCF, IL-11, and Flt3L. We found that Mll1−/− LSK/CD48neg single cells entered the cell cycle earlier and that each cell cycle was shorter than wild-type controls. Evidence for failure to suppress lineage-specific gene expression was also observed; specifically, five percent of the upregulated genes encoded erythroid-specific proteins. These included erythroid transcriptional regulators such as GATA1 and KLF1, but also structural proteins such as spectrin, KEL, and EpoR. The relationship between erythroid-lineage genes and Mll1 was unique, since no other lineage-specific programs were upregulated in Mll1−/− LSK/CD48neg cells. Among the genes downregulated upon Mll1 loss, the largest category was comprised of transcriptional regulators, including Mecom, Pbx1, and Prdm16, which are known to control HSC self-renewal and quiescence. As observed in many other tissues, Mll1−/− LSK/CD48neg cells also exhibited reduced Hoxa9 expression. Interestingly, not all identified MLL1 target genes required menin, a cofactor thought to participate in directing MLL1 to particular genomic loci in vivo, and not all targets were Mll1-dependent in nonhematopoietic tissues. Chromatin immunoprecipitation and functional studies suggest that the identified genes act within a series of parallel pathways as direct transcriptional targets of MLL1. Interestingly, reexpression of Prdm16 alone could rescue Mll1-deficient cells from rapid attrition in bone marrow chimeras. Furthermore, Prdm16 corrected the hyperproliferation phenotype of Mll1−/− LSK/CD48neg cells. These data demonstrate that MLL1 coordinately regulates proliferation, lineage-specific gene expression programs, and self-renewal. By elucidating the normal MLL1-dependent transcriptional network within HSCs, we show that this pathway is overlapping but distinguishable from the leukemogenic pathway, suggesting that targeted therapy with minimal side effects on hematopoiesis will be feasible. Disclosures: No relevant conflicts of interest to declare.
198. CD4+ IL13Rα2-Specific CAR T Cells Exhibit Potent Effector Function Against Glioblastoma

Adoptive T cell transfer, including chimeric antigen receptor (CAR) T cell therapy, has been successfully applied to the treatment of multiple types of cancer, but the variation in response rates among patients remains an important issue. Recent studies have demonstrated that CAR T cells vary in function and persistence, depending on the specific T cell subpopulation that is engineered and the phenotype of the final T cell product. Specifically, a starting population of central memory T cells (Tcm) has been shown to improve persistence and efficacy of CAR T cell therapy. Tcm consist of both CD4+ and CD8+ pools, but little is known about the contribution of each subset for CAR T cell function. Notably, although CD8+ T cells have long been considered the primary cytotoxic effector population, CD4+ T cells have also been shown to mediate anti-tumor response against some solid tumors which is CD8-independent. It is thus critical to identify the optimal composition of CD4+ and CD8+ CAR T cells for mediating the maximal anti-tumor effect. Here, using both in vitro and in vivo glioblastoma (GBM) models, we examined the anti-tumor activity of IL13Rα2-specific CAR T cells engineered from purified CD4+ or CD8+ Tcm pools. Surprisingly, we discovered a superior antitumor response from CD4+ IL13Rα2-CAR T cells as compared to CD8+ CAR T cells. After co-culture with primary patient-derived GBM cells in vitro, CD4+ CAR T cells displayed more potent tumor killing as compared to CD8+ CAR T cells, especially when effector cell numbers were more limited. Consistently, CD4+ CAR T cells maintained better effector function in vitro when re-challenged with tumor. These CD4+ CAR T cells produced higher levels of cytokine as compared to CD8+ T cells, a difference that was further maintained after tumor re-challenge. We also assessed whether the CD4 versus CD8 composition of the IL13Rα2-CAR T cell product would impact therapeutic efficacy in vivo using primary patient-derived GBM lines orthotopically implanted in NSG mice. When injected intracranial into GBM-bearing mice, the CD4+ CAR T cells resulted in durable antitumor efficacy, mediating tumor-free survival for over 200 days in 7of 7 experimental animals, which was unaffected by mixing with 10% of CD8+ CAR T cells. While CD8+ CAR T cells, as well as 50%-50% or 10%-90% CD4-CD8 mixed populations, also mediated significant antitumor activity, the majority of mice recurred and showed a less durable therapeutic response. These results demonstrate that CD4+ CAR T cells can have potent effector function and suggest that, for at least IL13Rα2-CARs, CD4+ T cells mediated superior anti-tumor immune responses as compared to CD8+ T cells. These studies provide important insight to further elucidate the optimal composition of the CAR T cell product for the treatment of cancer.
State Mandates, Housing Elements, and Low-income Housing Production:

In order to create low-income housing opportunities and mitigate exclusionary zoning, in 1968 Congress mandated that municipalities receiving comprehensive planning funds must create a housing element. In tandem, many states mandated that municipal housing elements must accommodate low-income housing needs. After examining empirical research for California, Florida, Illinois, and Minnesota, this review found aspirational success because those states rewarded the municipal planning process. In order to increase low-income housing, this review argues for state housing policy reform. Under US Department of Housing and Urban Development’s revised fair housing rule, which requires an assessment of local data, states can no longer ignore the exclusionary behavior of municipalities.
Remarks on the Concepts of Domain and Field

Every inquiry, or at least every inquiry that aims at knowledge, has a subject-matter — that which the inquiry is about, which is the object or set of objects studied. Let us, for the sake of brevity, and without further analysis for the present, call the set of things studied in an investigation the domain of the inquiry, and the particular things that make up the domain the items of the domain. (These “items” might, in particular inquiries, be spoken of as “objects,” “processes,” “behavior,” “facts,” or in still other ways [“fields,” “virtual bosons”]; but such ways of speaking involve problems which, being irrelevant to present purposes, I wish to avoid by speaking more generally and neutrally of “items.” Sometimes it is convenient to speak of classes of items as themselves items which are objects of investigation.) The domain of a scientific inquiry generally includes many items, the items studied being considered as examples of types or classes or sets of items.
Rough Control: A Perspective

Observing the current state of commercial and industrial AI, control and hybrid systems are said to have the highest potentials for massive practical applications of rough set theory. After a brief description of the control problem and fuzzy systems, the principles of rough control and a scenario of fine temperature control are discussed.
Secure Fog Computing for Smart Living

Fog computing is an attractive model for systems in which people live inside of the system with the goal of living smarter.This panel presentation discusses the security and privacy issues of people living within a Fog.
Laparoscopic removal of migrated intrauterine device

Intrauterine device (IUD) is a popular long-acting reversible contraceptive device with an estimated rate of use of about 5.3%. It is highly effective but not without complications, one of which is uterine perforation. The patient was a 32-year-old female who presented with nausea, vomiting and right upper quadrant abdominal pain that was tender on palpation. CT scan was performed and they found signs of acute calculous cholecystitis with incidental finding of a migrated IUD in the left lateral mid-abdomen within the peritoneal cavity. She underwent a laparoscopic cholecystectomy followed by a successful IUD retrieval. Most uterine perforations occur at the time of insertion; however, partial perforation with subsequent delayed complete perforation may also occur. This case emphasises the importance of a full workup for a missing IUD and that, if incidentally found, IUDs can be removed safely laparoscopically in conjunction with another procedure.
The development of gratitude in seven societies: Cross-cultural highlights

This study aimed to examine children’s expression of gratitude in Brazil, China, Guatemala, Russia, South Korea, Turkey, and the United States. Participants (N = 2,265) consisted of 7- to 14-year-olds (M = 10.56, SD = 2.09; 54.4% girls). Using hierarchical cluster analysis, we found four clusters of gratitude expression: (a) Russia and Turkey (moderate–high expression of connective, low concrete, and moderate verbal gratitude), (b) Brazil and the United States (low connective, higher rates of concrete, and moderate–high rates of verbal gratitude), (c) China and South Korea (higher rates of connective, lower concrete, and lower–moderate verbal gratitude), and (d) Guatemala (lower rates of concrete and connective gratitude, and higher rates of verbal gratitude). In addition, we found common trends in age-related differences for verbal and concrete gratitude among most societies. These findings support the argument for diligence in avoiding implicit generalizations based on research conducted mostly in Western Educated Industrialized Rich Democratic (WEIRD) societies.
Role of Population Genetics in the Sterile Insect Technique

The detection and analysis of genetic variation in natural and laboratory populations are reviewed. The application of population genetic methods and theory can help to plan and evaluate the implementation of area-wide integrated pest management (AW-IPM) programmes that use the sterile insect technique (SIT). Population genetic studies can play an important role in estimating dispersal rates and thus gene flow among target populations, determining if sibling species exist, establishing the origin of outbreaks or reintroductions, and supporting the quality control of mass-reared colonies. The target’s population history may be examined, in terms of “bottlenecks”, range fragmentations, and expansions. Genetic methods can be helpful in distinguishing wild insects from released sterile or substerile ones, and in ascertaining, together with mating cross-compatibility studies, the compatibility of mass-reared colonies with target wild insects.
Immunodeficiency-Associated Lymphoproliferative Disorder

Immunodeficiency-associated lymphoproliferative disorders (LPDs) can occur in the setting of HIV infection, after transplantation (posttransplant lymphoproliferative disorder, PTLD), or in other clinical conditions including primary immunodeficiency or the use of immunosuppressive drugs (iatrogenic immunodeficiency-associated LPD). LPDs in the setting of immunodeficiency share similar morphologic features, with a broad spectrum of findings from polymorphous lymphoplasmacytic proliferations to aggressive lymphoma. In patients diagnosed with an immunodeficiency-associated LPD, a staging bone marrow is recommended as part of the initial workup. This chapter illustrates the common bone marrow findings in immunodeficiency-associated LPD.
Hope communication as a predictor of documented and undocumented Latina/o high school students’ college intentions across an academic year

ABSTRACTDrawing from hope theory, we examined whether hope communication predicted undocumented and documented U.S. Latina/o youth’s college intentions across an academic year. With three waves of survey data from 172 documented and 253 undocumented Latina/o high school students, auto-regressive cross-lagged analyses revealed that parent, teacher, and friend hope communication at the beginning of the year indirectly increased students’ college intentions by the end of the year. A trend emerged whereby undocumented students reported significantly less hope communication and weaker college intentions than documented students within most of the waves. Our findings suggest that hope communication has the potential to increase the educational, economic, and social mobility of Latina/o immigrant students by increasing their intentions to attend college.
Steady inductive helicity injection and its application to a high-beta spheromak

A steady inductive helicity injection (SIHI) method is described that has the following properties: (a) helicity is injected at a nearly constant rate; (b) neither magnetic energy nor helicity flow out of plasma at any time; (c) no open field lines penetrate the walls; (d) the equilibrium is produced in a close-fitting flux conserver; (e) a rotating magnetic structure is produced directly; and (f) in the frame of the rotating field, the current profile is nearly time independent and nearly optimum for the application discussed. SIHI can be applied to any toroidal plasma. Application of SIHI to a high-beta spheromak is described.
Biochemical Applications of Fluorescence Spectroscopy

Fluorescence spectroscopy and fluorescence detection are major tools in the investigation of biomolecular systems, both in terms of their structure and function. The fluorescence may be elicited from fluorophores intrinsic to the system, or introduced through fluorescent probes which interact with specific components. In either case, minute quantities or changes can be determined, even approaching the single-molecule level.
Visual Displays for Communication in Cetaceans

Social mammals use facial signals and body postures, often highlighted by coloration, for well-developed visual communication. African forest monkeys (Cercopithecus sp.), for example, display an impressive repertoire of stereotyped head movements and facial expressions for courtship, aggression, fear, and appeasement (Kingdon, 1980). Thomson’s gazelles (Gazella thornsoni) rapidly alert conspecifics to danger by a tense, upright stance, directed gaze, and often a twitching of their edge-receptive flank, which is marked with an eye-catching black longitudinal stripe (Estes, 1967; Walther, 1969). This sequence of subtle body movements produces a “Morse code” of visual information about the potential threat of an approaching predator. To the untrained observer only obvious alarm signals and warnings, such as running and stotting (a stiff-legged, bounding gait), are appreciable (Caro, 1988). It recently has been found that some mammalian species display different warning signals for different predators (Seyfarth et al., 1980; Sherman, 1985), and this extra sophistication beyond mere communication of danger is probably widespread among animals.
Ultrastructure of Invertebrate Synapses

Invertebrate chemical synapses are characterized by a diversity of presynaptic vesicles and membrane-associated structures. They have in common with classical chemical synapses of vertebrates a pair of parallel densified membranes with a uniformly wide intercellular cleft containing intracleft material, a presynaptic aggregation of clear or dense-cored vesicles, and usually one or more mitochondria with nearby microtubules in the synaptic terminal or axonal varicosity. At these conventional synaptic foci some vesicles have thin filamentous connections to the presynaptic membrane. Invertebrate neuromuscular junctions often appear morphologically similar to interneuronal synapses because they lack the postsynaptic infoldings of vertebrate muscles. Electrical synapses presumably appear in all metazoa as morphologically identifiable gap junctions in which there is cytoplasmic continuity between two cells separated by a 2–3-nm-wide intercellular gap. In addition to these conventional synapses there are dyads, spine synapses, neuro-secretory-motor junctions, neuromuscular junctions with presynaptic dense bars, and gap junctions with vesicles in various invertebrate groups.
MicroRNA Regulation in Osteocytes

The role of microRNA (miR) regulation during the processes of bone homeostasis and remodeling has been a key research topic in recent years. Extensive work has gone into understanding the role of miR regulation in osteoblasts and osteoclasts; however, the role of miRs in osteocytes remains unclear. The aim of the present review is to describe the current knowledge regarding miR regulation in osteocytes. MiRs are key regulators of bone development and homeostasis, and the involvement of miRs in the regulation of osteocyte differentiation, viability, and function has recently been demonstrated. Findings from numerous studies have begun to identify various mechanisms of miR regulation in osteocytes. miRs have been shown to play a role in regulating osteocyte differentiation. For example, numerous miRs (including miR21, miR30, and miR23a) found to be upregulated during osteocyte differentiation target osteoblast-regulating mRNAs, whereas several downregulated miRs target key osteocyte-regulating genes. Further, miRs have been shown to regulate key signaling pathways controlling osteocyte viability and function. In particular, miR21 is involved in the survival signaling pathway downstream of connexin 43. Further, miR218, miR676, and miR324 regulate the expression of SOST/sclerostin, an osteocytic gene involved in the control of bone formation. Additionally, recent studies have demonstrated that miRs play a role in mediating cross-talk between osteocytes and other bone cells, as well as, with other musculoskeletal tissues including skeletal muscle and adipose tissue. miRs have been shown to be involved in regulating osteocyte differentiation, viability, and function. Further, recent studies have begun to highlight the potential involvement of miRs in mediating extracellular communication/regulation between osteocytes and other cells within the musculoskeletal system. However, more research on this topic is needed to determine the extent to which miRs regulate osteocytes and whether they are also involved in mediating cross-talk between musculoskeletal cells.
Advancements in the Aerosol Robotic Network (AERONET) Version 3 database – automated near-real-time quality control algorithm with improved cloud screening for Sun photometer aerosol optical depth (AOD) measurements

Abstract. The Aerosol Robotic Network (AERONET) has provided highly accurate, ground-truth measurements of the aerosol optical depth (AOD) using Cimel Electronique Sun–sky radiometers for more than 25 years. In Version 2 (V2) of the AERONET database, the near-real-time AOD was semiautomatically quality controlled utilizing mainly cloud-screening methodology, while additional AOD data contaminated by clouds or affected by instrument anomalies were removed manually before attaining quality-assured status (Level 2.0). The large growth in the number of AERONET sites over the past 25 years resulted in significant burden to the manual quality control of millions of measurements in a consistent manner. The AERONET Version 3 (V3) algorithm provides fully automatic cloud screening and instrument anomaly quality controls. All of these new algorithm updates apply to near-real-time data as well as post-field-deployment processed data, and AERONET reprocessed the database in 2018. A full algorithm redevelopment provided the opportunity to improve data inputs and corrections such as unique filter-specific temperature characterizations for all visible and near-infrared wavelengths, updated gaseous and water vapor absorption coefficients, and ancillary data sets. The Level 2.0 AOD quality-assured data set is now available within a month after post-field calibration, reducing the lag time from up to several months. Near-real-time estimated uncertainty is determined using data qualified as V3 Level 2.0 AOD and considering the difference between the AOD computed with the pre-field calibration and AOD computed with pre-field and post-field calibration. This assessment provides a near-real-time uncertainty estimate for which average differences of AOD suggest a +0.02 bias and one sigma uncertainty of 0.02, spectrally, but the bias and uncertainty can be significantly larger for specific instrument deployments. Long-term monthly averages analyzed for the entire V3 and V2 databases produced average differences (V3–V2) of + 0.002 with a ± 0.02 SD (standard deviation), yet monthly averages calculated using time-matched observations in both databases were analyzed to compute an average difference of −0.002 with a ±0.004 SD. The high statistical agreement in multiyear monthly averaged AOD validates the advanced automatic data quality control algorithms and suggests that migrating research to the V3 database will corroborate most V2 research conclusions and likely lead to more accurate results in some cases.
Dynamic Structural Responses of Long-Span Dome Structures Induced by Tornadoes

Abstract Long-span dome structures are widely used for public assembly venues because of their large column-free space and efficient use of materials. When occupied by hundreds or even thousands of people, it would be devastating if they fail or collapse, which unfortunately happen frequently during extreme events, especially under tornadic winds. Although static effects of tornadoes on civil structures have been extensively studied, their dynamic impact has not been sufficiently investigated. In this study, non-stationary characteristics of tornadoes and their dynamic impact on a long-span dome structure are systematically investigated. In particular, the time-variant wind pressure on the dome surface induced by translating tornadoes with different intensities is characterized through Computational Fluid Dynamics simulations. The obtained wind pressure is then mapped onto the finite element model of the dome structure, and transient time-history analyses are conducted to characterize the tornado-induced dynamic responses. It is observed that non-stationary wind pressure and the induced dynamic structural responses are significant, when core radius of the tornado approaches the dome. Wind flow of EF4 and EF5 tornadoes is found to be more turbulent than EF2 and EF3 tornadoes, and hence larger and more rapid fluctuations of dynamic responses.
Weight-related stigma mediates the relationship between weight status and bodily pain: A conceptual model and call for further research.

Abstract Women are disproportionately impacted by pain compared to men, highlighting the need to better understand factors that contribute to this gender disparity. Previous findings suggest weight-related stigma may be associated with pain among women attempting to lose weight. The goal of this study is to determine if experienced and/or internalized weight bias mediate the relationship between body mass index (BMI) and pain-related impairment in a large, community-based sample of women across the weight spectrum (N = 309; MAge = 56.5, SD = 14.5; MBMI = 28.5, SD = 7.1), and to evaluate whether this relationship differs for women with a pain condition. Analyses were performed using the Conditional-PROCESS Macro to examine the relationships between BMI, pain-related impairment, internalized and experienced weight-stigma, and the potentially moderating effect of pain-related conditions on these relationships. After adjusting for covariates, both experienced stigma and internalized weight stigma statistically mediated the BMI and pain-related impairment relationship; however, in the tests of moderated mediation, the indirect effect of internalized weight bias only held true for those without pain conditions. These findings offer a preliminary conceptual model and highlight the importance of pain research to include weight-related stigma.
“This Meeting at This Tree”: Reimagining the Town Hall Session:

Much of the language at academic conferences is purely metaphorical, so it is important to understand the cultural–historical significance of the metaphors used in constructing organizational gathe...
Outcomes of non-designated preliminary general surgery interns: A 25-year Mayo Clinic experience.

Abstract Background Non-designated preliminary, general surgery interns have no job security after year 1. Understanding how such non-designated preliminary, general surgery interns fare at any single institution might help future prelim applicants make better ranking decisions. We aimed to analyze the outcomes of residents pursuing a non-designated preliminary year in general surgery at a single institution. Methodology A retrospective cohort analysis of non-designated preliminary interns, who completed a preliminary year at our institution from 1993 to 2017, was conducted to understand their career path after the preliminary general surgery year. Results Three hundred and fifteen non-designated preliminary interns (232 international medical graduates and 83 American medical graduates) were identified. Two hundred and thirty-five (75%) matched into categorical residency spots (115 [49%] in general surgery, 18 [8%] each in orthopedic surgery and anesthesiology) after their preliminary year, 58 (18%) matched into a second year preliminary spot, and 22 (7%) left graduate medical education. American medical graduates (90%) more commonly matched into categorical spots than international medical graduates (69%; P Conclusion Most nondesignated, preliminary residents at our institution secured categorical spots for continuing graduate medical education. A preliminary internship year seems a useful endeavor for most trainees and even a second prelim year produces a categorical position for most of these driven and hard-working individuals.
Lung ultrasound: A useful additional tool in clinician's hands to identify pulmonary atelectasis in children with neuromuscular disease.

Introduction and objectives Patients with neuromuscular disease (NMD) are often exposed to ionizing radiations which could be reduced if a noninvasive and reliable diagnostic method is identified. The major aim of this study was to compare the use of chest X-ray (CXR) with lung ultrasound (LUS) in pediatric patients with NMD, to identify pulmonary atelectasis (PA). Materials and methods A prospective study was conducted on children affected by NMD. In all patients who underwent CXR, a LUS was also performed and results compared for the assessment of PA. Results Forty children affected by NMD were enrolled. Spinal muscular atrophy type 1 was the most common NMD, followed by spinal muscular atrophy type 2 and congenital myopathies. More than half of the subjects presented PA, more prevalent in the lung left lower lobes. LUS agreed with CXR results (negative or positive for atelectasis) in 31 patients (77.5%). In two patients, an agreement evaluation was not possible due to non-conclusive LUS. Conversely, LUS disagreed with CXR in seven patients, four of which were positive for atelectasis. If only complete agreement was considered, the statistical analysis between CXR and LUS showed: LUS sensitivity of 57%, LUS specificity of 82%, positive predictive value 80%, negative predictive value 61%. Conclusions This study suggests that the use of LUS should be recommended to early identify PA and reduce frequent ionizing exposition of these fragile patients. Finally, our study also suggests that LUS can provide relevant information for clinicians and respiratory physiotherapists.
Some observations on Reynolds number scaling in wall-bounded flows

Wall-bounded turbulence is sometimes described as consisting of hierarchies of similar structures. This is embodied in the Attached Eddy Model, and at high Reynolds numbers this model predicts a logarithmic variation of the turbulence intensity with distance from the wall. The high Reynolds number experiments described here confirm this behavior, but they also reveal new aspects such as the slower than expected rise in the near-wall peak, and the unexpected appearance of an outer layer peak. Turbulence remains an elusive phenomenon.
An Imperfect Storm: Identifying the Root Causes of COVID-19 Outbreaks in the World’s Largest Corrections Systems

We review the nature and extent of COVID-19 outbreaks across corrections systems globally, and document the types of front-end, in-prison, and back-end mitigation strategies used to address the COV...
High-Intensity CO 2 Laser Pumping of a 12 CH 3 F Laser

We report the observation of 21 new, efficient far-infrared (FIR) Raman laser lines in 12CH 3 F. These new lines are excited by high-intensity, off-resonant CO 2 TEA laser radiation in a waveguide laser system. Previous surveys of CH 3 F with high-power CO 2 TEA lasers have achieved strong, efficient laser emission at only two wave lengths, 496.1 μm (Refs. 1 and 2) and 192.8 μm.3 Fetterman et al.4 have obtained some additional lines in CH 3 F, demonstrating the importance of off-resonant optical pumping in pulsed FIR lasers. In their studies, as well as others, CO 2 TEA laser excitation of molecular gases has produced FIR radiation with a maximum of 1-2 GHz off resonance.5, 6 We recently reported7 fifteen new Raman lines in 12CH 3 F utilizing a CO 2 pump intensity of 10 - 20 MW/cm2. By using an oscillator-amplifier CO 2 laser system, we have increased the pump intensity to 40 - 60 MW/cm2. This has resulted in the observation of six additional lines with offsets as large as 20 GHz.
The Relationship between Early Alcohol Use Behaviors and Adolescent Pubertal and Psychosocial Development: A Latent Growth Analysis.

The present longitudinal study examines how age of alcohol initiation and regular use (weekly drinking for ≥6 months) relates to adolescent physiological development, social behaviors, psychologica...
The adolescent and young adult self-management and independence scale (AMIS-II): Expanding evidence for validity and reliability.

PURPOSE The purpose of this longitudinal study was to evaluate the internal consistency reliability and construct validity of the Adolescent/Young Adult Self-Management and Independence Scale-II (AMIS-II), an interview-based measure of self-management for youth with chronic health conditions. METHODS A diverse sample of adolescents and young adults (AYA) with spina bifida (SB) (n = 64 AYA; mean 20.88; age range 18-25 years) completed an AMIS-II interview. Six years earlier, parents from 55 families completed questionnaires that assessed children's responsibility for SB-related care (Sharing of Spina Bifida Management Responsibilities) and their ability to perform skills across condition-related tasks (The Spina Bifida Independence Survey). Parents also reported on child's communication skills, adaptive behaviors, and independent management of finances (Adaptive Behavior Assessment System-Second Edition; Scales of Independent Behavior-Revised). Descriptive and correlational analyses were conducted to assess the construct validity and the internal consistency reliability of the AMIS-II. RESULTS The AMIS-II demonstrated excellent internal consistency reliability (AMIS-II total scale α= 0.95; subscales α= 0.90 -0.91). Evidence in support of construct validity was found in associations between the AMIS-II and measures of child responsibility for SB-related care, ability to perform condition-related skills, and adaptive behaviors (r's = 0.378 -0.777; p's < 0.05). CONCLUSION This study provides further evidence of strong reliability and validity for the AMIS-II. Additional research with this measure will facilitate a better understanding of factors related to self-management behaviors in adolescents and young adults with spina bifida.
Next-Generation Immunotherapy Approaches in Melanoma

For patients with metastatic melanoma, immune checkpoint inhibition has drastically changed outcomes. Here, we review the current and next generations of immune-based anti-cancer therapeutics for patients with metastatic melanoma. The need for new anti-cancer therapeutics in patients with metastatic melanoma who have progression of disease despite immune checkpoint blockade is evident. Several novel agents are expected to have FDA approval within the next few years, as they have yielded impressive responses. Despite these optimistic agents, the field of immuno-oncology continues to expand and produce agents with novel mechanisms of action. The next generation of immunotherapy is based upon years of thoroughly researched immuno-oncology. Many of these agents are currently being evaluated in early phase clinical trials, and much of the preliminary data looks promising.
The Designed Bootstrap for Causal Inference in Big Observational Data

The combination of modern machine learning algorithms with the nonparametric bootstrap can enable effective predictions and inferences on Big Observational Data. An increasingly prominent and critical objective in such analyses is to draw causal inferences from the Big Observational Data. A fundamental step in addressing this objective is to design the Big Observational Data prior to the application of machine learning algorithms. The design step directly helps to reduce biases in the causal inferences that arise due to the non-randomized treatment assignment. In particular, performing the design step prior to implementing a machine learning algorithm ensures that subjects in different treatment groups with comparable covariates are subclassified or matched together, which reduces biases due to the confounding of covariates with treatment. However, the application of the traditional nonparametric bootstrap on Big Observational Data requires excessive computational efforts. This is because every bootstrap sample would need to be re-designed under the traditional approach, which can be prohibitive in practice. We propose a design-based bootstrap for deriving causal inferences with reduced bias from the application of machine learning algorithms on Big Observational Data. Our bootstrap procedure operates by resampling from the original designed observational data. It eliminates the need for additional, costly design steps on each bootstrap sample that are performed under the standard nonparametric bootstrap. We demonstrate the computational efficiency of this procedure compared to the traditional nonparametric bootstrap, and its equivalency in terms of confidence interval coverage rates for the average treatment effects, by means of simulation studies and a real-life case study. Ultimately, our procedure enables researchers to effectively use straightforward design procedures to obtain valid causal inferences with reduced computational efforts from the application of machine learning algorithms on Big Observational Data.
Under the guise of science: how the US Forest Service deployed settler colonial and racist logics to advance an unsubstantiated fire suppression agenda

Over the last century, the United States Forest Service (USFS) has reversed its stance on the ecological role of fire – from a militant enforcer of forest fire suppression to supporting prescribed ...
The Dif chemosensory pathway is directly involved in phosphatidylethanolamine sensory transduction in Myxococcus xanthus

Myxococcus xanthus cells glide on solid surfaces and are chemotactically stimulated by certain phosphatidylethanolamine species. The dif gene cluster consists of six genes, difABCDEG, five of which encode proteins homologous to known chemotaxis proteins. DifA and DifE are required for the biosynthesis of fibrils, an extracellular matrix comprised of polysaccharide and protein. Chemotactic stimulation by 1,2-O-Bis[11-(Z)-hexadecenoyl]-sn-glycero-3-phosphatidylethanolamine (16:1 PE) and dilauroyl PE (12:0 PE) requires fibrils. Although previous work has shown that difA and difE mutants are not stimulated by 12:0 PE, these results do not distinguish between a dependence on fibrils or a direct role in chemosensory transduction. Here we provide evidence that the Dif chemosensory pathway directly mediates PE sensory transduction. First, stimulation by and adaptation to 16:1 PE requires all of the dif genes, including difBDG, which are not essential for fibril biogenesis. Second, a specific residue within the first putative methylation domain of DifA is required for stimulation by 16:1 PE but not fibril biogenesis. Transmembrane signalling through a chimeric NarX-DifA chemoreceptor is required for fibril formation but not for stimulation by or adaptation to 16:1 PE. Third, difD and difE are required for stimulation by dioleoyl PE (18:1 PE) although the response does not require fibrils. Taken together these results argue that the Dif pathway mediates both matrix formation and lipid chemotaxis.
Fast algorithms for hard graph problems: bidimensionality, minors, and local treewidth

This paper surveys the theory of bidimensional graph problems. We summarize the known combinatorial and algorithmic results of this theory, the foundational Graph Minor results on which this theory is based, and the remaining open problems.
The utility of magnetic resonance imaging in the diagnostic evaluation of idiopathic olfactory loss.

Objectives/Hypothesis To report the utilization and cost effectiveness of magnetic resonance imaging (MRI) in the evaluation of patients with idiopathic olfactory loss. Study Design Case series with chart review. Methods A retrospective review of patients presenting with olfactory disorders at a university-based taste and smell center from July 1998 through October 2011 was performed to determine the diagnostic utility of MRI in the evaluation of patients with idiopathic olfactory loss. Results In a cohort of 839 patients with olfactory loss, idiopathic olfactory loss was most common, accounting for 247 patients—or 29% of this cohort. MRI was used in the evaluation of idiopathic olfactory loss 54.9% of the time, and abnormalities were identified in 4.6% of these patients. However, only 0.8% of these patients had olfactory loss attributable to imaging abnormalities. Therefore, the estimated cost per attributable abnormal finding was $325,000, given an average hospital charge of $2,500 per MRI. Conclusion In this cohort of patients with olfactory loss, the etiology most commonly remained idiopathic. Brain MRI, though frequently performed, demonstrated a very low diagnostic yield, with a rate of abnormal findings similar to that seen in the normal population. Based on these data, the routine use of MRI in patients presenting with isolated idiopathic olfactory loss may be unwarranted. Selection bias may contribute to the low yield of MRI among this cohort; further studies are needed to characterize those patients most likely to benefit from MRI evaluation. Level of Evidence 4. Laryngoscope, 124:365–368, 2014
The Psychobiology of Emotions

I. The Mind-Body Puzzle.- 1. Mind and Body.- 2. Neural Control Systems.- 3. Neurohormonal Control Systems.- II. Physiological Systems.- 4. The Cardiovascular System.- 5. The Thermoregulatory System.- 6. The Respiratory System.- 7. The Gastrointestinal System.- 8. The Urinary System.- 9. The Female and Male Reproductive Systems.- 10. The Skeletal Muscle System I: Nondinical Populations.- 11. The Skeletal Muscle System II: Clinical Populations.- III. Theories of Emotion.- 12. Biochemical Models.- 13. Physiological Models.- 14. Mentalistic Models.- 15. Interactionist Models I: Physiological Models.- 16. Interactionist Models II: Personality/Temperament Models.- 17. Beyond Tautologies.- References.- Author Index.
Strategy and the President's Legislative Policy Agenda: From Proposing Legislation to the Congressional Response, 1789-2002

Debate exists over whether presidents are sincere or strategic in submitting their legislative proposals to Congress and the implications of strategic versus sincere behavior on presidential success with Congress. This paper tests for strategic behavior in presidential proposing to Congress and the effects of that strategic behavior on subsequent congressional action. I develop two strategic hypotheses regarding presidential proposals, an expectation of success (defeat) and a presidential blame game hypothesis. Using data on presidential proposals from 1789-2002, analysis demonstrates support for both strategic hypotheses. Part two of the paper tests for the impact of strategic proposing on success with Congress. That analysis finds that the effect of divided government declines by about one-half after controlling for strategic presidential behavior, an effect consistent with the strategic proposing model. Second, I also test Cameron and Park's (2008) strategic burden sharing model, again finding strong support for this strategic behavior model. The conclusion discusses the implications of the findings on our understanding of presidential-congressional relations.
A Computer-Assisted Electrode System for Measuring Blood pH, pO2, pCO2, Sodium, and Potassium

An experimental automatic electrode system was constructed to determine the feasibility of making routine determinations of blood pH, pO2, pCO2, sodium, and potassium in intensive care units. The equipment standardizes itself automatically every 25 min, and is self-cleaning after a blood specimen has been analyzed. The analyzer is connected on-line to an IBM 1800 computer on an interrupt basis. There was no significant difference between the results for pH, pO2, and pCO2 obtained with this machine and those by manual methods. The precision obtainable for the five determinations is given. The relationship between blood and plasma sodium and potassium activities determined with the glass electrodes and plasma sodium and potassium concentrations determined by flame photometry is discussed.
A comparative study of Ba0.5Sr0.5Co0.8Fe0.2Ox (BSCF) and SrFeCo0.5Ox (SFC) ceramic membranes used for syngas production

Abstract Dense oxygen permeable ceramic membranes are promising materials for separating oxygen from air and for syngas production. In this work, the role of two different membrane materials, Ba0.5Sr0.5Co0.8Fe0.2Ox (BSCF) and SrFeCo0.5Ox (SFC), in the conversion of methane, has been studied. Pulse and temperature programmed desorption studies of CO and CO2 showed a higher CO and CO2 adsorption on BSCF compared to the SFC membrane. More CO adsorption resulted in more CO2 production. Raman spectroscopy of BSCF and SFC ceramic materials after CO and CO2 exposure showed carbonate species on these samples. Both H2 and O2 adsorption were significantly higher on BSCF, with significant water formation in the presence of hydrogen. Reaction investigations over Pt-based catalysts demonstrated higher methane conversion and a higher H2:CO ratio on the BSCF membrane than on the lower flux SFC membrane because of more interaction of the products with BSCF. Under reaction conditions, the simultaneous occurrence of steam and CO2 reforming of methane would lead to a higher methane conversion and a higher H2:CO ratio on BSCF. The onset temperature of oxygen release for BSCF was observed to be lower than that for SFC while the amount of oxygen release was significantly greater. These studies suggest that BSCF might be suitable for hydrocarbon conversion reactions at much lower temperatures than conventional dense ceramic membranes.
Two-stage classifications for improving time-to-failure estimates: a case study in prognostic of train wheels

In order to meet the need for higher equipment availability and lower maintenance cost, much attention is being paid to the development of prognostic systems. Such systems support a proactive maintenance strategy by continuously monitoring the components of interest and predicting their failures sufficiently in advance to avoid disruptions during operation. Recent research demonstrated the potential of a comprehensive data mining methodology for building prognostic models from readily available operational and maintenance data. This approach builds a binary classifier that can determine the likelihood of a failure within a broad target window but cannot provide precise time to failure (TTF) estimations. This paper introduces a two-stage classification approach that helps improve the precision of TTF estimations. The new approach uses the initial methodology to learn a variety of base classifiers and then relies on meta-learning to integrate them. The paper details the model building process and demonstrates the usefulness of the proposed approach through a real-world prognostic application.
Estimation of coral growth-rates from laboratory 45Ca-incorporation rates

Laboratory 45Ca-incorporation rates in hermatypic coral skeletons have previously been used successfully as an index of physiological function. This laboratory method would become more meanigful if it also provided an absolute measure of coral growth rates. In two coral species, Porites compressa and Pocillopora damicornis, 45Ca incorporation rates were obtained from short (0.5 h) laboratory incubations using apical (determined as fast growing) portions of freshly collected coral branches. 45Ca exchange across the coenosarc was not significant and not corrected for, whereas diurnal fluctuation in 45Ca in Pocillopora damicornis was significant and a necessary correction. A calculated surface area is used to express calcification rate. Typical growth rates calculated from the 45Ca-incorporation rates were 20 and 6 mm/year for Porites compressa and Pocillopora damicornis, respectively. These rates are considerably higher than those previously obtained in the laboratory, and compare favorably with field growth rates — 24 and 14 mm/year, respectively.
Evolution of influence: signaling in a lycaenid-ant interaction

Some phytophagous insects gain defense from natural enemies by associating with otherwise potentially harmful top predators. Many lycaenid butterfly caterpillars are involved in such interactions with ants: larvae provide carbohydrate rewards from the dorsal nectary organ (DNO) to associated ants in return for protection from natural enemies. The stability of these interactions involves signals that identify the lycaenid caterpillar as a mutualist. However, larvae of some lycaenid species, such as Lycaena xanthoides, are found in close association with ants but do not possess the reward producing DNO. Evaluating the relationship in a phylogenetic framework, we show that the association between L. xanthoides and ants likely evolved from a non-ant-associated ancestor. Behavioral trials also show that L. xanthoides larvae are capable of influencing ant behavior to increase ant tending when faced with a simulated predator attack, without providing DNO-derived rewards to ant associates. These results demonstrate that the DNO is not necessary to maintain associations between lycaenid larvae and ants. Third-party interactions may affect the evolution of mutualisms and consideration of underlying evolutionary history is necessary to understand contemporary species associations.