cssi/SciSciGPT-SciSciNet huggingface dataset:
More than a Word Cloud.

Word cloud generating applications were originally designed to add visual attractiveness to posters, websites, slide show presentations, and the like. They can also be an effective tool in reading and writing classes in English as a second language (ESL) for all levels of English proficiency. They can reduce reading time and help to improve writing skills and vocabulary comprehension. They can also be used to address elements of rhetoric in students’ essays and instructors’ assignment descriptions and syllabi. Word clouds can be used as a visual aid to present new vocabulary and a study tool for quizzes. Most applications work with printed and online texts and students’ authentic writing. They find corpus vocabulary in texts and use it to create word clouds. Knowing key words helps students understand and summarize the texts they read. When students determine which words they use most often in their writing, they are advised to learn the spelling and collocations of those words, find synonyms to avoid repetition, and use word maps to create a particular tone of voice to sound (for example) humorous or sad. This article introduces word cloud generators, which are free, user-friendly online tools that can be easily incorporated into ESL classroom activities to enhance student learning experience.
Absorption of cortisol from the colon in ulcerative colitis.

SummaryRectal Cortisol has been used in treatment of chronic ulcerative colitis with good results. Following administration of 200 mg of the steroid dissolved in 100 cc of normal saline, there was no significant increase in blood levels of cortisol. This was confirmed by absence in the plasma cortisol fraction of any appreciable radioactivity following instillation of cortisol-4-C14. By implication, our data suggest that the good clinical results obtained were probably the result of a local effect of the cortisol on the rectal mucosa.
The Cost of Getting Into Orthopedic Residency: Analysis of Applicant Demographics, Expenditures, and the Value of Away Rotations.

Objectives Little is known about the demographics and expenditures of applicants attempting to match into the competitive field of orthopedic surgery. In attempt to better inform potential applicants, the purposes of this work are to (1) better understand the demographics of successfully matched applicants, (2) determine the monetary cost of applying, and (3) assess the value of away rotations for improving chances of a successful match. Design Prospective comparative survey. Setting Mayo Clinic Department of Orthopedic Surgery, Rochester, MN. Participants A week following the 2015 Orthopedic Surgery Residency Match, a survey was sent to 1,091. The survey focused on applicant demographics, number of programs applied to, cost of applying, and the value of away rotations. Results A total of 408 applicants completed the survey (response rate = 37%). Of these, 312 (76%) matched and 96 (24%) did not match into a US Orthopedic Surgery Residency. Of the matched applicants, 300 (96%) were from US allopathic medical schools, 9 (3%) US Osteopathic Schools, and 3 (1%) were international graduates. Males comprised 84% of these applicants whereas 16% were female. The mean number of programs applied to was 71 (range: 20-140). On average, applicants were offered 16 interviews (range: 1-53) and they attended 11 (range: 0-12). Completing a rotation at a program increased an applicant׳s chances of matching into that program by a factor of 1.5 (60% vs 40%). Of the applicants who matched, most applicants matched to an orthopedic residency in the same region where the applicant attended medical school (58%). The average cost of the application was $1,664 (range: $100-$5,000) whereas the cost of interviews (travel, food, etc.) was $3,656 (range: $15-$20,000). Total expenditures ranged from $450 to $25,000 (mean = $5,415). Over 8% of matched applicants spent >$10,000. Conclusions Gaining acceptance into orthopedic surgery residency remains a very competitive process. Away rotations appear to correlate strongly with match status; however, the process remains quite expensive for applicants.
Approach Improvement of Land Policy for Macro-economic Regulation and Control

Land policy for macroeconomic regulation and control was made in a particular economic context.As time goes by and the economic environment changes,land policy in participating in the process of macro-control should also change accordingly.This article listed the new economic context of land-control means that there was the primary and secondary dislocation,rigidity was not strong,as well as the lack of effective co-ordination and other issues.Suggestions in response to these issued included: economic land policies should be promoted,rigidity of land policies should be enhanced,inter-sectoral coordination should be strengthen,etc.
Analysis on Monitoring Results of Microorganism Indexes in Drinking Water of Xi'an Railway Administration during 2006-2009

[Objective] To understand the microbial contamination of drinking water in the popedom of Xi'an railway administration,provide the basis for decision-making.[Methods]According to the relevant national standard method,the microorganism index of 812 drinking water samples was tested and evaluated in 4 years.[Results]737 of 812 drinking water samples were qualified,and the qualified rate was 90.8%.The qualified rate of centralized water source and scattered water source was 95.8% and 85.3% respectively.From 2006 to 2009,the qualified rate of microorganism indexes increased year by year.Among 75 unqualified samples,the unqualified samples number of scattered water source was more than that of centralized water source,and the unqualified sample number showed a descending trend during 2006-2009.[Conclusion]The microbial detection reaults of centralized water source was better than that of scattered water source.During 2006-2009,the qualified rate of microorganism indexes in water sources of Xi'an railway administration increased year by year,which was benefit from powerful health supervision and surveillance.
Chapter 6 – Naturalistic Driving Studies and Data Coding and Analysis Techniques

Publisher Summary This chapter describes the traffic conflict technique and the theory behind the power of instrumented vehicle or naturalistic driving studies, the life cycle of naturalistic driving studies, and powerful analytic techniques that can and have been used with these data. Naturalistic driving data provide powerful tools for safety researchers that incorporate some characteristics of epidemiological data analysis techniques with empirical data analysis techniques. Although these characteristics are very beneficial, they also provide novel new data and analytic methods in which to explore and study driver safety, specifically driver behavior. The life cycle of naturalistic driving studies includes the following: study design and data collection, data preparation and storage, data coding, and data analysis. Each of these steps is complex primarily due to the size and the extent of the data being collected. Naturalistic driving studies typically collect 6–8 gigabytes of video per minute, which can easily result in thousands of hours of video collected, and 6–10 TB of data that must be prepared, stored, coded, and analyzed. Naturalistic driving studies are typically lengthy and resource-intensive but worth the rich, detailed data that can be collected. These types of studies are complex and require extensive planning both prior to data collection and through the entire life cycle of the study to ensure that the initial research objectives are appropriately evaluated. Detailed planning at every step in the life cycle will result in a much easier and efficient data analysis phase of the project.
Writing Assignments: Where Writing Begins

I want to use this occasion1 to work on the paradox at the center of this passage from Beginnings: to begin to write is to “know” what cannot be known. It has become commonplace for English teachers to talk of writing as a “mode of learning,” or of writing as “discovery.” And it has become common to represent the writer’s struggle as a struggle for realization: “How can I know what I mean until I see what I’ve said?” This representation of writing is conventionally in service of a pedagogy whose primary aim is to enable students to work out something that is inside them: insight, vision, ideas, connections, wisdom.
Abelian Floquet symmetry-protected topological phases in one dimension

Time-dependent systems have recently been shown to support novel types of topological order that cannot be realized in static systems. In this paper we consider a range of time-dependent, interacting systems in one dimension that are protected by an Abelian symmetry group. We classify the distinct topological phases that can exist in this setting and find that they may be described by a bulk invariant associated with the unitary evolution of the closed system. In the open system, nontrivial phases correspond to the appearance of edge modes, which have signatures in the many-body quasienergy spectrum and which relate to the bulk invariant through a form of bulk-edge correspondence. We introduce simple models which realize nontrivial dynamical phases in a number of cases, and outline a loop construction that can be used to generate such phases more generally.
Influence of Initial Therapy on Progression of Renal Failure and Body Growth in Children with Posterior Urethral Valves

AbstractChildren with posterior urethral valves are at high risk for renal failure and growth retardation. It has been proposed that the type of initial surgical treatment (that is primary ablation versus high diversion) can affect the outcome of children with posterior urethral valves. We evaluated 43 children with posterior urethral valves treated and followed at our hospital from 1975 to 1990 (17 since birth and 26 referred patients). A total of 19 patients was treated by a high urinary diversion, (high urinary diversion group), 19 were treated by primary fulguration and 2 by vesicostomy (fulguration and vesicostomy group), and 3 underwent fulguration and unilateral diversion (mixed treatment group, excluded from study). The clinical outcome and body growth were compared for the high urinary diversion, and fulguration and vesicostomy groups. A normal stature (above the 25th percentile) was reached by 4 patients (21%) from the high urinary diversion group and 11 (52%) in the fulguration and vesicostomy ...
MRI measures of fat infiltration in the lower extremities following motor incomplete spinal cord injury: Reliability and potential implications for muscle activation

Muscle fat infiltration (MFI) is an expected consequence of incomplete spinal cord injury (iSCI). The MFI magnitude may have clinical value in determining functional recovery. However, there is a lack of understanding of how MFI relates to the volitional muscle activity in people with motor incomplete spinal cord injury (iSCI). Five iSCI and 5 uninjured age-matched control subjects participated in the study. In this preliminary study, we established the reliability of MFI quantification of select lower extremity muscles across different raters. Secondly, we assessed the magnitude and distribution of MFI in the lower legs of iSCI and uninjured control participants. Thirdly, we explored the relationship between MFI in the plantarflexor muscles and the ability to volitionally activate these muscles. High levels of inter-rater reliability were observed. The iSCI group had significantly elevated and a vastly different MFI distribution in the lower leg muscles compared to healthy controls. MFI was negatively correlated with volitional activation in iSCI. Our preliminary results sanction the importance of lower extremity MFI quantification as a potential measure in determining the functional outcomes in iSCI, and the subsequent pathological sequelae.
Development and Characterization of Antibodies to Carbohydrate Antigens

Antibodies to carbohydrate antigens are critical for the study of bacteria, tumors, blood groups, and cell-cell adhesion interactions; for the analysis of viral, hormone, and toxin receptors; and, finally, for analysis of the glycosylation of recombinant proteins. However, antibodies to carbohydrate structures are more difficult to develop because of the T-cell-independent response to carbohydrates. This can result in the production of low affinity and difficult to work with IgM antibodies to these molecules. Screening technologies that include IgM antibodies can cause selections of antibodies with low-affinity binding sites because of the net avidity enhancement. Unfortunately, the low-affinity binding site can also have a similar affinity for unwanted structures. Production of antibodies using cellular extracts can result in antibodies that react with multiple related structures, and therefore the resultant bioassays have sensitivity or specificity problems. Protein conjugates of saccharides for the production of polyclonal and monoclonal antibodies to carbohydrate structures can be used to solve these problems. For monoclonal antibody development to oligosaccharides, mapping with closely related saccharides allows the determination of the areas of the saccharide to which the antibody binds so that conclusions can be made concerning which saccharide structures will cross-react. Determination of the reactivity of the produced antibodies with related saccharide structures is essential prior to utilization.
Hamas: The Elephant in the Room

This chapter describes how UNSCO was quietly building up its own channels of communication with Hamas. The story of the author's first meeting with a Hamas leader in Gaza is unveiled and some examples of the UN's quiet diplomacy to preserve a fragile ceasefire and promote Palestinian unity are showcased. The chapter also offers reflections on the much debated and controversial issue: how to deal with “terrorist” non-state actors?
Single-Photon Radionuclide Imaging and SPECT

This chapter provides an overview of the basic physics of nuclear medicine gamma camera imaging. It covers basic gamma camera instrumentation, the physics and corrections required to form an image, and the basic principles of single-photon emission computed tomography (SPECT) and SPECT image reconstruction and finally concludes with examples of clinical applications to nuclear medicine imaging. The scintillation gamma camera is a versatile device that is used for a wide range of imaging applications that span all organ systems and a wide variety of diagnostic procedures.
Infrared preheating to improve interlayer strength of big area additive manufacturing (BAAM) components

The Big Area Additive Manufacturing (BAAM) system can print structures on the order of several meters at high extrusion rates, thereby having the potential to significantly impact automotive, aerospace and energy sectors. The functional use of such parts, however, may be limited by mechanical anisotropy, in which the strength of printed parts across successive layers in the build direction (z-direction) can be significantly lower than the corresponding in-plane strength (x-y directions). This has been primarily attributed to poor bonding between printed layers since the lower layers cool below the glass transition temperature (Tg) before the next layer is deposited. Therefore, the potential of using infrared heating is considered for increasing the surface temperature of the printed layer just prior to deposition of new material to improve the interlayer strength of the components. This study found significant improvements in bond strength for the deposition of acrylonitrile butadiene styrene (ABS) reinforced with 20% chopped carbon fiber when the surface temperature of the substrate material was increased from below Tg to close to or above Tg using infrared heating.
Optical pump — THz probe studies of size-dependent ultrafast charge carrier dynamics in WO 3 particles for photoelectrochemical cells

Terahertz (THz) spectroscopy is an excellent non-contact electrical probe of charge injection and conductivity with sub-picosecond time resolution. One may exploit this capability to study a variety of materials, and here we choose to probe the transient photoconductivity of tungsten (VI) oxide (WO 3 ), a wide band gap metal oxide. This semiconductor is of interest in renewable energy research and artificial photosynthesis because it can be used as the photoanode in photoelectrochemical cells. The ultrafast charge carrier dynamics on the picosecond timescale have yet to be investigated by any technique, let alone THz spectroscopy. Our particular interest is in the characterization and dynamics of photoinduced charge carriers that are required for efficient oxidation at the metal oxide/electrolyte interface.
A Bioengineered Positive Control for Rapid Detection of the Ebola Virus by Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP)

The Ebola virus (EBOV) causes a highly virulent and deadly disease. The 2014 Ebola outbreak in West Africa was the largest in history. The rapid spread highlighted the need for a quick and accurate diagnostic method that can be employed in resource-limited conditions. In this study, we developed a probe that can be used as an internal positive control, coupled with a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay to accurately detect EBOV. This RT-LAMP assay is a simple one-step reaction performed at a constant temperature, and the results can be visualized by a colorimetric change from violet to sky blue. Our assay enabled detection of 10 copies of synthetic EBOV RNA within 1 h. Compared to traditional RT-qPCR, RT-LAMP requires no sophisticated equipment, the results are easier to interpret, and they can be obtained in less time. These features make RT-LAMP an ideal method for detection of EBOV in low-resource settings.
Desuppressed Expressionsof MiR-29 targetsdisturb the Leukemeugenesis of MLL-AF9

The MLL--AF9 fusion oncogene is associated with acute leukemias in adults and children. Retroviral expression of MLL-AF9 in mouse hematopoietic stem/progenitor cells (HSPCs) rapidly induces acute myeloid leukemia (AML) and therefore serves as an excellent model to study MLL-AF9 induced leukemogenesis. We previously showed that miR-29 is highly expressed in human AML and positively regulates hematopoietic stem cell (HSC) self-renewal. Consistent with a role in AML, higher expression of miR-29 predicts poor survival in AML patients using the TCGA dataset. In addition, transduction of MLL-AF9 into microRNA-29 (miR-29a/b1) null Lin-c-Kit+Sca1+ (LSK) cells was sufficient to induce leukemic colony formation in vitro similar to WT LSK cells, but transplantation of MLL-AF9+ miR-29 null cells into lethally irradiated recipients resulted in an increased disease latency (median - 56 vs 151 days, p To understand why miR-29 null cells are relative resistant to MLL-AF9 mediated transformation, we first determined whether miR-29 null cells induce genes properly following MLL-AF9 transduction. RNA-sequencing of miR-29 null spleen B cells revealed that 1147 and 559 genes were significantly up- or down-regulated (adjusted p We found Meis1, Ccna2, Hoxa5 and Hoxa9 were significantly down-regulated in miR-29 null versus WT LSK cells, but were similarly induced in MLL-AF9 transformed blasts, suggesting that increased AML latency was not due to lack of ability to induce these known key regulators of leukemogenesis. As miR-29 directly binds to the 39-UTR of Dnmt3a, we sought to determine whether epigenetic dysregulation underlies the leukemic phenotype in miR-29 null cells. Performing ChIP-Seq for the active epigenetic mark H3K79me2 in c-Kit+Mac-1+ blasts, we identified 4281 and 3649 genes with this mark from WT and miR-29 null blasts, respectively, with an overlap of 3164 genes (66.39%). Next, we compared our data to H3K79me2 positive genes from WT LSK cells, granulocyte-macrophage progenitors (GMP), and MLL-AF9 transformed leukemic-GMP (L-GMP) and found that 45.6%, 48.0%, and 47.1% of these genes were also identified in MLL-AF9+miR-29 null cells, indicating that miR-29 loss reduces the induction ability of MLL-AF9 targets. We also observed that 379 genes associated with the H3K79me2 mark in both normal LSK cells and MLL-AF9+miR-29 null blasts were absent in L-GMP, suggesting that these genes confer self-renewal and proliferation capacity to normal HSCs, that their suppression of these genes are important in MLL-AF9 induction of AML, and that their reactivation in miR-29 null cells compromises MLL-AF9 leukemogenic ability. Interestingly, we were able to identify several potential miR-29 targets including Akt3, Map4k4, and Dnmt3a. Overall, our studies demonstrate that deletion of miR-29 abrogates the leukemogenesis capacity of MLL-AF9, and miR-29 null mice appear to be an important tool for identifying critical mediators of MLL-AF9 induced AML. Disclosures No relevant conflicts of interest to declare.
Decoupling of surface diffusion and relaxation dynamics of molecular glasses

Abstract Tobacco mosaic virus is used as a probe to measure surface diffusion of ultrathin films of N,N′-Bis(3-methylphenyl)-N,N′-diphenylbenzidine (TPD) (12 nm h h h is the film thickness) at various temperatures below the glass transition temperature, 𝐓 𝐠 𝐓𝐠, of all films. As the film thickness is decreased, 𝐓 𝐠 𝐓𝐠 decreases rapidly and the average film dynamics are enhanced by 6–14 orders of magnitude. We show that the surface diffusion is invariant of the film thickness decrease and the resulting enhanced overall mobility. The values of the surface diffusion coefficient and its temperature dependence are invariant of film thickness and are the same as the corresponding bulk values ( h = h=400 nm). For the thinnest films ( h h<20 nm), the effective activation energy for rearrangement (temperature dependence of relaxation times) becomes smaller than the activation energy for surface diffusion. These results suggest that the fast surface diffusion is decoupled from film relaxation dynamics and is a solely free surface property.
Decadal Prediction of Temperature: Achievements and Future Prospects

Decadal prediction refers to predictions on annual, multi-year, and decadal time scales. This paper reviews major developments in decadal prediction that have occurred in the past few years, including attribution of temperature anomalies in northern latitudes, the recent slowdown in the rate of global warming (the “hiatus”), and mechanisms of decadal predictability that do not involve interactive ocean circulations. In addition, this paper discusses certain advances that, in the opinion of the author, have not been given the attention they deserve in previous reviews, including a unified framework for quantifying decadal predictability, empirical models for decadal prediction, defining improved indices of decadal predictability, and clarification of the relation between power spectra and predictability.
Association between alcohol consumption trajectories and clinical profiles among women and men living with HIV.

Background: Alcohol use is common among persons living with HIV (PLWH). It is unclear how alcohol consumption changes over time and if these changes are associated with clinical profiles.Objective:...
Valve-sparing repair with intraoperative balloon dilation in tetralogy of Fallot: Midterm results and therapeutic implications

Abstract Objectives The significant morbidity of long-term pulmonary regurgitation (PR) has driven the development of pulmonary valve (PV) sparing repair strategies in patients with tetralogy of Fallot (ToF). We assessed mid-term PV function in patients who underwent primary ToF repair with valve-sparing intraoperative balloon dilation (IBD) technique. Methods We evaluated 162 consecutive patients with ToF and pulmonary stenosis (ToF-PS) who underwent valve-sparing repair with IBD under 1 year of age. Results Median age at surgery was 98 days (interquartile range [IQR], 72-126) and median follow-up was 2.5 years (IQR, 0.6-4.9). Median preoperative PV annulus z score was −2.2 (IQR, −2.5 to −1.8). Twenty-five patients (15.4%) required reintervention for residual valvular stenosis. Multivariable analysis demonstrated preoperative annulus z score less than −2.45 ( P = .036) and younger age at surgery ( P = .001) were independent risk factors for early reintervention for stenosis. Freedom from at least moderate PR was 77%, 61%, and 43% at 1, 3, and 5 years postrepair. Right ventricular dimensions were not significantly different compared with a matched cohort of patients undergoing transannular patch repair at midterm follow-up. Conclusions Patients with ToF-PS who undergo valve-sparing repair with IBD develop progressive PR. Compared with transannular patch repair, the extent of RV dilation at midterm follow-up is not significantly different. Patients younger than 3 months of age and those with an annulus z score less than −2.45 experience higher rates of early reintervention for PV stenosis. In these patient subgroups, alternative strategies should be considered. This study suggests valve-sparing repair with IBD does not preserve long-term PV function in patients with ToF-PS.
Low energy triode sputtering

Triode sputtering has separated the conventional diode sputtering plasma formation and sputtering functions to permit greater control of film thickness than that achieved with diode sputtering. The deposition rate is constant as a function of time and yield curves for various materials can be used to determine the required sputtering rate. The application of r.f. gives the possibility for sputtering of non-conductive materials such as glass or silicon monoxyde, etc. The low power input permits attainment of a given deposition rate with minimum heating of target and substrate. This permits metal and alloy films to be sputtered onto plastics with excellent adherence to some plastics without an undercoat. The higher energy of sputtered atoms (about 40 times that of evaporated atoms) results in excellent adherence. Beryllium copper films sputtered directly onto a glass substrate, without a base film of chromium, show good adherence and can be soldered successfully.
A Small-Molecule CD4-Mimetic Compound Protects Bone Marrow-Liver-Thymus Humanized Mice From HIV-1 Infection.

Background Small-molecule CD4-mimetic compounds (CD4mc) inhibit human immunodeficiency virus (HIV-1) entry by blocking binding to the CD4 receptor and by premature triggering of the viral envelope glycoprotein (Env) spike. Methods The efficacy of a CD4mc in protecting bone marrow-liver-thymus (BLT) humanized mice from vaginal HIV-1 challenge was evaluated. Results Intravaginal application of the CD4mc JP-III-48, either before or simultaneously with virus challenge, protected BLT humanized mice from HIV-1JR-CSF infection in a dose- dependent manner. Conclusion The direct antiviral effects of a CD4mc prevent HIV-1 infection in a murine model of sexual transmission.
From Montessori to Culturally Relevant Schools Under The Trees in Kenya

Kenya distinguishes itself from other sub-Saharan African countries with its well-established system of early childhood development and education (ECDE). This chapter describes environmental, economic and social-cultural circumstances in Kenya and how these affect ECDE program design, curriculum and preschool activities. The author will provide a brief historical overview of early childhood educational contexts in Kenya and how preschool teachers meet minimum standards of a quality program using Guidelines for Early Childhood Development in Kenya (NACECE (National Center for Early Childhood Education). (2003). Guidelines for early childhood development in Kenya. Nairobi: Author.) with an African approach. Specific focus will be given to the diverse and contrasting program settings for early childhood care and education from the affluent city suburbs to the rural agrarian farms and the arid and semi arid (ASAL) areas of Kenya.
Internal medicine trainees' knowledge and confidence in using the American Society of Hematology Choosing Wisely guidelines in hemostasis, thrombosis, and non-malignant hematology.

BACKGROUND Several specialty societies participate in the Choosing Wisely (CW) campaign in an attempt to reduce waste in health care spending. We surveyed internal medicine (IM) residents with an objective of classifying knowledge of and confidence in using the American Society of Hematology (ASH) CW principles in hemostasis, thrombosis, and non-malignant hematology. METHODS Multi-institutional study of IM residents at 5 academic training programs in the United States. A 10-question, case-based multiple choice test, with each question accompanied by a 5-point Likert-scale confidence assessment, was distributed electronically. Responses were summarized with frequencies and percentages or medians and ranges, as appropriate. Two sample t-tests or Wilcoxon rank-sum tests were used to compare confidence and knowledge scores. RESULTS Of 892 IM residents, 174 (19.5%) responded to all questions. Overall, residents answered a median of 7 of 10 questions correctly (range 2-10) and median resident confidence in their responses was 3.1 (on a 5-point scale). Correct responses were significantly associated with higher confidence for all but one question. Having a hematology rotation experience was significantly associated with more correct responses and with higher confidence (p = 0.001 and p<0.001, respectively). CONCLUSIONS IM residents at several academic hospitals have variable knowledge of ASH-CW guidelines in thrombosis and hemostasis/non-malignant hematology. Residents who have done hematology rotations, particularly a hematology consult rotation, were more likely to answer questions correctly and to be more confident that their answers were correct. Adequate clinical exposure and training in cost-effective care is essential to train clinicians who are cost-conscious in any specialty.
Predictive neuromechanical simulations indicate why walking performance declines with ageing

Key points Although the natural decline in walking performance with ageing affects the quality of life of a growing elderly population, its physiological origins remain unknown. By using predictive neuromechanical simulations of human walking with age-related neuro-musculo-skeletal changes, we find evidence that the loss of muscle strength and muscle contraction speed dominantly contribute to the reduced walking economy and speed. The findings imply that focusing on recovering these muscular changes may be the only effective way to improve performance in elderly walking. More generally, the work is of interest for investigating the physiological causes of altered gait due to age, injury and disorders. Abstract Healthy elderly people walk slower and energetically less efficiently than young adults. This decline in walking performance lowers the quality of life for a growing ageing population, and understanding its physiological origin is critical for devising interventions that can delay or revert it. However, the origin of the decline in walking performance remains unknown, as ageing produces a range of physiological changes whose individual effects on gait are difficult to separate in experiments with human subjects. Here we use a predictive neuromechanical model to separately address the effects of common age-related changes to the skeletal, muscular and nervous systems. We find in computer simulations of this model that the combined changes produce gait consistent with elderly walking and that mainly the loss of muscle strength and mass reduces energy efficiency. In addition, we find that the slower preferred walking speed of elderly people emerges in the simulations when adapting to muscle fatigue, again mainly caused by muscle-related changes. The results suggest that a focus on recovering these muscular changes may be the only effective way to improve performance in elderly walking.
Hierarchical Architectures for Reasoning

This chapter has a threefold purpose: (1) to introduce a general framework for parallel/distributed computation, the computational network; (2) to expose in detail a symbolic example of a computational network, related to expert systems, called an expert network; and (3) to describe and investigate how an expert network can be realized as a neural network possessing a hierarchical symbolic/sub-symbolic architectural organization.
Subversion of Systemic Glucose Metabolism as a Mechanism to Support the Growth of Leukemia Cells.

Summary From an organismal perspective, cancer cell populations can be considered analogous to parasites that compete with the host for essential systemic resources such as glucose. Here, we employed leukemia models and human leukemia samples to document a form of adaptive homeostasis, where malignant cells alter systemic physiology through impairment of both host insulin sensitivity and insulin secretion to provide tumors with increased glucose. Mechanistically, tumor cells induce high-level production of IGFBP1 from adipose tissue to mediate insulin sensitivity. Further, leukemia-induced gut dysbiosis, serotonin loss, and incretin inactivation combine to suppress insulin secretion. Importantly, attenuated disease progression and prolonged survival are achieved through disruption of the leukemia-induced adaptive homeostasis. Our studies provide a paradigm for systemic management of leukemic disease.
One Final Merger

At the end of April 2011, the financial markets were surprised by the news that the largest US health care company, Johnson & Johnson (J&J), acquired the entire Synthes firm for a total amount of USD 21.6 billion (CHF 19 billion). In one single deal, the previously independent firms Mathys, Stratec Medical, and Synthes USA—all involved with the beginning of the commercialization of the AO-designed implants combined under Synthes—had become a subsidiary of a large US healthcare company. What began in a small workshop run by Robert Mathys, Sr. in the small town of Bettlach in Switzerland and bootstrapped on little capital, had just been valued at USD 21.6 billion. The date of the announcement came 53 years after the first prototypes of the AO Instrumentarium had been fabricated by the initial design duo of Robert Mathys, Sr. and Maurice Muller.
Subgrouping breast cancer patients based on immune evasion mechanisms unravels a high involvement of transforming growth factor-beta and decoy receptor 3.

In the era of immunotherapy and personalized medicine, there is an urgent need for advancing the knowledge of immune evasion in different cancer types and identifying reliable biomarkers that guide both therapy selection and patient inclusion in clinical trials. Given the differential immune responses and evasion mechanisms in breast cancer, we expect to identify different breast cancer groups based on their expression of immune-related genes. For that, we used the sequential biclustering method on The Cancer Genome Atlas RNA-seq breast cancer data and identified 7 clusters. We found that 77.4% of the clustered tumor specimens evade through transforming growth factor-beta (TGF-β) immunosuppression, 57.7% through decoy receptor 3 (DcR3) counterattack, 48.0% through cytotoxic T-lymphocyte-associated protein 4 (CTLA4), and 34.3% through programmed cell death-1 (PD-1). TGF-β and DcR3 are potential novel drug targets for breast cancer immunotherapy. Targeting TGF-β and DcR3 may provide a powerful approach for treating breast cancer because 57.7% of patients overexpressed these two molecules. Furthermore, triple-negative breast cancer (TNBC) patients clustered equally into two subgroups: one with impaired antigen presentation and another with high leukocyte recruitment but four different evasion mechanisms. Thus, different TNBC patients may be treated with different immunotherapy approaches. We identified biomarkers to cluster patients into subgroups based on immune evasion mechanisms and guide the choice of immunotherapy. These findings provide a better understanding of patients’ response to immunotherapies and shed light on the rational design of novel combination therapies.
Developmental exposure to chemicals associated with unconventional oil and gas extraction alters immune homeostasis and viral immunity of the amphibian Xenopus.

Abstract Although aquatic vertebrates and humans are increasingly exposed to water pollutants associated with unconventional oil and gas extraction (UOG), the long-term effects of these pollutants on immunity remains unclear. We have established the amphibian Xenopus laevis and the ranavirus Frog Virus 3 (FV3) as a reliable and sensitive model for evaluating the effects of waterborne pollutants. X. laevis tadpoles were exposed to a mixture of equimass amount of UOG chemicals with endocrine disrupting activity (0.1 and 1.0 μg/L) for 3 weeks, and then long-term effects on immune function at steady state and following viral (FV3) infection was assessed after metamorphosis. Notably, developmental exposure to the mixture of UOG chemicals at the tadpole stage affected metamorphic development and fitness by significantly decreasing body mass after metamorphosis completion. Furthermore, developmental exposure to UOGs resulted in perturbation of immune homeostasis in adult frogs, as indicated by significantly decreased number of splenic innate leukocytes, B and T lymphocytes; and a weakened antiviral immune response leading to increased viral load during infection by the ranavirus FV3. These findings suggest that mixture of UOG-associated waterborne endocrine disruptors at low but environmentally–relevant levels have the potential to induce long-lasting alterations of immune function and antiviral immunity in aquatic vertebrates and ultimately human populations.
Developmental Regulation and Modulation of Neuronal Nicotinic Acetylcholine Receptor Channels

To date the best characterized receptor-channel complex is the muscle nicotinic acetylcholine receptor (AChR). Several studies demonstrate that muscle AChRs are subject to various forms of regulation. Distinct changes in channel properties, receptor distribution and subunit composition are observed over the course of development. Also, acute changes in the degree of receptor phosphorylation induce a functional change in the rate of receptor desensitization (for a review, see Schuetze and Role 1987). These extensive studies of muscle AChR regulation provide an important intellectual framework for studies of other ligand-gated channels in the central and peripheral nervous system.
Exogenous l-ARGININE does not stimulate production OF NO or cGMP within the rat corporal smooth muscle cells in culture.

Abstract Background and aim Nitric oxide (NO) is the intracellular chemical responsible for initiating a penile erection. Despite conflicting clinical data, it continues to be publicized and promoted that orally administered l -arginine, the putative substrate for NO, enhances the erectile response presumably by stimulating NO production by the corporal tissues resulting in an increase in cGMP production. To shed light on this issue, an in vitro study was conducted to explore the effect of direct exogenous administration of l -arginine as well as its precursor and metabolite, l -citrulline, on the NO-cGMP pathway within the cavernosal smooth muscle (CSM) cell. Materials and methods CSM cells obtained from 8 to 10 week old Sprague-Dawley rats were grown in Dulbecco media with 20% fetal calf serum and then incubated with or without l -arginine (L-ARG) or l -citrulline (L-CIT) in a time course and dose-response manner. Sildenafil (0.4 mM), IBMX (1 mM), l -NAME (3 μM), ODQ (5 μM) and Deta Nonoate (10 μM) were used as either inhibitors or stimulators of the NO-cGMP pathway. mRNA and protein were extracted and used for the determination of the phosphodiesterase 5 (PDE5). PDE5 activity was determined by luminometry. cGMP content was determined by ELISA. Nitrite formation, an indicator of NO production, was measured in the cell culture media by a colorimetric assay. The cationic (CAT-1) and neutral (SNAT-1) amino acid transporters for L-ARG and L-CIT, respectively, were determined by Western blot. Results When compared to untreated CSM cells, incubation with 0.25–4.0 mM of L-ARG or 0.3–4.8 mM of L-CIT anywhere between 3 and 24 h did not result in any additional nitrite or cGMP production. The addition of l -NAME, IBMX or ODQ to these L-ARG and L-CIT treated cells did not alter these results. L-CIT but not L-ARG increased PDE5 mRNA and protein content as well as the activity of the PDE5 enzyme. Both CAT-1 and SNAT-1 were expressed in the CSM cells. Conclusions This in vitro study demonstrates that exogenous administration of L-ARG or L-CIT failed to stimulate production of either NO or cGMP by the corporal CSM cells. A re-evaluation of the presumptive role of the exogenous administration of L-ARG in improving the synthesis of NO at least at the level of the CSM cells appears warranted.
Imaging Happiness: Meta Analysis and Review

A challenge in studying happiness is its conceptual nature. Is the happiness of hedonistic indulgence the same as the happiness of selfless volunteering? To understand some of these questions, a narrative review of 64 neuroimaging studies between 1995 and 2018 was conducted. Studies were grouped based on how they conceptualized happiness based on Seligman’s (Authentic happiness: using the new positive psychology to realize your potential for lasting fulfillment, Simon and Schuster, New York, 2002) authentic happiness theory. A qualitative narrative review was performed as well as an ALE meta analysis of activation regions. Happiness was identified in 33 separate brain regions across the telencephalon, diencephalon, and metencephalon. Stratifying results by definition of happiness, regions of activity were generally relevant to the tasks performed during the experiment and the kinds of tasks enjoyed by the phenomenon of happiness examined. The ALE analysis identified the claustrum, insula, basal ganglia, and thalamus as showing meaningful activation clusters across studies. Happiness as pleasure and engagement demonstrated close relevance of neural activity to literal activities being performed. Tasks for happiness as meaning, on the other hand, were generally more abstract. Likewise, there was less direct relationship between behavior and phenomenon of happiness, the insula most likely to activate for happiness as meaning. It was concluded that happiness is not best understood as an affective state, but better understood within its behavioral context, as an emergent property of activity. For pleasure and engagement, this meant a literal relationship between behavioral and neurological activity. For meaning, this meant the ongoing assessment of the moral implications of events. Limitations included cross sectional design and hemodynamic focus. Future research should consider concordance of happiness and brain activity across the lifespan. Additionally, future studies should consider the dynamics of neuropeptides.
Dewey and Bourdieu: Experience, Habit, and a New Direction for Education Reform

This paper examines John Dewey’s theory of experience and interaction along with Pierre Bourdieu’s educational theory about social stratification, and argues that combined, these theories should be reconsidered to forge a new path in the wake of negative educative experiences rendered by the impact of the modern educational reform movement, which is driven by neo-liberal aims that focus on practical skills, standardized testing, and school choice. Through the transmission of cultural capital to students and taking into consideration the impact of social stratification, the school can be used as a place where students can seek their purpose in life through positive experiences and interactions that provide the conditions necessary to attain the goals and hopes that they deserve.
Scientific testimonial standards for microbial forensic evidence

Abstract The last decade has seen a number of changes to expert testimonial standards in traditional forensic science fields, culminating in the Uniform Language for Testimony and Reporting (ULTR) guidance published by the Department of Justice. This chapter reviews issues that arose during the deliberations of the National Commission on Forensic Science before the adoption of ULTR standards, and their potential implications for Microbial Forensics testimony. A definition of error rate based on modern machine learning concepts can be used as a basis for understanding rigorous requirements for validation and the limits of testimony. Some habits of scientific discourse, especially hedging language, are possible pitfalls that weaken testimony. Statistically justified language for different kinds of microbial forensic inference is discussed for four examples: microbial identification, inferences about pathogen transmission, inferences about sources based on “morph” assays, and inferences about contamination and background when sensitive trace detection assays are used. There is a need for standards governing testimony when rigorous determination of error rates or other orthodox statistical measures of uncertainty is not possible.
Tuning Extracellular Electron Transfer by Shewanella oneidensis Using Transcriptional Logic Gates

Extracellular electron transfer pathways, such as those in the bacterium Shewanella oneidensis, interface cellular metabolism with a variety of redox-driven applications. However, designer control over EET flux in S. oneidensis has proven challenging since a functional understanding of its EET pathway proteins and their effect on engineering parameterizations (e.g., response curves, dynamic range) is generally lacking. To address this, we systematically altered transcription and translation of single genes encoding parts of the primary EET pathway of S. oneidensis, CymA/MtrCAB, and examined how expression differences affected model-fitted parameters for Fe(III) reduction kinetics. Using a suite of plasmid-based inducible circuits maintained by appropriate S. oneidensis knockout strains, we pinpointed construct/strain pairings that expressed cymA, mtrA, and mtrC with maximal dynamic range of Fe(III) reduction rate. These optimized EET gene constructs were employed to create Buffer and NOT gate architectures, that predictably turn on and turn off EET flux, respectively, in response to IPTG. Furthermore, we found that response functions generated by these logic gates (i.e., EET activity vs. inducer concentration) were comparable to those generated by conventional synthetic biology circuits, where fluorescent reporters are the output. Our results provide insight on programming EET activity with transcriptional logic gates and suggest that previously developed transcriptional circuitry can be adapted to predictably control EET flux.
Perineural and Vascular Invasion in an Endocrine Mucin-Producing Sweat Gland Carcinoma of the Ear With Associated Mucinous Carcinoma

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a low-grade, indolent tumor found almost exclusively on the eyelids that may histologically mimic metastatic breast carcinoma. To our knowledge, we present the first case of EMPSGC located on the external ear, and the first case with histologic evidence of vascular and perineural invasion. Due to the aggressive potential of this lesion, wide local excision and adjuvant radiation therapy were performed to help reduce the risk of recurrence.