cssi/SciSciGPT-SciSciNet huggingface dataset:
Enhancement of Umbilical Cord Blood Cell Hematopoiesis by Maitake Beta-Glucan Is Mediated by Granulocyte Colony-Stimulating Factor Production

Maitake beta-glucan (MBG) is an extract from the fruit body of the Grifola frondosa mushroom that is being widely used to treat cancer in Asia. We have previously reported that MBG enhances mouse bone marrow cell (BMC) hematopoiesis in vitro and protects BMC from doxorubicin (DOX) toxicity. In the current study, we investigated the ability of MBG to enhance hematopoiesis and to reduce the toxic effects of DOX on fresh human umbilical cord blood (CB) cells. MBG treatment significantly enhanced the colony formation unit (CFU) response of granulocytes-macrophages (CFU-GM response) over the whole dose range of 12.5 to 100 μg/ml (P < 0.05). The addition of MBG to DOX-treated CB cells significantly protected granulocyte-macrophage colony formation from the toxicity of DOX, which otherwise produced strong hematopoietic repression. MBG also partially replaced recombinant human granulocyte colony-stimulating factor (rhG-CSF), as shown by a significant augmentation of the CFU-GM response in the absence of rhG-CSF. We found that MBG induces granulocyte colony-stimulating factor (G-CSF) production in CB CD33+ monocytes, as detected by intracellular cytokine flow cytometric assessment. In contrast, we found that adult peripheral blood monocytes did not produce a significant G-CSF response to MBG, whereas both adult and CB monocytes produced G-CSF in response to lipopolysaccharide. These studies provide the first evidence that MBG induces hematopoietic stem cell proliferation and differentiation of CFU-GM in umbilical CB cells and acts directly to induce G-CSF.
In-situ non-disruptive cleaning of Ge(100) using H2O2(g) and atomic hydrogen

Abstract In-situ gas phase cleaning of the Ge(100) surface was studied at the atomic level using scanning tunneling microscopy (STM) and scanning tunneling spectroscopy (STS) while chemical analysis of the surface was performed using X-ray photoelectron spectroscopy (XPS). High purity H 2 O 2 (g) dosing removed carbon contamination from an air exposed Ge(100) sample. The oxide formed via H 2 O 2 (g) dosing was subsequently removed via either atomic hydrogen exposure at 300 °C or 550–700 °C annealing. STM imaging showed an air exposed Ge(100) surface after H 2 O 2 (g) dosing and 600–700 °C annealing produced a flat and ordered surface while STS verified the density of states (DOS) is equal to that of a Ge(100) surface which has been cleaned via sputter (500 °C) and annealing (700 °C). Combining H 2 O 2 (g) with atomic hydrogen dosing or annealing removed carbon via oxidation and oxygen via thermal desorption or reduction from an air exposed Ge(100) surface.
Modeling latent true scores to determine the utility of aggregate student perceptions as classroom indicators in HLM: The case of classroom goal structures

Abstract Measures of classroom climate such as classroom goal structures are often assessed through students’ perceptions; the aggregated means within classrooms are then sometimes labeled as “classroom characteristics.” The validity of these constructs is limited by the reliability of the measure at both the student and classroom level; yet, few studies accurately assess reliability when multilevel models are used. We demonstrate the use of a three-level hierarchical linear model to estimate latent true score measures of students’ perceptions of goal structures, appropriately adjusted for their nested structure. To investigate the distinctiveness of goal structures from teacher characteristics, we examined the inter-correlations among the student and classroom level variables, and predictors of each.
The Ant, Aphaenogaster picea, Benefits From Plant Elaiosomes When Insect Prey is Scarce

Myrmecochory is a facultative, mutualistic interaction in which ants receive a protein-rich food reward (elaiosome) in return for dispersing plant seeds. In North American northeastern hardwood forests, Aphaenogaster ants are the primary genus dispersing myrmecochorous plants. In these forests, myrmecochores occur in plant guilds of understory spring ephemerals or seasonal greens. This mutualism has been demonstrated for Aphaenogaster rudis (Emery) and individual plant species, but it has not been demonstrated for other Aphaenogaster species or guilds of myrmecochores as they naturally occur. Aphaenogaster picea (Wheeler) colonies were fed three treatments over 5 mo: 1) a mixture of only elaiosomes from an entire plant guild, 2) a diet of only insect protein and 3) a combination diet of both elaiosomes and insect protein. This experiment investigated two potential hypotheses through which elaiosomes can benefit ants: 1) elaiosome proteins can substitute for protein nutritional requirements when ants are prey-limited, and 2) elaiosome nutrition can supplement insect protein when prey is ample. First, a mixture of elaiosomes from four myrmecochorous plant species provided to A. picea colonies was sufficient to maintain worker production, larval growth, and fat stores when no other food was available. A. picea colonies consuming elaiosomes as their only protein source could be sustained for a growing season (5 mo). Second, colonies fed both elaiosomes and protein did not yield more productive colonies than a control diet of just insect protein. These results support the hypothesis that myrmecochory is indeed a facultative mutualism in which ants take advantage of the protein content of elaiosomes when it is favorable, but when they are not limited by insect prey they do not gain any additional benefit from elaiosomes.
Many means to a common end: the intricacies of (p)ppGpp metabolism and its control of bacterial homeostasis.

ABSTRACT In nearly all bacterial species examined so far, amino acid starvation triggers the rapid accumulation of the nucleotide second messenger (p)ppGpp, the effector of the stringent response. While for years the enzymes involved in (p)ppGpp metabolism and the significance of (p)ppGpp accumulation to stress survival were considered well defined, a recent surge of interest in the field has uncovered an unanticipated level of diversity in how bacteria metabolize and utilize (p)ppGpp to rapidly synchronize a variety of biological processes important for growth and stress survival. In addition to the classic activation of the stringent response, it has become evident that (p)ppGpp exerts differential effects on cell physiology in an incremental manner rather than simply acting as a biphasic switch that controls growth or stasis. Of particular interest is the intimate relationship of (p)ppGpp with persister cell formation and virulence, which has spurred the pursuit of (p)ppGpp inhibitors as a means to control recalcitrant infections. Here, we present an overview of the enzymes responsible for (p)ppGpp metabolism, elaborate on the intricacies that link basal production of (p)ppGpp to bacterial homeostasis, and discuss the implications of targeting (p)ppGpp synthesis as a means to disrupt long-term bacterial survival strategies.
Fast reconfiguration algorithms for time, space, and wavelength dilated optical Benes networks

Benes networks are rearrangeable nonblocking networks and are among the most efficient switching architectures in terms of the number of [image omitted] switching elements (SEs) used. In optical Benes networks, if two I/O connecting paths with the same (close) wavelength(s) share a common SE, crosstalk occurs. In order to reduce the crosstalk effect, three approaches, time, space and wavelength dilations have been proposed. In this paper, we present polylogarithmic-time reconfiguration algorithms for realizing any (partial) permutation in time, space and wavelength dilated optical Benes networks using a linear number of processors. Our algorithms are based on a logarithmic-time permutation decomposition algorithm and apply graph coloring techniques such as edge coloring, equitable coloring and vertex coloring.
Guidance For The Audit Committee: Acquiring Professional Services

Outside firms are often called upon to provide an entity with professional services. Such services might include external audit, systems, accounting, appraisal and valuation, actuarial, consulting, tax, or agreed-upon procedures work. The audit committee of the Board of Directors is typically the party within the entity responsible for hiring and overseeing these outside professional service providers. The Sarbanes-Oxley Act of 2002 mandates that certain professional services, which may have previously been performed by the firm engaged to do the external audit, cannot be performed by that public accounting firm. Thus, audit committees may be forced to contract with other professionals for services previously provided by the external auditors. The task of locating, contracting with, and overseeing the work of qualified firms for these professional services may seem daunting to the audit committee. This article presents steps the audit committee should take in selecting a professional service provider and overseeing that firm’s work. Also given are ways in which the entity’s internal audit activity can provide significant assistance to the audit committee undertaking its tasks.
Predicting morbidity and mortality of Carnegiea gigantea1

Abstract Research has shown that older plants of more than 20 species of tall, long-lived cacti of the Americas have surface bark injuries. This bark is caused by sunlight exposures over several decades. This bark formation (which first appears on south-facing surfaces) leads to premature morbidity and eventually premature mortality (rates of 2.3% per year for Carnegiea gigantea. Current research was aimed at changes in C. gigantea bark formation over a 4-yr period. Of the 89 C. gigantea analyzed, 35% died. Among survivors, surface areas with bark increased by 20% over the 4-yr period. Rib troughs of a more southerly orientation had more bark injuries (up to 15% more) than troughs with a more northerly orientation. Over time, the amount of bark on north-facing troughs becomes similar to bark levels on south-facing troughs. Machine learning techniques that used 18 parameters of bark percentages on cactus surfaces had an 84% probability of predicting cactus death with two independent methods. Machine learni...
Analysis of facial muscle activation in children with autism using 3D imaging

Autism Spectrum Disorder (ASD) impairs an individual's non-verbal skills including natural and contextual facial expressions. Such impairments may manifest as odd facial expressions (facial oddity) based on subjective evaluations of facial images. A few studies conducted on individuals with ASD have focused on the physiology of facial muscle usage by employing eletrophysiological sensors in response to visual stimuli. The sensors are placed directly on the face and may inhibit or limit the spontaneous facial response which may be too subtle for subjective human evaluations. This study uses a non-intrusive 3D facial imaging sensor that captures detailed geometric information of the face to facilitate quantification and detection of subtle changes in facial expression based on the physiology of facial muscle. A novel computer vision and data mining approach is developed from curve-based geometric feature of 3D facial data to discern the changes in the facial muscle actions. A pilot study is conducted with sixteen subjects (8 subjects with ASD and 8 typically-developing controls) where 3D facial images have been captured in response to visual stimuli involving 3D facial expressions. Statistical analyses reveal a significantly asymmetric facial muscle action in subjects with ASD compared to the typically-developing controls. This study demonstrates feasibility of using non-intrusive facial imaging sensor data in evaluating possible physiology-based impairments.
Teaching offensive security in a virtual environment

This tutorial presents lessons on how to teach offensive security in a virtual environment at University of Washington Tacoma and Michigan Technological University. Hands-on lab materials for participants to develop their own labs will be provided.
The Breck Trilogy: A Day in the Life of S. Breckinridge Tushingham, Tough on Scholarship, and Dean Breck

This series of three articles (that's why it's a trilogy, duh-h-h) chronicles the legal-academic career of one S. Breckinridge Tushingham ("Breck" for short). As the trilogy unfolds, Breck works his way up (or maybe it's down) from his first academic position to an established professorship to dean of the South Soybean (Soso) State University law school. In the process of recording his professional history, and thus memorializing it for the ages, Breck provides (probably defamatory) insights into the American legal academy.
Erratum to “Noise Suppression for Dual-Energy CT Through Entropy Minimization”

Presents corrections to, “Noise suppression for dual-energy CT through entropy minimization,” (Petrongolo, M. and Zhu, L., IEEE Trans. Med. Imag., vol. 34, no. 11, pp. 2286–2297, Nov. 2015).
A Data Management Tool for Dawn Science Planning

We describe adaptation of the Automated Scheduling and Planning Environment (ASPEN) planning engine for data management to support Dawn Science Planning for the Ceres encounter. Dawn is a mission to map the two bodies in the main asteroid belt: Vesta and Ceres. The Vesta encounter is complete and the Ceres encounter is currently in planning. One of the challenges of Dawn science planning is to optimize the gathering of images of the target bodies with limited onboard storage space while downlinking acquired science data. An adaptation of the ASPEN planning system has been developed that models the data acquisition of the Dawn spacecraft instruments as well as engineering data. This ASPEN adaptation also models the Dawn data storage buffers, playback modes, and downlink. Finally the adaptation also tracks relevant variables such as filter wheel motions. This tool supports Dawn science planners in assembly of a Dawn data management plan and science observation plan from a set of template data acquisition plan fragments, and reliably verifies that the plan satisfies relevant data throughput, engineering, and other operations constraints. Future plans include the development of more advanced plan repair and/or optimization techniques that offer the potential to enhance Dawn science operations.
The Late Quaternary Hominins of Africa: The Skeletal Evidence from MIS 6-2

The late Quaternary African hominin fossil record provides a tantalizing glimpse into considerable temporal and geographic morphological diversity within the genus Homo. A total of 50 sites that can be constrained from MIS 6-2 have yielded specimens ranging from isolated teeth to nearly complete skeletons. However, only a dozen or so provide particularly informative or interesting evidence spanning this period of nearly 200 kyr. In addition to the rather paltry nature of the record, one of the seemingly more intractable problems that bedevil its interpretation is the nature of the chronometric record for many of the sites. The Late Pleistocene terrestrial climatic record for Africa is also rather patchy, making continent-wide generalizations difficult. Attempts to link large-scale environmental perturbations in Africa to patterns of human evolution and behavior are even more problematic. Although the African fossil (and archaeological) record is most often viewed from the perspective of a single lineage culminating in the appearance of Homo sapiens and thence modern humans, the degree of morphological diversity evident even in this meager assemblage can be rather striking. Some of this diversity may be related to geographic and/or temporal differences, but in other instances, there are noticeable differences among remains that are contemporaneous, or at least penecontemporaneous. The Late Pleistocene African hominin fossil record, despite its manifestly incomplete nature, finds consistency with an impressive array of genetic evidence that points to an African origin for our species, and it also has consilience with genetic data that indicate a coalescence of lineages to the common ancestor of Homo sapiens at around the beginning of MIS 6. Although multiple lines of genetic evidence indicate a deep separation of lineages, with the ancestors of the southern African Khoesan diverging early on from that which gave rise to all other groups, there is a notable paucity of human remains that predate MIS 2 that exhibit strong phenetic resemblance to recent African populations. A number of the human dental samples from Late Pleistocene South African sites possess morphological variants that characterize the teeth of the recent inhabitants of sub-Saharan Africa, but these similarities do not necessarily signify a close evolutionary relationship with any of these populations because they appear to be plesiomorphic.
Diagnostic Hip Arthroscopy

Hip arthroscopy has become a powerful tool in the treatment of non-arthritic hip conditions and injuries. The proliferation of hip arthroscopy has fueled the vast expansion in the understanding of hip anatomy and pathology and has allowed systematic correlation of MR findings to arthroscopic findings. During arthroscopy, the hip is functionally divided into the central compartment and the peripheral compartment. Pathology pertaining to the labrum, acetabular rim, articular cartilage, and ligamentum teres is evaluated and addressed in the central compartment, while the peripheral compartment includes the femoral head neck junction and femoral neck. Careful evaluation of preoperative imaging including MRI allows the surgeon to efficiently detect and correct pathology during arthroscopy. Anatomical variants may mimic pathological conditions and the surgeon should be aware of potential variants when treating hip conditions arthroscopically.
The Model and Application of Multi-level Detaching Technique of Remote Sensing Alteration Information

According to the character of level structure of physical matter,this paper puts forward a multi-level detaching model for extraction of remote sensing alteration information based on several years' practice.Under the framework of this technical model,the simplification of the object for complicated extraction of remote sensing alteration information is discussed,and then the basic theory and structure of the model as well as the main technical system are discussed under the framework of the model and on the basis of an analysis of application instances.It is proved that the thinking of this model not only can simplify the problem of anomaly extraction but also is commendably applicable to the practice.
New Drugs for the Treatment of Schizophrenia

This article considers the newest agents available for the treatment of schizophrenia in the United States and elsewhere: clozapine, risperidone, and remoxipride. Most attention is provided to clozapine, which represents a major advance for the therapy for treatment-resistant schizophrenia. Risperidone has promise as a first-line drug with advantages in extrapyramidal symptoms (EPS) and possibly efficacy. Remoxipride appears to be a nonsedative antipsychotic with fewer EPS than haloperidol. Other novel drugs in testing also are mentioned.
Focal infection and diseases of the skin.

(1954). Focal Infection and Diseases of the Skin. Postgraduate Medicine: Vol. 15, No. 6, pp. 557-560.
Cerebral Hypoperfusion in Myotonic Dystrophy

Cerebral blood flow and perfusion measured by SPECT (Xenon and Tc-HMPAO), MRI findings, and neuropsychological function in 22 patients with myotonic dydtrophy (MD) were studied at the Departments of Neurology, Radiology, Psychiatry, and Pediatrics, Harbor-UCLA Medical Center, Torrance, CA.
Automated Measurement of Berry Size in Images

Abstract: Knowledge on berry size in grape vineyards can be a great asset for growers to help manage their crop whether for yield assessment or grape quality control. Having the ability to size berries of an entire field would allow growers to effectively monitor their vineyards at various stages of the growing season. Manual methods for determining berry size distribution of an entire field can be time consuming and rely on small sample sets which can lead to inaccuracies. This paper introduces an automated imaging system that measures diameter of grapes for every vine in an entire vineyard and generates a comprehensive map showing berry size variability which until now has not been available to growers. Believed to be the first example of mapping berry size across commercial vineyard blocks, this system uses computer vision techniques to locate and size the berries identifying submillimeter berry diameter differences. Maps of variability in berry size are shown to correlate with canopy size and yield. Diameter estimations are found to measure within 6% of manual measurements and a strong correlation is seen between estimated berry sizes and actual berry weights with r 2 = 0.96.
Checklist of Mosses (Bryophyta) of Bodamalai Hills in Eastern Ghats, Tamil Nadu

Bodamalai Hills, situated on the Southern Eastern Ghats of Tamil Nadu, were explored for mosses (bryophyta) for the first time. As a result a checklist of mosses has been prepared comprising 52 species belonging to 38 genera and 21 families. The dominant families with the maximum number of species are Pottiaceae, Bryaceae, Stereophyllaceae, Sematophyllaceae and Brachytheciaceae. The dominant genera are Brachymenium and Bryum and the dominant species are Barbula javanica and Bryum capillare.
Surgical and Endovascular Management of Acutely Ruptured Arteriovenous Malformations

Unruptured arteriovenous malformations (AVMs) have a bleeding rate of about 1–2% per year, but once ruptured, AVMs are far more likely to bleed again. While management of unruptured AVMs remains controversial, ruptured AVMs are treated to prevent death, neurological deficits, and long-term disability that come with hemorrhage. Modern AVM treatment is multimodal and includes microsurgical resection as well as endovascular embolization and radiosurgery, either as adjuncts or as alternatives to surgery. In the acutely ruptured AVMs, surgery for hematoma evacuation, and relief of mass effect and increased intracranial pressure is sometimes required. The Spetzler–Martin and Lawton–Young supplementary grading systems are used to describe AVMs and to predict neurological outcomes after AVM surgery. While microsurgical resection is invasive, it has superior cure rates and is safe in patients with favorable supplemented grades. Endovascular embolization is routinely used preoperatively to eliminate bleeding aneurysms or deep, surgically inaccessible feeding arteries. However, newer embolic agents and delivery systems have improved AVM obliteration rates with fewer complications, making curative embolization a competitive alternative to AVM surgery in highly selected cases. Radiosurgery is utilized for patients with high-grade AVMs with high surgical risk, but is also a competitive alternative for patients with small, low-grade lesions. Complete obliteration depends on the volume of the AVM and the dose of radiation delivered. Patients remain at risk for hemorrhage during the latency period. Regardless of the treatment, only complete angiographic obliteration is considered curative and eliminates the risk of future hemorrhage. The goal of treatment is complete AVM obliteration while preserving neurological function.
Bilateral Chylothorax Due to Blunt Trauma Without Radiographic Evidence of Traumatic Injury.

Chylothorax represents an uncommon clinical entity with multiple etiologies. Chylothorax following bluntthoracic trauma is typically associated with posterior rib fractures or thoracic vertebral fractures or dislocations.The occurrence of a traumatic chylothorax in the absence of associated injuries is a rare event. We reporta case of a 51-year-old patient who developed bilateral chylothorax after sustaining blunt trauma withoutradiographic evidence of traumatic injury. A 51-year-old male presented to the emergency departmentcomplaining of progressively worsening shortness of breath and associated chest pain for the prior one weekfollowing a fall down several concrete steps. On evaluation, the patient was found to have bilateral pleuraleffusions with no radiographic evidence of traumatic injury, including posterior rib or thoracic vertebral fractures.Subsequent thoracentesis and pleural fluid analysis were performed confirming the diagnosis of chylothorax.Management included repeated thoracentesis, diet modification and octreotide administration, which resultedin dramatic improvement and eventual resolution of symptoms. Non-iatrogenic traumatic bilateral chylothoraxin the absence of other radiographically demonstrated bony or soft tissue injury is a rare event. Chylothoraxshould be considered in the differential diagnosis of patients presenting with chest pain or shortness of breathfollowing blunt trauma and evidence of pleural effusion, even in the absence of obvious traumatic fracture orinjury on radiographic imaging.
EL GOCE TOTALITARIO — SALÒ DE PASOLINI

Ha duas caracteristicas fundamentais que definem o sentido espiri-tual e civilizatorio da tortura. Uma delas e de ordem politica. Em termos ex-tremamente rudimentares, isso pode ser formulado mediante a exemplaridade criminal com que certos setores que estao na vanguarda da organizacao politica e militar do estado de direito anunciam seu proprio poder de sedicao como a base para uma nova ordem de fato local ou global. E por causa dessa razao que a tortura — seja ela do tipo como a praticada du-rante a Inquisicao colonial do sec. XVI, seja ela da sorte como a praticada nas penitenciarias coloniais da Guerra Global atual — precisa ocultar a sua brutalidade primitiva, sangrenta e sacrificial da sociedade, enquanto que, ao mesmo tempo, precisa assegurar a exibicao de si mesma como uma demons-tracao publica de poder que e tao absoluta quanto arbitraria. Salo fornece uma denuncia da tortura, mas simultaneamente interpreta a tortura como a escrita secreta de uma modernidade que legitima e dissemina tortura enquanto linguagem. E, por ultimo, este filme tambem anuncia o advento de um novo fascismo global: o fascismo global que encara nossa face hoje.
Disordered system with n orbitals per site: n= [] limit

A model of a randomly disordered system with $n$ electronic states at each site of a $d$-dimensional lattice is introduced. It is a generalization of a model by Wigner to $d$ dimensions and an extension of the usually considered model for disordered systems to $n$ states per site. In the limit $n=\ensuremath{\infty}$, which is the limit of a dense system of weak scatterers, the one- and two-particle Green's function can be calculated exactly. The eigenstates are extended and the residual conductivity is finite, provided the Fermi energy is inside the band. Two special cases are considered more closely: (i) In the case of mere site-diagonal disorder the $n=\ensuremath{\infty}$ solution agrees with the $n=1$ coherent-potential approximation for a semicircle distribution of the site-diagonal elements. (ii) In a "local gauge invariant model," where the phases at different sites are completely uncorrelated, the Green's functions vanish unless the points coincide pairwise in local space. Except for a special case of the gauge-invariant model, the systems (i) and (ii) show the same long-range correlation between eigenstates over a length $L$ which diverges like ${|\ensuremath{\omega}|}^{\ensuremath{-}\frac{1}{2}}$ as the energy difference $\ensuremath{\omega}$ vanishes.
Excuses, justifications, and the just war tradition: are there good reasons to kill the Naked Soldier?

In war there is a phenomenon known as the Naked Soldier problem (NS). A combatant discovers a vulnerable enemy combatant who is unable to defend himself and usually unaware of the combatant’s prese...
Fundamental Methods for Optimizing Residuals Dewatering

The cost and difficulty of managing water and wastewater treatment residuals are directly related to the amount of water remaining in these residuals after dewatering. Thus, producing a drier product should be an important objective in residuals management. Yet, achieving this goal is not an easy task in a treatment facility with existing dewatering equipment, and with residuals flows and characteristics that both vary over time. In such a case, proper conditioner use and control are the only strategies available. Yet, while much research has focused on characterizing physical and chemical characteristics of residuals before and after dewatering, little information is available that can actually aid in optimizing the conditioner application prior to dewatering.
Early coverage expansions under the Affordable Care Act and Supplemental Security Income participation

Abstract We test whether early Affordable Care Act (ACA) Medicaid expansions in Connecticut (CT), Minnesota (MN), California (CA), and the District of Columbia (DC) affected Supplemental Security Income (SSI) receipt. We use a synthetic control approach, comparing the SSI receipt rate pre and post each early Medicaid expansion (“Early Expanders”) to the weighted receipt rate in states that expanded Medicaid in January 2014 (“Later Expanders”). In CT, the Medicaid expansion is associated with a statistically significant, 7 percent reduction in SSI beneficiaries among individuals aged 18–64. For DC, MN and CA, we do not find consistent evidence that the Medicaid expansions affected disability-related outcomes.
Coordinated d-cyclin/Foxd1 activation drives mitogenic activity of the Sonic Hedgehog signaling pathway

Sonic Hedgehog (Shh) signaling plays key regulatory roles in embryonic development and postnatal homeostasis and repair. Modulation of the Shh pathway is known to cause malformations and malignancies associated with dysregulated tissue growth. However, our understanding of the molecular mechanisms by which Shh regulates cellular proliferation is incomplete. Here, using mouse embryonic fibroblasts, we demonstrate that the Forkhead box gene Foxd1 is transcriptionally regulated by canonical Shh signaling and required for downstream proliferative activity. We show that Foxd1 deletion abrogates the proliferative response to SHH ligand while FOXD1 overexpression alone is sufficient to induce cellular proliferation. The proliferative response to both SHH ligand and FOXD1 overexpression was blocked by pharmacologic inhibition of cyclin-dependent kinase signaling. Time-course experiments revealed that Shh pathway activation of Foxd1 is followed by downregulation of Cdkn1c, which encodes a cyclin-dependent kinase inhibitor. Consistent with a direct transcriptional regulation mechanism, we found that FOXD1 reduces reporter activity of a Fox enhancer sequence in the second intron of Cdkn1c. Supporting the applicability of these findings to specific biological contexts, we show that Shh regulation of Foxd1 and Cdkn1c is recapitulated in cranial neural crest cells and provide evidence that this mechanism is operational during upper lip morphogenesis. These results reveal a novel Shh-Foxd1-Cdkn1c regulatory circuit that drives the mitogenic action of Shh signaling and may have broad implications in development and disease.
Defining a Process for Cross-Product User Interface Consistency

A small team of usability analysts created, implemented, and followed a company-wide process to increase user interface consistency across products. Key ingredients to success were: an effective process; ongoing, active, involvement from stakeholders; iterative design and review cycles; and easily accessible and reusable code. This effort changed the process of cross product user interface design at SAS, providing impetus to the development of products that are more consistent. Goals, process, results, and lessons learned are described.
Why This Book and Why Now? A Rationale and Systems Impact for Geriatric Trauma and Acute Care Surgery

The geriatric population is increasing. The number of geriatric patients suffering from injury or undergoing emergent surgery is also growing. All of this is occurring without adequate systems in place to meet the need of the complex elderly patient. This chapter addresses the overarching rationale for this book and the impact on the healthcare and trauma systems in response to this growth.
Introduction to Metric Fixed Point Theory

“The theory of fixed points is one of the most powerful tools of modern mathematics” quoted by Felix Browder, gave a new impetus to the modern fixed point theory via the development of nonlinear functional analysis as an active and vital branch of mathematics. The flourishing field of fixed point theory started in the early days of topology (the work of Poincare, Lefschetz–Hopf, and Leray–Schauder). This theory is applied to many areas of current interest in analysis, with topological considerations playing a crucial role, including the relationship with degree theory. For example, the existence problems are usually translated into a fixed point problem like the existence of solutions to elliptic partial differential equations, or the existence of closed periodic orbits in dynamical systems, and more recently the existence of answer sets in logic programming. Fixed point theory of certain important mappings is very interesting in its own right due to their results having constructive proofs and applications in industrial fields such as image processing engineering, physics, computer science, economics and telecommunication.
Functional Neuroradiology of Psychiatric Diseases

Functional neuroimaging offers a unique view of the link between brain activity and behavior – a relationship at the root of modern psychiatry. As a result, the application of blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to neuropsychiatric disorders began in earnest almost immediately after the technique was first described. As the complexity of the functional architecture of the brain has become more evident, attention has shifted from identifying centers of abnormal activation to characterizing abnormal networks, with increasing use being made of functional connectivity techniques [1]. The analysis of resting-state networks has also flourished, partly because it may sidestep a persistent challenge in the use of BOLD-fMRI in neuropsychiatric disease: selection of a paradigm that is appropriate for the clinical features of each type of mental illness. In the remainder of this chapter, recent trends in the application of functional neuroimaging to selected neuropsychiatric disorders are illustrated.
Adverse Childhood Experiences and Justice-Involved Youth: The Effect of Trauma and Programming on Different Recidivistic Outcomes:

Studies have demonstrated that adverse childhood experiences (ACEs) are prevalent in justice-involved youth and related to recidivism. However, the effect of programming on reducing reoffending for...
Unnatural verticilide enantiomer inhibits type 2 ryanodine receptor-mediated calcium leak and is antiarrhythmic.

Ca2+ leak via ryanodine receptor type 2 (RyR2) can cause potentially fatal arrhythmias in a variety of heart diseases and has also been implicated in neurodegenerative and seizure disorders, making RyR2 an attractive therapeutic target for drug development. Here we synthesized and investigated the fungal natural product and known insect RyR antagonist (−)-verticilide and several congeners to determine their activity against mammalian RyR2. Although the cyclooligomeric depsipeptide natural product (−)-verticilide had no effect, its nonnatural enantiomer [ent-(+)-verticilide] significantly reduced RyR2-mediated spontaneous Ca2+ leak both in cardiomyocytes from wild-type mouse and from a gene-targeted mouse model of Ca2+ leak-induced arrhythmias (Casq2−/−). ent-(+)-verticilide selectively inhibited RyR2-mediated Ca2+ leak and exhibited higher potency and a distinct mechanism of action compared with the pan-RyR inhibitors dantrolene and tetracaine and the antiarrhythmic drug flecainide. ent-(+)-verticilide prevented arrhythmogenic membrane depolarizations in cardiomyocytes without significant effects on the cardiac action potential and attenuated ventricular arrhythmia in catecholamine-challenged Casq2−/− mice. These findings indicate that ent-(+)-verticilide is a potent and selective inhibitor of RyR2-mediated diastolic Ca2+ leak, making it a molecular tool to investigate the therapeutic potential of targeting RyR2 hyperactivity in heart and brain pathologies. The enantiomer-specific activity and straightforward chemical synthesis of (unnatural) ent-(+)-verticilide provides a compelling argument to prioritize ent-natural product synthesis. Despite their general absence in nature, the enantiomers of natural products may harbor unprecedented activity, thereby leading to new scaffolds for probe and therapeutic development.
Abstract 1399: Ex-vivo targeting of urothelial carcinomas by fluorescent pHLIP imaging agents

Introduction: The detection of urothelial carcinomas of the bladder and upper tract is not satisfactory. Incomplete findings by contemporary imaging modalities provide a challenge in patient care, so there is a definitive need to improve diagnosis and treatment methods for urothelial carcinomas. Experimental procedures: ICG (indocyanine green) near infrared fluorescent (NIRF) dyes were conjugated with a pH-Low Insertion Peptide (pHLIP®), which senses and targets the acidity at the surfaces of cancer cells. In a few cases IR800 pHLIP® was used. Urinary neoplasm (kidney, ureter and bladder) specimens obtained through radical surgery were irrigated and incubated ex-vivo with ICG pHLIP® followed by fluorescence imaging. Pathology findings were correlated with the ICG pHLIP® NIRF imaging. Results: In the upper urothelial tract, nine of ten patients with nephroureterectomy had urothelial carcinomas (UTUC). Eighteen (100%) malignant lesions were found in NIRF imaging. Only thirteen (72%) of malignant lesions were found under white light macroscopic examination. ICG pHLIP® NIRF imaging gave a 28% increase in diagnosis of UTUC in ex-vivo specimens. There was no non-specific uptake in the non-tumoral tissue. The ICG pHLIP® imaging agent identified malignant upper tract urothelial lesions with 100% specificity and sensitivity. In the lower urinary tract, thirty-eight radical cystectomy specimens were incubated with pHLIP® conjugated with one of the NIRF dyes (ICG or IR800). In the thirty-eight bladders, eighty-one lesions were identified using fluorescent pHLIP®(specificity (97%) and sensitivity (100%)). White light cystoscopy did not detect 20.5% of lesions identified under NIRF cystoscopy (p Conclusions: The ICG pHLIP® NIRF revealed additional lesions not seen with white light ex-vivo cystoscopy or preoperative ureteroscopy. pHLIP® based agents promise to improve diagnostic accuracy for urothelial carcinomas and may enable targeted treatment. Citation Format: Borivoj Golijanin, Anna Moshnikova, Donald M. Engelman, Oleg A. Andreev, Yana K. Reshetnyak, Ali Amin, Dragan Golijanin. Ex-vivo targeting of urothelial carcinomas by fluorescent pHLIP imaging agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1399.
Bone grafts and bone morphogenetic proteins in spine fusion

Spinal fusions are being performed for various pathologies of the spine. Stabilizing vertebral segments by eliminating motion across those segments becomes critical in dealing with pathologies of the spine that lead to instability. The use of autograft has been the gold standard for spine fusion. However, due to complications such as donor site morbidity, increased operating time, and limited supply, the use of allograft as a graft extender has become an acceptable practice especially in fusions spanning multiple segments. The discovery and isolation of novel proteins (i.e., bone morphogenetic proteins, BMPs), which initiate the molecular cascade of bone formation, have experimentally been shown in numerous animal studies to be as effective as autografts. Although the use of BMPs has exciting applications in spine surgery, long-term clinical studies must be evaluated for its efficacy in various applications in humans. The use of biomimetic materials such as hydroxyapatite (HA), or tricalcium phosphate (TCP) has also been examined in several animal models as bone graft substitutes or carriers. Although these materials have shown some promise in specific site applications, more work remains in elucidating an efficacious combination of these materials and BMPs that can be as effective as autografts. This review will present the status of bone grafts, bone morphogenetic proteins, gene therapy, and work that has been done to facilitate spinal fusion and simultaneously eliminate the need for bone graft.
Central Lateral Thalamic Nucleus Stimulation Awakens Cortex via Modulation of Cross-Regional, Laminar-Specific Activity during General Anesthesia.

Experiments identify cortical layer specific effects during induced arousal from general anesthesia. In this issue of Neuron, Redinbaugh et al. (2020) find evidence that central lateral thalamic nucleus electrical stimulation reactivates the cortex by restoring deep-layer firing rates and modulating feedforward and feedback connectivity.
Preparation of cyclohexene isotopologues and stereoisotopomers from benzene

The hydrogen isotopes deuterium (D) and tritium (T) have become essential tools in chemistry, biology and medicine1. Beyond their widespread use in spectroscopy, mass spectrometry and mechanistic and pharmacokinetic studies, there has been considerable interest in incorporating deuterium into drug molecules1. Deutetrabenazine, a deuterated drug that is promising for the treatment of Huntington's disease2, was recently approved by the United States' Food and Drug Administration. The deuterium kinetic isotope effect, which compares the rate of a chemical reaction for a compound with that for its deuterated counterpart, can be substantial1,3,4. The strategic replacement of hydrogen with deuterium can affect both the rate of metabolism and the distribution of metabolites for a compound5, improving the efficacy and safety of a drug. The pharmacokinetics of a deuterated compound depends on the location(s) of deuterium. Although methods are available for deuterium incorporation at both early and late stages of the synthesis of a drug6,7, these processes are often unselective and the stereoisotopic purity can be difficult to measure7,8. Here we describe the preparation of stereoselectively deuterated building blocks for pharmaceutical research. As a proof of concept, we demonstrate a four-step conversion of benzene to cyclohexene with varying degrees of deuterium incorporation, via binding to a tungsten complex. Using different combinations of deuterated and proteated acid and hydride reagents, the deuterated positions on the cyclohexene ring can be controlled precisely. In total, 52 unique stereoisotopomers of cyclohexene are available, in the form of ten different isotopologues. This concept can be extended to prepare discrete stereoisotopomers of functionalized cyclohexenes. Such systematic methods for the preparation of pharmacologically active compounds as discrete stereoisotopomers could improve the pharmacological and toxicological properties of drugs and provide mechanistic information related to their distribution and metabolism in the body.
S043 mythbuster: truncal vagotomy and gastric drainage procedures.

You are sitting for your oral surgery board exam and the examiner asks what you do when you realize that you have accidentally cut the posterior vagus nerve during a hiatal hernia repair. Is the answer to proceed with a gastric drainage procedure correct? The prevailing dogma seems to be that inadvertent vagotomy will produce gastric stasis/paresis and the stomach will not empty and hence should be accompanied by a gastric drainage procedure. This report presents clinical outcomes of 49 patients who underwent truncal vagotomy without a drainage procedure (pyloroplasty or gastrojejunostomy). 49 patients underwent truncal vagotomy with laparoscopic adjustable gastric banding in an IRB (Investigational Review Board)-approved clinical trial to determine if the addition of a vagotomy would increase achieved weight loss when compared to gastric banding alone. The details of this trial were presented at SAGES (Martin and Earle in Surg Endosc 25:2522–2525, 2011) in 2010. The patients in this study have been followed for over ten years and their histories were examined to look for evidence of gastric stasis or intractable diarrhea or if they required further surgery for these complaints. 49 patients have been followed for a mean of 10.9 years. All except one have experienced a loss of hunger and cessation of gastric borborygmus. One patient showed mild delayed gastric emptying after developing diabetes. Two other patients with DM carry a diagnosis of gastroparesis. No patient has experienced intractable diarrhea. Five patients have had revisions to sleeve gastrectomy or gastric bypass for weight loss failure or esophageal dilatation and GERD. Review of these truncal vagotomy patients without drainage procedures at 10 years does not support the myth that the stomach will not empty after vagotomy and a gastric drainage procedure should always accompany truncal vagotomy.
Exploring COVID-19 in a social studies methods course: Preservice teachers harness the current pandemic to design inquiry-based WebQuests for elementary learners

COVID-19 quickly upended life in many ways, presenting teachers with the opportunity to confront the issue with their students or forge ahead in the midst of a societal crisis. Teachers can harness such current events with youth in ways that foster active democratic citizenship, but they must be prepared to implement such pedagogy. This article illuminates how preservice teachers in an elementary social studies methods course explored the global pandemic of COVID-19 to become more informed citizens and to plan for powerful inquiry-based learning of the current pandemic with young learners.
Reconciling larval and adult sampling methods to model growth across life-stages

Individual growth rates are intrinsically related to survival and lifetime reproductive success and hence, are key determinants of population growth. Efforts to quantify age-size relationships are hampered by difficulties in aging individuals in wild populations. In addition, species with complex life-histories often show distinct shifts in growth that cannot be readily accommodated by traditional modelling techniques. Amphibians are often characterized by rapid larval growth, cessation of growth prior to metamorphosis, and resumption of growth in the adult stage. Compounding issues of non-linear growth, amphibian monitoring programs typically sample larval and adult populations using dissimilar methods. Here we present the first multistage growth model that combines disparate data collected across life-history stages. We model the growth of the endangered Reticulated Flatwoods Salamander, Ambystoma bishopi, in a Bayesian framework, that accounts for unknown ages, individual heterogeneity, and reconciles dip-net and drift fence sampling designs. Flatwoods salamanders achieve 60% of growth in the first 3 months of life but can survive for up to 13 years as a terrestrial adult. We find evidence for marked variability in growth rate, the timing and age at metamorphosis, and maximum size, within populations. Average size of metamorphs in a given year appeared strongly dependent on hydroperiod, and differed by >10mm across years with successful recruitment. In contrast, variation in the sizes of emerging metamorphs appeared relatively constant across years. An understanding of growth will contribute to the development of population viability analyses for flatwoods salamanders, will guide management actions, and will ultimately aid the recovery of the species. Our model formulation has broad applicability to amphibians, and likely any stage-structured organism in which homogenous data cannot be collected across life-stages. The tendency to ignore stage-structure or omit non-conforming data in growth analyses can no longer be afforded given the high stakes of management decisions, particularly for endangered or at-risk populations.