cssi/SciSciGPT-SciSciNet huggingface dataset:
Mechanisms for lymphocytic choriomeningitis virus glycoprotein cleavage, transport, and incorporation into virions

The glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV) serves as virus attachment protein to its receptor on host cells and is a key determinant for cell tropism, pathogenesis, and epidemiology of the virus. The GP of LCMV is posttranslationally cleaved by the subtilase SKI-1/S1P into two subunits, the peripheral GP1, which is implicated in receptor binding, and the transmembrane GP2 that is structurally similar to the fusion active membrane proximal portions of the glycoproteins of other enveloped viruses. The present study shows that cleavage by SKI-1/S1P is not required for cell surface expression of LCMVGP on infected cells but is essential for its incorporation into virions and for the production of infectious virus particles. In absence of SKI-1/S1P cleavage, cell-to-cell propagation of the virus was markedly reduced. Further, proteolytic processing of LCMVGP depends on the presence of a cluster of basic amino acids at the C-terminus of the cytoplasmic domain of GP2, a structural motif that is conserved in Old World arenaviruses. The effect of the truncation of the cytoplasmic tail on cleavage suggests a structural interdependence between the cytoplasmic domain and the ectodomains of LCMVGP.
[3H]dihydroalprenolol binding in the rat brainstem.

Abstract The binding of [ 3 H]dihydroalprenolol to β-adrenergic receptors in the rat brainstem was studied. Propranolol inhibited dihydroalprenolol binding to a greater extent than did isoproterenol or epinephrine. Scatchard plots obtained with propranolol were biphasic whereas those obtained with isoproterenol and epinephrine were monophasic. The results indicate that in the brainstem propranolol displaces dihydroalprenolol from sites other than β-adrenergic receptors. Nonspecific binding of dihydroalprenolol in this tissue therefore cannot be assayed using propranolol but should be measured with isoproterenol or epinephrine.
Kitz-Wilson Mechanisms of Action of Neostigmine and Penicillin

The molecular mechanism of penicillin action is closely analogous to that of neostigmine. Both drugs react co- valently with the active-site serine of their target enzymes. In both cases, the susceptible enzymes self-catalyze their inac- tivation by their respective drugs. Kinetic analysis of cholinesterase by Richard J. Kitz and Irwin B. Wilson helped to es- tablish that concept. Neostigmine and penicillin are kindred examples of mechanism-based enzyme inhibition, a generally important phenomenon in pharmacology and physiology.
Integrating control design and sensor/actuator selection

This paper presents a system level optimal design solution by integrating the feedback control design and sensor/actuator selection. Instead of designing the feedback control law with predefined sensors and actuators, we determine the precision of sensor/actuator and the control law simultaneously such that the total sensor/actuator cost is minimized while the specified control performance is satisfied. Using covariance upper bounded output feedback control, this paper shows that the full order output feedback control design problem remains convex after freeing the selection of sensor/actuator precisions. All the design constraints - output performance, input effort and sensor/actuator cost, are converted to LMIs. Hence a global solution is achieved
Use of Multi Threaded Asynchronous DNA Sequence Pattern Searching Tool to Identifying Zinc-Finger-Nuclease Binding Sites on the Human Genome

In this paper we present the development and implementation of a comprehensive interoperable computation tool to assist biomedical researchers to conduct, analyze and interpret experiments on a significantly accelerated pace. Explosion of biological data due to large scale genomic research and advances in high throughput tools results in massive distributed datasets. High complex biological data require unconventional computational approaches and knowledge-based solutions. Distributed datasets need to be reduced to smaller datasets that can be efficiently queried. Lack of customized and tailored computational tools severely hampers efficient work in laboratories. In this paper we report on the development and use of a tailor-made computational tool for revealing the fundamental nature of DNA-Protein interactions of zinc finger type engineered DNA-binding proteins that are poised to be widely used as zinc finger nucleases (ZNFs) to regulating genes and precisely modifying the genome. Designing customized DNA-binding proteins for medical use requires the processing of very large datasets. We evaluate a cloud-based practical distributed file system with Map Reduce parallel processing and its column oriented Hbase databases. Proven genetic String algorithms are studied in distributed parallel framework. We address the practical implementation of transforming any String Algorithm to map reduce framework which can parallel process on each machine.
Acute Paget-Schroetter syndrome: does the first rib routinely need to be removed after thrombolysis?

Background Most clinicians feel that treatment for patients with acute primary axillosubclavian vein thrombosis (“effort thrombosis”) is catheter-directed thrombolysis followed by thoracic outlet decompression. Several investigators feel that first rib resection (FRR) is not indicated in every case. No randomized data exist to answer this question. Methods A MEDLINE search was done using the terms “Paget-Schroetter syndrome,” “upper extremity DVT,” “first rib resection,” “effort thrombosis,” and “primary upper extremity thrombosis,” with thrombolysis used as an “AND” term. We also specifically explored references cited to support either side of this argument in the past. Analysis was limited to patients aged 18 years or older with symptoms of 14-day duration or less undergoing thrombolysis for primary axillosubclavian vein thrombosis. Those studies that did not report follow-up, duplicate series from the same institution, and those in which patients were stented were excluded. Results were analyzed on an intent-to-treat basis, with groups assigned according to each authors' prospectively described algorithm. Results Twelve series were included. Patients were divided into 3 groups according to treatment after thrombolysis: FRR (448 patients), FRR plus endovenous balloon venoplasty (FRR + PLASTY; 68 patients), and those with no further intervention after thrombolysis (rib not removed; 168 patients). Symptom relief at last follow-up was significantly more likely in the FRR (95%) and FRR + PLASTY (93%) groups than in the rib not removed (54%) group (both Conclusions In patients with acute effort thrombosis who undergo thrombolysis, permanent symptom relief and long-term patency are more likely to be achieved in patients who undergo FRR with or without endovenous balloon venoplasty than those whose rib is left intact.
On the dimensionality of steady-state vowel normalization

Vowel classification is considered from the viewpoint of cluster separation in a vector space, with Mahalanobis distance as the criterion. The number of significant axes of variation needed to characterize each speaker, weighted with respect to cluster separation, is found from actual formant data to be on the order of four, and the potential improvement in separation accountable to structure in the data is estimated at about 3 db by comparison with results for the same procedure applied to random data.
Caring for Pregnant Adolescents: Perils and Pearls Of Communication

Pregnant adolescents view nurses as trustworthy and caring. It's critical that nurses recognize their significant influence on these patients and the importance of establishing effective and therapeutic communication with them.
Now and Always Our Chief: The Honorable Judith S. Kaye

This essay is part of volume celebrating the successful tenure of Chief Judge Judith Kaye of the New York Court of Appeals. The author shares personal and professional reflections on her encounters with Judge Kaye as a law student, legal practitioner, and law professor. The essay offers unique insights into the traits and habits that made Judge Kaye such a remarkable and beloved Chief Judge.
Estimation of potential evapotranspiration in the mountainous Panama Canal watershed

Spatially distributed hydrometeorological and plant information within the mountainous tropical Panama Canal watershed is used to estimate parameters of the Penman–Monteith evapotranspiration formulation. Hydrometeorological data from a few surface climate stations located at low elevations in the watershed are complemented by (a) typical wet- and dry-season fields of temperature, wind, water vapour and pressure produced by a mesoscale atmospheric model with a 3 × 3 km2 spatial and hourly temporal resolution, and (b) leaf area index fields estimated over the watershed during a few years using satellite data with two different spatial and temporal resolutions. The mesoscale model estimates of spatially distributed surface hydrometeorological variables provide the basis for the extrapolation of the surface climate station data to produce input for the Penman–Monteith equation. The satellite information and existing digital spatial databases of land use and land cover form the basis for the estimation of Penman–Monteith spatially distributed parameter values. Spatially distributed 3 × 3 km2 potential evapotranspiration estimates are obtained for the 3300 km2 Panama Canal watershed. Estimates for Gatun Lake within the watershed are found to reproduce well the monthly and annual lake evaporation obtained from submerged pans. Sensitivity analysis results of potential evapotranspiration estimates with respect to cloud cover, dew formation, leaf area index distribution and mesoscale model estimates of surface climate are presented and discussed. The main conclusion is that even the limited spatially distributed hydrometeorological and plant information used in this study contributes significantly toward explaining the substantial spatial variability of potential evapotranspiration in the watershed. These results also allow the determination of key locations within the watershed where additional surface stations may be profitably placed. Copyright © 2006 John Wiley & Sons, Ltd.
IL-21 Inhibits IFN-γ Production in Developing Th1 Cells through the Repression of Eomesodermin Expression

Exposure of naive Th cell precursors (Thp) to IL-21 inhibits IFN-gamma production from developing Th1 cells. The inhibition of IFN-gamma seen in IL-21-treated Thp cells is specific as the expression of other Th1 cytokines is unaffected. Recently, it has been reported that Eomesodermin (Eomes), a member of the T-box gene family, is expressed in developing CD8+ T cells and plays an important role in regulating IFN-gamma production and cytolytic effector function. In this study, we show that Eomes mRNA and protein are also expressed in developing Th1 cells, and exposure of naive Thp cells to IL-21 results in a decrease in Eomes expression. Moreover, the repression of Eomes expression by IL-21 is not due to an indirect effect of IL-21 on the expression of IFN-gamma or STAT4 and is independent of STAT1 and T-bet expression. Finally, we show that ectopic expression of Eomes prevents the inhibition of IFN-gamma production from IL-21-treated Thp cells. Taken together, these results demonstrate that Eomes plays a role in regulating IFN-gamma production in CD4+ T cells and IL-21 inhibits IFN-gamma production in developing Th1 cells through the repression of Eomes expression.
Calculation of hydrogen isotopic fractionations in biogeochemical systems

Hydrogen-isotopic data are often interpreted using mathematical approximations originally intended for other isotopes. One of the most common, apparent in literature over the last several decades, assumes that delta values of reactants and products are separated by a constant fractionation factor: δ_p = δ_r + e_(p/r). Because of the large fractionations that affect hydrogen isotopes, such approximations can lead to substantial errors. Here we review and develop general equations for isotopic mass balances that include the differential fractionation of each component in a mixture and discuss their use in three geochemical applications. For the fractionation of a single component, the reactant and product are related by δ_p = α_(p/r)δ_r + e_(p/r), where α and e refer to the same fractionation. Regression of δ_p on δ_r should give equivalent fractionations based on the intercept and slope, but this has not generally been recognized in studies of D/H fractionation. In a mixture of two components, each of which is fractionated during mixing, there is no unique solution for the three unknown variables (two fractionation factors and the elemental mixing ratio of the two hydrogen sources). The flow of H from CH_4 and H_2O to bacterial lipids in the metabolism of Methylococcus capsulatus provides an example of such a case. Data and conclusions from an earlier study of that system (Sessions et al., 2002) are reexamined here. Several constraints on the variables are available based on plausible ranges for fractionation factors. A possible refinement to current experimental procedures is the measurement of three different isotopes, which would allow unique determination of all variables.
Association between alcohol screening results and hospitalizations for trauma in Veterans Affairs outpatients.

Background: Alcohol consumption is a risk factor for traumatic injury, but it is unknown whether responses to alcohol screening questionnaires administered routinely in primary care are associated with subsequent hospitalization for traumatic injury. Objective: We evaluated the association between alcohol screening scores and the risk for subsequent hospitalizations for trauma among Veterans Affairs (VA) general medicine patients. Method: This study included VA outpatients (n = 32,623) at seven sites who returned mailed surveys (1997–1999). Alcohol Use Disorders Identification Test Consumption (AUDIT-C) scores grouped patients into six drinking categories representing nondrinkers, screen-negative drinkers, and drinkers who screened positive for mild, moderate, severe, and very severe alcohol misuse (scores 0, 1–3, 4–5, 6–7, 8–9, 10–12, respectively). VA administrative and Medicare data identified primary discharge diagnoses for trauma. Cox proportional hazard models were used to estimate the risk of traum...
Hellfire and Damnation: Four Ancient and Modern Views

Hell is a doctrine that has always had its uses. The range of those uses can be conveniently traced by examining a passage from Cold Comfort Farm, the comic novel by Stella Gibbons, first published in 1932. The novel is set in rural England during the third decade of the twentieth century, a time when automobiles were not entirely unknown but not yet widely in use. The scene to be examined involves Flora Poste and Amos Starkadder. Flora is a young, sophisticated woman who has gone to visit her relatives in the country, and Amos is her gray-haired, grizzled cousin, a Scotsman who lives on the farm with other kinfolk and who serves as a lay preacher in town at the Church of the Quivering Brethren. Flora accompanies Amos to a preaching service one evening. They arrive by horse and buggy, enter the hall, and take their seats. Flora sits in the back near the exit, Amos by the platform up front.
Fullerenes with complete Clar structure

It is known that the Fries number for a fullerene @C=(V,E,F) is bounded above by |V|3 and the fullerenes that attain this bound have been characterized. The corresponding bound for the Clar number is |V|6-2. In this paper, we characterize the fullerenes for which this bound is attained, and also characterize the fullerenes for which the upper bounds for the Clar and the Fries number are simultaneously achieved.
Inhibition of Salmonella enterica Serovar Typhimurium Lipopolysaccharide Deacylation by Aminoarabinose Membrane Modification

Salmonella enterica serovar Typhimurium remodels the lipid A component of lipopolysaccharide, a major component of the outer membrane, to survive within animals. The activation of the sensor kinase PhoQ in host environments increases the synthesis of enzymes that deacylate, palmitoylate, hydroxylate, and attach aminoarabinose to lipid A, also known as endotoxin. These modifications promote bacterial resistance to antimicrobial peptides and reduce the host recognition of lipid A by Toll-like receptor 4. The Salmonella lipid A 3-O-deacylase, PagL, is an outer membrane protein whose expression is regulated by PhoQ. In S. enterica serovar Typhimurium strains that had the ability to add aminoarabinose to lipid A, 3-O-deacylated lipid A species were not detected, despite the PhoQ induction of PagL protein expression. In contrast, strains defective for the aminoarabinose modification of lipid A demonstrated in vivo PagL activity, indicating that this membrane modification inhibited PagL's enzymatic activity. Since not all lipid A molecules are modified with aminoarabinose upon PhoQ activation, these results cannot be ascribed to the substrate specificity of PagL. PagL-dependent deacylation was detected in sonically disrupted membranes and membranes treated with the nonionic detergent n-octyl-beta-d-glucopyranoside, suggesting that perturbation of the intact outer membrane releases PagL from posttranslational inhibition by aminoarabinose-containing membranes. Taken together, these results suggest that PagL enzymatic deacylation is posttranslationally inhibited by membrane environments, which either sequester PagL from its substrate or alter its conformation.
A Comparison of Naturalistic and Analog Treatment Effects in Children with Expressive Language Disorder and Poor Preintervention Imitation Skills

The participants in this study were 4 children diagnosed with Expressive Language Disorder who displayed poor imitation skills, with scores significantly below typical levels on the Sentence Imitation subtest of the Test of Language Development-2: Primary (Newcomer & Hammill, 1988). The purpose of this study was to compare the treatment effects of both natu- ralistic (conversational recast) treatment and analog treatment in these participants. The results indicate that children with poor preintervention imitation skills required higher numbers of analog presentations to establish production of the language structures than was observed under the naturalistic treatment. Clinical implications of these results are discussed.
Techniques for improved placement-coupled logic replication

Several recent papers have utilized logic replication driven by placement-level timing analysis for improving clock period (e.g., [1], [8], [18], and [2]). All of these papers demonstrated, through various optimization strategies, the potential of the basic technique of replication. In this paper we propose a number of techniques aimed at more fully realizing this potential within the framework employed in [8]. As reported in [7], there are situations in which the approach of [8] fails to yield significant additional improvement due largely to the effects of reconvergence in the netlist. We suggest the use of rectilinear Steiner arborescence embedding as a tool for overcoming this limitation. We also propose techniques for fanout partitioning and cell relocation which are cognizant of both wirelength and timing impact for improved solution quality. We report the effect of other techniques including new replication cost computation, lower-bounding of achievable clock period, and wirelength estimation. We have implemented and experimented with these techniques in FPGA domain. In many cases we were able to approach a fixed flip-flop lower-bound on achievable clock period. Promising experimental results are reported with average 17.4% (up to 39.9%) delay reduction compared with the timing-driven placement from VPR[16] and average 9.3% (up to 37.2%) reduction compared with the basic fanin tree embedder from [8].
Million Book Project vs Google™ Print

Google's announcement that it intended to digitize all the books in several major research libraries was met with mixed reactions. John Wilkin at the University of Michigan declared “This is the day the world changes,” while Rory Litwin said inLibrary Juice that the move would “commercialize the great research libraries with a handshake, suddenly and epochally.” The four directors of the Universal Library and Million Book Project have received many questions about the comparative aspects of our work and Google Print. My purpose is to compare the two, talking about their genesis, the realities of collections and logistics, and the worries that arise from these realities.
Markup Rules And The Incidence Of A Value-Added Tax At Different Stages Of The Production And Distribution Process

The burden of a value-added tax is distributed each time the ownership of merchandise changes as the merchandise moves down-stream through distribution channels to consumers. Other things being equal, the burden of the tax on retailers or other vendors purchasing merchandise for resale is determined by the markup rule chose by retailers or other vendors. Given the markup rules discussed, a fixed-percentage markup is shown to minimize the value-added tax burden on firms purchasing merchandise for resale.
PATHOLOGICAL GAIT IN RESIDUAL POLIOMYELITIS

1. Photographic studies were made of the pathways of motion in the lower extremities of selected cases of residual infantile paralysis. 2. The importance of the technique of this particular investigation was the fact that the patient was not weighted down with cumbersome apparatus, and was not required to walk on a treadmill. Either of the above adds further embarrassment to the gait of a paralyzed individual already operating under reduced efficiency, and the recordings thus obtained do not portray the true state of locomotion. 3. The kinesiological soundness of operative procedures may be scrutinized by this method by means of preoperative and postoperative studies. 4. Shortening of two inches did not fundamentally affect the pathwyys. It produced some increased rotation in the frontal plane and was reflected in the profile view by an exaggerated undulatory hip pathway, and, to a lesser degree, by a corresponding change in the knee pathway. 5. In equinus deformities, owing to the relative increase in the length of the extremity, a great deal of increased flexion occurred in the knee and hip in order to enable the foot to clear the ground; in stance the forefoot either struck the ground before the heel or simultaneously, depending on the degree of equinus; after the impact of the forefoot some of the patients showed a marked rebound resulting from the stretch reflex. 6. In calcaneus deformities, the heel struck the ground first in stance and remained in contact for a longer time than normal; the ankle and toe pathways were depressed, indicative of the fact that the foot was able to clear the ground with greater ease than the normal; the subjects tended to pivot on the heel with the knee fully extended. 7. An analysis of one case of calcaneovalgus following an astragalectomy and transplantation of the peroneus longus to the tendo achillis revealed striking graphic improvement in the gait consisting of: disappearance of heel pivoting; slight flexion of the knee in stance; decrease in the duration of the heel contact with the ground; normal pattern of the ankle curve; and striking of the forefoot on the ground a moment before the heel in stance (slight overcorrection). 8. This is a preliminary report, but the results indicate very defininitely that additional work in this field would be of great value in clarifying many of the problems of this complex subject.
Regulation of brain glutamate metabolism by nitric oxide and S-nitrosylation

ly reduced in the brains of mice lacking endothelial nitric oxide synthase (eNOS �/� ) or neuronal nitric oxide synthase (nNOS �/� ). In particular, nNOS �/� animals showed decreased S-nitrosylation of proteins that participate in the glutamate/glutamine cycle, a metabolic process by which synaptic glutamate is recycled or oxidized to provide energy. 15 N-glutamine–based metabolomic profiling and enzymatic activity assays indicated that brain extracts from nNOS �/� mice converted less glutamate to glutamine and oxidized more glutamate than those from mice of the other genotypes. GLT1 [also known as EAAT2 (excitatory amino acid transporter 2)], a glutamate transporter in astrocytes, was S-nitrosylated at Cys 373 and Cys 561 in wild-type and eNOS �/� mice, but not in nNOS �/� mice. A form of rat GLT1 that could not be S-nitrosylated at the equivalent sites had increased glutamate uptake compared to wild-type GLT1 in cells exposed to an S-nitrosylating agent. Thus, NO modulates glutamatergic neurotransmission through the selective, nNOS-dependent S-nitrosylation of proteins that govern glutamate transport and metabolism.
Disposable Paper Masks: Effective Technique for Use in Daytime Polysomnography

ABSTRACT.In 40 consecutive daytime polysomnography studies, paper surgical masks proved effective for measuring nasal-oral airflow with an attached thermocouple. In 35 of the patients, long periods of sleep were obtained without complaints of discomfort, restricted breathing, or condensation.
Prestack first-break traveltime tomography using the double-square-root eikonal equation

The work was supported by Saudi Aramco and KAUST. Wethank Tariq Alkhalifah and Tim Keho for useful discussions.
Prediction of wing flows with separation

An efficient and accurate calculation method for the prediction of three-dimensional flows with large regions of separation is described. The method is based on a stability/transition interactive boundary layer approach employing an extension to threedimensional flows of the modified Cebeci-Smith turbulence model. The method is first applied to the calculation of the flowfield about wings at low Reynolds numbers where the transition location is calculated within the threedimensional separation bubble. The method is then applied to three-dimensional flows at higher Reynolds numbers and the boundary layer parameters are compared with experimental data. Results show good agreement with data and demonstrate the importance of calculating the onset of transition location. The method is also applied to the calculation of wing lift coefficients up to stall. Results demonstrate the ability of the method to predict three-dimensional separated flows reliably, including near stall conditions, showing the potential of the method as a practical and efficient design tool for high lift applications.
Russian Relations with Authority: the Call for Strength and Unity in Leadership

While 20th-century Russia differs from Machiavelli’s 16th-century Italy, the struggles surrounding the establishment of republican government continue to be relevant. As the unity of the powerful Soviet state has disappeared, many contemporary Russians have reacted against state enforced collectivity. As if old modes of community are anathema, individuals have focused on personal protection and survival to the detriment of the collective society. This has left the construction of the new society to the ambitions of the political and economic elite. Unfortunately, there is neither unity of purpose among the elite, nor agreement on the composition of the society between the elite and the mass public. In looking for a solution, the Russian lack of familiarity with instability found the broadly conservative population searching for stability, generally without ideological concerns, through the reinstitution of some observable form of strong central authority: for where the body of the people is so thoroughly corrupt that the laws are powerless for restraint, it becomes necessary to establish some superior power which, … with full and absolute powers may put a curb upon the excessive ambition and corruption of the powerful.2
Abstract B113: In vivo characterization of anti-PD-1 antibody REGN2810 in human PD-1 knock-in mice

The Programmed Death-1 (PD-1) receptor is an immunologic inhibitory checkpoint, expressed by activated T cells. PD-1 signals upon binding to its ligands PD-L1 and PD-L2 expressed on antigen presenting cells and some types of cancer cells, and delivers inhibitory signals to T cells, resulting in suppression of T-cell effector function. In cancer patients, PD-1 is expressed on tumor-infiltrating lymphocytes and inhibits antitumor immune responses through ligand binding. Clinically, it has been shown that antibodies (Abs) that block the interaction between PD-1 and PD-L1 can release the cytotoxic function of tumor-specific T cells, yielding durable objective responses in multiple cancer types. This study describes preclinical characterization of REGN2810, a fully human hinge-stabilized IgG4 monoclonal Ab that binds to the extracellular domain of human PD-1 with high affinity and specificity and inhibits interaction of PD-1 with its ligands. Taking advantage of the ability of human PD-1 to interact with murine PD-L1, we generated a mouse with human PD-1 gene knock-in allowing direct testing of our anti-human PD-1 Ab. Human PD-1 knock-in mice express a hybrid protein containing the extracellular portion of human PD-1, and transmembrane and intracellular domains of mouse PD-1. We demonstrated functional PD-1/PD-L1 signaling and immune responses in this model, and confirmed REGN2810 binding to hybrid PD-1 receptor on mouse T cells in vivo following REGN2810 injections. Prophylactic and therapeutic treatments of subcutaneous syngeneic tumors with REGN2810 in human PD-1 knock-in mice resulted in a dose-dependent suppression of tumor growth. Currently REGN2810 anti-PD-1 Ab is in phase 1 clinical trials for oncology indications. Citation Format: Elena Burova, Omaira Allbritton, William Poueymirou, Venus Lai, Janelle Waite, Dimitris Skokos, Nicholas Papadopoulos, Drew Murphy, Israel Lowy, Ella Ioffe, Gavin Thurston. In vivo characterization of anti-PD-1 antibody REGN2810 in human PD-1 knock-in mice. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B113.
KGF prevents hydrogen peroxide-induced increases in airway epithelial cell permeability

Keratinocyte growth factor (KGF) has recently been shown to protect rats from hyperoxia-induced lung injury. However, the mechanism of the protective effect of KGF remains unclear. To elucidate the mechanism of action of KGF, we determined the effect of KGF on the barrier function of epithelial monolayers exposed to H(2)O(2). Calu-3 (human airway epithelial cells) were grown on Transwell membranes, and the permeability to fluorescein isothiocyanate-albumin was measured. Exposure to 0.5 mM H(2)O(2) significantly increased permeability from 1.50 +/- 0.09 to 24.8 +/- 1.5 (mean +/- SE x 10(-6) cm/s; P < 0.001). Incubation of monolayers with 50 ng/ml KGF for 24 h significantly reduced basal albumin flux (0.85 +/- 0.09; P < 0.001), and pretreatment with KGF completely abolished the H(2)O(2)-induced permeability increase (1.08 +/- 0.09). The protective effect of KGF was dose dependent and was observed at concentrations as low as 1 ng/ml. Partial amelioration of the H(2)O(2)-induced permeability increase occurred after 1 h of exposure to KGF. Treatment of cells with calphostin C, an inhibitor of protein kinase C (PKC), had no effect on the permeability of control or H(2)O(2)-treated cells. Calphostin C abolished both the KGF-mediated decrease in basal albumin flux and the protective effect of KGF against H(2)O(2)-induced increases in permeability. KGF pretreatment also prevented H(2)O(2)-induced disruption of F-actin staining patterns, suggesting stabilization of the cytoskeleton. These studies demonstrate that KGF decreases albumin flux across airway epithelial monolayers and prevents H(2)O(2)-induced increases in permeability by a PKC-dependent process that may involve stabilization of the cytoskeleton.
A Modified Delphi Process to Define Competencies for Assessment Leads Supporting a Doctor of Pharmacy Program.

Objective. To define the competencies for individuals designated as assessment leads in colleges and schools of pharmacy. Methods. Twenty-three assessment experts in pharmacy participated in a modified Delphi process to describe competencies for an assessment lead, defined as the individual responsible for curricular assessment and assessment-related to doctor of pharmacy program accreditation. Round 1 asked open-ended questions about knowledge, skills, and attitudes. Round 2 grouped responses for comment and rating for consensus, which was prospectively set at 80%. Results. Twelve competencies were defined and grouped into 3 areas: Context for Assessment, Managing the Process of Assessment, and Leadership of Assessment Activities. In order to verify the panel’s work, assessment competencies from other disciplines were reviewed and compared. Conclusions. The competencies describe roles for assessment professionals as experts, managers, and leaders of assessment processes. They can be used by assessment professionals in self-assessing areas for professional development and by administrators in selecting, developing, and supporting designated leads.
How to Deal with Mistakes

Physicians have the opportunity to gain incredible fulfillment and job satisfaction. We are granted the opportunity to materially affect the lives of others and mitigate suffering like no other vocation.
Post-hysterectomy extrauterine cotyledonoid leiomyoma in a 42-year-old female.

Cotyledonoid dissecting leiomyoma was originally described in 1975 in a case report by David et al. as a “grape-like leiomyoma of the uterus”.1 In 1996, Roth et al. coined the name “cotyledonoid dissecting leiomyoma”, based on the tumor's resemblance to cotyledons of the placenta and the accompanying dissecting myometrial component.2 To the best of our knowledge, this is the first case presented of cotyledonoid dissecting leiomyoma (CDL) occurring after a hysterectomy and originating from an extrauterine site. CDL consists of an exophytic component of smooth muscle which is rich in blood supply and has a multinodular gross appearance, suggestive of placental tissue. It typically protrudes from the lateral surface of the uterine cornu into the broad ligament and pelvic cavity. This exophytic component is in continuity with intramural dissecting components, which consist of sinuous processes of neoplastic smooth muscle extending between normal myometrial smooth muscle.2 CDL is a benign process, as histologically there is no nuclear atypia, mitotic activity, or coagulative tumor necrosis, which are suggestive of leiomyosarcoma.4
Reactivity Trends of Singlet Photochemical Cycloadditions

The analysis of photochemical cycloadditions involves as a first task the identification of the excited diabatic surface manifold. Fortunately, in most organic photoreactions, the lowest excited diabatic surface at infinite intermolecular distance is of the DA* or D*A type. The second task is the classification of a photocycloaddition according to the interrelationship of the DA, D+A−, and DA* (or D*A) diabatic surfaces by reference to the definitions of section 3.6 and the appropriate data.
The stoichiometry dependence of the deformation of Co1 − δO☆

The flow stress tau has been measured for Co/sub 1-delta/O single crystals as a function of strain ..gamma.., between 1000 and 1400/sup 0/C, using strain rates of 5 x 10/sup -6/ to 5 x 10/sup -4/ s/sup -1/, and varying the oxygen partial pressure P/sub O/sub 2// from 10/sup -11/ to 1 atm in order to obtain deviations from stoichiometry delta ranging from approx. =2 x 10/sup -5/ to 10/sup -2/. The tau vs ..gamma.. curves have a pronounced upper yield. The stress then decreases to a minimum tau/sub s/ before additional hardening occurs. A study of the dependence of tau/sub s/ on P/sub O/sub 2// and epsilon indicates that for delta less than or equal to 10/sup -3/ the diffusion of the oxygen vacancy may control the deformation rate. For larger delta, deformation is controlled by diffusion of the oxygen interstitial. The results suggest that the Arrhenius plots are curved, possibly owing to extrinsic effects at the lowest temperature. Serrated flow is observed for small delta at 1000/sup 0/C. The activation energy for deformation is independent of delta, but is stress dependent because the strain-rate sensitivity is a function of temperature.
The Role of Lattice Oxygen in the Oxidative Coupling of Methane

The nature of the oxide site responsible for the oxidative coupling of methane has been the subject of much speculation with respect to the reaction mechanism. Under methane coupling conditions, various oxygen species may be present on a catalyst surface and thus the potential oxidants for methane and the intermediates formed from methane.
Distributed Consensus Control for General Uncertain Linear Multi-Agent Systems

This paper addresses the consensus problem for uncertain linear multi-agent systems with distributed state feedback protocol based on relative information of the neighboring agents. The agents share identical nominal linear time-invariant (LTI) dynamics subject to structured uncertainty. Through model transformation, the robust consensus control problem of high dimensional network reduced to scaled $H$ ∞ control problems of a set of independent n-dimensional linear systems. Sufficient analysis conditions are provided for the robust consensus of uncertain multi-agents with $H$ ∞ bound. Moreover, control synthesis condition is established as linear matrix inequalities (LMIs) and can be solved efficiently. Simulation study on a multi-agent system demonstrates the advantage of theoretical results.
Effects of Note-Taking Method on Knowledge Transfer in Inspection Tasks

International nuclear safeguards inspectors visit nuclear facilities to assess their compliance with international nonproliferation agreements. Inspectors note whether anything unusual is happening in the facility that might indicate the diversion or misuse of nuclear materials, or anything that changed since the last inspection. They must complete inspections under restrictions imposed by their hosts, regarding both their use of technology or equipment and time allotted. Moreover, because inspections are sometimes completed by different teams months apart, it is crucial that their notes accurately facilitate change detection across a delay. The current study addressed these issues by investigating how note-taking methods (e.g., digital camera, hand-written notes, or their combination) impacted memory in a delayed recall test of a complex visual array. Participants studied four arrays of abstract shapes and industrial objects using a different note-taking method for each, then returned 48–72 h later to complete a memory test using their notes to identify objects changed (e.g., location, material, orientation). Accuracy was highest for both conditions using a camera, followed by hand-written notes alone, and all were better than having no aid. Although the camera-only condition benefitted study times, this benefit was not observed at test, suggesting drawbacks to using just a camera to aid recall. Change type interacted with note-taking method; although certain changes were overall more difficult, the note-taking method used helped mitigate these deficits in performance. Finally, elaborative hand-written notes produced better performance than simple ones, suggesting strategies for individual note-takers to maximize their efficacy in the absence of a digital aid.
Factors Impacting Transition Readiness in Young Adults with Neuropathic Bladder

Summary Introduction Patients with spina bifida (SB) often have cognitive impairments making the difficult transition process to adult care even more challenging. Objective The objective of this study was to identify what patient factors impact transition readiness in this population. It is hypothesized that young adults with SB with more healthcare exposure were more likely to report readiness to transition. Methods Consecutive patients ≥ 18 years old in the adult SB clinic were evaluated using the validated Transition Readiness Assessment Questionnaire (TRAQ, 8/17-5/18). Five TRAQ domains assess 20 skills necessary to transition. Responses are 1 No, I do not know how"; 2 No, but I want to learn"; 3 No, but I am learning how to do this"; 4 Yes, I have started doing this"; 5 Yes, I always do this when I need to" (considered "fully transitioned"). Demographics, ambulatory status, shunt status, shunt revisions, number of medications, and prior bladder augmentation were assessed. Domain and total TRAQ scores were analyzed using non-parametric statistics and linear regression. Results Ninety-six patients (60.4% females, 70.8% shunted) participated at median age 25.5 years. Overall median TRAQ score was 4.0/5.0, indicating that patients were starting to transition. On univariate analysis, age >25 years was associated with higher TRAQ scores across every domain and overall (P ≤ 0.01). Female gender was also associated with higher TRAQ scores for "Appointment Keeping," "Tracking Health Issues" and overall (P ≤ 0.03). Race, ambulatory status, shunt status, number of shunt revisions, number of medications, and prior bladder augmentation were not associated with TRAQ scores (P ≥ 0.12). After adjusting for gender on bivariate analysis, age >25 years was associated with higher TRAQ scores for "Appointment Keeping," "Tracking Health Issues," "Talking with Providers," and "Managing Daily Activities" domains and overall (P ≤ 0.03), but not the "Managing Medications" domain (P = 0.07). Female gender was not independently associated with higher domain or overall TRAQ scores (P≥0.10). Discussion The transition readiness of young adults with SB compared based on demographic factors and factors increasing healthcare exposure is described. Limitations include the small sample size, potentially limiting generalizability, as well as cross-sectional nature. Conclusion Transitioning adults with SB had TRAQ scores indicating that they were not yet fully transitioned in terms of their healthcare-related behavior. Older age was the only factor associated with transition readiness, which was not impacted by other demographics. Increased attention to transition readiness and consideration of a longer transition process in this population is necessary.
Abstract A23: Proteogenomic discovery of novel tumor proteins as neoantigens for personalized T-cell immunotherapy in pediatric medulloblastoma

Medulloblastoma is a common childhood brain tumor for which current therapies fail to cure high-risk subgroups, including metastatic and recurrent disease. Toxicity limits further intensification of conventional chemo-radiation therapy, and most survivors endure significant lifelong sequelae from treatment. There is an urgent need to develop new tools to combat this cancer without increasing the late effects burden. Neoantigens, which are exclusively expressed on tumor cells, are one of the main targets of an effective antitumor T-cell response. The ideal target antigen is abundantly expressed by tumor cells but not by normal tissues, in order to limit off-target effects. Tumors translate a host of highly novel transcripts that are the result of aberrations in tumor DNA and the unmasking of alternative or novel exons. We used a novel proteogenomic approach to identify tumor-restricted peptides and used them to select and expand T cells capable of mounting a tumor-specific cytotoxic immune response, with no off-target effects for patients with MB. Using RNA-seq and WGS data, we created personalized custom searchable databases containing predicted novel proteins from somatic mutations, novel isoforms, and fusion proteins from 56 medulloblastoma tumors. By searching this database with raw mass spectrometry data from the paired medulloblastoma tumor, we have identified tens of peptides arising from the translation of tumor-specific transcripts; these peptides are potential neoantigens. Our data indicate that in cases of tumors with low mutation rates, such as pediatric brain tumors, novel isoforms are the main source of neoantigens. In a pilot study, we have tested these peptides for their ability to select and expand polyclonal populations of T cells from the same patient whose tumor was the source of the peptides. The immunogenicity of each individual peptide was then determined. Flow cytometry cellular characterization reveals populations of both CD4+ and CD8+ cells with an activation profile marked by IFN-γ and TNF-α production. Immunosuppressive marker profiles have also been characterized for these cells. Using cytotoxicity assays, we demonstrated that tumor-specific T cells can eliminate neoantigen-bearing tumor cells. These findings demonstrate an initial proof of principle that proteogenomics can be used to identify immunogenic tumor specific peptides and lay the groundwork for a personalized, targeted T-cell therapy for children with high-risk medulloblastoma. Citation Format: Samuel Rivero-Hinojosa, Melanie Grant, Aswini Panigrahi, Huizhen Zhang, Veronika Caisova, Catherine Bollard, Brian Rood. Proteogenomic discovery of novel tumor proteins as neoantigens for personalized T-cell immunotherapy in pediatric medulloblastoma [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A23.
QURIOUS: Question Generation Pretraining for Text Generation

Recent trends in natural language processing using pretraining have shifted focus towards pretraining and fine-tuning approaches for text generation. Often the focus has been on task-agnostic approaches that generalize the language modeling objective. We propose question generation as a pretraining method, which better aligns with the text generation objectives. Our text generation models pretrained with this method are better at understanding the essence of the input and are better language models for the target task. When evaluated on two text generation tasks, abstractive summarization and answer-focused question generation, our models result in state-of-the-art performances in terms of automatic metrics. Human evaluators also found our summaries and generated questions to be more natural, concise and informative.
Perspectives of East Tennessee's Rural Public Librarians About the Extent of Need for Professional Library Education: A Pilot Study

This article presents findings from a pilot study that explored the perspectives of East Tennessee's regional public librarians about their extent of need for professional library education and the knowledge, skills, abilities, and opportunities required in the region's rural libraries to best serve their communities. Data collection methods included: quantitative web-based survey with select open-ended questions; ongoing feedback from regional librarians in the University of Tennessee's School of Information Sciences' (SIS) advisory board and alumni networks; paraprofessional experiences shared by students in the SIS synchronous distance education program; anecdotal feedback collected from local/regional/state-level library networks; and strategic planning in East Tennessee's two regional libraries. Research findings indicate that East Tennessee's regional public librarians have a strong desire to access professional library education that integrates rural library management and information technology competencies to help their communities effectively address some of their unique debilitating challenges and circumstances.
Spectral Terms and Stereoisomers

We have dealt with the symmetry properties of atomic orbitals and wave functions. Electronic energy states of isolated atoms or ions are characterized by term symbols that correspond closely in symmetry properties to atomic orbitals. We must be able to derive the term symbols for any electron configuration and obtain the symmetry species for the corresponding energy states for any environment. Before beginning major topics, we examine the usefulness of symmetry and group theory in dealing with stereoisomers.