cssi/SciSciGPT-SciSciNet huggingface dataset:
Discovery of Novel Antiangiogenic Marine Natural Product Scaffolds.

Marine natural products (MNPs) are recognized for their structural complexity, diversity, and novelty. The vast majority of MNPs are pharmacologically relevant through their ability to modulate macromolecular targets underlying human diseases. Angiogenesis is a fundamental process in cancer progression and metastasis. Targeting angiogenesis through selective modulation of linked protein kinases is a valid strategy to discover novel effective tumor growth and metastasis inhibitors. An in-house marine natural products mini-library, which comprises diverse MNP entities, was submitted to the Lilly’s Open Innovation Drug Discovery platform. Accepted structures were subjected to in vitro screening to discover mechanistically novel angiogenesis inhibitors. Active hits were subjected to additional angiogenesis-targeted kinase profiling. Some natural and semisynthetic MNPs, including multiple members of the macrolide latrunculins, the macrocyclic oxaquinolizidine alkaloid araguspongine C, and the sesquiterpene quinone puupehenone, showed promising results in primary and secondary angiogenesis screening modules. These hits inhibited vascular endothelial growth factor (VEGF)-mediated endothelial tube-like formation, with minimal cytotoxicity at relevant doses. Secondary kinase profiling identified six target protein kinases, all involved in angiogenesis signaling pathways. Molecular modeling and docking experiments aided the understanding of molecular binding interactions, identification of pharmacophoric epitopes, and deriving structure-activity relationships of active hits. Marine natural products are prolific resources for the discovery of chemically and mechanistically unique selective antiangiogenic scaffolds.
Conducting Substance Use Research , by Audrey L. Begun and Tom Gregoire

Relative to other disciplines, substance use research in social work is still in its infancy, yet social work practitioners routinely encounter clients with substance use problems. Social work rese...
Humanized Anti-IL-5 Antibody Therapy

Eosinophils are suppressed by a new class of drugs targeting Interleukin-5 (IL-5), an eosinophil growth, activation, and survival factor. Humanized anti-IL-5 antibodies are effective in treating asthma patients with the severe eosinophilic form of the disease and are the first new class of asthma drugs approved in 12 years.
A connectionist modeling study of the neural mechanisms underlying pain’s ability to reorient attention

Connectionist modeling was used to investigate the brain mechanisms responsible for pain's ability to shift attention away from another stimulus modality and toward itself. Different connectionist model architectures were used to simulate the different possible brain mechanisms underlying this attentional bias, where nodes in the model simulated the brain areas thought to mediate the attentional bias, and the connections between the nodes simulated the interactions between the brain areas. Mathematical optimization techniques were used to find the model parameters, such as connection strengths, that produced the best quantitative fits of reaction time and event-related potential data obtained in our previous work. Of the several architectures tested, two produced excellent quantitative fits of the experimental data. One involved an unexpected pain stimulus activating somatic threat detectors in the dorsal posterior insula. This threat detector activity was monitored by the medial prefrontal cortex, which in turn evoked a phasic response in the locus coeruleus. The locus coeruleus phasic response resulted in a facilitation of the cortical areas involved in decision and response processes time-locked to the painful stimulus. The second architecture involved the presence of pain causing an increase in general arousal. The increase in arousal was mediated by locus coeruleus tonic activity, which facilitated responses in the cortical areas mediating the sensory, decision, and response processes involved in the task. These two neural network architectures generated competing predictions that can be tested in future studies.
eBee: Merging Quilting, Electronics & Board Game Design

eBee is a strategic board game that merges quilting, e-textiles and game design to bridge the gender, ethnic and generation gap in electronics. The game revolves around placing quilted tiles embedded with conductive fabric on a hexagonal grid. The goal is to complete a circuit by laying a path of conductive fabric between a centralized hub or power source, and satellite islands that illuminate when the circuit is completed. eBee aims to merge the social contexts of the female-friendly experience of a quilting bee, the multi-generational appeal of a board game, and the techno-creative practices the maker movement. While the game has stand-alone integrity as both an interactive artwork and a game, it also has the benefit of engaging players in learning about electricity. In addition to exhibiting and possibly selling the game as a completed product, we also plan to develop eBee workshops and an online set of instructables that encourage people to create their own eBees.
Platelet activation by cross-linking HLA class I molecules and Fc receptor.

The effect on platelet activation of monoclonal antibodies directed against common determinants of the HLA class I heavy chain molecule was studied. Cross-linking W6/32, an anti-HLA class I of IgG2a subclass, led to platelet activation. Two other antibodies of the same subclass did not have this effect on platelets. The lack of activity of the F(ab')2 fragments suggests that the activation signal is mediated by the platelet Fc receptor (Fc gamma RII). Indeed, except for a higher sensitivity of W6/32 to aspirin and apyrase, activations by cross- linking IV-3 (an anti-Fc gamma RII) and W6/32 are similar at the level of InsP3 formation, calcium mobilization, pH modifications, and activation of protein kinase C and myosin kinase. When HLA class I molecules and Fc gamma RII are cross-linked together, platelet activation occurs. This is not observed when a control IgG2a is substituted for W6/32 or when CD9 and Fc receptor are cross-linked together. This suggests that HLA class I molecules and Fc gamma RII synergize to activate platelets.
Staphylococcus aureus activation of NLRP3 inflammasome and necroptosis through MLKL exacerbates pneumonia

Staphylococcus aureus (SA) cause a highly inflammatory pneumonia associated with substantial pulmonary damage. We demonstrate that alveolar macrophages along with other immune effectors are deplete...
JC virus granule cell neuronopathy in the setting of chronic lymphopenia treated with recombinant interleukin-7

JC virus (JCV) is a human polyomavirus that infects the central nervous system (CNS) of immunocompromised patients. JCV granule cell neuronopathy (JCV-GCN) is caused by infection of cerebellar granule cells, causing ataxia. A 77-year-old man with iatrogenic lymphopenia presented with severe ataxia and was diagnosed with JCV-GCN. His ataxia and cerebrospinal fluid (CSF) improved with intravenous immunoglobulin, high-dose intravenous methylprednisolone, mirtazapine, and mefloquine. Interleukin-7 (IL-7) therapy reconstituted his lymphocytes and reduced his CSF JCV load. One month after IL-7 therapy, he developed worsening ataxia and CSF inflammation, which raised suspicion for immune reconstitution inflammatory syndrome. Steroids were restarted and his ataxia stabilized.
WE-DE-207B-10: Library-Based X-Ray Scatter Correction for Dedicated Cone-Beam Breast CT: Clinical Validation

Purpose: Scatter contamination is detrimental to image quality in dedicated cone-beam breast CT (CBBCT), resulting in cupping artifacts and loss of contrast in reconstructed images. Such effects impede visualization of breast lesions and the quantitative accuracy. Previously, we proposed a library-based software approach to suppress scatter on CBBCT images. In this work, we quantify the efficacy and stability of this approach using datasets from 15 human subjects. Methods: A pre-computed scatter library is generated using Monte Carlo simulations for semi-ellipsoid breast models and homogeneous fibroglandular/adipose tissue mixture encompassing the range reported in literature. Projection datasets from 15 human subjects that cover 95 percentile of breast dimensions and fibroglandular volume fraction were included in the analysis. Our investigations indicate that it is sufficient to consider the breast dimensions alone and variation in fibroglandular fraction does not significantly affect the scatter-to-primary ratio. The breast diameter is measured from a first-pass reconstruction; the appropriate scatter distribution is selected from the library; and, deformed by considering the discrepancy in total projection intensity between the clinical dataset and the simulated semi-ellipsoidal breast. The deformed scatter-distribution is subtracted from the measured projections for scatter correction. Spatial non-uniformity (SNU) and contrast-to-noise ratio (CNR) were used as quantitative metrics to evaluate the results. Results: On the 15 patient cases, our method reduced the overall image spatial non-uniformity (SNU) from 7.14%±2.94% (mean ± standard deviation) to 2.47%±0.68% in coronal view and from 10.14%±4.1% to 3.02% ±1.26% in sagittal view. The average contrast to noise ratio (CNR) improved by a factor of 1.49±0.40 in coronal view and by 2.12±1.54 in sagittal view. Conclusion: We demonstrate the robustness and effectiveness of a library-based scatter correction method using patient datasets with large variability in breast dimensions and composition. The high computational efficiency and simplicity in implementation make this attractive for clinical implementation. Supported partly by NIH R21EB019597, R21CA134128 and R01CA195512.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Hip and ankle responses for reactive balance emerge from varying priorities to reduce effort and kinematic excursion: a simulation study

Although standing balance is important in many daily activities, there has been little effort in developing detailed musculoskeletal models and simulations of balance control compared to other whole-body motor activities. Our objective was to develop a musculoskeletal model of human balance that can be used to predict movement patterns in reactive balance control. Similar to prior studies using torque-driven models, we investigated how movement patterns during a reactive balance response are affected by high-level task goals (e.g., reducing center-of-mass movement, maintaining vertical trunk orientation, and minimizing effort). We generated 23 forward dynamics simulations where optimal muscle excitations were found using cost functions with different weights on minimizing these high-level goals. Variations in hip and ankle angles observed experimentally (peak hip flexion=7.9-53.1°, peak dorsiflexion=0.5-4.7°) could be predicted by varying the priority of these high-level goals. More specifically, minimizing center-of-mass motion produced a hip strategy (peak hip flexion and ankle dorsiflexion angles of 45.5° and 2.3°, respectively) and the response shifted towards an ankle strategy as the priority to keep the trunk vertical was increased (peak hip and ankle angles of 13.7° and 8.5°, respectively). We also found that increasing the priority to minimize muscle stress always favors a hip strategy. These results are similar to those from sagittal-plane torque-driven models. Our muscle-actuated model facilitates the investigation of neuromechanical interactions governing reactive balance control to predict muscle activity and movement patterns based on interactions between neuromechanical elements such as spinal reflexes, muscle short-range stiffness, and task-level sensorimotor feedback.
Glass fiber-reinforced polymer packaged fiber Bragg grating sensors for low-speed weigh-in-motion measurements

The weight of rolling trucks on roads is one of the critical factors for the management of road networks due to the continuous increase in truck weight. Weigh-in-motion (WIM) sensors have been widely used for weight enforcement. A three-dimensional glass fiber-reinforced polymer packaged fiber Bragg grating sensor (3-D GFRP-FBG) is introduced for in-pavement WIM measurement at low vehicle passing speed. A sensitivity study shows that the developed sensor is very sensitive to the sensor installation depth and the longitudinal and transverse locations of the wheel loading position. The developed 3-D GFRP-FBG sensor is applicable for most practical pavements with a panel length larger than 6 ft, and it also shows a very good long-term durability. For the three components in 3-D of the developed sensor, the longitudinal component has the highest sensitivity for WIM measurements, followed by the transverse and vertical components. Field testing validated the sensitivity and repeatability of the developed 3-D GFRP-FBG sensor. The developed sensor provides the transportation agency one alternative solution for WIM measurement, which could significantly improve the measurement efficiency and long-term durability.
Crystal Structure of AgBi2I7 Thin Films.

Synthesis of cubic-phase AgBi2I7 iodobismuthate thin films and fabrication of air-stable Pb-free solar cells using the AgBi2I7 absorber have recently been reported. On the basis of X-ray diffraction (XRD) analysis and nominal composition, it was suggested that the synthesized films have a cubic ThZr2H7 crystal structure with AgBi2I7 stoichiometry. Through careful examination of the proposed structure and computational evaluation of the phase stability and bandgap, we find that the reported “AgBi2I7” films cannot be forming with the ThZr2H7-type structure, but rather more likely adopt an Ag-deficient AgBiI4 type. Both the experimental X-ray diffraction pattern and bandgap can be better explained by the AgBiI4 structure. Additionally, the proposed AgBiI4 structure, with octahedral bismuth coordination, removes unphysically short Bi–I bonding within the [BiI8] hexahedra of the ThZr2I7 model. Our results provide critical insights for assessing the photovoltaic properties of AgBi2I7 iodobismuthate materials.
Bone Marrow Endothelial Cell Support of Primitive Hematopoietic Cells

Hematopoietic stem cells (HSCs) in the bone marrow (BM) reside in specialized microenvironments known as the stem cell niche. Many reports have found the HSCs to be resident next to the endosteal surface of bone where cells of the osteoblastic lineage are a key component of the so-called endosteal niche. However, HSCs have also been found to reside adjacent to sinusoidal blood vessels. These observations have led to the proposal that HSCs in the adult BM may also reside in a vascular niche. However, the functional role of the vascular niche in hematopoiesis remains to be determined. We wished to evaluate the role that BM endothelial cells (BMECs) play in HSC physiology. To examine this we cultured BMEC-enriched cells in vitro , identified by expression of CD31, Tie-2, VE-cadherin and LDL uptake. We compared these cells to spleen derived ECs and BM stromal cells (BMSCs) in their ability to support primitive hematopoietic cells for extended periods in in vitro culture. We found that BMECs were superior in their ability to support the cobblestone area forming cell activity of VEGF-R1 + HSCs than spleen ECs or BMSCs. We also found that the number of cobblestone area cells was markedly reduced when VEGF-R1 − HSCs were cultured on any of the supportive cell layers, however this may be due to an intrinsic difference between these cells as a much higher proportion of VEGF-R1 + HSCs were found to be in the G 0 phase of the cell cycle than VEGF-R1 − cells. To evaluate the supportive role of BMECs, spleen ECs or BMSCs on hematopoietic progenitor cells (HPC) we cultured purified primitive cells on these supportive layers and the total number of colony-forming unit-culture (CFU-C) cells were examined after 4-days or 7-days co-culture with the feeder cells. The results showed that BMECs or spleen ECs can promote the generation of CFU-C from VEGFR1 + HSCs or VEGFR1 − HSCs, yet the tot al number of CFU-C produced from VEGFR1+ HSCs was greater than that from VEGFR1- HSCs. However, both of these cell types were able to support the generation of CFU-Cs to a greater degree than BMSCs. To examine the mechanism of enhanced support of VEGF-R1 + HSCs by the BMECs, we performed real-time PCR analysis for the expression of the VEGF-R1 ligands. Both BMECs and spleen ECs were found to express VEGF-A and –B to similar levels, however the expression of placental growth factor was higher in the BMECs. Whether the increased expression of this factor plays a functional role in the support of the HSCs in currently being evaluated. Our findings suggest that the ECs from BM or spleen can promote the proliferation of hematopoietic progenitor cells, while BMECs can maintain the long-term culture of VEGFR1 + HSCs in vitro . The functional relevance of this in vivo is currently being investigated.
Dynamics of Lysine as a Heme Axial Ligand: NMR Analysis of the Chlamydomonas reinhardtii Hemoglobin THB1

Nitrate metabolism in Chlamydomonas reinhardtii involves THB1, a monomeric hemoglobin thought to function as a nitric oxide dioxygenase (NOD). NOD activity requires dioxygen and nitric oxide binding followed by a one-electron oxidation of the heme iron and nitrate release. Unlike pentacoordinate flavohemoglobins, which are efficient NODs, THB1 uses two iron axial ligands: the conserved proximal histidine and a distal lysine (Lys53). As a ligand in both the oxidized (ferric) and reduced (ferrous) states, Lys53 is expected to lower the reorganization energy associated with electron transfer and therefore facilitate reduction of the ferric enzyme. In ferrous THB1, however, Lys53 must be displaced for substrate binding. To characterize Lys53 dynamics, THB1 was studied at various pH, temperatures, and pressures by NMR spectroscopy. Structural information indicates that the protein fold and Lys53 environment are independent of the oxidation state. High-pressure NMR experiments provided evidence that displacemen...
Can mergers increase output? Evidence from the lodging industry

We find that hotel mergers increase occupancy. In some specifications, price also rises. Because these effects occur only in markets with high capacity utilization and high uncertainty, we reject simple models of price or quantity competition in favor of models of “revenue management,” where firms price to fill available capacity in the face of uncertain demand.
Imaging Redox State in Mouse Muscles of Different Ages

Aging is the greatest risk factor for many diseases. Intracellular concentrations of nicotinamide adenine dinucleotide (NAD+) and the NAD+-coupled redox state have been proposed to moderate many aging-related processes, yet the specific mechanisms remain unclear. The concentration of NAD+ falls with age in skeletal muscle, yet there is no consensus on whether aging will increase or decrease the redox potential of NAD+/NADH. Oxidized flavin groups (Fp) (e.g. FAD, i.e., flavin adenine dinucleotide, contained in flavoproteins) and NADH are intrinsic fluorescent indicators of oxidation and reduction status of tissue, respectively. The redox ratio, i.e., the ratio of Fp to NADH, may be a surrogate indicator of the NAD+/NADH redox potential. In this study we used the Chance redox scanner (NADH/Fp fluorescence imaging at low temperature) to investigate the effect of aging on the redox state of mitochondria in skeletal muscles. The results showed that there are borderline significant differences in nominal concentrations of Fp and NADH, but not in the redox ratios when comparing 3.5-month and 13-month old muscles of mice (n = 6). It may be necessary to increase the number of muscle samples and study mice of more advanced age.
Gay-Straight Alliances as Settings for Youth Inclusion and Development: Future Conceptual and Methodological Directions for Research on These and Other Student Groups in Schools

Outside the immediate classroom setting, efforts within other school spaces also can shape school climate, address inequality, and affect student performance. Nevertheless, in this respect there has been little research on school-based extracurricular groups focused on issues of social inclusion and justice. An exception to this lack of focus has been Gay-Straight Alliances (GSAs), which promote social inclusion and justice for sexual and gender minority youth (e.g., lesbian, gay, bisexual, transgender, or questioning youth; LGBTQ) through support, socializing, education, and advocacy. As this literature has matured, we detail and provide examples of the following conceptual and methodological recommendations to address emerging research needs for GSAs: (1) Move from a monolithic to contextualized treatment of GSAs, (2) attend to heterogeneity among members, (3) utilize multiple data sources for triangulation, (4) apply a range of methodological approaches to capitalize on strengths of different designs, ...
Model Studies of the Rheology of Blood in Microvessels

In the microcirculation, blood cannot be treated as a homogeneous fluid, but rather as a suspension. The individual cellular elements influence the hemodynamics. In this chapter, we shall study the behavior of red cells in microvessels. We will focus on the general features of cell-vessel interaction and their effect on the apparent viscosity of blood. Model experiments are used in these studies. In our models, the plasma is simulated by a silicone fluid, the red cells are simulated by gelatin pellets. With the model approach, apparent viscosity of blood in pulmonary capillaries is obtained. The Fahraeus-Lindqvist effect, Inversion of Fahraeus-Lindqvist effect, velocity distribution in microvessels, hematocrit in very narrow tubes, etc. are investigated.
Structure Based Design of a Grp94-Selective Inhibitor: Exploiting a Key Residue in Grp94 To Optimize Paralog-Selective Binding

Grp94 and Hsp90, the ER and cytoplasmic hsp90 paralogs, share a conserved ATP-binding pocket that has been targeted for therapeutics. Paralog-selective inhibitors may lead to drugs with fewer side effects. Here, we analyzed 1 (BnIm), a benzyl imidazole resorcinylic inhibitor, for its mode of binding. The structures of 1 bound to Hsp90 and Grp94 reveal large conformational changes in Grp94 but not Hsp90 that expose site 2, a binding pocket adjacent to the central ATP cavity that is ordinarily blocked. The Grp94:1 structure reveals a flipped pose of the resorcinylic scaffold that inserts into the exposed site 2. We exploited this flipped binding pose to develop a Grp94-selective derivative of 1. Our structural analysis shows that the ability of the ligand to insert its benzyl imidazole substituent into site 1, a different side pocket off the ATP binding cavity, is the key to exposing site 2 in Grp94.
Pinch-Effect Oscillations in an Unstable Tokamak Plasma

If Tokamak toroidal discharges are operated with $ql3$, relaxation oscillations are observed to occur involving alternate contraction and expansion of the plasma. It is shown that the detailed properties determined for these oscillations on the Canberra experiment can be explained on the basis of the newly discovered trapped-particle pinch effect.
New far-UV instrumentation enabled by recent advances in mirror coating processes

Recent technological advances have opened up new instrument capabilities for ultraviolet (UV) astronomy. Of particular interest are advanced deposition processes that have increased the performance of Lithium Fluoride (LiF) overcoated mirrors while mitigating the procedures required for their handling, raising the reflectivity from ∼ 65% to greater than 80% in the Lyman UV (λ > 1000 A). Traditional magnesium fluride (MgF2) protected aluminum mirrors have a reflectivity truncated at 1150 A, missing crucial tracers of warm gas and molecules. The hygroscopic sensitivity of LiF has traditionally added to mission risk and cost. The addition of a thin capping layer of another material (AlF3, MgF2) on top of the LiF has been shown to mitigate the degradation by providing a barrier against moisture. These advances open up a new paradigm in UV astronomy by enabling multi-passed optical designs without the crippling 1000 - 1150 A throughput losses inherent to conventional mirror coatings. We present recent progress in the testing of enhanced lithium fluoride (eLiF) coated optics, and discuss potential instrument concepts for UV astronomy in the next decade.
Partial resistance to Phytophthora infestans in four Solanum crosses

Thirty progeny from each of fourSolanum crosses were evaluated in the field at Mount Vernon, WA, in 1996 and 1997 for partial resistance toPhytophthora infestans. Of the four parents, three have high levels of partial resistance toP. infestans; one derived from somatic hybridization ofS. bulbocastanum, the other two from traditional breeding efforts for multiple disease resistance. Data were collected from each cross to estimate area under the disease progress curve (AUDPC), days to 5% disease severity threshold (DT5), and sporangia production (SP). All of these variables differed significantly among the progeny within each cross in each year. Correlation analysis indicated that DT5 was highly correlated with AUDPC for all four populations for both years. Log-transformed SP was significantly (P>0.001) correlated to AUDPC values for one population in both years, but the significance of the correlation was variable between years for the remaining three crosses. The variable DT5, which is composed of three components (infection efficiency, latent period, and lesion growth rate), was the most important in identifying progeny with partial resistance to late blight in all four crosses in this study.
Viscoelasticity in Three Dimensions

Thus far, we have restricted our attention to problems in which there was only one stress σ (or possibly τ) and one strain e (or possibly γ), and the viscoelastic law (1.23) and its equivalents (2.6), (2.7), (5.6) were appropriate to describe the behavior of the material. When there is more than one stress component, we need a generalization of the viscoelastic law, which corresponds to the three-dimensional form of Hooke’s law and contains it as a special case. We shall now find a logical approach to the general constitutive equations of viscoelastic materials and then apply them to a few typical cases.
ALLERGY SKIN TESTS FOR INHALANTS AND FOODS: Comparison of Methods in Common Use

Many types of skin tests have evolved from Blackley's early scratch tests. This review highlights both the similarities between current skin tests and their differences. All current skin tests are capable of detecting allergic hypersensitivity, but the tests differ in their sensitivity, specificity, safety, reproducibility, and applications. Common factors in initial and final test doses, and in test dose increments, are identified. Test methods that quantitatively measure a range of allergen concentrations have diagnostic advantages in terms of safely detecting a wide range of allergic sensitivities. Failure to detect the full spectrum of allergic disease can lead to treatment failure; therefore, complete skin testing is desirable. This is especially important when dealing with exquisitely sensitive patients, such as many grass or ragweed sensitized patients, but is equally vital when evaluating low sensitivity patients, including many who are mold or food sensitive. Quantitation also improves test reproducibility, which is why it is used for antigen standardization. Finally, quantitation has advantages when used to initiate and escalate allergen immunotherapy. In vivo testing continues to evolve. New types of prick testing devices, and refinements of intradermal and patch test methods, continue to be reported. All allergists need to stay current with developments in vivo testing, so that they can offer their patients diagnosis that is appropriate to each individual situation.
Efficacy of Repeat Midurethral Sling for Persistent or Recurrent Stress Urinary Incontinence: A Fellows Pelvic Research Network Study.

Objective The objective of this study is to compare quality of life and success rates of repeat midurethral slings (RMUS) using retropubic (RP) and transobturator (TO) routes. Materials and methods Multicenter retrospective cohort with prospective follow-up of patients undergoing RMUS from 2003 to 2016. Prospective Urinary Distress Inventory (UDI-6) and Patient Global Impression of Improvement (PGI-I) were collected by phone. Primary outcome was success of repeat sling by approach (RP vs TO), defined as responses of no to UDI-6 number 3 and very much better or much better on PGI-I. Results A total of 122 patients prospectively completed UDI-6. Average ± SD time to failure after initial sling was 51.6 ± 56.1 months; mean follow-up after repeat sling was 30.7 months. Route of initial sling was RP 30.3%, TO 49.2%, and minisling 16.4%. Of the patients, 55.8% met our success definition following RMUS. About 71.3% were very much better or much better on PGI-I, and 30.3% reported stress urinary incontinence (SUI) on UDI-6. Of the RMUS, 73.8% were RP versus 26.2% TO.There was no difference in success between repeat RP and TO routes (53.3% versus 63.3%, P = 0.34), nor for individual components: PGI-I response of very much better or much better (68.9% vs 78.1%), UDI-6 total score (25.9 vs 22.7, P = 0.29), or SUI on UDI-6 number 3 (32.2% vs 25.0%, P = 0.45), although the predetermined sample size was not met. No predictors of success or failure of RMUS were identified. Conclusions Majority of patients are very much better or much better after RMUS, although 30% still report bothersome SUI. No difference in success was observed between RP and TO RMUS.
American Bucks and Austrian Buccaneers: Sun Valley—The Making of America’s First Winter Resort

Gunter Bischof’s chapter sketches the making of Sun Valley, Idaho, as the first American winter destination and the role Austrian consultants and ski instructors played in the development of Sun Valley. Bischof suggests that the role of the Austrian ski instructors (mostly from the Tyrol region) was essential not only in the making of Sun Valley, but also in the building of the 10th Mountain Division during World War II and the diffusion of skiing and winter resort construction after the war. As well as examining primary sources, such as the Harriman Papers at the Library of Congress and the Friedl Pfeiffer Papers at the Denver Public Library, Bischof builds on recent published and unpublished work on the establishment of skiing and winter destinations in tourism.
Two RNase H2 Mutants with Differential rNMP Processing Activity Reveal a Threshold of Ribonucleotide Tolerance for Embryonic Development.

Summary RNase H2 has two distinct functions: initiation of the ribonucleotide excision repair (RER) pathway by cleaving ribonucleotides (rNMPs) incorporated during DNA replication and processing the RNA portion of an R-loop formed during transcription. An RNase H2 mutant lacking RER activity but supporting R-loop removal revealed that rNMPs in DNA initiate p53-dependent DNA damage response and early embryonic arrest in mouse. However, an RNase H2 AGS-related mutant with residual RER activity develops to birth. Estimations of the number of rNMPs in DNA in these two mutants define a ribonucleotide threshold above which p53 induces apoptosis. Below the threshold, rNMPs in DNA trigger an innate immune response. Compound heterozygous cells, containing both defective enzymes, retain rNMPs above the threshold, indicative of competition for RER substrates between active and inactive enzymes, suggesting that patients with compound heterozygous mutations in RNASEH2 genes may not reflect the properties of recombinantly expressed proteins.
Molybdenum Complexes that Contain a Calix[6]azacryptand Ligand as Catalysts for Reduction of N2 to Ammonia.

[CAC(OMe)6]Mo(N) (3, where [CAC]3– is a calix[6]azacryptand ligand derived from a [6]calixarene) has been prepared in a reaction between Li3[CAC(OMe)6] and (t-BuO)3Mo(N). An X-ray structural study ...
Experiments on Discrete Roughness Element Technology for Swept-Wing Laminar Flow Control

Micrometer-sized spanwise-periodic discrete roughness elements (DREs) were applied to and tested on a 30 deg swept-wing model in order to study their effects on boundary-layer transition in flight ...
Practical Olefin Hydroamination with Nitroarenes.

An operationally simple radical hydroamination of olefins with nitro(hetero)arenes is presented, giving access even to hindered amines.
Factors Associated with and Temporal Trends in the Use of Radiation Therapy for the Treatment of Pituitary Adenoma in the National Cancer Database.

Objective Radiation therapy represents an uncommon but important component of treatment plans for some pituitary adenomas (PAs). Although radiation therapy has been used to treat pituitary adenomas for over a century, general trends in the usage of radiation therapy for this purpose have not been reviewed. Additionally, there are few large studies evaluating how radiation therapy is used for the treatment of these benign tumors. Investigating these trends and identifying any variations in radiation therapy utilization would help to better inform treatment decisions and improve patient outcomes. Design Present study is a retrospective analysis of cases using the National Cancer Database. Setting The research was organized at a tertiary academic medical center. Participants Patients were diagnosed with pituitary adenoma between 2004 and 2014 within the National Cancer Database (NCDB). Methods Temporal trends in the usage of radiation therapy to treat pituitary adenoma were analyzed through a retrospective analysis of 77,142 pituitary adenoma cases from the NCDB between 2004 and 2014. Univariate and multivariate analyses were to examine the relationship between patient, tumor, and treatment factors, and the incorporation of radiation therapy into the treatment of pituitary adenomas. We adjusted for potential confounders such as age, sex, race, comorbidity score, facility type, and year of diagnosis. Results A total of 77,142 patients met inclusion criteria. Inclusion of radiation therapy in pituitary adenoma treatment was 8.0% in 2004 and steadily declined to a low of 3.1% in 2014. Overall, patients were less likely to receive radiation for their pituitary adenoma over time (p Conclusion In this sample of pituitary adenoma patients treated at NCDB institutions between 2004 and 2014, we found a steady decline in the incorporation of radiation therapy in treatment, as well as in the use of any type of intervention for PA treatment, suggesting a rise in noninterventional observation of PA.
Ladd’s Procedure

Surgical Procedures: This chapter describes the endoscopic/surgical Ladd’s procedure as performed by the following approaches: open and laparoscopic. The text includes an introduction that outlines the indications, risks, alternatives, essential steps, needed equipment, and variations in technique for the procedure in question. This is followed by a template operative dictation that provides the reader with an operative report, such as that found in a patient chart or electronic medical record. A description is provided of the following critical concepts for this procedure: inspect the bowel for the presence of malrotation, carefully divide Ladd’s bands, place right colon on left side of the abdomen, mobilize duodenum and straighten and direct inferiorly, place small bowel on right side of abdomen, and broaden mesentery.
Advances and Future Directions of Diagnosis and Management of Pediatric Abusive Head Trauma: A Review of the Literature

Abusive head trauma (AHT) is broadly defined as injury of the skull and intracranial contents as a result of perpetrator-inflicted force and represents a persistent and significant disease burden in children under the age of 4 years. When compared to age-matched controls with typically single occurrence accidental traumatic brain injury (TBI), mortality after AHT is disproportionately high and likely attributable to key differences between injury phenotypes. This article aims to review the epidemiology of AHT, summarize the current state of AHT diagnosis, treatment, and prevention as well as areas for future directions of study. Despite neuroimaging advances and an evolved understanding of AHT, early identification remains a challenge for contemporary clinicians. As such, the reported incidence of 10-30 per 100,000 infants per year may be a considerable underestimate that has not significantly decreased over the past several decades despite social campaigns for public education such as "Never Shake a Baby." This may reflect caregivers in crisis for whom education is not sufficient without support and intervention, or dangerous environments in which other family members are at risk in addition to the child. Acute management specific to AHT has not advanced beyond usual supportive care for childhood TBI, and prevention and early recognition remain crucial. Moreover, AHT is frequently excluded from studies of childhood TBI, which limits the precise translation of important brain injury research to this population. Repeated injury, antecedent abuse or neglect, delayed medical attention, and high rates of apnea and seizures on presentation are important variables to be considered. More research, including AHT inclusion in childhood TBI studies with comparisons to age-matched controls, and translational models with clinical fidelity are needed to better elucidate the pathophysiology of AHT and inform both clinical care and the development of targeted therapies. Clinical prediction rules, biomarkers, and imaging modalities hold promise, though these have largely been developed and validated in patients after clinically evident AHT has already occurred. Nevertheless, recognition of warning signs and intervention before irreversible harm occurs remains the current best strategy for medical professionals to protect vulnerable infants and toddlers.
CARDIOVASCULAR EVENTS ASSOCIATED WITH COMBINATION MEK/BRAF INHIBITORS (ANALYSIS OF THE FDA ADVERSE EVENTS REPORTING SYSTEM)

BRAF and MEK inhibitors have revolutionized the treatment of melanoma, lung and colon cancers. Recent reports suggest increased cardiovascular toxicity with the combination (BRAF/MEK inhibition) therapy but large-scale post-marketing data is lacking. We used the FDA adverse events reporting system
Value Similarities with Grandparents among College Students: Gender, Family Lineage, and Relationship Closeness

There may be a greater impact of grandparents on value similarity for grandchildren as grandparents and grandchildren nowadays share more time together than prior generations. However, less is know...
Methylmercury: Human exposure, animal behavior, and insight on molecular mechanism

Abstract The potential risk for methylmercury (MeHg) exposure to humans continues to be substantial. It is a concern not only for those exposed in excess, but for all fish-consuming individuals. The long-term consequences of acute or chronic low-dose MeHg exposure remain uncertain. Extreme MeHg exposure incidents have offered a glimpse of the mechanism of toxicity, and incited further research. Minamata and other high-level MeHg contamination incidents demonstrated the severe consequences of exposure, particularly to the developing nervous system. Although epidemiological studies have been incongruent, it is paramount that researchers obtain a fundamental grasp on mechanisms of toxic insult, particularly as it relates to dissemination of MeHg to the brain. MeHg excretion requires demethylation. This process is protracted in the central nervous system (CNS), rendering the brain particularly vulnerable to toxicity. Moreover, the relative ease with which MeHg crosses the blood-brain barrier reinforces residence in the brain. Distribution to cortical astrocytes and subsequent dysfunction precede MeHg-induced neurotoxicity. The mechanism(s) by which MeHg elicits toxicity are complex. It is most likely that the combined effects on glutamate cycling and oxidative stress ultimately cause MeHg-induced neurotoxicity. This chapter addresses contemporary issues on the continued health risks associated with this metal.
Towards scalable zero-shot modulation recognition

With the advent of Dynamic Spectrum Access networks, practical modulation recognition (ModRec) has become an important problem with critical applications to spectrum enforcement and resource allocation. Existing ModRec frameworks hinge on exhaustive classifier training and require labeled observations for all modulations before recognition can be performed. As a result, a general ModRec system based on fully supervised classification quickly becomes intractable due to the emergence of new proprietary waveforms and the need to collect labeled training data for them and retrain the system. This underpins the need to perform modulation classification of previously unobserved modulations. Thus, the question emerges can learned classifiers be transferred to "unobserved" modulations?In this paper, we investigate the utility of zero-shot learning to address the above challenge in the context of ModRec. We design ModRec-0, which employs unseen modulations’ constellation diagrams within a zero-shot framework to transfer learned classifiers from observed modulations. We propose several important properties to enable this transfer, such as the number of constellation points, phase and amplitude levels. Our system is flexible in that additional such properties as well as a variety of classification features can be incorporated. We evaluate our framework on synthetic and real over-the-air traces and investigate the necessary conditions such as SNR levels and observed training classes for successful transfer. We demonstrate that ModRec-0 achieves over 85% average accuracy across multiple modulation classes both in synthetic and real-world traces.
Resisting the “death of diversity”: A historical analysis of the formation of the César E. Chávez Center for Higher Education at Cal Poly Pomona, 1990–1995

This article chronicles the strategies and efforts Chicana/o and Latina/o student activists employed in the demand and creation of the Cesar E. Chavez Center for Higher Education (CECCHE) at Cal Poly Pomona (CPP) between 1990 and 1995. We situate the center’s establishment as the result of student activism. CPP served as a stage whereon students resisted negative campus racial climate by institutionalizing the CECCHE as a counterspace. Student activism at CPP reflected broader resistance efforts in California in the 1990s. The student leaders, like activists from California’s social movements, resisted conservative rhetoric and systemic racism by mobilizing cross-racial coalitions and enacting public protest. Using critical race history, we analyze ten oral histories of students, faculty, and administrators involved in the establishment of CPP’s first Chicana/o and Latina/o cultural center. We situate the formation of the CECCHE as an example of student of color commitment to antiracist activism in higher education.
DMFT Exchange-Correlation Potentials for Time-Dependent DFT

We present details of several approaches on how to obtain the XC potential for TDDFT by using DMFT. After summarizing the progress in the field, including potentials developed by using other approaches to strongly correlated systems, we discuss properties of the adiabatic DMFT XC potential derived for the 3D Hubbard model, including its weak and strong sides. We also show how to obtain a nonadiabatic XC potential (kernel) in the linear-response regime by using DMFT results for charge and spin susceptibilities. In the last section, we present details on how one can obtain the TDDFT XC potential by solving the Sham–Schlueter equation that includes DMFT electron self-energy. We propose algorithms to solve this equation in the case of different approximations for the electron self-energy.
Repair and Internal Brace Augmentation of the Medial Ulnar Collateral Ligament

The ulnar collateral ligament (UCL) is the primary restraint to valgus stress at the elbow particularly during the late cocking and early acceleration phases of throwing. Injuries to this ligament are being recognized earlier and in younger overhead throwing athletes. These patients represent a different cohort of patients than later career patients with chronic injury who require UCL reconstruction. Many of these younger athletes are able to pursue nonoperative measures successfully to return to sport at an effective level; however, a small subset of athletes require surgical intervention to restore medial elbow stability during overhead throwing. This cohort of patients are candidates for UCL repair which has several benefits outlined in this chapter. This chapter reviews UCL repair history, biomechanics, surgical indications, surgical technique and lastly reviews outcomes of UCL repair in the literature.
Understanding Agile for Strategic Communicators: Foundations, Implementations, and Implications

Disruptive change has become the new normal for business and society. In turn, Agile thinking, values, and principles are permeating a growing number of organizations as they try to navigate such c...
No-Substitution $k$-means Clustering with Optimal Center Complexity and Low Memory.

We consider $k$-means clustering in the online no-substitution setting where one must decide whether to take each data point $x_t$ as a center immediately upon streaming it and cannot remove centers once taken. Our work is focused on the \emph{arbitrary-order} assumption where there are no restrictions on how the points $X$ are ordered or generated. Algorithms in this setting are evaluated with respect to their approximation ratio compared to optimal clustering cost, the number of centers they select, and their memory usage. Recently, Bhattacharjee and Moshkovitz (2020) defined a parameter, $Lower_{\alpha, k}(X)$ that governs the minimum number of centers any $\alpha$-approximation clustering algorithm, allowed any amount of memory, must take given input $X$. To complement their result, we give the first algorithm that takes $\tilde{O}(Lower_{\alpha,k}(X))$ centers (hiding factors of $k, \log n$) while simultaneously achieving a constant approximation and using $\tilde{O}(k)$ memory in addition to the memory required to save the centers. Our algorithm shows that it in the no-substitution setting, it is possible to take an order-optimal number of centers while using little additional memory.