cssi/SciSciGPT-SciSciNet huggingface dataset:
Emergence and Evolution of Modern Molecular Functions Inferred from Phylogenomic Analysis of Ontological Data

The biological processes that characterize the phenotypes of a living system are embodied in the function of molecules and hold the key to evolutionary history, delimiting natural selection and change. These processes and functions provide direct insight into the emergence, development, and organization of cellular life. However, detailed molecular functions make up a network-like hierarchy of relationships that tells little of evolutionary links between structure and function in biology. For example, Gene Ontology terms represent widely-used vocabularies of processes and functions with evolutionary relationships that are implicit but not defined. Here, we uncover patterns of global evolutionary history in ontological terms associated with the sequence of 38 genomes. These patterns unfold the metabolic origins of modern molecular functions and major biological transitions in evolution toward complex life. Phylogenies reveal the primordial appearance of hydrolases and transferases, with ATPase, GTPase, and helicase activities being the most ancient. This indicates that ancient catalysts were crucial for binding and transport, the emergence of nucleic acids and protein biopolymers, and the communication of primordial cells with the environment. Finally, the history of biological processes showed that cellular biopolymer metabolic processes preceded biopolymer biosynthesis and essential processes related to macromolecular formation, directly challenging the existence of an RNA world. Phylogenomic systematization of biological function takes the structure and function paradigm to a completely new level of abstraction, demonstrating a "metabolic first" origin of life. The approach uncovers patterns in the morphing of function that are unprecedented and necessary for systematic views in biology.
Bone loss after bariatric surgery: causes, consequences, and management

Summary Bariatric surgery is an effective and increasingly common treatment for severe obesity and its many comorbidities. The side-effects of bariatric surgery can include detrimental effects on bone and mineral metabolism. Bone disease in patients who have had bariatric surgery is affected by preoperative abnormalities in bone and mineral metabolism related to severe obesity. Changes that arise after bariatric surgery are specific to procedure type: the most pronounced abnormalities in calciotropic hormones and bone loss are noted after procedures that result in the most malabsorption. The most consistent site for bone loss after all bariatric procedures is at the hip. There are limitations of dual-energy x-ray absorptiometry technology in this population, including artefact introduced by adipose tissue itself. Bone loss after bariatric surgery is probably multifactorial. Proposed mechanisms include skeletal unloading, abnormalities in calciotropic hormones, and changes in gut hormones. Few data for fracture risk in the bariatric population are available, and this is a crucial area for additional research. Treatment should be geared toward correction of nutritional deficiencies and study of bone mineral density in high-risk patients. We explore the skeletal response to bariatric surgery, potential mechanisms for changes, and strategies for management.
Low-temperature thermochronologic constraints on the kinematic histories of the Castle Cliffs, Tule Springs, and Mormon Peak detachments, southwestern Utah and southeastern Nevada

We use apatite and zircon (U-Th)/He thermochronometry to evaluate the timing, magnitude, and spatial pattern of Miocene strain within the Beaver Dam Mountains, Tule Springs Hills, and Mormon Mountains of southwestern Utah and southeastern Nevada (USA). The region is host to three major low-angle structures, the Castle Cliffs, Tule Springs, and Mormon Peak detachments, the origin and role of which in regional extension are vigorously debated. We analyzed 36 samples collected from Precambrian basement gneisses and Paleozoic to Jurassic siltstones and sandstones exposed in the footwalls of these detachments. Zircon He ages from the footwall of the Castle Cliffs detachment record rapid footwall exhumation ca. 18–17 Ma. At structurally higher positions, apparent ages become progressively older, defining a zircon He partial retention zone. Paleodepth reconstructions of the data using published cross sections suggest 180 °C, or greater, of cooling or 6.8–8.2 km of total exhumation, yielding a maximum of ∼13 km of extension across this detachment. In contrast, zircon and apatite ages from the footwall of the Mormon Peak record rapid exhumation at 14–13 Ma and 5.8–7.1 km of vertical exhumation. Using a range of restored fault dips (20°–28°) for the Mormon Peak detachment, the thermochronology data record 10.9–19.5 km horizontal extension. Data from the Tule Springs detachment also show a similar timing of exhumation and indicate that there has been 5.0–6.8 km of vertical exhumation and a minimum of ∼5 km of extension. The results demonstrate that extension initiated in the east along the Castle Cliffs detachment and migrated westward with time. Although our data indicate that existing extension estimates across this system of detachment faults are too high (40 km versus 54 km), the pattern of cooling ages and protracted cooling history recorded in these ranges are inconsistent with rootless gravity slide interpretations and low-magnitude extension models.
Predicting Low Dose Effects for Chemicals in High Through-Put Studies

High through-put studies commonly use automated systems with 96-well plates in which multiple chemicals are tested at multiple doses using log-2 dose increments after a suitable incubation period. There are typically multiple (ranging from five to eleven) doses on each chemical, and occasionally plate replications of the dose-response studies. The target endpoint for such studies is typically the LC50, but for some chemicals, there may be multiple doses below a benchmark dose where there is no apparent adverse response relative to control response. We show how an estimation approach can lead to clearly interpretable results about response in the low dose region using data from a high throughput study of 2189 chemicals on yeast. Accurate estimates can be obtained of response for study chemicals by using best linear unbiased predictors (BLUPs) in a mixed model, and summarized via plots with expected response (assuming no low-dose effect) with confidence intervals for response below the benchmark dose for each chemical, providing an informative summary of response at low doses. We conclude that this approach can provide valuable insights that would be missed if the observational data were only considered through the lens of statistical methods appropriate for experimental studies.
Global statistics of lightning in anvil and stratiform regions over the tropics and subtropics observed by the Tropical Rainfall Measuring Mission

[1] The statistics of lighting in the anvil and stratiform regions of convective systems are summarized from Tropical Rainfall Measuring Mission (TRMM) satellite observations from 1998 to 2009. The locations of lightning flashes in convective systems are determined by combining three-dimensional precipitation radar (PR) observations with lightning flash center locations from lightning imaging sensor observations. The geographical distributions of flashes in the anvil and stratiform regions of thunderstorms over the tropics and subtropics are presented. Flashes in stratiform regions are found to account for 5.6% of all lightning flashes observed within the TRMM PR swath, while flashes in nonraining anvil regions made up another 5.5% of the sample. Diurnally, flashes in anvil regions peak earlier than flashes in stratiform regions (15:30 LT as opposed to 17:30 LT). Seasonal and regional variations of these flashes are discussed. Features in PR observations that likely contribute to charge separation are identified as contiguous areas with 6 km echoes exceeding 30 dbZ. Lightning flashes are then assigned to one of these features by the nearest neighbor method. Convective properties of features linked with lightning in stratiform and nonraining anvil regions are then analyzed. We find that features associated with lightning flashes in anvil regions are relatively weak and occur in small systems composed of a single convective region, while flashes in the stratiform regions are also relatively weak but more likely occur in multicell systems. About 15% of features with lightning are associated with at least one stratiform or anvil flash.
An Uncertain Diagnosis

There is a substantial literature in medical journals examining the marketing and promotional efforts of pharmaceutical firms. This literature is generally critical of those efforts, focusing on the negative aspects of promotion. Although the literature is expressed in empirical and scientific terms and makes use of data, it suffers from some weaknesses. If the same methods and level of rigor were used in analyzing another problem in medicine, scientific journals would reject the research and the Food and Drug Administration would not approve the remedy.
Electrical Properties of Pb5Ge3O11-Based Ferroelectric Glass-ceramics

The pulsed-laser deposition (PLD) technique utilizes one of the most energetic beams available to form thin films of the superconducting oxide YBa2Cu3O7 (YBCO). IN this study we examine the growth of YBCO at very high laser fluences (25 to 40 J/cm2); a more typical fluence for PLD would be nearer to 3 J/cm2. the use of high fluences leads to unique film microstructures which, in some cases, appear to be related to the correspondingly higher moveabilities of the adatoms. Films grown on vicinal substrates, using high laser fluences, exhibited well-defined elongated granular morphologies (with excellent transition temperature, Tc, and critical current density, Jc). Films grown on vicinal substrates using off-axis magnetron sputtering, plasma-enhanced metal organic chemical vapor deposition (PE-MOCVD), or PLD at more typical laser fluences showed some similar morphologies, but less well-defined. Under certain growth conditions, using high laser fluences with (001) oriented substrates, the YBCO films can exhibit a mixture of a- and c-axis growth where both crystallographic orientations nucleate on the substrate surface at the same time, and grow in concert. the ratio of a-axis oriented to c-axis oriented grains is strongly affected by the pulse repetition rate of the laser.
Forms and the Four Kinds of Stuff

Near the beginning of the second main part of the Timaeus (47e-69a), Plato once again argues against an opponent who accepts an ontology in which essences are not starting-points.1 His opponents are the Ionian cosmologists. As starting-points in their ontology, they accept neither the Receptacle nor Forms. The starting-points in their ontology are sensible objects, such as the portions of fire, water, etc., that are traditional in Greek cosmology. Plato has his character, Timaeus, argue against this ontology.2 He argues that the Ionian ontology is part of a conception of reality that is inconsistent with the possibility of knowledge about matters involving stuffs of the four kinds.
Digital Twin: Mitigating Unpredictable, Undesirable Emergent Behavior in Complex Systems

Systems do not simply pop into existence. They progress through lifecycle phases of creation, production, operations, and disposal. The issues leading to undesirable and unpredicted emergent behavior are set in place during the phases of creation and production and realized during the operational phase, with many of those problematic issues due to human interaction. We propose that the idea of the Digital Twin, which links the physical system with its virtual equivalent can mitigate these problematic issues. We describe the Digital Twin concept and its development, show how it applies across the product lifecycle in defining and understanding system behavior, and define tests to evaluate how we are progressing. We discuss how the Digital Twin relates to Systems Engineering and how it can address the human interactions that lead to “normal accidents.” We address both Digital Twin obstacles and opportunities, such as system replication and front running. We finish with NASA’s current work with the Digital Twin.
Development of high damage threshold laser-machined apodizers and gain filters for laser applications

We have developed high damage threshold filters to modify the spatial profile of a high energy laser beam. The filters are formed by laser ablation of a transmissive window. The ablation sites constitute scattering centers which can be filtered in a subsequent spatial filter. By creating the filters in dielectric materials, we see an increased laser-induced damage threshold from previous filters created using ‘metal on glass’ lithography.
Race, justice, policing, and the 2016 American presidential election

Scholars have long been interested in the intersection of race, crime, justice, and presidential politics, focusing particularly on the “southern strategy” and the “war on crime.” A recent string of highly-publicized citizen deaths at the hands of police and the emergence of the Black Lives Matter movement have brought renewed visibility to this racially-driven intersection, and in particular to issues involving contact with and attitudes toward the police. Using data from the 2016 Pilot Study of the American National Election Studies, this study explores how contact with the criminal justice system and perceptions of police injustice shape political behavior in the modern era, with a specific emphasis on prospective participation and candidate choice in the 2016 presidential election. The results indicate that being stopped by the police—an experience that can feel invasive and unjust—may motivate political participation, while spending time in jail or prison—an experience associated with a marginalization from mainstream civic life—appears to discourage political participation. Perceiving the police as discriminatory also seems to motivate political engagement and participation, though in opposite directions for conservative versus liberal voters. In addition, perceptions of police injustice were related to candidate choice, driving voters away from Donald Trump. Affective feelings about the police were not associated with candidate choice. Perceptions of the police appear to act in part as a proxy for racial resentments, at least among potential voters in the Republican primary. In sum, the intersection of race, justice, and policing remains highly relevant in U.S. politics.
Testing the cross-brand and cross-market validity of a consumer-based brand equity (CBBE) model for destination brands

Abstract Different studies on consumer/customer-based brand equity (CBBE), have revealed varying pictures of components and divergent relationships. The current study analyzed a large dataset with path analysis to test: 1) the validity of a general CBBE model (familiarity, image, quality, brand value, consumer value, and loyalty); 2) the validity of a customer model (+satisfaction) using data for a single destination brand; 3) the cross-brand validity of the general model for five U.S. destination brands; and 4) the cross-market validity of both models for different segments based on nationality, gender, and past visitation. The results revealed that familiarity and image were the two most prominent components explaining loyalty in both models, although both consumer value and brand value also had some mediating effects on loyalty. The model was variant for different destinations, variant for different nationalities, partially variant for different genders, and invariant for visitors and non-visitors of one destination brand.
Dermal pharmacokinetics of pyrazinamide determined by microdialysis sampling in rats.

Studies have demonstrated the efficacy of pyrazinamide (PZA) against stages of the Leishmania parasite that causes cutaneous leishmaniasis. Although PZA is widely distributed in most body fluids and tissues, the amount of drug reaching the skin is unknown. This study aimed to investigate the pharmacokinetics of PZA in rat dermal tissue by dermal microdialysis. Skin pharmacokinetics was assessed by implanting a linear microdialysis probe in the dermis of ten rats. In addition, blood samples were collected to assess plasma pharmacokinetics. Unbound microdialysate (N = 280) and plasma (N = 120) concentrations following single intravenous doses of 25 mg/kg or 50 mg/kg PZA were quantified by a validated HPLC method. Probe calibration was performed by retrodialysis. Non-compartmental analysis and non-linear mixed-effects modelling were performed using WinNonlin and NONMEM v.7.3. PZA rapidly permeated into the dermis and reached high levels, with mean maximum concentrations (Cmax) of 22.4 ± 7.1 µg/mL and 48.6 ± 17.3 µg/mL for the two doses studied. PZA showed significant distribution to the skin (fAUCdermal/fAUCplasma = 0.82 ± 0.31 and 0.84 ± 0.25 for 25 mg/kg and 50 mg/kg doses, respectively). Active unbound concentrations in dermal tissue reached lower levels than free plasma concentrations, indicating that free PZA levels in plasma were in equilibrium with tissue levels. These results showed equivalent unbound drug tissue concentrations and corresponding unbound plasma levels. This study shows that PZA distributes rapidly into dermal interstitial fluid space in rats and therefore may be a potential agent in the treatment of cutaneous leishmaniasis.
Optimization of a fast neutron scintillator for real-time pulse shape discrimination in the transient reactor test facility (TREAT) hodoscope

We present a multi-channel, fast-neutron/photon detection system that uses ZnS(Ag) scintillator detectors. The system employs field-programmable gate arrays to pulse-shape analysis for real-time all-digital neutron/photon differentiation, producing particle-dependent pulse height and temporal distributions while allowing count rates in excess of 1,000,000 events per second per channel. The system size is scalable in blocks of 16 channels.
Incorporating sex as a biological variable in neuroscience: what do we gain?

In recent years, several funding agencies have introduced requirements for researchers to consider sex as a biological variable in preclinical research. In this Comment article, McCarthy and colleagues discuss the potential impact of these policies for neuroscience research.
Spatiotemporal distribution of indoor particulate matter concentration with a low-cost sensor network

Abstract Real-time measurement of particulate matter (PM) is important for the maintenance of acceptable air quality. The high cost of conventional instruments typically limits the number of monitoring sites, which in turn undermines the accuracy of real-time mapping of sources and hotspots of air pollutants with sufficient spatial resolution. In this study, a wireless network of low-cost particle sensors that can be deployed indoors was developed. To overcome the well-known limitations of low sensitivity and poor signal quality associated with low-cost sensors, a sliding window and a low pass filter were developed to enhance the signal quality. Utility of the networked system with improved sensitivity was demonstrated by deploying it in a woodworking shop. Data collected by the networked system was utilized to construct spatiotemporal PM concentration distributions using an ordinary Kriging method and an Artificial Neural Network model to elucidate particle generation and ventilation processes.
Revision PCL Reconstruction Review/Update

The primary goal of this review is to update recent literature on revision PCL reconstruction and to discuss factors relevant to surgical failure, surgical indications and goals, patient evaluation, surgical decision-making, graft selection, surgical technique, associated surgical procedures, postoperative rehabilitation, and revision PCL reconstruction results. Specifically, it is paramount to consider and treat posteromedial and posterolateral instability. Success in revision surgery focuses on appropriate graft choice and precise tunnel placement at anatomical attachment sites. Furthermore, correct tensioning of the graft, secondary or backup fixation and well-designed PT and rehab protocols are integral components. The factors causing failure of the primary reconstruction should be identified, as revision surgery must address the errors and follow strict surgical principals to be successful. There are many variables that play a role in successful revision posterior cruciate ligament (PCL) reconstruction. In general, as in most ligament reconstruction surgery, it is important to identify and address all associated pathology such as lower extremity malalignment and additional instability.
An adaptive semi-iterative method for symmetric semidefinite linear systems

The development of semi-iterative methods for the solution of large linear nonsingular systems has received considerable attention. However, these methods generally cannot be applied to the solution of singular linear systems. We present a new adaptive semi-iterative method tailored for the solution of large sparse symmetric semidefinite linear systems. This method is a modification of Richardson iteration and requires the determination of relaxation parameters. We want to choose relaxation parameters that yield rapid convergence, and this requires knowledge of an interval [a, b] on the real axis that contains most of the nonvanishing eigenvalues of the matrix. Such an interval is determined during the iterations by computing certain modified moments. Computed examples show that our adaptive iterative method typically requires a smaller number of iterations and much fewer inner product evaluations than an appropriate modification of the conjugate gradient algorithm of Hestenes and Stiefel. This makes our scheme particularly attractive to use on certain parallel computers on which the communication required for inner product evaluations constitutes a bottleneck.
Corticosteroid-Binding Globulin (CBG)

In the late 1960s, some more or less preliminary observations had been made that pointed to the liver as the most likely site of CBG synthesis (Vol. I, p. 289). These studies were continued in the subsequent years, and definite proof is now available for the hepatic origin of this steroid-binding protein.
3.21 The Wittig Rearrangement

The Wittig rearrangement of a metallated allyl or benzyl ether derivatives leads to cleavage of the ether C–O bond and formation of a new C–C bond to provide an alcohol product. Wittig rearrangements provide a versatile and valuable approach to the synthesis of a broad array of homoallylic alcohol derivatives, and in many instances the transformations proceed in good chemical yield with a high degree of stereoselectivity. This chapter summarizes recent advances in [1,2]-, [2,3]-, and [1,4]-Wittig rearrangement methodology that have been described in the literature since the publication of the first edition of Comprehensive Organic Synthesis . The chapter is subdivided into sections based on the type of Wittig rearrangement reaction and the specific substrate classes that can be employed for a given rearrangement type. The mechanisms of the different rearrangement pathways are described, as models for the stereoselectivities that are observed in these transformations. Recent studies on catalytic Wittig rearrangements, enantioselective Wittig rearrangements, and cascade reactions involving Wittig rearrangement steps are also highlighted.
The Bcl-2 gene family and apoptosis

Apoptosis, or programmed cell death, is an essential process for normal embryonic development, maintaining homeostasis in adult tissues, and suppressing carcinogenesis. The bcl-2 protein, discovered in association with follicular lymphoma, plays a prominent role in controlling apoptosis and enhancing cell survival in response to diverse apoptotic stimuli. The evolutionarily conserved bcl-2 protein is now recognized as being a member of a family of related proteins which can be categorized as death agonists or death antagonists. Progress in defining the role of bcl-2 and its family members in regulating apoptosis is rapidly advancing. This review describes, in detail, current bcl-2 family members and the possible mechanisms of function which allow the bcl-2 family of proteins to either promote or suppress cell death.
Intracellular Factors Involved in Gene Expression of Human Retroviruses

Retroviruses contain a limited genetic repertoire. Though a number of these viruses contain transactivator proteins that increase their level of gene expression, they all require host cell transcription factors that bind to their long terminal repeat (LTR) in order to modulate basal level gene expression. Following retrovirus integration into the host-cell genome, proviral gene regulation occurs in a manner similar to that of endogenous cellular genes. The integrated provirus is flanked by two LTRs with the 5′ LTR element serving as the binding site for the cellular transcription factors and transcription initiation. A variety of modulators of different cellular signal transduction pathways are able to directly alter the binding or activity of cellular transcription factors that attach to both viral and cellular promoters. Activation of these specific transcription factors have profound effects on retroviral gene expression as will be discussed in this chapter. Unique features in the DNA and RNA regulatory regions of the 5′ proviral LTR also render it a target for various viral transactivator proteins such as the Tat proteins of human immunodeficiency virus (HIV) types 1 and 2 (see Chapters 1 and 3, this volume); the Tax proteins of human T-cell leukemia virus (HTLV) types I and II (Green and Chen, 1994); and the Bel protein of human foamy virus (HFV) or the human spuma retrovirus (HSRV) (see Chapter 4, this volume). In addition to the direct effects of transactivators on viral gene expression, other virally encoded regulatory proteins such as the Rev protein of HIV and the Rex protein of HTLV-I and -II also act in concert with cellular factors to affect the differential splicing and nuclear transport of the viral mRNAs, thereby indirectly modulating the level of viral expression.
When is the energy of the 1D damped Klein-Gordon equation decaying?

We study time decay of the energy for the one dimensional damped Klein-Gordon equation. We give an explicit necessary and sufficient condition on the continuous damping function $$\gamma \ge 0$$ for which the energy $$\begin{aligned} E(t)=\int _{-\infty }^\infty |u_x|^2+|u|^2+ |u_t|^2 dx \end{aligned}$$ decays, whenever $$(u(0), u_t(0))\in H^2(\mathbb R)\times H^1(\mathbb R)$$ .
TIMING AND PREDICTORS OF ORAL ANTICOAGULATION RESUMPTION AFTER ANTICOAGULATION RELATED INTRACRANIAL HEMORRHAGE

For patients with atrial fibrillation (AF) who have survived an intracranial hemorrhage (ICH), whether or not they should resume oral anticoagulation (OAC) remains unclear. We evaluated what patient characteristics increase the likelihood of OAC resumption after an ICH. We used 2006-2016 claims
Directed Hydrogen Bond Placement: Low Viscosity Amine Solvents for CO2 Capture

Capture of CO2 from power generation is required for its conversion or sequestration. Toward this goal, numerous CO2 capture processes have been developed, with the most widely deployed technology utilizing aqueous solutions of amines. Our group has focused on the design of several classes of water-lean solvents in order to identify molecular-level descriptors to control materials properties such as viscosity and regeneration energy. Density functional theory calculations and classical molecular dynamic simulations have shown that strategic placement of hydrogen bonding and tuning of the acid/base equilibria are critical for controlling viscosity at CO2-rich loadings. Here, we extend these principles to a new class of pyridine-based molecules with a secondary amine functionality for binding CO2. The result is a class of water-lean amines that retains high gravimetric capacity (20%) while exhibiting the lowest CO2-rich viscosities (<150 cP, 40 °C) of any 100% concentrated amine currently known. Additionall...
CHAPTER 6 – CONCLUSIONS

Publisher Summary This chapter focuses on the quantum theory by amendments which would give the theory a cryptodeterministic character, or to make the theory look like a local causal theory for elementary particles. Mathematicians can disprove any theory by adopting axioms that contradict the theory. Gleason troubles could be avoided by adopting Tutsch's rule, which led back to the Wiener and Siegel 1953 generalization of the polychotomic algorithm. This theory led to serious paradoxes. Theories of the second kind lead in a less sophisticated way to deviations from quantum theory. In fact, these theories were constructed with the purpose of contradicting quantum theory, where quantum theory does not explain the behavior of composite systems in a way that makes the individual elementary particles or quanta behave individually locally causally. Unless Holt's experimental results would be confirmed and the results of Freedman and Clauser would be shown to be faulty, theories of the second kind for their disagreement with experimental data need to be thrown.
Before teotihuacan—altica, exchange, interactions, and the origins of complex society in the northeast basin of mexico

For several decades, little research has been directed towards understanding the beginnings of complex society in the Teotihuacan Valley. Recent archaeological investigations at the Early–Middle Formative site of Altica provide a fresh perspective on dating the initial establishment of agricultural villages, early social and economic differentiation, and the development of intra-and interregional exchange networks to test comparative models of political economy.
On the Motion of the Heliospheric Magnetic Structure Through the Solar Wind Plasma

A reference frame in the solar wind can often be found wherein the flow vector is everywhere approximately parallel to the magnetic-field vector . This is the frame of the heliospheric magnetic str...
Using product development information to spur the adoption of continuous improvement products

Continuous improvement products (CIPs) are designed so that firms can make post-purchase improvements without requiring the user to fully replace the product. Although CIPs are becoming increasingly common in the marketplace, there are challenges in having customers adopt these products. In this multimethod research using two different types of studies, we find that sharing information about development progress increases adoption of the current version of the CIP, and that this relationship is mediated by the perceived commitment of developers to the product. Furthermore, we find that product familiarity moderates this mediation relationship. Our research offers insight to scholars interested in this new wave of products, and offers direction for managers in how to market their CIPs. Specifically, we recommend that firms developing CIPs use product development information as a marketing tool to communicate their commitment to the continued improvement of the product and to spur the purchase of the current versions of their CIPs.
Abstract GMM-037: CARBONIC ANHYDRASE 9 AND TUMOR HYPOXIA ARE ASSOCIATED WITH RECURRENCE AND RESISTANCE IN BRCA1-EXPRESSING HGSOC

Tumor hypoxia contributes to poor outcome in multiple cancer types, in part by influencing the expression of DNA repair enzymes. The objective of this study was to examine the possible relationship between Carbonic Anhydrase 9 (CA-IX, an indicator of tumor hypoxia), BRCA1 expression (a potential indicator of competent DNA repair), and patient outcome in epithelial ovarian cancer. BRCA1 and CA-IX were evaluated by immunohistochemistry in a tissue microarray of 167 epithelial ovarian cancer (EOC) patient samples, and their respective expression correlated to other biological parameters in all patients. The correlations between BRCA1 and CA-IX expression, and clinical outcome were determined in the High Grade Serous Ovarian Carcinoma (HGSOC) samples (N = 101) on the array using Spearman9s correlation and log-rank (Mantel-Cox) tests. Elevated expression of BRCA1 strongly correlated with shorter intervals for disease recurrence and mortality (median time to recurrence = 1.05 yrs vs 1.94 yrs, P CONCLUSION: The co-expression of CA-IX and BRCA1 may be a useful prognostic indicator for rapid recurrence in high grade serous ovarian cancer. Dissecting the mechanisms regulating therapeutic resistance in hypoxic ovarian cancer cells could lead to more effective treatment options for HGSOC patients. Citation Format: Adam J. Krieg, Shawn Campbell, Paulette Mhawech-Fauceglia, Jeong Youn Lim, Tanja Pejovic. CARBONIC ANHYDRASE 9 AND TUMOR HYPOXIA ARE ASSOCIATED WITH RECURRENCE AND RESISTANCE IN BRCA1-EXPRESSING HGSOC [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr GMM-037.
Bon Voyage to the New Journal "ICTUS": Gest Editorial

We present the editorial by invitation for the first issue of the jurnal "ICTUS", written by Dr. Louis R Caplan, professor of Neurology at Harvard University.
Implementation of an E-Learning Academic Elective for Hands-On Basic Surgical Skills to Supplement Medical School Surgical Education.

Objective To examine the feasibility and utility of a completely online surgical skills elective for undergraduate medical students. Design The fully asynchronous, one-week, online learning elective addressed surgical instrument identification, knot tying, and suturing. Tools for knowledge acquisition and self-practice were outlined and individualized performance feedback on technical skills performance was incorporated from peers and experts through video conference. Setting University of Rochester School of Medicine & Dentistry, Rochester, NY. Participants A total of 86 third- and fourth-year medical students enrolled and successfully completed the elective. Results At elective completion, nearly all students met their course objectives and significantly increased their confidence in surgical instrument identification, knot tying, and suturing. Objective measures of student knowledge and technical skills acquisition were overwhelmingly positive, and faculty and students were very satisfied with providing and receiving performance feedback. Students reported that expert feedback was more useful than peer feedback, and more students than faculty reported that the online modality was equivalent to an in-person session for performance review. Conclusions This innovative online surgical skills elective improved undergraduate medical student confidence, knowledge, and skillset with surgical instrument identification, knot tying, and suturing while also facilitating effective expert feedback on individual performance.
Remote Health Monitoring in Children: Needfinding in Parents

Wearable devices seem to be ubiquitous in today’s world. From a runner tracking their jogging route, to the gamification of exercising by achieving steps, to keeping up with notifications from apps...
The Role of Risk Preferences in Responses to Messaging About COVID-19 Vaccine Take-Up

Development of an effective COVID-19 vaccine is widely considered as one of the best paths to ending the current health crisis. While the ability to distribute a vaccine in the short-term remains u...
Major Complexity Index and College Skill Production

We propose an easily computable measure called the Major Complexity Index (MCI) that captures the latent skills taught in different majors. By applying the Method of Reflections to the major-to-occupation network, we construct a scalar measure of the relative complexity of majors. Our measure provides strong explanatory power of major average earnings and employment. Further evidence suggests that the MCI is strongly associated with advanced skills such as quantitative problem-solving, and the use of computing technology. We also provide a two-stage algorithm to partial out selection on observables which opens up possibilities of applying the complexity measure in various contexts.
Surgical Enucleation of the Right Eye Following Traumatic Injury in an Eastern Screech–owl (Megascops asio)

Surgical enucleation using a transaural approach was successfully performed following traumatic globe injury in an Eastern screech–owl (Megascops asio). Initial stabilization of this patient consisted of intraosseous administration of crystalloids and hypertonic saline, anti–inflammatory drugs, and broad–spectrum antibiotics. At surgery, general anesthesia was achieved using butorphanol as a premedicant and isofluorane in oxygen as an induction and maintenance anesthetic agent. Postoperative care included meloxicam for 7 days, trimethoprim/sulfadiazine for 14 days, and topical wound management. The surgical site healed in an uncomplicated manner. The bird was successfully flight tested and eventually released back into its natural habitat. Considerations for release and permanent captive placement in raptors with unilateral vision impediments are discussed.
Pathwise Average Cost Per Unit Time Problem for Stochastic Differential Games with a Small Parameter

A two person zero-sum stochastic differential game problem for wideband noise driven system is considered. We will consider the payoff structure in the pathwise sense. Under sufficiently general conditions, it will be shown that the optimal equilibrium policies of the limit process when applied to the physical processes, will be δ-equilibrium as the parameters e → 0 and T → ∞ Martingale convergence techniques will be used in the analysis. A Chattering result is also derived. The entire problem will be set in relaxed control framework.
Differential Emotions Theory and Emotional Development

Differential emotions theory (DET) packs the infant. Infants gain possession of a limited set of discrete emotions in the first months of life, and these emotions are organized as a modular system with a high degree of independent functioning. The number of emotions, their expressive signatures, and their links to one another undergo remarkable change over time, to be sure, as do system organization and articulation. The core processes in emotional development, however, consist of the construction and consolidation of affective—cognitive structures, which mediate intersystem coordination of the emotions, cognitive, and motor systems.
Form and Function in Business Organizations

In this piece, I argue that the recent proliferation of forms of business organizations in addition to the traditional partnership and corporation may have arisen from the implicit recognition that various organizations may serve needs of business people in different types of businesses, and that traditional theory of the firm explanations are too narrowly focused on market failure explanations for firm formation. I identify at least five different factors that may motivate people to form a business organization and discuss how these different factors may militate in favor of one business form rather than another. I conclude that the collections of rules that have evolved to govern different business organizations may be internally coordinated with each other in subtle ways that matter given the distinct uses to which each form has traditionally been put. Further, I argue that it is important to maintain standard form firms even though the parties may be almost totally free to contract around the standard terms, because default rules matter most when in disputes for which the parties have not planned, and because standard form firms may assist the parties in reaching agreement in a multilateral negotiation.
Intracellular injection in fixed slices in combination with neuroanatomical tracing techniques and electron microscopy to determine multisynaptic pathways in the brain.

Intracellular Lucifer Yellow filling in fixed tissue has been recently introduced as a novel neuroanatomical approach to reveal the detailed morphology of individual neurons in isolated preparations of the central nervous system. Since dye injections are performed under visual control, the method is characterized by a high degree of inherent staining selectivity, thus circumventing the element of randomness often considered to be the crux of classical Golgi-impregnation techniques. Moreover, the opportunity to optically monitor the injection procedure renders fixed slice preparations highly advantageous to be used in combination with retrograde fluorescent tracing. Subsequently, dye-filled neurons may be subjected to a simple photoconversion procedure leading to the intracellular formation of a stable polymer thus obtaining permanent specimens for light microscopy purposes. Due to the osmiophilic nature of the precipitate the photoconverted material is equally suitable for correlated electron microscopy, thus enabling the analysis of neuronal microcircuitry. At the ultrastructural level, sources of afferent input to identified projection neurons may be revealed by lesion-induced anterograde degeneration of synaptic terminals, therefore enabling the direct demonstration of multisynaptic links. Finally, morphologically identified neurons may be immunocytochemically characterized at the pre- and postembedding levels. It is therefore suggested that their methodological versatility and relative technical ease render intracellular fixed-slice injections a promising complement to the catalogue of anatomical techniques. © 1993 Wiley-Liss, Inc.
Childhood Experiences of Alcoholic African-American and Caucasian Women

Abstract Three hundred nine African-American and Caucasian alcoholic and nonalcoholic females ranging in age from 20 to 49 years old were individually administered a 77-page questionnaire. Results of a series of multivariate odds-ratio analyses based on self-report from memories of childhood indicate that alcoholic women reported significantly more nightmares, bedwetting, temper tantrums, phobias, bruxism, and nervous problems than nonalcoholic women. They reported significantly more school-related problems including expulsion/suspension, skipping school, trouble with school authorities, and dropping out of high school compared to nonalcoholic women. Feelings of nervousness, loneliness, and embarrassment around peers were reported significantly more often by alcoholic women. The prediction of alcoholism by childhood behavioral dysfunction differed as a function of race or age on only 4 of the 20 variables examined.
Parity and disparity in first course treatment of invasive breast cancer

Background Adherence to first course treatment guidelines for breast cancer may not be uniform across racial/ethnic groups and could be a major contributing factor to disparities in outcome. In this population-based study, we assessed racial differences in initial treatment of breast cancer. Methods Surveillance, Epidemiology, and End Results (SEER) program data were used to study all primary invasive breast cancers diagnosed during 2000–2001 among Black (n = 877) and White (n = 2437) female residents of the five Atlanta SEER counties, counties with several large teaching hospitals. Differences in treatment delay, cancer directed surgery, and receipt of chemotherapy, radiotherapy, or hormonal therapy were analyzed according to guidelines for treatment. Analyses utilized frequency distributions, χ2 tests of independence and statistics in and across strata. Results Black women experienced longer treatment delays, regardless of stage at diagnosis, and were 4–5 fold more likely to experience delays greater than 60 days (P < 0.001). For local–regional disease, more Black women did not receive cancer directed surgery (7.5% vs. 1.5% of white women, P < 0.001), but did receive breast conserving surgery (BCS) equivalently. Only 61% of Black vs. 72% of White women received radiation with BCS (P < 0.001). Black women eligible for hormonal therapy were less likely to receive it (P < 0.001). Conclusion Our findings suggest treatment standards are not adequately or equivalently met among Black and White women, even in an area where teaching hospitals provide a substantial portion of breast cancer care. Treatment differences can adversely affect outcome and reasons for the differences need to be addressed.
Request routing with a backerror propagation network

A pilot project of the Center involves automatic document delivery in response to computerized Interlibrary loan requests. Each document request includes an unstructured comment field that patrons occasionally use to indicate whether or not they want the National Library of Medicine to fill that request. These comments vary widely in content, but were found to always contain the test 'NLM.' This paper describes a technique to automatically reduce the amount of operator intervention to resolve ambiguities in the intent of the patron as to whether the request should be filled or not.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Lycopene attenuated hepatic tumorigenesis via differential mechanisms depending on carotenoid cleavage enzyme in mice

Obesity is associated with increased liver cancer risks and mortality. We recently showed that apo-10'-lycopenoic acid, a lycopene metabolite generated by beta-carotene-9',10'-oxygenase (BCO2), inhibited carcinogen-initiated, high-fat diet (HFD)-promoted liver inflammation, and hepatic tumorigenesis development. The present investigation examined the outstanding question of whether lycopene could suppress HFD-promoted hepatocellular carcinoma (HCC) progression, and if BCO2 expression is important using BCO2-knockout (BCO2-KO) and wild-type male mice. Results showed that lycopene supplementation (100 mg/kg diet) for 24 weeks resulted in comparable accumulation of hepatic lycopene (19.4 vs. 18.2 nmol/g) and had similar effects on suppressing HFD-promoted HCC incidence (19% vs. 20%) and multiplicity (58% vs. 62%) in wild-type and BCO2-KO mice, respectively. Intriguingly, lycopene chemopreventive effects in wild-type mice were associated with reduced hepatic proinflammatory signaling (phosphorylation of NK-κB p65 and STAT3; IL6 protein) and inflammatory foci. In contrast, the protective effects of lycopene in BCO2-KO but not in wild-type mice were associated with reduced hepatic endoplasmic reticulum stress-mediated unfolded protein response (ER(UPR)), through decreasing ER(UPR)-mediated protein kinase RNA-activated like kinase-eukaryotic initiation factor 2α activation, and inositol requiring 1α-X-box-binding protein 1 signaling. Lycopene supplementation in BCO2-KO mice suppressed oncogenic signals, including Met mRNA, β-catenin protein, and mTOR complex 1 activation, which was associated with increased hepatic microRNA (miR)-199a/b and miR214 levels. These results provided novel experimental evidence that dietary lycopene can prevent HFD-promoted HCC incidence and multiplicity in mice, and may elicit different mechanisms depending on BCO2 expression.