cssi/SciSciGPT-SciSciNet huggingface dataset:
Editorial: A Picture of Erythropoiesis at the Combined Morphologic and Molecular Levels

Abstract THORELL 1 IN 1947 published his study of the changes in nucleic acid, mixed proteins and hemoglobin in erythroblasts at different stages of maturation. It was the first bridge in erythropoiesis between the morphologic and molecular levels. His conclusion which attracted most attention was that hemoglobin synthesis did not begin until about the beginning of the polychromatic stage. A few years later, with the advent of radioautography it became possible to observe directly, rates of synthesis of DNA, RNA and protein in individual cells in vivo and in vitro. Not long afterwards came the demonstration of the relation of DNA and RNA to protein synthesis as a mechanism of conveying genetic information and of metabolic control. Now, one can make a tentative venture to relate the morphologic and molecular features of erythropoiesis in some detail. Two examples have been selected. One is the abrupt onset of hemoglobinization midway through maturation. The other is the macrocytosis of hemolytic anemia.
Potential Energy Surfaces and Stability of O in Elemental and Compound Semiconductors

Potential energy surfaces and electronic structures of interstial oxygen (O i ) in cubic C, Si, AIP, SiC , and BN have been calculated. The equilibrium site is a bent-bridged bond. In compound semiconductors, O i has a larger degree of bonding with the most electronegative of the host atoms (P, C , or N) than with the least electronegative one. In addition to the barrier for rotation of O, about the axis, which does not involve breaking a bond, we calculated the barriers for migration between adjacent bond-centered sites. There are two such barriers in compound semiconductors. In order to estimate the relative stability of O i in the various hosts, we calculated the energies involved in inserting O 2 into the lattice and dissociating it into two isolated O i 's.
Mabel M. Gabriel, Masters of Campanian Painting

(1954). Mabel M. Gabriel, Masters of Campanian Painting. The Art Bulletin: Vol. 36, No. 3, pp. 235-238.
AMINO ACID TRANSPORT BY RAT PARATHYROID GLANDS IN VIVO: EFFECT OF LOW CALCIUM DIET.

SummaryActive transport of α-aminoisobutyric acid by rat parathyroid tissue was much greater than by thyroid tissue under control conditions. Calcium deprivation doubled the parathyroid weight and tripled the α-aminoisobutyric acid transport into parathyroid cells, but had no effect on thyroid cells. The magnitude of this transport phenomenon is apparently a measure of physiologic activity of the parathyroid glands.The authors are indebted to Miss Ethel Hoffeins and Mrs. Joaquina Greene for technical assistance.
Markov Modeling and Its Application in the Stock Market

We assume that the changing of the stock price is the homogeneous Markov chain,there are up and down states,initial probability is stationary.Then we build mathematical model and give the maximum likehood estimators of the unknown parameter in the model.At last,we apply this model to analyze the index of Shanghai and Shenzhen and changing of one of stocks,obtain satisfactory results.
Behavior-Focused Alternative Schools: Impact on Student Outcomes

Behavior-focused alternative schools serve students who have been unsuccessful in other school settings due to low academic achievement coupled with significant behavior challenges. In this study, we investigated the effectiveness of secondary behavior-focused alternative schools on four different student outcome variables: (a) school attendance, (b) credits earned, (c) number of office referrals, and (d) number of suspensions. Using longitudinal data from a large urban school district and propensity score matching, we examined the extent to which outcomes of secondary students attending behavior-focused alternative schools differed compared to a matched sample of students attending traditional secondary schools. Findings from Poisson regression analyses indicate that enrollment in a behavior-focused alternative school significantly predicts earning fewer credits in one semester, lower attendance, and a lower number of office referrals. Implications for policy, practice, and further research relative to t...
Transactivation and transrepression studies with p53.

The methods outlined in this chapter are designed to facilitate the study of the transactivation and transrepression properties of p53 (as well as p63 and p73). Once a gene of interest is identified, its presumptive promoter region can be cloned upstream of a luciferase gene in a plasmid. The most common reason for transfection experiments is to study gene expression patterns in the presence or absence of a particular gene product (e.g., p53). Three methods of transfection are outlined in this chapter: (i) cationic lipofection; (ii) calcium phosphate precipitation; and (iii) BES precipitation. The first method is ideal for the study of transactivation and transrepression properties of p53 (or other transcription factors). The last two are more suited for experiments where larger numbers of transfected cells are needed. Several examples of transfections and their respective results are provided.
Mary’s Return: the State of Scotland, 1558–1562

On a cold and rainy day in the summer of 1561, a lone ship arrived on the southeastern Scottish coast. The ship, travelling from France, had sailed without a letter guaranteeing safe travel from the English queen, Elizabeth I, and its passengers had not been certain that they would arrive easily in the northern country. One of the travellers was a young woman, aged eighteen and recently widowed. Two years before, people had hailed this young woman as the Queen of France, Scotland and England, but now, uncertain of her future, she had lost two of her titles, and young Mary was returning to the land of her birth to rule in her own name as simply the Queen of Scots. Her reception in her native land, though, was not certain. Mary had left Scotland almost twelve years previously to be raised in France as the future bride of the dauphin, Francis. When she departed, Scotland was in the midst of a war with her southern neighbour, the so-called ‘Rough Wooing’ of the 1540s. The country was Catholic and remained true to the auld alliance with France against her traditional enemy of England. Mary’s mother, Mary of Guise, had remained in Scotland as regent, hoping for a continuation of the French Catholic alliance and friendship within the land. By 1561, though, the situation had changed completely. Instead of returning to the kingdom of the auld alliance with France from her childhood, Mary disembarked in an alien land, Protestant and friendly to the English. The young Queen of Scots could have had no idea what to expect from her subjects, and her unannounced arrival meant that the celebrations characteristic to the return of a monarch to her native land did not erupt immediately.
A new scheme for cache coherence in multiprocessor systems

The proposed scheme exploits the concepts of shared cache and private cache techniques. The caches are separated as shared block caches and private block caches instead of using only private or shared caches in the multiprocessor system. Shared block caches are worked in semi-critical section. The simulation results show significant improvement in the system power over that reported by the available research on pure private or shared cache schemes.
Abstract LB-030: Building personalized genetic models of human cancer in zebrafish to predict response to therapy and characterize disease mechanisms

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA A key challenge posed by personalized medicine is the ability to functionally characterize specific mutations identified in human tumors in order to guide treatment decisions. Transgenic approaches in zebrafish offer an opportunity to model individual patient tumors in order to develop personalized models. To test this concept, we performed a genetic characterization of a patient with thyroid carcinoma and created an in vivo personalized thyroid cancer model in zebrafish. Our studies suggest that this approach can be used to build preclinical models suitable for chemical-genetic studies. Chromosomal rearrangements in RET often lead to chimeric in-frame fusions of its kinase domain with one of several partners, resulting in ectopic, ligand-independent activation of RET. RET/PTC1 encodes a CCDC6 - RET fusion and results in ectopic transcriptional activation of RET in thyrocytes and is associated with papillary thyroid cancer (PTC). Cabozantinib, a selective RET inhibitor, restricts growth of RET/PTC1 cell lines and shows marked activity in patients with RET -mutant medullary thyroid cancer. However, its efficacy is limited due unknown mechanisms of resistance. Genetic analysis of the index patient's tumor revealed a RET/PTC1 rearrangement, alterations in the TERT promoter and a focal loss of TP53 . We performed molecular analyses of the index patient at distinct points throughout disease to generate a genomic timeline of disease and identify putative landmarks and molecular subtypes of disease. To functionally assess genetic alterations in the index patient, we transiently expressed RET/PTC1 in zebrafish thyroid follicular cells using a zebrafish thyroglobulin promoter. We observed tumor growth by 14 days post fertilization (dpf) in transgenic larvae, with histopathologic characteristics consistent with PTC. A transcriptional profile of RET/PTC1 transgenic zebrafish tumors revealed a set of genes associated with thyrocyte differentiation, as well as transcriptional signatures associated with cell proliferation and cAMP signaling in human thyrocytes. Ex vivo treatment of zebrafish RET/PTC1 tumors with cabozantinib, blocks RET activation and downstream signaling. As a whole, these studies provide proof-of-concept data to develop a transgenic zebrafish platform for patient specific models of thyroid carcinoma and other solid tumors. Citation Format: Jacques A. Villefranc, Chantal Pauli, Viviana Anelli, Sagar Chhangawala, Rohan Bareja, Theresa Scognamiglio, Andrea Sboner, Mark A. Rubin, Yariv Houvras. Building personalized genetic models of human cancer in zebrafish to predict response to therapy and characterize disease mechanisms. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-030.
Investigating the effects of wettability and gaseous nanobubbles on roughened wall–fluid interface using molecular dynamics simulation

AbstractThis paper reports on the use of molecular dynamics (MD) simulation to investigate the coupling effects of wettability, surface roughness and interfacial nanobubbles (INBs) on wall–fluid interfaces. The fluid properties close to the wall–fluid interface, such as potential energy, density, diffusion coefficients of fluid molecules and effective slip length are simulated. In the cases without surface nanobubbles, regions with lower potential energy have a higher probability of hosting water molecules. The local translational and rotational diffusion coefficients of water within the cavities are strongly influenced by wettability but largely unaffected by hydrodynamic effects. In cases where INBs exist, variations in wettability result in distinctly different argon morphologies. Argon nanobubbles form a convex shape on Wenzel-like interfaces but a shallow concave shape on Cassie-like interfaces. The phenomenon of water molecules invading grooves tends to occur on Wenzel-like interfaces; however, this...
Robotic imitation from human motion capture using Gaussian processes

Programming by demonstration, also called "imitation learning," offers the possibility of flexible, easily modifiable robotic systems. Full-fledged robotic imitation learning comprises many difficult subtasks. However, we argue that, at its core, imitation learning reduces to a regression problem. We propose a two-step framework in which an imitating agent first performs a regression from a high-dimensional observation space to a low-dimensional latent variable space. In the second step, the agent performs a regression from the latent variable space to a high-dimensional space representing degrees of freedom of its motor system. We demonstrate the validity of the approach by learning to map motion capture data from human actors to a humanoid robot. We also contrast use of several low-dimensional latent variable spaces, each covering a subset of agents' degrees of freedom, with use of a single, higher-dimensional latent variable space. Our findings suggest that compositing several regression models together yields qualitatively better imitation results than using a single, more complex regression model
District of Columbia City-wide Patient Navigation Research Program (DC-PNRP)

A70 Introduction: Minority breast cancer mortality rates in Washington, DC are among the Nation’s highest with a significant differential compared to whites. Evidence suggests the cause of this disparity is late stage at diagnosis and/or delayed initiation of treatment. Purpose: DC-PNRP is one of nine U.S. sites included in a joint National Cancer Institute - American Cancer Society (NCI/ACS) national research program evaluating whether or not using patient navigators (trained health workers assisting patients in reducing barriers to obtaining health care while addressing cultural/psychological factors) can reduce the breast cancer disparity in DC. Study Procedures: Our hypotheses include: Patient navigation will be more effective than “usual care” in decreasing time from suspicious breast finding to diagnostic resolution and time from diagnosis to breast cancer treatment initiation. We expect to enroll approximately 1400 women at the point of abnormal breast finding with minorities targeted at all seven participating DC sites. The comparison groups include historical controls selected from medical records at the recruitment sites for the time period prior to initiation of navigation at those sites, and concurrent controls selected from DC Department of Health records. The study is on a five-year timeline with data collection beginning February 2007 and extending to 2010. Local area training was conducted to supplement National introductory and follow-up training seminars. Summary of Results To-Date: A complex infrastructure was established with site-specific Standard Operating Procedures providing for common data collection and communication links to assure protocol adherence. An intricate national committee system was developed to assure agreement on data elements and procedures across sites. Participation rates for navigated patients across the DC sites are highly variable ranging from 5% to 100% with an overall rate of 34%. The racial/ethnic distribution of enrolled navigated patients includes approximately 57% Black, 9% White, and 35% Hispanic. Conclusion: A city-wide patient navigation program can be established among non-affiliated care centers to assure the underserved receive timely, high-quality care. Existence of the well-established DC Cancer Consortium, plus the commitment of DC’s major medical centers to reducing cancer disparities, suggests DC-PNRP will continue to be sustainable and successful after conclusion of the research study.
Shigatoxin Triggers Thrombotic Thrombocytopenic Purpura in Genetically Susceptible ADAMTS13-Deficient Mice.

The life threatening disease TTP is associated with ultra-large von Willebrand Factor multimers (UL-VWF) in the circulation due to inherited or acquired deficiency of the ADAMTS13 metalloprotease. Here we show that ADAMTS13-deficient mice generated by gene targeting are viable and exhibit normal survival through 2 years of age. Despite the absence of VWF-cleaving protease activity (
Jun Dimerization Protein 2 Activates Mc2r Transcriptional Activity: Role of Phosphorylation and SUMOylation.

Jun dimerization protein 2 (JDP2), a basic leucine zipper transcription factor, is involved in numerous biological and cellular processes such as cancer development and regulation, cell-cycle regulation, skeletal muscle and osteoclast differentiation, progesterone receptor signaling, and antibacterial immunity. Though JDP2 is widely expressed in mammalian tissues, its function in gonads and adrenals (such as regulation of steroidogenesis and adrenal development) is largely unknown. Herein, we find that JDP2 mRNA and proteins are expressed in mouse adrenal gland tissues. Moreover, overexpression of JDP2 in Y1 mouse adrenocortical cancer cells increases the level of melanocortin 2 receptor (MC2R) protein. Notably, Mc2r promoter activity is activated by JDP2 in a dose-dependent manner. Next, by mapping the Mc2r promoter, we show that cAMP response elements (between −1320 and −720-bp) are mainly required for Mc2r activation by JDP2 and demonstrate that −830-bp is the major JDP2 binding site by real-time chromatin immunoprecipitation (ChIP) analysis. Mutations of cAMP response elements on Mc2r promoter disrupts JDP2 effect. Furthermore, we demonstrate that removal of phosphorylation of JDP2 results in attenuated transcriptional activity of Mc2r. Finally, we show that JDP2 is a candidate for SUMOylation and SUMOylation affects JDP2-mediated Mc2r transcriptional activity. Taken together, JDP2 acts as a novel transcriptional activator of the mouse Mc2r gene, suggesting that JDP2 may have physiological functions as a novel player in MC2R-mediated steroidogenesis as well as cell signaling in adrenal glands.
Boost composite converter design based on drive cycle weighted losses in electric vehicle powertrain applications

A weighted design optimization is introduced to minimize total loss of electric vehicle drivetrain power electronics over EPA standard drive cycles. It is shown that the net loss of the conventional boost converter can be reduced by a factor of 1.5 with this approach, while computational effort is reduced by three orders of magnitude. Even larger efficiency improvements are achieved by optimized boost composite converters: losses are reduced by factors of 4.5, 2.9, and 4.3 for US06, UDDS, and HWFET driving cycles, respectively. These design optimization results are experimentally verified with a 30 kW laboratory prototype boost composite converter, which demonstrates 98.4% average efficiency over the US06 driving cycle.
Unlikely identification of an 8/8 OR 10/10 matched donor for patients with uncommon haplotypes

Aim Despite over 6 million subjects contributing to the NMDP HLA haplotype frequency reference data (HFD), haplotypes cannot be predicted from the HLA assignments of some patients searching for an unrelated donor (URD) in the Be The Match Registry®. The aims of this study were to determine the incidence of these patient searches and whether patient haplotypes lacking from the HFD can be found among the low-resolution typed URD pool. Methods From March 2014–2015, USA transplant centers submitting new NMDP searches with uncommon patient haplotypes (UPH), defined as a lack of haplotype pairs in any single race group in the HFD based upon HLA-A–C–B–DRB1–DQB1, were identified. Laboratory verification of patients’ HLA assignments was requested. Up to 20 USA based NMDP potential 10/10 or 8/8 donors were typed per patient to determine the likelihood of an allele match. Results The incidence of patient searches without pairs in a single race group in the HFD was 1.2% (144 of 12172 preliminary searches). Of the 144 patients, 27 had two haplotypes projected in disparate race tables, while 117 (81%) had at least one uncommon haplotype previously uncharacterized in the HFD. Non-White patients had the highest incidence of UPH. No patients with UPH had a 10/10 donor identified. Five patients, all with uncommon DRB1–DQB1 associations, had 8/8 donors identified (i.e., DQ mismatched). Conclusions HLA HFD that supports the HapLogic? matching algorithm is comprehensive as UPH patient searches were infrequent. Since these patients are unlikely to have a fully 10/10 matched donor identified, alternative stem cell sources including cord blood or a mismatched URD should be identified early in the search process. Many instances of typing corrections after initial HLA entry emphasize the importance of verifying the unique HLA assignments of these patients. UPH patients with haplotypes identified in disparate race groups but no pairs in a single race group highlights the need to better characterize patient HLA and mixed race/ethnicity for URD searching. Download : Download full-size image
Functional integration of humans and spacecraft through physics, physiology, safety and operability

Design criteria for human-rated space systems can be broken down into four top-level functional categories grouped by parameters of physics, physiology, safety and operability. Starting with a minimal function design baseline, a set of non-negotiable requirements can be derived that provide the requisite physical protection from the space environment and meet the basic physiological needs of the crew, but nothing more. This can be thought of as a ‘technically feasible, but programmatically unacceptable’ initial solution from which to start the iterative trade study process that will ultimately make the system safer and/or nicer (i.e., more operable). Safety aspects include risk mitigation approaches such as added redundancy, increased factor of safety or consumable margins. Operability can be further categorized into accommodation (what the vehicle provides the crew beyond the bare necessities) and utilization (what the crew does for the vehicle/mission), which can be evaluated through human factors analysis and testing. This framework provides clear and relatively simple guidelines for defining a set of baseline, minimum functionality conceptual design requirements that can theoretically accomplish the stated mission objectives. It can also serve as a verification and validation method to be used throughout the design process for ensuring that any additional features requested to be incorporated into the spacecraft beyond the minimal baseline are systematically rationalized for inclusion. Employing this philosophy from the beginning of a program can help to reduce the typical mass overruns that tend to occur from baselining legacy solutions and to minimize ‘scope creep’ by making it necessary to rigorously justify each function that is added over and above the minimum baseline in terms of improved safety or operability. This work outlines how a human spacecraft design scheme such as this can be defined and implemented.
Refined Model of the Oxidation States and Structures of the Mn/Ca/Cl Cluster of the Oxygen Evolving Complex of Photosystem II

Central to the problem of photosynthetic oxygen evolution is the structure and function of the Mn/Ca/Cl complex that appears to be the locus of charge accumulation and water splitting. In the recent past our group has presented a topological model for the structure of the tetranuclear Mn cluster, the oxidation state assignments of the S-states of the Kok cycle, the orientation of the Mn-Mn vectors relative to the membrane normal, and evidence for the proximity of Ca to the Mn (1–3).
Protein Expression and Purification of the Hsp90-Cdc37-Cdk4 Kinase Complex from Saccharomyces cerevisiae .

Interactions between Hsp90, its co-chaperone Cdc37 and kinases have been biochemically studied for over three decades and have been shown to be functionally important in organisms from yeast to humans. However, formation of a stable complex for structural studies has been elusive. In this protocol we describe expression and purification of Hsp90-Cdc37-Cdk4 kinase protein complex from Saccharomyces cerevisiae utilizing the viral 2A sequences to titrate the three proteins at similar levels.
Optimization of Patient Selection for Neoadjuvant Chemotherapy in Muscle-invasive Urothelial Carcinoma of the Bladder.

Abstract Background Radical cystectomy (RC) is delayed in a subset of patients who respond poorly to neoadjuvant chemotherapy (NAC). The present study investigated the clinicopathologic characteristics predicting extravesical disease at RC and the factors associated with NAC tolerability to improve patient selection and the sequence of definitive therapy. Materials and Methods Patients with cT2 urothelial carcinoma of the bladder who underwent NAC were stratified by the final pathologic stage: complete (ypT0N0), partial (≤ pT2), and nonresponse (> pT2 and/or N+). Patients treated with upfront cystectomy were divided into those with organ-confined (≤ pT2) and those with extravesical disease (> pT2 and/or N+). Results Of 145 patients, 89 received NAC and 56 underwent upfront RC. The univariate predictors of extravesical disease in the patients treated with upfront RC included increased age (P = .021), higher Eastern Cooperative Oncology Group performance status (P Conclusion Redundant clinicopathologic features predicted adverse cystectomy pathology in patients treated with both NAC and upfront RC. The results of the present study demonstrated an inferior pathologic response to alternative NAC regimens in clinically organ-confined disease and implicated cardiovascular comorbidities and nutritional status in the tolerability and response to NAC. Our findings predicate the importance of using patient-specific factors to guide the sequence of definitive treatment toward timely, centralized care to improve clinical outcomes.
Studies on the gross structure, cross-linkages, and terminal sequences in ribonuclease.

This article was a progress report on Anfinsen's effort to investigate the fine and gross structures of bovine pancreatic ribonuclease, particularly the N and C terminal sequences and the nature of cross-linkages in RNase. In it, Anfinsen, Redfield, Choate, Page, and Carroll described the gross structure and indicated that the fine structure should soon be apparent.
Cytopathology in the Diagnosis of Lymphoma

Fine needle aspiration (FNA) is a relatively simple, safe, and cost-effective procedure that has been used for decades in the evaluation of lymphadenopathy and mass lesions. However, its role in the diagnosis of lymphoma remains controversial. The key to enhancing the accuracy of FNA diagnosis of lymphoma is the multiparameter approach in which the cytomorphologic features should be interpreted in correlation with the results of ancillary studies and clinical context. This chapter focuses on the lymphomas that are more commonly encountered in cytopathology. The cytomorphologic, immunophenotypic, and molecular genetic features of various lymphoma subtypes and their diagnostic pitfalls are discussed.
Lemur catta (Ring-tailed lemur)

One pair of the submetacentric autosomes is especially large. Several pairs of the acrocentric autosomes are very small elements. Two pairs of small acrocentric autosomes bear secondary constriction near the centromere.
Maladaptive left ventricular remodeling in women: An analysis from the Women's Ischemia Syndrome Evaluation–Coronary Vascular Dysfunction study

Abstract Background Women represent approximately half of heart failure hospitalizations and are disproportionately affected by heart failure with preserved ejection fraction (HFpEF). Women with signs and symptoms of ischemia, preserved left ventricular ejection fraction (LVEF), and no obstructive coronary artery disease (CAD) often have elevated left ventricular end-diastolic pressure (LVEDP). However, isolated elevated LVEDP in the absence of coronary microvascular dysfunction (CMD) is not understood. Methods Among 244 women with signs and symptoms of ischemia, no obstructive CAD, and preserved LVEF who underwent invasive coronary reactivity testing (CRT), 43 (18%) women had no evidence of CMD. LVEDP was measured at time of CRT, and left ventricular (LV) volumes and mass were assessed by cardiac magnetic resonance (CMR) imaging. Results Of the 43 women without CMD, 24 (56%) had elevated LVEDP [mean 18 mm Hg (SD = 3)] compared to 19 (44%) with normal LVEDP [11 mm Hg (SD = 3)]. The elevated LVEDP group had a comparatively higher systolic and diastolic blood pressure, lower LV end-diastolic volume index (EDVI), and higher mass-to-volume ratio. Other functional parameters were not significantly different. Conclusions Among women with signs and symptoms of ischemia without obstructive CAD, absence of CMD, and preserved LVEF, isolated elevated LVEDP is associated with a significantly higher systolic and diastolic blood pressure, higher LV mass-to-volume ratio and lower LV EDVI. These results suggest these women have maladaptive remodeling to blood pressure. Given the relatively high prevalence of HFpEF in women, these hypothesis-generating results suggest that further study of ventricular remodeling is warranted.
Rechallenge of lamotrigine after development of rash

Lamotrigine (LTG) is associated with the potential for a life-threatening rash (eg, Stevens-Johnson syndrome or toxic epidermal necrolysis). The incidence has been linked to rapid titration and an interaction with valproic acid that can increase the level of LTG. Providers often have difficulty discriminating between serious versus benign rashes, and the package insert recommends discontinuing the medication at the first sign of a rash. Therefore, many patients end up being taken off LTG when it may have been effective for them. We present a case where LTG is reintroduced with a faster initial titration than what is noted in the literature after development of a rash. This case is also unique in that the patient had been on LTG for years prior to emergence of the rash and demonstrates that retrials can be successful.
Photonic Neural Network Nonlinear Activation Functions by Electrooptic Absorption Modulators

We report on using the transfer function of electrooptic absorption modulators as nonlinear activation functions of photonic neurons and show 95% accuracy of MNIST classification inference on an AlexNet in optical artificial neural networks.
Lexington and Concord: The Battle Heard Round the World. By George C. Daughan. (New York, NY: W. W. Norton and Company, 2018. Pp. xiv, 349. $27.95.)

As we approach the 250th anniversary of the American Revolution, the key episodes leading to the War of Independence are gaining renewed attention after a post‐Bicentennial lull. George Daughan's n...
A Retrospective Study of Venetoclax-Based Salvage Regimen As a Bridge to Allogeneic Hematopoietic Cell Transplantation (HCT) in High-Risk Acute Myeloid Leukemia (AML) Patients

Identification of anti-apoptotic properties of the Bcl2 protein has offered novel treatment options in many malignancies including AML. Venetoclax, a Bcl2 inhibitor, has shown promising results as upfront therapy in elderly patients (pts) and relapse/refractory (R/R) AML, when combined with hypomethylating agents (HMA). Yet, due to the high relapse risk, allogenic HCT remains as the only curative option for these high risk populations. To date, outcomes of HCT after prior therapy with Venetoclax + HMA have not been described. Also, as Venetoclax induces aplasia of antigen presenting cells expressing Bcl2, we hypothesized that pre-HCT treatment with venetoclax may be associated with a lower risk for GvHD. We retrospectively analyzed 26 consecutive AML pts who underwent HCT at our institution from 2016 to 2018 with final line of systemic therapy of venetoclax + HMA. Pts were not eligible for upfront standard induction chemotherapy (n=8) or had R/R disease (n=18). Fifteen pts received ≥2 lines of therapy and 3 had previous HCT. CR/CRi was achieved in 62% (n=16), of which 3 pts had minimal residual disease and the rest (n=10) had persistent disease prior to HCT. Donors were matched related (n=8), matched unrelated (n=16), or haploidentical (n=2). Conditioning regimen was myeloablative (38.5%) or reduced intensity (61.5%). Most pts (n=24, 92.3%) received PBMCs as the graft source. Tacrolimus/Sirolimus (Tac/Sir) was administered in most pts (n=20, 77%) for GvHD prophylaxis. Descriptive statistics were used for baseline characteristics. Kaplan-Meier and cumulative incidence curves were constructed for overall survival (OS), progression-free survival (PFS), relapse, none-relapse mortality (NRM), and aGvHD. Median age at the time of HCT was 59 years (range: 18-73). Median time to neutrophil and platelet engraftment were 17 days (range: 14-20) and 20 days (range: 16-61), respectively. With a median follow up of 4.5 months (range: 1.4-18.6), 6 months relapse rate was 12% (95% CI: 0.16-0.54) and 100 day NRM was 4% (95% CI: 0.02-0.34). Grade II-IV aGvHD at 100 days was noted in 34% (95% CI: 0.15-0.51). One-year OS and PFS for all pts were 72% (95% CI: 0.43-0.88) and 40% (95% CI: 0.16-0.63), respectively. For patients in CR at the time of HCT, 1-year OS was 80% (95%CI: 37-95) and PFS was 38% (95%CI: 0.08-0.69) (Fig 1). Only one patient who had been treated with three lines of systemic therapy prior to HCT experienced veno-occlusive disease. Thus, administration of Venetoclax-based salvage regimen as a bridge to HCT is safe with no added immediate toxicities post-HCT. Our early outcome data are promising for this otherwise high-risk population. Our data also justify further studies on the role and impact of Venetoclax and its anti-Bcl2 properties as a component of the conditioning regimen or as post-HCT maintenance.
Giant bilateral pulmonary arteriovenous malformations with refractory hypoxaemia

A 63 year old woman with alcoholic cirrhosis presented with a 2 week history of platypnoea (dyspnoea worse on sitting up). She had a history of upper gastrointestinal bleeding …
Bilirubin Correlation May Preclude MRCP in Acute Cholecystitis Patients With Normal Common Bile Duct Diameter

OBJECTIVE. In patients with acute cholecystitis (AC), accurate identification of a common bile duct (CBD) stone before cholecystectomy is of concern for surgeons, gastroenterologists, and radiologi...
Development and validation of an UPLC-MS/MS assay for quantitative analysis of the ghrelin receptor inverse agonist PF-5190457 in human or rat plasma and rat brain

PF-5190457 is a ghrelin receptor inverse agonist that is currently undergoing clinical development for the treatment of alcoholism. Our aim was to develop and validate a simple and sensitive assay for quantitative analysis of PF-5190457 in human or rat plasma and rat brain using liquid chromatography-tandem mass spectrometry. The analyte and stable isotope internal standard were extracted from 50 μL plasma or rat brain homogenate by protein precipitation using 0.1 % formic acid in acetonitrile. Chromatography was carried out on an Acquity UPLC BEH C18 (2.1 mm × 50 mm) column with 1.7 μm particle size and 130 A pore size. The flow rate was 0.5 mL/min and total chromatographic run time was 2.2 min. The mobile phase consisted of a gradient mixture of water: acetonitrile 95:5 % (v/v) containing 0.1 % formic acid (solvent A) and 100 % acetonitrile containing 0.1 % formic acid (solvent B). Multiple reaction monitoring was carried out in positive electro-spray ionization mode using m/z 513.35 → 209.30 for PF-5190457 and m/z 518.47 → 214.43 for the internal standard. The recovery ranged from 102 to 118 % with coefficient of variation (CV) less than 6 % for all matrices. The calibration curves for all matrices were linear over the studied concentration range (R 2 ≥ 0.998, n = 3). The lower limit of quantification was 1 ng/mL in rat or human plasma and 0.75 ng/g in rat brain. Intra- and inter-run mean percent accuracies were between 85 and 115 % and percent imprecision was ≤15 %. The assays were successfully utilized to measure the concentration of PF-5190457 in pre-clinical and clinical pharmacology studies of the compound.
Limbic and prefrontal neural volume modulate social anxiety in children at temperamental risk

BACKGROUND Clinical levels of a social anxiety disorder (SAD) often appear during childhood and rise to a peak during late adolescence. The temperament trait behavioral inhibition (BI), evident early in childhood, has been linked to increased risk for SAD. Functional and structural variations in brain regions associated with the identification of, and response to, fear may support the BI-SAD relation. Whereas relevant functional studies are emerging, the few extant structural studies have focused on adult samples with mixed findings. METHODS A moderated-mediation model was used to examine the relations between BI, SAD symptoms, and brain-volume individual differences in a sample of children at risk for anxiety (ages 9-12; N = 130, 52 BI). RESULTS Our findings indicate that at higher levels of BI, children with smaller anterior insula volumes showed stronger correlations between BI and SAD. In addition, larger ventrolateral prefrontal cortex (vlPFC) volumes were associated with fewer SAD symptoms. CONCLUSIONS These findings support previous reports linking SAD levels with variations in volume and reactivity in both limbic (insula) and prefrontal (vlPFC) regions. These findings set the foundation for further examination of networks of neural structures that influence the transition from BI to SAD across development, helping further clarify mechanisms of risk and resilience.
The South Florida Study Area

South Florida is a popular destination for new residents and tourists, attracting a great deal of residential property investment from other parts of the United States as well as Canada and Latin America. Its flat coastal topography, rarely rising above 10 meters above sea-level, makes it susceptible to both storm surge and tidal flooding. The limestone bedrock underlying many of the urban areas adds to the flood risks. Settlement of Florida followed rail and interstate connection, the draining of former wetlands to create residential property, and the development of air conditioning to facilitate year-round occupation. The specific portions of Florida studied in the research reported here include postal code zones (zip-codes) in the urban areas of Tampa-Saint Petersburg-Clearwater, Fort Myers, Key West, Miami-Dade County, Fort Lauderdale, West Palm Beach and Palm Beach, and Vero Beach. Most of these areas experienced real estate speculation, with accompanying boom-and-bust periods, as well as numerous home sales to non-resident owners who do not have the same connection to the region as owner-occupiers. Despite repeated flooding, Floridians have shown an ambivalence about their susceptibility to sea-level rise.
Floods, Lawsuits, and Water Infrastructure Management

AbstractClimate change and land development are causing more flood damage in the United States, which leads to more litigation. This is a rising concern to USACE, which owns many dams, levees, and ...
P17 Health and Diabetes Perspectives of Mexican-Origin Males at Risk for Type 2 Diabetes (HD-MxOM): A Qualitative Study

Background The combination of rapid population growth and diabetes prevalence disparities convey an alarming health trajectory for the Hispanic population. Hispanics represent the largest minority group in the United States, with current trends expected to double the Hispanic population to 111 million by 2060. The prevalence of diabetes among Hispanics is 16.4%, second only to non-Hispanic blacks, and Hispanics hold the third highest prevalence of prediabetes at 31.7%. Furthermore, males of Mexican descent have the highest rates of diabetes (14.2%), overweight (80%) and obesity (43%) across all ethnic groups. Objective Explore the perspectives on diabetes, nutrition, and health among native Spanish-speaking, Mexican origin males at risk for type 2 diabetes (T2D). Study Design, Setting, Participants The present qualitative study utilized audio-recorded, semi-structured interviews of Spanish-speaking, Mexican-origin males, between the ages of 40 and 64 at risk for T2D. At risk for T2D was defined as >40 years of age, (BMI >27), and formal exercise less than 3 times per week. Measurable Outcome/Analysis Data collected included clinical (height, weight, waist circumference, blood pressure) and demographic (time living in the US, marital status, employment, income, educational attainment, and physical activity). The audio data from the 15 participants were transcribed and underwent 3 cycle coding for categorization and thematic analysis. Results Barriers to health behavior among Mexican-origin males include: poor understanding of diabetes and nutrition knowledge, unreliable sources of health information, medical machismo, and socioeconomic status. Novel findings include perspectives of intense diabetes severity, personal responsibility for health, and sociocultural barriers such as pediatric health formation. Conclusions HD-MxOM represents the first, theory-based study for the exploration of diabetes perspectives among Mexican-origin males. The emergent themes include a poor understanding of diabetes and nutrition, inhibitory sociocultural forces such as medical machismo and valemadrismo, and low health prioritization. These findings provide educators and clinicians essential information for optimization of program development and clinical interaction with Hispanic men.
OPTIK: a database for understanding catchment areas to guide mobilization of cancer center assets

An increasingly diversified demographic landscape in rural and urban America warrants the attention of The University of Kansas Cancer Center (KU Cancer Center) researchers, clinicians, outreach staff and administrators as the institution assesses ways to reach its expansive, bi-state catchment area. Within the counties of the KU Cancer Center catchment area, patient level and public health data are available and categorized by varying geographic regional boundaries. Multiple data sources and different data collection processes complicate summarizing catchment area data. A curated data warehouse that retrieves and structures the data, with a common denominator, can support meaningful use of the data in a standard and consistent format. The KU Cancer Center built a data warehouse to Organize and Prioritize Trends to Inform KU Cancer Center (OPTIK), which functions to streamline the process of synthesizing data regarding Kansas and Missouri demographics, cancer risk factors and incidence and mortality rates. OPTIK standardizes these diverse data sources to enable analyses of the cancer burden at local, regional and national levels while upholding a strict standard of patient privacy. The OPTIK database enables researchers to use available data and create heat maps and other visualizations to aid in funding proposals, presentations and research activities. Furthermore, using knowledge provided by OPTIK, the KU Cancer Center is able to prioritize action items for research and outreach and more effectively communicate the impact of those efforts.
Biopolitics, Orientalism, and the Asian Immigrant as Monster in Salazar’s La medianoche del japonés and Rodríguez’s Asesinato en una lavandería china

This chapter studies the biopolitical repercussions of monstrifying ethnic minorities by comparing a Peruvian novel in which a Japanese immigrant is described as a monster with a Mexican novel in which Chinese Mexican characters have actually become vampires. In different ways, Salazar’s La medianoche del japones (1991) and Rodriguez’s Asesinato en una lavanderia china (1996) echo, through images of monsters and vampires, the widespread fear of an Asian Other awkwardly integrated into the body of the nation, even though the authors and narrators are sympathetic to their Asian characters. The presence of Asian bodies within the body of the nation disturbs the conventional mestizo identities of Peru and Mexico. The discourse of mestizaje renders Asian immigrants as abject bodies, as a disease that must be extricated. The literary monstrification of the Asian outsider could, therefore, be a symptom or reification of the disappointment for the failure of homogenizing national projects. In a way, the representation of the immigrant or Asian Other as a vampire or other type of monster helps differentiate between one’s own sense of (national) self and the threatening, repulsive, “foreign” Other, thus disrupting the aforementioned “strangely familiar” feeling.
Activin B Promotes the Initiation and Progression of Liver Fibrosis

Background & AimsLiver fibrosis is a pivotal pathology in multiple hepatic disease indications, profoundly characterizing disease severity and outcomes. The role of activin B, a TGF{beta} superfamily cytokine, in liver health and disease is largely unknown. We aimed to investigate whether activin B modulates liver fibrogenesis. MethodsLiver and serum activin B, along with its analog activin A, were analyzed in patients with liver fibrosis from different etiologies and in mouse acute and chronic liver injury models. Activin B, activin A, or both was immunologically neutralized in mice with progressive or established carbon tetrachloride (CCl4)-induced liver fibrosis. The direct effects of activin B and A on hepatocytes and hepatic stellate cells (HSCs) were evaluated in vitro. ResultsAs a result, hepatic and circulating activin B was increased in human patients with liver fibrosis caused by several liver diseases. In mice, hepatic and circulating activin B exhibited persistent elevation following the onset of several types of liver injury, whereas activin A displayed transient increases. The results revealed a close correlation of activin B with liver injury regardless of etiology and species. We found that neutralizing activin B largely prevented, as well as remarkably regressed, CCl4-induced liver fibrosis, which was augmented by co-neutralizing activin A. Mechanistically, activin B directly promotes hepatocyte death, induces a profibrotic expression profile in HSCs, and stimulates HSCs to form a septa structure. In addition, activin B and A interdependently upregulated the transcription of profibrotic factors including connective tissue growth factor and TGF{beta}1 in injured livers. ConclusionsWe demonstrate that activin B, cooperating with activin A, directly acts on multiple liver cell populations, and drives the initiation and progression of liver fibrosis. Our finding inspires the development of a novel therapy of chronic liver diseases.
Collaborative Care in the Identification and Management of Psychosis in Adolescents and Young Adults

Pediatricians are often the first physicians to encounter adolescents and young adults presenting with psychotic symptoms. Although pediatricians would ideally be able to refer these patients immediately into psychiatric care, the shortage of child and adolescent psychiatry services may sometimes require pediatricians to make an initial assessment or continue care after recommendations are made by a specialist. Knowing how to identify and further evaluate these symptoms in pediatric patients and how to collaborate with and refer to specialty care is critical in helping to minimize the duration of untreated psychosis and to optimize outcomes. Because not all patients presenting with psychotic-like symptoms will convert to a psychotic disorder, pediatricians should avoid prematurely assigning a diagnosis when possible. Other contributing factors, such as co-occurring substance abuse or trauma, should also be considered. This clinical report describes psychotic and psychotic-like symptoms in the pediatric age group as well as etiology, risk factors, and recommendations for pediatricians, who may be among the first health care providers to identify youth at risk.