cssi/SciSciGPT-SciSciNet huggingface dataset:
Dimensioning WDM Networks for Dynamic Routing of Evolving Traffic

New Internet applications are increasingly generating high-bandwidth and short-lived demands. If network resources are available, establishing a lightpath on demand only takes a few minutes on today's reconfigurable optical networks. These demands thus create a more variable and unpredictable environment for long-term network planning. At the same time, upgrading backbone networks remains expensive and infrequent. Dimensioning network resources to sustain variable traffic demands for a long time, while requiring fewer upgrades to achieve high performance, has become a challenging problem. Two kinds of dimensioning problems for optical opaque networks are proposed and studied in this paper: basic dimensioning allocates network resources for a newly built network, and incremental dimensioning allocates extra resources for future demand growth and variations. We propose new metrics to quantify the traffic load and the traffic pattern evolution for dynamically routed networks. We evaluate the performance under load scaling, traffic evolution, and misdimensioning. We show that a dimensioned network can sustain a much higher load while providing the same performance compared with misdimensioned ones. Our approach is better adapted to traffic evolution than a uniform allocation and an asymptotic optimization approach proposed earlier.
Determination of Sialic Acid and 2-Keto-3-Deoxyoctonic Acid Derivatives

Deoxyribose reacts with thiobarbituric acid after periodate oxydation, as discovered by Warawdekar and Saslaw (1957), Other deoxycarbohydrates, such as 2-keto-3-deoxy (KDO) derivatives as well as sialic acid will also give a pink colored reaction product after above treatment. Exercise No. 43 in this Manual gives a paper- and thin-layer chromatographic spray reagent for the detection of such carbohydrates. This Exercise is a colorimetric method for the quantitative determination of sialic acid (Part A) and of 2-keto-3-deoxyoctonic acid (Part B) contents in hydro-lysates. The procedure is based on the method of Warren (1963) for sialic acid, and of Weissbach and Hurwitz (1959) for 2-keto-3-deoxyoctonic acid determination.
Biblical Limits on the Role of Civil Government

This paper suggests that the Bible supports a very limited civil government. The Bible teaches that the authority of civil government, like all human authority, finds its source in God himself. God grants authority, and authority ungranted is authority denied. It appears that God’s grant of authority to civil government is found in Genesis 9:6, in his command that human beings exact corrective justice for violations against God’s image in human beings.
Cataract Surgery Outcomes in Uveitis: The Multicenter Uveitis Steroid Treatment Trial

Purpose To assess the visual outcomes of cataract surgery in eyes that received fluocinolone acetonide implant or systemic therapy with oral corticosteroids and immunosuppression during the Multicenter Uveitis Steroid Treatment (MUST) Trial. Design Nested prospective cohort study of patients enrolled in a randomized clinical trial. Participants Patients that underwent cataract surgery during the first 2 years of follow-up in the MUST Trial. Methods Visual outcomes of cataract surgery were evaluated 3, 6, and 9 months after surgery using logarithmic visual acuity charts. Change in visual acuity over time was assessed using a mixed-effects model. Main Outcome Measures Best-corrected visual acuity. Results After excluding eyes that underwent cataract surgery simultaneously with implant surgery, among the 479 eyes in the MUST Trial, 117 eyes (28 eyes in the systemic, 89 in the implant group) in 82 patients underwent cataract surgery during the first 2 years of follow-up. Overall, visual acuity increased by 23 letters from the preoperative visit to the 3-month visit (95% confidence interval [CI], 17–29 letters; P P P P P P > 0.05, test of interaction). After adjusting for other risk factors, there was no significant difference in the improvement in visual acuity between the 2 treatment groups (implant vs. systemic therapy, 2 letters; 95% CI, −10 to 15 letters; P = 0.70). Conclusions Cataract surgery resulted in substantial, sustained, and similar visual acuity improvement in the eyes of patients with uveitis treated with the fluocinolone acetonide implant or standard systemic therapy.
Financial Considerations Related to Materials Management

Financial management is the study and practice of monetary decision making within a company. Financial managers are members of a management team responsible for assessing the financial implications of any decision made by the firm.1 There are many stages during the growth or the contraction of a company where financial decisions determine its success or failure. For example, expansion funds can be obtained from many sources, such as the sale of stocks or bonds, bank loans, and capital equipment leasing. Input into each financial decision comes from members of the management team, which includes groups such as materials management, engineering, and marketing. However, the financial management group makes the final decision in choosing the best alternative, evaluating the present and future impact of the decision.
Hippocampal Changes in Febrile Infection-Related Epilepsy Syndrome (FIRES)

Febrile seizures are the most common seizure disorder in childhood, associated with a significant rise in body temperature. However, post-infectious refractory afebrile form of seizures in previously healthy children is being increasingly recognized in around the world, which evolves into a chronic refractory form of epilepsy. The term 'Febrile infection-related epilepsy syndrome' (FIRES) has been proposed for these conditions and represents a refractory severe post-infectious epileptic condition in previously normal children.We report the initial and follow-up MR imaging findings in a 5year-old with refractory epilepsy post-febrile seizures.In summary, acute post-infectious seizures are increasingly being recognized across the globe with the newly coined term 'Febrile infection-related epilepsy syndrome'(FIRES) for this group of immune-mediated epileptic encephalopathy in previously healthy children. This has three phases: episode of simple febrile infection, followed by acute refractory seizures and lastly the chronic phase of neuropsychological impairments and seizures.
Hospital Utilization of Nationally Shared Liver Allografts from 2007 to 2012.

Due to the current geographic disparities in liver allocation a policy, which endorses broader sharing of allografts, has been proposed. We performed a retrospective cohort study to identify how nationally shared allografts, under the current policy, affect perioperative outcomes and resource utilization following liver transplantation (LT). Univariate and multivariate analysis identified how patient characteristics and hospital outcomes were associated with national sharing. This analysis was based on 12,282 deceased donor liver transplants performed between 2007 and 2012 using the scientific registry of transplant recipients linked to the University HealthSystem Consortium database. Compared to locally distributed livers, nationally shared livers are more likely to have a donor risk index >1.8 (64.3 vs. 11.6 %), to be classified as expanded criteria donors (44.6 vs. 24.8 %), and transplanted into healthier recipients. Nationally shared LTs were more likely to be performed at high-volume centers (49.1 vs. 30.6 %), resulted in longer length of stay (11 vs. 9 days), and had higher in-hospital mortality (6.6 vs. 3.3 %). Additionally, nationally shared allografts were independent predictors of in-hospital mortality (OR 1.64, 95 % CI 1.13–2.39) and length of stay (OR 1.12, 95 % CI 1.02–1.21). These data suggest that increased national sharing of livers may result in inferior patient outcomes and increased resource utilization.
Modern Hypertension Management: The Who and the Where.

See related article, pp 1145–1151 Detection and successful management of arterial hypertension is one of the major success stories of recent decades. Large fractions of those with hypertension in the US population have been identified and successfully treated with antihypertensive medication. Prevention of cardiovascular disease has been achieved. In a recent national survey, it is estimated that ≈80% of those with hypertension are aware of their diagnosis, ≈75% are treated, and ≈51% are controlled on the basis of the Joint National Committee-7 guideline.1 However, there is little reason to be complacent and lessen the effort to find and treat more of the population. Management of hypertension and the other widespread cardiovascular risk factors, dyslipidemia and adult diabetes mellitus, has been the province of office- or clinic-based primary care, that is, general internal medicine and family practice. In the United States, primary care medicine has become an endangered species because medical school graduates increasingly seek careers in several medical specialties, hospitalist medicine, and emergency medicine.2 There is an urgent need to augment and modify traditional primary care for expansion of the national effort in preventive cardiology. An expanded role for pharmacists to participate in care …
Importance of teamwork, communication and culture on failure‐to‐rescue in the elderly

Background Surgical mortality increases significantly with age. Wide variations in mortality rates across hospitals suggest potential levers for improvement. Failure-to-rescue has been posited as a potential mechanism underlying these differences. Methods A review was undertaken of the literature evaluating surgery, mortality, failure-to-rescue and the elderly. This was followed by a review of ongoing studies and unpublished work aiming to understand better the mechanisms underlying variations in surgical mortality in elderly patients. Results Multiple hospital macro-system factors, such as nurse staffing, available hospital technology and teaching status, are associated with differences in failure-to-rescue rates. There is emerging literature regarding important micro-system factors associated with failure-to-rescue. These are grouped into three broad categories: hospital resources, attitudes and behaviours. Ongoing work to produce interventions to reduce variations in failure-to-rescue rates include a focus on teamwork, communication and safety culture. Researchers are using novel mixed-methods approaches and theories adapted from organizational studies in high-reliability organizations in an effort to improve the care of elderly surgical patients. Conclusion Although elderly surgical patients experience failure-to-rescue events at much higher rates than their younger counterparts, patient-level effects do not sufficiently explain these differences. Increased attention to the role of organizational dynamics in hospitals' ability to rescue these high-risk patients will establish high-yield interventions aimed at improving patient safety.
Vulnerability of fishing communities undergoing gentrification.

Abstract Maine hosts numerous rural fishing villages that contribute greatly to the State's economy and culture. The cumulative effects of fisheries regulation, stock depletion, amenity migration and rural restructuring have impacted these communities in complex ways. Drawing on ethnographic research, interviews, and secondary data we have identified the patterns of change as symptomatic of gentrification, and we have investigated how these changes are affecting the communities' vulnerability and resilience. Gentrification of coastal property by amenity migrants is responsible for the displacement of community members, including fishermen. The loss-of-access to the waterfront has increased their sensitivity to future threats. Further changes in the demographics and economies of the communities have increased social and cultural conflicts. Nevertheless, this paper also demonstrates that gentrification can increase the resilience of the community. Amenity migrants have the capacity and desire to provide social and philanthropic support, and rural restructuring introduces new economic opportunities and sources of revenue. The underlying consequences of gentrification are difficult to discern from secondary data alone, and we argue that the ethnographic approach is crucial. Through interview responses we have identified an identity crisis in these communities undergoing gentrification, with many of the conflicts over the future importance of fishing to the community.
Modal Dynamics and Stability of Large Multi-megawatt Deepwater Offshore Vertical-axis Wind Turbines: Initial Support Structure and Rotor Design Impact Studies

The availability of offshore wind resources in coastal regions, along with a high concentration of load centers in these areas, makes offshore wind energy an attractive opportunity for clean renewable electricity production. High infrastructure costs such as the offshore support structure and operation and maintenance costs for offshore wind technology, however, are significant obstacles that need to be overcome to make offshore wind a more cost-effective option. A vertical-axis wind turbine (VAWT) rotor configuration offers a potential transformative technology solution that significantly lowers cost of energy for offshore wind due to its inherent advantages for the offshore market. This paper presents an initial design impact study for assessing the dynamic stability of large multi-megawatt deepwater offshore VAWTs. The analysis and understanding of very large, highly flexible VAWT structures is further complicated by the rigid body modes of a floating support structure. A newly developed design tool for offshore VAWTs is employed to assess the stability of very large multi-megawatt VAWT configurations in a deepwater environment. To gain a fundamental understanding of tower resonance in VAWTs, an analytical expression for characterizing critical per-rev excitations for VAWT configurations is developed and presented. The influence of various support condition on structural modes of a VAWT is also investigated. For offshore deployment, a monopile support condition may exacerbate resonance concerns while floating platform supports may provide a means to alleviate resonance concerns. The effect of the large rotating structure on the rigid body modes of the turbine/platform system is also examined.
Exploiting Natural Fluctuations to Identify Kinetic Mechanisms in Sparsely Characterized Systems

From biochemistry to ecology, many biological systems are stochastic, complex, and sparsely characterized. In such systems, each component may respond to changes in any directly or indirectly connected components, thus requiring knowledge of the whole to predict the dynamics of the parts. Here, we address this challenge by deriving relations between properties of fluctuations that only reflect local interactions between a subset of components but are invariant to all indirectly connected dynamics. This greatly reduces the number of assumptions when evaluating dynamic models experimentally. We illustrate the approach by revisiting systematic single-cell gene expression data, and we show that the observed fluctuations contradict the assumptions made in most published models of stochastic gene expression, even when accounting for the possibility of systematic experimental artifacts.
Emerging IT for Medication Adherence

Medication adherence is one of the most complex and persistent challenges in healthcare. Solutions have been designed with varying degrees of success. Here, the authors present a roadmap that shows how emerging IT can play a major role in improving medication adherence. Specifically, they discuss five major technologies for medication adherence: smartphone apps, smart medication boxes, smart pills, sensors, and implantable devices. They show how these technologies support and integrate into a roadmap for higher medication adherence. The hope is that IT professionals will address many of the challenges and opportunities identified in the article.
Meta-Analysis of the English Version of the Beck Depression Inventory–Second Edition

This meta-analysis reviewed 144 studies from 1996 to 2013 using the Beck Depression Inventory–Second Edition. Internal consistency was .89 and test–retest reliability .75. Convergent comparisons we...
Cloning and expression of a new mammalian chaperonin gene from a multipotent hematopoietic progenitor clone

Molecular chaperones assist in the folding and assembly of proteins in cells. Although chaperonins have been shown in prokaryotes, mitochondria, and chloroplasts long-ago, a cytoplasmic heteromeric chaperonin complex was isolated only recently and found to contain at least five to six polypeptides, one of which was identified as the product of the T complex polypeptide-1 (TCP-1) gene. We have isolated and cloned a novel gene called A45 from a cDNA library constructed from poly (A)+ RNA of a multipotent hematopoietic progenitor clone. The A45 cDNA encodes a predicted polypeptide of M(r) 58,118 that exhibits 32% overall amino acid sequence identity to TCP-1 and contains the putative adenosine triphosphate-binding domain and two characteristic consensus regions that are conserved in all chaperonins. The A45 gene is expressed in hematopoietic precursors cells at a much higher level than in nonhematopoietic cells and tissues. We conclude that A45 represents a new member of the mammalian chaperonins that is involved in the folding and assembly of polypeptides.
Trends in medical malpractice claims in patients with cleft or craniofacial abnormalities in the United States

Abstract Objective To describe medical malpractice trends in patients with cleft and/or craniofacial abnormalities. Methods and materials A modified Delphi approach was used to gather search terms. Search settings included “all jury verdicts and settlements”, with jurisdiction of “all states” and “all federal courts” (by court and circuit). A retrospective review of WestLawNext legal database was conducted. Cases were excluded if they did not have a direct association from the patient's craniofacial anomaly or if they were not related to malpractice. Results Forty-two cases met inclusion criteria. Cases closed between 1981 and 2014 were included. The mean payment among claims with an indemnity payment was $3.9 million. Of cases brought to trial, 62% were in favor of the plaintiff. Amongst physicians named as co-defendants, pediatricians were most commonly named (24%), followed by plastic surgeons (16%), obstetricians (7.8%), and radiologists (7.8%). “Missed diagnosis” was the most common type of negligent claim (45%), followed by “surgical error” (21%), and “medication error” (17%). “Anoxic brain injury” resulted in the highest median indemnity payment for complication of patient management ($3.5 million), followed by “wrongful birth” ($1.03 million), and “minor physical injury” ($520,000). No specific type of negligent claim (p = 0.764) nor complication of patient management (p = 0.61) was associated with a greater indemnity payment. Mean indemnity payment was $920,000 prior to 2001 and $4.4 million after 2001 (p = 0.058). Conclusions Mean indemnity payments were fourteen-fold greater in patients as compared to those in the overall population ($3.9 million versus $274,887) and seven-fold greater than those in the average pediatric population ($3.9 million versus $520,923). All healthcare providers should be aware of the associated medical malpractice claims that may be incurred when treating patients at risk for these conditions.
Memory and Motor Processes of Password Entry Error

Passwords are tightly interwoven with the digital fabric of our current society. Unfortunately, passwords that provide better security generally tend to be more complex, both in length and composit...
A virtual clinical trial using projection-based nodule insertion to determine radiologist reader performance in lung cancer screening CT

Task-based image quality assessment using model observers is promising to provide an efficient, quantitative, and objective approach to CT dose optimization. Before this approach can be reliably used in practice, its correlation with radiologist performance for the same clinical task needs to be established. Determining human observer performance for a well-defined clinical task, however, has always been a challenge due to the tremendous amount of efforts needed to collect a large number of positive cases. To overcome this challenge, we developed an accurate projection-based insertion technique. In this study, we present a virtual clinical trial using this tool and a low-dose simulation tool to determine radiologist performance on lung-nodule detection as a function of radiation dose, nodule type, nodule size, and reconstruction methods. The lesion insertion and low-dose simulation tools together were demonstrated to provide flexibility to generate realistically-appearing clinical cases under well-defined conditions. The reader performance data obtained in this virtual clinical trial can be used as the basis to develop model observers for lung nodule detection, as well as for dose and protocol optimization in lung cancer screening CT.
The impact of pregnancy on headache evaluation in the emergency department, a retrospective cohort study.

Headache is one of the most common emergency department complaints with three million visits annually in the USA. This is further complicated with 30% of those emergency visits being for a hypertensive disorder of pregnancy. There is no currently well-established guideline for diagnostic imaging with a common concern being ionizing radiation exposure in pregnancy. The purpose of this study was to assess the difference in imaging studies ordered for pregnant and non-pregnant patients who reported to a tertiary care emergency department with headache. The purpose of this study was to assess the difference in imaging studies ordered for pregnant and non-pregnant patients who reported to a tertiary care emergency department with headache. This retrospective cohort study identified all reproductive age female patients who presented to the emergency department with a chief complaint of “headache.” They were then divided into cohorts based on pregnancy status. Rates and types of imaging studies utilized in patient evaluation were then compared. Two thousand seven hundred ninety patients met our criteria for evaluation; 95 were found to be pregnant. Head CTs were ordered significantly less and MRIs were ordered significantly more in the pregnant cohort as compared to the non-pregnant cohort with a P value of <0.0001 and an odds ratio of 4.21 and a P value of 0.0127 and an odds ratio of 0.49, respectively. Our data shows a difference in evaluation for pregnant patients as compared to their non-pregnant cohort. CT should not be considered contraindicated in the pregnant population and the amount of ionizing radiation to the fetus is well within the maximum safe dose, particularly with appropriate shielding. The time difference, cost, fetal exposure risk, and availability of CT compared to MRI should be taken into account when establishing a criterion for diagnostic evaluation. This difference validates the need for further research into a well-established guideline for the emergent evaluation of headache in the ED without special bias placed on pregnancy status.
Analysis of Adjuvant Endocrine Therapy in Practice From Electronic Health Record Data of Patients With Breast Cancer

PurposeAdjuvant endocrine therapy is a long-term drug therapy prescribed to prevent recurrence of hormone receptor–positive breast cancer. Data on adjuvant endocrine therapy are reported though clinical trials, which may differ from treatment practice and outcomes in the general population of patients with breast cancer. With secondary use of electronic health record (EHR) data, we summarize adjuvant endocrine treatment practice and outcomes in real-world settings.MethodsWe analyzed treatment data derived from EHR data on 1,587 patients with stage I to III breast cancer at a National Cancer Institute–designated comprehensive cancer center to learn the frequencies of real-world adjuvant endocrine drug switches and discontinuation and to explore the potential cause for drug switches and discontinuation from medical records. We measured rates of drug use, drug switches, early drug discontinuation, adverse events, recurrence, and death. We also measured adverse events and change in menopause status as potenti...
Lessons learned from a phase II clinical trial of laparoscopic HIPEC for gastric cancer.

Over the last two decades, intraperitoneal chemotherapy has been found to have activity for select subgroups of patients with carcinomatosis from colon, ovarian, appendiceal, and recently, gastric origins. However, there is little data to support an aggressive surgical approach of cytoreduction (debulking) and hyperthermic intraperitoneal perfusion with chemotherapy (HIPEC) for patients with gastric cancer and positive cytology or carcinomatosis. The morbidity and mortality rates of cytoreduction and HIPEC, in combination with gastrectomy, are significant and the survival rates of this approach may not extend beyond that of treatment with systemic chemotherapy. The objective of this clinical trial, therefore, was to perform HIPEC in a neoadjuvant fashion via a minimally invasive approach without cytoreduction for patients with gastric cancer and positive cytology or low volume carcinomatosis. Patients found to have resolution of all extra-gastric disease are then candidates for gastrectomy. Patients with gastric and gastroesophageal adenocarcinoma and positive peritoneal cytology or radiologically-occult carcinomatosis that have completed treatment with systemic chemotherapy were offered participation in the study. We have performed 38 laparoscopic HIPEC procedures in 19 patients. Laparoscopic HIPEC consists of Mitomycin C 30 mg and Cisplatin 200 mg in 3–7 L of infusate circulated using an extracorporeal circulation device at a flow rate of 700–1500 mL/minute for 60 min. The Laparoscopic HIPEC procedure may be performed up to five times. In this video, we sought to present the surgical technique refined during our development and completion of this Phase II clinical trial (NCT02092298). The purpose of this presentation is to (1) demonstrate the technique of laparoscopic HIPEC and (2) review the surgical lessons learned from performing multiple HIPEC procedures prior to attempted gastrectomy.
Increasing positive and decreasing negative teacher responses to student behavior through training and feedback.

Teachers tasked with educating students in an inclusive environment must effectively work with ongoing behavior issues in the classroom. Increasing teacher praise statements while reducing negative statements provides one method for increasing appropriate student behavior and reducing and potentiall
The Performance and Pedagogy of Migration in the Foreign Language Classroom: Staging Roland Schimmelpfennig's Der goldene Drache

This article explores how drama pedagogy in the foreign language classroom serves as a unique avenue for approaching the global issue of migration in the context of German-speaking Europe. The article focuses on how staging a contemporary play about migration, such as Roland Schimmelpfennig's Der goldene Drache (2009), in German for an English-speaking student and community audience can serve as a particularly rich example of cross-cultural translation. The article outlines the various steps in experiential learning involved in a German-language drama course and reflects on the potential for students and their instructor to be culturally transformed through the language of drama and the representation of migration. A brief discussion of Schimmelpfennig's play and its production in the context of a German drama course at a Midwestern university illustrates what the performance and pedagogy of migration might look like in the German foreign language classroom.
The Gift That Keeps on Giving: Culturally Relevant Integration of Spirituality in Family Therapy With African American Families

The connection between spirituality and health and social/emotional well-being is well established. While the majority of the U.S. population describe themselves as spiritually oriented, many believe the importance they place on spirituality will be disregarded or viewed negatively by therapists. Hines argues that to advocate for and conduct culturally relevant, effective engagement, assessment and intervention, especially with African Americans and other populations of color who historically have faced social, economic and political oppression, requires the integration of spirituality. Offering observations that are clearly linked to her rearing in the Protestant traditions as well as her own spiritual and cultural journey and family therapy practice, the author shares examples of strategies that have helped her clients to actively integrate their spiritual beliefs and practices into their daily lives, strengthen their resilience, and resolve personal and relational challenges.
Quantity of Reporting About Hazards: The Case of Naturally Occurring Radon

People have intellectual and visceral motives for their behavior. The first is often weaker than the second, which is why many dieters succumb to the sight of food. Environmental hazards may be viscerally motivating too, when they are immediate and threatening, like the thunder and lightning of a storm, or a recent earthquake, to which people usually make reasonable alleviating responses (Quarantelli and Dynes, 1972). But most environmental hazards are too distant or improbable to be viscerally threatening — for example, naturally occurring indoor radon, or future earthquakes. We know intellectually that these are potentially harmful, but they do not evoke anxiety. Therefore, though risk analysts tell us that as rational calculating actors we ought to protect ourselves, most of us do nothing.
The CGRP-Receptor Component Protein: A Regulator for CLR Signaling

Calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) are potent vasoactive neuropeptides that have a pleiotropic set of important physiologic functions. Despite their emerging physiologic roles, there are few therapeutic strategies targeting CGRP and AM. This is in part due to the fact that these two neuropeptides are inherently unstable and easily digested in the gut, and therefore do not make ideal therapeutic ligands. In addition, the receptor for CGRP and AM was difficult to identify, making it difficult to test non-peptide compounds for efficacy. It is now known that the receptor for CGRP and AM contains multiple proteins: a ligand-binding protein named calcitonin receptor-like receptor (CLR) and an accessory protein named receptor activity modifying protein (RAMP) that confers pharmacologic specificity for AM or CGRP. A third protein is required for signaling of the CLR/RAMP heterodimer, named CGRP-receptor component protein (RCP). RCP was initially characterized in cell culture, but a growing series of studies has implicated it’s role for in vivo signaling at CLR and suggests that RCP can modulate CLR signaling in response to physiologic stimuli. RCP is found throughout evolution, and this review will discuss potential mechanisms of RCP function in a physiologic setting.
Gene Expression Arrays in Pancreatic Cancer Drug Discovery Research

The development of gene expression arrays to simultaneously quantify the expression of thousands of genes has been a leap forward in our attempt to understand the biology of pancreatic cancer in a variety of contexts. When combined with supervised and unsupervised interrogations using complex mathematical algorithms, researchers have been able to unveil specific molecular features of subsets of tumors. This has subsequently led to a greater understanding of the heterogeneity of pancreatic cancer genesis, metastasis, and resistance to drug therapy. Further, these studies have provided lists of proteins that could potentially be targeted to modify these phenomena, as well as serve as biomarkers during the drug discovery process and translation to the clinic. This chapter focuses on approaches to the application of gene expression arrays that have been able to address these questions, with special consideration of how they can and are being used to uncover and develop new therapies for pancreatic cancer.
18: Characterization of human interferon-alpha subtypes and mutants

IFN- α subtypes and mutants have been cloned in our laboratory in a yeast expression system. The mutants were constructed with point mutations at the C-termini working under the hypothesis that so doing would increase binding affinity of the IFN to its receptor and hence its activity. The following subtypes, IFN- α 1a, IFN- α 2c, IFN- α 6, IFN- α 8b and IFN- α 14c were purified by HPLC and characterized. Their antiproliferative activities were tested on Daudi (Burkitt’s lymphoma) cells and their antiviral activities were tested on A549 (human adenocarcinoma epithelial) cells, OVCAR-3 (ovarian cancer) cells and HUH7 (hepatocellular carcinoma) cells. IFN- α 8b and IFN- α 2c had the highest antiproliferative activities. IFN- α 8b had the highest antiviral activity while IFN- α 6 had the lowest on the three cell lines tested. In addition, in both A549 and HUH7 cells, the antiviral activities of IFN- α 8b were seen to be a log greater than that of IFN- α 2c. To determine relationships of these IFNs to the interferon-alpha receptor 2 (IFNAR2), soluble, extracellular IFNAR2 (IFNAR2-EC) neutralization assays were done in which the IFNs were exposed to IFNAR2-EC in the antiviral assays. Addition of the soluble IFNAR2-EC decreased the antiviral activities of all of the IFN subtypes ten-fold except for IFN- α 1a whose antiviral activity was decreased two fold. Western blot analyses of STAT pathways in A549 cells did not show any apparent correlation with phosphorylation of STAT 1, 2 or 3 (1 h post IFN treatment) and either antiviral or antiproliferative activities. Western blot analyses done to detect selected Interferon Stimulated Genes (ISGs), at both 6 and 15 h timepoints, show that the ISGs RIG-G, UBE2l6 and Mx1 were most up regulated in cells treated with IFN- α 1a, - α 2c and - α 14c, while PKR and IRF9 were equally up regulated by all of the IFN subtypes tested. We plan to more broadly characterize both the subtypes and mutants.
Asymmetric Hydrogenation of Imines

Homogeneous catalytic asymmetric hydrogenation has evolved into a significantly useful methodology for the prepartion of enantiopure compounds. Significant advances in asymmetric hydrogenation of imines have enabled a straightforward and powerful approach to various chiral amines. An overview of the many variants of the chiral transition metal catalysts, illustrations of synthetic applications, and discussions of emerging and future strategies from a mechanistic perspective are presented.
Essential fatty acid deficiency in cultured SK-N-SH human neuroblastoma cells.

SK-N-SH neuroblastoma cells grown under standard culture conditions contain significant amounts of Mead acid (20:3ω9) in phospholipids, indicating essential fatty acid (EFA) deficiency. The amount of esterified 20:3ω9 was augmented by growth in a chemically defined EFA-free medium, whereas its presence could be virtually eliminated by supplementation of the culture medium with either arachidonic (20:4ω6; AA), eicosapentaenoic (20:5ω3; EPA), or linolenic (18:3ω3) acids. Substitution of Mead acid for ω6 fatty acids, particularly evident in phosphatidylinositol (PI), indicates a compensatory replacement of ω9 for ω6 fatty acids during EFA deficiency. Studies evaluating [3H]scopolamine binding to the M3 muscarinic acetylcholine receptors (mAChRs) present in these neurotumor cells as well as effects of carbachol on phosphoinositide turnover and intracellular Ca2+ mobilization, indicate that the biosubstitution of 20:4ω6 with 20:3ω9 does not detectably impair these measures of signal transduction. Stimulation of mAChRs with carbachol increased the cellular mass of diacylglycerol (DAG) approximately 60%. On the basis of distinctive fatty acid “signatures” of each of the phospholipid classes, it is concluded that the DAG initially released following muscarinic stimulation is derived from phosphoinositide breakdown. After several minutes, however, a significant amount of DAG comes from phosphatidylcholine (PC) as well. In contrast to DAG, the composition of phosphatidate (PA) following receptor stimulation closely resembles that of the phosphoinositides, even at the later time points examined. These results support a selective phosphorylation of DAG arising from the stimulated breakdown of phosphoinositides, favoring the conservation of the 1-stearoy1, 2-arachidonoy1 (or 20:3ω9) moiety.
Response of Cloud Tops to Radiative Forcing

The temporal response of cloud top thermodynamics and microphysics to longwave radiative cooling is examined using a one-dimensional model with high spectral and vertical resolution.
Evaluation of patient- versus provider-collected vaginal swabs for microbiome analysis during pregnancy.

We aimed to evaluate if patient- and provider-collected vaginal swabs in pregnant women reflect similar bacterial community characteristics. Pregnant patients performed a self-collected vaginal swab, then underwent a provider-collected swab via speculum exam. DNA pyrosequencing of the 16S rRNA gene V1V3 and V3V5 variable regions was performed. Relative abundance of taxa, alpha diversity, and beta diversity of patient- and provider-collected swabs were compared. Ninety-four vaginal swabs from 47 women were analyzed. On non-metric multi-dimensional scaling plots, paired patient- and provider-collected swabs clustered closely. The median Pearson correlation coefficient was 0.993 (interquartile range 0.951–0.999) for V1V3 and 0.987 (interquartile range 0.902–0.999) for V3V5. Among paired V1V3 and V3V5 sequences, 83.0% and 73.9% showed strong Pearson correlation (> 0.9), respectively, between patient- and provider-collected swabs; V1V3 and V3V5 sequences with weaker Pearson correlation (< 0.9) had correlation coefficients 0.57–0.89 and 0.49–0.89, respectively. No taxa were preferentially detected by sampling method, with relative abundance of taxa highly conserved. No significant difference in Shannon diversity for V1V3 (p = 0.22) and V3V5 (p = 0.11) sequences among paired samples was seen. We demonstrate that bacterial communities defined from patient- and provider-collected vaginal swabs in pregnant women are similar, validating utilization of patient-collected swabs for vaginal bacterial microbiome sampling during pregnancy.
Early transjugular intrahepatic portosystemic shunt in US patients hospitalized with acute esophageal variceal bleeding

BACKGROUND AND AIM Early transjugular intrahepatic portosystemic shunt (TIPS) used as preventive therapy prior to recurrent bleeding has been recommended in patients presenting with acute esophageal variceal bleeding (EVB) who are at high risk of further bleeding and death. We investigated the impact of early TIPS on outcomes of US patients hospitalized with EVB from 2000 to 2010. METHODS The Nationwide Inpatient Sample database was queried to identify patients with EVB and decompensated cirrhosis (because early TIPS is recommended only in high-risk patients). The primary outcome was in-hospital death, and secondary outcomes included rebleeding and hepatic encephalopathy. Early preventive TIPS was defined by placement within 3 days of hospitalization for acute EVB after one session of endoscopic therapy. Rescue TIPS was defined as TIPS after two interventions for EVB. RESULTS The study included 142 539 patients. From 2000 to 2010, the age-adjusted in-hospital mortality rate decreased 37.2% from 656 per 100 000 to 412 per 100 000 (P <0.01), while early and rescue TIPS increased (0.22% to 0.70%; P < 0.01 and 1.1% to 6.1%; P < 0.01). On multivariate analysis, as compared with no TIPS, early TIPS was associated with decreased inpatient mortality (risk ratio [RR] = 0.87; 95% confidence interval [CI], 0.84-0.90) and rebleeding (RR = 0.56; 95% CI, 0.45-0.71) without an increase in hepatic encephalopathy (RR = 1.01; 95% CI, 0.93-1.11). CONCLUSION Early preventive TIPS in patients with EVB and decompensated cirrhosis was associated with significant in-hospital reductions in rebleeding and mortality without a significant increase in encephalopathy in "real-world" US clinical practice.
Abstract 1957: Novel substrates for NanoLuc luciferase with improved brightness and signal duration for bioluminescence imaging in vivo

NanoLuc® luciferase, and its substrate furimazine, are becoming a preferred bioluminescent system in cellular and biochemical assays due to its brightness and glow-type kinetics. The construct Antares, made by fusing NanoLuc to the cyan-excitable orange-red fluorescent protein CyOFP, combines the high catalytic rate of NanoLuc with the high quantum yield and red-shifted emission of CyOFP (584 nm), which is well suited for in vivo imaging. Transgenic mice were created to constituently express Antares and these mice were used to screen coelenterazine analogues for a substrate that showed appropriate distribution and brightness in vivo . Our new Antares (NanoLuc) substrates are administered i.p. , have improved solubility over furimazine, exhibit long (>30 min) signal kinetics, and are brighter than D-luciferin/Luc2 expressed on the same promoters. Citation Format: Joel R. Walker, Yunhee Park, Michael Lin, Thomas A. Kirkland, Mary P. Hall, Lance P. Encell, Younghee Oh, Lan Liu. Novel substrates for NanoLuc luciferase with improved brightness and signal duration for bioluminescence imaging in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1957.
Cytokines in Cytokine Storm Syndrome

As the eponymous mediators of the cytokine storm syndrome, cytokines are a pleomorphic and diverse set of soluble molecules that activate or suppress immune functions in a wide variety of ways. The relevant cytokines for each CSS are likely a result of differing combinations of environmental triggers and host susceptibilities. Because cytokines or their receptors may be specifically targeted by biologic therapeutics, understanding which cytokines are relevant for disease initiation and propagation for each unique CSS is of major clinical importance. This chapter reviews what is known about the role of cytokines across the spectrum of CSS.
On the surface energy balance closure at different temporal scales

Abstract Measurements of the surface energy fluxes (turbulent and radiative) and other ancillary atmospheric/soil parameters made in the Columbia River Basin (Oregon) in an area of complex terrain during a 10-month long portion of the second Wind Forecast Improvement Project (WFIP 2) field campaign are used to study the surface energy budget (SEB) and surface fluxes over different temporal scales. This study analyzes and discusses SEB closure based on half-hourly, daily, monthly, seasonal, and sub-annual (~10-month) temporal averages. The data were collected over all four seasons for different states of the underlying ground surface (dry, wet, and frozen). Our half-hourly direct measurements of energy balance show that the sum of the turbulent sensible and latent heat fluxes systematically underestimate positive net radiation by around 20–30% during daytime and overestimate negative net radiation at night. This imbalance of the surface energy budget is comparable to other terrestrial sites. However, on average, the residual energy imbalance is significantly reduced at daily, weekly, and monthly averaging timescales, and moreover, the SEB can be closed for this site within reasonable limits on seasonal and sub-annual timescales (311-day averaging for the entire field campaign dataset). Increasing the averaging time to daily and longer time intervals substantially reduces the ground heat flux and storage terms, because energy locally entering the soil, air column, and vegetation in the morning is released in the afternoon and evening. Averaging on daily to sub-annual timescales also reduces random instrumental measurement errors and other uncertainties as well as smooths out a hysteresis effect (phase lag) in the SEB relationship between different components. This study shows that SEB closure is better for dry soils compared to wet soils and the statistical dependence of the turbulent fluxes and net radiation for freezing soil surfaces appears weak, if not non-existent, apparently due to lack of the latent heat of fusion term in the traditional SEB equation.
The Role of Immune Cells and Cytokines in Intestinal Wound Healing

Intestinal wound healing is a complicated process that not only involves epithelial cells but also immune cells. In this brief review, we will focus on discussing the contribution and regulation of four major immune cell types (neutrophils, macrophages, regulatory T cells, and innate lymphoid cells) and four cytokines (interleukin-10, tumor necrosis factor alpha, interleukin-6, and interleukin-22) to the wound repair process in the gut. Better understanding of these immune factors will be important for developing novel targeted therapy.
Pretransplantation Cognitive Dysfunction in Advanced-Age Hematologic Cancers: Predictors and Associated Outcomes.

ABSTRACT Patients presenting for treatment of hematologic cancers may be at increased risk for cognitive dysfunction before allogeneic hematopoietic stem cell transplantation (HSCT) due to advanced age, previous chemotherapy treatment, deconditioning, and fatigue. Cognitive dysfunction may affect treatment decision making, ability to recall or follow post-HSCT treatment recommendations and overall survival (OS). A total of 448 patients admitted for HSCT between 2011 and 2014 were administered the Montreal Cognitive Assessment (MoCA) by occupational therapists during admission before transplantation, and 260 were reassessed following transplantation and before discharge. We examined select predictor variables, including age, Karnofsky Performance Status, sex, disease type, psychotropic medications, and select outcome variables, including OS, and nonrelapse mortality (NRM). Before transplantation, 36.4% of patients met criteria for cognitive dysfunction. Age was found to be a significant predictor, along with disease type (myelodysplastic syndrome [MDS], myeloproliferative disorder [MPD]). No significant association was found between cognitive dysfunction and OS or NRM. Longitudinal analysis from pretransplantation to post-transplantation indicated significant decline following HSCT. Notably, one-third of the study cohort showed cognitive dysfunction at hospital discharge. A significant proportion of HSCT candidates present with cognitive dysfunction, with older patients and those diagnosed with MDS and MPD at greatest risk in this cohort. Attention to cognitive dysfunction before transplantation may alert the treatment team to high-risk cases that require increased oversight, inclusion by caregivers, and referral to occupational therapy at discharge. Longitudinal follow-up studies are needed to clarify the specific effect of HSCT on cognitive dysfunction and the impact of cognitive dysfunction on transplantation outcomes.