cssi/SciSciGPT-SciSciNet huggingface dataset:
Residential Segregation in Norfolk, Virginia: How the Federal Government Reinforced Racial Division in a Southern City, 1914-1959

This thesis examines how Norfolk, Virginia maintained residential segregation between the years 1914, when the city passed its first segregation ordinance, and 1959, when it received the All-America City Award for its massive slum clearance projects. By focusing on federal government initiatives in Norfolk, it shows that Norfolk’s leaders used the federal government’s assistance to map, analyze, and remove the city’s African American slums. Ultimately, it highlights the central role the federal government played in perpetuating residential segregation in Norfolk and how it opened a space for Norfolk’s leaders to act on their prejudice. This thesis demonstrates that in the 1910s and 1920s, Norfolk’s leaders used residential segregation ordinances, restrictive covenants, and white terror to divide the city by race. Then in the 1930s and 1940s, federal government initiatives, such as “redlining” and segregating defense housing projects, validated Norfolk’s discriminatory housing practices and emboldened Norfolk’s leaders to continue to segregate the city. Finally, it shows that in the 1950s, the federal government funded projects in Norfolk that cleared African American slums, demolished mixed-race neighborhoods, and created buffer zones that preserved residential and school segregation. Notable sources include the Lawrence M. Cox personal papers at Old Dominion University, historical surveys and maps from Charles K. Agle’s analysis of Norfolk in 1949, a 1940 map of Norfolk’s neighborhoods by the Home Owners’ Loan Corporation (HOLC), and numerous newspaper articles from the Norfolk Journal and Guide, Norfolk Ledger-Dispatch, and the Norfolk Virginian-Pilot. Results of this research demonstrate that the federal government played a significant role in segregating Norfolk’s neighborhoods and helped create the racially homogenous neighborhoods that exist in Norfolk today.
Isolated coronary artery bypass grafting in patients seventy years of age and older: early and late results.

Increasing longevity makes the consideration of coronary bypass common in elderly patients. Seventy-five patients 70 years of age or older undergoing coronary artery bypass grafting (CABG) for angina pectoris were compared to a control group of 75 patients under 70 years of age. The groups were matched for male : female ratio (46:29), previous infarction (28/75), unstable angina (27/75), and the requirement for preoperative intra-aortic balloon pumping (7/75). Patients under 70 years of age had an average preoperative New York Heart Association (NYHA) class of 3.0 ± 0.6 (SEM) and an average left ventricular end-diastolic pressure of 15.5 ± 0.8 mm Hg, compared to 3.3 ± 0.6 and 12.9 ±1.1 mm Hg, respectively, for the older group. Average grafts per patient were 2.7 ± 0.8 in the younger group and 2.8 ± 0.1 in the older group. Overall operative mortality for patients under 70 was 4% (3/75) versus 12% (9/75) (p = 0.06) for patients 70 and older. The incidence of chronic stable angina was 2% (1/48) versus 6% (3/48) (p = 0.30). Perioperative infarctions occurred in 7% of those under 70 and 5% of those 70 or older (p = 0.54). Those under 70 averaged 13.8 ± 0.6 postoperative hospital days versus 18.4 ± 1.2 hospital days for the older group (p
A Generalized Mixed Effect Kijima Model and Application in Optimal Maintenance Planning

The Kijima model has been widely used in reliability literature to analyze repairable systems with various degrees of repair efficiency including “perfect repair,” “minimal repair,” and situations in between. Most existing studies, however, treat repair efficiency as a fixed value even though repair efficiency can vary among a series of repairs. In this paper, we propose a generalized mixed effect Kijima model to characterize the variation of repair efficiency. In particular, the newly proposed “mixed effect” model incorporates a fixed time-dependent effect and a random effect of repair efficiency, while the term “generalized” refers to the fact that the classic Kijima model is generalized to handle more maintenance situations such as “better than new” and “worse than old” situations after repair. To estimate the model parameters given a series of observed system failure times, we develop a stochastic approximation expectation maximization algorithm which is a type of maximum likelihood estimation method. Further, an optimal periodic maintenance planning is developed based on the proposed reliability model. A simulation study and a real-world case study are conducted to demonstrate the developed methods.
TCT-798 Stent Graft Treatment For Instent-Restenosis And De novo Lesions Associated With Very High Rates Of Failure In Infra-Inguinal Arterial Disease

Stent graft placement for femoro-popliteal arterial obstructive disease is an FDA approved indication for the Gore Viabahn (WL Gore, Flagstaff, AZ, USA) stent, for both denovo and instent restenosis (ISRS) lesions. To date there is little data on Viabahn stent graft outcomes in patients with De novo
Impact of Surgical Specialty on Outcomes Following Carotid Endarterectomy.

Background The impact of surgeon specialty on outcomes following carotid endarterectomy (CEA) has been widely debated within the literature. Previous studies on this subject are often limited by small sample sizes, single-intuition designs, variability in patients and procedures, and potential confounding factors such as institution type and volume. Objective To identify similarities and differences between surgeon specialties in postoperative stroke and mortality rates for patients undergoing unilateral CEAs by utilizing a large, multicenter prospective database. Methods We utilized a large national prospective database (National Surgical Quality Inpatient database) and investigated all patients with a 1-sided, surgically naive CEA, performed by either a general, vascular, cardiothoracic, or neurological surgeon. We employed a logistic regression analysis to control for the most salient variables identified via univariate analysis. Our primary outcomes were all-cause mortality and stroke. Results There were 42 369 patients included across all specialties. Patients from each specialty were similar in demographics but varied in medical history. Multivariate analysis demonstrated that among the specialties only general surgeons had significantly greater postoperative stroke rates (2.3%) when compared to vascular surgeons (1.5%; P = .003, odds ratio [OR] 1.574, confidence interval [CI]: 1.168-2.121). In contrast, surgical specialty was not a significant risk factor for 30-d postoperative mortality (0% in cardiothoracic surgeons; 0.8% in vascular surgeons; 1.1% in general surgeons; 1.8% in neurosurgeons; Cardiothoracic surgeons: P = .995, OR: 0 [no incidences of mortality]; neurosurgeon: P = .118, OR: 0.2057, CI: 0.833-2.057; general surgeon P = .210, OR: 1.326, CI: 1.853-2.062). Most secondary outcomes (myocardial infarction, infection, reoperation, pneumonia) were similar between specialties (P = .339-.816). However, length of stay (P < .001), operative duration (P < .001), incidence of venous thromboembolism (P < .001), and the postoperative requirement for a ventilator greater than 48 h (P = .004) were all the greatest among neurosurgeons. Conclusion Multidisciplinary approaches with improved communication among surgical specialties may enhance patient management and improve success after CEA. Though there were differences in postoperative stroke and other secondary outcomes, no differences were observed among specialties in mortality after unilateral CEA in more than 40 000 patients.
Instrumentation, Control and Management of Batch Reactors Using Distributed Controls

Abstract The work reported here demonstrates the implementation of various instrumentation, control, and management functions by using a distributed control system. A batch reactor is used for demonstrating the results. Starting with smart instruments (transmitters), feedforward, cascade, adaptive features of feedback control are configured. More significantly, all versatilities for user convenience and management ease are included in addition to safety, alarm and control integrity. The system uses a reactor simulator to predict the results of reaction on new recipes which are never tried. Furthermore, a complete data acquisition, logging, and storing capabilities resident in control room plus remotely by P.C.‘s are all utilized. In conclusion, this wOrk is .the demonstration of the capabilities of state-of-the-art distributed controls as used In a pilot reactor plant.
Treatment of fatigue with methylphenidate, modafinil and amantadine in multiple sclerosis (TRIUMPHANT-MS): Study design for a pragmatic, randomized, double-blind, crossover clinical trial

BACKGROUND Fatigue is the most common symptom of multiple sclerosis (MS). Amantadine, modafinil and amphetamine-like stimulants are commonly used in clinical practice for treatment of fatigue; however, the evidence supporting their effectiveness is sparse and conflicting. OBJECTIVE To describe the design of a trial study funded by Patient-Centered Outcome Research Institute (PCORI) that will compare the efficacy of commonly used fatigue medications in patients with MS. DESIGN/METHODS The study is a randomized, placebo-controlled, crossover, four-sequence, four-period, double-blind, multicenter trial of three commonly used medications for the treatment of MS-related fatigue (amantadine, modafinil, methylphenidate) versus placebo in fatigued subjects with MS. Adult patients with MS, with an Expanded Disability Status Scale of <7.0 are eligible to participate. Participants will be randomized to one of four predefined sequences of medication administration. Each sequence comprises four 6-week periods of treatment with one of the 3 study drugs or placebo, and three 2-week washout periods between medication periods. RESULTS 136 participants will be randomized over two years in two academic centers in the United States starting in the Summer 2017. Complete enrollment is expected by early 2019. The primary outcome of the study is the modified fatigue impact scale (MFIS) score while participants receive the maximally tolerated dose of each study medication (or placebo). Safety and tolerability of the medications and heterogeneity of treatment effect will also be assessed. CONCLUSIONS Results of the proposed study will provide evidence-based and personalized treatment options for patients affected by MS-related fatigue. Clinicaltrials.gov registration number: NCT03185065.
South Korea’s Deterrence Strategy Against North Korea’s WMD

This paper examines how South Korea might be able to deter the growing threat from North Korea’s nuclear weapons and missile programs. North Korea’s six nuclear weapons experiments with various types of missile test fires using solid fuel and new technology pose a security threat to South Korea and the USA. The credibility of the North’s WMD capability and the military balance of two Koreas are critically analyzed. South Korea’s superior conventional weapons system, supported by U.S. strategic weapons and intelligence systems, could fend off North Korean nuclear weapons and missile attacks. However, it is imperative that the U.S.-ROK alliance continues to develop a stringent nuclear deterrence strategy and deploy a series of countermeasures, including preemptive strikes and a multilayered missile defense system, such as Kill Chain, KAMD, and THAAD, all to guard against a potential nuclear weapon attack from North Korea.
Hybrid Masculinity and Young Men's Circumscribed Engagement in Contraceptive Management.

This research explores how gender shapes contraceptive management through in-depth interviews with 40 men and women of color ages 15 to 24, a life stage when the risk of unintended pregnancy is hig...
‘Classic’ Biomarkers of Liver Injury

In the current frenzy to find new biomarkers, it may be instructive to consider how a small set of serum chemical tests for liver injury or dysfunction came to be considered ‘classic’. What are they and how did they come to deserve to be referred to as ‘classic’? Were they qualified, validated, or approved for use by methods described elsewhere in this book? Do they need to be in retrospect? My answer is ‘no’ and ‘no’. This chapter explores the reasons why.
Compulsory Education Cycles Down

A component of the ideal of universal education, compulsory education is distinctive as an imperative of forcible exercise; not only may one enjoy it, one must. Why? The liberal story is the triumphal one that, it is a case of forcing citizens (or citizens-to-be via their parents) to be free. The beneficent state must act as guarantor of children’s best interests, keeping them out of factories, etc. This picture is too simple, though. Not merely an ideal, compulsory education should also be seen as a temporary excrudescence of a certain period in the history of capitalist production. Following Marx, it is no coincidence that compulsory education arises along with the advent of industrialism, an era where the owners of capital required “all hands on deck” for accumulating capital via the large-scale extraction of surplus labor value from ever-expanding numbers. Schooling provides a complex yet crucial aid in this process, one whose continuing mechanisms have finally led to an impasse. Intensive automation and other processes have now reduced the need for human labor inputs on anything like the traditional scale. Correspondingly, compulsory education is now cycling down in frightening new ways will force us once again to ask uncomfortable questions about our educational institutions.
Some Results on Energy

The concept of energy we are dealing with here is a generalization of that dealt with in the classical theory. Although rightfully observed by P.A. Meyer in [4] p. 140, that such a generalization “loses delicacy as it gains generality”, we will try to add a few results which may somewhat simplify a way in dealing with this concept. To be more precise, in the literature dealing with concept of energy, the basic tools are Dirichlet spaces techniques [7] and the kernel theory, which are both natural offshoots of the classical theory. The symmetry of kernels plays the basic role there.
Social work students’ perceptions of obesity

Research indicates that mental health and medical professionals often hold negative views of overweight or obese people. Little is known about weight prejudice among social work students. In order ...
Quantification of Degree of Liver Fibrosis Using Fibrosis Area Fraction Based on Statistical Chi-Square Analysis of Heterogeneity of Liver Tissue Texture on Routine Ultrasound Images.

Rationale and Objectives We present a novel method to quantify the degree of liver fibrosis using fibrosis area fraction based on statistical chi-square analysis of heterogeneity of echo texture within liver on routine ultrasound images. We demonstrate, in a clinical study, that fibrosis area fraction derived this way has the potential to become a noninvasive, quantitative radiometric discriminator of normal or low-grade liver fibrosis (Ishak fibrosis score range = F0–3) and advanced liver fibrosis or cirrhosis (Ishak fibrosis score range = F4–6) on routine ultrasound images. Materials and Methods This retrospective patient study was institutional review board approved. Ultrasound images of 100 patients (61 males, 39 females; 18–81 years) who underwent nontargeted ultrasound-guided biopsy were randomly divided into two groups: a training group consisted of 31 cases, and a validation group that contained the rest cases. An investigator manually selected a primary region of interest (ROI; approximately 4–6 cm2) in the liver tissue while avoiding nonhepatic parenchyma. The primary ROI contained a large number of secondary ROIs (25 × 25 pixels) to maintain the precision of statistical analysis. Sample variance σ2 of image gradient (a texture feature related to the amount of edge structures) was calculated in secondary ROIs in a roster scan fashion. A theoretical derivation was presented to estimate population variance σ 0 2 ~ of image gradient across the primary ROI from mean gradient µ of secondary ROIs. The χ2 (χ2 = σ2/ σ 0 2 ~ ) was computed at each secondary ROI, forming a χ2 map of liver tissue heterogeneity. A cut-off value was optimized from datasets in the training group by comparing to the fibrosis grades determined by biopsy. This cut-off value was then applied to the datasets in the validation group to convert the χ2 maps into binary images, from which fibrosis area fractions (fraction of fibrosis area to the total area of the primary ROI) were calculated and entered in a statistical analysis. Results In the training group, the optimal setting was found to be T χ 2 = 6.0, which resulted a maximum discrimination of F0–3 vs F4–6: p Conclusion The presented method is a promising noninvasive tool for distinguishing normal or low-grade liver fibrosis (F0–3) and advanced liver fibrosis or cirrhosis (F4–6) from routine ultrasound images. These findings support the further development of texture heterogeneity analysis, particularly fibrosis area fraction, as a quantitative biomarker for distinguishing various liver fibrosis grades.
Pre-clinical evaluation of the modified Miles assay as a surrogate marker of systemic anti-angiogenic activity

1173 Background: Vascular endothelial growth factor (VEGF), originally discovered as vascular permeability factor (VPF), is a critical molecule in tumor mediated angiogenesis. A number of novel drugs that specifically inhibit angiogenesis are in clinical trials however, surrogate markers of drug activity are lacking. The Miles assay can be used to assess alterations in vessel permeability mediated by a number of molecules including VEGF. Unfortunately, the administration of VEGF to patients with cancer or other angiogenic dependant diseases may stimulate further disease progression. Histamine is a molecule with a defined activity in vascular leak that is routinely used to quantitate the allergic potential to drugs in normal individuals as well as those with a variety of diseases including cancer. We now report the utilization of the histamine challenge assay as a surrogate marker of activity for anti-angiogenic drugs in a pre-clinical murine model. Methods: All animal experiments were performed in accordance with IRB-approved protocols at Children’s Hospital, Boston using 8 week-old SCID mice. Approximately 1-2 days prior to the experiment, animals were shaved to expose the skin. After recovery of the skin 1-2 days later, animals were anesthetized and injected with Evan’s blue dye either by tail vein or through the orbital plexus. 50ul of 1ng/ul VEGF, 50ul containing 1ug histamine or 50ul of saline were injected intradermally using a 30g needle into the skin over lying the back near the base of the tail. One side received histamine or VEGF, the other saline. Similar experiments were performed injecting approximately 5ul intradermally into the ears. After an appropriate period of time, the skin was opened and exposed to assess the intensity of Evan’s blue dye extravasation. The areas of blue (vascular leak) were quantitated. Results: Animals were treated with a large array of anti-angiogenic agents including drugs that down-regulate bFGF, VEGF, or endothelial cell function. Drugs targeting VEGF or endothelium significantly inhibited the vascular leak induced by intradermal VEGF. More importantly, a similar effect was noted with histamine-induced vascular leak. The inhibition followed a dose response curve. Alterations on the immunohistochemical structure of the skin area correlated with the patterns observed based on the treatment groups. Conclusion: Histamine-mediated vascular leak can be used to evaluate the systemic potency of anti-angiogenic drugs administered in a pre-clinical model. This technique is appropriate for evaluation in human clinical trials of novel anti-angiogenic drugs given the extensive experience with histamine administration in humans. Clinical trials to assess this have been proposed.
Membranous nephropathy and cancer in the era of PLA2R testing

Membranous nephropathy has historically been associated with a higher risk of malignancy compared to the general population. Following a membranous nephropathy diagnosis, physicians screen patients...
Robust Online Social Network Inference

Information cascades represent traces of information propagation in latent unknown networks. The underlying information diffusion dynamics are captured from collected cascade data and used to infer online social network connectivity and structure which is useful for several applications such as influence maximization and rumor blocking. Our goal is to make the network inference process robust to missing cascade entries. As a first approach, we attempt to recover the missing elements and use the recovered cascades to solve the inference problem. The second approach consists in using expectation maximization algorithm to jointly recover missing entries and solve the network inference problem iteratively. Experiments are implemented on synthetic as well as large scale real social networks to validate and compare the proposed methods.
A 34-Year-Old Man with Right Hand and Left Foot Numbness

Leprosy is a common cause of neuropathy in the developing world but may also be seen in developed countries among immigrants or in endemic areas within the United States. While most patients develop a rash or skin hypopigmentation, some lack skin manifestations, thus making them harder to diagnose. Nerve biopsy may be necessary to confirm the diagnosis. We present a case in which superficial radial nerve biopsy demonstrated inflammatory infiltrates and acid fast bacilli within Schwann cell processes, confirming leprous neuropathy. The characteristic pathologic findings are discussed.
Multi-GBq production of the radiotracer [18F]fallypride in a droplet microreactor

Microfluidics offers numerous advantages for the synthesis of short-lived radiolabeled imaging tracers: performing 18F-radiosyntheses in microliter-scale droplets has exhibited high efficiency, speed, and molar activity as well as low reagent consumption. However, most reports have been at the preclinical scale. In this study we integrate a [18F]fluoride concentrator and a microdroplet synthesizer to explore the possibility of synthesizing patient doses and multi-patient batches of clinically-acceptable tracers. In the integrated system, [18F]fluoride (up to 41 GBq [1.1 Ci]) in [18O]H2O (1 mL) was first concentrated ∼80-fold and then efficiently transferred to the 8 μL reaction chip as a series of small (∼0.5 μL) droplets. Each droplet rapidly dried at the reaction site of the pre-heated chip, resulting in localized accumulation of large amounts of radioactivity in the form of dried [18F]TBAF complex. The PET tracer [18F]fallypride was synthesized from this concentrated activity in an overall synthesis time of ∼50 min (including radioisotope concentration and transfer, droplet radiosynthesis, purification, and formulation), in amounts up to 7.2 GBq [0.19 Ci], sufficient for multiple clinical PET scans. The resulting batches of [18F]fallypride passed all QC tests needed to ensure safety for clinical injection. This integrated technology enabled for the first time the impact of a wide range of activity levels on droplet radiosynthesis to be studied. Furthermore, this substantial increase in scale expands the applications of droplet radiosynthesis to the production of clinically-relevant amounts of radiopharmaceuticals, and potentially even centralized production of clinical tracers in radiopharmacies. The overall system could be applied to fundamental studies of droplet-based radiochemical reactions, or to the production of radiopharmaceuticals labeled with a variety of isotopes used for imaging and/or targeted radiotherapeutics.
Males and females exhibit similar muscle glycogen recovery with varied recovery food sources

Research has elucidated the impact of post-exercise carbohydrate nutrition and environmental conditions on muscle glycogen re-synthesis. However, research has minimally considered the implications of glycogen recovery in females and has mostly focused on commercial sport nutrition products. The purpose of this study was to determine the effects of varied mixed macronutrient feedings on glycogen recovery and subsequent exercise performance in both sexes. Males (n = 8) and females (n = 8) participated in a crossover study. Subjects completed a 90-min cycling glycogen depletion trial, then rested for 4 h. Two carbohydrate feedings (1.6 g kg−1) of either sport supplements or potato-based products were delivered at 0 and 2 h post-exercise. Muscle biopsies (glycogen) and blood samples (glucose, insulin) were collected during the recovery. Afterwards, subjects completed a 20 km cycling time trial. There was no difference between sexes or trials for glycogen recovery rates (male: 7.9 ± 2.7, female: 8.2 ± 2.7, potato-based: 8.0 ± 2.5, sport supplement: 8.1 ± 3.1 mM kg wet wt−1 h−1, p > 0.05). Time trial performance was not different between diets (38.3 ± 4.4 and 37.8 ± 3.9 min for potato and sport supplement, respectively, p > 0.05). These results indicate that food items, such as potato-based products, can be as effective as commercially marketed sports supplements when developing glycogen recovery oriented menus and that absolute carbohydrate dose feedings (g kg−1) can be effectively applied to both males and females.
Association between post-stroke disability and 5-year hip-fracture risk: The Women's Health Initiative

Abstract Background Hip fractures are a significant post-stroke complication. We examined predictors of hip fracture risk after stroke using data from the Women's Health Initiative (WHI). In particular, we examined the association between post-stroke disability levels and hip fracture risk. Methods The WHI is a prospective study of 161,808 postmenopausal women aged 50-79 years. Trained physicians adjudicated stroke events and hip fractures. Our study included stroke survivors from the observational and clinical trial arms who had a Glasgow Outcome Scale of good recovery, moderately disabled, or severely disabled and survived more than 7 days post-stroke. Hip fracture-free status was compared across disability levels. Secondary analysis examined hip fracture risk while accounting for competing risk of death. Results Average age at time of stroke was 74.6±7.2 years; 84.3% were white. There were 124 hip fractures among 4,640 stroke survivors over a mean follow-up time of 3.1±1.8 years. Mortality rate was 23.3%. Severe disability at discharge (Hazard Ratio (HR): 2.1 (95% Confidence Interval (CI): 1.4-3.2), but not moderate disability (HR: 1.1 (95%CI: 0.7-1.7), was significantly associated with an increased risk of hip fracture compared to good recovery status. This association was attenuated after accounting for mortality. White race, increasing age and higher Fracture Risk Assessment Tool (FRAX)-predicted hip fracture risk (without bone density information) were associated with an increased hip fracture risk. After accounting for mortality, higher FRAX risk and white race remained significant. Conclusion Severe disability after stroke and a higher FRAX risk score were associated with risk of subsequent hip fracture. After accounting for mortality, only the FRAX risk score remained significant. The FRAX risk score appears to identify stroke survivors at high risk of fractures. Our results suggest that stroke units can consider the incorporation of osteoporosis screening into care pathways.
SNS-032, a novel inhibitor of cyclin-dependent kinases 2, 7 and 9, blocks transcription of cyclin D1 and Mcl-1, causing cell death in mantle cell lymphoma cell lines

756 SNS-032 is a potent, selective inhibitor of cyclin-dependent kinases (Cdk) 2, 7 and 9 that inhibits both the cell cycle and transcription. Cdk7/cyclin H and Cdk9/cyclin T control RNA polymerase II (pol II)-dependent transcription. Phosphorylation of Ser5 (Cdk7) and Ser2 (Cdk9) of the pol II C-terminal domain (CTD) activates transcription initiation and elongation. Because lymphoid malignancies are dependent upon the continual expression of anti-apoptotic proteins for survival, we hypothesize that transient inhibition of transcription will cause a critical decrease in such proteins (e.g., Mcl-1, XIAP) and initiate apoptosis. Thus, Cdk7 and Cdk9 are attractive targets for cancer therapy in this context. Our studies in primary chronic lymphocytic leukemia (CLL) lymphocytes demonstrated that SNS-032 effectively decreases the phosphorylation of pol II CTD and inhibits transcription; this is associated with diminished levels of anti-apoptotic proteins and activation of apoptosis. The present study focuses on mantle cell lymphoma (MCL) cell lines (Granta 519, Jeko-1, Mino and SP-53) to evaluate this hypothesis in a growing cell model. The biology of MCL is characterized by the t(11:14)(q13;q32) translocation, which leads to the over-expression of Cyclin D1 which sustains the malignancy. Interestingly, the transcript and protein of Cyclin D1 are both short-lived, and thus may be targeted by SNS-032, providing further biological context to test this strategy. In addition, Cdk2, which is highly expressed in MCL cells, is also blocked by SNS-032. SNS-032 (0.3 to 1 µM) inhibited the phosphorylation of RNA pol II CTD at both the Ser2 and Ser5 sites; this is associated with inhibition of RNA synthesis in all MCL lines. As a result, the transcripts and protein levels of short lived protein decreased, including Cyclin D1 and Mcl-1, and apoptosis was induced within 24 hr in all cell lines except for Granta, shown by PARP cleavage and the emergence of a subG1 population. This is consistent with SNS-032 acting as a transcriptional inhibitor. Apoptosis was strongly induced by 0.3 µM SNS-032 in Jeko and Mino cells after a 24 hr exposure, despite their deficiency in p53 function, indicating that the SNS-032 induced apoptosis was independent of p53. Although apoptosis was not detected in Granta cells, clonogenic assays showed a strong, time-dependent inhibition of colony formation, with an IC50 of about 50 nM after 24 hr incubation, indicating that SNS-032 effectively jeopardized MCL repopulating ability. Thus, SNS-032 appears to block transcription by inhibition of Cdk7 and Cdk9, an action that leads to the decrease of survival proteins and Cyclin D1, and the death of MCL cell lines.
Interest Development, Knowledge Learning, and Interactive IR: Toward a State-based Approach to Search as Learning

To support complex search tasks that involve prolonged search sessions and learning goals of varying difficulty, information retrieval (IR) researchers need a more comprehensive understanding of in-situ learning progresses and related factors. Among many cognitive factors associated with learning and searching, we consider interest development as an important dimension because it significantly affects users' learning performances but still remains understudied in interactive IR (IIR). To address this gap, our perspective paper proposes an interest-search-learning (ISL) model to reconceptualize learning in search and characterize the dynamic interplay of interest development, knowledge learning, and searching. Specifically, it achieves three interrelated goals: 1) characterizing the interactions between interest development, learning, and search behaviors; 2) synthesizing and proposing useful measures for capturing in-situ progresses and state variations in interest development and knowledge learning related to search behaviors; 3) identifying new research questions and directions linked to conceptualizing, building, and evaluating learning-centric IR systems. This paper uniquely integrates findings from three research communities (i.e. interest development, learning, IIR) into a cohesive framework and better structures our understanding of the multidimensional cognitive changes in search as learning (SAL). Including the exploration of interest development in SAL research will expand both conceptual and practical visions of AI-assisted learning.
Artificial Intelligence and Machine Learning: What you always wanted to know but were afraid to ask

ABSTRACT The access to increasing volumes of scientific and clinical data, particularly with the implementation of electronic health records, has reignited an enthusiasm for artificial intelligence and its application to the health sciences. This interest has reached a crescendo in the past few years with the development of several machine learning and deep learning based medical technologies. The impact to research and clinical practice within gastroenterology and hepatology has already been significant, but the near future promises only further integration of artificial intelligence and machine learning into this field. The concepts underlying artificial intelligence and machine learning initially seem intimidating, but with increasing familiarity they will become essential skills in every clinician's toolkit. In this Review, we provide a guide to the fundamentals of machine learning, a concentrated area of study within artificial intelligence that has been built upon a foundation of classical statistics. The most common machine learning methodologies, including those involving deep learning, are also described.
Digital Computers and Environment Control

Concepts of environment are presented and the limitations on the achievement of environmental control imposed by classical methods are examined. The particular aspects of environmental engineering and control examined are: (1) The role of the digital computer in manipulation of the environment, (2) the related techniques that have helped improve the generality and credibility of solutions to environmental problems,(3) the educational (especially self-educational) responses that engineers have made in order to use these techniques effectively, and (4) the promise held by these improved and powerful techniques.
Reporting of cigar use among adolescent tobacco smokers

Abstract Introduction With the changing landscape of tobacco products, the divide between cigarettes and cigars is obscured, so understanding adolescent reporting of cigar use is needed to improve best practices for surveillance, screening, and prevention/intervention. This study examined adolescents' reported cigar use and correlates of use. Methods Participants (N = 186) were 13–17 year old tobacco users participating in a prospective study of adolescent smoking behaviors. Measurement occurred at baseline and 24-months, and included demographics, nicotine dependence, tobacco use, and quit attempts. Cigar use was assessed as, “have you smoked a cigar in the last 30 days” and by brand specific use in the past 30 days. Findings Cigar use was reported by 51 adolescents (27%), and increased to 76 (41%) when identifying by brand name. African Americans (32%) were more likely to smoke cigars than whites (10%, p p = .04), and multiracial participants (24%, p = .05). Cigarette-only users smoked more per day ( p = .04) and had higher cotinine levels ( p = .05) than cigar users. Number of prior quit attempts ( p = .84) did not differ by group. Group differences in addiction were found between cigar users and cigarette only users ( p p Conclusions Assessment of brand-specific cigars nearly doubled the reporting among adolescent users. Cigar users differed from cigarette-only users in consumption and likelihood of abstinence at 24-months. For more accurate surveillance and to inform treatment considerations, surveys of adolescent tobacco use should include cigars, including brand names, in the assessment strategy.
Properties of the genome in normal and SV40 transformed WI38 human diploid fibroblasts. I. Composition and metabolism of nonhistone chromosomal proteins.

Abstract The composition and metabolism of nonhistone chromosomal proteins associated with the genome of normal and SV40 transformed WI38 human diploid fibroblasts were examined. Evidence is presented which indicates variations in the relative protein content, specific activity and phosphorylation of several defined molecular weight classes of these chromosomal polypeptides. In addition, it is shown that blocking DNA replication with cytosine arabinoside does not inhibit the incorporation of 3 H-leucine into nonhistone chromosomal proteins of SV40 transformed cells. The possibility that the nonhistone chromosomal proteins of human diploid fibroblasts transformed by SV40 virus may be involved in the regulation of viral induced alterations in gene expression is discussed.
The Existence of Pairwise Stable Networks

We examine networks connecting individuals, where the payoff to an individual from an economic or social activity depends on the full network of connections among individuals. Individuals can form and sever links connecting themselves to other individuals based on the improvement that the resulting network offers them relative to the current network. As individuals do this, we obtain sequences of networks called `improving paths.’ We study conditions under which such sequences cycle, and conditions under which such sequences lead to a stable network. Specifically, we give conditions necessary and sufficient to rule out cycles, which are in turn sufficient conditions for existence of pairwise stable networks. Journal of Economic Literature Classification Numbers: A14, D20, J00. Humanities and Social Sciences 228-77, Caltech, Pasadena, CA 91125, USA (jacksonm@hss.caltech.edu) Department of Economics, Southern Illinois University, Carbondale, IL 62901, USA (wattsa@siu.edu) This paper was prepared for a lecture presented at the 9th SJE-KISDI International Symposium: Cost Allocation and Telecommunications, Seoul National University. We thank the participants for the helpful discussion and especially to Youngsub Chun for the invitation to participate.
Reducing Carcinogenicity and Mutagenicity Through Mechanism-Based Molecular Design of Chemicals

The sections in this article are Introduction Mechanisms of Chemical Carcinogenesis and Structure–Activity Relationship (SAR) General Molecular Parameters Affecting the Carcinogenic and Mutagenic Potential of Chemicals Physicochemical Properties Molecular Weight Molecular Size and Shape Solubility Volatility Nature and Position of Substituents Molecular Flexibility, Polyfunctionality, and Spacing/Distance Between Reactive Groups Resonance Stabilization of the Electrophilic Metabolites Specific Structural Criteria of Different Classes of Chemical Carcinogens and Mutagens Aromatic Amines and Azo Dyes/Pigments Polycyclic Aromatic Hydrocarbons (PAHs) N-Nitrosamines Hydrazo, Aliphatic Azo and Azoxy Compounds, and Arydialkyltriazenes Organophosphorus Compounds Carbamates Epoxides and Aziridines Lactones and Sultones Alkyl Esters of Moderately Strong and Strong Acids Haloalkanes and Substituted Haloalkanes N-Mustards and S-Mustards N-Nitrosamides Aldehydes and Substituted Aldehydes Michael Addition Acceptors Arylating Agents Acylating Agents and Isocyanates Organic Peroxides Quinones and Quinoid Compounds Molecular Design of Chemicals of Low Carcinogenic and Mutagenic Potential General Approaches Specific Approaches Aromatic Amines and Azo Dyes/Pigments Polycyclic Aromatic Hydrocarbons (PAHs) N-Nitrosamines Hydrazo, Aliphatic Azo and Azoxy Compounds, and Arydialkyltriazenes Organophosphorus Compounds Carbamates Epoxides and Aziridines (Ethylenimines) Lactones and Sultones Alkyl Esters of Moderately Strong and Strong Acids Haloalkanes and Substituted Haloalkanes N-Mustards and S-Mustards N-Nitrosamides Aldehydes and Substituted Aldehydes Michael Addition Acceptors Arylating Agents Acylating Agents and Isocyanates Organic Peroxides Quinones and Quinoid Compounds Conclusion Disclaimer Keywords: carcinogenicity; mutagenicity; mechanism-based molecular design; structure–activity relationship; safer chemicals; green chemistry
Hemoglobinuria as a symptom of ruptured ectopic pregnancy

Abstract Hemoglobin in the urine would be more frequently encountered if one would search for it. The importance of chemical and spectroscopic tests is stressed. Hemoglobinuria is a not infrequent accompaniment of ruptured ectopic pregnancy with intraadbominal hemorrhage, and may be a significant symptom of the disease. Therefore, whenever the possibility of a ruptured ectopic pregnancy is considered in the differential diagnosis, the appearance of hemoglobinuria should be determined and evaluated in the presenting syndrome.
Multitargeted low-dose GLAD combination chemoprevention: a novel and promising approach to combat colon carcinogenesis.

Preclinical studies have shown that gefitinib, licofelone, atorvastatin, and α-difluoromethylornithine (GLAD) are promising colon cancer chemopreventive agents. Because low-dose combination regimens can offer potential additive or synergistic effects without toxicity, GLAD combination was tested for toxicity and chemopreventive efficacy for suppression of intestinal tumorigenesis in adenomatous polyposis coli (APC)Min/+ mice. Six-week-old wild-type and APCMin/+ mice were fed modified American Institute of Nutrition 76A diets with or without GLAD (25 + 50 + 50 + 500 ppm) for 14 weeks. Dietary GLAD caused no signs of toxicity based on organ pathology and liver enzyme profiles. GLAD feeding strongly inhibited (80–83%, P 95% fewer polyps with sizes of >2 mm compared with control mice and showed 75% and 85% inhibition of colonic tumors in males and females, respectively. Molecular analyses of polyps suggested that GLAD exerts efficacy by inhibiting cell proliferation, inducing apoptosis, decreasing β-catenin and caveolin-1 levels, increasing caspase-3 cleavage and p21, and modulating expression profile of inflammatory cytokines. These observations demonstrate that GLAD, a novel cocktail of chemopreventive agents at very low doses, suppresses intestinal tumorigenesis in APCMin/+ mice with no toxicity. This novel strategy to prevent colorectal cancer is an important step in developing agents with high efficacy without unwanted side effects.
Late‐life depression in older African Americans: a comprehensive review of epidemiological and clinical data

Objective The population of older African Americans is expected to triple by 2050, highlighting the public health importance of understanding their mental health needs. Despite evidence of the negative impact of late-life depression, less is known of how this disorder affects the lives of older African Americans. Lack of studies focusing on how depression presents in older African Americans and their subsequent treatment needs lead to a gap in epidemiologic and clinical knowledge for this population. In this review, we aim to present a concise report of prevalence, correlates, course, outcomes, symptom recognition, and treatment of depression for these individuals. Method We performed a literature review of English-language articles identified from PubMed and Medline published between January 1990 and June 2012. Studies included older adults and contained the key words ‘geriatric depression in African Americans’, ‘geriatric depression in Blacks’, and ‘geriatric depression in minorities’. Results Although in most studies, older African Americans had higher or equivalence prevalence of depression compared with Caucasian Americans, we also found lower rates of recognition of depression and treatment. Many studies reported worse outcomes associated for depression among older African Americans compared with older Caucasians. Conclusions Serious racial and ethnic disparities persist in the management of older African Americans with depression. Understanding their unmet needs and improving depression care for these individuals is necessary to reduce these disparities. Copyright © 2012 John Wiley & Sons, Ltd.
Coherent Sheaves and Cohesive Sheaves

We consider coherent and cohesive sheaves of O over open sets ω ⊂ ℂ n . We prove that coherent sheaves, and certain other sheaves derived from them, are cohesive; and conversely, certain sheaves derived from cohesive sheaves are coherent. An important tool in all this, also proved here, is that the sheaf of Banach space valued holomorphic germs is flat.
Juvenile idiopathische Arthritis

Die juvenile idiopathische Arthritis (JIA) ist eine heterogene Gruppe von Erkrankungen mit den gemeinsamen Merkmalen einer chronischen Arthritis von zumindest 6 Wochen Dauer und dem Auftreten vor dem vollendeten 16. Lebensjahr wahrscheinlich auf autoimmunologischer oder autoinflammatorischer Basis, deren Hauptmanifestation die Synovitis groser und/oder kleiner Gelenke darstellt. Als Folge davon kommt es an den betroffenen Gelenken zu Schwellung, Schmerzen, Rotung, Uberwarmung und Bewegungseinschrankung bis hin zu sind Knorpel- und Knochendestruktion, Fehlstellung und knocherner Ankylose sowie Wachstumsstorungen. Daneben konnen verschiedene extraartikulare Manifestationen auftreten. Mit einer Inzidenz von 10–20 und einer Pravalenz von 50–150/100.000 Kindern und Jugendlichen unter 16 Jahren ist die JIA die haufigste chronische systemische Autoimmunerkrankung im Kindesalter. Es erkranken Kinder aller Altersstufen, wobei eine JIA im 1. Lebensjahr selten ist. In einzelnen Unterformen uberwiegen Madchen deutlich.
Implementing division in SPICE (provides 'instantaneous' RMS of a waveform or a perfect peak detector)

A mathematical operation of division was performed in the I-G (interactive graphics) SPICE IV/G6. The division operation uses an analog computer scheme to realize itself. This scheme incorporates already existing operations in SPICE (multiplication, algebraic summation, and a gain provision) to provide for the division operation, which does not exist in the I-G SPICE. The division operation was found necessary for modeling and simulation of the dynamics of AC systems in terms of providing for an instantaneous RMS (root mean square) of an AC waveform, in a sense in which it is physically interpreted in an AC machine, or, equivalently, for providing a perfect peak director. The division operation is fundamentally necessary for completing the arithmetical capabilities of I-G SPICE. >
Autophagy inhibition enhances vorinostat-induced apoptosis via ubiquitinated protein accumulation

Autophagy is an evolutionarily conserved cell survival pathway that enables cells to recoup ATP and other critical biosynthetic molecules during nutrient deprivation or exposure to hypoxia, which are hallmarks of the tumour microenvironment. Autophagy has been implicated as a potential mechanism of resistance to anticancer agents as it can promote cell survival in the face of stress induced by chemotherapeutic agents by breaking down cellular components to generate alternative sources of energy. Disruption of autophagy with chloroquine (CQ) induces the accumulation of ubiquitin-conjugated proteins in a manner similar to the proteasome inhibitor bortezomib (BZ). However, CQ-induced protein accumulation occurs at a slower rate and is localized to lysosomes in contrast to BZ, which stimulates rapid buildup of ubiquitinated proteins and aggresome formation in the cytosol. The histone deacetylase (HDAC) inhibitor vorinostat (VOR) blocked BZ-induced aggresome formation, but promoted CQ-mediated ubiquitinated protein accumulation. Disruption of autophagy with CQ strongly enhanced VOR-mediated apoptosis in colon cancer cells. Accordingly, knockdown of the essential autophagy gene Atg7 also sensitized cells to VOR-induced apoptosis. Knockdown of HDAC6 greatly enhanced BZ-induced apoptosis, but only marginally sensitized cells to CQ. Subsequent studies determined that the CQ/VOR combination promoted a large increase in superoxide generation that was required for ubiquitinated protein accumulation and cell death. Finally, treatment with the CQ/VOR combination significantly reduced tumour burden and induced apoptosis in a colon cancer xenograft model. Collectively, our results establish that inhibition of autophagy with CQ induces ubiquitinated protein accumulation and VOR potentiates CQ-mediated aggregate formation, superoxide generation and apoptosis.
Lactoferrin Reverses Respiratory Abnormalities in Respiratory Syncytial Virus (RSV) Infection of Mice

Lactoferrin Reverses Respiratory Abnormalities in Respiratory Syncytial Virus (RSV) Infection of Mice