cssi/SciSciGPT-SciSciNet huggingface dataset:
Initiation of antiretroviral therapy 48 hours after infection with simian immunodeficiency virus potently suppresses acute-phase viremia and blocks the massive loss of memory CD4+ T cells but fails to prevent disease.

We investigated whether a 28-day course of potent antiretroviral therapy, initiated at a time point (48 h postinoculation) following simian immunodeficiency virus (SIV) inoculation when the acquisition of a viral infection was virtually assured, would sufficiently sensitize the immune system and result in controlled virus replication when treatment was stopped. The administration of tenofovir 48 h after SIV inoculation to six Mamu-A*01-negative rhesus macaques did, in fact, potently suppress virus replication in all of the treated rhesus macaques, but plasma viral RNA rapidly became detectable in all six animals following its cessation. Unexpectedly, the viral set points in the treated monkeys became established at two distinct levels. Three controller macaques had chronic phase virus loads in the range of 1 × 103 RNA copies/ml, whereas three noncontroller animals had set points of 2 × 105 to 8 × 105 RNA copies/ml. All of the noncontroller monkeys died with symptoms of immunodeficiency by week 60 postinfection, whereas two of the three controller animals were alive at week 80. Interestingly, the three controller macaques each carried major histocompatibility complex class I alleles that previously were reported to confer protection against SIV, and two of these animals generated cytotoxic T-lymphocyte escape viral variants during the course of their infections.
Herpes Simplex Virus 2 MicroRNA miR-H6 Is a Novel Latency-Associated Transcript-Associated MicroRNA, but Reduction of Its Expression Does Not Influence the Establishment of Viral Latency or the Recurrence Phenotype

The herpes simplex virus 2 (HSV-2) viral microRNA (miRNA) designated miR-H6 is located upstream of the latency-associated transcript (LAT) promoter region on the strand opposite the LAT. Deletion of the LAT promoter and part of LAT exon 1 abolished HSV-2 miR-H6 expression in acutely and latently infected guinea pig dorsal root ganglia (DRG), suggesting that this region is needed both for the expression of LAT-encoded miRNAs and for miR-H6 expression in vivo. Relative to cells infected with a viral rescuant, miR-H6 expression was significantly reduced in cells infected with a mutant HSV-2 virus, NotPolyA, with an insertion of a simian virus (SV40) polyadenylation signal sequence between the LAT promoter and miR-H6 sequences. In addition, expression of miR-H6, but not LAT or viral DNA, was significantly reduced in both mouse trigeminal ganglia (TG) and guinea pig DRG latently infected with the NotPolyA mutant. Guinea pigs infected with NotPolyA experienced reduced neurological complications of acute infection relative to those infected with the rescuant, but the recurrence phenotype of the NotPolyA mutant was similar to those of its rescuant and wild-type HSV-2, indicating that reduction of miR-H6 expression is not by itself able to alter the establishment of latency for the wild-type virus or the recurrence phenotype. Furthermore, the mutation in NotPolyA did not affect the propensity of wild-type HSV-2 to establish latency in neurons positive for subtype marker KH10. In contrast to published reports regarding its HSV-1 homolog, HSV-2 miR-H6 did not affect ICP4 expression in transfected or infected cells. We hypothesize that viral miRNAs associated with LAT expression are likely to work collectively, contributing to the phenotype attributed to the LAT.
Estimating radiated power from a conducting tethered satellite system

In anticipation of the upcoming TSS-1 experiment, theoretical calculations are made of radiated power from a conducting tethered satellite system. The radiation results from the steady motion of the system through the ionospheric plasma and it is stimulated by collection and emission of charge by the noninsulated surfaces of the tethered end connectors. A model of the current system is developed which incorporates the tether wire, satellite surfaces, and sheath currents. The radiation impedance of the current model is calculated using the previously developed theory of Barnett and Olbert (1986). The results confirm the low-frequency Alfven wave description with a predicted radiation impedance of a few tenths of an ohm in the Alven wave limit. Calculations are also made in the lower hybrid and whistler wave band. A larger impedance of about 13 ohm is found for the frequency range 5-50 kHz. By estimating the passive ion current drawn by the system a prediction of the total radiated power is also made. The result of 0.38 mW raises the question of whether or not wave emissions from a passive current collecting system may be detectable by either ground- or space-based platforms.
Mesolimbic dopamine mediates gastric mucosal protection by central neurotensin

Bilateral microinjection (1.0 microliter/side) of neurotensin (NT; 0.3, 1.5, and 3.0 micrograms/side) into the nucleus accumbens (NACB) and ventral tegmental area (VTA) but not in substantia nigra and striatum reduced gastric mucosal injury produced by 2 h of cold-water restraint (CWR). The minimal effective dose for NT-induced protection was 10-100 times lower when administered directly into NACB than into the lateral ventricle. These effects were blocked by pretreatment with the dopamine (DA) receptor antagonist, haloperidol (Hal; 0.5 microgram/side) given directly into NACB. Injection of 6-hydroxydopamine into VTA depleted endogenous DA and inhibited gastric mucosal protection against CWR-induced injury afforded by NT pretreatment. NT, given into either VTA and NACB, inhibited pentagastrin-stimulated gastric acid secretion. These results suggest that VTA and NACB, which represent the mesolimbic DA system, are important locations for interaction between NT and DA receptors to produce gastric mucosal protection against CWR-induced injury.
57 COGNITIVE FUNCTIONING AND CARDIOVASCULAR RISK: THE BOGALUSA HEART STUDY

Purpose of Study There is growing evidence that mid-life cardiovascular (CV) risk factors such as untreated hypertension, diabetes mellitus, hyperlipidemia and physical inactivity predispose people to various forms of late-life cognitive impairment, including Alzheimer9s disease. How early in life these factors begin to operate remains unknown. The Bogalusa Heart Study, an ongoing, long term community study of childhood and young adulthood CV risk factors in a biracial population, offers an ideal opportunity to examine the early antecedents of later life cognitive decline. Objective To examine the feasibility of evaluating cognitive function in the present middle-aged BHS cohort and its relation to present and early life CV risk factors. Methods Participants in the Bogalusa Heart Study, ages 24 to 44 years, were individually administered a battery of standard neuropsychological tests of verbal fluency, reading, digit span and similarities (Wechsler Adult Intelligence Scale), and the logical memory, verbal paired associates and visual reproduction tests from the Wechsler Memory Scale (third edition). Preliminary statistical correlations of test scores with various CV risk factors, e.g. systolic and diastolic blood pressure, were performed. Summary of Results The battery takes approximately 45 minutes to complete. Having flexible times to administer the battery was helpful in increasing enrollment. Participants were eager to participate. Although a few expressed some anxiety about their performance, all were able to complete the battery. Preliminary analysis of the correlations between the test results and CV risk data from the first 35 participants has allowed us to compute the power needed for a larger planned study. Conclusions The protocol is well received by participants, and a large scale study is feasible in the BHS cohort. Screening will continue until we obtain 100-120 participants. At that time we will examine correlations between test scores and CV risk factors and prepare a major proposal to examine the early CV risk factors that impact cognitive functioning in middle life.
Why Occupy? Modeling Military Occupation Decisions ⁄

In this project, I examine the decisions of major powers to pursue military occupation as a strategy to stabilize less powerful states. To do so, I develop a baseline game theoretic model that examines the strategic decisions of major powers to pursue short-term intervention and long-term occupation in a potentially unstable target state. The model indicates military occupation decisions are a function of both interpower politics and the domestic political conditions in the target state. In addition to these implications, I discuss a number of potential extensions of the baseline model that could provide a more complete theory of occupation and intervention.
Improved red blood cell preservation correlates with decreased loss of bands 3, 4.1, acetylcholinestrase, and lipids in microvesicles.

In earlier studies we have shown that a final concentration of 0.69% glycerol in blood mixed with an experimental additive solution, EAS 25, improves the in vitro quality and in vivo survival of red blood cells (RBCs). The objective of this study was to determine if the better preservation of RBCs in EAS 25 is correlated with the improved maintenance of membrane lipids and proteins and decreased vesiculation. Split units of RBCs were stored in Adsol or EAS 25 (mmol/L: adenine 2/2, dextrose 122/110, mannitol 42/55, glycerol 0/150, NaCl 154/50). After 12 weeks storage, RBC and microvesicle membranes were analyzed for cholesterol, phospholipid, diphenyl hexatriene fluorescence anisotropy, and acetylcholinesterase (AchE) activity. Bands 3 and 4.1 were identified in the microvesicle membranes by immunoblotting. The RBC membrane cholesterol, phospholipids, and AchE remained higher in EAS 25 than in Adsol (P < .001). Vesicle membrane lipids and AchE in EAS 25 were significantly less than in Adsol (P < .001). The fluidity of stored cells in both the solutions was greater than the prestorage samples. Immunoblotting analyses showed that bands 3 and 4.1 were greatly reduced in the microvesicle membranes shed by the RBCs stored in EAS 25 compared with those formed in Adsol.
Numerical Simulation of the Signal Generation and Detection Process in a Pyroelectric Calorimeter

Pyroelectric thin film calorimeters [1] have proven to have unsurpassed time resolution and sensitivity as thermal wave detectors. Theoretical understanding of the complex signal generation and detection process, however, has been rather limited. Interpretation of experimental data was qualitative and based only on prominent features, such as time to maximum and amplitude of maximum in a pulsed experiment. To achieve a more full understanding required for quantitative analysis of experimental data, an extensive investigation of the signal generation process was carried out here.
Shielding Technology and the Bush Initiative - Shielding for Lunar and Martian Missions

§¶ # ** †† ‡‡ §§ ¶¶ ## *** Past space missions beyond the confines of Earth’s protective magnetic field have been of short duration, and protection from the effects of solar particle events was of primary concern. Aluminum alloy structures provided sufficient protection to meet requirements to prevent early radiation syndrome and were further successfully employed as protection against trapped protons in low Earth orbit (LEO). Aluminum alloys have been the materials of choice for the first 40 years of the space program. The extension of operations beyond LEO to enable routine access to other interesting regions of space will require protection from the hazards of the accumulated exposures of Galactic Cosmic Rays (GCR), and efficient fragmentation of GCR ions with minimal production of secondary particles in shielding materials is essential to protecting the astronauts. Aliphatic polymer composites are the most efficient structural materials exhibiting significantly improved radiation shielding properties, but they are limited in meeting the requirements of the service environment. Aromatic polymer composites developed mainly for high-speed aircraft applications have improved thermal-mechanical properties over aluminum alloys, as well as improved radiation shielding performance. Aliphatic/aromatic hybrid polymers are being developed to give a range of thermal-mechanical properties. The development of functionally graded structures will provide optimum solutions to multifunctional materials requirements in the near-term space program, with far-term utility.
Why is Our Population of Uninsured and Underinsured Persons Growing? The Consequences of the “Deindustrialization” of the United States:

In this article the authors discuss the consequences of the “deindustrialization” of America for the health benefits coverage of the U.S. population, the majority of which receive their health benefits through their workplace. The shift of employment from industry to services, from union to nonunion, from full-time to part-time employment, and from high-paying to low-paying jobs is having a most profound impact on the health benefits coverage of the U.S. population.
Oxidation of Elastomers in Aqueous Environments

Abstract Crosslinked 1,4-poly butadiene (BR) and styrene-butadiene rubber (SBR) were oxidized in various ionic environments (water, neutral salt solutions, acidic and basic buffers). The acceleration of oxidation when the elastomer was immersed in neutral and basic aqueous solutions, compared to dry air, is consistent with nucleophilic attack by peroxy anions on polymer hydroperoxides to give free radicals capable of initiating further oxidation. Acidic solutions retarded oxidation, compared to air, presumably because of decomposition of hydroperoxides to nonradical products. This phenomenon is in addition to the well-known effects of extraction of antioxidants by liquid media, and the accelerating effect of transition metal ions. The accelerating effect of basic solutions was greatest at the polymer surface, providing an inexpensive route to surface modification of elastomers. As an example, scrap rubber crumb was treated with aqueous alkaline hydrogen peroxide solution or sodium hypochlorite solution an...
Deprenyl and Parkinson's disease: new use for an old drug.

Parkinson’s patients treated with deprenyl note modest but consistent clinical improvement.
Carefree Handling using Reactionary Envelope Protection Method

The operational envelope of a flight vehicle is constrained by a number of critical parameters known as limit parameters. These parameters are constrained to remain within certain bounds to ensure operational safety and in some cases performance of the vehicle. In the case of manned vehicles the task of maintaining vehicle operation within the operational flight envelope by monitoring limit parameter values vests with the pilot. In most situations this task of envelope protection increases pilot workload. Envelope protection systems reduce operational workload by monitoring and informing the pilot of approaching envelope boundaries. Recently, envelope protection methods that translate limit proximity information to its equivalent in the control channel have gained more acceptance. Reactionary envelope protection method is an approach developed for automatic envelope protection in Unmanned Aerial Vehicles. The approach relies on prescribing a safe-response profile for the limit parameter response near the limit boundary and then providing appropriate corrections to the control channel so that limit parameter response tracks the safe-response profile. In this paper, an extension to the reactionary envelope protection method is presented that allows control margins to be calculated for envelope protection. The development of this extension will allow the reactionary envelope protection method to be utilized within an envelope protection system for piloted vehicles. The proposed extension is used to implement a reactionary envelope protection system for R22 manifold pressure limit protection. Results comparing estimated reactionary envelope protection control limits againts previously validated envelope protection methods are also presented.
MOOCs in the humanities Can they reach underprivileged students

Massive open online courses (MOOCs) have been heralded as a democratizing force bringing higher education to the world’s neediest students. But do MOOCs effectively confront the well-documented challenges of online education for underprivileged students? This textual analysis examines MOOC offerings in the humanities and finds that courses are designed for relatively well-prepared students, not underprivileged students.
Chemical and Electrochemical Manipulation of Mechanical Properties in Stimuli-Responsive Copper-Cross-Linked Hydrogels

Inspiration for the design of new synthetic polymers can be found in the natural world, where materials often exhibit complex properties that change depending on external stimuli. A new synthetic electroplastic elastomer hydrogel (EPEH) that undergoes changes in mechanical properties in response to both chemical and electrochemical stimuli has been prepared based on these precedents. In addition to having the capability to switch between hard and soft states, the presence of both permanent covalent and dynamic copper-based cross links also allows this stimuli-responsive material to exhibit a striking shape memory capability. The density of temporary cross links and the mechanical properties are controlled by reversible switching between the +1 and +2 oxidation states.
Power Electronics in Implements for Trackage Traction and Navigations

At present, power electronics technology is quickly extending and applying to the implements for trackage traction and navigations. Following successful application in trains and locomotives, the research and development of the all-electric-system boats ships, and the all-electric-system airplanes has already been put on the agenda. This paper has commented the comprehensive report--"Power electronics and future marine electrical systems", which is published in ((IEEE Transaction on Industry Application, Vol.42,No.1,2006}} ,and is now made an excerpt translated into Chinese from it ,as the appendix of this paper. That is a new application field of the development of power electronics. This paper has pointed the advantages of the all-electric-system, which is applied in the implements for trackage traction and navigations using the power electronics technology, also its included contents, and the main train of thought and the introduction of the authors of the commented report.
Disease Burden and Quality of Life of Rheumatoid Arthritis in China: A Systematic Review

Objective To get known about the disease burden and quality of life(QOL) of rheumatoid arthritis(RA) in China by conducting a systematic review.Methods The observational studies about the disease burden and QOL of RA in China were systematically searched in the following databases: CNKI,CBM,VIP,WanFang Data,MEDLINE/Pub Med,EMbase,and Science Citation Index.The retrieval time was from January 1st,1990 to July 31st,2010.According to the inclusion and exclusion criteria,the literature was screened,the data were extracted,and the methodological quality of the included studies was assessed.The morbidity of RA was pooled by adopting generic inverse variance model,the meta-analyses on 8 dimensions of SF-36 life quality score(LQS) was conducted by suing RevMan5.0 software,the weighted mean difference(WMD) was regarded as the indicator of intervention effect,and the impact of studies' quality on the results was assessed by sensitivity analysis.Results A total of 20 studies with medium quality in general were included.The morbidity of RA was 14.7/100 000.The disability adjusted of life years(DALYs) per capita were 4.92.If excluding the cost resulted from DALY,the overall economic cost was RMB 1 250.45 yuan per capita per year;While considering DALY,the cost was RMB 15 717.91 yuan per capita per year.The average cost of outpatient medications was RMB 8 018±17 238 yuan per capita per year.The weighted morbidity was 0.42%(95%CI 0.39% to 0.45%),and it was higher in female than male(P0.05).There was no secular trend and difference between southern and northern(P0.05),but there were statistical significances in the WMD of 8 dimensions of SF-36 LQS.Sensitivity analyses revealed that the weighted pooled results were stable.Conclusion The epidemiological and economic burden of rheumatoid arthritis are heavier in China,which needs to be concerned by both government and society.
Serotonin elicits long-lasting enhancement of rhythmic respiratory activity in turtle brain stems in vitro

Brain stem preparations from adult turtles were used to determine how bath-applied serotonin (5-HT) alters respiration-related hypoglossal activity in a mature vertebrate. 5-HT (5–20 μM) reversibly...
By Her Grace: The Limits of Imperial Power and Religious Authority in Early Portuguese-Gold Coast Relations

In 1540, an elder Twi-speaking enslaved woman named Graca was accused of engaging in “idol worship” by Joao da Mata, her supervisor at the Sao Jorge da Mina fortress on the Gold Coast, and a young Portuguese officer, Joao Vaz de Paiva. Graca was dispatched to the Holy Office in Lisbon to stand trial in front of the judges of the Inquisition, at a time this religious institution was still getting its act together. The defendant, Graca, was painted by the prosecutor as one who was unchristian, ignorant of the faith and the Portuguese language, and who only cared about her idolatrous life and rituals. But upon Graca’s request, she gets an attorney who—through Graca’s testimony—presents a more complex story, wherein she was in fact a Christian and was the victim of a plot by an envious “mulatta” Margarida Rodrigues who, with her lover and Graca’s supervisor Joao da Mata, created the hysteria and accusations which led to Graca’s eventual trip to Lisbon. In the end, in spite of weak evidence and a strong case mounted by Graca, she was “sentenced to life imprisonment and sent to be indoctrinated.” This paper aims to use Graca inquisition file and other contemporary sources to explore the real limits of Portuguese global and imperial power, and especially its religious authority, in the context of sixteenth century Portuguese-Gold Coast relations. That Graca was 60 to 70 years old at the time of her trial meant that she was either born or a very young child when the Portuguese began to establish their commercial forts on the Gold Coast, and as such represents not only a first generation perspective on those relations but also offers rare insights into matters of religious conversion and enslavement, tensions between local beliefs and those articulated by a nascent global empire, and the transnational claims made to territory and over its peoples along religious fault lines.
Potential and Pitfalls of Therapy with α-Particles

Because of the short path length in tissues (<100 μm) and the high linear energy transfer (∼100 keV/μm), α-particle therapy offers the potential for specific tumor cell killing with a low level of damage to surrounding tissues ([1][1]). Clinical applications for which this approach is favorable
Chromatin Regulation by Long Non-coding RNAs

After the discovery of thousands of long noncoding RNAs (lncRNAs) in the mammalian genome, it became evident that hundreds of these transcripts are associated with chromatin-modifying complexes across multiple and distinct cell types. Furthermore, a number of lncRNAs have been shown to guide and tether chromatin-modifying complexes to specific genomic loci both in cis and in trans. These exciting findings suggest a general mechanism of lncRNA-mediated chromatin formation in mammals. In this chapter, we will discuss evidence supporting a model that lncRNAs provide the targeting specificity of specific protein complexes to chromatin.
Remembering the Revolution: Wordsworth, Benjamin, and Mnemonic Critique

That The Prelude records Wordsworth’s turn into himself and away from politics has become a commonplace in Romantic studies. However, the work of Walter Benjamin—a radical who finds revolutionary p...
Cost-effectiveness of everolimus plus exemestane in post-menopausal hormone receptor positive metastatic breast cancer.

6548 Background: Everolimus in combination with exemestane is approved for the treatment of postmenopausal women with hormone-receptor (HR) positive, HER2-negative metastatic breast cancer (MBC). T...
Quality Indicators in Endoscopic Ablation for Barrett's Esophagus.

Barrett’s esophagus (BE) is a well-established premalignant condition for esophageal adenocarcinoma (EAC); a cancer that is associated with a poor 5-year survival rate. Several strategies have been explored in the context of reducing the burden of EAC. Endoscopic eradication therapy (EET) is considered the standard of care for the management of patients with BE with dysplasia and early neoplasia; a practice that has been endorsed by all gastroenterology societal guidelines. The effectiveness of EET has been demonstrated in multiple studies and contemporary management includes a combination of endoscopic mucosal resection (EMR) of all visible lesions followed by eradication of the remaining BE using ablative techniques of which radiofrequency ablation (RFA) has the best evidence supporting effectiveness and safety. These techniques are being used increasingly at academic tertiary care centers and community practices. In this era of value-based health care, there is increased focus on the establishment, documentation, and reporting of quality indicators; indicators that are important to physicians, patients, and payers. The purpose of this review is to highlight the current status of quality indicators in EET for the management of patients with BE-related neoplasia and discuss the future steps required to ensure that these quality indicators are uniformly incorporated into practice.
Abstract 3580: GATK CNV: copy-number variation discovery from coverage data

We propose and evaluate a novel algorithm for inferring germline and somatic copy number variation from whole exome sequencing (WES) and whole genome sequencing (WGS) data. Starting with the depth of aligned short reads from a cohort of samples, we use a Bayesian model for learning sequencing bias and simultaneously detecting CNV events using a hidden Markov model for change-point detection. A unified framework is used to call both germline and somatic CNVs. Denoising and event discovery are performed self-consistently to achieve maximum accuracy. In contrast to previous methods, our model naturally accounts for mixed sex cohorts and can detect events on sex chromosomes. Furthermore, we can detect excessively noisy samples and extract useful information within a probabilistic framework. Our implementation can also utilize Spark clusters, enabling the processing of larger cohorts and allowing for improved runtime performance. We benchmark the new method for precision, recall, and reproducibility of both germline and somatic variants. Evaluations are performed on a cohort of WES samples from The Cancer Genome Atlas with matching WGS data. For germline variants, we use blood normal samples and compare our calls on WES data against Genome STRiP calls on WGS data. We find that GATK CNV yields remarkably higher precision and recall compared to XHMM and CODEX software packages. For somatic variants, we compare our calls against TITAN and find a remarkably high concordance. Citation Format: Mehrtash Babadi, David I. Benjamin, Samuel K. Lee, Andrey Smirnov, Aaron Chevalier, Lee Lichtenstein, Valentin Ruano Rubio. GATK CNV: copy-number variation discovery from coverage data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3580. doi:10.1158/1538-7445.AM2017-3580
Case Study of Today’s Automotive Dealerships: Introduction and Delivery of Advanced Driver Assistance Systems:

Vehicle manufacturers have developed advanced driver assistance systems (ADASs) to reduce driver workload and enhance safety. The delivery of these systems to consumers occurs through dealerships not owned by manufacturers. Limited research is available on how dealerships provide consumers with information and training on ADASs. In an exploratory study seeking information on new safety technologies, semistructured blind interviews of salespeople at 18 Boston, Massachusetts, area dealerships were conducted in the context of potential vehicle purchase across six vehicle brands. Although some dealerships were making concerted efforts to introduce and educate customers on ADASs, a number of salespeople interviewed were not well positioned to provide adequate information to their customers. In select instances, salespeople explicitly provided inaccurate information on safety-critical systems. The dealerships in the sample that represented mass-market brands (Ford and Chevrolet) were the poorest performers. Sal...
Rectal resection for benign disease: a new technic.

A technic of rectal resection for benign diseases has been described, in which the cleavage plane between the rectal submucosa and muscularis is used. Dissection within the muscularis without mobilization or eversion of the rectum protects pararectal viscera. Pelvic peritoneal closure is facilitated and sexual function in the male is not impaired. This operative technic has been used successfully in two male patients. These encouraging results suggest further clinical trial when proctectomy for benign disease is indicated.
Case 3: Progressive Leg Pain and Weakness in a 16-year-old Boy.

1. Amanda Begley, MD* 2. Alicia Briggs, MD* 3. Christopher Williams, MD† 1. *Department of Pediatrics, Norwalk Hospital, Norwalk, CT 2. †Department of Pediatrics, University of Vermont College of Medicine, Burlington, VT A 16-year-old boy presents with progressive lower extremity pain and weakness. One month ago, the patient joined the basketball team after living a sedentary lifestyle. Since then, he has developed shin splints and a dull aching pain in his ankles and lower back. He treated the pain with ibuprofen and stretching exercises, resulting in some relief. The day before admission he had severe pain in his hamstrings and also developed lower extremity weakness and numbness during practice. On the morning of admission, his symptoms are too severe for him to be able to walk. The patient states that his pain is predominantly in his hamstrings and that he feels a “pulling sensation.” He also complains of bilateral numbness and cold sensitivity on his posterior calves and on his feet below the ankles. He recently had coldlike symptoms with no other recent illnesses. He admits to losing 10 lb (4.5 kg) in the past month, which he attributes to participating in daily conditioning exercises. He denies any recent urinary symptoms. Physical examination reveals a large teenage boy, mildly somnolent from narcotics given for pain. Vital signs show a …
Extreme-event geoelectric hazard maps

Abstract Maps of geoelectric amplitude covering about half the continental United States are presented that will be exceeded, on average, once per century in response to an extreme-intensity geomagnetic disturbance. These maps are constructed using an empirical parameterization of induction: convolving latitude-dependent statistical maps of extreme-value geomagnetic disturbances, obtained from decades of 1-minute magnetic observatory data, with local estimates of Earth-surface impedance obtained at discrete geographic sites from magnetotelluric surveys. Geoelectric amplitudes are estimated for geomagnetic waveforms having a 240-s (and 1200-s) sinusoidal period and amplitudes over 10 min (1 h) that exceed a once-per-century threshold. As a result of the combination of geographic differences in geomagnetic variation and Earth-surface impedance, once-per-century geoelectric amplitudes span more than two orders of magnitude and are a highly granular function of location. Specifically for north-south 240-s induction, once-per-century geoelectric amplitudes across large parts of the United States have a median value of 0.34 V/km; for east-west variation, they have a median value of 0.23 V/km. In Northern Minnesota, amplitudes exceed 14.00 V/km for north-south geomagnetic variation (23.34 V/km for east-west variation), while just over 100 km away, amplitudes are only 0.08 V/km (0.02 V/km). At some sites in the northern-central United States, once-per-century geoelectric amplitudes exceed the 2 V/km realized in Quebec during the March 1989 storm.
Nearshore Larval Retention and Cross-Shelf Migration of Benthic Crustaceans at an Upwelling Center

Planktonic larvae are considered to be highly susceptible to offshore transport in productive upwelling regions, thereby increasing dispersal and limiting recruitment. However, larvae of 42 species of nearshore benthic crustaceans primarily developed on the inner shelf at locations both in (98.5%) and away (99.8%) from a perennial upwelling center during the peak upwelling season in a recruitment-limited region characterized by strong, persistent upwelling. During three cross-shelf cruises conducted at each location, larvae of 21 species remained on the inner shelf at both sites by occurring below a shallow Ekman layer of seaward-flowing surface waters throughout development while larvae of the other species migrated to mid-shelf (four species) or offshore (14 species) by occurring closer to the surface early in development. Postlarvae apparently returned to adult habitats inshore either by descending to landward-flowing upwelled waters or ascending to the surface where behavior allows them to be transported shoreward by internal waves, diel wind cycles or wind relaxation events. Thus, the cause of recruitment limitation along upwelling coasts does not appear to be due to losses from offshore transport, requiring new research directions to advance our understanding of population dynamics, structure and connectivity.
HYDROGRAPH SYNTHESIS BY DIGITAL COMPUTER

THE STUDY CONSISTS OF HYDROGRAPH SYNTHESIS BASED ON AN INVESTIGATION OF RUNOFF FROM SMALL DRAINAGE BASINS IN TEXAS. A TECHNIQUE FOR DETERMINATION OF THE TEMPORAL DISTRIBUTION OF INFILTRATION CAPACITY IS DEVELOPED. CORRELATIONS BETWEEN A CRITICAL HYDROGRAPH PARAMETER, LAG, AND BASIN CHARACTERISTICS ARE MADE. ALSO, CORRELATIONS ARE MADE BETWEEN BASIN CHARACTERISTICS AND THE COEFFICIENTS FROM SNYDER'S SYNTHETIC UNIT-HYDROGRAPH EQUATIONS. A METHOD FOR FITTING HYDROGRAPH DATA TO MATHEMATICAL FUNCTIONS IS DEVELOPED. A NONLINEAR LEAST-SQUARES METHOD IS PRESENTED FOR FITTING THE SEVEN POINTS OBTAINED BY A MODIFIED SNYDER PROCEDURE TO THE PEARSON TYPE III MATHEMATICAL FUNCTION. /ASCE/
Interleukins in Cancer Therapy

The interleukins function as intercellular hormones, and have the capacity to alter the activity of a target cell population. Immunotherapy with interleukin-2 (IL-2) constitutes a new treatment strategy for malignancies otherwise not responsive to traditional cytotoxic chemotherapy.
Gas-Liquid Chromatographic Analysis of Amino Acids

Automatic amino acid analyzers separate the components on columns filled with ion exchange resins. The equipment is quite expensive, the operation is cumbersome, and requires a well trained operator. A somewhat less quantitative and less accurate but far simpler and much less expensive procedure for qualitative and quantitative determination of amino acids has been provided by the method developed first by Graff et al. (1963) and further elaborated by Coulter and Hann (1968). The procedure converts amino acids into their n-propyl-N-acetylated esters. These derivatives are sufficiently volatile for separation in GLC. The method described in this Exercise is based on the work of Coulter and Hann.
Spatial Recall: Memory in Architecture and Landscape

Contributors -- Introduction / Marc Treib -- Body. 1. Space, place, memory, and imagination : the temporal dimension of existential space / Juhani Pallasmaa -- 2. Re-creating the past : notes on the neurology of memory / Susan Schwartzenberg -- 3. The place of memory / Donlyn Lyndon -- 4. Indelible marker, palimpsest, thin air / Alice Aycock -- Landscape. 5. Rivers, meanders, and memory / Matt Kondolf -- 6. Displacements : canals, rivers, and flows / Georges Descombes -- 7. Land, cows, and pyramids / Adriaan Geuze -- Building. 8. The Mediterranean cemetery : landscape as collective memory / Luigi Latini -- 9. The place of place in memory / Esther da Costa Meyer -- 10. Remembering ruins, ruins remembering / Marc Treib -- 11. The memory industry and its discontents : the death and life of a keyword / Andrew Shanken -- 12. Mnemonic value and historic preservation / Jorge Otero-Pailos -- Acknowledgments -- Index.
Abstract LB-266: Identification of novel checkpoint kinase inhibitor ASR352 with selective activity against 5-FU resistant colorectal cancer cells

Colorectal cancer (CRC) remains the third most common cancer in the United States, with a high mortality rate. More than 1.2 million new cases of CRC are diagnosed every year. Approximately 25% of these patients have metastatic lesions at diagnosis and almost 50% of these patients will eventually develop metastases. 5-Fluorouracil (5-FU) based cytotoxic chemotherapeutics such as FOLFOX and FOLFIRI have demonstrated improved response rates. 5-FU treatment induces DNA damage and stalling of DNA replication forks towards one sided double-strand breaks thus leading to apoptosis. However, these tumors quickly develop resistance to FOLFOX and FOLFIRI by stopping DNA damage process, and at the same time, this treatment regime leads to significant toxicity, cost, and patient inconvenience. To overcome the drug resistance developed in 5-FU based CRC chemotherapy, we looked for critical role of checkpoint kinase 1 (Chk1) that promotes DNA replication forks. Therefore, Chk1 kinase has been a target for developing mono or combination therapeutic agents. Recently, we demonstrated that an orphan azaadamantane molecule NSC30049 (NSC49L) is effective alone, and in combination potentiates 5-FU-mediated growth inhibition of CRC heterogeneous bulk and FOLFOX-resistant cell lines in culture with minimal effect on normal colonic epithelial cells. The pharmacokinetic analysis showed a higher bioavailability of this compound, however, with a short plasma half-life apparently due to reactive alkyl chloride group. To overcome this problem, we designed and synthesized several novel azaadamantane NSC49L analogs, and their cytotoxic efficacy against HCT116 and HT29 colorectal cancer cell lines was evaluated either alone or in combination with 5-FU with different concentrations for 48 h by MTT essay. ASR352 was identified as the best of all synthesized analogs. ASR352 was equally effective as NSC49L in (i) reducing the viability of 5-FU treated HCT116 and HT29 cell lines in a dose-dependent manner, (ii) inhibiting the FOLFOX-resistant HCT116 and HT29 cell lines, (iii) reducing the sphere formation capacity of CA2 cells, a CRC stem cell line, and (iv) causing the abrogation of 5-Fu induced G2/M and S phase arrests in HT29 cells. In addition,ASR352 inhibited the hydroxyurea (HU)-induced phosphorylation of Chk1 (P-Ser317), Chk1 (P-Ser345) and Chk1 (P-Ser296) in HT29 cell lines. In conclusion, a new clinical relevant drug-like molecule ASR352, that targets Chk1 pathway to reduce viability of particularly the 5-FU resistant CRC cells, has been identified. Citation Format: Srinivasa Ramisetti, Sangyub Kim, Deepkamal Karelia, Junxuan Lu, Shantu Amin, Satya Narayan, Arun K. Sharma. Identification of novel checkpoint kinase inhibitor ASR352 with selective activity against 5-FU resistant colorectal cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-266.
Development of nonhuman primate models for prostate specific antigen (PSA) biology studies

2903 Prostate specific antigen (PSA) is released at increased levels into the blood early in the development of prostatic diseases and therefore is widely used for screening, diagnosing and monitoring of prostate cancer, although it is also elevated in other prostatic disorders. Serum PSA level is the most widely used clinical biomarker for any cancer. The PSA gene is only found in humans and other nonhuman primates. Currently there is a lack of a truly appropriate animal model for the study of PSA and causes of individual variation in serum PSA level. Previous studies have shown that the baboon prostate is anatomically and histologically similar to its human counterpart and therefore can be used as a model for prostatic diseases. The purpose of this study was to assay and compare serum PSA levels of three nonhuman primate species commonly used in research with the aim of establishing a nonhuman primate model to study PSA biology. Methods: Serum was collected from baboons, rhesus macaques and cynomolgus monkeys of different ages maintained at the Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, in San Antonio, Texas. Serum PSA assay was done using the ultrasensitive radioimmunoassay method (AniLytics, Inc., Gaithersburg, MD). Results: The results showed that serum PSA levels in baboons ranged from 0.06-0.78ng/ml while those of rhesus macaques and cynomolgus monkeys ranged from 0.07-2.35ng/ml and 0.1 to 5.23ng/ml respectively Conclusions: a) Serum PSA can be measured in nonhuman primates, b) PSA values in nonhuman primates are comparable to those reported in humans without prostate disease, c) cynomolgus monkeys have the highest serum PSA values and also their values increased with age, d) nonhuman primates especially cynomolgus monkeys may be used for studies of PSA biology.
Phentolamine Infusion Therapy

Phentolamine (phentolamine mesylate), a non-selective alpha-adrenergic receptor antagonist, has traditionally been used in hypertensive crises due to pheochromocytoma, extravasation management, and local anesthesia reversal. But recent research has also suggested applications beyond these indications including uses for abdominal cancer pain and neuropathic pain.
A major role for noncoding regulatory mutations in the evolution of enzyme activity

The quantitative evolution of protein activity is a common phenomenon, yet we know little about any general mechanistic tendencies that underlie it. For example, an increase (or decrease) in enzyme activity may evolve from changes in protein sequence that alter specific activity, or from changes in gene expression that alter the amount of protein produced. The latter in turn could arise via mutations that affect gene transcription, posttranscriptional processes, or copy number. Here, to determine the types of genetic changes underlying the quantitative evolution of protein activity, we dissected the basis of ecologically relevant differences in Alcohol dehydrogenase ( Adh ) enzyme activity between and within several Drosophila species. By using recombinant Adh transgenes to map the functional divergence of ADH enzyme activity in vivo, we find that amino acid substitutions explain only a minority (0 to 25%) of between- and within-species differences in enzyme activity. Instead, noncoding substitutions that occur across many parts of the gene (enhancer, promoter, and 5′ and 3′ untranslated regions) account for the majority of activity differences. Surprisingly, one substitution in a transcriptional Initiator element has occurred in parallel in two species, indicating that core promoters can be an important natural source of the tuning of gene activity. Furthermore, we show that both regulatory and coding substitutions contribute to fitness (resistance to ethanol toxicity). Although qualitative changes in protein specificity necessarily derive from coding mutations, these results suggest that regulatory mutations may be the primary source of quantitative changes in protein activity, a possibility overlooked in most analyses of protein evolution.
An intramolecular arene-triflate coupling reaction for the regiospecific synthesis of substituted benzofluoranthenes

An intramolecular triflate-arene coupling reaction mediated by bis(triphenylphosphine)palladium(II) chloride has been developed for the synthesis of each of the isomeric benzofluoranthenes. This reaction, which results in formation of a new five-membered ring, proceeds in highest yield when performed using 0.1 equiv of the palladium catalyst, 3 equiv of lithium chloride, and 1.2 equiv of 1,8-diazabicyclo[5.4.0]undec-7-ene in N,N-dimethylformamide at 140 o C. The biaryl precursors needed for the coupling reaction can be prepared by [1,2-bis(diphenylphosphino)ethane]nickel (II) choride catalyzed coupling of an aryl bromide with an [o-(methoxymethoxy)aryl]magnesium bromide (prepared by ortho-lithiation of an aryl methoxymethyl ether followed by transmetalation with magnesium bromide). Using this procedure benzo[a]fluoranthene, benzo[b]fluoranthene, benzo[j]fluoranthene, and benzo[k]fluoranthene were prepared in yields of 84%, 85%, 93%, and 64%, respectively.
Downregulation of Notch Signaling in Kras-Induced Gastric Metaplasia

Activating mutations and amplification of Kras and, more frequently, signatures for Kras activation are noted in stomach cancer. Expression of mutant KrasG12D in the mouse gastric mucosa has been shown to induce hyperplasia and metaplasia. However, the mechanisms by which Kras activation leads to gastric metaplasia are not fully understood. Here we report that KrasLSL-G12D/+;Pdx1-cre, a mouse model known for pancreatic cancer, also mediates KrasG12D expression in the stomach, causing gastric hyperplasia and metaplasia prior to the pathologic changes in the pancreas. These mice exhibit ectopic cell proliferation at the base of gastric glands, whereas wild-type mice contain proliferating cells primarily at the isthmus/neck of the gastric glands. Notch signaling is decreased in the KrasLSL-G12D/+;Pdx1-cre gastric mucosa, as shown by lower levels of cleaved Notch intracellular domains and downregulation of Notch downstream target genes. Expression of a Notch ligand Jagged1 is downregulated at the base of the mutant gland, accompanied by loss of chief cell marker Mist1. We demonstrate that exogenous Jagged1 or overexpression of Notch intracellular domain stimulates Mist1 expression in gastric cancer cell lines, suggesting positive regulation of Mist1 by Notch signaling. Finally, deletion of Jagged1 or Notch3 in KrasLSL-G12D/+;Pdx1-cre mice promoted development of squamous cell carcinoma in the forestomach, albeit short of invasive adenocarcinoma in the glandular stomach. Taken together, these results reveal downregulation of Notch signaling and Mist1 expression during the initiation of Kras-driven gastric tumorigenesis and suggest a tumor-suppressive role for Notch in this context.
BINDING OF CIS AND TRANS ISOMERS OF 4,4′-DINITRO STILBENE-2,2′-DISULFONATE (DNDS) TO THE ERYTHROCYTE ANION TRANSPORTER

Publisher Summary This chapter discusses the interaction between 4,4'-dinitro-stilbene-2,2'-disulfonate (DNDS) and chloride by measuring the binding of DNDS to the intact red cell membrane in the presence of varying concentrations of chloride on the outside of the cell. These binding studies show that chloride is a competitive inhibitor of DNDS binding. In the absence of extracellular chloride, the affinity of the transporter for DNDS is about 200 nM and the inhibition constant of chloride for DNDS binding is around 10 mM. Only the trans-isomer of DNDS binds to the red cell with an appreciable affinity. It has been found that the number of stilbene binding sites per red cell varies among different donors and seems correlated with the maximal rate of anion exchange flux. The anion transports inhibitor DNDS binds to the red cell membrane. It binds to a single class of sites as the graph is linear. Binding is specific in that the cis-isomer binds to the site with a much smaller affinity that the trans-isomer. In the cis-isomer, the aromatic rings are closer to each other and it is possible that the cis-isomer cannot reach the binding site for steric reasons. Extracellular chloride affects the binding of DNDS to the membrane. Chloride does not change the maximal number of available binding sites, but it reduces the affinity of binding. This is indicative of competitive behavior, that is, the binding of extracellular chloride and DNDS are mutually exclusive.