cssi/SciSciGPT-SciSciNet huggingface dataset:
Comparative effectiveness and safety of drug therapy for pulmonary arterial hypertension: a systematic review and meta-analysis.

Background Current treatments for pulmonary arterial hypertension (PAH) have been shown to improve dyspnea, 6-min walk distance (6MWD), and pulmonary hemodynamics, but few studies were designed to compare treatment regimens or assess the impact of treatment on mortality. Methods We conducted a systematic review to evaluate the comparative effectiveness and safety of monotherapy or combination therapy for PAH using endothelin receptor antagonists, phosphodiesterase inhibitors, or prostanoids. We searched English-language publications of comparative studies that reported intermediate or long-term outcomes associated with drug therapy for PAH. Two investigators abstracted data and rated study quality and applicability. Results We identified 28 randomized controlled trials involving 3,613 patients. We found no studies that randomized treatment-naive patients to monotherapy vs combination therapy. There was insufficient statistical power to detect a mortality difference associated with treatment. All drug classes demonstrated increases in 6MWD when compared with placebo, and combination therapy showed improved 6MWD compared with monotherapy. For hospitalization, the OR was lower in patients taking endothelin receptor antagonists or phosphodiesterase-5 inhibitors compared with placebo (OR, 0.34 and 0.48, respectively). Conclusions Although no studies were powered to detect a mortality reduction, monotherapy was associated with improved 6MWD and reduced hospitalization rates. Our findings also suggest an improvement in 6MWD when a second drug is added to monotherapy.
The Practical Side of Technology Transfer

Technology transfer is the application of new technical ideas into products. For ideas applied into products intended for government or military use, there are several applicable metrics that are used to guide decisions about readiness. In making decisions about development, it is important to involve stakeholders from the technology side and the application side. It is always a challenge to develop a new product or technology. It is not normally successful. From a technical standpoint, it is about technical maturity. From a marketing standpoint, it is about integration into a supply chain. From a management systems view, it is a shift in the paradigms of quality. Technology transfer is defined as applying new ideas into products
Sexual dimorphism in miR-210 expression and mitochondrial dysfunction in the placenta with maternal obesity

Sexual dimorphism in miR-210 expression and mitochondrial dysfunction in the placenta with maternal obesity
CHAMP: concurrent hierarchical and multilevel program for simulation of VLSI circuits

The design and implementation of a hierarchical switch-level simulator for complex digital circuits is discussed. The hierarchy is exploited to reduce the memory requirements of the simulation, thus allowing the simulation of circuits that are too large to simulate at the flat level. The algorithm used in the simulator operates directly on the hierarchical circuit description. Speedup is obtained through the use of high-level models. The simulator has been implemented on a SUN workstation and used to simulate a switch-level description of the Motorola 68000 microprocessor. >
Short-term intermittent hypoxia enhances sympathetic responses to continuous hypoxia in humans.

Short-term intermittent hypoxia leads to sustained sympathetic activation and a small increase in blood pressure in healthy humans. Because obstructive sleep apnea, a condition associated with inte...
New Dielectrics for Gate Oxides and Surface Passivation on GaN

In this paper, the authors report the nitride surface preparation and growth of these crystalline oxide dielectrics, efforts to improve the oxide/nitride interface properties by reducing the lattice mismatch and accelerated aging effects for these dielectrics on the nitride semiconductors. The authors review progress in obtaining low interface state densities and reducing current collapse with these dielectrics on GaN and examine the thermal stability and compatibility with processing schemes for HEMTs
Metastatic renal cell carcinoma presenting as gastric polyps: A case report and review of the literature

Abstract INTRODUCTION Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and is responsible for over 13,000 deaths in the U.S. annually. The fatalities are largely due to distant metastasis, with lung, liver, bone and brain being most commonly affected organs. Gastric metastasis from RCC is a rare event (less than 20 cases reported in the English language literature) and usually presents as a large, solitary mass or ulcer (average size of 4.8 cm) resembling primary gastric cancer. Here we report the first case of metastatic RCC presenting as small gastric polyps. PRESENTATION OF CASE The patient was a 60-year-old African American woman with a history of clear cell RCC (pT1bNX). She underwent esophagogastroduodenoscopy and colonoscopy 5 months after nephrectomy due to anemia. Two non-ulcerated, 0.6-cm benign-appearing polyps were found at the greater curvature of the gastric body, which were subsequently removed endoscopically. Unexpectedly, histopathologic examination of the gastric polyps revealed nested collections of vacuolated epithelioid cells in a background of delicate, arborizing vasculature, immediately beneath the congested and hyperplastic foveolar epithelium. A diagnosis of metastatic RCC was rendered after confirming the renal epithelial origin by immunohistochemical stains. DISCUSSION Gastric metastasis from RCC usually presents as a large, solitary mass or ulcer, but it can be subtle and present as multiple, small benign-appearing polyps. CONCLUSION A careful follow up and thorough endoscopic and histopathologic examinations should be conducted in patients with a history of RCC who present with gastrointestinal manifestations.
CONTINUOUS PROPIONIC ACID FERMENTATION OF HYDROLYZED COD (GADUS MORHUA) GURRY

Hydrolyzed cod gurry to which 4.0% glucose was added yielded a final pH of 4.5 after 96 h of incubation at 32C following inoculation with a 1.0% (v/v) inoculum (∼ 108 cells/mL) of a propionic acid producing bacterial culture. The use of a 90% (v/v) inoculum still resulted in a prolonged incubation time of 72 h to reach a pH of 4.5. A continuous propionic acid fermentation was successfully achieved for a period of 18 days with the addition of 2.5% to 4.0% glucose and a nutrient feed rate of 30 mL/h using a 500 mL fermentation vessel. A constant pH of 4.5 with an accompanying propionic acid concentration of 1.4% was maintained. Extrapolation of experimental data indicated that a glucose concentration of 2.2% is optimum.
Acute Otitis Media Due to Penicillin-Nonsusceptible Streptococcus pneumoniae Before and After the Introduction of the Pneumococcal Conjugate Vaccine

BACKGROUND The impact of the 7-valent pneumococcal conjugate vaccine (PCV7 [Prevnar]) on penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) recovered from children with acute otitis media (AOM) is unclear. METHODS At 5 hospitals, 505 pneumococcal isolates were collected from children with AOM between 1 January 1999 and 31 December 2002. Molecular subtyping was performed on 158 isolates. RESULTS Overall, the percentage of AOM cases due to non-PCV7 serogroups (including serotype 3) increased over time (from 12% in 1999 to 32% in 2002; P < .01) and according to the number of PCV7 doses received (18% [< or = 1 dose] vs. 35% [2-4 doses]; P < .01). The percentage of cases due to vaccine-related serotypes (including serotype 19A) increased according to the number of PCV7 doses received (10% [< or = 1 dose] vs. 19% [2-4 doses]; P = .05) but not over time, whereas the percentage of cases due to serotype 19F remained unchanged both over time and according to the number of PCV7 doses received. The frequency of penicillin nonsusceptibility among PCV7 serotypes (range, 65%-75%) and non-PCV7 serogroups (range, 11%-27%) did not significantly change overall. Although no change was detected among isolates collected from children with spontaneous drainage, the percentage of pneumococci recovered at the time of myringotomy and/or tympanostomy tube placement that were nonresistant to penicillin decreased over time (from 73% in 1999 to 53% in 2002; P = .03). All of the serotype 3 strains were genetically related, whereas 88% of the isolates that were either serotype 19F or serotype 23F were related to 1 of 3 international clones. CONCLUSIONS Among children with AOM, the proportion of cases due to non-PCV7 serogroups increased, vaccine-related serotypes increased, and serotype 19F remained unchanged. Although a decrease in the proportion of cases due to PNSP occurred among children who required myringotomy and/or tympanostomy tube placement, the proportion of PNSP remained unchanged overall and among children with spontaneous drainage. Because future trends in the susceptibility patterns of pneumococcal isolates recovered from children with AOM are not easy to predict, continued surveillance is essential.
Overview of the ANITA project

The ANITA project is designed to investigate ultra-high energy (>1017 eV) cosmic ray interactions throughout the universe by detecting the neutrinos created in those interactions. These high energy neutrinos are detectable through their interactions within the Antarctic ice sheet, which ANITA will use as a detector target that effectively converts the neutrino interactions to radio pulses. This paper will give an overview of the project including scientific objectives, detection description and mission design.
Approximate methods for predicting J-integral of a circumferentially surface-cracked pipe subject to bending

This study proposes two new methods to estimate the energy release rate of a circumferentially cracked pipe with an internal, constant-depth, finite-length surface flaw subjected to pure bending loads. The methods are based on the deformation theory of plasticity, constitutive law characterized by Ramberg-Osgood model, and an equivalence criterion incorporating reduced thickness analogy for simulating system compliance due to the presence of a crack. Closed-form solutions were developed in terms of elementary functions for an approximate evaluation of J-integral. They are general and can be applied in the complete range between elastic and fully plastic conditions. Several numerical examples are presented to illustrate the proposed methods. The comparisons with the results of elastic-plastic finite element analysis showed satisfactory prediction of J-integral by one of the proposed methods.
Chelator-induced inhibition of copper metalloenzymes in denitrifying bacteria

Copper (Cu) is required by the enzyme nitrous oxide reductase (N2OR), which catalyzes the last step of the complete denitrification pathway in denitrifying bacteria. Some denitrifiers also require copper for nitrite reductase (NiRK), whereas others use the iron nitrite reductase (NiRS). We report the inhibition of the activity of these enzymes in three strains of denitrifiers (two containing NiRK, the other NiRS), by forming nonbioavailable complexes with 1,4,8,11-tetraazacyclotetradecane1,4,8,11-tetraacetic acid hydrochoride hydrate (TETA), a strong Cu(II) chelator, and tetrathiomolybdate (TTMo), a strong Cu(I) chelator. Both ligands complex Cu with stability constants comparable to naturally occurring ligands and much more strongly than other widely used chelators, such as ethylenediaminetetraacetic acid. Addition of TETA to growth media lowered free Cu2+ concentrations below 10216 mol L21 and induced Cu limitation in all organisms. While Cu is strongly complexed in seawater, 10216 mol L21 free Cu2+ is lower than most reported values, suggesting that the organisms have evolved highaffinity Cu transport systems. TTMo had different effects, and inhibited NiRK more effectively than N2OR. It is likely that TTMo inhibits NiRK through direct, noncompetitive inhibition, as reported for other reduced sulfur compounds, rather than by inducing Cu limitation. The activity of NiRK may be sensitive to trace levels of reduced sulfur, which could account for its scarcity in marine systems. While Cu limitation of denitrification is probably uncommon in aquatic systems, the presence of reduced sulfur compounds may induce Cu limitation or enzyme inhibition leading to the accumulation of nitrite and nitrous oxide.
Experimental and modeling investigation of metal release from metal-spiked sediments

In sediments that contain iron monosulfide, cadmium, nickel, lead, zinc, and silver(I) form insoluble metal sulfides that lower the metal ion activity in the sediment-pore water system, thereby reducing toxicity. However, metal sulfides are susceptible to oxidation by molecular oxygen resulting in metal solubilization. To better understand the sources and sinks of metal sulfides in sediments, iron monsulfide-rich freshwater sediments were spiked with cadmium, nickel, lead, zinc, or silver(I) and placed into cylindrical cores with an overlying layer of oxygen-saturated water. Measurements of the dissolved metal concentration in the overlying water were made as a function of time and the vertical profiles of acid-volatile sulfide (AVS) and simultaneously extracted metal (SEM) were measured after 150 d. A one-dimensional reactive and transport model has been employed to help elucidate processes controlling the fate of metals in sediments. The model incorporates metal-sulfide formation, metal-sulfide oxidation, and metal partitioning onto sediment organic carbon and iron oxyhydroxide to simulate the vertical transport of metals throughout the sediment core.
Packaging Reliability-How to Define and Measure It

Microelectronic packaging employs many combinations of materials and processes to effect the interconnection of active and passive components and to provide interfaces with system levels of equipment. Reliability of these first-level packages is a key element in user acceptance and economics of electronic equipment. Complex interactions of design, materials, and processes may significantly affect package reliability. A tutorial approach to reliability methodology for first-level packaging as practiced in one company is presented. It emphasizes the identification of physical processes of degradation, approaches for mathematical modeling to relate accelerated testing to field application, and statistical quantification of unreliability (the complement of reliability). Application of this methodology is exemplified in the evaluation of several potential failure mechanisms discovered during the introduction of a new alloy for fiip-chip interconnection to the IBM packaging technology.
Periodicities in Strings

In this talk we summarize what is known about the periodicities of strings. A period of a string is a shift that causes a string to match itself. We define z compact represention of the set of all periods of a string, called the (auto) correlation of the string. Two sets of necessary and sufficient conditions are obtained characterizing the correlations of strings. It is shown that the number of distinct correlations of strings of length n is of the order n logn . By using generating function methods we enumerate the strings having a given correlation, and investigate certain related questions. A more expanded version of these results appears in an article [0] by the author and A.M. Odlyzko.
The Functional Benefits of Criticality in the Cortex

Rapidly growing empirical evidence supports the hypothesis that the cortex operates near criticality. Although the confirmation of this hypothesis would mark a significant advance in fundamental understanding of cortical physiology, a natural question arises: What functional benefits are endowed to cortical circuits that operate at criticality? In this review, we first describe an introductory-level thought experiment to provide the reader with an intuitive understanding of criticality. Second, we discuss some practical approaches for investigating criticality. Finally, we review quantitative evidence that three functional properties of the cortex are optimized at criticality: 1) dynamic range, 2) information transmission, and 3) information capacity. We focus on recently reported experimental evidence and briefly discuss the theory and history of these ideas.
Full-System Critical Path Analysis

Many interesting workloads today are limited not by CPU processing power but by the interactions between the CPU, memory system, I/O devices, and the complex software that ties all the components together. Optimizing these workloads requires identifying performance bottlenecks across concurrent hardware components and across multiple layers of software. Common software profiling techniques cannot account for hardware bottlenecks or situations where software overheads are hidden due to overlap with hardware operations. Critical-path analysis is a powerful approach for identifying bottlenecks in highly concurrent systems, but typically requires detailed domain knowledge to construct the required event dependence graphs. As a result, to date it has been applied only to isolated system layers (e.g., processor microarchitectures or message-passing applications). In this paper we present a novel technique for applying critical-path analysis to complex systems composed of numerous interacting state machines. We avoid tedious up-front modeling by using control-flow tracing to expose implicit software state machines automatically, and iterative refinement to add necessary manual annotations with minimal effort. By applying our technique within a full-system simulator, we achieve an integrated trace of hardware and software events with minimal perturbation. As a result, we can perform this analysis across the user/kernel and hardware/software boundaries and even across multiple systems. We apply this technique to analyzing network performance, and show that we are able to find performance bottlenecks in both hardware and software, including some surprising bottlenecks in the Linux 2.6.13 kernel.
Lightweight self-organizing frameworks for metacomputing

A novel component-based, service-oriented framework for distributed metacomputing is described. Adopting a provider-centric view of resource sharing, this project emphasizes lightweight software infrastructures that maintain a minimal state, and interface to current and emerging distributed computing standards. Resource owners host a software backplane onto which owners, clients, or third-party, resellers may load components or component-suites that deliver value added services without compromising owner security or control. Standards-based descriptions of services facilitate publication and discovery via established schemes. The architecture of the container framework, design of components, security and access control schemes, and preliminary experiences are described in this paper.
Challenges In Cross-Cultural Business Education

One of the most important and lasting legacies of the 20 th century is globalization and the increased integration among countries and economies leading to more interactions among the peoples of different cultures. This effect has also percolated into the business environment and into the realm of business education. We have seen the internationalization of the business curriculum, the creation of more study abroad programs for students, and the increased efforts towards exchange programs for educators. Conflicts in cross-cultural learning environments have been examined primarily from the perspective of the student, with limited research on the experiences of the teacher. We use Hofstedes (1980) cultural dimensions to identify the characteristics of teacher-student pairs from different cultures, explore the potential conflicts that may be created, and offer suggestions for developing strategies to be a globally competent teacher.
Network analysis of human post-mortem microarrays reveals novel genes, microRNAs, and mechanistic scenarios of potential importance in fighting huntington's disease.

Huntington's disease is a progressive neurodegenerative disorder characterized by motor disturbances, cognitive decline, and neuropsychiatric symptoms. In this study, we utilized network-based analysis in an attempt to explore and understand the underlying molecular mechanism and to identify critical molecular players of this disease condition. Using human post-mortem microarrays from three brain regions (cerebellum, frontal cortex and caudate nucleus) we selected in a four-step procedure a seed set of highly modulated genes. Several protein–protein interaction networks, as well as microRNA–mRNA networks were constructed for these gene sets with the Elsevier Pathway Studio software and its associated ResNet database. We applied a gene prioritizing procedure based on vital network topological measures, such as high node connectivity and centrality. Adding to these criteria the guilt-by-association rule and exploring their innate biomolecular functions, we propose 19 novel genes from the analyzed microarrays, from which CEBPA, CDK1, CX3CL1, EGR1, E2F1, ERBB2, LRP1, HSP90AA1 and ZNF148 might be of particular interest for experimental validation. A possibility is discussed for dual-level gene regulation by both transcription factors and microRNAs in Huntington's disease mechanism. We propose several possible scenarios for experimental studies initiated via the extra-cellular ligands TGFB1, FGF2 and TNF aiming at restoring the cellular homeostasis in Huntington's disease.
Medical care of patients with brain tumors.

Purpose of review Patients with brain tumors require close attention to medical issues resulting from their disease or its therapy. Effective medical management results in decreased morbidity and mortality and improved quality of life. The most frequent neurology-related issues that arise in these patients include seizures, peritumoral edema, venous thromboembolism, fatigue, and cognitive dysfunction. This article focuses on the most recent findings for the management of the most relevant medical complications among patients with brain tumors. Recent findings Increasing evidence suggests that anticoagulation in patients with thromboembolic complications is safe even when they are receiving antiangiogenic therapy. There are also increasing data to support the use of newer, non-enzyme-inducing antiepileptic drugs, which have the advantage of lacking interactions with antineoplastic agents and are as effective as their older counterparts at preventing seizures. Relatively few studies have addressed the management of fatigue and depression, and definitive recommendations cannot be made. Summary Corticosteroids to treat vasogenic edema should be used at the minimum amount required to control symptoms and should be tapered as quickly as possible. Anticonvulsants should be used only if patients have had seizures. Non-enzyme-inducing antiepileptic drugs are preferred to minimize interactions with concurrently administered chemotherapy. Thromboembolic complications are common and are preferably treated with low-molecular-weight heparins. Only patients with hemorrhagic complications require an inferior vena cava filter. Cognitive deficits are frequent in patients with brain tumors and include problems such as poor short-term memory, distractibility, personality change, emotional lability, loss of executive function, and decreased psychomotor speed. Stimulants can help to improve these symptoms.
Unplanned Readmission to the Pediatric Cardiac Intensive Care Unit: Prevalence, Outcomes, and Risk Factors.

Background:Factors leading to cardiac intensive care unit (CICU) readmission and the impact on mortality have yet to be well delineated. We sought to define the prevalence and outcome for unscheduled CICU readmission. Secondary objectives were to identify indications and risk factors for unscheduled CICU readmission.Methods:Retrospective analysis of prospectively collected registry data at a tertiary care children’s hospital. Pediatric and adult patients with congenital and acquired heart disease who survived to initial CICU discharge were included. Patients with unexpected return to the CICU for acute change in clinical status were defined as unscheduled readmissions.Results:Of the 645 discharges that met inclusion criteria, 37 resulted in unplanned readmission to the CICU. Patients requiring unscheduled readmission had higher mortality rates (16.2% vs 0.5%, P < .0001). Cardiac symptoms were the most common reason for readmission. On multivariate analysis, genetic anomaly (P = .001) and longer length of ...
Antimicrobial resistance in staphylococci.

Staphylococci have developed a variety of strategies for dealing with the presence of antibiotics encountered in clinical environments. Resistance to β-lactams and other antimicrobial agents has been accomplished by a diverse array of molecular mechanisms. Options available to treat infections caused by staphylococci resistant to methicillin are limited, and the next generation of antibiotics to be introduced, should glycopeptide resistance become an important clinical problem, is not yet on the horizon.
Schleiermacher’s Translation Theory and Varieties of Foreignization

AbstractForeignizing translation – allowing the features of the source language to influence the language of the target text – is the most prominent issue in the translation theory of the German romantics. Its major proponent, Friedrich Schleiermacher, saw it as key to the aesthetic and cultural education of the German nation. But what did foreignization in romantic practice look like? This article compares the work of August Wilhelm Schlegel, arguably the foremost romantic translator (though his work is not overtly foreignizing) with that of Johann Heinrich Voss, one of the period’s most heavily foreignizing translators and avowed enemy of all things romantic. The goal is to arrive at a fuller picture of the role played by foreignization in German romantic translation, both in theory and practice.
SU-C-204-04: Irradiation of Human Cell Lines Using Various Ions

Purpose: The purpose of this study is to investigate and quantify the biological effects of ion radiation using several human cell lines. We aim to answer the question of whether carbon ion the most ideal ion species for heavy ion radiotherapy. Methods: The cells were irradiated at different positions along the pristine Bragg peak of several ions with different atomic number. The biological effectiveness was evaluated using the clonogenic cell survival assay. Irradiation of three human lung cancer cell lines and a fibroblast cell line were undertaken using the charged particle beam at the NASA Space Radiation Laboratory at Brookhaven National Lab. Four mono-energetic ion beams (carbon, oxygen, helium and lithium) were used to irradiate the cells. Water or media-filled T25 flasks were lined up along the beam line so that the cell-containing surfaces of the flasks were placed at a specific depth along the pristine Bragg curve. Four depths along the curve, representing entrance point, rising peak, peak and distal fall off, were selected to determine biological effectiveness. Gaf-chromic films were placed between the flasks to monitor the irradiation as soon as it was finished. Results: For all ion radiations, the maximum cell killing effect occurs at either peak or distal fall off, depending on the cell lines. For instance, for the fibroblast cell line AGO1522, RBEs of 1.4, 1.2, 1.4 and 1.9 were observed at the Bragg peak for Helium, Lithium, Carbon and Oxygen ions. Comparing positions, RBEs of 0.9, 1.2, 1.4 and 1.8 were observed for carbon irradiation of AGO-1522 cells positions corresponding to entrance, rising peak, peak and distal fall off. Conclusion: RBE values differ with position in the Bragg peak, ion species and cell line. Ions other than carbon may prove more effective in certain irradiation conditions and may contribute to optimized heavy ion therapy.
Pathophysiology of Calcium, Phosphorus, and Magnesium in Chronic Kidney Disease

Calcium, phosphorus and magnesium homeostasis is altered in CKD. Hypocalcemia, hyperphosphatemia and hypermagnesemia are not seen until advanced CKD because adaptations develop. Increased parathyroid hormone secretion maintains S[Ca] within normal limits by increasing calcium efflux from bone, renal calcium reabsorption and phosphate excretion. Similarly, renal phosphate excretion in CKD is maintained by increased secretion of parathyroid hormone and fibroblast growth factor 23 (FGF23). However, the phosphaturic effect of FGF23 is reduced by downregulation of its cofactor Klotho, necessary for binding FGF23 to FGF receptors. Intestinal phosphate absorption is diminished in CKD due in part to reduced levels of 1,25 dihydroxyvitamin D. Unlike calcium and phosphorus, renal magnesium handling is not regulated by a hormone, but fractional excretion of magnesium increases as CKD progresses. Because 60 to 70% of magnesium is reabsorbed in the thick ascending limb of Henle, activation of the calcium-sensing receptor by magnesium may facilitate magnesium excretion in CKD. Modification of the TRPM6 channel in the distal tubule may also have a role in renal magnesium handling. Besides abnormal bone morphology and vascular calcification, abnormalities in mineral homeostasis are associated with increased cardiovascular risk, increased mortality and progression of CKD.
Neural Progenitor Cells Promote Axonal Growth and Alter Axonal mRNA Localization in Adult Neurons.

Abstract The inhibitory environment of the spinal cord and the intrinsic properties of neurons prevent regeneration of axons following CNS injury. However, both ascending and descending axons of the injured spinal cord have been shown to regenerate into grafts of embryonic neural progenitor cells (NPCs). Previous studies have shown that grafts composed of glial-restricted progenitors (GRPs) and neural-restricted progenitors (NRPs) can provide a permissive microenvironment for axon growth. We have used cocultures of adult rat dorsal root ganglion (DRG) neurons together with NPCs, which have shown significant enhancement of axon growth by embryonic rat GRP and GRPs/NRPs, both in coculture conditions and when DRGs are exposed to conditioned medium from the NPC cultures. This growth-promoting effect of NPC-conditioned medium was also seen in injury-conditioned neurons. DRGs cocultured with GRPs/NRPs showed altered expression of regeneration-associated genes at transcriptional and post-transcriptional levels. We found that levels of GAP-43 mRNA increased in DRG cell bodies and axons. However, hepcidin antimicrobial peptide (HAMP) mRNA decreased in the cell bodies of DRGs cocultured with GRPs/NRPs, which is distinct from the increase in cell body HAMP mRNA levels seen in DRGs after injury conditioning. Endogenous GAP-43 and β-actin mRNAs as well as reporter RNAs carrying axonally localizing 39UTRs of these transcripts showed significantly increased levels in distal axons in the DRGs cocultured with GRPs/NRPs. These results indicate that axon growth promoted by NPCs is associated not only with enhanced transcription of growth-associated genes but also can increase localization of some mRNAs into growing axons.
The Pagan City, the Christian City, and the Secular City

This essay, given as the first of three lectures comprising the Charles E. Test Lectures at the Madison program at Princeton in May 2017, initiates the project of defending T. S. Eliot’s suggestion that the future of Western societies will be determined by a contest between Christianity and “modern paganism.” The essay attempts to give an account of “paganism” as immanent religiosity, in contrast to the transcendent religiosity of later Judaism and Christianity. It then discusses the displacement of paganism by Christianity in late antiquity, but suggests (using Ronald Dworkin as the central example) that paganism has enjoyed a revival in recent times. Hence, our current cultural struggles are less helpfully thought of as clashes of “religion v. secularism” than as a struggle between competing forms of religiosity.
A unified approach to targeting the lysosome’s degradative and growth signaling roles

Lysosomes serve dual roles in cancer metabolism, executing catabolic programs (i.e., autophagy and macropinocytosis) while promoting mTORC1-dependent anabolism. Antimalarial compounds such as chloroquine or quinacrine have been used as lysosomal inhibitors, but fail to inhibit mTOR signaling. Further, the molecular target of these agents has not been identified. We report a screen of novel dimeric antimalarials that identifies dimeric quinacrines (DQ) as potent anticancer compounds, which concurrently inhibit mTOR and autophagy. Central nitrogen methylation of the DQ linker enhances lysosomal localization and potency. An in situ photoaffinity pulldown identified palmitoyl-protein thioesterase 1 (PPT1) as the molecular target of DQ661. PPT1 inhibition concurrently impairs mTOR and lysosomal catabolism through the rapid accumulation of palmitoylated proteins. DQ661 inhibits the in vivo tumor growth of melanoma, pancreatic cancer, and colorectal cancer mouse models and can be safely combined with chemotherapy. Thus, lysosome-directed PPT1 inhibitors represent a new approach to concurrently targeting mTORC1 and lysosomal catabolism in cancer.Significance: This study identifies chemical features of dimeric compounds that increase their lysosomal specificity, and a new molecular target for these compounds, reclassifying these compounds as targeted therapies. Targeting PPT1 blocks mTOR signaling in a manner distinct from catalytic inhibitors, while concurrently inhibiting autophagy, thereby providing a new strategy for cancer therapy. Cancer Discov; 7(11); 1266-83. ©2017 AACR.See related commentary by Towers and Thorburn, p. 1218This article is highlighted in the In This Issue feature, p. 1201.
Using Diagrams to Access a Case Base of Architectural Designs

We describe the linking of a ‘computer as cocktail napkin’ program that interprets hand-drawn sketches and diagrams with Archie III, a case based design aid, to support case-based reminding in conceptual design. The Archie case base includes stories, problems, and responses indexed and accessed by carefully chosen features. In addition to text, photographs, and drawings, many items in Archie’s case base are illustrated by simple diagrams. We have added these diagrams to Archie’s indexing scheme, so a hand-drawn sketch can be used to retrieve items tagged with similar diagrams.
Differential Correlation Detects Complex Associations Between Gene Expression and Clinical Outcomes in Lung Adenocarcinomas

We propose a simple data analysis procedure that aims to uncover an association between gene expression and the status of a clinical outcome variable. Rather than focus on differences in group means, as is usually done, we search for pairs of genes such that the strength or direction of their association is linked to the value of the outcome variable. This more complex pattern of gene expression, which we call “differential correlation”, may be especially relevant in studying clinical outcomes such as survival and grade, since it has often been difficult to identify marker genes whose mean expression varies directly with such outcomes. In applying our method to two lung cancer microarray data sets, we discovered that a substantially greater number of genes are likely to be associated with clinical outcomes such as tumor stage via differential correlation than are associated via changes in mean expression.
Mouse class 3 aldehyde dehydrogenases: positive and negative regulation of gene expression.

Class 3 aldehyde dehydrogenases include the 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD; dioxin)-inducible cytosolic form (ALDH3c) and the constitutive microsomal form (ALDH3m). Using the rat ALDH3c cDNA as a probe, we have cloned and sequenced the murine microsomal aldehyde dehydrogenase-3 (Aldh-3m) cDNA; the gene is located on mouse chromosome 11, and alignment with the rat ALDH3m amino acid sequence (Miyauchi et al., 1991) shows 95% identity [V. Vasiliou, C.A. Kozak, R. Lindahl and D.W. Nebert, manuscript in preparation]. We have also cloned and sequenced the murine Aldh-3c cDNA [V.V. and D.W.N., manuscript in preparation]. Using a variety of genetically different mice and cell culture lines, we have recently compared the positive and negative regulatory mechanisms of Aldh-3c and Aldh-3m gene expression (Vasiliou et al., 1992). Although both genes are TCDD-inducible, we have determined that the murine Aldh-3c, but not Aldh-3m, can be classified as a bona fide member of the murine aromatic hydrocarbon-responsive [Ah] battery. How we arrived at this classification is the principal subject of this Chapter.
Budgeting for Mandatory Spending: Prologue to Reform

This paper identifies a feature of the federal budget process that, consistent with the findings of behavioral research, increases the difficulty for policymakers of restraining the growth of mandatory spending to sustainable rates: budgetary accounting. Specifically, use of cash‐basis accounting, on‐budget payment accounts, and a narrow definition of debt defers recognition of the cost of mandatory spending until benefits are payable and politically unavoidable. Acting to control “future” costs is cognitively more difficult for decision‐makers than addressing cost now as obligated. The paper proposes a trial of alternative budgetary accounting for mandatory spending that saliently recognizes cost as it accrues.
Data Quality and Measurement Errors

Various system and environmental effects on the quality of polarimetric measurements are discussed in this chapter. It starts with calibration of the reflectivity factor Z and differential reflectivity ZDR. The biases in Z and ZDR caused by attenuation/differential attenuation in rain and hail as well as wet radome are illustrated and quantified. Various techniques for attenuation/differential attenuation correction at different radar wavelengths are described, and numerous results of correction are presented. The effects of partial beam blockage on the Z, ZDR, and ρhv fields are demonstrated, and ways to mitigate these are suggested. Contamination of radar signals by ground clutter is reviewed, the method used on the WSR-88D is briefly described, and potential of the polarimetric information to better identify ground clutter is suggested. Contamination of the radar variables by white noise is explained, and corrections are outlined. Progressive beam broadening with range and stronger impact of nonuniform beam filling are listed as culprits for the deterioration of polarimetric variables with range. These effects are demonstrated and approximately quantified. Depolarization by oriented ice crystals also affects the polarimetric variables, and some examples are included. Three-body scattering signature in differential reflectivity and correlation coefficient is shown and conceptually explained. Finally, statistical errors associated with computations of the polarimetric variables and spectral moments are quantified.
Co-clustering of High-order Data via Regularized Tucker Decompositions

Computational methods for identifying hidden structures in high-order data are critical for exploratory data analysis tasks. This work proposes a joint dimensionality reduction and co-clustering algorithm for tensors. A compressed representation of a tensor is obtained via a Tucker-like decomposition model, whose factor matrices capture the tensor co-clustering structure. Factor matrices correspond to the cluster centroids of the tensor fibers per mode, whose entries interact nonlinearly to build the tensor approximation. The algorithm, developed based on the alternating-direction method of multipliers, has computational complexity similar to that of a single Tucker decomposition.
Mass spectrometric study of drug binding to proteins

3182 The objective was to characterize intact complexes of drugs with proteins, particularly human serum albumin and a variety of enzymes using mass spectrometry to calculate the number of bound drug molecules. Drugs studied: (a) Antineoplastic: tamoxifen (372 Da); doxorubicin (544 Da), methotrexate (454 Da), bleomycin (1416 Da), suramin (1429 Da) and the novel benzyl styryl sulfone analog ON 1910Na (474 Da); (b) Other Drugs: Digoxin (791 Da); fluphenazine (438 Da), and trifluoroperazin (408 Da). Proteins studied: albumin (66 kDa) and the enzymes: papain (21 kDa), elastase (25 kDa), trypsin (24 kDa) and carbonic anhydrase (29 kDa). Methodology: One µL aliquots of incubates (30 min, 37°C) or plasma sample from patients on Phase I clinical trials with ON 01910.Na were injected directly into the ion source of a triple quadrupole mass spectrometer. Positive electrospray or nanospray mass spectra were obtained and molecular masses of the intact drug-protein complexes were obtained from multiple charged ion patterns. Results: (a) Complex formation between the drug and protein commenced immediately upon exposure. (b) Albumin-drug interactions yielded mixtures simultaneously containing complexes with a varying number of bound drug molecules, e.g., up to 21 molecules of tamoxifen per albumin molecule vs. only up to 8 molecules of digoxin per albumin; (c) The number of bound molecules for each drug was different for different enzymes, e.g., carbonic anhydrase attached 13 molecules of tamoxifen vs. 11 molecules of digoxin; (d) Drug binding followed an apparently discontinuous digital progression, e.g., 10, 11, 13, 17, 19, and 21 molecules of tamoxifen bound to albumin but not 12, 14, 15, 16, 18, or 20; (e) Similar unique phenomena occurred using several antineoplastic drugs as well as other drugs; and also using several different enzymes. We hypothesize that conformational changes caused by binding may account for the exclusion of certain binding complexes, and that conformational changes may influence protein behavior and enzymatic activity. (Supported by the T. J. Martell Foundation for Leukemia, Cancer and AIDS Research and by Onconova Therapeutics, Inc.)
Spin-phonon coupling and dynamic zero-field splitting contributions to spin conversion processes in iron(II) complexes.

Magnetization dynamics of transition metal complexes manifest in properties and phenomena of fundamental and applied interest [e.g., slow magnetic relaxation in single molecule magnets, quantum coherence in quantum bits (qubits), and intersystem crossing (ISC) rates in photophysics]. While spin–phonon coupling is recognized as an important determinant of these dynamics, additional fundamental studies are required to unravel the nature of the coupling and, thus, leverage it in molecular engineering approaches. To this end, we describe here a combined ligand field theory and multireference ab initio model to define spin–phonon coupling terms in S = 2 transition metal complexes and demonstrate how couplings originate from both the static and dynamic properties of ground and excited states. By extending concepts to spin conversion processes, ligand field dynamics manifest in the evolution of the excited state origins of zero-field splitting (ZFS) along specific normal mode potential energy surfaces. Dynamic ZFSs provide a powerful means to independently evaluate contributions from spin-allowed and/or spin-forbidden excited states to spin–phonon coupling terms. Furthermore, ratios between various intramolecular coupling terms for a given mode drive spin conversion processes in transition metal complexes and can be used to analyze the mechanisms of ISC. Variations in geometric structure strongly influence the relative intramolecular linear spin–phonon coupling terms and will define the overall spin state dynamics. While the findings of this study are of general importance for understanding magnetization dynamics, they also link the phenomenon of spin–phonon coupling across fields of single molecule magnetism, quantum materials/qubits, and transition metal photophysics.
Incidental findings: A practical protocol for reporting elevated depressive symptoms in behavioral health research.

Abstract Intervention studies conducted in caregivers often focus on improving mental health. Consequently, researchers may discover incidental findings like elevated depressive symptoms. Researchers have an ethical obligation to report incidental findings to participants, but no protocols exist for reporting behavioral health symptoms. The purpose of this paper was to describe a protocol for reporting elevated depressive symptoms to participants, based on the protocol used in a national randomized clinical trial of stress-reduction methods for 348 grandmothers raising grandchildren. Each questionnaire included the CES-D scale, and was scored immediately after completion. We established a cut-off score of 30 based on previous research. A registered nurse on the research team called participants with scores over 30 and ascertained whether the participant 1) was aware of the problem and 2) had sought help, and then offered additional resources. Overall, 94 (27%) participants had a CES-D score > 30. The majority (91%) were aware of the problem. About a third of the participants were on medication for their symptoms, and a third were seeing a therapist. Nine participants were not aware they had depressive symptoms. This paper outlines the ethical premise for developing our protocol, details of protocol development, and discussion for how research teams can apply this protocol to their work.
Learning from Studs Terkel: listening while making places and spaces for effective interviews during fieldwork

Human geographers use many types of research techniques, often in a mixed methods format where multiple approaches and technologies are incorporated in a single study. This reflects the synthetic n...
A Novel Machine Learning Approach to Estimating KPI and PoC for LTE-LAA-Based Spectrum Sharing

Machine learning (ML) approaches have been extensively exploited to model and to improve wireless communication networks in the past few years. Nonetheless, the estimation of key performance indicators (KPIs) and their uncertainties in Long Term Evolution License Assisted Access (LTE-LAA) based coexistence systems is not adequately addressed. For example, it is not clear if an ML method can accurately predict achievable KPIs (e.g. throughput) and the probability of coexistence (PoC) of LTE-LAA coexistence systems based on partial or no information of MAC and physical layer protocols and parameters. In this paper, we develop a novel ML method by combining a neural network with a logistic regression algorithm to track and estimate KPIs and PoC of coexisting LTE-LAA and wireless local area network (WLAN) links. This ML method can be applied when KPI samples at the base stations (BSs) and access points (APs) are available, without using knowledge of MAC and physical layer parameters. Comparison between the ML and simulation results indicate that the proposed ML method can track the system KPIs and predict the system PoC with good accuracy.
Managing structural variability in agent-based models with feature coherence graphs

Exploratory modelling requires not only parametric but also structural and representational variability. The ability to systematically vary and experiment with multiple model features is paramount for problems that involve uncertainty and representational ambiguity. To facilitate such variation, a coherence-driven strategy is introduced for the management and evaluation of feature selections. The feature coherence specification and its associated metaprogramming system open new avenues for programmable abductive model building, as well as model introspection while automating the selection of model variants in the context of an evolving analysis. As learning takes place through simulation experiments, an increasingly accurate feature coherence model emerges to serve as an explanatory model that reveals which features cohere and are conducive to generating targeted systemic behaviours.