cssi/SciSciGPT-SciSciNet huggingface dataset:
Leucine supplementation differentially enhances pancreatic cancer growth in lean and overweight mice

The risk of pancreatic cancer, the 4th deadliest cancer for both men and women in the United States, is increased by obesity. Calorie restriction (CR) is a well-known dietary regimen that prevents or reverses obesity and suppresses tumorigenesis in a variety of animal models, at least in part via inhibition of mammalian target of rapamycin (mTOR) signaling. Branched-chain amino acids (BCAA), especially leucine, activate mTOR and enhance growth and proliferation of myocytes and epithelial cells, which is why leucine is a popular supplement among athletes. Leucine is also increasingly being used as a treatment for pancreatic cancer cachexia, but the effects of leucine supplementation on pancreatic tumor growth have not been elucidated. Supplementation with leucine increased pancreatic tumor growth in both lean (104 ± 17 mm3 versus 46 ± 13 mm3; P <0.05) and overweight (367 ± 45 mm3 versus 230 ± 39 mm3; P <0.01) mice, but tumor enhancement was associated with different biological outcomes depending on the diet. In the lean mice, leucine increased phosphorylation of mTOR and downstream effector S6 ribosomal protein, but in the overweight mice, leucine reduced glucose clearance and thus increased the amount of circulating glucose available to the tumor. These findings show that leucine supplementation enhances tumor growth in both lean and overweight mice through diet-dependent effects in a murine model of pancreatic cancer, suggesting caution against the clinical use of leucine supplementation for the purposes of skeletal muscle enhancement in cachectic patients.
Reflections on Putin and the Media

A political scientist investigates the extent to which, under Vladimir Putin, the Kremlin consolidated control over the Russian media. Conceptually, a contrast is drawn between the Soviet and post-Soviet systems of media control. Data-bases are used to illuminate imbalances of television coverage of presidential candidates and public officials as well as the evolution of popular distrust of the media. Comparisons are drawn with President Alberto Fujimori's defunct regime in Peru and speculation is offered as to the fragility of the Kremlin's control over the media.
Work in Progress: Introduction to Engineering Ethics through Student Skits in the Freshman Engineering Program at Virginia Tech

An engineering ethics assignment through student skits was piloted in the spring 2006 with 180 freshman students enrolled in an introductory engineering course at Virginia Tech. Students, assigned into groups of 4-8, were given one of five ethics case studies documenting realistic engineering scenarios, a set of guidelines, a performance assessment rubric, and instructed to prepare a 5-10 minute skit integrating the essential elements of the given case study. The student groups were given two weeks to organize, prepare, and practice before performing their skit for the class. Students were required to complete a hand-out, provided during the skit session, identifying which of twelve Rules of Practice as part of the National Society of Professional Engineers (NSPE) ethical codes had been violated and provide a brief response to a set of open-ended ethical questions. Results of the student hand-out, student surveys and focus group interviews are discussed.
Error control coding of television signals by multidimensional filtering

The design of image prefilters for error control is considered and seen to be dual to the well-known problem of designing anti-aliasing filters for signal decimation. Filters formed from unitary transforms are seen to yield computationally efficient two-step implementations obtained by orthogonal decomposition. Filters which perform optimally in the presence of background noise are introduced and seen to require only P multiplications for each column of N pixels, where P=2 and N=240 for TV signals in NTSC format. The amount of signal distortion due to this prefiltering is small and often imperceptible. >
Melanchthonian Method as a Guide to Reading Confessions of Faith: The Index of the Book of Concord and Late Reformation Learning

Horst Kunze, the contemporary German authority on indexing, writes, “An index is not a tool that has its own independent existence. It is an aid for the use of another literary object. It is like a signpost. Like a signpost it has no other purpose than to point the way in certain directions.” Indices seldom attract scholarly investigation. Casual users accept the index as a more or less objective guide to the contents of a book. However, the index prepared in 1580 for the initial publication of the Book of Concord, appearing in several of its first printings, was designed to point in specific directions, to cultivate a particular way for its primary audience to read the volume and put it to use. It took the form of loci communes—topics—as they had been developed a generation earlier by Martin Luther's Wittenberg colleague Philip Melanchthon for the proper, fruitful, study of theology. By selecting the doctrinal topics and categories into which pastors and teachers were to organize the content of this volume for their own use, this index offers one of the first theological commentaries on the Book of Concord. The index also reveals how Melanchthon's theological method continued to dominate the way the heirs of the Wittenberg Reformation thought—in spite of the fact that it directs readers away from and against the theology of some of Melanchthon's followers whom scholars have dubbed with his name, “Philippists.” (In fact, some contemporaries objected to the Book because they believed it to be anti-Melanchthonian.)
Biological Responses in Known Bystander Cells Relative to Known Microbeam-Irradiated Cells

Abstract Ponnaiya, B., Jenkins-Baker, G., Brenner, D. J., Hall, E. J., Randers-Pehrson, G. and Geard, C. R. Biological Responses in Known Bystander Cells Relative to Known Microbeam-Irradiated Cells. Radiat. Res. 162, 426–432 (2004). Normal human fibroblasts in plateau phase (≅95% G1 phase) were stained with the vital nuclear dye Hoechst 33342 (blue fluorescence) or the vital cytoplasmic dye Cell Tracker Orange (orange fluorescence) and plated at a ratio of 1:1. Only the blue-fluorescing nuclei were microbeam-irradiated with a defined number of 90 keV/μm α particles. The orange-fluorescing cells were then “bystanders”, i.e. not themselves hit but adjacent to cells that were. Hit cells showed a fluence-dependent induction of micronuclei as well as delays in progression from G1 to S phase. Known bystander cells also showed enhanced frequencies of micronuclei (intermediate between those seen in irradiated and control cells) and transient cell cycle delays. However, the induction of micronuclei in bystander c...
You can't always get what you want: educational attainment, agency, and choice

Using educational attainment to indicate socioeconomic status, the authors examined models of agency and effects of choice among European American adults of different educational backgrounds in 3 studies. Whereas college-educated (BA) participants and their preferred cultural products (i.e., rock music lyrics) emphasized expressing uniqueness, controlling environments, and influencing others, less educated (HS) participants and their preferred cultural products (i.e., country music lyrics) emphasized maintaining integrity, adjusting selves, and resisting influence. Reflecting these models of agency, HS and BA participants differently responded to choice in dissonance and reactance paradigms: BA participants liked chosen objects more than unchosen objects, but choice did not affect HS participants' preferences. Results suggest that HS and BA models of agency qualitatively differ, despite overlap between HS and BA worlds.
General method for calculation of hydrogen-ion concentration in multicomponent acid-base mixtures

A generalized method for the rapid evaluation of complicated ionic equilibria in terms of the hydrogen-ion concentration was developed. The method was based on the derivation of a single general equation that could be used to evaluate any mixture. A tableau method also was developed which allowed calculation of the numerical solution to the general equation without computer analysis or graphical or intuitive approximations. Examples illustrating the utility of the method are presented. These examples include a mixture of barbital, citric acid, boric acid, monobasic sodium phosphate, and sodium hydroxide. Calculated hydrogen-ion concentrations showed good agreement with experimental values for simple and complex solutions. The major advantages of the method are its simplicity and the obtainment or numerical solutions without initial approximations in the calculations. However, activity corrections are not included in the calculations.
Liver-directed therapies in metastatic colorectal cancer

Colorectal cancer (CRC) is a major health concern in the United States (US) with over 140,000 new cases diagnosed in 2012. The most common site for CRC metastases is the liver. Hepatic resection is the treatment of choice for colorectal liver metastases (CLM), with a 5-year survival rate ranging from 35% to 58%. Unfortunately, only about 20% of patients are eligible for resection. There are a number of options for extending resection to more advanced patients including systemic chemotherapy, portal vein embolization (PVE), two stage hepatectomy, ablation and hepatic artery infusion (HAI). There are few phase III trials comparing these treatment modalities, and choosing the right treatment is patient dependent. Treating hepatic metastases requires a multidisciplinary approach and knowledge of all treatment options as there continues to be advances in management of CLM. If a patient can undergo a treatment modality in order to increase their potential for future resection this should be the primary goal. If the patient is still deemed unresectable then treatments that lengthen disease-free and overall-survival should be pursued. These include chemotherapy, ablation, HAI, chemoembolization, radioembolization (RE) and stereotactic radiotherapy.
Disenchanting the World: The Impact of Technology on Relationships

We explore the impact of technology on the strength of friendship ties. Data come from about two millions ties that members of CouchSurfing—an international hospitality organization whose goal is to promote travelling and friendship between its members—developed between 2003 and 2011 as well as original and secondary ethnographic data. The community, and the data available about its members, grew exponentially during our period of analysis, yet friendships between users tended to be stronger in the early years of CouchSurfing, when the online reputation system was still developing and the whole network was enmeshed in considerable uncertainty. We argue that this case illustrates a process of disenchantment created by technology, where technology increases the ease with which we form friendships around common cultural interests and, at the same time, diminishes the bonding power of these experiences.
Arithmetical Results, Dirichlet Series

We begin this chapter with a discussion of the sieve method of Selberg [1]. We shall confine ourselves to a result which is sufficient for our future needs. Its proof is not long.
The association between maternal height and pregnancy outcomes in twin gestations

AbstractObjective: We sought to assess the association between maternal height and the risk of preterm birth, fetal growth restriction and mode of delivery in twin gestations.Study design: Cohort study of patients with twin pregnancies delivered from 2005 to 2014. We compared pregnancy outcomes between patients of short stature ≤159 cm to those of normal stature ≥160 cm. Patients with monoamniotic twins and major fetal anomalies were excluded. Pearson’s correlation, Chi-square and Student’s t-test were used as appropriate.Results: Six hundred and sixty-six patients were included, 159 (23.9%) of whom had short stature (mean height 155.8 ± 2.5 cm) and 507 (76.1%) of whom had normal stature (mean height 167.2 ± 5.5 cm). There were no differences in outcomes between the groups in regards to preterm birth, gestational age (GA) at delivery, birth weight of either twin, preeclampsia, gestational diabetes or cesarean section rate. Results were similar when the groups were stratified by parity. As a continuous var...
Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems

The NOP receptor (nociceptin/orphanin FQ opioid peptide receptor) is the most recently discovered member of the opioid receptor family and, together with its endogenous ligand, N/OFQ, make up the fourth members of the opioid receptor and opioid peptide family. Because of its more recent discovery, an understanding of the cellular and behavioral actions induced by NOP receptor activation are less well developed than for the other members of the opioid receptor family. All of these factors are important because NOP receptor activation has a clear modulatory role on mu opioid receptor-mediated actions and thereby affects opioid analgesia, tolerance development, and reward. In addition to opioid modulatory actions, NOP receptor activation has important effects on motor function and other physiologic processes. This review discusses how NOP pharmacology intersects, contrasts, and interacts with the mu opioid receptor in terms of tertiary structure and mechanism of receptor activation; location of receptors in the central nervous system; mechanisms of desensitization and downregulation; cellular actions; intracellular signal transduction pathways; and behavioral actions with respect to analgesia, tolerance, dependence, and reward. This is followed by a discussion of the agonists and antagonists that have most contributed to our current knowledge. Because NOP receptors are highly expressed in brain and spinal cord and NOP receptor activation sometimes synergizes with mu receptor-mediated actions and sometimes opposes them, an understanding of NOP receptor pharmacology in the context of these interactions with the opioid receptors will be crucial to the development of novel therapeutics that engage the NOP receptor.
Exploring the catalytic mechanism of alkanesulfonate monooxygenase using molecular dynamics.

The complex mechanistic properties of alkanesulfonate monooxygenase (SsuD) provide a particular challenge for identifying catalytically relevant amino acids. In response, a joint computational and experimental study was conducted to further elucidate the SsuD mechanism. Extensive unbiased molecular dynamics (MD) simulations were performed for six SsuD systems: (1) substrate-free, (2) bound with FMNH2, (3) bound with a C4a-peroxyflavin intermediate (FMNOO–), (4) bound with octanesulfonate (OCS), (5) co-bound with FMNH2 and OCS, and (6) co-bound with FMNOO– and OCS. A previous theoretical study suggested that salt bridges between Arg297 and Glu20 or Asp111 initiated conformational changes critical for catalysis. However, our MD simulations and steady-state kinetic experiments did not corroborate this result. Similar kcat/Km values for both the E20A and D111A SsuD variants to wild-type SsuD suggest that the salt bridges are not critical to the desulfonation mechanism. Instead, the predicted role of Arg297 is...
COURTSHIP BEHAVIOR AND CONTROL OF REPRODUCTIVE ISOLATION IN DROSOPHILA MOJAVENSIS.

Etude experimentale pour identifier le ou les moments specifiques, pendant la periode d'interactions male-femelle avant copulation, pour lesquels l'appariement entre individus de populations differentes se revele impossible
Crystal Engineering with the Uranyl Cation III. Mixed Aliphatic Dicarboxylate/Aromatic Dipyridyl Coordination Polymers: Synthesis, Structures, and Speciation

Seven novel U(VI)-bearing compounds have been synthesized using hydrothermal conditions and characterized via single crystal X-ray diffraction. These materials are the result of systematically pairing aliphatic dicarboxylic acids and dipyridyl (1,2-bis(4-pyridyl)ethane and trans-1,2-bis(4-pyridyl)ethylene) molecules with the uranyl cation and are a conclusion to parts I and II of this study. A common factor of this family of materials is that the carboxylate group preferentially coordinates to the uranyl center, whereas the dipyridyl plays one of two roles: space filling or direct coordination uranyl cation. The role of the dipyridyl appears to be directly related not only to the length of the aliphatic dicarboxylate with which it is paired but also to the rigidity of the dipyridyl species. Further, this family of materials shows a tendency toward specific primary and secondary building units formed by the oligomerization of the uranyl cation despite the diversity suggested by other studies. This tendency...
Abstract 1633: The sphingosine kinase inhibitor SKI-II blocks survival and MAPK signaling in human breast cancer in vitro

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Endocrine resistance is a major contributor to treatment failure in breast cancer. A close examination of the signaling mechanisms by which cells may impart their resistance presents an attractive strategy for the development of viable treatment options. Sphingosine kinase (SK), and its product, sphingosine-1-phosphate (S1P), have been increasingly implicated in many disease states and SK/S1P signaling is a known regulator of apoptosis and cell survival. Furthermore, inhibition of sphingosine kinase has been shown to be anti-proliferative as well as apoptotic in a multitude of human cancer cell lines. In this study, we investigated the biological activity of the sphingosine kinase inhibitor, SKI-II (4-[[4-(4-Chlorophenyl)-2-thiazolyl]amino]phenol) and its ability to disrupt cell signaling in estrogen-dependent and endocrine-resistant breast cancer. SKI-II blocked both viability and survival at low micromolar IC50 concentrations in endocrine therapy-resistant MDA-MB-231, MDA-MB-468 and MDA-MB-361 cells in addition to endocrine therapy-sensitive MCF-7 breast cancer lines. Additionally, treatment with SKI-II significantly (p<0.05) decreased proliferation, as seen in Ki-67 immunostaining. The potent biological activity of this inhibitor led us to characterize the precise molecular mechanisms in which SKI-II imparts its effects. Sphingosine kinase is known to affect various signaling cascades, and its effect on the MAPK and PI3K/Akt pathways are cell line dependent. Growth factor signals such as MAPK can cross-talk with estrogen receptor and confer hormone therapy resistance. Therefore, we chose to investigate several signaling cascades to determine if SK inhibition mediates its effect through disruption of signaling. SKI-II diminished phosphorylation of ERK1/2 in both a time-dependent and dose-dependent manner. Treatment with SKI-II also inhibited phosphorylation of p38/MAPK at similar concentrations. This blockade of MAPK signaling may contribute to SKI-II's dual anti-cancer effect, which can target ER activation in an estrogen-dependent and an estrogen-independent manner. Targeting the production of sphingosine-1-phosphate through pharmacological inhibition presents a potentially useful method to reset the cell signaling aberrations -which lead to endocrine resistance, and may contribute to overall greater efficacy of current therapeutic interventions by re-sensitizing cells to endocrine therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1633.
Energy conservation and consumption reduction by TRT in Meishan Steel & Iron Corporation

TRT is a generating unit of energy conservation and environmental protection. The article introduces the operation status of units facility technology, main factor affecting TRT generating and energy conservation technique reformation of the three units. Through the detailed measures such as changing decompression valve, cleaning up lamina ashes on schedule, decreasing pipe pressure, installing high voltage evaporator and reforming of decompression valve executive machine, the above pressure of high boiler gets along with stable states. The economy of the units has been improved and the energy conservation effect is better.
Intra-arterial chemotherapy as an adjuvant to surgery in transitional cell carcinoma of the bladder.

AbstractRegional chemotherapy with intra-arterial cis-platinum and doxorubicin as an adjuvant to total cystectomy and urinary diversion has been evaluated in a phase I to II study. In the first 17 patients chemotherapy consisted of 40 to 75mg. per m.2 cis-platinum intra-arterially during 30 minutes, 30 to 40mg. per m.2 doxorubicin intra-arterially during 60 minutes (11 patients) or 12 hours (6 patients) and 400 to 500mg. per m.2 cyclophosphamide intravenously. The remaining 8 patients received 70 to 100mg. per m.2 cis-platinum intra-arterially during 30 minutes. Intra-arterial chemotherapy was administered through a percutaneous catheter placed in the hypogastric artery before each course. Courses were repeated at 4-week intervals. A total of 25 patients received 58 courses (median 2 per patient). Clinical stages of disease in the patients entering the protocol were T3aNxMo (8), T3bNx-2Mo (12) and T4a-bNxMx-1 (5). Clinical response was assessed in 24 of 25 patients: 6 achieved a complete clinical response...
A new approach for quantitative analysis of l-phenylalanine using a novel semi-sandwich immunometric assay

Here, we describe a novel method for l-phenylalanine analysis using a sandwich-type immunometric assay approach for use as a new method for amino acid analysis. To overcome difficulties of the preparation of high-affinity and selectivity monoclonal antibodies against l-phenylalanine and the inability to use sandwich-type immunometric assays due to their small molecular weight, three procedures were examined. First, amino groups of l-phenylalanine were modified by “N-Fmoc-l-cysteine” (FC) residues and the derivative (FC-Phe) was used as a hapten. Immunization of mice with bovine serum albumin/FC-Phe conjugate successfully yielded specific monoclonal anti-FC-Phe antibodies. Second, a new derivatization reagent, “biotin linker conjugate of FC-Phe N-succinimidyl ester” (FC(Biotin)-NHS), was synthesized to convert l-phenylalanine to FC-(Biotin)-Phe as a hapten structure. The biotin moiety linked to the thiol group of cysteine formed a second binding site for streptavidin/horseradish peroxidase (HRP) conjugates for optical detection. Third, a new semi-sandwich-type immunometric assay was established using pre-derivatized l-phenylalanine, the monoclonal anti-FC-Phe antibody, and streptavidin/HRP conjugate (without second antibody). Using the new “semi-sandwich” immunometric assay system, a detection limit of 35 nM (60 amol per analysis) and a detection range of 0.1–20 μM were attained using a standard l-phenylalanine solution. Rat plasma samples were analyzed to test reliability. Intra-day assay precision was within 6 % of the coefficient of variation; inter-day variation was 0.1 %. The recovery rates were from 92.4 to 123.7 %. This is the first report of the quantitative determination of l-phenylalanine using a reliable semi-sandwich immunometric assay approach and will be applicable to the quantitative determination of other amino acids.
Associations between Tobacco, Alcohol, and Drug Use with Coronary Artery Plaque among HIV-Infected and Uninfected Men in the Multicenter AIDS Cohort Study.

Background We characterized associations between smoking, alcohol, and recreational drug use and coronary plaque by HIV serostatus within the Multicenter AIDS Cohort Study (MACS).
CONSTITUTIVE EQUATIONS FOR THE COMPUTING PERSON

Publisher Summary This chapter discusses some of the precautions required while choosing a constitutive equation when setting out to do computing. Depending on the kinematic problem in hand, one of the several mathematical representations of the material can be chosen. The chapter discusses the behavior of (1) rate-type equations; (2) Green–Rivlin or integral type expansions, and (3) differential constitutive equations. The rate-type equations include the Criminale–Ericksen-Filbey equation, which is an exact representation of isotropic fluid behavior in viscometric flows. The chapter describes the stability of the rheological problem. Sometimes, there might be genuine flow instability, which is observable experimentally. Another cause of problems is lack of convergence because of inadequate numerical schemes. However, assuming that these problems have been avoided, there still remains the possibility that the description of the material, constitutive equation, chosen is the cause of lack of convergence.
The influence of seed dispersal mechanisms on the genetic structure of plant populations

The plant electrophoretic literature was reviewed to determine whether seed dispersal mechanisms effectively predict the distribution of genetic variation within and among plant populations. To consider the relationship between seed dispersal and genetic differentiation on a local scale, nine species of tropical trees from the same lowland forest community in Panama were examined electrophoretically. In both cases, the association between seed dispersal and the distribution of genetic variation was not as significant as expected. To better understand the processes underlying the development of genetic structure within plant populations, the genetic consequences of two generalized patterns of seed dispersal were explored. In the Platypodium model, seeds were wind disseminated and leptokurtically distributed, while the Piper model had the highly clumped dispersal pattern characteristic of many species with animalingested seeds. Variable breeding structures and the selective mortality of seeds and seedlings were also incorporated, since these factors can have important effects on population structure. The problem of obtaining quantitative estimates of these evolutionary parameters from natural populations is discussed. An analytical procedure (paternity exclusion analysis) is suggested which could be instrumental in elucidating those mechanisms which interact to produce genetic structure in natural plant populations.
The synthesis of phosphate and vanadate apatites using an aqueous one-step method

Abstract A modification of the aqueous addition method for the synthesis of apatites is described. This one-step method does not require addition of reagents and no adjustment of solution pH and therefore requires less equipment and less time than the traditional aqueous addition method. It can be used with a variety of starting materials to produce both phosphate and vanadate apatites with good purity and yield. The method generally produces smaller crystallites with average size in the 30–50 nm range. The effects of synthesis variables such as the nature of the reactants, control of pH, and digestion temperature and time are discussed.
Technology scaling effects on the ESD design parameters in sub-100 nm CMOS transistors

A new phenomenon, reported in this paper for the first time, produces a dramatic reduction of the nMOS and pMOS triggering voltage (V/sub Tl/) under ESD conditions for an ultra-scaled 90 nm CMOS technology used in high performance applications. This V/sub Tl/ reduction is caused by the merging of pocket implants in short gate length transistors. This has a serious impact on the ESD sensitivity of output drivers, placing restrictions on the design of effective protection devices and burn-in voltage during product screening.
Fragmentation of Red Cell Ghosts in Relation to the Problem of Red Cell Structure

Human red cell ghosts are prepared by methods which yield ghosts with a volume between one-half and one-fifth that of the intact red cell. These ghosts, when heated to temperatures between 49 and 54°C, break into a number of fragments whose total volume is approximately the same as that of the ghost before it fragmented. This indicates that the ghosts prepared by these methods are solid bodies rather than hollow shells. The ghosts contain from one-third to one-fifteenth of the Hb of the intact red cell, probably as an integral part of their structure. This structure is discussed in relation to a proposed structure for the red cell itself. The evidence points to the red cell being composed of lipid, Hb and proteins other than Hb, to these being oriented to a decreasing, but never negligible, extent from without inwards, and to the properties of the ghost (volume, Hb content, chemical composition, etc.) being largely dependent on the way in which it is prepared.
An Introduction to Survival Analysis

Publisher Summary Survival analysis makes inference about event rates as a function of time. This chapter provides an introduction to some commonly used statistical methods for the analysis of survival time data in medical research. The two primary methods to estimate the true underlying survival curve are Kaplan–Meier and Cox regression. Kaplan–Meier is simple and supports stratification factors, but cannot evaluate covariates. The Cox model does provide a framework for making inferences about covariates and requires proportional hazards, although it is quite flexible when used and interpreted correctly. Independent censoring, either directly in the Kaplan–Meier or given covariates in the Cox model, is a requirement for consistent unbiased estimates. Survival analysis can handle right censoring, staggered entry, recurrent events, competing risks, and much more as long as we have available representative risk sets at each time point to allow users to model and estimate event rates. The analysis of survival time data is complicated by the fact that the follow-up length is often different for each participant, and the event of interest, such as myocardial infarction, is often not observed in all the subjects by the end of the study. For those participants in whom the event is not observed, what is known is that their survival times are longer than their time spent in the study, but their exact survival times are unknown. The chapter also discusses features of survival time data and product-limit estimator for the survival function.
Protein Tertiary Structure Prediction

One of the most important scientific achievements of the twentieth century was the discovery of the DNA double helical structure by Watson and Crick in 1953. Strictly speaking, the work was the result of a three-dimensional modeling conducted partly based on data obtained from x-ray diffraction of DNA and partly based on chemical bonding information established in stereochemistry. It was clear at the time that the x-ray data obtained by their colleague Rosalind Franklin were not sufficient to resolve the DNA structure. Watson and Crick conducted one of the first-known ab initio modeling of a biological macromolecule, which has subsequently been proven to be essentially correct. Their work provided great insight into the mechanism of genetic inheritance and paved the way for a revolution in modern biology. The example demonstrates that structural prediction is a powerful tool to understand the functions of biological macromolecules at the atomic level. We now know that the DNA structure, a double helix, is rather invariable regardless of sequence variations. Although there is little need today to determine or model DNA structures of varying sequences, there is still a real need to model protein structures individually. This is because protein structures vary depending on the sequences. Another reason is the much slower rate of structure determination by x-ray crystallography or NMR spectroscopy compared to gene sequence generation from genomic studies. Consequently, the gap between protein sequence information and protein structural information is increasing rapidly. Protein structure prediction aims to reduce this sequence–structure gap.
Design of Lotteries and Waitlists for Affordable Housing Allocation

We study a setting in which dynamically arriving items are assigned to waiting agents, who have heterogeneous values for distinct items and heterogeneous outside options. An ideal match would both target items to agents with the worst outside options, and match them to items for which they have high value. Our first finding is that two common approaches -- using independent lotteries for each item, and using a waitlist in which agents lose priority when they reject an offer -- lead to identical outcomes in equilibrium. Both approaches encourage agents to accept items that are marginal fits. We show that the quality of the match can be improved by using a common lottery for all items. If participation costs are negligible, a common lottery is equivalent to several other mechanisms, such as limiting participants to a single lottery, using a waitlist in which offers can be rejected without punishment, or using artificial currency. However, when there are many agents with low need, there is an unavoidable tradeoff between matching and targeting. In this case, utilitarian welfare may be maximized by focusing on good matching (if the outside option distribution is light-tailed) or good targeting (if it is heavy-tailed). Using a common lottery achieves near-optimal matching, while introducing participation costs achieves near-optimal targeting.
Pharmacogenetics of Solid Tumors: Directed Therapy in Breast, Lung, and Colorectal Cancer: A Paper from the 2008 William Beaumont Hospital Symposium on Molecular Pathology

Genetic variability in drug-metabolizing enzymes and signaling pathways affects chemotherapy-related toxicity and treatment outcome in cancer. In breast and colorectal cancer, polymorphisms in metabolic enzymes involved in tamoxifen and irinotecan therapies has led the U.S. Food and Drug Administration to address genetic factors relevant to patient consideration of treatment with these compounds. Tamoxifen therapeutic failure in breast cancer has been associated with reduced CYP2D6 activity due to inefficient activation of tamoxifen. Irinotecan toxicity in colorectal cancer is more common in patients with reduced-activity UGT1A alleles, resulting in excessive exposure to the potent SN-38 metabolite. In colorectal and lung cancers, somatic mutations in the epidermal growth factor receptor and downstream signaling molecules have been associated with the therapeutic outcome of epidermal growth factor receptor-directed therapies. This review discusses the current knowledge regarding the utility of single gene—UGT1A1, CYP2D6, EGFR, and KRAS—or multigene analysis, for optimizing breast, colorectal, and lung cancer therapy. Current advances in these areas highlight how pharmacogenetics help personalized decision-making for patient management.
Reconciling fracture toughness parameter contradictions in thin ductile metal sheets

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purpose.
NEAREST NEIGHBOR RULE CLASSIFICATION OF STATIONARY AND NONSTATIONARY TIME SERIES

A unified methodological nearest neighbor rule approach is introduced for the classification of stationary and nonstationary time series. In that approach a measure of dissimilarity is computed between a new to-be-classified time series and each of a set of categorically labeled sample time series. The new time series is classified with the label of the particular time series which is least dissimilar. The dissimilarity measure between the time series is computed as an estimate of the Kullback-Leibler number between the corresponding time series populations as if the time series were normally distributed. The population screening classification problem and the normalized baseline classification problems are distinguished. The probability of misclassification properties of the nearest neighbor rule method are developed for each variety of classication problem. The methodology is applied in depth to population screening problems including the classification of anesthesia levels of humans in surgery by the analysis of stationary time series electroencephalograms and a study of the information for discrimination in human evoked potentials that is based upon the analysis of ensembles of time series with mean value time functions and nonstationary covariances. The emphasis in the normalized baseline classification problem examples is in the automatic classification of faults in rotating machinery in which the time series may be considered to be stationary, locally stationary or have a mean value time function and a stationary covariance.
Images of the Global Hispanophone: Transnational Iconography in Saharaui Literature

ABSTRACTThis study focuses on the linguistic iconography of Saharaui refugee poets who write in Spanish from a transnational perspective between Spain and its former colonial territories in the Western Sahara. It analyzes the interplay between Western cultural icons and Saharaui iconography in the protest poetry of Bubisher (2003) and Um Draiga (2006) and argues that both works juxtapose traditional Saharaui and Western iconographic forms to critique dominant Western narratives, affirm historical memory, and argue for political and cultural sovereignty.
Proviral sequencing suggests the majority of the HIV reservoir is expressed over time but significant decay is obscured by clonal expansion

After initiating antiretroviral therapy (ART), a rapid decline in plasma viremia is followed by reservoir stabilization. Viral outgrowth assay suggests the reservoir continues to decline slowly, but variation over time and among individuals complicates our understanding of selective pressures during ART. We used full-length sequencing to study more than 800 HIV proviruses of two subjects on ART at four time points over nine years to investigate the selection pressures influencing the dynamics of the reservoir. We found that intact as well as defective proviruses capable of significant protein expression decrease over time. Moreover, proviruses lacking genetic elements to promote viral protein expression, yet containing strong splice donor sequences increase relative to other defectives over time, especially among clones. Our work suggests that HIV expression occurs to a significant extent during ART and results in HIV clearance, but this is obscured by clones generated by donor splice site-enhanced clonal expansion.
CHAPTER 1 – HISTORICAL NOTES

Publisher Summary This chapter presents a chronological list of events that place the present into the context of the past. The events, from 1944 to 1969, are significant in the development of mathematical software and computer science. The first issues of the journal Mathematical Tables and Aids to Computation (MTAC) were primarily concerned with tables of mathematical functions. One can view these tables as the precomputer analogs of mathematical software, but there was nothing therein that one could view at present as mathematical software. These were small sections entitled Mechanical Aids to Computation, which contained mostly reviews of books. MTAC evolved into the primary publication medium for computer science and excluded almost all of computer science not associated with numerical analysis or number theory. In 1944, a computer-oriented article was issued that discussed variable spacing of tabulated functions so as to minimize the number of cards needed to give a specified accuracy with a particular interpolation scheme.
Infection with Persister Forms of Staphylococcus aureus Causes a Chronic Persistent Skin Infection with More Severe Lesion that Takes Longer to Heal and is not Eradicated by the Current Recommended Treatment in Mice

Staphylococcus aureus is an opportunistic pathogen that can cause persistent infections clinically. Treatment for chronic S. aureus infections ranges from at least one week to several months and such infections are prone to relapse likely due to the presence of persistent forms of bacteria such as persister cells. Persister cells, which are bacterial cells that become dormant under stress conditions, can be isolated in vitro but their clinical significance in in vivo infections are largely unclear. Here, we evaluated S. aureus persistent forms using stationary phase cultures and biofilm bacteria (enriched in persisters) in comparison with log phase cultures in terms of their ability to cause disease in a mouse skin infection model. Surprisingly, we found that infection of mice with stationary phase cultures and biofilm bacteria produced a more severe chronic skin infection with more pronounced lesions which took longer to heal than log phase (actively growing) cultures. After two week infection, the bacterial load and skin tissue pathology, as determined by hyperplasia, immune cell infiltration, and crust/lesion formation, of mice infected with the more persistent forms (e.g. stationary phase bacteria and biofilm bacteria) were greater than mice infected with log phase bacteria. Using our persistent infection mouse model, we showed that the clinically recommended treatment for recurrent S. aureus skin infection, doxycycline + rifampin, was not effective in eradicating the bacteria in the treatment study, despite reducing lesion sizes and pathology in infected mice. Analogous findings were also observed in a Caenorhabditis elegans model, where S. aureus stationary phase cultures caused a greater mortality than log phase culture as early as two days post-infection. Thus, we established a new model for chronic persistent infections using persister bacteria that could serve as a relevant model to evaluate therapeutic options for persistent infections in general. Our findings connect persisters with persistent infections, have implications for understanding disease pathogenesis, and are likely to be broadly valid for other pathogens.
Latino Families and Schools: Identifying Challenges and Highlighting Strengths to Support Children’s Early Learning

The present chapter focuses on low-income Latino families and their children within the context of the schools they attend in the USA. Latino children enter kindergarten with a range of academic and self-regulation skills, but parents and children can face multiple challenges navigating the educational context. The chapter explores risk factors (i.e., policies and demographics) experienced by low-income Latino families and how these factors shape their children’s experiences in school. It also focuses on the importance of foundational skills such as self-regulation for Latino children’s school success and interventions to promote these skills. The chapter then highlights the strengths these families bring to support their children’s early learning and educational experiences. Discussion focuses on ways that schools can capitalize on the strengths that Latino families bring to collaboratively support children’s academic achievement and educational equity.
Percutaneous cryoablation of renal masses under CT fluoroscopy: radiation doses to the patient and interventionalist

Computed tomographic (CT) fluoroscopy-guided percutaneous cryoablation is an effective therapeutic method used to treat focal renal masses. The purpose of this study is to quantify the radiation dose to the patient and interventional radiologist during percutaneous cryoablation of renal masses using CT fluoroscopic guidance. Over a 1-year period, the CT fluoroscopy time during percutaneous cryoablation of renal masses was recorded in 41 patients. The level of complexity of each procedure was designated as simple, intermediate, or complex. Patient organ radiation doses were estimated using an anthropomorphic model. Dose to the interventional radiologist was estimated using ion chamber survey meters. The average CT fluoroscopy time for technically simple cases was 47 s, 126 s for intermediate cases, and 264 s for complex cases. The relative risk of hematologic stomach and liver malignancy in patients undergoing this procedure was 1.003–1.074. The lifetime attributable risk of cancer ranged from 2 to 58, with the highest risk in younger patients for developing leukemia. The estimated radiation dose to the interventionalist without lead shielding was 390 mR (3.9 mGy) per year of cases. The radiation risk to the patient during CT fluoroscopy-guided percutaneous renal mass cryoablation is, as expected, related to procedure complexity. Quantification of patient organ radiation dose was estimated using an anthropomorphic model. This information, along with the associated relative risk of malignancy, may assist in evaluating risks of the procedure, particularly in younger patients. The radiation dose to the interventionist is low regardless of procedure complexity, but highlights the importance of lead shielding.
Walking Hand in Hand—Flannery O’Connor’s Artistic and Spiritual Companions

T.S. Eliot once suggested that the best way to get to know a work of art is to put it next to another work of art. The truth of this statement can be extended to the artist: to get to know an artis...
Modeling CAR T-Cell Therapy with Patient Preconditioning

The Federal Drug Administration approved the first Chimeric Antigen Receptor T-cell (CAR T-cell) therapies for the treatment of several blood cancers in 2017, and efforts are underway to broaden CAR T technology to address other cancer types. Standard treatment protocols incorporate a preconditioning regimen of lymphodepleting chemotherapy prior to CAR T-cell infusion. However, the connection between preconditioning regimens and patient outcomes is still not fully understood. Optimizing patient preconditioning plans and reducing the CAR T-cell dose necessary for achieving remission could make therapy safer. In this paper, we test treatment regimens consisting of sequential administration of chemotherapy and CAR T-cell therapy on a system of differential equations that models the tumor-immune interaction. We use numerical simulations of treatment plans from within the scope of current medical practice to assess the effect of preconditioning plans on the success of CAR T-cell therapy. Model results affirm clinical observations that preconditioning can be crucial for most patients, not just to reduce side effects, but to even achieve remission at all. We demonstrate that preconditioning plans using the same CAR T-cell dose and the same total concentration of chemotherapy can lead to different patient outcomes due to different delivery schedules. Results from sensitivity analysis of the model parameters suggest that making small improvements in the effectiveness of CAR T-cells in attacking cancer cells will significantly reduce the minimum dose required for successful treatment. Our modeling framework represents a starting point for evaluating the efficacy of patient preconditioning in the context of CAR T-cell therapy.
The B56α subunit of PP2A is necessary for mesenchymal stem cell commitment to adipocyte.

Adipose tissue plays a major role in maintaining organismal metabolic equilibrium. Control over the fate decision from mesenchymal stem cells (MSCs) to adipocyte differentiation involves coordinated command of phosphorylation. Protein phosphatase 2A plays an important role in Wnt pathway and adipocyte development, yet how PP2A complexes actively respond to adipocyte differentiation signals and acquire specificity in the face of the promiscuous activity of its catalytic subunit remains unknown. Here, we report the PP2A phosphatase B subunit B56α is specifically induced during adipocyte differentiation and mediates PP2A to dephosphorylate GSK3β, thereby blocking Wnt activity and driving adipocyte differentiation. Using an inducible B56α knock-out mouse, we further demonstrate that B56α is essential for gonadal adipose tissue development in vivo and required for the fate decision of adipocytes over osteoblasts. Moreover, we show B56α expression is driven by the adipocyte transcription factor PPARγ thereby establishing a novel link between PPARγ signaling and Wnt blockade. Overall, our results reveal B56α is a necessary part of the machinery dictating the transition from pre-adipocyte to mature adipocyte and provide fundamental insights into how PP2A complex specifically and actively regulates unique signaling pathway in biology.