cssi/SciSciGPT-SciSciNet huggingface dataset:
Optimal In Silico Target Gene Deletion through Nonlinear Programming for Genetic Engineering

Background Optimal selection of multiple regulatory genes, known as targets, for deletion to enhance or suppress the activities of downstream genes or metabolites is an important problem in genetic engineering. Such problems become more feasible to address in silico due to the availability of more realistic dynamical system models of gene regulatory and metabolic networks. The goal of the computational problem is to search for a subset of genes to knock out so that the activity of a downstream gene or a metabolite is optimized. Methodology/Principal Findings Based on discrete dynamical system modeling of gene regulatory networks, an integer programming problem is formulated for the optimal in silico target gene deletion problem. In the first result, the integer programming problem is proved to be NP-hard and equivalent to a nonlinear programming problem. In the second result, a heuristic algorithm, called GKONP, is designed to approximate the optimal solution, involving an approach to prune insignificant terms in the objective function, and the parallel differential evolution algorithm. In the third result, the effectiveness of the GKONP algorithm is demonstrated by applying it to a discrete dynamical system model of the yeast pheromone pathways. The empirical accuracy and time efficiency are assessed in comparison to an optimal, but exhaustive search strategy. Significance Although the in silico target gene deletion problem has enormous potential applications in genetic engineering, one must overcome the computational challenge due to its NP-hardness. The presented solution, which has been demonstrated to approximate the optimal solution in a practical amount of time, is among the few that address the computational challenge. In the experiment on the yeast pheromone pathways, the identified best subset of genes for deletion showed advantage over genes that were selected empirically. Once validated in vivo, the optimal target genes are expected to achieve higher genetic engineering effectiveness than a trial-and-error procedure.
Tumor control in definitive irradiation of localized carcinoma of the prostate

At the Mallinckrodt Institute of Radiology, Washington University, 343 patients with carcinoma of the prostate were treated with definitive radiotherapy. All patients are available for minimal 3 year follow-up; the median period of observation is 5.2 years. The incidence of pelvic recurrence with or without distant metastases was 0% in 10 patients with Stage A2, 11% in 113 patients with Stage B, 34% in 204 patients with Stage C, and 40% in 16 patients with Stage D1. There was no significant difference in pelvic tumor control when correlated with the degree of differentiation of the tumors in each stage. In Stage B, patients who exhibited complete regression 3 months after completion of therapy had a pelvic failure rate of 5%, those with 50-75% regression-8% and less than 50% regression-18%. In Stage C, patients with more than 50% tumor regression had a pelvic failure rate of 25%, in contrast to 37% when less than 50% regression was noted at 3 months after completion of irradiation. However, there was no correlation between tumor regression and NED survival. In patients with Stage B, there was no significant correlation between doses of irradiation ranging from 6000 to 7000 cGy and pelvic tumor control. In Stage C, patients receiving doses higher than 6500 cGy had a probability of failure rate in the pelvis of 25% (40/173), in comparison with 44% with doses between 6000-6500 cGy (15/32). The 10 year NED survival for Stage A2 was 100%, Stage B-70%, and Stage C-40%. In Stage B, there was no correlation between local tumor control and 5 year overall survival. However, at 10 years 88 patients without evidence of local failure or distant metastases had a survival rate of 70% in contrast to only 25% if they recurred. In Stage C, 110 patients without local recurrence or distant metastases had a 40% 10 year survival in contrast to 20% in 55 patients who had pelvic recurrence (with or without distant metastases) and 39 patients with distant metastases only. In 105 patients with Stage B tumor controlled in the pelvis, the incidence of distant metastases was 16%, in contrast to 50% in eight patients with pelvic failure. In Stage C, only 26% of 149 patients with pelvic tumor controlled developed distant disease, versus 60% in 55 patients failing in the pelvis. Ninety-five percent of the pelvic failures and 80% of the distant metastases appeared within 5 years after therapy. The administration of hormones did not significantly influence either the probability of pelvic tumor control or the appearance of distant metastases.
Dynamic Response of Complex Structural Intersections Using Hybrid Methods

A novel application of Lagrange multipliers to couple domains modeled independently with linear elastodynamic and reduced-order theories is presented herein. This method is developed from a variational formulation of the continuous problem and is easily implemented within a finite element code. Applications include, but are not limited to, modeling of inhomogeneities such as joints, cracks, holes, and welds within a frame-like structure. Results from this method compare well with a full elastodynamic discretization and existing methods for modeling such problems.
THE CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR AND ATP

A controversy in the field of cystic fibrosis (CF) research has arisen concerning the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in the transport of ATP. Does the CFTR actually conduct ATP or does it regulate the conductance of ATP? Recent findings either support or reject the hypothesis that the CFTR can transport ATP. In addition, recent research from several laboratories has suggested that ATP mediates its effects after traversing the plasma membrane and reaching the extracellular surface. The current model suggests that the released ATP exerts its various influences via a purinergic receptor to regulate outwardly rectifying chloride channels and epithelial sodium channels.
Periodic structures generated in a cloud of cold atoms

We have demonstrated a method of generation and real-time detection of nanostructures in a cold Rb cloud. These structures, which are periodic gratings of atomic density, appear as a result of interference of atoms diffracted by pulses of an optical standing wave of wavelength $\ensuremath{\lambda}.$ We have detected structures of period $\ensuremath{\lambda}/2$ and $\ensuremath{\lambda}/4.$ Calculations indicate that these density gratings have period $\ensuremath{\lambda}/2N$ for integer N. While the structures with the period $\ensuremath{\lambda}/2$ are easily detected by Bragg scattering of an optical probe beam, the shorter-period structures are not. For their detection we have developed a three-pulse echo method, in which the shorter-period gratings get converted into the structures with period $\ensuremath{\lambda}/2,$ readily detected in real time. Applications related to lithography are discussed.
Neural network application for supplier selection

An efficient decision-making model was developed to select suppliers using multi-layer feed forward neural networks. A set of input functions for supplier selection criteria was defined to create input data for training the model. Both types of criteria, qualitative and quantitative, were considered in the model. Fuzzy techniques were applied to convert qualitative data to quantitative data. Pairwise comparisons matrices were applied for output values and weight assignment. The neural network model structure was designed and tested based on backpropagation. The results of the neural network model indicated that the proper structure of the model had a crucial effect on its performance. The selection of appropriate initial weights, learning rate and momentum were critical in improving the model performance. To prove the capability of the proposed model, suppliers of three products were ranked based on the proposed model and the results were compared with the managers' ranking. The proposed neural network model can use historical data of suppliers to evaluate their performance in the vendor supplier selection decision. The vendor can update the suppliers' database information over time for future decisions.
Clients' perceptions of discharge housing decisions after stroke rehabilitation.

OBJECTIVE The purpose of this research was to examine the perceptions of older persons with stroke concerning the discharge housing decisions made during their rehabilitation program. The research explored clients' locus of control, their perceptions of the role of the rehabilitation team and their family in the decision, and their perceptions of their activities of daily living skills. METHOD Sixty-two subjects with stroke completed four measures: (a) the Functional Independence Measure (FIM), (b) a housing information questionnaire, (c) a semistructured interview, and (d) the Bialer Locus of Control Scale. Rehabilitation team members also completed the FIM and housing information questionnaire for each subject. These instruments were used to collect data relating to clients' perceptions of their functional status, discharge from the hospital, housing options available, and locus of control. RESULTS Despite the team or family opinions on discharge housing, subjects saw housing decisions as primarily their own. The majority of subjects were reluctant to consider alternatives to returning home, even though they have self-care deficits and frequently reported that the presence of a spouse and family members were important to support their return home. Subjects generally seemed unaware of the influence of team and family opinions and the impact of their functional status on their discharge housing. Subjects' locus of control seemed unrelated to satisfaction with the discharge decision process. CONCLUSION Clients who have had a stroke could use assistance to determine housing that is appropriate for their living skills. Discussions with clinicians concerning accommodation options may lead to a smoother transition from the hospital to longer term housing for clients after stroke.
Abstract P2-09-04: Measurements of advocate participation in and contributions to the Mayo Clinic breast cancer SPORE

[Background] Patient advocates bring a unique, valuable perspective and presence to SPOREs. However, although patient advocates are recommended members of SPORE grants, guidelines are not given on the role of advocates or on measurement of the performance of advocates. [Methods] The Mayo Clinic Breast Cancer SPORE Patient Advocate Advisory Committee has developed a participation measurement tool. This tool will underpin and augment evaluations of the individual advocate contributions by the program PI and the SPORE project leaders. The Advocate Advisory Committee Chair will review the evaluations with the individual advocates. Annually, the advocate committee will review the performance of the group by the standard of the metrics. [Results] Advocates kept a log of their SPORE activities for four months then worked with a statistician to discern patterns of measurable, evaluable behaviors. The determined evaluable areas are training, scientific activity, meeting attendance, communication. Currently, those metrics are being tracked. Advocates developed the metrics together and report activities at the monthly advocate meetings. Currently, activities are simply tracked and categorized. No minimum standards are set. This will be the third step in the development of the metrics. [Conclusions] This approach is the first step in the development of meaningful evaluation of advocate SPORE activities. It quantifies the participation of advocates in the SPORE and provides the basis for developing a qualitative performance evaluation. The SPORE PI and the Committee Chair will use the evaluations to interpret the involvement of advocates in SPORE research and activities and to plan interventions to strengthen the advocate contributions to the SPORE. Citation Format: Cynthia Chauhan, Wayland Eppard, Lori Denison, Debra Gearhart, Lawanna Holmes, Ruth Kraft, Linda Miller, Mary A Sitta, Mary L Smith, James Ingle, Matthew Goetz. Measurements of advocate participation in and contributions to the Mayo Clinic breast cancer SPORE [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-09-04.
The use of intravenous colistin among children in the United States: results from a multicenter, case series.

Background A rapid increase in multidrug-resistant Gram-negative infections has led to a reemergence of colistin use globally. Although it is well described among adults, colistin use and its associated toxicities in children are poorly understood. We report findings from the largest case series of pediatric colistin use to date.
The use of amides and other organic nitrogen sources by the phytoplankton Emiliania huxleyi

Although dissolved organic nitrogen (DON) is beginning to be seen as a potentially important nitrogen source for phytoplankton, much remains to be learned about its components and their utilization. Emiliania huxleyi, a cosmopolitan eukaryotic phytoplankton species abundant in oligotrophic oceans and during blooms in some coastal regions, was screened for use of various DON compounds. Hypoxanthine and other purines support the nickeldependent growth of most E. huxleyi strains. Acetamide and formamide but not longer chain aliphatic amides were found to be excellent nitrogen sources for growth; other phytoplankton were also found to utilize acetamide but not formamide. In E. huxleyi, small amides are transported into the cell followed by degradation to ammonia, possibly by amide-specific enzymes. The related molecules hydroxyurea and thiourea were toxic to the cells and caused an increase in fluorescence consistent with blockage of photosystern II. This fluorescence increase was inhibited by urea and acetamide, suggesting transport of hydroxyurea, thiourea, urea, and acetamide by the same or closely related transporters. Dissolved organic nitrogen (DON) is the major chemical form of N, other than N gas, in marine waters. This pool of N includes a range of compounds whose concentrations have been measured (e.g. amino acids and urea), but is mostly composed of compounds whose identities and concentrations are poorly known (Sharp 1983; Antia et al. 1991; Hopkinson et al. 1993). Because N is thought to control primary productivity in some areas of the world’s oceans, the production rates and biological availability of this pool are clearly important issues. 15N tracer experiments suggest that this pool can be rapidly produced from inorganic N additions and can be available for subsequent utilization (Bronk and Glibert 1991, 1993, 1994; Bronk et al. 1994). The study of the biological utilization of DON can take several approaches. One method is the generation and use of lSN-labeled natural DON for uptake experiments (Bronk and Glibert 1993).
Evaluation of Escherichia coli O157:H7 growth media for use in test-and-hold procedures for ground beef processing

Since the mid-1990s, the beef industry has used a process called test and hold, wherein beef trim and ground beef are tested to keep products contaminated with Escherichia coli O157:H7 out of commerce. Current O157:H7 detection methods rely on a threshold level of bacterial growth for detection, which is dependent on the growth medium used. Twelve media were examined for growth and doubling time: buffered peptone water (BPW), SOC (which contains tryptone, yeast extract, KCl, MgCl2, and glucose), buffered peptone water plus SOC (BPW-SOC), Bacto-NZYM, RapidChek E. coli O157:H7 medium, BioControl EHEC8 culture medium, Neogen Reveal for E. coli O157:H7--Eight Hour medium (Neogen Reveal 8), BAX System medium for E. coli O157:H7 (BAX) BAX System medium for E. coli O157:H7 MP (BAX-MP), modified E. coli broth, nutrient medium, and tryptic soy broth (TSB). All media were tested at 37 or 42 degrees C under static or shaking conditions. The eight media with the highest total CFU per milliliter and most rapid doubling times were BPW-SOC, NZYM, RapidChek, EHEC8, Neogen Reveal 8, BAX, BAX-MP, and TSB. The ability of these eight media to enrich E. coli O157:H7 in ground beef was further evaluated through time-course experiments using immunomagnetic separation. Of these media, TSB was the easiest to prepare, had a wide application base, and was the least expensive. In the test-and-hold process, the normal ratio of medium to product is 1:10. In this study, a 1:3 ratio worked as well as a 1:10 ratio. Processors using test-and-hold procedures could use 1 liter of TSB to enrich for E. coli O157:H7 in a 375-g sample instead of the usual 3.375 liters, thus saving reagents, time, and labor while maintaining accuracy.
Swing- and support-related muscle actions differentially trigger human walk–run and run–walk transitions

SUMMARY There has been no consistent explanation as to why humans prefer changing their gait from walking to running and from running to walking at increasing and decreasing speeds, respectively. This study examined muscle activation as a possible determinant of these gait transitions. Seven subjects walked and ran on a motor-driven treadmill for 40s at speeds of 55, 70, 85, 100, 115, 130 and 145% of the preferred transition speed. The movements of subjects were videotaped, and surface electromyographic activity was recorded from seven major leg muscles. Resultant moments at the leg joints during the swing phase were calculated. During the swing phase of locomotion at preferred running speeds (115, 130, 145%), swing-related activation of the ankle, knee and hip flexors and peaks of flexion moments were typically lower ( P P
Solid electrolyte properties of LaF3

The small-signal ac response of cells with LaF3 or the solid solutions La1-xBaxF3-x and ionically blocking electrodes has been measured in the frequency range 0.1-3 × 104Hz, and for temperatures from 220 to 650 K. The bulk electrolyte conductivity of LaF3 crystals is anisotropic up to 415 K. For polycrystalline samples grain boundary effects markedly influence the frequency dispersion. Above room temperature these effects mask the bulk electrolyte conductivity in the accessible frequency range. The composition dependence of the bulk electrolyte conductivity of La1-xBaxF3-x solid solutions is compared with 19F NMR data, and used to discuss recently reported association effects in LaF3. Reported anomalies in the electrical properties of LaF3 are used to exemplify the need to study the frequency dispersion over a wide frequency range.
Why Do Women Choose or Decline Maternal Serum Screening

Abstract Objective In Newfoundland and Labrador (NL), maternal serum screening (MSS) is offered during the second trimester of pregnancy to detect fetuses with an increased risk for a birth defect. A recent study of MSS found low uptake (22%) in the province. We surveyed postpartum women in NL to (1) determine where women learn about MSS, (2) understand women's reasons for having or refusing MSS, and (3) describe women's process of decision-making about MSS. Methods We surveyed postpartum women throughout NL to learn where women found out about MSS, whether or not they had MSS and why, and how they made their decision about MSS. Results Almost one fifth of mothers were unaware of MSS. Approximately one third (34.6%) of women who had heard of MSS had undergone screening in their most recent pregnancy. Common reasons for having MSS were a desire to undergo all available testing and wanting to know about the health of the baby. Common reasons for not undergoing MSS were opposition to terminating the pregnancy and feeling that the results would not be definitive. Conclusion A majority of pregnant women in NL do not want MSS. Women's personal values influence their MSS decisions and account for the low utilization rates in the province.
Class III beta-tubulin isotype (beta III) in the adrenal medulla: I. Localization in the developing human adrenal medulla

Background The class III beta-tubulin isotype (beta III) is present in neurons of the central and peripheral nervous systems at the earliest stages of morphological differentiation (Easter et al., J Neurosci 13:285-299, 1993; Katsetos et al., J Neuropathol Exp Neurol 52:655-666, 1993). The localization of this protein by immunohistochemistry in the different cell types of the developing human adrenal medulla is described. Methods A mouse monoclonal antibody, TuJ1, was used to localize beta III in formalin-fixed, paraffin-embedded sections from 18 human fetal and adult adrenal glands. Tissue sections were also studied with rabbit antisera recognizing either S-100 protein or glial fibrillary acidic protein (GFAP). Results In the developing human adrenal medulla, beta III immunoreactivity was maximal in migrating sympathoadrenal neuroblasts/immature neurons through the end of the second trimester. Clusters of beta III-positive migrating cells, focally forming Homer Wright rosettes, could be identified in a gradient of adrenocortical invasion, i.e., through the permanent cortex and within sinusoids of the fetal cortex en route to the medulla. Outside the adrenal gland, strong beta III staining was observed in peripheral nerve bundles, sympathetic ganglia, and paraganglia at various developmental stages. In adrenal glands from 23 weeks of gestation on, and throughout adult life, all ganglion cells were beta III immunoreactive. In contrast, not all chromaffin cells exhibited beta III staining, but when present, the staining was finely granular. Sustentacular and satellite cells, adrenocortical cells and other mesenchymal elements were betaIII-negative. In sections of fetal and adult adrenal glands, S-100 protein had a sustentacular localization. No GFAP staining was present in sustentacular cells from either fetal or adult adrenals. Conclusions In the developing human adrenal medulla, there is a peak of beta III expression during the active wave of migration of sympathetic neuroblasts. In the mature medulla, beta III is invariably present in adrenergic neurons. However, not all chromaffin-like cells express beta III, suggesting that the presence or absence of this protein identifies two subpopulations of chromaffin cells.
Mental patients, prisoners, and students with simulated partners in a mixed-motive game:

Is behavior in the Prisoner's Dilemma game (PDG) a valid indicator of personality? Deutsch (1958) has postulated a "strong connection" between personality and choice behavior. By describing this two-person, non-zero-sum game as a test of trust and suspicion, cooperation and competition, and trustworthiness and untrustworthiness, Deutsch has highlighted its psychological relevance. Early published studies concerning the relation of selected personality variables to game behavior reported positive findings (Deutsch, 1960; Lutzker, 1960; McClintock, Harrison, Strand, and Gallo, 1963; Marlowe, 1963). Recent studies, however, have failed to substantiate the existence of expected relationships (Bixenstine, Chambers, and Wilson, 1964; Pilisuk, Potter, Rapoport, and Winter, 1965; McClintock, Gallo, and Harrison, 1965; Wrightsman, 1966). In addition, Rapoport and Chammah (1965) have concluded that, although college men are more cooperative than college women, the effects
Transition From Rolling to Firm Adhesion Is Regulated by the Conformation of the I Domain of the Integrin Lymphocyte Function-associated Antigen-1

The integrin lymphocyte function-associated antigen-1 (αLβ2), which is known for its ability to mediate firm adhesion and migration, can also contribute to tethering and rolling in shear flow. The αL I domain can be mutationally locked with disulfide bonds into two distinct conformations, open and closed, which have high and low affinity for the ligand intercellular adhesion molecule 1 (ICAM-1), respectively. The wild type I domain exists primarily in the lower energy closed conformation. We have measured for the first time the effect of conformational change on adhesive behavior in shear flow. We show that wild type and locked open I domains, expressed in αLβ2 heterodimers or as isolated domains on the cell surface, mediate rolling adhesion and firm adhesion, respectively. αLβ2 is thus poised for the conversion of rolling to firm adhesion upon integrin activationin vivo. Isolated I domains are surprisingly more effective than αLβ2 in interactions in shear flow, which may in part be a consequence of the presence of αLβ2 in a bent conformation. Furthermore, the force exerted on the C-terminal α-helix appears to stabilize the open conformation of the wild type isolated I domain and contribute to its robustness in supporting rolling. An allosteric small molecule antagonist of αLβ2 inhibits both rolling adhesion and firm adhesion, which has important implications for its mode of action in vivo.
Urothelial Cancers: Ureter, Renal Pelvis, and Bladder

Objectives To review the diagnosis, treatment, and nursing management of patients with urothelial cancers. Data Sources PubMed, Ovid MEDLINE, Text books, and clinical experience. Conclusion Progress is being made in the surgical and systemic management of urothelial cancers, and the oncology nurse is in a position to make an impact on patient education and overall quality of life. Implications for Nursing Practice Nursing care begins at pre-diagnostic testing and continues through treatment for metastatic disease. Nurses must be knowledgeable about diagnostic tests, treatment options, and the quality-of-life implications of associated surgeries and/or treatments to support and guide patients. Education should be comprehensive, addressing not only treatment side effects but also long-term implications on patients' lives and lifestyles.
Temperature Effects on the Perturber Induced Shift of Dopant Ionization Energies in He and Ne

Abstract In this Letter, temperature effects on the perturber induced shift Δ D ( ρ P ) [ ρ P ≡ perturber number density ] of the dopant ionization energy in the repulsive gases Ne and He are investigated at low to medium perturber number densities (i.e., ρ P ⩽ 6.0 × 10 21 cm - 3 ). We show that these effects arise from changes in the ensemble averaged dopant/perturber polarization energy rather than from changes in the energy of the quasi-free electron.
Musical Interpretation: Philosophical and Practical Issues.

This article builds an interdisciplinary perspective on the nature of western classical music performance by combining concepts from literary theory, music philosophy and music education philosophy. The article concludes with practical proposals for the education of music performers.
Regulation of the membrane mucin Muc4 in corneal epithelial cells by proteosomal degradation and TGF-β

MUC4 is a heterodimeric membrane mucin, composed of a mucin subunit ASGP-1 (MUC4α) and a transmembrane subunit ASGP-2 (MUC4β), which has been implicated in the protection of epithelial cell surfaces. In the rat stratified corneal epithelium Muc4 is found predominantly in the most superficial cell layers. Since previous studies in other tissues have shown that Muc4 is regulated by TGF-β via a proteosomal degradation mechanism, we investigated the regulation of corneal Muc4 in stratified cultures of corneal epithelial cells. Application of proteosome or processing inhibitors led to increases in levels of Muc4, particularly in the basal and intermediate levels of the stratified cultures. These changes were accompanied by increases in Muc4 ubiquitination, chaperone association and incorporation into intracellular aggresomes. In contrast, treatment with TGF-β resulted in reduced levels of Muc4, which were reversed by proteosome inhibition. The results support a model in which Muc4 precursor is synthesized in all layers of the corneal epithelium, but Muc4 is degraded in basal and intermediate layers by a proteosomal mechanism at least partly dependent on TGF-β inhibition of Muc4 processing.
A CLASSICAL N = 4 SUPER W ALGEBRA

I construct classical superextensions of the Virasoro algebra by employing the Ward identities of a linearly realized subalgebra. For the N = 4 superconformal algebra, this subalgebra is generated by the N = 2 U(1) supercurrent and a spin 0 N = 2 superfield. I show that this structure can be extended to an N = 4 super W3 algebra, and give the complete form of this algebra.
The Relationship Between Posture and Balance Disturbances in Women with Osteoporosis

In the population diagnosed with osteoporosis, balance impairments may contribute to frailty. Consequences of osteoporosis include thoracic kyphosis caused by compression fractures. This author investigated whether postural changes could negatively impact balance in women with osteoporosis. Fifty-two women diagnosed with osteoporosis were measured for both balance and kyphosis. Those who failed the balance test had a statistically greater degree of kyphosis than those who passed, even after controlling for age differences. This study quantified past studies, which suggested a relationship between balance and posture.
Overview of the Consortium for the Advanced Simulation of Light Water Reactors (CASL)

The Consortium for Advanced Simulation of Light Water Reactors (CASL) was established in July 2010 for the purpose of providing advanced modeling and simulation solutions for commercial nuclear reactors. The primary goal is to provide coupled, higher-fidelity, usable modeling and simulation capabilities than are currently available. These are needed to address light water reactor (LWR) operational and safety performance-defining phenomena that are not yet able to be fully modeled taking a first-principles approach. In order to pursue these goals, CASL has participation from laboratory, academic, and industry partners. These partners are pursuing the solution of ten major “Challenge Problems” in order to advance the state-of-the-art in reactor design and analysis to permit power uprates, higher burnup, life extension, and increased safety. At present, the problems being addressed by CASL are primarily reactor physics-oriented; however, this paper is intended to introduce CASL to the reactor dosimetry community because of the importance of reactor physics modelling and nuclear data to define the source term for that community and the applicability and extensibility of the transport methods being developed.
Predicting Adult Crime Status from Type of Delinquency

In this chapter we begin to examine the relationship between adult criminality in the 1958 birth cohort and the nature or seriousness of prior juvenile offending. We know from our findings in the two previous chapters the importance of the frequency and timing of offending, but now our concern is to determine whether the commission of some forms of delinquency are more likely to lead to offending later in life after the delinquent becomes an adult. We will then extend this focus to include an analysis of the juvenile careers of delinquents who may engage in specialized delinquency or concentrate in certain offenses.
Use of Gene Targeting to Study Recombination in Mammalian Cell DNA Repair Mutants

Gene targeting by homologous recombination in mammalian cells is an important tool for generating genetically modified mice used for modeling human diseases. Gene targeting approaches are also useful for studying the mechanisms of homologous recombination. We have developed gene targeting methods that we have specifically used to investigate the mechanisms of recombination in cultured mammalian cells. In this chapter, we describe the generation of Chinese hamster ovary (CHO) cell gene disruption ("knockout") mutants in the repair/recombination gene ERCC1. Using this approach, we have constructed pairs of isogenic ERCC1-proficient and -deficient (null) CHO cell lines and used them as recipients for gene targeting assays in which a hemizygous mutant hamster adenine phosphoribosyltransferase (APRT) locus is corrected by homologous recombination with plasmid vectors containing hamster APRT DNA sequence homologous to the target gene in each cell line. The configuration of the targeting vector leads to experimental outcomes in which certain classes of APRTrecombinants are over- or under-represented depending on the repair gene status of the transfection recipient. We describe methods both for targeted gene knockout of ERCC1, and for APRT targeted gene correction by homologous recombination, and some of our experimental results using these approaches.
A Convention for Proposing Amendments: The Constitution's Other Method

When introducing S.817, the Constitutional Convention Implementation Act of 1981 (Hatch-DeConcini), Senator Orrin Hatch (R-Utah) said, "I emphasize again the basic purpose for including the convention method of amendment in Article V-the need for the States to be able to amend the Constitution in the face of an intransigent national Government."1 He described the "other method" of amending the Constitution provided for in Article V, the convention method, as "one of the basic elements for preserving some semblance of balance between the national and State governments." This version of legislation to provide procedures for a convention to propose amendments is more state-oriented than the previous bills (S.215, 1971 and S.3, 1979), and that fact suggests a slight change in recognition of the virtues of the American federal system. Support for a convention to propose a constitutional amendment has surfaced several times in this century, although with no direct success. The first effort, on behalf of direct election of senators, led to the Seventeenth Amendment. The second, a response to the Supreme Court's apportionment decisions in 1962-1964 (including Baker v. Carr, Lucas v. Colorado, and Reynolds v. Sims), produced nothing. In both cases the number of state petitions came very close to the two-thirds required by Article V of the U.S. Constitution. Since 1975 a campaign organized by the National Taxpayers Union has produced thirty of the requisite thirtyfour applications for a convention to propose an amendment to mandate a balanced federal budget. The drive for a balanced budget amendment to the U.S. Constitution is one answer to the question, how can we limit (federal) government spending? Such an amendment has been introduced in the 97th Congress, as Senate Joint Resolution 58, and among its sponsors are Senator Strom
Intracellular Nanoscale Imaging with Fluorescence Photoactivation Localization Microscopy

Diffraction limits resolution in optical microscopy, but many biological phenomena occur on molecular length scales. Recently, methods to circumvent the diffraction limit have been presented. Fluorescence photoactivation localization microscopy (FPALM) uses multiple iterations of photoactivation, imaging, and photobleaching of subsets of photoactivatable fluorescent probe (PAFP) molecules to generate images with resolution of 10-40 nanometers. The three-dimensional position, brightness, polarization, and other single molecule information are obtained from the raw image(s) of each PAFP. The process is repeated for many subsets to build up data on many molecules. The positions of all localized molecules are used to construct an image of the sample with nanoscale resolution. Results will be shown for a variety of biological systems, including live and fixed cells expressing PAFP fusions of membrane, cytoplasmic, cytoskeletal, and nuclear proteins. Bi-plane FPALM can image in three dimensions, and polarization FPALM can image molecular positions and anisotropies simultaneously. Using these powerful capabilities, many potentially interesting biological problems can be addressed.
Abstract P1-12-08: Factors associated with delays in chemotherapy initiation among patients with breast cancer

Background: National guidelines endorse time-dependent quality metrics for breast cancer care. We examined factors associated with delays in chemotherapy initiation at an NCI designated comprehensive cancer center. Methods: We identified 523 patients who received post-operative adjuvant chemotherapy between January 2011 and December 2013 at our center. We defined 28 days from last definitive surgery (LDS) to chemotherapy as the target timeframe, and unacceptable delay in chemotherapy initiation (UCD) as more than 42 days from LDS. Multivariate regression models were used to identify factors associated with UCD and the impact of Oncotype testing in HR+ patients. Results: Median days between LDS and chemotherapy initiation was 34 (IQR 15), with 30% of patients starting within 28 days of LDS and 23% having UCD (Table 1). Tumor characteristics such as subtype and stage affected UCD; patients with HR+ or HER2+ tumors were more likely to be delayed compared to those with TNBC. Patients with stage I disease were more likely to be delayed as well as patients undergoing mastectomy or mastectomy with reconstruction. Patients whose pathology sign-out was more than 10 days post-operatively were more likely to be delayed. A higher proportion of UCD was found in HR+ patients (31%) who received an Oncotype recurrence score compared to those who did not (20%). Conclusions: This study provides insight into populations that may be at risk to experience delays in chemotherapy initiation, directing interventions to improve the timeliness of care. Citation Format: Losk K, Vaz Duarte Luis I, Camuso K, Lloyd M, Kadish S, Hirshfield-Bartek J, Cutone L, Golshan M, Lin N, Bunnell C. Factors associated with delays in chemotherapy initiation among patients with breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-12-08.
Settling into the midstream? Lessons for governance from the decade of nanotechnology

This paper analyzes scholarly papers published from 2003 through 2013 on the general theme of nanotechnology and governance. It considers three general points: (1) the “problem” of nanotechnology; (2) general lessons for governance obtained; and (3) prospects for aligning the US regulatory system to the next generation of complex engineered nano-materials. It argues that engineered nano-materials and products are coming to market within an already mature regulatory framework of decade-old statutes, long-standing bureaucratic rules and routines, narrowly directive judicial decisions, and embedded institutional norms. That extant regulatory regime shapes how policymakers perceive, define, and address the relative benefits and risks of both proximate and yet-to-be idealized nano-materials and applications. The paper concludes that fundamental reforms in the extant regime are unlikely short of a perceived crisis.
Evolution — an Overview

We might continue from Carboniferous time to the present detailing the new types of plants that evolved. But it may be more instructive to stop, examine the whole picture, and pose another question. Has evolution proceeded at a uniform rate since the beginning or have there been some major bursts of activity?
Patient Information Processing

The verbal or written disclosure of risk information is dependent upon the health professional. However, the patient cannot be totally passive. To be successfully communicated, not only does risk information need to be disclosed, but it needs to be attended, understood, integrated, remembered, and ultimately put to proper use when decisions are made and behaviors undertaken. Even if emphasized by a physician, the patient must be able to fully process risk information for it to be of value.
Toroidal silicon polarization analyzer for resonant inelastic x-ray scattering

Resonant Inelastic X-ray Scattering (RIXS) is a powerful probe for studying electronic excitations in materials. Standard high energy RIXS measurements do not measure the polarization of the scattered x-rays, which is unfortunate since it carries information about the nature and symmetry of the excitations involved in the scattering process. Here we report the fabrication of thin Si-based polarization analyzers with a double-concave toroidal surface, useful for L-edge RIXS studies in heavier atoms such as the 5-d transition metals.
Behaving better: stem cells singled out.

In this issue of Blood, Kokkaliaris et al use a sophisticated imaging approach to track the behavior of individual murine hematopoietic stem cells (HSCs) cultured on stromal cells. The authors identify cell death as a critical factor limiting the in vitro culture of HSCs, which can be mitigated by the matrix protein dermatopontin (DPT). These studies lay the groundwork for the in vitro manipulation of HSCs for therapeutic purposes.1
NPIC: seeing the secrets, growing the leaders

The National Photographic Interpretation Center (NPIC), the US intelligence community’s center for aircraft and satellite imagery analysis from 1961–96, is one of the more underexposed organization...
Karl Kraus as “Volksklassiker”? Upton Sinclair and the Translation of Die letzten Tage der Menschheit (Including an unpublished Kraus manuscript)

Anhand eines bisher unveroffentlichten Briefentwurfs wird erlautert, warum Karl Kraus schlieslich nicht auf einen Vorschlag Upton Sinclairs einging, Die letzten Tage der Menschheit ins Englische ubersetzen und in einer sozialistischen Sammlung von “Volksklassikern” erscheinen zu lassen. Der Aufsatz berucksichtigt sowohl die Bestande des Kraus-Archivs als auch den Upton-Sinclair-Nachlas der Indiana University.
Bladder perforation after augmentation cystoplasty: Determining the best management option.

Introduction Delayed bladder perforation is a well-described complication after augmentation cystoplasty. Although the frequency, risk factors, and diagnostic challenges are well documented, discussions regarding management strategies are sparse. Objective We evaluated our experience of managing augmented bladder perforation to interrogate the hypothesis that non-operative management can be used effectively. Study design We retrospectively evaluated the management of 10 patients with augmented bladder perforations over a 16-year period (Jan 2000–Jan 2016). Patients who demonstrated clinical deterioration, severe peritonitis, or extensive extravasation on imaging underwent exploratory laparotomy and primary closure. Clinically stable patients with minimal extravasation were managed non-operatively with maximal bladder drainage, and those with loculated fluid collections in feasible locations for drainage underwent an image-guided percutaneous drain placement. Results Underlying diagnoses included four patients with myelomeningocele, three with sacral agenesis, two with spinal cord injuries, and one with bladder exstrophy. Three of the four patients with myelomeningocele had concomitant ventriculoperitoneal shunts. Six patients had continent catheterizable channel creation and two patients had bladder neck reconstructions during the original operation. Four patients were managed with exploratory laparotomy and primary closure. Among the six patients managed non-operatively, three underwent image-guided drain placement in addition to maximal bladder drainage. Four patients developed re-perforation. Two of the four surgically managed patients developed re-perforation. Two of the three patients managed only with maximal bladder drainage developed re-operation. None of the patients managed non-operatively with drain placement suffered from re-perforation. Four perforation episodes were alcohol-related, two occurred after high-impact sporting activity, and two patients reported non-compliant catheterization. Discussion Non-operative management with maximal bladder drainage and selective image-guided drain placement can be successfully deployed in clinically stable patients with limited extravasation. Ensuring low intraluminal detrusor pressures and empty bladder with maximal drainage is critical for spontaneous sealing of the perforation site. Exploratory laparotomy and primary closure remains our approach for those presenting with clinical deterioration or significant extravasation on imaging. The majority of our perforations and re-perforation episodes seemed to stem from preventable behavioral risk factors. Conclusions Our findings support the hypothesis that non-operative management with maximal bladder drainage and image-guided drain placement can be effective in stable patients with limited extravasation. Summary figure. Management decision and results. Figure options Download full-size image Download high-quality image (275 K) Download as PowerPoint slide
On Non-Heuristic Motion Planning in Unknown Environment

Abstract This work is concerned with planning collision-free paths for robotic systems in an environment with obstacles, when any point of the (multi-link) robot body can be subject to collision. A class of non-heuristic algorithms is presented based on a model whereby the information about the scene is considered to be uncertain or unknown, and the system has a feedback information about its immediate surroundings. Such local information is shown to be sufficient to guarantee reaching a global goal, while generating reasonable (if. in general, not optimal) paths. Here, a case of a planar arm with revolute joints is studied. No constraints on the shape of the robot or the obstacles are imposed. The general idea is to reduce the problem of motion planning to analysis of simple closed curves on the surface of an appropriate two-dimensional manifold.
Prevalence of sleep problems and quality of life in an older population.

Study Objectives: To determine the prevalence of insomnia traits in a population and the effect of these traits on health-related quality of life. Design: The Epidemiology of Hearing Loss Study is a population-based study in Beaver Dam, Wisconsin. Setting: Participants were interviewed as part of the 5-year follow-up examination (1998-2000) of the Epidemiology of Hearing Loss Study. Participants were interviewed at the study office in Beaver Dam, WI, by telephone, or at their residence. Participants: 2800 adults aged 53-97 years. Interventions: N/A Measurements and Results: Participants were asked to what extent they experienced difficulty getting to sleep, waking up at night and having a hard time getting back to sleep, and waking up repeatedly during the night for any reason. A response of often or almost always was coded as positive for an insomnia trait. The SF-36 was administered to assess mental and physical function. Twenty-six percent of the population reported one insomnia trait, 13% reported two, and 10% reported three. All eight domains and the Mental and Physical Component Summary scores of the SF-36 decreased significantly (F-test for linear trend statistically significant at p<0.0001) as the number of reported insomnia traits increased. Conclusions: These results indicate that symptoms of insomnia are common among older adults and are associated with a decrease in health related quality of life.
Lymphocele After Vein Harvesting

Approach that effectively solves this complication avoiding multiple needle punctures of evacuating attempts that never work.