cssi/SciSciGPT-SciSciNet huggingface dataset:
Opposite Consequences of Tonic and Phasic Increases in Accumbal Dopamine on Alcohol-Seeking Behavior.

Summary Despite many years of work on dopaminergic mechanisms of alcohol addiction, much of the evidence remains mostly correlative in nature. Fortunately, recent technological advances have provided the opportunity to explore the causal role of alterations in neurotransmission within circuits involved in addictive behaviors. Here, we address this critical gap in our knowledge by integrating an optogenetic approach and an operant alcohol self-administration paradigm to assess directly how accumbal dopamine (DA) release dynamics influences the appetitive (seeking) component of alcohol-drinking behavior. We show that appetitive reward-seeking behavior in rats trained to self-administer alcohol can be shaped causally by ventral tegmental area-nucleus accumbens (VTA-NAc) DA neurotransmission. Our findings reveal that phasic patterns of DA release within this circuit enhance a discrete measure of alcohol seeking, whereas tonic patterns of stimulation inhibit this behavior. Moreover, we provide mechanistic evidence that tonic-phasic interplay within the VTA-NAc DA circuit underlies these seemingly paradoxical effects.
Symbiosis in Action: Reconfigurable Architectures and EDA

Spatial compute architectures, like Field Programmable Gate Arrays (FPGAs), constitute a key architectural pillar in modern heterogeneous compute platforms. Spatial architectures need a sophisticated Electronic Design Automation (EDA) compiler to optimally map and fit a user's workload/design onto the underlying spatial device. This EDA compiler not only helps users to custom-configure the spatial device but is also critically required for architectural exploration of new spatial architectures. The FPGA industry has had a long history of innovation in this symbiotic relationship between EDA and reconfigurable spatial architectures. This talk will walk down the memory lane of multiple waves of such innovation, amplifying how the complexity of EDA technology has not only scaled with Moore's law scaling of size and complexity of silicon hardware, but also how it has been pivotal in the architectural design of modern FPGAs. A general overview of modern FPGA EDA flows and key differences compared to Application-Specific Integrated Circuit (ASIC) EDA flows will be discussed. State-of-the-art FPGAs, Stratix® 10 and AgileX™ from Intel incorporate an advanced register-rich HyperFlex™ architecture that introduces disruptive optimization opportunities in the EDA compiler. Such physical synthesis optimization technologies like logic retiming, clock skew optimization, time borrowing, and their synergies and challenges will be discussed. Solving these challenges enables FPGAs to achieve non-linear performance improvements. Logic retiming was first introduced as a powerful sequential design optimization technique three decades ago, yet gained limited popularity in the ASIC industry, because of the lack of scalable sequential verification techniques. This talk will highlight the root causes of this issue and present innovations in retiming technology and constrained random simulation that allow the successful verification of retimed circuits, thereby enabling the use of logic retiming for FPGAs. FPGAs have traditionally targeted Register-Transfer Level (RTL) designers. To enable wider adoption of FPGAs, Intel has developed several High-Level Design (HLD) tools, frameworks, libraries, and methodologies, raising the level of programming abstraction. This talk will provide a glimpse into Intel's HLD offerings that enable software developers in the broader ecosystem to leverage FPGAs. Academic researchers will also be provided with some key research vectors to help propel the FPGA industry further.
Chapter 2 – Random Variables

This chapter discusses random variables including events defined by random variables, discrete random variables, continuous random variables, cumulative distribution function, probability mass function of discrete random variables, and probability distribution function of continuous random variables.
XerD-dependent integration of a novel filamentous phage Cf2 into the Xanthomonas citri genome.

Abstract Filamentous Inoviridae phages integrate into the chromosome of plant pathogens Xanthomonas as prophages, but their diversity and integrative mechanism are not completely understood. A proviral Cf2 sequence of 6454 bases from Xanthomonas citri genome was revived as infectious virions able to lysogenize its host. Unlike other Xanthomonas phages (Cf1c, φLf, Xf109, XacF1), Cf2 phage has RstA/RstB replication protein, and its attP has XerD binding arm and dif central region but lacks XerC binding arm. XerC+/Xf109 and XerD+/Cf2 attPs are in the opposite direction in phage genomes. Moreover, XerCD binding and XerD catalysis for strand exchange are necessary for site-specific integration of XerD+/Cf2 and XerC+/Xf109 attPs. Taken together, these results provide a new insight into the mechanism of XerCD-mediated recombination at XerD + attP.
Ultrasound imaging to monitor response of orthotopic pancreatic cancer xenografts treated with TRA-8 anti-DR5 MAb and gemcitabine

1603 Objectives: TRA-8 MAb binds to TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) death receptor 5 (DR5) and enhances the cytotoxicity of gemcitabine against human pancreatic cancer cells. The objectives of this study were to develop an orthotopic model of pancreatic cancer and to use ultrasound imaging to monitor response to TRA-8 and gemcitabine treatment. Methods: The MIA PaCa-2 cell line was evaluated for cytotoxicity after treatment with TRA-8 and/or gemcitabine. Twenty-four hours after gemcitabine treatment, cells were treated with various concentrations of TRA-8, and 24 h later processed using an ATPLite assay system. Results are presented as the concentration of TRA-8, gemcitabine, or TRA-8 + gemcitabine to produce 50% cytotoxicity (IC50) as compared to untreated control cells. Orthotopic tumors were established by injecting 2x106 MIA PaCa-2 cells into the pancreas of SCID mice. Twenty-one days after tumor implantation, each mouse underwent abdominal ultrasound examination to verify tumor presence and quantify tumor surface area (length x width). Mice were then assigned to one of four groups (n = 10/group) to provide an equal mean tumor size in each group. The treatment groups were: untreated, gemcitabine (120 μg/kg I.P. on days 23 and 30 post-implant), TRA-8 (200 µg I.P. on days 22, 26, 29, and 33), or combination therapy of gemcitabine and TRA-8. Mice were subjected to additional ultrasound examinations on days 41 and 83. Mean tumor size was calculated for the 4 treatment groups and compared to that from the first ultrasound examination. Animals were also followed for survival. Results: MIA PaCa-2 cells were sensitive to TRA-8 and gemcitabine treatment in vitro (IC50 = 16.5 ng/ml and 300 nM, respectively). Combination treatment with 30 nM gemcitabine and 5 ng/ml TRA-8 yielded reduction in cell viability greater than individual treatment with gemcitabine (68% reduction vs. 37%, p Conclusions: Inhibition of orthotopic pancreatic tumor growth after treatment with TRA-8 and gemcitabine can be monitored by ultrasound imaging. This provides a non-invasive procedure to predict response to treatment. Research Support (if any): This work was supported by NIH grant P20 CA10195.
Adversarial Machine Learning for Inferring Augmented Cyber Agility Prediction

Security analysts conduct continuous evaluations of cyber-defense tools to keep pace with advanced and persistent threats. Cyber agility has become a critical proactive security resource that makes it possible to measure defense adjustments and reactions to rising threats. Subsequently, machine learning has been applied to support cyber agility prediction as an essential effort to anticipate future security performance. Nevertheless, apt and treacherous actors motivated by economic incentives continue to prevail in circumventing machine learning-based protection tools. Adversarial learning, widely applied to computer security, especially intrusion detection, has emerged as a new area of concern for the recently recognized critical cyber agility prediction. The rationale is, if a sophisticated malicious actor obtains the cyber agility parameters, correct prediction cannot be guaranteed. Unless with a demonstration of white-box attack failures.The challenge lies in recognizing that unconstrained adversaries hold vast potential capabilities. In practice, they could have perfect-knowledge, i.e., a full understanding of the defense tool in use. We address this challenge by proposing an adversarial machine learning approach that achieves accurate cyber agility forecast through mapped nefarious influence on static defense tools metrics. Considering an adversary would aim at influencing perilous confidence in a defense tool, we demonstrate resilient cyber agility prediction through verified attack signatures in dynamic learning windows. After that, we compare cyber agility prediction under negative influence with and without our proposed dynamic learning windows. Our numerical results show the model’s execution degrades without adversarial machine learning. Such a feigned measure of performance could lead to incorrect software security patching.
Heterozygous GBA D409V and ATP13a2 mutations do not exacerbate pathological α-synuclein spread in the prodromal preformed fibrils model in young mice.

Abstract Autophagic dysregulation and lysosomal impairment have been implicated in the pathogenesis of Parkinson's disease, partly due to the identification of mutations in multiple genes involved in these pathways such as GBA, SNCA, ATP13a2 (also known as PARK9), TMEM175 and LRRK2. Mutations resulting in lysosomal dysfunction are proposed to contribute to Parkinson's disease by increasing α-synuclein levels, that in turn may promote aggregation of this protein. Here, we used two different genetic models–one heterozygous for a mutated form of the GBA protein (D409V), and the other heterozygous for an ATP13a2 loss-of-function mutation, to test whether these mutations exacerbate the spread of α-synuclein pathology following injection of α-synuclein preformed fibrils in the olfactory bulb of 12-week-old mice. Contrary to our hypothesis, we found that mice harboring GBA D409V+/− and ATP13a2+/− mutations did not have exacerbated behavioral impairments or histopathology (α-synuclein, LAMP2, and Iba1) when compared to their wildtype littermates. This indicates that in the young mouse brain, neither the GBA D409V mutation or ATP13a2 loss-of-function mutation accelerate the spread of α-synuclein pathology. As a consequence, we postulate that these mutations increase Parkinson's disease risk only by acting in one of the initial, upstream events in the Parkinson's disease pathogenic process. Further, the mutations, and the molecular pathways they impact, appear to play a less important role once the pathogenic process has been triggered and therefore do not specifically influence α-synuclein pathology spread.
SU-E-J-170: Dosimetric Consequences of Uncorrected Rotational Setup Errors During Stereotactic Body Radiation Therapy (SBRT) Treatment of Pancreatic Cancers

Purpose: To explore the dosimetric consequences of uncorrected rotational setup errors during SBRT for pancreatic cancer patients. Methods: This was a retrospective study utilizing data from ten (n=10) previously treated SBRT pancreas patients. For each original planning CT, we applied rotational transformations to derive additional CT images representative of possible rotational setup errors. This resulted in 6 different sets of rotational combinations, creating a total of 60 CT planning images. The patients’ clinical dosimetric plans were then applied to their corresponding rotated CT images. The 6 rotation sets encompassed a 3, 2 and 1-degree rotation in each rotational direction and a 3-degree in just the pitch, a 3-degree in just the yaw and a 3-degree in just the roll. After the dosimetric plan was applied to the rotated CT images, the resulting plan was then evaluated and compared with the clinical plan for tumor coverage and normal tissue sparing. Results: PTV coverage, defined here by V33 throughout all of the patients’ clinical plans, ranged from 92–98%. After an n degree rotation in each rotational direction that range decreased to 68–87%, 85–92%, and 88– 94% for n=3, 2 and 1 respectively. Normal tissue sparing defined here by the proximal stomach V15more » throughout all of the patients’ clinical plans ranged from 0–8.9 cc. After an n degree rotation in each rotational direction that range increased to 0–17 cc, 0–12 cc, and 0–10 cc for n=3, 2, and 1 respectively. Conclusion: For pancreatic SBRT, small rotational setup errors in the pitch, yaw and roll direction on average caused under dosage to PTV and over dosage to proximal normal tissue. The 1-degree rotation was on average the least detrimental to the normal tissue and the coverage of the PTV. The 3-degree yaw created on average the lowest increase in volume coverage to normal tissue. This research was sponsored by the AAPM Education Council through the AAPM Education and Research Fund for the AAPM Summer Undergraduate Fellowship Program.« less
Breast Cancer and Sexuality

Sexuality is often a neglected component of treatment for an individual diagnosed with cancer. Research suggests that many long-term cancer survivors experience global and profound sexual dysfunction. Common sexual difficulties associated with breast cancer and its treatment include decreased sexual desire, sexual arousal difficulties, change in responsiveness to physical sensations, experience of pain during intercourse, and loss of pleasure from sex. Chemotherapy, radiation therapy, fatigue, medications, and other comorbid medical illnesses may impair the female sexual response. As patients experience increased disease-free survival time, they require more attention to be directed to this important quality-of-life issue. In response to the need for professional education and clinical services for individuals who experience sexual difficulties as the result of medical illness, a unique multidisciplinary program was developed: The Sexual Health and Rehabilitation Program (SHARP) at Beth Israel Medical Cen...
On the Parallel Complexity of Solving Recurrence Equations

We show that recurrence equations, even the simple ones, are not likely to admit fast parallel algorithms, i.e., not likely to be solvable in polylogarithmic time using a polynomial number of processors. We also look at a restricted class of recurrence equations and show that this class is solvable in O(log2n) time, but not likely in O(log n) time.
Uptake of 14C-labeled dicarboxylic amino acids in hepatocytes and hepatoma cells.

Abstract In previous studies, we observed decreased uptake of 14 C-labeled l-aspartate and l-glutamate in s.c. transplants of several rapidly growing hepatomas relative to that in normal liver. The present report extends these observations to isolated cells and indicates that circulation differences cannot be the major factor. Mean net uptakes for the two dicarboxylic amino acids in cells from the rapidly growing Morris Hepatomas 7288ctc and 7777 were 5 to 26% of corresponding values for normal hepatocytes. Rates for net uptake in Hepatoma 7787 cells were intermediate between those of the rapidly growing hepatomas and hepatocytes, while the rates for Hepatoma 5123C cells and hepatocytes were similar. The contribution of sodium-dependent uptake to the mean total net uptake of [ 14 C]aspartate and [ 14 C]glutamate tended to be higher in hepatoma cells than in hepatocytes. Studies with isolated hepatocytes and Hepatoma 5123C cells showed no significant effect on uptake by 10 mm α-(methylamino)isobutyric acid and 10 mm 2-amino-2-carboxybicyclo[2.2.1]heptane. On the other hand, l-cysteic acid, l-alanosine, and N -phosphonacetyl-l-aspartic acid were shown to be effective inhibitors of sodium-dependent uptake in Hepatoma 5123C cells. The data suggest that the A and L systems are not major contributors to the uptake of dicarboxylic amino acids in hepatic cells. It was concluded that decreased uptake of dicarboxylic amino acids in rapidly growing hepatomas may accompany decreased metabolism of these dietary nonessential amino acids.
Together in the Scrum

This article examines the work practices of news photographers and a nascent revolution in the context of news production. Two photographic forms—print and television—have traditionally operated in separate professional spheres. Now convergent internet technology is compelling newspaper organizations to demand that their photographers learn to shoot and edit video. The work of these new broadband journalists is appearing on the web as everything from musical slide shows to highly produced, narrated video stories. Using ethnographic field visits, interviews, and discourse from trade organizations, this article examines print, television, and broadband photojournalistic practice and the revolutionary changes underway in visual newswork.
Inestabilidad, costo de vida y salarios reales en Venezuela en el siglo XIX

Resumen es: El siglo xix fue una epoca tumultuosa en Venezuela. Guerras, revueltas sociales e inestabilidad politica caracterizaron este periodo. Asimismo, la econom...
Turbine Engine Cost Reduction Using Life Cycle Cost Techniques

This paper describes the technical approach and development of methodologies used to conduct design trade studies from a Life Cycle Cost standpoint. A discussion of computer program capability is followed by a general discussion of several engine design trade studies. The potential for influencing engine design using a Life Cycle Cost methodology is emphasized.
Dynamic proportional-integral augmentation of conventional control algorithms

Previous work showed how robust PI and PID controller structures can be augmented with an additional time dependent gain to improve performance. Further enhancements are shown with the addition of dynamic integral action to the feedback loop. Robustness is guaranteed with the use of internal model control tuning.
Microarray-based analysis of plasma cirDNA epigenetic modification profiling in xenografted mice exposed to intermittent hypoxia

Intermittent hypoxia (IH) during sleep is one of the major abnormalities occurring in patients suffering from obstructive sleep apnea (OSA), a highly prevalent disorder affecting 6-15% of the general population, particularly among obese people. IH has been proposed as a major determinant of oncogenetically-related processes such as tumor growth, invasion and metastasis. During the growth and expansion of tumors, fragmented DNA is released into the bloodstream and enters the circulation. Circulating tumor DNA (cirDNA) conserves the genetic and epigenetic profiles from the tumor of origin and can be isolated from the plasma fraction. Here we report a microarray-based epigenetic profiling of cirDNA isolated from blood samples of mice engrafted with TC1 epithelial lung cancer cells and controls, which were exposed to IH during sleep (XenoIH group, n = 3) or control conditions, (i.e., room air (RA); XenoRA group, n = 3) conditions. To prepare the targets for microarray hybridization, we applied a previously developed method that enriches the modified fraction of the cirDNA without amplification of genomic DNA. Regions of differential cirDNA modification between the two groups were identified by hybridizing the enriched fractions for each sample to Affymetrix GeneChip Human Promoter Arrays 1.0R. Microarray raw and processed data were deposited in NCBI's Gene Expression Omnibus (GEO) database (accession number: GSE61070).
EmrA1 membrane fusion protein of Francisella tularensis LVS is required for resistance to oxidative stress, intramacrophage survival and virulence in mice.

Summary Francisella tularensis is a category A biodefence agent that causes a fatal human disease known as tularaemia. The pathogenicity of F. tularensis depends on its ability to persist inside host immune cells primarily by resisting an attack from host-generated reactive oxygen and nitrogen species (ROS/RNS). Based on the ability of F. tularensis to resist high ROS/RNS levels, we have hypothesized that additional unknown factors act in conjunction with known antioxidant defences to render ROS resistance. By screening a transposon insertion library of F. tularensis LVS in the presence of hydrogen peroxide, we have identified an oxidant-sensitive mutant in putative EmrA1 (FTL_0687) secretion protein. The results demonstrate that the emrA1 mutant is highly sensitive to oxidants and several antimicrobial agents, and exhibits diminished intramacrophage growth that can be restored to wild-type F. tularensis LVS levels by either transcomplementation, inhibition of ROS generation or infection in NADPH oxidase deficient (gp91Phox−/−) macrophages. The emrA1 mutant is attenuated for virulence, which is restored by infection in gp91Phox−/− mice. Further, EmrA1 contributes to oxidative stress resistance by affecting secretion of Francisella antioxidant enzymes SodB and KatG. This study exposes unique links between transporter activity and the antioxidant defence mechanisms of F. tularensis.
Good’s Syndrome: Successful Management of Thymoma With Hypoimmunoglobulinemia

We report a case of Good's syndrome managed with surgery and immunotherapy in a 58-year-old man who presented with a left arm skin infection and cough for 2 months. Imaging and laboratory studies revealed a large anterior mediastinal mass and panhypoimmunoglobulinemia, respectively. A biopsy was consistent with thymoma, and a diagnosis of Good's syndrome was established. Thymectomy was followed by intravenous immunoglobulin G and filgrastim with complete recovery through 9 months after discharge. Good's syndrome remains a rare entity often associated with poor prognosis. Adequate surgical resection remains key to outcomes, whereas immunotherapy aids in reducing postoperative complications and may improve survival.
Experimental Seed Predator Removal Reveals Shifting Importance of Predation and Dispersal Limitation in Early Life History Stages of Tropical Forest Trees

Recruitment limitation of trees in tropical forests can occur because of high rates of seed predation or low rates of seed dispersal, but the degree to which limitation is influenced by variation in seed predator abundance, and hence variation in seed predation and dispersal, is not well understood. We experimentally reduced the density of a granivorous small mammal (Heteromys desmarestianus) by 90 % to assess the degree to which its rates of seed predation and dispersal limit seed to seedling survival of nine species of trees in a Neotropical lowland forest. Overall, the proportion of seeds that germinated was influenced more by high rates of predation than by limited dispersal. Reduction in density of H. desmarestianus resulted in an order of magnitude decrease in fruit removal rates and an order of magnitude increase in both the absolute and relative numbers of seeds that germinated. However, the proportion of seeds that were cached remained relatively constant across all periods and between control grids and removal plots. In removal plots, H. desmarestianus dispersed and cached about 10 % of the fruits they handled, of which approximately 25 % germinated. This was 2 to 3 times greater than the germination rates of undispersed seeds, and for two species dispersed seeds were the only ones that germinated. The results suggest the simultaneous occurrence of both seed predation and dispersal limitation for trees with animal-dispersed seeds, but there may also be a hierarchy of importance in the relative strength of these two mechanisms that is determined by the dynamics of seed predator populations.
Aqueous magnetic fluids stabilized by surfactant bilayers

Surfactant bilayer-stabilized aqueous magnetic fluids have been characterized in terms of their magnetic properties, particle size and size distributions, and surfactant bilayer structure. Thermal analysis showed the existence of two distinct populations of surfactants on the particle surface and possible interpenetration between the tails of the primary and secondary surfactants, which was confirmed in a small angle neutron scattering study using contrast matching.
The formation of filaments from barnacle myosin

Abstract 1. 1. A method for the preparation of barnacle myosin has been developed. 2. 2. The length of filaments formed from barnacle myosin has been measured and contrasted with rabbit myosin filaments. 3. 3. Under similar ionic conditions, the length of filaments formed from barnacle myosin is smaller than the length of filaments formed from rabbit myosin. This is in contrast to the fact that, in vivo, the myosin-containing filaments from the barnacle are much larger than those from vertebrate striated muscle.
Estimating the dimension of a fractal point process

We discuss issues involved in estimating the dimension of a fractal point process. We first define the term fractal point process and provide some examples of experimental phenomena for which they serve as suitable models. We then develop mathematical formulations of fractal point processes, and present two methods for dimension estimation and an analysis of their performance. Finally, we compare this analysis with results from both simulated and natural examples of fractal point processes.
Toward the semantic geospatial web

With the growth of the World Wide Web has come the insight that currently available methods for finding and using information on the web are often insufficient. In order to move the Web from a data repository to an information resource, a totally new way of organizing information is needed. The advent of the Semantic Web promises better retrieval methods by incorporating the data's semantics and exploiting the semantics during the search process. Such a development needs special attention from the geospatial perspective so that the particularities of geospatial meaning are captured appropriately. The creation the Semantic Geospatial Web needs the development multiple spatial and terminological ontologies, each with a formal semantics; the representation of those semantics such that they are available both to machines for processing and to people for understanding; and the processing of geospatial queries against these ontologies and the evaluation of the retrieval results based on the match between the semantics of the expressed information need and the available semantics of the information resources and search systems. This will lead to a new framework for geospatial information retrieval based on the semantics of spatial and terminological ontologies. By explicitly representing the role of semantics in different components of the information retrieval process (people, interfaces, search systems, and information resources), the Semantic Geospatial Web will enable users to retrieve more precisely the data they need, based on the semantics associated with these data.
LIVING ON THE EDGE: CHILDREN AS ‘OUTSIDERS’

Cultural geography draws attention to the position of ‘insider’ and ‘outsider’ groups in society, each with their own ‘ways of seeing’. This article focuses on a significant outsider group, who have seldom been acknowledged in contemporary geographical studies, older children. Despite a burgeoning body of research which highlights the singular environmental needs of older children, most large-scale environments are designed to reflect only adult values and usages. The visions of environmental planners and landscape architects implicitly reflect the dominant perceptions of a society, such that groups already on the edge become further marginalised by policy making. Older children are seemingly invisible on the landscape. At best they are provided with some kind of token space, commonly a playground, but otherwise they are required to fit into the alien environments of the adult world. This article evaluates the outcomes of conventional environmental planning, reports on a survey of 9–11 year old children's ways of seeing' familiar outdoor places and argues for an action plan which recognises children as full and active members of society.
Phase‐selective route to high Tc superconducting Tl2Ba2Can−1CunO2n+4 films: Combined metalorganic chemical vapor deposition using an improved barium precursor and stoichiometry‐controlled thallium vapor diffusion

Films of the Tl2Ba2Can−1CunO2n+4 high Tc superconductors (n=2 or 3) can be prepared with a high degree of phase selectivity using a combination of metalorganic chemical vapor deposition (MOCVD) and vapor diffusion. Ba‐Ca‐Cu‐O films are first prepared by MOCVD using the volatile metalorganic precursors Ba(hexafluoroacetyl‐ acetonate)2(tetraglyme), Ca(dipivaloylmethanate)2, and Cu(acetylacetonate)2. The ‘‘second‐generation’’ barium precursor exhibits significantly improved thermal stability and volatility over previously used compounds. Thallium is then incorporated into these films by vapor diffusion using a Tl‐Ba‐Ca‐Cu oxide mixture of controlled composition as the source of volatile thallium oxides. Phase control is achieved by a combination of improved stoichiometry of the deposited film, a result of the new Ba source, and annealing with the appropriate oxide mixture. The resultant films consist predominantly of the Tl2Ba2Ca2Cu3Ox or Tl2Ba2CaCu2Ox phase, each having preferential orientation of the cryst...
Duty hour reform and internal medicine residency training: no time to lose.

In the six years since restrictions were placed on resident work hours, much discussion and debate have ensued regarding the impact of these limitations on resident education and patient care. In 2008, the Institute of Medicine released a report encouraging further limits on resident work hours including a maximum shift of 16 hours unless five hours of protected sleep was provided.1 In response to this, the Accreditation Council for Graduate Medical Education (ACGME) is currently reviewing resident duty hours with a pledge to “completely examine resident duty hour standards, with a goal of making them better.”2 Although further duty hour limits for residents seem likely, there is no consensus on the impact of the initial regulations on patient care and education. In light of this, we believe internal medicine residency educators must actively participate in these discussions and serve as advocates for patients and residents through innovation and research.
Neonatal androgenization and the development of estrogen responsivity in male and female rats

Abstract Male and female rats castrated in adulthood, male rats castrated on the day of birth, and female rats administered 250 μg of testosterone propionate on the day of birth were administered various doses of estradiol benzoate in adulthood and tested for the display of lordosis. The females and neonatally castrated males exhibited a dose-dependent response to estrogen. The control males and neonatally androgenized females showed few lordosis responses when mounted by nonexperimental males regardless of the dose of estrogen administered. The combination of progesterone with the estrogen treatment did not facilitate lordosis responding in the males and neonatally androgenized females, nor did an extensive adaptation period to the test arena, nor did 10 days of treatment with 200 μg estradiol benzoate daily. It was concluded that males and neonatally androgenized females are less responsive to estrogen in adulthood than are females and neonatally castrated males.
Effects of noise, correlations, and errors in the preparation of initial states in quantum simulations

In principle, a quantum system could be used to simulate another quantum system. The purpose of such a simulation would be to obtain information about problems which are difficult to simulate on a classical computer due to the exponential increase of the Hilbert space with the size of the system and which cannot be readily measured or controlled in an experiment. The system will interact with the surrounding environment and with the other particles in the system, and be implemented using imperfect controls, making it subject to noise. It has been suggested that noise does not need to be controlled to the same extent as it must be for general quantum computing. However, the effects of noise in quantum simulations are not well understood and how best to treat them in most cases is not known. In this paper we study an existing quantum algorithm for simulating the one-dimensional Fano-Anderson model using a liquid-state NMR device. We examine models of noise in the evolution using different initial states in the original model. We also add interacting spins to simulate a realistic situation where an environment of spins is present. We find that states which are entangled with their environment, and sometimes correlated but not necessarily entangled, have an evolution which is described by maps which are not completely positive. We discuss the conditions for this to occur and also the implications.
Two Motifs in the Translational Repressor PHAS-I Required for Efficient Phosphorylation by Mammalian Target of Rapamycin and for Recognition by Raptor *

Mammalian target of rapamycin (mTOR) is the central element of a signaling pathway involved in the control of mRNA translation and cell growth. The actions of mTOR are mediated in part through the phosphorylation of the eukaryotic initiation factor 4E-binding protein, PHAS-I. In vitro mTOR phosphorylates PHAS-I in sites that control PHAS-I binding to eukaryotic initiation factor 4E; however, whether mTOR directly phosphorylates PHAS-I in cells has been a point of debate. The Arg-Ala-Ile-Pro (RAIP motif) and Phe-Glu-Met-Asp-Ile (tor signaling motif) sequences found in the NH2- and COOH-terminal regions of PHAS-I, respectively, are required for the efficient phosphorylation of PHAS-I in cells. Here we show that mutations in either motif markedly decreased the phosphorylation of recombinant PHAS-I by mTOR in vitro. Wild-type PHAS-I, but none of the mutant proteins, was coimmunoprecipitated with hemagglutinin-tagged raptor, an mTOR-associated protein, after extracts of cells overexpressing raptor had been supplemented with recombinant PHAS-I proteins. Moreover, raptor overexpression enhanced the phosphorylation of wild-type PHAS-I by mTOR but not the phosphorylation of the mutant proteins. The results not only provide direct evidence that both the RAIP and tor signaling motifs are important for the phosphorylation by mTOR, possibly by allowing PHAS-I binding to raptor, but also support the view that mTOR phosphorylates PHAS-I in cells.
Chromium-molybdenum steels for fusion reactor first walls — a review

Abstract Chromium-molybdenum steels have recently become of interest as a first wall and blanket structural material for fusion reactors. This application will be assessed, and possible approaches on how CrMo alloys may be further developed for this application will be proposed. Generally, the CrMo steels can be divided into two categories: unmodified, basically CrMoC steels and CrMoC steels modified by the addition of carbide-forming elements. Extensive research and development efforts have been conducted on the unmodified steels, especially 2 1 4 Cr-1 Mo and 12 CrMo steels. Considerable work has also been done on 12 CrMo steels modified with additions of V, Nb, Ti and W. In recent years much of the research effort on this type of alloy has been directed at developing modified CrMo steels with less than 12% Cr (generally ⩽9%) for applications where the “stainless” properties imparted by chromium additions of at least 12% are not needed. We will examine the unmodified and modified steels in terms of hardenability, precipitation processes (stability at elevated temperatures), strength, and toughness. Where possible, we will discuss the effects of irradiation on these properties. Such a study leads to the types of tradeoffs that may be necessary between the well-researched unmodified 2 1 4 Cr-1 Mo steel and a high-chromium modified steel.
Selectivities in methylcyclopentane and n-hexane conversion on some metal-loaded SAPO-11 catalysts

Abstract The medium pore silicoaluminophosphate molecular sieve SAPO-11 of mild acidity was loaded with platinum or palladium by ion exchange and wet impregnation and investigated as to activity and selectivity in methylcyclopentane (MCP) hydrogenolysis and n-hexane (nHEX) conversion at 1 atm and 673 K. For MCP high selectivities for benzene formation were observed, while for nHEX high selectivities for the formation of iso-hexane isomers were found. In addition an unusually high n-hexane selectivity in the ring opening reaction of MCP and the formation of benzene for a set of NaN 3 -treated Pd/ SAPO-11 and Pt/SAPO-11 catalysts were observed for both the MCP and nHEX reactions. The somewhat peculiar selectivity patterns in this class of molecular sieve catalysts are interpreted in terms of a series of reaction pathways incorporating both confinement effects and shape selectivity factors as being of importance in determination of the observed product distributions.
Algorithm for fast implementation of vector-type Preisach hysteresis models

An alternative implementation of vector-type Preisach models is proposed. Input curves are represented by polygonal lines and history is treated as a collection of vertices on these lines. Computation of output increments is reduced to computing the contribution due to each vertex separately. Contribution of each vertex, in turn, can be found using experimental or precomputed data from partially reversing input curves. >
Rapid assay to detect peptidases in column effluent fractions using L-amino acid oxidase.

Abstract A rapid, sensitive method to detect peptidase activity which utilizes an amino acid oxidase-coupled reaction adapted for microassay in wells of disposotrays is described. Susceptible amino acids in the presence of oxidase produce hydrogen peroxide, which combines with dianisidine to give a colored product. Immediately following column chromatography effluent fractions can be scanned simultaneously for peptidase activity toward several substrates. Color production enables direct visualization of relative rates of peptide cleavage as hydrolysis proceeds. This microassay enables one to simultaneously localize peptidases in effluent fractions following chromatography, gain information concerning substrate specificity of each peptidase eluted, and estimate the relative rates of hydrolysis of a given peptide by several enzymes.
Calcium imaging of auditory nerve fiber terminals in the cochlear nucleus

One important model for understanding neuronal computation is how auditory information is transformed at the synapses made by auditory nerve (AN) fibers on the bushy cells (BCs) in the anteroventral cochlear nucleus (AVCN). This transformation is influenced by synaptic plasticity, the mechanisms of which have been studied primarily using postsynaptic electrophysiology. However, it is also important to make direct measurements of the presynaptic terminal to consider presynaptic mechanisms. Here we introduce a technique for doing that using calcium imaging of presynaptic AN terminals, by injecting dextran-conjugated fluorophores into the cochlea. To measure the calcium transients, we used calcium-sensitive fluorophores, and measured the changes in fluorescence upon stimulation. As an example of the application of this technique, we showed that activation of GABA(B) receptors reduces presynaptic calcium influx. This technique could be further extended to study the effects of activity- and other neuromodulator-dependent plasticities on AN terminals.
Book Review: Transmedia Television: New Trends in Network Serial Production, by M. J. Clarke

Transmedia Television: New Trends in Network Serial Production. M. J. Clarke. New York: Bloomsbury, 2013. 242 pp. $100 hbk. $29.95 pbk.Critical approaches to media scholarship often avoid incorporating the process of production from the perspective of the producers. Transmedia Television: New Trends in Network Serial Production by M. J. Clarke, who earned his PhD in Film and Television from UCLA in 2010, attempts to challenge this trend by taking up the intimidating task of reaching out to producers to integrate "industrial data in the form of both business strategy and individual practice with textual data through the analysis of programming and [suggest] the ways in which programming trends replicate, complicate, or anticipate the conditions of production itself." The result is a book that seeks to advance our understanding of how today's television functions to create meaning as well as researchers' methods for understanding those functions.Transmedia Television is written in two parts. The book begins with a short but effective introduction that explains Clarke's approach to research that includes the nature of production and argues for the consideration of ancillary paratexts in media research. Part 1 examines four of these ancillary texts: the comic book, the tie-in novel, the video game, and the mobisode. Each of these is part of what Clarke calls "tentpole TV," an attempt by media producers to bring transmedia storytelling to the television experience. This section focuses on how these four types of texts are produced and used in relationship to the television series. These chapters provide some useful evidence as to why contemporary television is struggling to find its form in an everchanging landscape.While Part 1 focuses heavily on the production aspect of tentpole TV, Part 2 turns to three textual analyses of twenty-first-century television programs. Clarke uses these critical analyses to explore the ways in which transmedia television must account for problems of time, space, and continuity. Chapter 5, for example, is a detailed study of Lost to explore two trends, non-linear episodic texts and persistent master narratives, which are seemingly at-odds. Chapter 7's argument that reflexivity in the show Alias works to respond not only to its own characters and narrative but also to the nature of its production also provides some valuable insight.Part 1 of Transmedia Television feels like a failed exercise, not on the part of Clarke but on the part of the media producers themselves. When Clarke is able to incorporate the feedback from producers, it is often only the producers of the ancillary texts that contribute, and much of what they have to say involves a lack of communication, cooperation, or interest on the part of the television producers to dedicate themselves to the tentpole TV experience. This is best exemplified in the chapter on the mobisode, where Clarke opens up by admitting the mobisode is already "largely a dead end in the practice of transmedia. …
Protein kinases C isozymes are differentially expressed in human breast carcinomas.

Aims The protein kinase C (PKC) family of enzymes has been implicated in cellular proliferation, differentiation, and apoptosis. However, the distribution of specific PKC isoforms with varying functions in normal and malignant human tissues remains to be determined. The objective of this study was to investigate the expression of certain PKC isoforms (α, βI, βII, e) in human breast cancer specimens relative to adjacent uninvolved tissue (n = 24) and in the normal breast tissue obtained from patients undergoing reduction mammoplasty (n = 12).
Corneal stem cells: bridging the knowledge gap.

Stem cell research offers hope to countless patients whose conditions have heretofore been deemed incurable. Better understanding of stem cell behaviors and functions will lead to insights into biological mysteries encompassing the fields of angiogenesis, development, tissue homeostasis, wound healing, and carcinogenesis. Clarity of vision requires smooth ocular surface on which the corneal epithelial cells undergo continuous turnover every 3 to 10 days. Tragically, many patients are blinded and devastated by severe ocular surface diseases due to limbal stem cell deficiency even though, besides opaque cornea, their eyes are otherwise healthy. Corneal stem cell transplantation offers hope by creating clear windows for these eyes; unfortunately, the long-term successful outcome remains limited. The nature of corneal epithelial stem cell is poorly understood, but many circumstantial evidences suggest the presence of “source cells” in the limbal region of the eye. Nonetheless, the precise biomarker of corneal...
Fluorometric assay of O-linked glycoproteins by reaction with 2-cyanoacetamide

A simple assay for O-glycosylated glycoproteins involving the liberation of oligosaccharides by beta-elimination with dilute alkali and the subsequent derivatization of the reducing end with 2-cyanoacetamide is reported. The method can be used to quantitate microgram amounts of mucin within 30 min. The assay is 30 times less sensitive to protein or N-linked glycoproteins and 100 times less sensitive to DNA than to the corresponding weight of canine tracheal mucin. Of the substances tested, only cesium chloride and potassium thiocyanate caused substantial interference, but in neither case was this sufficiently serious to prevent the method being used for monitoring mucin purification schemes utilizing these reagents. The coefficients of variation for replicate analyses of canine tracheal mucin (14.0, 5.0, and 2.0 micrograms) were 3.6, 6.5, and 12.3%, respectively.
Realpolitik, Punishment and Control: Thucydides on the Moralization of Conflict

The pages of Thucydides show us many expressions of what one might call the amoral doctrine in international politics, namely, that politics between political communities are not properly subject to ethical evaluation. This article traces Thucydides' understated critique of this idea. I first show that concerns about transgression and punishment inexorably influence political action. Moreover, Thucydides suggests a connection between the aspirations of realpolitik and the desire of the political community to preserve the freedom to effect justice and not subordinate its will to the dictates of necessity – especially necessities imposed by other political bodies. I then describe Thucydides' explanation for why political communities persist in regarding themselves primarily as moral agents rather than security-maximizers. I finally describe what Thucydides regards to be a more genuine realism. This truer realism maintains the possibility of constrained moral choice while still engendering a prudent pessimis...
Transcriptomic study reveals widespread spliced leader trans-splicing, short 5'-UTRs and potential complex carbon fixation mechanisms in the euglenoid Alga Eutreptiella sp.

Eutreptiella are an evolutionarily unique and ecologically important genus of microalgae, but they are poorly understood with regard to their genomic make-up and expression profiles. Through the analysis of the full-length cDNAs from a Eutreptiella species, we found a conserved 28-nt spliced leader sequence (Eut-SL, ACACUUUCUGAGUGUCUAUUUUUUUUCG) was trans-spliced to the mRNAs of Eutreptiella sp. Using a primer derived from Eut-SL, we constructed four cDNA libraries under contrasting physiological conditions for 454 pyrosequencing. Clustering analysis of the ∼1.9×106 original reads (average length 382 bp) yielded 36,643 unique transcripts. Although only 28% of the transcripts matched documented genes, this fraction represents a functionally very diverse gene set, suggesting that SL trans-splicing is likely ubiquitous in this alga’s transcriptome. The mRNAs of Eutreptiella sp. seemed to have short 5′- untranslated regions, estimated to be 21 nucleotides on average. Among the diverse biochemical pathways represented in the transcriptome we obtained, carbonic anhydrase and genes known to function in the C4 pathway and heterotrophic carbon fixation were found, posing a question whether Eutreptiella sp. employs multifaceted strategies to acquire and fix carbon efficiently. This first large-scale transcriptomic dataset for a euglenoid uncovers many potential novel genes and overall offers a valuable genetic resource for research on euglenoid algae.