cssi/SciSciGPT-SciSciNet huggingface dataset:
Improving Fluorouracil Chemotherapy with Novel Orally Administered Fluoropyrimidines

During the 40 years since the initial synthesis of fluorouracil, there have been many attempts to improve fluoropyrimidine chemotherapy. These have included the utilisation of different schedules of fluorouracil administration, modulation of the metabolism of fluorouracil with other drugs to increase its therapeutic benefit, and the synthesis of prodrugs of fluorouracil that are potentially more effective and less toxic. Of particular interest at present is the clinical evaluation of several new fluoropyrimidine drugs that can be orally administered. These include capecitabine, tegafur/uracil (UFT®), eniluracil (GW-776C85; 5-ethynyluracil), S-1, and emitefur (BOF-A2). The pharmacological principles that have influenced the development of these new drugs are initially presented. This is followed by a review of our current knowledge of the clinical pharmacology of each of these new agents, focusing on antitumour activity and toxicity from studies conducted in the US. Studies of capecitabine, tegafur/uracil, and early studies with eniluracil indicate that these drugs have at least similar activity to protracted fluorouracil infusion but with additional quality-of-life and economic benefits.
Advanced control and processing capabilities in the aquarius scatterometer flight electronics

The Aquarius mission requirement for 0.1 dB scatterometer measurement stability has driven the radar's control and processing hardware design. Two new aspects of the flight electronics that contribute toward the overall stability will be discussed in this paper: 1) a high- rate radar timing mode for verifying performance on the ground, and 2) an onboard processor for flagging echoes corrupted by radio-frequency interference (RFI).
Hanohano: Hawaiian Antineutrino Observatory

Design studies are underway for the deep ocean antineutrino observatory Hanohano. The 10 kton monolitic underwater detector will be able to make precision measurement of neutrino mixing parameters (including θ13 and neutrino mass hierarchy) if stationed around 60 km offshore, from the nuclear reactor. Hanohano will be a mobile detector and placing it in a mid-Pacific location will provide the first ever flux measurement of geoneutrinos (antineutrinos emitted in the radioactive decay series of uranium and thorium), coming from the Earth's mantle and perform a sensitivity search for a hypothetical natural fission reactor in the Earth's core. Additional deployment at a different mid-ocean location will lead to tests of lateral heterogeneity of uranium and thorium in the Earth's mantle. These measurements would provide an important insight into deep-Earth geophysics, mantle composition and understanding of the Earth's heat flow and sources of energy inside the Earth.
Cyclic steady states of treaded rolling bodies

Author(s): Govindjee, S; Potter, T; Wilkening, J | Abstract: The analysis of spinning axisymmetric bodies undergoing finite deformation is useful for understanding the behavior of a wide variety of engineering systems - for example, rolling tires. However, progress beyond the axisymmetric case has been lacking. In this work, we present a methodology for the treatment of treaded rolling bodies by devising a Newton-Krylov shooting scheme for the computation of cyclic steady states of motion. The scheme advocated permits one to determine the entire transient (cyclically steady) motion of a spinning treaded body with consideration of viscoelasticity as well as contact. We demonstrate the viability of the method through three examples, (1) a viscoelastic cylinder with eight sinusoidal tread blocks, (2) a viscoelastic cylinder with 16 square tread blocks, and (3) a viscoelastic oval in which repeated contact and separation from a rigid plane excites distinct transient vibrational modes in the body during each cycle. For practical values of the viscoelastic relaxation time, the new approach is found to converge faster than the naive approach of evolving an initial guess over many cycles until a cyclic steady state is reached.
YOUNG WOMEN AND GANG VIOLENCE: GENDER, STREET OFFENDING, AND VIOLENT VICTIMIZATION IN GANGS*

Drawing on multiple data sources in St. Louis, this article examines how gendered situational dynamics shape gang violence, including participation in violent offending and experiences of violent victimization. Combining an analysis of in-depth interviews with young women in St. Louis gangs with an examination of homicide reports from the same city, we find that young women, even regular offenders, highlight the significance of gender in shaping and limiting their involvement in serious violence. They use gender both to accomplish their criminal activities and to temper their involvement in gang crime. Consequently their risk for serious physical victimization in gangs is considerably less than young men's. St. Louis homicide data collaborate these qualitative findings. Not only are young women much less likely to be the victims of gang homicide, but the vast majority of female gang homicide victims were not the intended targets of the attack. In contrast, homicide reports suggest that the majority of mal...
In Search of Human Placentophagy: A Cross-Cultural Survey of Human Placenta Consumption, Disposal Practices, and Cultural Beliefs

Maternal placentophagy, the consumption of the placenta or “afterbirth” by the mother following parturition, is an ubiquitous behavior among eutherian mammals, including non-human primates. Here we report on a cross-cultural survey of 179 human societies regarding the consumption, treatment, and disposal of human placenta, in addition to accompanying cultural beliefs and perceptions about the organ. The conspicuous absence of cultural traditions associated with maternal placentophagy in the cross-cultural ethnographic record raises interesting questions relative to its ubiquitous presence among nearly all other mammals, and the reasons for its absence (or extreme rarity) among prehistoric/historic and contemporary human cultures.
Time-constrained failure diagnosis in distributed embedded systems

Advanced automotive control applications such as steer and brake-by-wire are typically implemented as distributed systems comprising many embedded processors, sensors, and actuators interconnected via a communication bus. They have severe cost constraints but demand a high level of safety and performance. Motivated by the need for timely diagnosis of faulty actuators in such systems, we present a general method to implement failure diagnosis under deadline and resource constraints. Actuators are diagnosed in distributed fashion by processors to provide a global view of their fault status. The diagnostic tests are implemented in software using analytical redundancy and execute concurrently with the control tasks. The proposed method solves the test scheduling problem using a static list-based approach which guarantees actuator diagnosis within designer-specified deadlines while meeting control performance goals. As a secondary objective, it also minimizes the number of required processors. We present simulation results evaluating the effectiveness of the proposed method under various design constraints.
Molecular, Biological, and In Vivo Characterization of the Guinea Pig Cytomegalovirus (CMV) Homologs of the Human CMV Matrix Proteins pp71 (UL82) and pp65 (UL83)

We recently identified the genes encoding the guinea pig cytomegalovirus (GPCMV) homologs of the upper and lower matrix proteins of human CMV, pp71 (UL82) and pp65 (UL83), which we designated GP82 and GP83, respectively. Transient-expression studies with a GP82 plasmid demonstrated that the encoded protein targets the nucleus and that the infectivity and plaquing efficiency of cotransfected GPCMV viral DNA was enhanced by GP82. The transactivation function of GP82 was not limited to GPCMV, but was also observed for a heterologous virus, herpes simplex virus type 1 (HSV-1). This was confirmed by its ability to complement the growth of an HSV-1 VP16 transactivation-defective mutant virus in an HSV viral DNA cotransfection assay. Study of a GP82 “knockout” virus (and its attendant rescuant), generated on a GPCMV bacterial artificial chromosome construct, confirmed the essential nature of the gene. Conventional homologous recombination was used to generate a GP83 mutant to examine the role of GP83 in the viral life cycle. Comparison of the one-step growth kinetics of the GP83 mutant (vAM409) and wild-type GPCMV indicated that GP83 protein is not required for viral replication in tissue culture. The role of GP83 in vivo was examined by comparing the pathogenesis of wild-type GPCMV, vAM409, and a control virus, vAM403, in guinea pigs. The vAM409 mutant was significantly attenuated for dissemination in immunocompromised strain 2 guinea pigs, suggesting that the GP83 protein is essential for full pathogenicity in vivo.
Equatorial plasma bubbles observed by DMSP satellites during a full solar cycle: Toward a global climatology

[1] We have examined more than 75,000 latitudinal profiles of plasma densities measured by ion detectors on five Defense Meteorological Satellite Program (DMSP) satellites in the evening local time (LT) sector between 1989 and 2001. This survey established detection frequencies of equatorial bubbles (EPBs) at 840 km over the recent solar cycle. The annual rate of EPB detections decreased by more than an order of magnitude from >1000 during solar maximum to 100 km lower during solar minimum than solar maximum. However, the overall effect is to increase the growth rate of the Rayleigh–Taylor instability at solar maximum in the bottomside F layer only by about a factor of 2. We suggest that the variability of electric fields in the postsunset equatorial ionosphere is the source of the observed discrepancy between EPB detections under solar maximum/minimum conditions.
Laser Annealing of Ion Implanted Silicon

Pulsed laser annealing of ion implanted silicon leads to the formation of supersaturated alloys by nonequilibrium crystal growth processes occurring at the interface during liquid phase epitaxial regrowth. The interfacial distribution coefficients from the melt (k?) and the maximum substitutional solubilities (Csmax) are far greater than equilibrium values. Both k? and Csmax are functions of growth velocity. Mechanisms limiting substitutional solubilities are discussed.
The black diaspora

Providing a history of black people outside Africa, this book describes the societies from which Africans were seized for slavery, their long struggle for freedom, and their experience today in different countries, from Britain and America to Jamaica, Haiti and Brazil. It sets out to show how the diaspora has enriched world culture, in music, language and literature, the visual arts, sport and religion. The author left South Africa in 1960 for political exile in Britain, where he convened the 1964 International Conference of Economic Sanctions against South Africa.
Induced ordered weighted averaging operators

We briefly describe the Ordered Weighted Averaging (OWA) operator and discuss a methodology for learning the associated weighting vector from observational data. We then introduce a more general type of OWA operator called the Induced Ordered Weighted Averaging (IOWA) Operator. These operators take as their argument pairs, called OWA pairs, in which one component is used to induce an ordering over the second components which are then aggregated. A number of different aggregation situations have been shown to be representable in this framework. We then show how this tool can be used to represent different types of aggregation models.
Hydrophobicity of Oligopeptides having Un-ionizable Side Chains

The hydrophobicity of any peptide is a physicochemical property not only of the amino acid sequence, but also of the secondary and tertiary structure. It is also an essential factor to consider in peptide drug delivery, which has become increasingly important in recent years with the discovery of many peptides with potential pharmaceutical uses. The hydrophobicities (log P) of dito pentapeptides reported by Akamatsu and Fujita have been correlated with 12 parameters including 7 indicator variables. We have tried to simply this equation by using more common and simple parameters. Good correlations have been obtained for log P with a five-parameter equation using the sum of the hydrophobicity of component amino acids (log Paa), molecular weight (log MW), the frequency of beta-turn formation (F beta) of peptides, which is an important tertiary structural parameter, the dipole moment (mu) calculated with a computer-assisted program, and the number of amino acids in a peptide (N). This equation should be useful in drug delivery in predicting the relative hydrophobicity of new peptides with no ionizable side chains.
Carbon fixation by basalt-hosted microbial communities.

Oceanic crust is a massive potential habitat for microbial life on Earth, yet our understanding of this ecosystem is limited due to difficulty in access. In particular, measurements of rates of microbial activity are sparse. We used stable carbon isotope incubations of crustal samples, coupled with functional gene analyses, to examine the potential for carbon fixation on oceanic crust. Both seafloor-exposed and subseafloor basalts were recovered from different mid-ocean ridge and hot spot environments (i.e., the Juan de Fuca Ridge, the Mid-Atlantic Ridge, and the Loihi Seamount) and incubated with 13C-labeled bicarbonate. Seafloor-exposed basalts revealed incorporation of 13C-label into organic matter over time, though the degree of incorporation was heterogeneous. The incorporation of 13C into biomass was inconclusive in subseafloor basalts. Translating these measurements into potential rates of carbon fixation indicated that 0.1 – 10 nmol C g-1rock d-1 could be fixed by seafloor-exposed rocks. When scaled to the global production of oceanic crust, this suggests carbon fixation rates of 10^9 – 10^12 g C yr-1, which matches earlier predictions based on thermodynamic calculations. Functional gene analyses indicate that the Calvin cycle is likely the dominant biochemical mechanism for carbon fixation in basalt-hosted biofilms, although the reductive acetyl-CoA pathway and reverse TCA cycle likely play some role in net carbon fixation. These results provide empirical evidence for autotrophy in oceanic crust, suggesting that basalt-hosted autotrophy could be a significant contributor of organic matter in this remote and vast environment.
Network-adaptive video streaming using multiple description coding and path diversity

This paper presents a TCP-friendly rate allocation algorithm for multiple description coding combined with path diversity. A 3-D SPIHT-based multiple description coding is used to generate two independent substreams and each substream is protected with an FEC-based unequal error protection algorithm. In the proposed video streaming framework, two senders simultaneously stream complementary substreams to the receiver over different paths. The proposed rate allocation algorithm coordinates distributed video streaming from multiple senders to a single receiver to minimize the overall distortion. Simulation results show that the proposed algorithm increases tolerance to packet loss due to network congestion and achieves higher visual quality compared to non-adaptive methods.
Time-delay Fizeau phase-conjugate interferometer.

A time-delay Fizeau phase-conjugate interferometer is constructed by using a BaTiO3 crystal in a degenerate four-wave-mixing configuration. The slow response time of BaTiO3 is used to build a phase-conjugate mirror that functions as a holographic memory. An optical wave and its time-delayed version are stored inside the crystal sequentially while their phase-conjugate waves are generated simultaneously. Superposition of the two phase-conjugate waves produces an interferogram as a result of the relative phase change of the input waves. The simplicity and real-time operation of this technique lead to several advantages over the conventional holographic interferometry. The use of photorefractive crystal eliminates the darkroom process and reposition procedure. A higher accuracy can be achieved because the interfering waves are phase-conjugate waves. The principle of this technique is presented and the experimental results and its applications are discussed.
Micronutrient Research, Programs, and Policy: From Meta-analyses to Metabolomics

Micronutrient deficiencies are widespread among women and children in undernourished populations. Research has identified effective approaches to their prevention, including supplementation, fortification, and dietary and other public health interventions. These interventions have made tremendous improvements in the quality of life, health, and survival of populations around the world, yet the impact varies by nutrient, population, and the outcomes chosen that reflect nutritionally driven change. The WHO guides governments and agencies toward effective strategies to prevent micronutrient deficiencies in women and children, but these are often informed by imperfect studies with limited measures of impact and the inadequate program evaluations and survey databases produced by the nutrition community. The resulting knowledge gaps limit our ability to discern what interventions are effective, under what conditions, among whom, and perhaps most important, why. However, we are moving into an era of opportunity to apply the tools of modern nutrition science, including improved methods of assessing nutritional status, “omics,” bioarchival access, systems biology thinking, and interdisciplinary collaborations, that can deepen and broaden our understanding of how micronutrients affect health, how their deficiencies diminish human capacity, and how interventions can improve the well-being of those in need. Relevant training and greater cross-disciplinary efforts will be required to ensure a cell-to-society approach that can systematically address where, to whom, and how to provide micronutrients in the future. Adv. Nutr. 5: 344S–351S, 2014.
Mo‐Doped BiVO4 Photoanodes Synthesized by Reactive Sputtering

We report a scalable and reproducible method for reactive co-sputtering of Mo-doped BiVO4 thin films with broad compositional control. Optimal photoanode performance is achieved at a Mo concentration of 3 at. %. Incorporation of Mo promotes growth of large grains and reduces majority carrier transport limitations, resulting in maximum AM1.5G photocurrent densities of 3.5 mA cm(-2) at 1.23 V vs. RHE in pH 6.8 buffer solution containing 0.1 M Na2 SO3 as a hole scavenger. Operation as a front-illuminated water oxidation photoanode is achieved by balancing the operational stability, catalytic activity, and parasitic optical absorption of a FeOOH oxygen evolution catalyst. FeOOH/Mo:BiVO4 thin film photoanodes enable water oxidation under the front-side illumination conditions used in integrated tandem water splitting devices.
Analysis of Electrochemical and Thermal Behavior of Li-Ion Cells

This paper seeks to gain a better understanding of the thermal behavior of Li-ion cells using a previously developed twodimensional, first principles-based thermal-electrochemical modeling approach. The model incorporates the reversible, irreversible, and ohmic heats in the matrix and solution phases, and the temperature dependence of the various transport, kinetic, and mass-transfer parameters based on Arrhenius expressions. Experimental data on the entropic contribution for the manganese oxide spinal and carbon electrodes, recently published in the literature, are also incorporated into the model in order to gauge the importance of this term in the overall heat generation. Simulations were used to estimate the thermal and electrical energy and the active material utilization at various rates in order to understand the effect of temperature on the electrochemistry and vice versa. In addition, the methodology of using experimental data, instead of an electrochemical model, to determine the heat-generation rate is examined by considering the differences between the local and lumped thermal models, and the assumption of using heat generation rate determined at a particular thermal environment under other conditions. Model simulations are used to gain insight
Least-squares Fourier phase estimation from the modulo 2π bispectrum phase

The recovery of Fourier phases from measurements of the bispectrum occupies a vital role in many astronomical speckle imaging schemes. In arecent paper [J. Opt. Soc. Am. A 7, 14 (1990)] it was suggested that a least-squares solution to this problem must fail if the bispectrum phase is known only modulo 2π. Here an alternative nonlinear least-squares algorithm is presented that differs from the linear method discussed in the aforementioned paper and that permits the fitting of Fourier phases directly to modulo 2π measurements of the bispectrum phase, thus eliminating any need for phase unwrapping. Numerical simulations of this method confirm that it is reliable and robust in the presence of noise and verify its enhanced performance when compared with a linear least-squares method that includes the unwrapping of the bispectral phase before Fourier phase retrieval.
Chemocatalytic hydrolysis of cellulose at 37 °C, 1 atm

The metal salt – Bronsted acidic ionic liquid system composed of ZnCl2·1.74H2O-1-(1-propylsulfonic)-3-methylimidazolium chloride can directly hydrolyze untreated cellulose in 78% total reducing sugar and 19% glucose yield at 37 °C, 1 atm in 4.0 days. The new chemical catalyst is used at a temperature lower than typical cellulase enzyme operating conditions.
Conserved Molecular Underpinnings and Characterization of a Role for Caveolin-1 in the Tumor Microenvironment of Mature T-Cell Lymphomas

Neoplasms of extra-thymic T-cell origin represent a rare and difficult population characterized by poor clinical outcome, aggressive presentation, and poorly defined molecular characteristics. Much work has been done to gain greater insights into distinguishing features among malignant subtypes, but there also exists a need to identify unifying characteristics to assist in rapid diagnosis and subsequent potential treatment. Herein, we investigated gene expression data of five different mature T-cell lymphoma subtypes (n = 187) and found 21 genes to be up- and down-regulated across all malignancies in comparison to healthy CD4+ and CD8+ T-cell controls (n = 52). From these results, we sought to characterize a role for caveolin-1 (CAV1), a gene with previous description in the progression of both solid and hematological tumors. Caveolin-1 was upregulated, albeit with a heterogeneous nature, across all mature T-cell lymphoma subtypes, a finding confirmed using immunohistochemical staining on an independent sampling of mature T-cell lymphoma biopsies (n = 65 cases). Further, stratifying malignant samples in accordance with high and low CAV1 expression revealed that higher expression of CAV1 in mature T-cell lymphomas is analogous with an enhanced inflammatory and invasive gene expression profile. Taken together, these results demonstrate a role for CAV1 in the tumor microenvironment of mature T-cell malignancies and point toward potential prognostic implications.
Abstract MP19: Serum 25-hydroxyvitamin D is associated with incident heart failure in whites but not blacks: The Atherosclerosis Risk in Communities Study (ARIC)

Background: Suboptimal 25-hydroxyvitamin D [25(OH)D] is a potential cardiovascular risk factor, likely influencing cardiovascular events via established risk factors, namely hypertension, diabetes, and inflammation. Emerging evidence also suggests that the association between 25(OH)D and cardiovascular risk is stronger in whites than blacks, but these preliminary findings need further confirmation. Hypotheses: Serum 25(OH)D is inversely associated with incident heart failure, and (a) partly mediated by traditional cardiovascular risk factors and (b) stronger among whites than blacks. Methods: A total of 12,215 ARIC Study participants free of heart failure at baseline in 1990-92 (median age 56, 24% black) were followed through 2010. Total serum 25(OH)D was measured in stored samples at baseline using LCMS. Month of blood draw was accounted for. Incident heart failure events were identified via active surveillance and defined by a hospital discharge code of ICD9-428 and parallel ICD codes for deaths. Multivariable Cox proportional hazards regression models were employed. Results: During a median of 17 years of follow-up, there were 1,799 incident heart failure events. Median 25(OH)D was 26.2 and 19.0 ng/mL in whites and blacks, respectively. The association between 25(OH)D and heart failure varied by race (p-interaction = 0.01). Among whites, those in the lowest quintile of 25(OH)D were at 2-fold greater risk of heart failure relative to those in the highest quintile ( Table ). The HR was attenuated, but remained statistically significant after multivariable adjustment. In blacks there was no association between 25(OH)D and heart failure. Results were similar when race-specific quintiles were used. Conclusions: Low serum 25(OH)D was independently associated with risk of incident heart failure among whites, but not among blacks in this community-based population. Further work is needed to determine what mechanisms underlie racial variation in the association between vitamin D status and risk of heart failure. ![][1] [1]: /embed/graphic-1.gif
A Partial Contour Similarity-Based Approach to Visual Affordances in Habile Agents

In a typical tool use task, we can view both the relationship between the agent and the tool and the relationship between the tool and the target in terms of affordances. One set of affordances relates to the ability of the agent to manipulate the tool, while a second set of affordances relates to the ability of the agent to manipulate the target by means of the tool. In both cases, effective tool use is facilitated by the coupling of one object to another: agent-to-tool-to-target. In this paper, we focus on the visual identification of such affordances via contour similarity. Objects with complementary contour segments can fit together, which suggests possible opportunities for effective interactions. We present a system for the identification and evaluation of partial contour-based matches and analyze the system’s behavior. We propose a set of sample tool-use scenarios as part of our analysis. We demonstrate the use of the system in providing guidance to an autonomous robotic agent performing tool selection tasks.
Applying Failure Mode and Effects Analysis to Supplier Selection

Supplier selection is a critical decision in supply chain management. Although organizations devote significant resources to establish detailed operating plans with suppliers, a few have developed mature risk management programs to deal with supplier failures. Past performances and survey data indicate that supplier failures are common. Supplier selection should include considerations for supplier risks. Different suppliers provide different levels of risk for an organization. Failure Mode and Effects Analysis (FMEA) is a well-established technique for evaluating and prioritizing risks. This paper seeks to provide a tool to help supply chain decision makers evaluate various supplier options by quantifying the risks associated with each supplier.
Prospective randomized controlled trial of combination ranibizumab (Lucentis) and bromfenac (Xibrom) for neovascular age-related macular degeneration: a pilot study.

PURPOSE To evaluate whether bromfenac eyedrops and ranibizumab intravitreal injections would provide added efficacy over ranibizumab alone. METHODS This was a single-site, multiinvestigator, prospective, open-label, interventional, Phase II study of patients with new or recurrent exudative/neovascular age-related macular degeneration. Thirty eyes were enrolled consecutively and were randomized in a ratio of 2:1 to combination therapy with intravitreal ranibizumab and topical bromfenac, and ranibizumab alone. All patients received ranibizumab monthly therapy for 4 months then as needed monthly in accordance with standard of care. Patients receiving bromfenac self-administered 1 drop twice a day for 12 months. Patients were followed for 12 months. RESULTS There were no safety concerns with the combination therapy. No statistically significant differences were identified in Early Treatment Diabetic Retinopathy Study best-corrected visual acuity or the number of injections required. However, the mean 12-month change in central macular thickness in the combination group was -81.56 μm while in the ranibizumab group alone the change was -42.50 μm (P = 0.03). The proportion of eyes experiencing a decrease in CMT of 50 μm or more was also significantly higher in those receiving combination therapy (P = 0.046). CONCLUSION This pilot study is the first to prospectively identify a biologic signal that may indicate combination therapy with an easily administered well-tolerated eyedrop and ranibizumab is efficacious for the treatment of neovascular age-related macular degeneration. Further studies are warranted to validate this finding.
The Drivers of Public Sector Pension Reform Across the U.S. States

This study analyzes the diffusion of public sector pension reforms across the American states between 1999 and 2012, a policy area notable for its fiscal implications as much as its recent political polarization. Previous enactment in other, non-contiguous states was the largest and most consistent driver of reform. Otherwise, empirical findings suggest that reform antecedents varied by reform type. Existing funding levels reduced the likelihood that states would cut benefits, change pension governance, or reduce cost of living allowances, but had no effect otherwise. Evidence for partisan legislative influence is weak, although Republican control had partial, positive effects on the enactment of pension governance reforms and increases to the retirement age. Across the board, other relevant factors such as constitutional pension protections, collective bargaining rights, and union membership density had no effect. That external contagion pressures have a more robust influence than endogenous conditions r...
Impact of age, redundancy, and perceptual noise on visual search.

Literature related to the efficacy and to the definition and measurement of breast self-examination (BSE) is reviewed with particular attention to its relevance for women over 65. Overall, data on the efficacy of BSE suggest that it has a small but measurable impact on earlier detection of breast cancer as measured by clinical stage and tumor size and sometimes by pathological stage. The largest differences are between some BSE and no BSE. An analysis of BSE suggests that instructions could be simplified for older women in order to increase the reliability and acceptability of the examination. A research agenda is proposed which includes (a) testing BSE instructions tailored for older women, (b) studying the intervening steps between BSE and cancer diagnosis, (c) testing methods to increase acceptance by older women, and (d) investigating the relationship between BSE and earlier detection of breast cancer in older women.
Synthetic hydrogel supports the function and regeneration of artificial ovarian tissue in mice

Many prepubertal girls and young women suffer from premature ovarian insufficiency induced by chemotherapy given for treatment of cancer and autoimmune diseases. Auto-transplantation of cryopreserved ovarian tissue could restore the lost ovarian endocrine function and fertility. Unfortunately, tissue ischemia, inconsistent graft quality and the risk of re-introducing malignant cells may stand in the way of the clinical translation of this approach. To address these risks and limitations, we engineered an artificial ovary from immature follicles using a synthetic hydrogel, poly(ethylene glycol) vinyl-sulfone (PEG-VS), as a supportive matrix. Enzymatically-isolated follicles from 6 - 7 day old mice ovaries were encapsulated in 7% PEG-VS hydrogels modified with 0.5mM RGD and crosslinked with a tri-functional matrix metalloproteinase (MMP)-sensitive peptide. PEG hydrogels with the encapsulated follicles were orthotopically implanted into ovariectomized mice to investigate if PEG hydrogel supports folliculogenesis and steroidogenesis in vivo. After 30 days, grafts revealed multiple fully developed antral follicles and corpora lutea, which corresponded with regular ovulation cycles and follicle-stimulating hormone (FSH) levels. The elevated levels of FSH, caused by bilateral ovariectomy, were reversed by the implanted follicles and maintained at physiological levels for 60 days. Importantly, primordial and primary follicles still represented 60% of the follicular pool, demonstrating selective recruitment of primordial follicles into the growing pool. Functioning blood vessels in the grafts 30 and 60 days after implantation proved the capability of PEG hydrogels to undergo graft remodeling and revascularization. Our results demonstrate that PEG hydrogels with encapsulated immature ovarian follicles successfully functioned as an artificial ovarian tissue for 60 days in vivo.
Blood phenylalanine levels and intelligence of 10-year-old children with PKU in the National Collaborative Study.

Abstract Dietary intakes and blood phenylalanine levels of 125 10-year-old children with PKU are reported. Of those patients, 59 discontinued the special diet at 6 years, 16 discontinued at 8 years, 5 discontinued at 6 years but returned to the diet at 8½ years, and 45 continued the diet to 10 years. Phenylalanine intake was determined by 2-day diet records. Blood phenylalanine concentrations revealed a lack of clear distinction between the diet groups; therefore, regression analysis was performed on the group as a whole. The analyses revealed significant relationships between blood phenylalanine levels from ages 6 to 10 years and each of the cognitive outcome variables, after the influences of parental IQ and the age at which treatment was initiated were controlled for. Intelligence test scores were also related to phenylalanine levels between ages 3½ and 5½ years. The findings suggest that dietary restriction of phenylalanine should continue in patients with PKU through at least 10 years of age. J Am Diet Assoc 88:1226, 1988.
Abstract 4406: Inducible knockdown of insulin receptor substrate I desensitizes ER alpha response to both agonist (estradiol) and antagonist (fulvestrant) in MCF-7L breast cancer cells

Insulin receptor substrate (IRS) proteins are adaptor proteins phosphorylated by insulin and insulin-like growth factor (IGF) receptors. In addition to their roles in regulating IGF and insulin responses, IRS proteins function in other pathways in normal and malignant physiology. Our data suggested that IRS1 enhanced IGF/insulin stimulated proliferation while IRS-2 was important in regulating motility. Therefore IRS proteins could be potential therapeutic target for cancer therapy. We have previously shown that reduced IRS1 can hinder cancer cell growth and tumorigenicity stimulated by IGF-I, IGF-II and insulin. In this study, we evaluated whether inducible IRS1 suppression affected estrogen receptor-alpha (ER) responsiveness to ER agonist estradiol and antagonist fulvestrant. We evaluated several doxycycline inducible shRNA IRS1 constructs (Thermo Scientific pTRIPZ inducible Lentiviral IRS1 shRNA) expressed in the ER+ MCF-7L cell line. Doxcycline treatment reduced IRS1 mRNA and protein levels confirmed by qRT-PCR and immunoblot in several independently selected clones. We used a representative clone (3G5) to evaluate effects on ER function. After IRS1 inducible knockdown, estradiol (E2) stimulated growth was suppressed. To investigate if reduced IRS1 regulated E2 stimulated binding of ER to the pS2 estrogen response element (ERE), chromatin immunoprecipitation (ChIP) assays were performed. Compared to non-induced MCF-7L cells, inducible IRS1 suppression demonstrated significantly reduced binding of ER to this promoter. The pharmacologic antagonist of IRS proteins, NT157, also resulted in diminished ER binding to pS2 promoter. mRNA of several ER regulated genes, such as PGR, TFF1, etc, showed downregulation in response to E2 when IRS-1 was suppressed. We have shown that the pure steroidal ER antagonist fulvestrant activates EGFR signaling in an ER dependent manner through upregulation of EGFR ligands. However, inducible IRS1 suppression blocked this ER-dependent activation of EGFR phosphorylation by fulvestrant yet EGFR phosphorylation remained intact when stimulated by addition of EGF. These data suggest that regulation of EGFR ligands by fulvestrant also requires IRS-1 expression. We conclude that ER function is affected by IRS-1 expression. Thus, IRS-1 may also be a target in endocrine responsive and resistant breast cancers. Citation Format: Xihong Zhang, Sidhant Varma, Douglas Yee. Inducible knockdown of insulin receptor substrate I desensitizes ER alpha response to both agonist (estradiol) and antagonist (fulvestrant) in MCF-7L breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4406.
From Teachers to Professors: A Tale of Identities, Ideologies, Change, Conflict and lots of other good Organizational ‘Stuff’ (a work of ethnographically informed scholarly fiction)

Drawing upon the genre of ethnographic fiction, this paper explores the challenges that occur when third- and fourth-tier colleges and universities seek accreditation from AACSB. Deans and change leaders normally see the process of achieving accreditation in terms of bureaucratic and behavioral change. This paper argues that more focus must be placed on understanding how the demands of accreditation challenge faculty members' self-image. Therefore, achieving accreditation requires individuals to have a change in their self-identity so that behavioral change can follow.
Intramyocellular ceramides and skeletal muscle mitochondrial respiration are partially regulated by toll-like receptor 4 during hindlimb unloading

Physical inactivity and disuse result in skeletal muscle metabolic disruption, including insulin resistance and mitochondrial dysfunction. The role of the Toll-like receptor 4 (TLR4) signaling pathway in contributing to metabolic decline with muscle disuse is unknown. Therefore, our goal was to determine whether TLR4 is an underlying mechanism of insulin resistance, mitochondrial dysfunction, and skeletal muscle ceramide accumulation following muscle disuse in mice. To address this hypothesis, we subjected (n = 6-8/group) male WT and TLR4-/- mice to 2 wk of hindlimb unloading (HU), while a second group of mice served as ambulatory wild-type controls (WT CON, TLR4-/- CON). Mice were assessed for insulin resistance [homeostatic model assessment-insulin resistance (HOMA-IR), glucose tolerance], and hindlimb muscles (soleus and gastrocnemius) were used to assess muscle sphingolipid abundance, mitochondrial respiration [respiratory control ratio (RCR)], and NF-κB signaling. The primary finding was that HU resulted in insulin resistance, increased total ceramides, specifically Cer18:0 and Cer20:0, and decreased skeletal muscle mitochondrial respiration. Importantly, TLR4-/- HU mice were protected from insulin resistance and altered NF-κB signaling and were partly resistant to muscle atrophy, ceramide accumulation, and decreased RCR. Skeletal muscle ceramides and RCR were correlated with insulin resistance. We conclude that TLR4 is an upstream regulator of insulin sensitivity, while partly upregulating muscle ceramides and worsening mitochondrial respiration during 2 wk of HU.
Plasma Biomarkers for Monitoring Brain Pathophysiology in FMR1 Premutation Carriers.

Premutation carriers have a 55-200 CGG expansion in the fragile X mental retardation 1 (FMR1) gene. Currently, 1.5 million individuals are affected in the United States, and carriers are at risk of developing the late-onset neurodegenerative disorder Fragile X-associated tremor ataxia syndrome (FXTAS). Limited efforts have been made to develop new methods for improved early patient monitoring, treatment response and disease progression. To this end, plasma metabolomic phenotyping was obtained for 23 premutation carriers and 16 age- and sex-matched controls. Three biomarkers, phenylethylamine normalized by either aconitate or isocitrate and oleamide normalized by isocitrate, exhibited excellent model performance. The lower phenylethylamine and oleamide plasma levels in carriers may indicate, respectively, incipient nigrostriatal degeneration and higher incidence of substance abuse, anxiety and sleep disturbances. Higher levels of citrate, isocitrate, aconitate and lactate may reflect deficits in both bioenergetics and neurotransmitter metabolism (Glu, GABA). This study lays important groundwork by defining the potential utility of plasma metabolic profiling to monitor brain pathophysiology in carriers before and during the progression of FXTAS, treatment efficacy and evaluation of side effects.
Holes in the Head: The Art and Archeology of Trepanation in Ancient Peru, by John W. Verano

I usually find it easy to categorize books into scholarly monographs, textbooks, edited volumes (typically with a few chapters that I really want to consult), and lighter books that are just fun to...
Weight-Gain Reduction Among 2-Year College Students: The CHOICES RCT

Introduction The young adult years have been recognized as an influential period for excess weight gain. Non-traditional students and those attending 2-year community colleges are at particularly high risk for a range of adverse weight-related outcomes. Design Choosing Healthy Options in College Environments and Settings was an RCT with students randomly assigned into a control or intervention condition after baseline assessment. The study was designed to evaluate if a 24-month weight-gain prevention intervention reduces the expected increase in BMI and overweight prevalence in young adults attending 2-year colleges. Two cohorts were recruited, corresponding to the fall and spring semesters. Data collection occurred at four time points for each cohort, with baseline occurring in fall 2011 for Cohort 1 and spring 2012 for Cohort 2. The 24-month follow-up occurred in fall 2013 for Cohort 1 and spring 2014 for Cohort 2. Data analysis occurred in 2015–2016. Setting/participants This research was conducted with 441 students from three community colleges in Minnesota. Intervention The 24-month intervention began with a 1-credit college course on healthy weight behaviors. A social networking and social support website was introduced as part of the course and participation encouraged for the duration of the trial. Main outcome measures Changes in BMI, weight, body fat percentage, waist circumference, and weight status were assessed. Results Retention of the cohorts at 24 months was 83.4%. There was not a statistically significant difference in BMI between conditions at the end of the trial. However, there was a statically significant difference in the prevalence of overweight/obesity between treatment conditions at 24 months. Also, participants randomized to the intervention who were overweight or obese at baseline were more than three times as likely to transition to a healthy weight by the end of the trial as compared with control students. Conclusions The intervention was not successful in achieving BMI differences between treatment groups. However, an 8% reduction in the prevalence of overweight and obesity over time may have population-level significance. Trial registration This study is registered at www.clinicaltrials.gov NCT01134783.
An RF-Powered FDD Radio for Neural Microimplants

We present a radio system that could be used in millimeter-scale wireless neural implants. The system is RF-powered and demonstrates Mbps data rates required for neuromodulation and recording applications. The radio transmits at 58 Mb/s and receives at 2.5 Mb/s maximum data rates. The transceiver uses a duplexer to achieve full-duplex communication via frequency-division duplexing at 1.74 and 1.86 GHz for TX and RX, respectively. The average power consumption of the transmitter is 93 $\mu \text{W}$ at 58 Mb/s, while that of the receiver is 7.2 $\mu \text{W}$ at 2.5 Mb/s. The transceiver was fabricated using 40-nm LP CMOS process and occupies 0.8 mm2 of die area. Including the off-chip duplexer, the system occupies 2 $\times $ 1.6 $\times $ 0.6 mm3.
Pharmacological inhibition of LSD1 and mTOR reduces mitochondrial retention and associated ROS levels in the red blood cells of sickle cell disease

Sickle cell disease (SCD), an inherited blood disorder caused by a point mutation that renders hemoglobin susceptible to polymerization when deoxygenated, affects millions of people worldwide. Manifestations of SCD include chronic hemolytic anemia, inflammation, painful vaso-occlusive crises, multisystem organ damage, and reduced life expectancy. Part of SCD pathophysiology is the excessive formation of intracellular reactive oxygen species (ROS) in SCD red blood cells (RBCs), which accelerates their hemolysis. Normal RBC precursors eliminate their mitochondria during the terminal differentiation process. Strikingly, we observed an increased percentage of RBCs retaining mitochondria in SCD patient blood samples compared with healthy individuals. In addition, using an experimental SCD mouse model, we demonstrate that excessive levels of ROS in SCD are associated with this abnormal mitochondrial retention. Interestingly, the LSD1 inhibitor, RN-1, and the mitophagy-inducing agent mammalian target of rapamycin (mTOR) inhibitor, sirolimus, increased RBC lifespan and reduced ROS accumulation in parallel with reducing mitochondria-retaining RBCs in the SCD mouse model. Furthermore, gene expression analysis of SCD mice treated with RN-1 showed increased expression of mitophagy genes. Our findings suggest that reduction of mitochondria-retaining RBCs may provide a new therapeutic approach to preventing excessive ROS in SCD.
Two-dimensional electron liquid in a weak magnetic field.

We present an effective theory describing the low-energy properties of an interacting two-dimensional electron gas at large noninteger filling factors {nu}{much_gt}1. Assuming that the interaction is sufficiently weak, {ital r}{sub {ital s}}{lt}1, we integrate out all the fast degrees of freedom, and derive the effective Hamiltonian acting in the Fock space of the partially filled Landau level only. This theory enables us to find two energy scales controling the electron dynamics at energies less than {h_bar}{omega}{sub {ital c}}. The first energy scale, ({h_bar}{omega}{sub {ital c}}/{nu})ln({nu}{ital r}{sub {ital s}}), appears in the one-electron spectral density as the width of a pseudogap. The second scale, {ital r}{sub {ital s}}{h_bar}{omega}{sub {ital c}}, is parametrically larger, it characterizes the exchange-enhanced spin splitting and the thermodynamic density of states.
Kinship, nomadism, and humanitarian aid among Somalis in Ethiopia

This paper draws on extended ethnographic and health policy research in eastern Ethiopia to reconsider kinship and nomadism among Somalis, as both of these cultural features transform in the contexts of recurrent humanitarian crises and episodic relief operations. The emergence and importance of new patterns of travel and migration among Somalis in Ethiopia reveal significant changes in the configurations and enactments of Somali kinship, on which many Somalis' mobility depends. Conversely, an analysis of Somalis' dynamic sub-clan groupings and geographically dispersed kinship networks also highlights emergent patterns of mobility and migration that enable access to training opportunities and employment with relief organisations, as well as to distributions of humanitarian aid. Based on these findings, this paper argues that kinship and nomadism—both long central to Somalis' identities in Ethiopia—remain interdependent, coevolved, and key to their resilience and livelihoods in the face of recurrent crises and intermittent humanitarian responses.