cssi/SciSciGPT-SciSciNet huggingface dataset:
Influence of Charged Groups on the Properties of Zwitterionic Moieties: A Molecular Simulation Study

Zwitterionic carboxybetaine and sulfobetaine materials have shown an excellent ability to resist nonspecific protein adsorption. It is desirable to obtain a better understanding of zwitterionic materials based on their molecular structures. This work aims to understand the roles of charged groups in zwitterionic moieties and to design new protein-resistant zwitterionic moieties beyond carboxybetaine and sulfobetaine. We conducted molecular simulations to study the hydration, self-association, and protein interactions of 12 zwitterionic moieties derived from three anionic groups (carboxylic, sulfonate, and sulfate) and four cationic groups (quaternary ammonium, tertiary ammonium, secondary ammonium, and primary ammonium). The partial charges of atoms in these moieties were obtained from quantum chemical calculations. Hydration was studied by evaluating the hydration free energy of moieties and the hydration structure and dynamics of the charged groups. All zwitterionic moieties have strong hydration, but their structural and dynamic properties depend on the types of cationic and anionic groups involved. The self-association and protein interactions of zwitterionic moieties also show relationships with the charged groups. Our simulation results indicate good protein-resistant ability of several zwitterionic moieties, one of which has also been shown by recent experiments.
Antidiuretic hormone in the urine and pituitary of the kangaroo rat.

SummaryThe kangaroo rat (Dipodomys merriami) excretes large amounts of antidiuretic hormone in the urine (up to 50 milli-units per ml). The presence of this high concentration of hormone is believed to be related to the ability of this desert rodent to excrete the most concentrated urine of any mammal and to reflect a correspondingly high rate of secretion of antidiuretic hormone by the posterior pituitary. In 2 other mammals, the dog with powerful osmotic stimulation of the cerebrum, and the laboratory rat (Long-Evans strain) deprived of water for 48-72 hours, the maximum concentration of hormone in the urine is about 6 m.u. per ml. The hormone in kangaroo-rat urine undergoes sedimentation in the ultracentrifuge and thus resembles endogenous antidiuretic hormone in canine urine. The pituitary of kangaroo rats contains more antidiuretic hormone than that of normal laboratory rats although the latter are 5 to 6 times larger. After 72 hours of thirst the laboratory rat's pituitary contains an increased amou...
How Much Political Power do Economic Forces Have? Conflicts Over Social Insurance Reform in Brazil

The failure of attempts at neoliberal social security reform in Brazil since 1990 demonstrates the limited political influence of seemingly powerful economic forces, especially private business and international financial institutions. Besides power-dispersing constitutional structures, the fragmentation of social forces, the weakness of political parties, and the internal segmentation of the state apparatus have hindered the efforts of Brazilian governments to gain the political support necessary to cut entitlements and thus stem the rapid rise in pension spending.
Deciding the existence of a time-sharing ability: a combined methodological and theoretical approach

Experimental and statistical methods for examining individual differences in dual-task performance and time-sharing ability are reviewed and criticized. Previous data and analysis procedures are generally inadequate to evaluate a time-sharing ability. Errors resulting from unsophisticated use of correlational and factor analytic procedures are described. Four previous studies that concern time-sharing are considered in detail. The nature of task selection, scoring methods, and control of practice and reliability issues are discussed. Based on a reanalysis of available data, a time-sharing ability is not rejected. Simulation, incorporation of theory in planning models, and crucial tests of the hypotheses are proposed as methods for assessing the time-sharing ability.
Comparative Television Advertising in the United States: A Thirty-Year Update

abstract“Strictly” comparative television commercials make explicit references to identifiable competitors, whereas “implied” ones make implicit comparisons to “ordinary brands” or other brands in general. This study assesses the frequency of comparative television advertising use in the United States and represents the literature's first longitudinal update for both products and services in more than three decades. Findings reveal (1) likely increases in the use of both strictly and implied comparative advertising and (2) the frequent use of a previously uninvestigated type, and (3) suggest today's advertisers attempt to avoid excessive intensity and negativity with their comparative advertising.
Increased variance in temperature and lag effects alter phenological responses to rapid warming in a subarctic plant community

Summer temperature on the Cape Churchill Peninsula (Manitoba, Canada) has increased rapidly over the past 75 years, and flowering phenology of the plant community is advanced in years with warmer temperatures (higher cumulative growing degree days). Despite this, there has been no overall shift in flowering phenology over this period. However, climate change has also resulted in increased interannual variation in temperature; if relationships between phenology and temperature are not linear, an increase in temperature variance may interact with an increase in the mean to alter how community phenology changes over time. In our system, the relationship between phenology and temperature was log-linear, resulting in a steeper slope at the cold end of the temperature spectrum than at the warm end. Because below-average temperatures had a greater impact on phenology than above-average temperatures, the long-term advance in phenology was reduced. In addition, flowering phenology in a given year was delayed if summer temperatures were high the previous year or 2 years earlier (lag effects), further reducing the expected advance over time. Phenology of early-flowering plants was negatively affected only by temperatures in the previous year, and that of late-flowering plants primarily by temperatures 2 years earlier. Subarctic plants develop leaf primordia one or more years prior to flowering (preformation); these results suggest that temperature affects the development of flower primordia during this preformation period. Together, increased variance in temperature and lag effects interacted with a changing mean to reduce the expected phenological advance by 94%, a magnitude large enough to account for our inability to detect a significant advance over time. We conclude that changes in temperature variability and lag effects can alter trends in plant responses to a warming climate and that predictions for changes in plant phenology under future warming scenarios should incorporate such effects.
Allosteric Regulation Mechanism of Trimeric Membrane

One of the structurally well characterized allosterically regulated systems is the BetP membrane transporter protein. It is a trimeric protein that transports osmolytes but only when the cytoplasmic osmotic pressure exceeds a threshold. The regulatory domain mainly consists of three helical C-terminal regions of the trimeric complex. Based on the partially resolved crystal structures, each C-terminal region has contacts with one of its neighbors. It has been proposed that this cross-contact activates the substrate transport. However, how these C-terminal domains interact is still unknown since two C-terminal regions are missing from every available BetP structure. Furthermore, how the regulatory domain affects the functional domain is still a mystery. Here we present several major findings based on an a recently developed computational technique named xMDFF which resolves the structural information with the guidance of experimental X-ray diffraction data. In addition, we performed an extensive set of molecular dynamics simulations and allosteric network analyses to characterize the propagation of allosteric effects. The missing C-terminal regions have been reconstructed for three crystal structures of BetP with equivalent or better R-free/R-work and cross-correlation scores than the previously reported ones. The new structures revealed that the orientation of the C-terminal domains is symmetric in one case while being asymmetric in the others, indicating that the regulatory domain at active state is not a single state as has been previously believed. Simulation results showed that there are multiple ways for the C-terminal regions to interact with each other and the transition between symmetric and asymmetric arrangement was also observed. In addition, the network analyses showed multiple paths connecting the regulatory domain and the EH2 helix, a potential secondary substrate binding site. Together, these results lay out a new general mechanism for the allosteric regulations for multicomponent membrane transporters like BetP.
The Impact of Changing Products Liability Laws on Channel Members

“Products liability” is the name currently given to the liability of a seller, or other supplier of chattels, to one with whom he is not in privity of contract, who suffers damage caused by the chattel. It may rest upon the supplier’s negligence, a warranty, or it may be a matter of strict liability in tort [Prosser, 1971]. The old doctrine of “caveat emptor” has been replaced with “caveat venditor,” as products liability laws allow buyers to recover damages from manufacturers, wholesalers and retailers. In 1931, Chief Judge Cardoza said in Ryan V. Progressive Grocery Stores, 255 N.Y. 388, 175 N.E. 105, “The burden may be heavy. It is one of the hazards of business.” Could he have envisioned that by 1965 the annual number of products liability cases would be 50,000 but by 1976 the number would be 1.5 million per year [U.S. News and World Reports, 1976] or that in 1975 companies would pay $1 in products liability claims per every $1,000 in sales, but that only one year later they would be paying $2 per $1,000 in sales [Gilliss, 1980]? Whether this is caused by litigants using the “deep pockets” theory, the contingency fee method of attorney payment, a broader view of products liability by the courts or the development of strict liability in tort, channel members must know the possible plaintiffs, causes of action, and defenses.
Inkjet printing and surface treatment of an optimized polyurethane-based ink formulation as a suitable insulator over silver for contact with aqueous-based fluids in low-voltage applications

An optimized, formulated polyurethane (PU)-based insulating ink, which was inkjet printed and cured as a tri-layer on top of an inkjet-printed and sintered commercial silver ink base metal fused to polyethylene terephthalate substrate, demonstrated a resistivity of >1.2 × 108 Ω cm at a film thickness of 100 μm when exposed to an aqueous saline solution and a voltage differential of <2 V. This insulating property is highly desirable for biofluids-contacting biosensors. Three PU-based insulator ink formulations were made with different levels of ethylene glycol and carboxymethylcellulose additives to improve ink volatility, viscosity, and dispersion properties. Based on the resultant ink properties important to printing, one of these formulations was selected for further evaluation. The effects of the type and extent of surface conditioning involving UV–O3 and/or thermal treatments on print quality and completed insulator functionality are discussed. Print quality is assessed by visual and profilometry measurement.
Nazi Germany: Training Forced Labor

This essay explores training surrounding the forced foreign labor during World War II including the Jewish councils in Eastern Europe under Nazi occupation. Jews, Russians, and Roma were involved in mandatory training courses to enhance the labor skills. Such training courses were run so that workers could qualify for labor certificates in German industry. Many Jews (erroneously) believed that if they could demonstrate their usefulness to German industry, this would reduce their chances of being exterminated.
Going beyond ‘do no harm’: a critical annotation

The Op-Ed article in the New York Times (November 4th, 2016), “On Assisted Suicide, Going Beyond Do No Harm” by Haider Javed Warraich provides an articulate and timely plea for more widespread availability and application of physician-assisted dying, or “suicide”, as part of end-oflife (EOL) medical care. While this profound intervention should be considered by physicians and others as an option for those able to express their wishes at the EOL, it must be considered in the context of the ethical principles appropriate for all health care interventions and recognized for its limited role in the overall approach to compassionate care for terminally ill people.
Breakthrough Fungal Infections in Patients With Leukemia Receiving Isavuconazole

We retrospectively assessed breakthrough invasive fungal infections (b-IFIs) in 100 consecutive patients with leukemia receiving single-agent isavuconazole; 13 had documented b-IFIs (candidiasis in 6, mucormycosis in 4). All b-IFIs were observed in patients with prolonged neutropenia and active leukemia.
Risk Management and Data Needs: A State of the Practice Survey of State Highway Agencies:

Risk management analysis is one of the new requirements under MAP-21 that separates transportation asset management programs from business as usual for the state departments of transportation (DOTs...
Stochastic Programming: Solution Techniques and Approximation Schemes

Solutions techniques for stochastic programs are reviewed. Particular emphasis is placed on those methods that allow us to proceed by approximation. We consider both stochastic programs with recourse and stochastic programs with chance-constraints.
Cyclic adenosine 3':5'-monophosphate metabolism in normal and SV40-transformed WI-38 cells.

Abstract Intact SV40-transformed WI-38 cells (VA13-2RA) responded to catecholamines, prostaglandins, and adenosine with much more dramatic increases in cyclic adenosine 3':5'-monophosphate (cyclic AMP) than did normal WI-38 cells. Further, the responses of VA13-2RA to the catecholamines were independent of the cell population density, whereas the responses of WI-38 were diminished as they approached confluence. Time course studies likewise showed clear differences between VA13-2RA and its normal counterpart, in that the maximal intracellular cyclic AMP levels in response to prostaglandin E1 (PGE1) were reached much later in the transformed than in the normal cells (20 min versus 5 min). Further, the rapid decline in cellular cyclic AMP levels seen in WI-38 (as in most cell systems) was much attenuated in VA13-2RA. Basal cyclic AMP levels were lower in the transformed than in the normal cells, as has been the case with many other systems. Theophylline appeared to have two distinct effects in WI-38, namely, synergism (with prostaglandins), as expressed by increased cellular cyclic AMP levels, and reduction of cyclic AMP accumulation in the media. On the other hand, theophylline had only small (or in some cases no) effects on cyclic AMP accumulation in VA13-2RA. Adenylate cyclase activities in cell-free preparations of WI-38 and VA13-2RA cells differed in several respects. Although homogenates of WI-38 were more active than VA13-2RA preparations in the presence of PGE1 (10 µm) and NaF (10 mm), VA13-2RA activity exceeded WI-38 activity by more than 3-fold in the presence of epinephrine and, in fact, cyclic AMP accumulation in homogenates of the transformed cells was significantly greater in the presence of epinephrine than with NaF. Finally, WI-38 homogenates showed much greater cyclic nucleotide 3':5'-monophosphate phosphodiesterase activity than VA13-2RA preparations (131 ± 8 versus 7.1 ± 5.4 nmoles of cyclic AMP destroyed per mg of protein per 30 min).
Mobile Virtualization Technologies

In order to achieve increased adoption and sustainability “bring your own device” (BYOD) schemes within the enterprise, mobile virtualization is rapidly becoming a very attractive choice because it provides both employee and enterprise with flexibility while addressing the privacy concerns of the user and meeting the organizations security requirements. Allowing BYOD devices in the enterprise requires policies in place that govern how devices will be used and how they will be managed while maintaining end user flexibility. A number of technologies for mobile virtualization have been developed over the last few years which range from sophisticated mobile device policy management, to hypervisors and container based separation [JaKa01].
Examining the Use of Social Media in Customer Co- Creation: A Blog Mining Study

Social media have been used by some companies to support customer co-creation in recent years. However, few academic studies have been done to investigate the use of social media for customer co-creation. To understand the current state-of-theart and future trends about the use of social media for customer co-creation, we conducted a blog mining study to analyze relevant posts on blogs. This blog study reveals some interesting patterns, themes and future trends in this specific area.
Counter-regulatory response to hypoglycemia in the follicular and luteal phases of the menstrual cycle.

Objective To assess whether the phase of the menstrual cycle influences the counter-regulatory response to hypoglycemia. Design Prospective randomized euglycemia-hypoglycemia clamp studies in the follicular and luteal phases of the menstrual cycle in the same woman. Settings Clinical Research Center, Yale University School of Medicine. Patients Eight regularly menstruating nonobese women. Main Outcome Measures Counter-regulatory hormonal response to hypoglycemia-epinephrine, norepinephrine, glucagon, Cortisol, GH, and PRL; glucose homeostasis: rates of whole-body glucose appearance and utilization, and the rate of hepatic glucose production. Results In the follicular and luteal phases of the cycle fasting glucose levels (88±1 and 85±2mg/dL, mean±SEM, respectively; conversion factor to SI units, 0.05551), basal glucose turnover (2.37±0.20 and 2.63±0.13mg/kg per minute), basal insulin levels (10±1 and 9±1 μ U/mL; conversion factor to SI units, 6.0), and insulin levels during the clamp study (53±3 and 45±4 μ U/mL) were not significantly different. During the euglycemic phase of both studies, glucose utilization rose twofold (to 4.73±0.31 and 4.39±0.31mg/kg per minute): hepatic glucose production was suppressed; and counter-regulatory hormones remained unchanged. Induction of hypoglycemia produced increases in the concentrations of counter-regulatory hormones that were indistinguishable in both phases of the cycle. Similarly, the increase in hepatic glucose production provoked during hypoglycemia was similar in each phase of the cycle (1.20±0.24 and 1.28±0.36mg/kg per minute). Conclusion The counter-regulatory hormonal response to hypoglycemia, as well as the metabolic sequelae of these hormonal changes, are similar in the follicular and luteal phases of the menstrual cycle.
HYPOTHYROIDISM IN DOGS : 66 CASES (1987-1992)

Sixty-six dogs with hypothyroidism were identified from dogs examined over a 5-year period. Hypothyroidism was diagnosed only if the dog had a low, resting serum thyroxine concentration and serum thyroxine concentration was not higher than the lower limits of the reference range 6 hours after IV administration of bovine thyrotropin. The prevalence of hypothyroidism was 0.2%. Neutering was determined to be the most significant gender-associated risk factor for development of hypothyroidism. Neutered male and spayed female dogs had a higher relative risk of developing hypothyroidism than did sexually intact females. Sexually intact females had a lower relative risk. Breeds with a significantly increased risk, compared with other breeds, were the Doberman Pinscher and Golden Retriever. The most common clinical findings were obesity (41%), seborrhea (39%), alopecia (26%), weakness (21%), lethargy (20%), bradycardia (14%), and pyoderma (11%). Low voltage R-waves were found on 58% of ECG. Clinicopathologic abnormalities included hypercholesterolemia (73%), nonregenerative anemia (32%), high serum alkaline phosphatase activity (30%), and high serum creatine kinase activity (18%). Serum total triiodothyronine concentrations were within reference ranges in 15% of the hypothyroid dogs. Response to treatment was good in most dogs, but those with severe concurrent disease or neurologic abnormalities were less likely to respond with complete resolution of clinical signs.
Regulation of Cardiovascular Control Mechanisms by Angiotensin-(1–7) and Angiotensin-Converting Enzyme 2

Among the molecular forms of angiotensin peptides generated by the action of renin on angiotensinogen (Aogen), both angiotensin II (Ang II) and the amino terminal heptapeptide angiotensin-(1–7) [Ang-(1–7)] are critically involved in the long-term control of tissue perfusion, cell-cell communication, development, and growth. Whereas an impressive body of literature continues to uncover pleiotropic effects of Ang II in the regulation of cell function, research on Ang-(1–7) has a shorter history as it was only 16 yr ago that a biological function for this heptapeptide was first demonstrated in the isolated rat neuro-hypophysial explant preparation (1). On the contrary, the synthesis of angiotonin/ hypertensin (now Ang II) was first obtained in 1957 (2), three decades ahead of the discovery of Ang-(1–7) biological properties.
Effects of music listening on creative cognition and semantic memory retrieval

Listening to music can affect cognitive abilities and may impact creative cognition. This effect is believed to be caused by music’s impact on arousal and mood. However, this causal relationship ha...
Lobbying and the Petition Clause

Contrary to popular opinion, the Supreme Court has not yet resolved whether lobbying is constitutionally protected. Belying this fact, courts, Congress, and scholars mistakenly assume that lobbying is protected under the Petition Clause. Because scholars have shared the mistaken assumption that the Petition Clause protects the practice of “lobbying”, no research to date has looked closely at the Petition Clause doctrine and the history of petitioning in relation to lobbying. In a recent opinion addressing petitioning in another context, the Supreme Court unearthed the long history behind the right to petition and argued for the importance of this history for future interpretation of the Petition Clause.Following the Supreme Court’s direction, this Article examines the implications of the history of petitioning for lobbying and, drawing from recent empirical research on lobbying, argues that the way Congress engages with the public through our current lobbying system actually violates the right to petition. At the Founding, and for much of this Nation’s history, the right of petition protected a formal, transparent platform for individual — and, in particular, minority — voices to participate in the lawmaking process. Without regard to the number of signers or the political power of the petitioner, petitions received equal process and consideration. This platform allowed both the enfranchised and unenfranchised to gain access to lawmakers on equal footing. Women, African Americans, and Native Americans all engaged in petitioning activity, and Congress attended to each equally.Moving beyond ahistorical, decontextualized interpretations of the Petition Clause, this Article posits that our current lobbying system — wherein access and procedure are informal, opaque, and based on political power — actually violates the right to petition, which provided access and formal procedure without respect to the political power of the petitioner. The history of petitioning teaches that affording access to the lawmaking process on the basis of an individual’s political power makes as little sense as affording access to courts on such a basis.This history suggests the need for revisiting the Petition Clause doctrine. On the one hand, it argues for a stronger petition right, especially a right to consideration and response. On the other hand, it suggests a narrowed petition right that protects only practices that correspond with the traditional practice of petitioning. Fundamentally, this Article demonstrates that a contextualized understanding of the Petition Clause, grounded in an accurate historical frame, requires comprehensive reform of our lobbying system and a formalization of the petition process in order to preserve our republican form of government.Final version of the article now available. This article is part of a much larger project on lobbying and petitioning, however, so feedback is still quite welcome: mmckinley (at) law (dot) harvard (dot) edu.
Multifidelity probability estimation via fusion of estimators

Abstract This paper develops a multifidelity method that enables estimation of failure probabilities for expensive-to-evaluate models via information fusion and importance sampling. The presented general fusion method combines multiple probability estimators with the goal of variance reduction. We use low-fidelity models to derive biasing densities for importance sampling and then fuse the importance sampling estimators such that the fused multifidelity estimator is unbiased and has mean-squared error lower than or equal to that of any of the importance sampling estimators alone. By fusing all available estimators, the method circumvents the challenging problem of selecting the best biasing density and using only that density for sampling. A rigorous analysis shows that the fused estimator is optimal in the sense that it has minimal variance amongst all possible combinations of the estimators. The asymptotic behavior of the proposed method is demonstrated on a convection-diffusion-reaction partial differential equation model for which 105 samples can be afforded. To illustrate the proposed method at scale, we consider a model of a free plane jet and quantify how uncertainties at the flow inlet propagate to a quantity of interest related to turbulent mixing. Compared to an importance sampling estimator that uses the high-fidelity model alone, our multifidelity estimator reduces the required CPU time by 65% while achieving a similar coefficient of variation.
A descriptive report of outcomes of primary mucinous ovarian cancer patients receiving either an adjuvant gynecologic or gastrointestinal chemotherapy regimen.

Objective We described progression-free survival and overall survival in patients with primary mucinous ovarian cancer receiving adjuvant gynecologic versus gastrointestinal chemotherapy regimens. Methods We identified all primary mucinous ovarian cancer patients receiving adjuvant gynecologic or gastrointestinal chemotherapy regimens at a single institution from 1994 to 2016. Gynecologic pathologists using strict pathologic/clinical criteria determined diagnosis. Adjuvant therapy was coded as gynecologic or gastrointestinal based on standard agents and schedules. Clinical/pathologic/treatment characteristics were recorded. Wilcoxon rank-sum test was used for continuous variables, and Fisher’s exact test for categorical variables. Progression-free and overall survival were calculated using the Kaplan-Meier method, applying landmark analysis. Results Of 62 patients identified, 21 received adjuvant chemotherapy: 12 gynecologic, 9 gastrointestinal. Median age (in years) at diagnosis: 58 (range 25–68) gynecologic cohort, 38 (range 32–68) gastrointestinal cohort (p=0.13). Median body mass index at first post-operative visit: 25 kg/m2 (range 18–31) gynecologic cohort, 23 kg/m2 (range 18–31) gastrointestinal cohort (p=0.23). History of smoking: 6/12 (50%) gynecologic cohort, 3/9 (33%) gastrointestinal cohort (p=0.66). Stage distribution in gynecologic and gastrointestinal cohorts, respectively: stage I: 9/12 (75%) and 3/9 (33%); stage II: 2/12 (17%) and 1/9 (11%); stage III: 1/12 (8%) and 5/9 (56%) (p=0.06). Grade distribution in gynecologic and gastrointestinal cohorts, respectively: grade 1: 8/12 (67%) and 1/9 (13%); grade 2/3: 4/12 (33%) and 7/9 (88%) (p=0.03). Three-year progression-free survival: 90.9% (95% CI 50.8% to 98.7 %) gynecologic, 53.3% (95% CI 17.7% to 79.6%) gastrointestinal. Three-year overall survival: 90.9% (95% CI 50.8% to 98.7%) gynecologic, 76.2% (95% CI 33.2% to 93.5%) gastrointestinal. Conclusion Ongoing international collaborative research may further define associations between chemotherapy regimens and survival.
Mars in ice ages for ∼25% of post-Noachian geologic history

Abstract Mars is currently a hyperarid, hypothermal desert planet, whose surface inventory of water is primarily confined to the north and south polar ice caps. Previous studies have shown that Mars has undergone massive shifts in its spin-axis obliquity (present-day is 25.2°) due to secular spin orbit resonances. During periods of higher obliquity, water-ice from the polar caps is mobilized to the mid-latitudes ( ∼ 35 ° obliquity) and even the equator ( ≥ 45 ° obliquity), where it is deposited as snow and accumulates over time to form thick regional surface ice sheets. Abundant evidence exists today for the remnants of these ice ages in the form of debris-covered glaciers and ice deposits, but due to the chaotic nature of orbital simulations beyond ∼20 Ma, it has remained unclear to what temporal extent Mars has experienced such ice ages. Recent developments have suggested that impact events which formed in martian surface ice deposits exhibit a distinctive double-layered ejecta morphology. In tandem with cratering statistics, this observation offers the potential to better our understanding of the history of ice ages on Mars. This work explores the timing of ice age events by evaluating the size-frequency distribution of craters forming in surface ice. Using Hartmann isochron model ages, this work shows that Mars has experienced mid-latitude ice ages for up to a cumulative ∼680 Myr out of the past 3.6 Ga, and experienced equatorial ice ages for up to a cumulative ∼250 Myr within the same time period. The results of this study indicate that Mars has experienced mid-latitude/equatorial ice age states for up to approximately 25% of its post-Noachian geologic history, emphasizing that much of the geologic history of Mars is dominated by the presence of widespread non-polar surface ice sheets.
Selective Inhibition of CDK4 and CDK6 Primes Chemoresistant MCL Cells for Killing by Proteasome Inhibitor Bortezomib by Activating Cell Cycle-Coupled Apoptosis

Mantle Cell Lymphoma (MCL) remains generally incurable, suggesting that more effective control of unrestrained tumor growth is essential. Loss of cell cycle control is a hallmark of cancer, in particular of MCL where cell cycle progression through G1 is accelerated due to elevation of cyclin-dependent kinase 4 (CDK4) and constitutive cyclin D1 expression. Thus, one rational approach to improve MCL therapy is to target CDK4/6 in combination with cytotoxic killing. Although success in targeting the cell cycle in cancer with broad-spectrum CDK inhibitors has been modest, PD 0332991, the only known CDK4/6-specific inhibitor with oral bioavailability, has been shown to selectively and potently inhibit CDK4/6 in MCL cells ex vivo. Additionally, in a proof-of-mechanism study in patients with recurrent MCL, we have found that PD 0332991 is well tolerated, and effective in inhibiting CDK4 and CDK6 and suppressing tumor growth in vivo. Of note, 50% of the patients (8/16) have achieved a stable disease for greater then 40 weeks (Leonard et al, abstract submitted to ASH 2008). These findings suggest that selective targeting of CDK4 and CDK6 with PD 0332991 is a promising therapy for MCL. To advance targeting of the cell cycle in cancer, we have developed two novel approaches to both inhibit tumor cell proliferation and activate cell cycle-coupled apoptosis in MCL. We show in primary MCL tumor cells and MCL cell lines by BrdU pulse labeling and DNA content analysis that selective inhibition of CDK4/6 with PD 0332991 leads to a complete G1 arrest, despite high level of c-Myc expression and extensive chromosomal abnormality. As PD 0332991 acts reversibly, removal of PD 0332991 immediately releases the G1 block and induces synchronous (>90%) G1-S cell cycle progression and S phase entry. This sensitizes chemoresistant MCL cells to killing by suboptimal doses of cytotoxic agents such as bortezomib, through activating cell cycle-coupled apoptosis during S phase entry. Synergistic killing of MCL cells by induction of cell cycle synchronization with PD 0332991 in combination with bortezomib is mediated by induction of mitochondrial membrane depolarization and activation of caspase-9. In a complementary study, we have demonstrated that selective targeting of CDK4 and CDK6 by PD 0332991 similarly primes chemoresistant primary myeloma cells for cytotoxic killing by activating cell cycle-coupled apoptosis, and induces synergistic tumor suppression in animal models. Selective targeting of CDK4 and CDK6 by PD 0332991 in combination with cytotoxic killing, therefore, represents a promising new strategy for cell cycle-based therapy for MCL and other hematopoietic malignancies.
On sex and Discipline

This essay examines the current debate between proponents of "queer theory" and "gay and lesbian studies" in order to understand the way each sets forth a political agenda for disciplinary and institutional social change. The author surmises that the utopian hope invested in each critical perspective evinces an affinity that is often overlooked in the way the debate is presented. Further, she argues that neither queer theory nor gay and lesbian studies currently pays adequate attention to the "local" politics of the institution, and she raises the possibility of a political horizon for institutional change which we might call "queering the academy."
Photosynthetic regulation in seed heads and flag leaves of sagebrush-steppe bunchgrasses.

Native sagebrush-steppe bunchgrass populations are threatened by the spread and dominance of exotic invasive annual grasses, in part due to low, episodic seed production. In contrast, the widespread exotic bunchgrass, crested wheatgrass, readily produces viable seed cohorts. The mechanisms underlying these differences are unclear. To address this, we measured seed head specific mass (g m-2) and net photosynthetic assimilation (A net) as a function of internal [CO2] (A/Ci curves) in pre- and post-anthesis seed heads and flag leaves of crested wheatgrass and four native bunchgrasses to determine if differences in allocation and photosynthetic characteristics of seed heads was consistent with differential reproductive success. Crested wheatgrass seed heads had 2-fold greater specific mass compared to the native grasses, concurrent with greater CO2-saturated photosynthesis (A max), mesophyll carboxylation efficiency (CE), and higher intrinsic water-use efficiency (WUE i ; A net/stomatal conductance (g s)), but with similar relative stomatal limitations to photosynthesis (RSL). Post-anthesis seed head A max, CE, RSL and g s decreased in native grasses, while crested wheatgrass RSL decreased and CE increased dramatically, likely due to tighter coordination between seed head structural changes with stomatal and biochemical dynamics. Our results suggest native sagebrush-steppe bunchgrasses have greater stomatal and structural constraints to reproductive photosynthesis, while the exotic grass has evolved seed heads functionally similar to leaves. This study shows elucidating reproduction-related ecophysiological mechanisms provide understanding of plant attributes that underlie restoration success and could help guide the development of native plant materials with functional attributes needed to overcome demographic bottlenecks that limit their restoration into degraded sagebrush-steppe.
Mining Partially Labeled Data from Edge Devices to Detect and Locate High Impedance Faults

The security of active distribution systems is critical to grid modernization along with deep renewable penetration, where the protection plays a vital role. Among various security issues in protection, conventional protection clears only 17.5% of staged high impedance faults (HIFs) due to the limited electrical data utilization. For resolving this problem, a detection and location scheme based on μ-PMUs is presented to enhance data processing capability for HIF detection through machine learning and big data analytics. To detect HIFs with reduced cost on data labeling, we choose expectation-maximization (EM) algorithm for semi-supervised learning (SSL) since it is capable of expressing complex relationships between the observed and target variables by fitting Gaussian models. As one of the generative models, EM algorithm is compared with two discriminative models to highlight its detection performance. To make HIF location robust to HIF impedance variation, we adopt a probabilistic model embedding parameter learning into the physical line modeling. The location accuracy is validated at multiple locations of a distribution line. Numerical results show that the proposed EM algorithm greatly saves labeling cost and outperforms other SSL methods. Hardware-in-the-loop simulation proves a superior HIF location accuracy and detection time to complement the HIF's probabilistic model. With outstanding performance, we develop software for our utility partner to integrate the proposed scheme.
4.24 – Metallothionein and Intracellular Sequestration of Metals

Metallothioneins (MTs), low molecular weight proteins with high cysteine (Cys) content, have high affinity for both essential (zinc and copper) and nonessential (cadmium and mercury) metals. There are four major isoforms of MT, and these MT genes are localized on chromosome 16 in human and chromosome 8 in mouse. Isoforms MT-1 and MT-2 are expressed in most organs, whereas the isoforms MT-3 and MT-4 are expressed mainly in the brain and stratified squamous epithelium, respectively. A number of biological functions have been proposed for MT including storage and detoxification of certain metals and antioxidant property. High levels of MT are expressed in fetal liver, certain proliferating cells, and tumor cells and are localized in the nucleus of these cells. These proteins are induced by several stress conditions, hormones, and exposure to metals. A positive association between MT gene polymorphism and diabetes has been reported.
Exploring Abstraction Functions in Fuzzing

Fuzz testing has emerged as the preeminent automated security analysis technique in the real world. To keep up with the shifting security landscape, researchers have innovated the fuzzing process to identify more and more complex vulnerabilities. One innovation is an approach inspired by genetic programming: the fuzzer generates test-cases, evaluates the quality of the test-case, and uses this evaluation to select test-cases for further iterations of the process. While this innovation has impressive results: without a formal, scientific model on which to base these improvements, the field of fuzzing has been explored in an ad hoc way. As a result, it is difficult to understand the relative merit of different techniques. In this paper, we formalize the input evaluation and selection components of fuzzing, borrowing concepts from the field of static analysis, and providing a base for future expansion of and research into fuzzing techniques. In building this formalism, we observed that the impact of different abstraction functions in modern fuzzing techniques is under-explored in prior research. Without a formal base on which to reason about their contributions, researchers of fuzzing techniques have missed the potential for improvements to this critical component of fuzzing approaches. We explore the implications of our formalization-derived observation on the effectiveness of evolutionary fuzzing techniques in the second half of the paper, showing that the application of different abstraction functions, and the use of multiple abstraction functions in tandem, improves state-of-the-art fuzzing techniques.
Opioid use as a potential risk factor for pancreatic cancer in the United States: An analysis of state and national level databases

Pancreatic cancer (PC) rate is increasing in the U.S. The use of prescription and illicit opioids has continued to rise nationally in recent years as well. Opioids have been shown to have a deleterious effect on multiple types of cancer with recent data suggesting opium use as a risk factor for PC. Using national databases, we tested whether opioid usage pattern over time could explain the state and national-based variations in PC rates in the U.S. Opioid death rate (as a surrogate for prescription and illicit opioid use) was extracted from the CDCs Wonder online data through the Vital Statistics Cooperative Program. Incidence of pancreatic cancer was retrieved from the online CDCs data base gathered from the U.S. Cancer Statistics Working Group. Prevalence of obesity, tobacco and alcohol use was collected from Behavioral risk factor surveillance system. Mixed-effects regression models were used to test the association between levels of PC rate and opioid death/use rates during the years 1999-2016. A rise in PC was seen over time at the national and state levels. Similarly, the opioid death rates increased over time. Among other potential PC risk factors, only obesity prevalence showed an increase during the study period. A state's opioid death rate at 4 years prior significantly predicted initial incidence of PC (β = 0.1848, p<0.0001) and had a significant effect on the estimated annual change in the rate of PC (β = -.0193,p<0.0001). Opioid use may be an un-identified risk factor contributing to the increasing incidence of PC in the U.S. These novel findings need to be verified by population-based studies.
Text Message Medication Adherence Reminders Automated and Delivered at Scale Across Two Institutions: Testing the Nudge System: Pilot Study

Background: Medication refill behavior in patients with cardiovascular diseases is suboptimal. Brief behavioral interventions called Nudges may impact medication refill behavior and can be delivere...
An efficient algorithm for estimating population history from genetic data

Legofit is a statistical package that uses genetic data to estimate the history of population size, subdivision, and admixture. This article describes a new deterministic algorithm, which makes Legofit orders of magnitude faster and more accurate.
A Lightweight Hardware-based Authentication for Secure Smart Grid Energy Storage Units

Next generation smart power grid offers advanced features to enhance the traditional power grid by enabling faster and more user-friendly two-way communications between utility centers and the consumers for a faster, greener, safer, more reliable, and increasingly efficient power delivery. The energy storage units and smart charging stations have become the essential components of a smart power grid. An efficient authentication and key management scheme is proposed in this work to realize a secure and trusted smart charging coordination system using a low-cost data encryption standard (DES) design and a lightweight physical unclonable function. The proposed scheme is implemented and tested on a re-programmable platform using Artix-7 FPGA device. The experimental results demonstrate that the proposed scheme can be efficiently realized on a off-the-shelf hardware, preserve the privacy of energy storage unit owners, and provide low-cost authentication for different NIST security levels.
Feminist Online Identity: Analyzing the Presence of Hashtag Feminism

In theory, the concept of hashtag feminism has created a virtual space where victims of inequality can coexist together in a space that acknowledges their pain, narrative, and isolation. As social scientists Susan Herring, Kirk Job-Sluder, Rebecca Scheckles, & Sasha Barab (2002) state, these properties make online forums appeal favorable to vulnerable populations seeking support from ‘disease or abuse, and to members of minority, social and political groups such as homosexuals, racial minorities, and feminists’ (p. 371). However, in identifying online communities such as Twitter and Facebook as safe spaces for expressing feminism views and politics, its ramifications present dire consequences which lead to online harassment, hate speech, disagreements, and a miscommunication in rhetoric. It is with these consequences that the academic discourse becomes lost in transmitting the message of what feminism is and how feminists are identified. Using the ongoing debate that feminism does not acknowledge real life experience outside of academic terrain, this paper explores how hashtag feminists identify in redefining feminism in their generation. Using the public platform of Twitter and Facebook (less specifically), this paper will explore the online followings of women who identify as hashtag feminists, and how their dialogue has set the tone for the era of internet activism.
Activation of renal NHE3 by angiotensin II requires NHERF1 (893.33)

Na+/H+ exchanger (NHE3) plays a pivotal role in the reabsorption of Na+ and HCO3- in the kidney. The NHE3 activity is tightly regulated by hormones and growth factors to maintain fluid and blood pressure homeostasis. We have previously shown that NHE3 activity and trafficking is stimulated by low dose angiotensin II (Ang II) dependent on IRBIT and CaMKII. However, it remains unclear how IRBIT mediates the exocytosis of NHE3 protein. In this study, we found that IRBIT binds to NHERF1 in OKP cells, which was enhanced by Ang II. Overexpression of IRBIT or Ang II treatment increased NHERF1 and NHE3 binding, whereas knockdown of IRBIT attenuated the interaction. Knockdown of NHERF1 expression by lentiviral shRNA completely blocked the stimulatory effect of Ang II on NHE3 exocytosis and transport activity. Moreover, inhibition of CaMKII by KN-93 abolished the Ang II-induced NHERF1-NHE3 interaction and membrane expression of NHE3, IRBIT and NHERF1. In conclusion, activation of NHE3 exocytosis by Ang II is depend...
High speed, high reliability Si-based light emitters for optical interconnects

The barrier to the industrial implementation of optical interconnects on an IC, center around the fabrication of optical elements on wafers through conventional Si processes. It has been shown previously that Si-based p+-n+ diodes operating in avalanche breakdown mode emit light in the 400-900 nm range. This paper focuses on demonstrating that these Si-based light emitters can operate in the GHz range and provide reliable operation. The modulation of the light emitter was verified using a Hamamatsu streak camera for operation up to 50 psec of pulse width signals. The reliability of these emitters was verified through accelerated AC, DC, and temperature stressing. None of the stressing methods altered the total junction light emission. Low current DC stressing, however, did cause reversible light coalescence. A model has been developed to explain this phenomena.