cssi/SciSciGPT-SciSciNet huggingface dataset:
Cytokine Actions of Angiotensin II

During the last few years, there has been an exponential rise in understanding functions and signal transduction mechanisms for angiotensin II (Ang II) type 2 receptors (AT2s).1 2 These studies are particularly relevant in view of the pivotal role of upregulation of AT2 in mediating tissue remodeling in many cardiovascular diseases, including vascular injury, atherosclerosis, cardiac hypertrophy, myocardial infarction, and congestive heart failure.1 Furthermore, Ang II type 1 receptor (AT1) antagonists, commonly used for treatment of hypertension and congestive heart failure, increase plasma levels of Ang II and upregulate AT2 expression. Under these conditions, the increase in AT2 is unopposed by AT1.1 3 Thus, understanding the role of AT2 in cardiovascular remodeling as well as the consequences of AT2 stimulation or inhibition during medical therapy is clinically important. AT2s only partially share the signaling mechanisms with AT1s and, in fact, counteract the signaling mechanisms activated by AT1s2 (Figure⇓). This negative nature of AT2 signaling has made the elucidation of its function more difficult than that of AT1. However, recent studies on the cardiovascular functions of AT2 seem to have reached a consensus: AT2s exert growth inhibitory effects either by suppressing cell proliferation and hypertrophy4 5 or by stimulating apoptosis.1 2 6 These actions alone may not explain the diverse cardiovascular phenomena attributed to AT2, resulting in unanswered questions. Why are AT2s abundant in growing fetal tissues? Why are AT2s abundant in tissues undergoing remodeling? Recently, an elegant genetic study has provided an answer to some of these questions, showing that an important function of AT2 in the fetal kidney is to stimulate apoptosis. Targeted …
On the fracture toughness of advanced materials

Few engineering materials are limited by their strength; rather they are limited by their resistance to fracture or fracture toughness. It is not by accident that most critical structures, such as bridges, ships, nuclear pressure vessels and so forth, are manufactured from materials that are comparatively low in strength but high in toughness. Indeed, in many classes of materials, strength and toughness are almost mutually exclusive. From a fracture-mechanics perspective, the ability of a microstructure to develop toughening mechanisms acting either ahead or behind the crack tip can result in resistance-curve (R-curve) behavior where the fracture resistance actually increases with crack extension; the implication here is that toughness is often developed primarily during crack growth and not for crack initiation. Biological materials are perfect examples of this; moreover, they offer microstructural design strategies for the development of new materials for structural applications demanding combinations of both strength and toughness.
Thermal management issues in a PEMFC stack – A brief review of current status

Understanding the thermal effects is critical in optimizing the performance and durability of proton exchange membrane fuel cells (PEMFCs). A PEMFC produces a similar amount of waste heat to its electric power output and tolerates only a small deviation in temperature from its design point. The balance between the heat production and its removal determines the operating temperature of a PEMFC. These stringent thermal requirements present a significant heat transfer challenge. In this work, the fundamental heat transfer mechanisms at PEMFC component level (including polymer electrolyte, catalyst layers, gas diffusion media and bipolar plates) are briefly reviewed. The current status of PEMFC cooling technology is also reviewed and research needs are identified.
Science Signaling Podcast: 4 March 2014

This Podcast features an interview with Geoffrey Abbott, author of a Research Article that appears in the 4 March 2014 issue of Science Signaling , about a potassium channel and a solute transporter that contribute to seizure susceptibility. Mice lacking the potassium channel regulatory subunit KCNE2 have cardiac arrhythmia and are prone to seizures. Abbott et al . report that the cerebrospinal fluid (CSF) from Kcne2 −/− mice had decreased abundance of myo -inositol compared to CSF from wild-type mice, and administering myo -inositol rescued seizure susceptibility in Kcne2 −/− mice. KNCE2 colocalized with the potassium channel pore-forming subunit KCNQ1 and the myo -inositol transporter SMIT1 in the choroid plexus, the tissue that produces and secretes CSF. The authors identified a mechanism whereby the SMIT1-KCNQ1-KCNE2 complex removes excess myo -inositol from the CSF.
Deaf Studies: A Critique of the Predominant U.S. Theoretical Direction

The focus and concerns establishing Deaf Studies in the 1970s have rigidified into a reactive stance toward changing historical conditions and the variety of deaf lives today. This critique analyzes the theoretical foundation of this stance: a tendency to downplay established research in the field of Deaf Studies and linguistics, the employment of outdated examples of discrimination, an uncritical acceptance of Derrida's phonocentrism, flawed uses of Saussure's linguistic theory, and reliance on the limiting metaphor of colonialism. The purpose of the critique ultimately is to point Deaf Studies in a new direction. Issues with conceptualizing an expanded Deaf Studies are the focus of a companion article (this issue), "Inclusive Deaf Studies: Barriers and Pathways.".
MIMO Equalization and Cancellation for 10Gbase-T 1

Traditionally equalization is performed individually for 10GBASE-T, and FEXT is treated as noise to be cancelled at the receiver. However, FEXT contains information about the symbols transmitted from remote transmitters and it can be viewed as a signal rather than noise to facilitate signal recovery. This paper proposes to use MIMO (multi-input multi output) equalization technique to deal with FEXT in 10GBASE-T. In the proposed MIMO technique, FEXT is treated as signal, which improves SNR. Instead of using long FEXT cancellers, MIMO-DFE with short length is used to remove post-cursor ISI. Our simulation results show that, by using the proposed MIMO equalization, we are able to achieve SNR (signal to noise ratio) improvement around 0.5~9dB with 13% less complexity than the traditional equalization technique in twisted-pair channel environment.
Photodegradation of common environmental pharmaceuticals and estrogens in river water

Photodegradation rates of five pharmaceuticals (gemfibrozil, ibuprofen, ketoprofen, naproxen, and propranolol) and of four estrogens (estriol, estrone [E1], 17beta-estradiol [E2], and 17alpha-ethinylestradiol [EE2]), which are common contaminants in the aquatic environment, were measured in both purified and river water at environmentally relevant concentrations (1-2 microg/L) and different oxygen concentrations. Solutions were irradiated with a xenon arc lamp (765 W/m2; 290 nm < lambda < 700 nm) and analyzed using a high-performance liquid chromatography-tandem mass spectrometry method with electrospray ionization for pharmaceuticals and atmospheric pressure photoionization for estrogens. In river water, half-lives were 4.1 min [corrected] for ketoprofen, 1.1 h [corrected] for propranolol, 1.4 h for naproxen, 2 to 3 h for estrogens, and 15 h for gemfibrozil and ibuprofen. In air-saturated purified water, rates generally were slower except for that of ketoprofen, which reacted with a half-life of 2.5 min. Naproxen, propranolol, and E1 reacted with half-lives of 1.9, 4.4, and 4.7 h, respectively. The EE2, estriol, E2, gemfibrozil, and ibuprofen reacted with half-lives of 28.4, 38.2, 41.7, 91.4, and 205 h, respectively. The presence of oxygen doubled the direct photolysis rates of naproxen and propranolol. In nonautoclaved river water, 80% of E2 rapidly biotransformed to E1 within less than 20 min, whereas all other compounds remained stable over 22 h.
Macrophage-secreted cytokines drive pancreatic acinar-to-ductal metaplasia through NF-κB and MMPs

In response to inflammation, pancreatic acinar cells can undergo acinar-to-ductal metaplasia (ADM), a reprogramming event that induces transdifferentiation to a ductlike phenotype and, in the context of additional oncogenic stimulation, contributes to development of pancreatic cancer. The signaling mechanisms underlying pancreatitis-inducing ADM are largely undefined. Our results provide evidence that macrophages infiltrating the pancreas drive this transdifferentiation process. We identify the macrophage-secreted inflammatory cytokines RANTES and tumor necrosis factor α (TNF) as mediators of such signaling. Both RANTES and TNF induce ADM through activation of nuclear factor κB and its target genes involved in regulating survival, proliferation, and degradation of extracellular matrix. In particular, we identify matrix metalloproteinases (MMPs) as targets that drive ADM and provide in vivo data suggesting that MMP inhibitors may be efficiently applied to block pancreatitis-induced ADM in therapy.
The measurement of cyclic GMP and cyclic AMP phosphodiesterases.

Abstract Methods are described for measuring phosphodiesterases for cGMP and cAMP in the range of activity yielding 10 −12 to 10 −8 mol of product. The 5′-GMP formed is measured by conversion to GDP with guanylate kinase. Amounts of GDP greater than 10 −10 mol are measured directly with an enzyme system which results in stoichiometric oxidation of NADH. This is either determined by the decrease in fluorescence or the excess NADH is destroyed with acid and the NAD + measured by its fluorescence in strong NaOH. With smaller amounts of GDP, sensitivity is amplified 1000-fold with the succinic thiokinase-pyruvate kinase cycle. In the case of cAMP diesterase, larger amounts of 5′-AMP are measured in the same way as 5′-GMP, except that adenylate kinase is substituted for guanylate kinase. With smaller amounts, the 5′-AMP is converted to ATP, and sensitivity is amplified with the adenylate kinase-pyruvate kinase cycle. As little as 20 ng dry weight of average brain is sufficient for accurate assay of the diesterase activity toward either cAMP or cGMP. When there is danger of significant destruction of AMP or GMP by tissue 5′-nucleotidase, this is prevented by adding GMP to the cAMP reagent, AMP to the cGMP reagent, or 5′-UMP to either reagent.
Quality Assurance in Sub-Saharan Africa

This article assesses the status and practice of higher education quality assurance in sub- Saharan Africa, focusing on degree-granting tertiary institutions. A main finding is that structured national-level quality assurance processes in African higher education are a very recent phenomenon and that most countries face major capacity constraints. Only about a third of them have established structured national quality assurance mechanisms, often only as recently as during the last ten years. Activities differ in their scope and rigor, ranging from simple licensing of institutions by the minister responsible for higher education, to comprehensive system-wide program accreditation and ranking of institutions. Within institutions of higher learning, self-assessment and academic audits are gradually being adopted to supplement traditional quality assurance methods. However, knowledge about and experience with self-assessments are limited. The main challenges to quality assurance systems in Africa are cost and human capacity requirements.
Antimalarial Efficacy of Hydroxyethylapoquinine (SN-119) and Its Derivatives

Quinine and other cinchona-derived alkaloids, although recently supplanted by the artemisinins (ARTs), continue to be important for treatment of severe malaria. Quinine and quinidine have narrow therapeutic indices, and a safer quinine analog is desirable, particularly with the continued threat of antimalarial drug resistance. Hydroxyethylapoquinine (HEAQ), used at 8 g a day for dosing in humans in the 1930s and halving mortality from bacterial pneumonias, was shown to cure bird malaria in the 1940s and was also reported as treatment for human malaria cases. Here we describe synthesis of HEAQ and its novel stereoisomer hydroxyethylapoquinidine (HEAQD) along with two intermediates, hydroxyethylquinine (HEQ) and hydroxyethylquinidine (HEQD), and demonstrate comparable but elevated antimalarial 50% inhibitory concentrations (IC50) of 100 to 200 nM against Plasmodium falciparum quinine-sensitive strain 3D7 (IC50, 56 nM). Only HEAQD demonstrated activity against quinine-tolerant P. falciparum strains Dd2 and INDO with IC50s of 300 to 700 nM. HEQD had activity only against Dd2 with an IC50 of 313 nM. In the lethal mouse malaria model Plasmodium berghei ANKA, only HEQD had activity at 20 mg/kg of body weight comparable to that of the parent quinine or quinidine drugs measured by parasite inhibition and 30-day survival. In addition, HEQ, HEQD, and HEAQ (IC50 ≥ 90 μM) have little to no human ether-a-go-go-related gene (hERG) channel inhibition expressed in CHO cells compared to HEAQD, quinine, and quinidine (hERG IC50s of 27, 42, and 4 μM, respectively). HEQD more closely resembled quinine in vitro and in vivo for Plasmodium inhibition and demonstrated little hERG channel inhibition, suggesting that further optimization and preclinical studies are warranted for this molecule.
A recombinant protein and a chemically synthesized peptide containing the active peptides of the platelet collagen receptors inhibit ferric chloride-induced thrombosis in a rat model

We have previously reported that a recombinant protein (M(r) 47 kDa), which contains both active peptide of platelet receptors for types I and III collagen inhibits both types I and III collagen-induced platelet aggregation. In order to eliminate non-reactive portion of the protein, we have constructed a recombinant of rHyB (M r 6 kDa). In addition, we chemically synthesized a hybrid peptide with 30 amino acid residues (cHyB, M r 3 kDa) that contains each of the active peptide derived from platelet receptors for types I and III collagen and a linker of 12 amino acid residues. In the present investigation, we report that both rHyB and cHyB inhibit type I and type III collagen-induced platelet aggregation, and the adhesion of radiolabeled platelets onto rabbit aortic segments in a dose-dependent manner. We have used an animal model, which employs FeCl3 to induce thrombi formation to study the effectiveness of both rHyb and cHyB on preventing thrombi formation. We obtained results that show that both rHyB and cHyB can inhibit thrombi formation in a dose-dependent manner. These results suggest that either rHyB or cHyB may be a possible therapeutic agent in preventing thrombi formation.
Stepping over obstacles of different heights and varied shoe traction alter the kinetic strategies of the leading limb.

This study aims to investigate the effects of shoe traction and obstacle height on friction during walking to better understand the mechanisms required to avoid slippage following obstacle clearance. Ten male subjects walked at a self-selected pace during eight different conditions: four obstacle heights (0%, 10%, 20% and 40% of limb length) while wearing two different pairs of shoes (low and high traction). Frictional forces were calculated from the ground reaction forces following obstacle clearance, which were sampled with a Kistler platform at 960 Hz. All frictional peaks increased with increases in obstacle height. Low traction shoes yielded smaller peaks than high traction shoes. The transition from braking to propulsion occurred sooner due to altered control strategies with increased obstacle height. Collectively, these results provided insights into kinetic strategies of leading limb when confronted with low traction and high obstacle environments. This study provides valuable information into the...
Stress, Marital Satisfaction, and Psychological Distress Among African Americans

This study examines relationships among financial strain, unfair treatment, and martial satisfaction among African Americans. Using data from the National Survey of American Life, findings indicated that social stressors that occur inside of the home (i.e., financial strain) as well as those experienced outside of the home (i.e., unfair treatment) have negative consequences for marital quality and psychological distress. Furthermore, the combination of experiencing unfair treatment and financial strain has particularly deleterious mental health consequences for married African Americans. Results also highlight the protective effect of marital satisfaction on psychological distress as well as its potential to buffer the negative effects of unfair treatment and financial strain on psychological distress. Implications for policy to improve marital quality and promote the mental health of African Americans are discussed.
Diophantine inferences from statistical aggregates on few-valued attributes

Research on protection of statistical databases from revelation of private or sensitive information [Denning, 1982, ch. 6] has rarely examined situations where domain-dependent structure exists for a data attribute such that only a very few independent variables can characterize it. Such circumstances can lead to Diophantine (that is, integer-solution) equations whose solution can lead to surprising or compromising inferences on quite large data populations. In many cases the Diophantine equations are linear, allowing efficient algorithmic solution. Probabilistic models can also be used to rank solutions by reasonability, further pruning the search space. Unfortunately, it is difficult to protect against this form of data compromise, and all countermeasures have disadvantages.
Triplet state absorption in carbon nanotubes: a TD-DFT study.

We predict properties of triplet excited states in single-walled carbon nanotubes (CNTs) using a time-dependent density-functional theory (TD−DFT). We show that the lowest triplet state energy in CNTs to be about 0.2−0.3 eV lower than the lowest singlet state energies. Like in π-conjugated polymers, the lowest CNT triplets are spatially localized. These states show strong optical absorption at about 0.5−0.6 eV to the higher lying delocalized triplet states. These results demonstrate striking similarity of the electronic features between CNTs and π-conjugated polymers and provide explicit guidelines for spectroscopic detection of CNT triplet states.
Conformational dynamics of Ca2+-dependent responses in the polycystin-2 C-terminal tail.

PC2 (polycystin-2) forms a Ca 2+ -permeable channel in the cell membrane and its function is regulated by cytosolic Ca 2+ levels. Mutations in the C-terminal tail of human PC2 (HPC2 Cterm) lead to autosomal dominant polycystic kidney disease. The HPC2 Cterm protein contains a Ca 2+ -binding site responsible for channel gating and function. To provide the foundation for understanding how Ca 2+ regulates the channel through the HPC2 Cterm, we characterized Ca 2+ binding and its conformational and dynamic responses within the HPC2 Cterm. By examining hydrogen–deuterium (H–D) exchange profiles, we show that part of the coiled-coil domain in the HPC2 Cterm forms a stable helix bundle regardless of the presence of Ca 2+ . The HPC2 L1EF construct contains the Ca 2+ -binding EF-hand and the N-terminal linker 1 region without the downstream coiled coil. We show that the linker stabilizes the Ca 2+ -bound conformation of the EF-hand, thus enhancing its Ca 2+ -binding affinity to the same level as the HPC2 Cterm. In comparison, the coiled coil is not required for the high-affinity binding. By comparing the conformational dynamics of the HPC2 Cterm and HPC2 L1EF with saturating Ca 2+ , we show that the HPC2 Cterm and HPC2 L1EF share a similar increase in structural stability upon Ca 2+ binding. Nevertheless, they have different profiles of H–D exchange under non-saturating Ca 2+ conditions, implying their different conformational exchange between the Ca 2+ -bound and -unbound states. The present study, for the first time, provides a complete map of dynamic responses to Ca 2+ -binding within the full-length HPC2 Cterm. Our results suggest mechanisms for functional regulation of the PC2 channel and PC2’s roles in the pathophysiology of polycystic kidney disease.
Justice and the Peace: A Time‐Sensitive Empirical Evaluation

Prevalent in current discussions of peace-building are various claims about the ways in which justice-seeking mechanisms - like human rights trials and truth and reconciliation commissions - can quell violent conflict. In fact, ‘transitional justice’ has attained the status of orthodoxy among global peace-promoting actors and international institutions. Though propositions about the pacifying effects of transitional justice mechanisms have swirled about for over a decade, to date very few comprehensive studies have adequately evaluated them. In fact, many ‘realist’ scholars oriented toward producing political order remain justifiably skeptical regarding the impact of transitional justice institutions: what if they actually are destabilizing and cause a relapse into violent conflict? Furthermore, there has been little interaction between legalistic approaches emphasizing ‘unproven possibilities’ and scientific approaches emphasizing ‘empirical realities.’ More specifically, those deeply involved with transitional justice have rarely crossed paths with those enmeshed in conflict studies. We seek to address the lack of hypothesis-testing and dialogue by constructing an integrated model of peace transition, duration, and conflict recurrence that incorporates the newest information on cross-national transitional justice efforts. Utilizing the PRIO dataset, we test the proposition that domestic trials and truth commissions are more effective than political amnesties and repression for producing a lasting peace. Depending on the model chosen, we show that transitional justice mechanisms at worst have no effect, and at best slightly extend the duration of peace following violent conflict. Our findings encourage a reevaluation of the peace v. justice debate, one that moves toward more humility on each side.
Past and future of hardware and architecture

We start by looking back at 50 years of computer architecture, where philosophical debates on instruction sets (RISC vs. CISC, VLIW vs. RISC) and parallel architectures (NUMA vs clusters) were settled with billion dollar investments on both sides. In the second half, we look forward. First, Moore's Law is ending, so the free ride is over software-oblivious increasing performance. Since we've already played the multicore card, the most-likely/only path left is domain-specific processors. The memory system is radically changing too. First, Jim Gray's decade-old prediction is finally true: "Tape is dead; flash is disk; disk is tape." New ways to connect to DRAM and new non-volatile memory technologies promise to make the memory hierarchy even deeper. Finally, and surprisingly, there is now widespread agreement on instruction set architecture, namely Reduced Instruction Set Computers. However, unlike most other fields, despite this harmony has been no open alternative to proprietary offerings from ARM and Intel. RISC-V ("RISC Five") is the proposed free and open champion. It has a small base of classic RISC instructions that run a full open-source software stack; opcodes reserved for tailoring an System-On-a-Chip (SOC) to applications; standard instruction extensions optionally included in an SoC; and it is unrestricted: there is no cost, no paperwork, and anyone can use it. The ability to prototype using ever-more-powerful FPGAs and astonishingly inexpensive custom chips combined with collaboration on open-source software and hardware offers hope of a new golden era for hardware/software systems.
A Man for All Reasons: The Use of Tocqueville's Writing in U. S. Judicial Opinions

The United States has never been given to particular adoration of foreign observers of its mores, who quite often turn out to be critics rather than admirers. Nevertheless, one of its favorite visitors since his one and only appearance on the scene in 1831-1832 is the 25-year-old magistrate Alexis de Tocqueville, sent by his government to study penal reform in the new republic. Tocqueville and his good friend Gustave de Beaumont, like young adventurers before and since, took the opportunity to extend their stay, and turned their tour of prisons into a journey through the young nation that furnished the raw material for what readers ever since have considered to be the single most insightful study of the United States ever written. Since the publication of Tocqueville's study, titled De la democratie en Amerique, which appeared in English in 1835, the second volume following in 1840, all manner of students of U. S. society have pored over it, studying it, quoting and misquoting it, and claiming it as support for their varied ideas. Both conservatives and liberals have claimed Tocqueville as a founding father of their thought. But as John Lukacs points out, Tocqueville cannot be so simply categorized. Through all of these evaluations, assessments and hagiographies, commentators sometimes lose sight of the fact that Tocqueville was, by training and choice, an attorney, and what is more, a civil law trained attorney, a magistrate, a member of the Legislative Assembly, a drafter of the Constitution of France's Second Republic and a member of Louis-Napoleon Bonaparte's Cabinet. Ultimately, as one student of his thought points out, it may not matter.As a civilian, Tocqueville was trained in a newly formed legal regime. As an attorney practicing within a code enacted only a year before his birth, he had a vital interest in determining how such new codes could be integrated into existing social, political, and legal environments. His interest in the new republic across the ocean, which was engaged in a similar experiment, was at once philosophical and practical. Thus, what use U. S. judges have made of his words in their own opinions is certainly of interest.
Abstract 4275: PLA2activities in human epithelial ovarian cancer ascites

Ascites production is characteristic of late stage human epithelial ovarian cancer (EOC) and it correlates with tumor spread clinically. However, the role of this microenvironment in cancer cells and the mechanisms by which ascites promotes tumor development are not well understood. In recent years, phospholipase A 2 (PLA 2 ) enzymes have been identified as cancer therapeutic targets focusing mainly on secreted PLA 2 s (sPLA 2 s). In this work, we optimized and validated the quantitative analytic methods to measure PLA 2 activities in human EOC ascites and tissues. We found, for the first time, that both cytosolic PLA 2 (cPLA 2 ) and calcium-independent PLA 2 (iPLA 2 ), but not sPLA 2 and autotaxin (ATX), activities (not their expression levels) in human EOC tissues and ascites (the tumor microenvironment) were significantly elevated. In addition, while cell-free (S1) and vesicle-free (S4) human EOC ascites had potent promoting activities in proliferation, migration, and invasion of human EOC cells, the PLA 2 activities were involved and account for a significant portion of these activities. Moreover, in vivo studies demonstrated that methyl arachidonyl fluorophosphonate (MAFP, a dual inhibitor of cPLA 2 and iPLA 2 ), was highly effective in inhibiting EOC tumorigenesis/metastasis in xenograft models, supporting PLA 2 activities as new targets for EOC. LPA, an enzymatic product of ATX and PLA 2 enzymes, mediates a significant part of the cellular effects of ascites as evidenced by 1) LPA is produced in cell-free ascites; 2) LPA production and their sensitivities to inhibitors correlate well with the cellular effects in ascites; and 3) the cellular activities were sensitive to LPAR inhibitor and siRNA against LPARs. While cPLA 2 and iPLA 2 are cytosolic enzymes, our findings indicate that they are associated with cell- and microvesicle-free ascites. In summary, our work implies the potential marker and therapeutic values of PLA 2 activity in ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4275. doi:1538-7445.AM2012-4275
Immunohistochemistry of Capillary Hemangioblastoma: Immunoperoxidase-labeled Antibody Staining Resolves the Differential Diagnosis with Metastatic Renal Cell Carcinoma, But Does Not Explain the Histogenesis of the Capillary Hemangioblastoma

We used a battery of antigens to determine whether immunohistochemistry can (a) contribute to resolving the histogenesis of the stromal component of the capillary hemangioblastoma, and (b) answer cases of difficult pathologic differential diagnosis with metastatic clear cell carcinoma. The stromal cells of the capillary hemangioblastoma are antigenically polymorphous and may express immunoreactive erythropoietin, renin, keratin, Leu M1, Leu 7, actin, neuron-specific enolase, S100 protein, and glial fibrillary acidic protein. However, the use of epithelial membrane antigen allows certain histopathologic distinction between capillary hemangioblastoma and metastatic clear cell carcinoma.
Reversible Hydrogen Uptake in Carbon-Based Materials

Several approaches for achieving reversible hydrogen uptake by carbon are considered, including intercalation, adsorption by a graphite surface, hydrogenation of fullerenes, and the filling of carbon nanotubes. Most scenarios suggest that it is difficult to achieve an atomic uptake [H/C] ratio exceeding unity. Evidence for H 2 uptake by various carbon materials is reviewed.
Statistical assessment for abuse deterrent formulation in clinical abuse potential studies

s / Drug and Alcohol Dependence 146 (2015) e202–e284 e245 Patterns of concurrent substance use among prescription stimulant misusers: Results from the national survey on drug use and health Lian-Yu Chen1, R. Crum1,2,3, Christopher N. Kaufmann1, Silvia S. Martins4, Eric C. Strain2, R. Mojtabai1,2 1 Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States 2 Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States 3 Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States 4 Epidemiology, Mailman School of Public Health, New York, NY, United States Aims: To examine patterns of concurrent substance use among adults who used prescription stimulants non-medically. Methods: We used latent class analysis (LCA) to examine patterns of past-year problematic substance (i.e. had any criteria of abuse or dependence) in a sample of 6244 adult participants of NSDUH 2006–2011 who reported past-year non-medical use of prescription stimulants. Multivariate latent regression was used to determine the association of socio-demographics, mental health and deviant behavior characteristics with the latent classes. Results: A four-class model had the best model fit. The largest class was comprised of individuals with low probabilities of any problematic substance use (low substance users, 49.1%); the smallest class was comprised of individuals with high probabilities of problematic use of multiple drugs and alcohol (polysubstance users, 5.3%). A third class was comprised of those who were problematic users of all types of prescription drugs (prescription drug users, 11.8%). A fourth class included participants with high probabilities of problematic alcohol and marijuana use (33.8%). Regression results showed that prescription drug users and polysubstance usersweremore likely to report past-yearmental health problems, deviant behaviors, and mental or substance treatment use, while alcohol/marijuana users reported more deviant behaviors andsubstance treatmentuse, compared to lowsubstanceusers. Conclusions: Nonmedical users of prescription stimulants are a heterogeneous group, with a large subgroup rarely having any substance problems. These sub-groups have distinct patterns of mental health comorbidity, behavior problems and service use, which can offer implications for prevention and treatment of nonmedical stimulant use. Financial support: DA023186. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.132 Statistical assessment for abuse deterrent formulation in clinical abuse potential studies
Type 2 Diabetes: Why We Are Winning the Battle but Losing the War? 2015 Kelly West Award Lecture

Diabetes is among the biggest of the 21st-century global health challenges. In the U.S. and other high-income countries, thanks to investments in science, dedication to implementing these findings, and measurement of quality of care, there have been improvements in diabetes management and declines in rate of diabetes complications and mortality. This good news, however, is overshadowed by the ever-increasing absolute numbers of people with diabetes and its complications and the unprecedented growth of diabetes in low- and middle-income countries of the world. To comprehensively win the war against diabetes requires 1) concerted attention to prevention and 2) expansion of global research to better inform population-level policies to curb diabetes but also to better understand individual- and population-level variations in pathophysiology and phenotypes globally so that prevention and treatment can be tailored. For example, preliminary data show that thin people in low- and middle-income countries such as India commonly experience type 2 diabetes. Global studies comparing these thin Asian Indians with other high-risk groups such as Pima Indians, a population with a high mean BMI, suggest that type 2 diabetes may not be a single pathophysiological entity. Pima Indians may represent the well-studied phenotype of poor insulin action (type 2A), whereas Asian Indians represent the grossly understudied phenotype of poor insulin secretion (type 2B). This has major implications for diagnosis, prevention, and treatment and highlights the mismatch between where diabetes burdens occur (i.e., low- and middle-income countries) and where research happens (i.e., high-income countries). Correcting this imbalance will advance our knowledge and arsenal to win the global war against diabetes.
Analysis of the Surveillance of Influenza in Guangzhou City in 2004

Objective To understand the epidemic situation and epidemic character of influenza in Guangzhou, and suggest some measures for prevention and control of the disease. Method To erect a influenza surveillance network, taking epidemical and etiological surveillancel. Result Epidemical surveillance: 265 335 influenza like cases were reported, accounting for 6.3%(265335/4214659) of the total outpatient. 31 outbreaks were reported. All of them were H3N2. Etiological surveillance:2134 mouth rinsing samples were collected and 242 (11.34%) were positive in influenza virus detection. Of the positive results,233 cases were influenza H3N2 viruses and 9 cases were influenza B viruses. Conclusion The epidemical peak of influenza in Guangzhou is from April to August and the predominant strain is influenza H3N2 viruses.
Effects of cardiopulmonary bypass on eicosanoid metabolism during pediatric cardiovascular surgery.

Cardiopulmonary bypass in children with congenital heart disease is associated with significant morbidity manifested by increased complement degradation products, heightened pulmonary vascular activity, and coagulopathy. In adults with cardiac disease, the prostaglandins (eicosanoids) have been shown to contribute to the pathophysiologic response to extracorporeal circulation. This study assessed the effect of cardiopulmonary bypass in infants and children on two potent eicosanoids: thromboxane, a vasoconstrictor and platelet aggregating agent, and prostacyclin, a vasodilator and platelet disaggregating agent. The biochemical profiles of thromboxane and prostacyclin were evaluated in temporal relationship to selected parameters of platelet loss and pulmonary vascular hemodynamics during and after cardiopulmonary bypass. Twenty-one children, aged 3 days to 9 years, with congenital heart defects who were undergoing repair with cardiopulmonary bypass were studied. Nine pediatric patients undergoing palliative heart operations with no cardiopulmonary bypass served as the control group. In the group having cardiopulmonary bypass, the thromboxane concentration significantly increased during bypass (195 ± 10 to 910 ± 240 pg/ml, ± standard error of the mean, p
“There Were Rapes!” Sexual Assaults of African American Women and Children in Jim Crow

Using data from 92 interviews, this article examines the narratives of African Americans' experiences as children and young adults during Jim Crow in the Southeast and Southwest. It gives voice to the realities of sexual assaults committed by ordinary White men who systematically terrorized African American families with impunity after the post-Reconstruction south until the 1960s. The interviewees discuss the short- and long-term impact of physical, mental, emotional, and sexual assaults in their communities. We discuss the top four prevalent themes that emerged related to sexual assault, specifically (a) the normalization of sexual assaults, (b) protective measures to avoid White violence, (c) the morality of African American women, and (d) the long-term consequences of assaults on children.
Effects of active region design on gain and carrier injection and transport of CW $(20\bar{2}\bar{1})$ semipolar InGaN laser diodes

High-power CW semipolar laser diodes (LDs) were studied. Improved efficiencies (threshold, differential, and wall plug) were observed when the number of quantum wells (QWs) in the active region was reduced from 4 to 2. Threshold current densities as low as 2.6 kA/cm2 were obtained. The differential efficiency of a 5 µm wide by 1200 µm long LD with a 2-QW active region was 54% and the wall plug efficiency was 11%. Experimental and analytical analyses of the devices suggested carrier leakage from an ineffective electron-blocking layer, providing an explanation for the high voltage observed in all the devices.
Degrees of freedom of the single antenna gaussian wiretap channel with a helper irrespective of the number of antennas at the eavesdropper

A Gaussian wiretap channel with a helper, i.e., a cooperative jammer, is considered and its secure degrees of freedom (s.d.o.f.) is computed. Previous work showed that the s.d.o.f. is upper bounded by 1 over 2 in this model when all parties are equipped with one antenna each. In this paper, the more challenging scenario where the eavesdropper has multiple antennas is tackled. Relying on structured signaling and cooperative jamming, specifically, by real interference alignment, it is shown that s.d.o.f. of 1 over 2 is achievable irrespective of the number of antennas the eavesdropper may have as long as the cooperative jammer has the same number of antennas as the eavesdropper. The design insight revealed is that the price to pay for the increase in the number of antennas at the eavesdropper is an equivalent increase in the number of antennas at the cooperative jammer in order to maintain the same s.d.o.f.
Phase-Locked Frequency Chains to 130 THz at NRC

In the seventies several schemes were designed at NRC for relating CO2 laser frequencies near 30 THz to the Cs standard [1]; two of these were implemented, and were used in our measurement of the speed of light [2] and of the HeNe/CH4 laser frequency [3,4].
Human papillomavirus-induced oropharyngeal cancer in Hispanics in the United States.

Objectives/Hypothesis Determine disparities in survival outcome and clinical presentation between Hispanic and non-Hispanic white patients with human papillomavirus–positive oropharyngeal squamous cell carcinoma. Study Design Retrospective clinical research. Methods Clinical data on Hispanics and non-Hispanic white patients with diagnosis of human papillomavirus/p16–positive oropharyngeal squamous cell carcinoma were drawn from a tumor registry from the University of Miami Hospitals and Clinics from 2008 to 2014. Of 436 patients with oropharyngeal squamous cell carcinoma, 237 patents met inclusion criteria. Patient's age, gender, smoking history, alcohol history, race/ethnicity, tumor T stage, nodal N stage, and composite TNM stage were included in the analysis. Associations between race and other categorical variables were explored with χ2 test or Fisher exact test where appropriate. Survival curves were generated using the Kaplan-Meier method. Results Significant differences in clinical presentation was detected between Hispanic (N = 70) and non-Hispanic white (N = 167) patients. Hispanic human papillomavirus–positive oropharyngeal squamous cell carcinoma patients showed a higher proportion of women with disease, a higher proportion of patients presenting with tonsil rather than tongue base primary subsite cancer, and a higher proportion of patients who do not consume alcohol compared to non-Hispanic white human papillomavirus–positive oropharyngeal squamous cell carcinoma patients. A statistically significant survival difference between these two ethnic groups was not detected in the current dataset. Conclusions Unique differences in clinical presentations between Hispanic patients and non-Hispanic whites with human papillomavirus–positive oropharyngeal squamous cell carcinoma were detected. This may be the first study to report novel clinical presentation in Hispanic human papillomavirus–positive patients with oropharyngeal squamous cell carcinoma living in the United States. Level of Evidence 4. Laryngoscope, 2016
Spatiotemporal variability of meteorological droughts in southeastern USA

Droughts in the southeast USA have been linked to economic losses and intractable water conflicts. The region has witnessed several severe droughts events during the period from 1901 to 2005. In this study, spatiotemporal variability in meteorological drought characteristics in the southeast were analyzed using two different datasets by the means of standard precipitation index and standard precipitation evapotranspiration index for the period 1901–2005 for agricultural and non-agricultural seasons. The study periods were divided into three epochs 1901–1935, 1936–1970, and 1971–2005 and drought characteristics, in terms of severity, frequency, number, and trends were analyzed. Additionally, areal extent, drought severities and return periods associated with three severe drought years 1904, 1954, and 2000 were analyzed. Except for the state of Florida, results indicate decrease in drought severity during the recent epoch of 1970–2005 in the study domain. Trend analysis confirms that the study domain has become wetter over the last 105 years. Wetting trends were more prominent in the agricultural season. Additionally, droughts seem to have migrated from the western part of the study area encompassing the states of Alabama, Tennessee, Louisiana, and Mississippi to the Florida panhandle region during the recent epoch. Droughts exhibited higher spatiotemporal variability during the agricultural season compared to the non-agricultural seasons. Results also showed that early to mid-1950s experienced some of the most severe droughts in the study domain. Some of the drought events, such as the drought of 1954 and 2000, have been equivalent to a 100-year drought event in the southeast. The results from this study form the benchmark for studying the impacts of future climate change projections on meteorological droughts in the southeast.
Abiraterone or Enzalutamide in Advanced Castration-Resistant Prostate Cancer: An Indirect Comparison

BACKGROUND To perform a comparative effectiveness analyses between enzalutamide and abiraterone acetate in both the pre-docetaxel and post-docetaxel settings based on published phase III randomized trials. METHODS The primary measure of efficacy was the posterior probability that enzalutamide outperforms abiraterone acetate (AA) with prednisone in terms of overall survival (OS) on average. Indirect meta-estimates were generated from four randomized studies in the context of a Bayesian hierarchical model with study-specific efficacy estimates meta-analyzed on the log scale. RESULTS We found weak evidence that enzalutamide outperforms AA with prednisone in terms of OS in the pre-docetaxel and post-docetaxel settings. However, we found strong evidence that enzalutamide outperforms AA with prednisone in terms of radiographic PFS, time until PSA progression, and PSA response rate in both the pre- and post-docetaxel settings. Rates of grade 3 or worse adverse events were broadly similar between treatment (enzalutamide or AA) and control arms (placebo or placebo with prednisone) in all included randomized studies. CONCLUSIONS There is strong evidence that enzalutamide outperforms AA with prednisone in terms of radiographic PFS and PSA progression and PSA response rate but not OS in the pre and post-docetaxel settings. These results may further guide clinicians in making treatment recommendations for patients with advanced prostate cancer. Prostate 77: 639–646, 2017. © 2017 Wiley Periodicals, Inc.
Abstract #1109: The signaling pathway PAR1-PAFR-MCAM/MUC18 links inflammation with melanoma metastasis

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO The development of tumor metastasis comprises a complex cascade of events that involves multiple intercellular interactions. Cellular and molecular pathways that regulate platelet activation, blood coagulation, and inflammation are critical players in tumor growth and metastasis. In particular, thrombin and platelet activating factor (PAF), through the activity of their specific G-protein-coupled receptors, act as putative mediators of tumor growth, angiogenesis, and metastasis. Surprisingly little is known about their mechanism(s) of action. Here, we demonstrate a novel signaling axis whereby the activation of Protease-Activated Receptor 1 (PAR1) regulates melanoma cell adhesion to endothelial cells, diapedesis, and lung metastasis via PAF receptor-mediated expression of the Melanoma Cell Adhesion Molecule MCAM/MUC18, thus linking the inflammatory microenvironment with melanoma metastasis. Indeed, in A375SM and C8161-c9 metastatic melanoma cells, silencing of PAR1 with small hairpin RNA resulted in downregulation of expression of PAFR and a decrease in PAF production. Silencing of either PAR1 or PAFR expression abrogated expression of MCAM/MUC18, a critical marker of homo- and heterotypic adhesion in melanoma. Overexpression of PAFR led to restoration of MCAM/MUC18 expression in PAR1shRNA cells, suggesting that PAFR acts downstream of PAR1. PAR1 silencing resulted in a loss of MCAM/MUC18 promoter activity, which was associated with the decreased binding and activity of CREB. Silencing of PAR1 or CREB also induced stronger in vivo binding of EGR1 and inhibition of Sp1 binding to MCAM/MUC18 promoter. Furthermore, silencing of PAR1 resulted in dramatic inhibition of melanoma cell adhesion and migration over the Human Dermal Microendothelial Cells (HDMECs), as well as a decreased retention of melanoma cells in lungs of nude mice after tail vein injection. Silencing MCAM/MUC18 produced similar non-metastatic phenotype. However, while melanoma cell adhesion to HDMECs, diapedesis and retention in lungs were rescued upon overexpression of PAFR in PAR1shRNA cells, only adhesion was rescued by overexpression of MCAM/MUC18. This suggested that in addition to MCAM/MUC18, other downstream targets of PAR1/PAFR signaling axis were required for metastatic dissemination of melanoma cells. Indeed, RT-PCR analysis in PAR1shRNA and PAFRshRNA cells revealed that PAR1 and PAFR modulate expression of the MMP-2 and VEGF, which are known to increase tumor cell invasiveness, vascular permeability, and metastatic dissemination into lungs. Overall, our results suggest that PAR1 and PAFR are critical targets for intervention with melanoma metastasis. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1109.