cssi/SciSciGPT-SciSciNet huggingface dataset:
Enhancing functional platelet release in vivo from in vitro–grown megakaryocytes using small molecule inhibitors

In vitro-grown megakaryocytes for generating platelets may have value in meeting the increasing demand for platelet transfusions. Remaining challenges have included the poor yield and quality of in vitro-generated platelets. We have shown that infusing megakaryocytes leads to intrapulmonary release of functional platelets. A Src kinase inhibitor (SU6656), a Rho-associated kinase inhibitor (Y27632), and an aurora B kinase inhibitor (AZD1152) have been shown to increase megakaryocyte ploidy and in vitro proplatelet release. We now tested whether megakaryocytes generated from CD34+ hematopoietic cells in the presence of these inhibitors could enhance functional platelet yield following megakaryocyte infusion. As expected, all inhibitors increased megakaryocyte ploidy, size, and granularity, but these inhibitors differed in whether they injured terminal megakaryocytes: SU6656 was protective, whereas Y27632 and AZD1152 increased injury. Upon infusion, inhibitor-treated megakaryocytes released threefold to ninefold more platelets per initial noninjured megakaryocyte relative to control, but only SU6656-treated megakaryocytes had a significant increase in platelet yield when calculated based on the number of initial CD34+ cells; this was fourfold over nontreated megakaryocytes. The released platelets from drug-treated, but healthy, megakaryocytes contained similar percentages of young, uninjured platelets that robustly responded to agonists and were well incorporated into a growing thrombus in vivo as controls. These studies suggest that drug screens that select megakaryocytes with enhanced ploidy, cell size, and granularity may include a subset of drugs that can enhance the yield and function of platelets, and may have clinical application for ex vivo-generated megakaryocytes and platelet transfusion.
Validation of the Unfaulted Error Bounds for ARAIM

This paper examines how to evaluate observed instantaneous signal-in-space errors and determine suitable upper bounds on their likely distribution. We compare this performance against the commitments and broadcast values from the satellites to determine whether the provided values are sufficient or not. An important aspect is to characterize the errors in light of known or predictable characteristics. Oftentimes, errors are grouped together to create a single averaged distribution. However, there may be times and conditions where performance is notably worse. We need to separate out such conditions and evaluate the distributions individually so as not to form overly optimistic estimates of the error bounds. Further, we must ensure that these parameters will continue to bound future fault-free behavior. We will describe the conservative steps taken in the estimation process and the validation effort, both with the real data and versus the stated commitments from the constellation service providers. Copyright © 2018 Institute of Navigation
Plant Community Responses to Mastication and Mulching of One-Seed Juniper (Juniperus monosperma)

Abstract Mechanical cutting and mastication of juniper trees aims to restore grassland habitat by reducing the density of encroaching woody species. However, the associated soil disturbance may also create conduits for invasive species, a risk that must be mitigated by land managers. We characterized herbaceous communities in treated and adjacent untreated areas in a pinon-juniper (Pinus edulis and Juniper monosperma) woodland in northern Arizona 2.5 years after treatment. Untreated plots had 4 × the herbaceous cover (82%) than treated plots (21%). Within treated plots, native species cover (19%) was 10 × higher than invasive species cover (2%). Furthermore, treated plots exhibited greater plant community variability and diversity than untreated plots, driven by an increase in the diversity of native grasses and non-native forbs. No new recruits were Arizona listed noxious weeds, indicating that, at least in the short term, mastication is not producing invasive species hot spots in this pinon-juniper woodland.
Maintenance of Mouse Gustatory Terminal Field Organization Is Dependent on BDNF at Adulthood.

The rodent peripheral gustatory system is especially plastic during early postnatal development and maintains significant anatomical plasticity into adulthood. Thus, taste information carried from the tongue to the brain is built and maintained on a background of anatomical circuits that have the capacity to change throughout the animal9s lifespan. Recently, the neurotrophin brain-derived neurotrophic factor (BDNF) was shown to be required in the tongue to maintain normal levels of innervation in taste buds at adulthood, indicating that BDNF is a key molecule in the maintenance of nerve/target matching in taste buds. Here, we tested whether maintenance of the central process of these gustatory nerves at adulthood also relies on BDNF by using male and female transgenic mice with inducible CreERT2 under the control of the keratin 14 promoter or under control of the ubiquitin promoter to remove Bdnf from the tongue or from all tissues, respectively. We found that the terminal fields of gustatory nerves in the nucleus of the solitary tract were expanded when Bdnf was removed from the tongue at adulthood and with even larger and more widespread changes in mice where Bdnf was removed from all tissues. Removal of Bdnf did not affect numbers of ganglion cells that made up the nerves and did not affect peripheral, whole-nerve taste responses. We conclude that normal expression of Bdnf in gustatory structures is required to maintain normal levels of innervation at adulthood and that the central effects of Bdnf removal are opposite of those in the tongue. SIGNIFICANCE STATEMENT BDNF plays a major role in the development and maintenance of proper innervation of taste buds. However, the importance of BDNF in maintaining innervation patterns of gustatory nerves into central targets has not been assessed. Here, we tested whether Bdnf removal from the tongue or from all structures in adult mice impacts the maintenance of how taste nerves project to the first central relay. Deletion of Bdnf from the tongue and from all tissues led to a progressively greater expansion of terminal fields. This demonstrates, for the first time, that BDNF is necessary for the normal maintenance of central gustatory circuits at adulthood and further highlights a level of plasticity not seen in other sensory system subcortical circuits.
New strategies in controlling drug resistance.

BACKGROUND: Chronic myeloid leukemia (CML) is most often caused by the translocation of chromosomes 9 and 22 to create the fusion protein, BCR-ABL. This constitutively active tyrosine kinase promotes cell division and blocks apoptosis, leading to unregulated growth of hematopoietic stem cells. Imatinib is a small molecule that binds to BCR-ABL at the site in which adenosine triphosphate (ATP) binds and blocks BCR-ABL function by blocking its ability to use ATP. As a front-line therapy, imatinib has been tremendously successful, with 80% to 90% of patients with chronic phase (CP) CML remaining progression free for more than 5 years. Increasingly, however, imatinib-resistant clones are appearing that allow the disease to progress. Dealing with the rise of these resistant clones has presented an important challenge to health care providers. OBJECTIVE: To review the mechanisms by which CML becomes resistant to imatinib and to discuss the new therapeutic alternatives to imatinib and when they should be conside...
Transcatheter Aortic Valve Implantation: Review of Current Evidence

Symptomatic severe aortic stenosis (AS) has a poor prognosis when treated medically and inevitably leads to an insidious functional deterioration, heart failure, and death [1]. Surgical aortic valve replacement (SAVR) is the current standard of care and is an accepted method to alleviate symptoms and prolong survival. For an array of reasons, approximately 30 % do not undergo SAVR [2]. However, since Dr. Alain Cribier pioneered the first transcatheter aortic valve replacement (TAVR) procedure in 2002 [3], this relatively new technique has been used extensively in over 40 countries accumulating to >50,000 implantations [4–19]. With results from the randomized PARTNER trial [20], TAVR has emerged as the standard of care for extremely high-risk or “inoperable” patients and is a valid alternative to surgery for selected high-risk but “operable” patients with symptomatic AS [21]. Currently, two different TAVR devices are widely available and used: the balloon-expandable Edwards SAPIEN Transcatheter Heart Valve (Edwards Lifesciences, Irvine, CA) and the self-expanding Medtronic CoreValve™ (Medtronic, Minneapolis, MN). Both devices received CE Mark approval for European commercial sale in 2007, and the Edwards SAPIEN valve received FDA pre-market approval in the USA in November 2011.
The Art and Science of Constructing a Memristor Model

Constructing an accurate and predictive compact mathematical model for an electronic circuit element that displays memristor behavior is extremely challenging, but it is also essential for designing and modeling complex integrated circuits that contain the element. Although the fundamental equations that specify the device physics may be known, they usually comprise a set of coupled nonlinear integro-differential equations that are extremely challenging to solve in three dimensions. A numerical solution of the equations can require supercomputers and long times, and thus this approach is useless for interactive simulation of large circuits that contain many such elements. Thus, the equations must be simplified dramatically, and it is not always clear which terms are the most important for the behavior of the device. On the other hand, a purely black box approach of fitting a set of experimental measurements to a convenient functional form runs the risk of poorly representing the behavior of the device in operating regimes outside the range in which the data were collected. Thus, a hybrid approach is necessary, in which the mathematical formalism for a memristor provides the framework for the model and knowledge of the device physics defines the state variable(s), operating limits, and asymptotic behavior necessary to make the model useful. After describing the challenge, the art and science of constructing a memristor model are illustrated by two examples: a locally active and volatile device based on a thin film of niobium dioxide that undergoes an insulator-to-metal transition because of Joule heating and a nonvolatile memory device based on titanium dioxide in which the effective width of an electron tunnel barrier is determined by oxygen vacancy drift caused by an applied electric field.
Pulling Back the “Post-Racial” Curtain: Critical Pedagogical Lessons from Both Sides of the Desk

Though popular belief and social science analyses often assert the racial tolerance and liberality of institutions of higher education and the white students who attend them, our research reveals young, educated white students’ everyday lives are anything but racially neutral. We pull back the curtain on these “post-racial” assumptions by presenting journal data collected from white students around the U.S. over many years. Our data documents that racist performances are a normal, habituated part of most white students’ social worlds. Nonetheless, we also find that asking students to research and write about their own lives in the context of instruction that addresses the critical realities of systemic racism can be a powerful educational tool. We explore the limits of mainstream educational and multiculturalism approaches in probing the deep realities of systemic racism; address the challenges of confronting our white students’ deeply embedded racial framing; and characterize strategies progressive, antiracist educators should consider in developing a race critical pedagogy for white students.
ALKYLALUMINIUM COMPOUNDS IN CARBENIUM ION POLYMERIZATION

ABSTRACT Cationic polymerizations can be efficiently initiated and high molecular-weight polymers can be synthesized by employing certain protogens (compounds giving rise to protons, e.g., Bronsted acids) and cationogens (compounds giving rise to carbocations e.g., alkyl halides) in conjunction with alkylaluminium coinitiators like Et2AlCl. Research in this field will be surveyed and complemented by recent findings. Important differences between the various aluminium-containing Lewis acids will be highlighted and the synthesis of quaternary-carbon containing compounds with Me3Al/RCl systems will be discussed. The effect of solvent (CH3C1, CH3Br, CH3I, and cyclopentane) on the alkylation of tertiary butyl halides (t-BuCl and t-BuBr) with trimethylaluminium has been studied and will be examined. This reaction in the course of which neopentane is formed, may be regarded as a model for cationic polymerization initiation and termination. The concept of initiation with polymeric halides leading to interesting novel graft copolymers will be discussed. Finally, the discovery of initiation by chlorine cations will be described.
The lived experience of a NICU father: A descriptive phenomenological study

Abstract The birth of an infant requiring admittance to the Neonatal Intensive Care Unit may produce heightened stress for parents. Despite a plethora of research examining the mothers' experiences during this time, limited research is available regarding the fathers' experiences. The aim of this study was to explore the lived experience of fathers whose child was admitted to the Neonatal Intensive Care Unit. This study was built on the philosophical principles of Descriptive Phenomenology, which aims to accurately describe fathers' lived experiences. Six fathers were purposefully recruited for their emic understanding of having a child in the neonatal intensive care unit. Fathers completed audio-recorded semi-structured interviews. Thematic analysis, using Colaizzi's method, revealed five themes: horrible storm, piece by piece, “I'm the father”, the gift of support, and little fighters. The results of this study will help health care professionals in the development of interventions that promote family-centered and developmentally supportive care.
Statutes and the Common Law of Contracts: A Shared Methodology

This chapter explores the intersection between, or the impact of, statutes on contract law, and compares the relative importance of, and intersections between, statutory and common law in contract.
Artificial Intelligence: A Vector for the Evolution of Health Professions and the Organization of Hospitals

Today’s health professions face major challenges that require assistance in terms of day-to-day practices, as well as improvements in collective modes of practice and management processes.
Bet hedging buffers budding yeast against environmental instability

To grow and divide, cells must extract resources from dynamic and unpredictable environments. Organisms thus possess redundant metabolic pathways for distinct contexts. In budding yeast, ATP can be produced from carbon by mechanisms that prioritize either speed (fermentation) or yield (respiration). We find that in the absence of predictive cues, cells vary in their intrinsic ability to switch metabolic strategies from fermentation to respiration. We observe subpopulations of yeast cells which either rapidly adapt or enter a shock state characterized by deformation of many cellular structures, including mitochondria. This capacity to adapt is a bimodal and heritable state. We demonstrate that metabolic preparedness confers a fitness advantage during an environmental shift but is costly in a constant, high-glucose environment, and we observe natural variation in the frequency of prepared cells across wild yeast strains. These experiments suggest that bet-hedging has evolved in budding yeast.
Line mixing and broadening of carbon dioxide by argon in the v3 bandhead near 4.2 µm at high temperatures and high pressures

Abstract Temperature-dependent line mixing and line broadening parameters were empirically-determined for rovibrational transitions (J = 99–145) in the (0000 → 0001) and (0110 → 0111) bandheads of carbon dioxide near 4.2 µm. Collisional effects by argon on the high rotational energy lines (E″ = 3920–8090 cm − 1 ) in the R-branch were studied over a range of temperatures from 1200–3000 K in a shock tube. Measured absorption spectra comprising the target lines in an argon bath gas at near-atmospheric pressures were fit with Voigt profiles to determine line-broadening coefficients, with temperature dependence accounted by a power law. With line broadening established, line-mixing effects were examined at elevated pressures up to 58 atm and similar temperatures, reflecting conditions in high-pressure combustion environments. A modified exponential gap model for line mixing was developed to capture the pressure and temperature dependence of collisional transfer rates for the bandhead region using the relaxation matrix formalism.
Order-Optimal Scaling of Covert Communication over MIMO AWGN Channels

Covert communication, i.e., communication with a low probability of detection (LPD), has attracted a huge body of work. Recent studies have concluded that the maximal covert coding rate of the discrete memoryless channels and the additive white Gaussian noise (AWGN) channels is diminishing with the blocklength: the maximum information nats that can be transmitted covertly and reliably over such channels is only on the order of the square root of the blocklength. In this paper, we study covert communication over multiple-input multiple-output (MIMO) AWGN channels. We derive the order-optimal scaling law of the number of covert nats when the maximal covert coding rate of MIMO AWGN channels is diminishing with the blocklength. Furthermore, we provide a comparative discussion for the case in which secrecy and energy undetectability constraints are combined.
Cost Analysis of Outpatient Anterior Cervical Discectomy and Fusion at an Academic Medical Center without Dedicated Ambulatory Surgery Centers.

Background Anterior cervical discectomy and fusion (ACDF) are increasingly performed at ambulatory surgical centers (ASCs). Academic centers lacking dedicated ASCs must perform these at large university hospitals, which pose unique challenges to cost savings and efficiency. Objective To describe the safety and cost of outpatient ACDF at a major academic medical center without a dedicated ASC. Methods ACDFs performed from 2015 to 2018 were retrospectively reviewed. Cases were performed at the major tertiary university hospital or a satellite university hospital dedicated to outpatient surgery. Patient demographics, surgical characteristics, perioperative complications, fusion at 12 months, and cost were collected. Results A total of 470 patients were included. The mean age was 56 years, with 255 women (54.3%). When comparing same-day discharge, overnight observation, or inpatient admission, there were no differences in age, gender, or number of levels fused. Same-day and overnight observation cases were associated with shorter procedure duration and less estimated blood loss. There were no differences in perioperative complications, 30-day readmissions, or fusion at 12 months. Direct and total costs were lowest for same-day cases, followed by overnight observation and inpatient admissions (P Conclusion Academic centers without dedicated ASCs can safely perform ACDF as a same-day or overnight observation procedure with significant reductions in cost. The lack of a dedicated ASC should not preclude academic centers from allocating appropriately selected patients into same-day or overnight observation care pathways. This strategy can improve resource utilization and preserve precious hospital resources for the most critically ill patients while also allowing these centers to build viable outpatient spine practices.
Dynamical Lamb effect in a superconducting circuit

The dynamical Lamb effect is predicted to arise in superconducting circuits when the coupling of a superconducting qubit with a resonator is periodically switched ``on'' and ``off'' nonadiabatically. We show that by using a superconducting circuit which allows one to switch between longitudinal and transverse coupling of a qubit to a resonator, it is possible to observe the dynamical Lamb effect. The switching between longitudinal and transverse coupling can be achieved by modulating the magnetic flux through the circuit loops. By solving the Schr\"odinger equation for a qubit coupled to a resonator, we calculate the time evolution of the number of excitations in the qubit and the resonator due to the dynamical Lamb effect. The number of excitations created in the system is maximum when the coupling is periodically switched between longitudinal and transverse using a square-wave or sinusoidal modulation of the magnetic flux with frequency equal to the sum of the average qubit and photon transition frequencies.
Lessons on Mobile Apps for COVID-19 from China

Abstract The COVID-19 pandemic has impacted the global society and human life profoundly. Many countries have launched COVID-19 mobile apps with a wide range in how these apps work. While it is hoped that these apps can assist in the fight against COVID-19, many are worried about user privacy. China implemented “health code” systems, which assigned neighborhoods and citizens a specific health code, meant to indicate their risk of having been exposed to COVID-19. The most widely used health code systems were hosted on the popular apps WeChat and Alipay, each with billions of users. Some experts argued that China's use of mobile applications was essential to its successful combat against COVID-19. Included in this study are a summary of mobile technology usage in China, a review of previous studies of mobile technology in healthcare, and a brief survey of some existing mobile applications for COVID-19 that were implemented. Also included are outcomes of interviews with healthcare and public safety experts and a public survey to understand how mobile applications were used in China's response to COVID-19. The interviews revealed four important themes: personal privacy, community involvement, government involvement, and situational specificity. It was found that a key concern was maintaining a balance between collecting and utilizing personal information, as well as protecting this information. In addition, close collaboration between local communities and the national government was essential. Mobile applications assisted in communication and coordination but did not replace the work of people such as delivery drivers and contact tracers. Our results also showed that there was room for improvement, especially accessibility for the elderly or those unfamiliar with technology. Similar results were obtained from our survey. It was interesting to find that the apps were mostly used for “accessing information on COVID-19.” In addition, respondents overwhelmingly identified “information” as the most valuable feature of COVID-19 apps. Both interview and survey results revealed the importance of providing information as a primary function of COVID-19 apps. Based on our findings we distilled four main lessons: mobile applications should assist in existing COVID-19 responses, inform users, protect users’ personal information, and adapt to users’ environments. We recommend that public health officials and app developers take these lessons into consideration when developing COVID-19 related mobile applications. In addition, we encourage researchers to utilize this report as a jumping off point for further research.
World Trade Center Health Program: 20 years after 9/11.

The September 11, 2001 terrorist attacks in New York City, at the Pentagon in Arlington, Virginia, and at the crash site near Shanksville, Pennsylvania caused over 3000 deaths in the immediate aftermath, and adversely affected the health of hundreds of thousands of responders—those involved in the rescue, recovery and clean-up efforts following the 9/11 attacks—and survivors—building occupants, residents, workers and students attending schools in the New York City disaster area. The James Zadroga 9/11 Health and Compensation Act of 2010 enacted by Congress and signed into law by President Obama created the World Trade Center (WTC) Health Program to provide healthcare to responders and survivors affected by toxic agent exposures arising from the 9/11 terrorist attacks and their aftereffects. Originally authorised for only 5 years, the WTC Health Program was reauthorised by Congress in 2015 until the year 2090—thereby assuring a lifetime of care for those affected by 9/11 (42 US Code §§ 300 mm—300 mm-61). Currently, the WTC Health Program has enrolled over 110 000 members, and is growing (6% in the past year). Unlike a traditional health plan which covers a broad scope of medical conditions, the WTC Health Program is a limited benefits health plan. Medical treatment benefits are provided only for those conditions determined to be related scientifically to toxic agent exposures encountered by 9/11 responders and survivors (covered conditions list available at https://www.cdc.gov/wtc/conditions.html). A total of 64 015 (58%) members have been awarded …
Factors influencing design and selection of GTAW robotic welding machines for the Space Shuttle main engine

Proposed hardware and software for microprocessor-controlled power supplies and welding machines are described. The application of the automatic seven-axis welding machine, which is to be preprogrammed to allow minimum intervention by the welding operator during the actual process, to the welding of the Space Shuttle main engine is discussed. The production requirements for the gas tungsten arc welds for the Space Shuttle main engine are examined. Consideration is given to positioner design, welding variables, inert shielding gas management, filler metal wire control, the up loading and down loading of data from off-line computers, process improvements, tooling, the welding variable library, and adaptive sensor control.
N-CAM Binding Inhibits the Proliferation of Hippocampal Progenitor Cells and Promotes Their Differentiation to a Neuronal Phenotype

Cell adhesion molecules (CAMs) play important roles during the development of the nervous system. On the basis of our previous observations that binding of the neural CAM (N-CAM) inhibits astrocyte proliferation and alters gene expression, we hypothesized that N-CAM may influence the balance between the proliferation and the differentiation of neural progenitor cells. Rat and mouse hippocampal progenitor cells were cultured and showed dependence on basic FGF for proliferation, immunoreactivity for nestin, the presence of limited numbers of differentiated cells, and the ability to generate glial cells and neurons under different culture conditions. Addition of soluble N-CAM reduced cell proliferation in a dose-dependent manner with no evidence of apoptosis. The inhibition of proliferation by N-CAM was accompanied by an induction of differentiation to the neuronal lineage, as indicated by a twofold increase in the percentage of microtubule-associated protein 2-positive cells even in the presence of mitogenic growth factors. Experiments using hippocampal cells from N-CAM knock-out mice indicated that N-CAM on the cell surface is not required for these effects, suggesting the existence of heterophilic signaling. These results support a role for N-CAM and N-CAM ligands in the inhibition of proliferation and the induction of neural differentiation of hippocampal neural progenitor cells.
Zero Withdrawal Anesthetic for All Finfish and Shellfish

Abstract The critical need in the United States for a zero withdrawal time anesthetic or sedative is widely recognized by fish culturists and fishery managers for both public and private aquaculture and fisheries management. There has also been confusion concerning whether such drugs as clove oil or eugenol are appropriate to use as anesthetics in aquaculture and fisheries. Recently, the American Fisheries Society was asked to help resolve this confusion by establishing a dialogue among stakeholders. A consortium of stakeholders, including a proactive pharmaceutical sponsor, has made a serious effort to gain a New Animal Drug Application approval of a potential zero withdrawal anesthetic called AQUI-S®. The present article is an attempt to address the circumstances related to an approval for a zero withdrawal anesthetic to include (1) need, (2) stakeholder groups, (3) candidate anesthetics, and (4) approval effort on candidate AQUI-S®.
Ultrasonic attenuation investigation of the reentrant superconductor Er 0.705 H 0.295 Rh 4 B 4

Temperature-dependent and magnetic-field-dependent ultrasonic attenuation measurements in ${\mathrm{Er}}_{0.705}$${\mathrm{Ho}}_{0.295}$${\mathrm{Rh}}_{4}$${\mathrm{B}}_{4}$ reflect the unusual magnetic and superconducting properties of this sample. Experimental data agree with theoretical predictions and verify that electromagnetic interaction is the predominant interaction in that sample at low temperatures.
Injury-induced "switch" from GTP-regulated to novel GTP-independent isoform of tissue transglutaminase in the rat spinal cord.

We recently found that alternative transcripts of tissue transglutaminase (tTG or TG2) were present in hippocampal brain regions of Alzheimer’s disease (AD), but not in control, nondemented, age-matched brains. Since antecedent non-severe trauma has been implicated in AD and other neurodegenerative diseases, such as Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), we were interested in whether alternative transcripts might be detected in a model of neurotrauma, controlled-contusion spinal cord injury (SCI) in the rat. Implicated in diverse roles from growth and differentiation to apoptotic cell death, only bifunctional tTG, of the nine member TG family, has dual catalytic activities: guanine trinucleotide (GTP) hydrolyzing activity (GTPase), as well as protein cross-linking. These functions imply two physiological functions: programmed cell life and death. These may have profound roles in the nervous system since studies in cultured astrocytes found tTG short (S) mRNA transcripts induced by treatment with injury-related cytokines. In the developing rat spinal cord, tTG activity is concentrated in ventral horn alpha motoneurons, but neither studies of spinal cord tTG gene expression, nor evaluation of the GTP-regulated isoforms in tissues, have been reported. We now report increased tTG protein and gene expression occurring rapidly after SCI. In parallel, novel appearance of a second, short form transcript, in addition to the normal long (L) isoform, occurs by 8 h of injury. Up-regulation of tTG message and activity following neural injury. with appearance of a truncated GTP-unregulated S form, may represent new approaches to drug targets
Molecular and Biochemical Evidence for the Involvement of Calcium/Calmodulin in Auxin Action

The use of (35)S-labeled calmodulin (CaM) to screen a corn root cDNA expression library has led to the isolation of a CaM-binding protein, encoded by a cDNA with sequence similarity to small auxin up RNAs (SAURs), a class of early auxin-responsive genes. The cDNA designated as ZmSAUR1 (Zea mays SAURs) was expressed in Escherichia coli, and the recombinant protein was purified by CaM affinity chromatography. The CaM binding assay revealed that the recombinant protein binds to CaM in a calcium-dependent manner. Deletion analysis revealed that the CaM binding site was located at the NH(2)-terminal domain. A synthetic peptide of amino acids 20-45, corresponding to the potential CaM binding region, was used for calcium-dependent mobility shift assays. The synthetic peptide formed a stable complex with CaM only in the presence of calcium. The CaM affinity assay indicated that ZmSAUR1 binds to CaM with high affinity (K(d) approximately 15 nM) in a calcium-dependent manner. Comparison of the NH(2)-terminal portions of all of the characterized SAURs revealed that they all contain a stretch of the basic alpha-amphiphilic helix similar to the CaM binding region of ZmSAUR1. CaM binds to the two synthetic peptides from the NH(2)-terminal regions of Arabidopsis SAUR-AC1 and soybean 10A5, suggesting that this is a general phenomenon for all SAURs. Northern analysis was carried out using the total RNA isolated from auxin-treated corn coleoptile segments. ZmSAUR1 gene expression began within 10 min, increased rapidly between 10 and 60 min, and peaked around 60 min after 10 microM alpha-naphthaleneacetic acid treatment. These results indicate that ZmSAUR1 is an early auxin-responsive gene. The CaM antagonist N-(6-aminohexyl)5-chloro-1-naphthalenesulfonamide hydrochloride inhibited the auxin-induced cell elongation but not the auxin-induced expression of ZmSAUR1. This suggests that calcium/CaM do not regulate ZmSAUR1 at the transcriptional level. CaM binding to ZmSAUR1 in a calcium-dependent manner suggests that calcium/CaM regulate ZmSAUR1 at the post-translational level. Our data provide the first direct evidence for the involvement of calcium/CaM-mediated signaling in auxin-mediated signal transduction.
Conversion of Choledochojejunostomy Stents to Jejunal Feeding Tubes for Postoperative Enteral Alimentation

The problem of protein calorie malnutrition following major gastrointestinal surgery can be treated with central venous or enteric alimentation, with the latter being preferred. The authors describe a simple technique for the conversion of biliary stents placed after pancreaticoduodenal surgery into jejunal feeding tubes when the stenting function is no longer needed. Three illustrative cases are presented. In each case, the procedure took less than 30 min and had no associated morbidity. This technique allows early conversion from central venous to enteric alimentation without the need to create a second surgical enterostomy. (Journal of Parenteral and Enteral Nutrition12:225-226, 1988)
Surface Textural Properties of Icy Satellites: A Comparison between Europa and Rhea

Solar phase curves for Rhea are presented using new telescopic opposition data along with Voyager imaging observations. Two viable solutions were found to Hapke's model which was used to describe this phase curve. The porosity derived from the model's opposition parameters show that the optically active portion of Rhea's regolith has a porosity between 80 and 95 percent, which is slightly lower than the porosity seen on Europa and higher than the porosity measured for the Moon using similar methods. The macroscopic roughness is comparable to that measured by Vebiscer and Veverka for Rhea. The single particle scattering functions found in this study are predominantly forward scattering, which contradicts the results of Vebiscer and Veverka.
Graded sparing of visually-guided orienting following primary visual cortex ablations within the first postnatal month.

Abstract We compared the abilities of intact cats and cats that incurred lesions of areas 17 and 18 in adulthood, at one month of age (P28), or on the day of birth (P1), to detect and orient towards visual stimuli either moved into or illuminated in the periphery of the visual field, and to detect and orient towards a stationary, broad-band white-noise auditory stimulus. For all groups of cats, movement of a stimulus into the visual field was a more potent stimulus for evoking visually-guided orienting movements than illumination of a static light-emitting diode (LED). The potency of the auditory stimulus was also extremely high. Proficiency on both visual tasks was graded according to the age at which areas 17 and 18 were ablated in the sequence: adult, P1, P28 and intact in the sequence worst⇒best performance. The superior performance of the P1- and P28-groups provided evidence for sparing of visually-guided orienting, but the sparing was incomplete because it did not match performance of intact cats. Lesions of areas 17 and 18 incurred in adulthood had no significant impact on orienting to auditory white-noise stimuli. However, orienting performance to auditory stimuli presented in the peripheral quadrants was slightly superior in the P28 group and reduced in the P1 group. Thus, the visual sparing exhibited by the P1 group may be at the expense of highly proficient orienting to auditory cues. Overall, these results extend our knowledge by showing that in addition to P1-cats, cats that incur lesions of areas 17 and 18 at one month-of-age also exhibit sparing of visually-guided orienting, and that the sparing is not confined to a single stimulation paradigm. Finally, the covariation in the magnitude of pathway modifications with the scale of the orienting proficiency in P1- and P28 cats helps to solidify the linkage between rewired brain pathways and spared visually-guided behaviors.
The Single-End Invasion: An Asymmetric Intermediate at the Double-Strand Break to Double-Holliday Junction Transition of Meiotic Recombination

We identify a novel meiotic recombination intermediate, the single-end invasion (SEI), which occurs during the transition from double-strand breaks (DSBs) to double-Holliday junction (dHJs). SEIs are products of strand exchange between one DSB end and its homolog. The structural asymmetry of SEIs indicates that the two ends of a DSB interact with the homolog in temporal succession, via structurally (and thus biochemically) distinct processes. SEIs arise surprisingly late in prophase, concomitant with synaptonemal complex (SC) formation. These and other data imply that SEIs are preceded by nascent DSB-partner intermediates, which then undergo selective differentiation into crossover and noncrossover types, with SC formation and strand exchange as downstream consequences. Late occurrence of strand exchange provides opportunity to reverse recombinational fate even after homologs are coaligned and/or synapsed. This feature can explain crossover suppression between homeologous and structurally heterozygous chromosomes.
Critical flow rate of anode fuel exhaust in a PEM fuel cell system

Abstract A manual purge line was added into the exterior fuel exhaust stream of a Ballard PEM stack in a Nexa™ power module. With the addition of manual exhaust purge, high levels of inert gases were intentionally added to the anode feed without changing normal operational procedures. A new method of determining the critical minimum flow rate in the anode exhaust stream was given by an anode mass balance. This type of operation makes dual use of membranes in the MEAs as both gas purifiers and as solid electrolytes. The PEM stack was successfully operated with up to ca. 7% nitrogen or carbon dioxide in the absence of a palladium-based hydrogen separator at ca. 200 W power level. Nitrogen in the anode stream was concentrated from 7.5% to 91.6%. The system maintained a fuel efficiency of 99% at a manual purge rate of 2.22 ml s−1 and no auto purge. The fuel cell stack efficiency was 64% and the stack output efficiency was 75%. The overall system efficiency was 39%. After troublesome CO and H2S poisons were removed, a hydrocarbon reformate containing high levels of CO2 and H2O was further used in the Nexa™ stack. The size and complexity of the fuel processing system may be reduced at a specified power level by using this operational method.
Calcium-induced Troponin Flexibility Revealed by Distance Distribution Measurements between Engineered Sites

The contraction of vertebrate striated muscle is regulated by Ca2+ binding to troponin C (TnC). This causes conformational changes which alter the interaction of TnC with the inhibitory protein TnI and the tropomyosin-binding protein TnT. We have used the frequency domain method of fluorescence resonance energy transfer to measure TnT-TnC and TnT-TnI distances and distance distributions, in the presence of Ca2+, Mg2+, or EGTA, in TnC.TnI.TnT complexes. We reconstituted functional, ternary troponin complexes using the following recombinant subunits whose sequences were based on those of rabbit skeletal muscle: wild-type TnC; TnT25, a mutant C-terminal 25-kDa fragment of TnT containing a single Trp212 which was used as the sole donor for fluorescence energy transfer measurements; Trp-less TnI mutants which contained either no Cys or a single Cys at position 9, 96, or 117. Energy acceptor groups were introduced into TnC or TnI by labeling with dansyl aziridine or N-(iodoacetyl)-N'-(1-sulfo-5-naphthyl)ethylenediamine. Our results indicate that the troponin complex is relatively rigid in relaxed muscle, but becomes much more flexible when Ca2+ binds to regulatory sites in TnC. This increased flexibility may be propagated to the whole thin filament, releasing the inhibition of actomyosin ATPase activity and allowing the muscle to contract. This is the first report of distance distribution measurements between troponin subunits.
Polyspermy-preventing mechanisms in the golden hamster egg.

The zona pellucida of a fertilized egg recovered from an artificially inseminated female reacts to capacitated spermatozoa differently from the zona pellucida of an unfertilized egg. The zona of a fertilized egg shows a sperm-refractory response, “zona reaction,” so that capacitated spermatozoa neither firmly attach to nor penetrates it. On the other hand, the zona of an unfertilized egg shows no such sperm-refractory response and many spermatozoa attach to and penetrate it. The zona reaction was observed not only in recently penetrated eggs but also throughout cleavage. Judging from the earliest fertilization stage at which we observed a complete zona reaction, it is estimated that this reaction is completed in less than 15 minutes after sperm attachment to the vitellus. One hundred per cent of the fertilized eggs recovered from females five hours after artificial insemination were refertilized in vitro after removal of the zona pellucida by trypsin-treatment. The incidence of refertilization decreased when the eggs were recovered at later times. Only 3% of the eggs recovered at nine hours after artificial insemination were refertilized. Judging from the fertilization stage at which eggs were no longer refertilizable, it has been estimated that the completion of the vitelline surface block to polyspermy is established in not less than two nor more than three to three and one-half hours. Possible causes of polyspermy encountered with in vitro fertilized eggs are discussed.
Nanotribological behavior of tethered reinforced polymer nanolayer coatings

Abstract We fabricated molecularly thick thermoplastic elastomeric films with organized microdomain structure and intriguing nanotribological properties. Molecular films from poly[styrene-b-(ethylene-co-butylene)-b-styrene] (SEBS) were obtained by a melt/solution grafting to a functionalized silicon surface modified with epoxy-terminated self-assembling monolayers. We varied the thickness of grafted block–polymer films from 1.35 nm (disordered polymer layer) to 9 nm (well defined nanophase structure) and tested their friction, adhesion, shear and wearing properties on a microscale with scanning probe microscopy. Tethered SEBS monolayers, composed of a rubber matrix reinforced by a two-dimensional net of glassy polystyrene (PS) microdomains, possess a friction coefficient as low as 0.02 and shear strength in the range 0.15–1.5 GPa. Chemically tethered SEBS monomolecular films are much more stable under shear stresses than conventional molecular coatings.
Use of coastal economic valuation in decision making in the Caribbean: Enabling conditions and lessons learned

Abstract Caribbean economies depend on coastal ecosystem services, including tourism, fisheries, and shoreline protection. However, coastal ecosystems continue to degrade due to human pressures. Many pressures arise from decisions that fail to take full range of ecosystem values and benefits into account. Economic valuation can contribute to better-informed decision making about coastal resource use and development. More than 100 studies in the Caribbean contain monetary values of coastal ecosystem goods and services. However, only a minority of these studies have had an observable influence on policy, management, or investment decisions. Through a series of interviews, we identified 17 valuation studies that have directly influenced decision making. Due to the difficulty of tracking influence, our review was not exhaustive. These 17 “success stories” highlight the potential for economic valuation to improve decision making. Building on literature on the challenges of integrating science into policy, we used these 17 cases to identify enabling conditions for informing decision making. These conditions include a clear policy question, strategic choice of study area, strong stakeholder engagement, effective communications, access to decision makers, and transparency in reporting results. Our findings suggest that valuation practitioners can and should do more to ensure that valuation studies inform decision making.
The aryl hydrocarbon receptor in early vertebrates

Abstract The Ah receptor (AhR), which mediates effects of dioxins and related halogenated aromatic hydrocarbons, belongs to the emerging bHLH-PAS family of transcription factors. A reverse-transcription-polymerase chain reaction (RT-PCR) method using degenerate primers was used to search for the AhR in early vertebrates, including bony, cartilaginous, and jawless fish. AhR cDNA sequences were obtained for the killifish Fundulus heteroclitus , smooth dogfish Mustelus canis , the little skate Raja erinacea and the sea lamprey Petromyzon marinus . Further studies revealed evidence for a second AhR gene (AHR2) in Fundulus and Mustelus . The fish AhR1 and AhR2 genes are as different from each other as each is from mammalian AhRs, suggesting that they are the result of an ancient gene duplication, possibly occurring prior to the divergence of lineages leading to present-day mammals and fish. These studies demonstrate the conservation of AhR structure over more than 500 million years of vertebrate evolution. A search of the GenBank protein sequence database revealed a possible AhR homolog in the nematode Caenorhabditis elegans . Phylogenetic analysis of fish AhR sequences in comparison to mammalian AhRs and other members of the bHLH-PAS gene family provides an evolutionary perspective to the study of dioxin toxicity and Ah receptor function.
Estimating maximum limits to mutagenic potency from cytotoxic potency

RAPID and reliable screening methods are required for identifying environmental mutagens and estimating their mutagenic potency in preparation for use of more elaborate tests to assess the genetic risk to man. Many compounds are effectively screened by in vitro mutagenesis assays using either bacterial or mammalian cells. Although tests with mammalian cells are not as rapid and inexpensive as microbial assays, they are needed to confirm and extend the bacterial results, and probably provide a better assessment of potential risk to humans than do microbial tests. However, the screening of all potential mutagens with mammalian cell mutagenicity assays, although desirable, does not seem feasible unless, as we propose, test compounds are first pre-screened on the basis of their cytotoxic potency. On theoretical grounds, one expects a certain minimum cytotoxic potency to correlate with mutagenic potency, particularly when the latter is measured using forward mutations that result in inactive gene products. Specifically, cells cannot divide unless a substantial fraction of their genome is functionally intact; mutagenic agents should thus be obligatory cytotoxic agents, with a given mutagenicity conferring a certain irreducible cytotoxicity. We show here that the cytotoxic potency of 22 chemical mutagens is highly correlated with their mutagenic potency as assayed in five rodent and human in vitro cell systems. This relationship implies that the maximum potential mutagenic potency of such compounds may be reliably estimated from rapid and straightforward measurements of their cytotoxic potency, the latter defined as the failure of cultured cells to undergo continued cell division. The estimate is necessarily a maximum one, as an agent may exert cytotoxic effects by pathways independent of its mutagenic action.