cssi/SciSciGPT-SciSciNet huggingface dataset:
The Effects of Mask Selection and Securement on Percussive Therapy

Background: IPV is used by some as a treatment option for atelectasis and mucus clearance in patients. The goal of this study is to assess different mask types, securement methods, and their impacts on pressure amplitudes (∆P) and mean airway pressure (MAP). Given that the device has a wide range of frequencies, we will assess the low and high frequency to create an impact range. Our hypothesis is that the ∆P and MAP of the percussive device is not dependent on the type of mask or securement method that is utilized. Methods: The IPV from PercussionAire (Sand Point, ID) was set to Demand CPAP/PEEP off, Insp. Flow to max, and Insp. time to neutral. The phasitron was then connected to an IngMar Medical (Pittsburgh, PA) ASL 5000 Active Servo Lung and set to passive lung settings and a COPD profile (CS 55 mL/cm H2O, RAW 22 cm H2O/L/s). Measurements of average PIP, PEEP, and MAP were recorded for two frequencies (high and low). For the low frequency run, the IPV was set to the lowest frequency, placed on the ASL for 1 min, measurements recorded and repeated 4 times. IPV then changed to highest frequency and measurements recorded 5 times. The different user interfaces were the BiPAP PerformaTrak Full Mask (Respironics, Murrysville, PA) using provided straps, BiPAP mask held on Mannequin head by researcher to assure no leak, Ambu Spur II (Ambu, Glen Burnie, MD) mask held on head. The three user interfaces were tested on both the high and low frequencies. Results: After averaging PIP and PEEP for all five trials, the ∆P was then calculated for each of the user interfaces at low and high frequencies. The ∆P on low frequency using the strapped BiPAP was 10.48, held BiPAP 13.2, and Ambu masks 9.6 cm H2O respectively. ∆P on high frequency using the strapped BiPAP was 8.62, held BiPAP 9.41, and Ambu masks 8.65 cm H2O respectively. MAP on low frequency using the strapped BiPAP was 4.14, held BiPAP 5.63, and Ambu masks 4.08 cm H2O respectively. MAP on high frequency using the strapped BiPAP was 3.99, held BiPAP 4.39, and Ambu masks 4.22 cm H2O respectively. Conclusions: Of the mask selection and securements studied, the held BiPAP mask delivered the greatest average ∆P and MAPs to the carina in both low and high frequencies. There was a difference in mask selection as opposed to our original hypothesis; however, further research is needed to determine clinical significance of these differences and their impacts on atelectasis and secretion removal.
Clinical Course for Patients With Trisomy 13 and 18 Pursuing Life-Prolonging Therapies Versus Comfort-Directed Care:

Background:Care for infants with Trisomy 13 and 18 is evolving with more children being offered medical and surgical interventions. Parents and clinicians of children diagnosed with trisomy 13 and ...
${\mathcal {W}}$-algebras and Whittaker categories

This article is concerned with Whittaker models in geometric representation theory, and gives applications to the study of affine $${\mathcal {W}}$$ -algebras. The main new innovation connects Whittaker models to invariants for compact-open subgroups of the loop group. This method, which has a counterpart for p-adic groups, settles a conjecture of Gaitsgory in the categorical setting. This method shows that Whittaker sheaves in geometric representation theory admit t-structures, as had previously been observed in some special cases. We then apply this method to the setting of affine $${\mathcal {W}}$$ -algebras. We study a new family of modules for affine $${\mathcal {W}}$$ -algebras, which can be thought of as analogues of certain tautological (“generalized vaccuum”) modules over the Kac-Moody algebra. Using the above t-structure, we obtain an affine analogue of Skryabin’s theorem that connects affine $${\mathcal {W}}$$ -algebras and Whittaker models. This theorem allows various geometric methods to be used to study affine $${\mathcal {W}}$$ -algebras. As one such application, we offer a new proof of one of Arakawa’s foundational results in the theory.
Creativity

This paper is an analysis of the concept of creativity. Tradition is followed in distinguishing three related but increasing complex concepts. The first concerns mere making or bringing into existence. It is not examined at length. The second builds on the first but includes the notion of novelty. The third incorporates the second but adds the notion of value. The latter two concepts of creativity are explored in great detail.
Criminal Protection Orders: Implications of Requested Versus Issued Orders on Domestic Violence Revictimiztion and Mental Health Among Women:

Criminal protection orders (POs), with varying degrees of restrictions on offenders’ behavior, are issued by the criminal justice (CJ) system to enhance the safety and well-being of victims of dome...
Can the Modular Helium Reactor Compete in the Hydrogen Economy

In today’s energy economy, hydrogen is primarily used in the petroleum refining and petrochemical industries. The dominant technology for generating hydrogen is Steam Methane Reforming (SMR), which uses natural gas as both feedstock and fuel. In the much-discussed future hydrogen economy, hydrogen could become a major carrier of energy for distributed use, such as in fuel-cell vehicles. This paper compares the cost of hydrogen production using natural gas and SMR technology with the cost of nuclear-powered hydrogen production using a Modular Helium Reactor (MHR). A time series model of natural gas prices is estimated and used to simulate the cost of hydrogen from SMR to 2030: it is never above $11.80/GJ or $12.45/million BTU (in 2001 dollars). A cost engineering model of the General Atomics’ MHR shows a range of hydrogen production costs, none of which are below $11.80/GJ. For the MHR to be competitive in the pipeline hydrogen market, there must be an increase of 50-100% in the price of natural gas.
State Fragility: Concept and Measurement

The international donor community has grave concerns about the prospects for poverty reduction in what it terms fragile states. A state is classified as fragile if its country policy and institutional assessment (CPIA) score falls below a particular threshold. Recognizing that all states are fragile to varying degrees, this paper questions the method used by the international community to deem a country fragile. This paper develops a framework that uses fuzzy-set theory to deem a country as fragile. Fuzzy sets allow for gradual transition from one state to another while also allowing one to incorporate rules and goals, and hence are more appropriate for measuring outcomes that are ambiguous. Such ambiguity is an inherent characteristic of cross-country fragility classifications. The paper applies its framework to 76 low-income countries, for which the CPIA data are publicly available. The fragile state group that this framework provides is compared to that which the international donor community has constructed.
The Forms Had a Function

The Official Forms appended to the Federal Rules of Civil Procedure are a seeming anachronism, more appropriate for a much simpler time that hardly characterizes modern day federal civil litigation. Perhaps the form for a negligence complaint is the most striking in this regard, offering only that at a certain time and place “the defendant negligently drove a motor vehicle against the plaintiff,” causing harm. Not only does such a complaint fail to typify the negligence claims one might find on any federal docket, but it neither seems to reflect the much greater complexity that characterizes modern litigation and life in general.What then could be the continuing point of having the forms at all? Indeed, that is the question the Advisory Committee on Civil Rules (“Advisory Committee”) has asked and answered quite recently: It has concluded that the Official Forms no longer serve any useful purpose and may therefore be discarded into the waste bin of history. Seemingly without much further thought, the Standing Committee promptly concurred, putting the forms on an all-but-certain course toward oblivion. Might it be true that the forms have outlived their usefulness? And if no longer of any use, were the forms ever of any real utility? On the occasion of the pending abrogation of the Official Forms, this article takes the opportunity to review the history and use of the forms, finding that they had more value than the current rulemakers cared to acknowledge: The principal function of the forms was to reify the liberal vision of the Federal Rules and to guard against deviations therefrom. Unfortunately, as that liberal vision has given way to a more restrictive view in what Stephen Subrin refers to as the “fourth era” of civil procedure, the unyielding simplicity and permissiveness of the forms have become too much for the otherwise changing system to bear. Below, then, is a eulogy of the forms.
Changes in the Proteins of Milk destabilized during Frozen Storage

IT has been well established that concentrated frozen milk that has been stored tends to form a precipitate on thawing1−3. This destabilization of the colloidal proteins of milk seems to be induced by lactose crystallization and is characterized by an induction period before a sharp precipitation occurs4. The precipitated protein seems to be mainly calcium caseinate. Although much is known about the influence of processing variables on the colloidal instability of the frozen milk, little is known about the changes occurring in the milk proteins. This report presents evidence on some changes in the electrophoretic properties of the precipitated proteins and the serum proteins of the destabilized concentrated frozen milk.
Inhibition by adenosine of histamine and leukotriene release from human basophils

Adenosine inhibited the release of histamine and leukotriene C4 (LTC4) from immunologically-activated basophils in a dose-dependent manner. Structural congeners of adenosine also attenuated the elaboration of these two mediators from stimulated basophils and a rank order of potency for the inhibition was observed following the sequence 2-chloroadenosine greater than or equal to N-ethylcarboxamidoadenosine (NECA) greater than adenosine greater than or equal to R-phenylisopropyladenosine (R-PIA) greater than or equal to S-PIA. These same nucleosides modulated the generation of LTC4 more potently than the release of histamine. A number of methylxanthines, which are antagonists of cell surface adenosine receptors, reversed the inhibition by adenosine and its congeners of the release of both histamine and LTC4 to varying extents. Dipyridamole and nitrobenzylthioinosine (NBTI), agents that block the intracellular uptake of adenosine, antagonized the inhibition of histamine release by adenosine (and 2-chloroadenosine) but failed to reverse the attenuation of LTC4 generation by the nucleoside. These same uptake blockers were unable to antagonize the inhibitory effects of NECA on either histamine or LTC4 release. In purified basophils, NECA and R-PIA, and in that order of decreasing reactivity, increased total cell cyclic adenosine monophosphate (cAMP) levels and inhibited the stimulated release of mediators. In total, these results suggest that the basophil possesses a cell surface adenosine receptor which, on the basis of both pharmacological and biochemical criteria, most closely conforms to an A2/Ra-like receptor. However, in addition to an interaction at the cell surface, studies with agents that block the intracellular uptake of adenosine suggest that the nucleoside may also exert intracellular effects when countering the release of histamine (but not LTC4).
What Criteria Define a Successful Career in Psychology? it Depends on Who you Ask

Predicting which students have the ability and motivation to become successful psychologists is an endeavor that all graduate psychology departments undertake to some degree. However, before prediction of "success" in psychology can take place, it is first necessary to develop what the important criteria of success in psychology are. For this purpose, the importance of various criteria of academic success in psychology was rated during three different stages of career development. From two universities, 71 faculty and graduate students were surveyed. Results from a series of principle component analyses using orthogonal and oblique rotation methods strongly suggested that there are a relatively large number of factors that are important. A nine-factor solution seemed to provide the best fit to the data, both in terms of conceptual consistency and variance explained. This solution indicated that there is wide diversity of opinion among psychologists as to what are the most important criteria of success in ...
A three-dimensional analysis of fretting fatigue

Abstract Three-dimensional finite element analyses of fretting contact fatigue between a sphere and a flat surface of the same material are presented. A radial expansion of the displacement fields around the contact center is used to map the entire three-dimensional fields into a radial–axial plane of reference which contains the slip direction. The computational results for the limiting case of the onset of rigid body sliding are first shown to be in agreement with known theoretical results. The present computations are then used to capture the evolution of surface and sub-surface fields for different levels of partial slip, interfacial friction and externally imposed mean stress values. It is shown that the magnitude as well as distribution of the fields change markedly by the sign of the superimposed mean stress; this result has significant implications for fretting fatigue in the presence of a residual surface stress induced by shot peening or coating. The computational model is also used to simulate the evolution of fretting damage in prior experiments conducted on a bearing steel and an aluminum alloy with the sphere on flat surface fretting arrangement. It is shown that the model captures many of the salient features of fretting damage and failure documented in the experiments. Conditions governing the occurrence of elastic shakedown and the onset of surface plasticity are also briefly examined to illustrate the capability of the present computational approach.
Stress integration for the constitutive law of the upper convected Maxwell fluid near the corners in a driven cavity

Abstract We consider the integration of stresses for the upper convected Maxwell fluid near the corner singularities in driven cavity flow. The velocity field is prescribed as Newtonian. We find that near the upstream corner, the stresses behave like r−4/3 except near the stationary wall, where the stress grows like r−2 and near the moving wall, where the stress is infinite along the entire wall. We assume that the downstream corner is well separated from the upstream corner. In that case, the stresses at the downstream corner have only a weak (logarithmic) singularity throughout most of the flow region. Strong growth of stresses occurs as the downstream wall is approached. While stresses grow like r−2 at the wall, there is a region near the wall where much stronger growth, proportional to r−4, occurs. Reasons are given why solutions for the full equations of the UCM model (if such solutions exist at all) should be very different from the ones found here where the velocity field is a priori prescribed.
Univentricular heart in adults: Report of nine cases with review of the literature

Nine patients with univentricular heart 17 years of age or older were followed up for a mean duration of 13 years (range 5 to 26 years). Five patients had type A and four patients had type C univentricular heart. Pulmonary stenosis was present in eight of nine patients. Palliative shunt surgery was performed in seven patients, ventricular septation was performed in one patient, and no surgical intervention was performed in one patient. Eight patients were in New York Heart Association functional class II and one patient was in New York Heart Association functional class III. Long term follow-up of these patients suggests that a selected group of adults with univentricular heart may achieve a relatively long survival and good functional class with conservative management.
Abstract B22: Re-expression of miR-200 by natural agents regulates the expression of PTEN and MT1-MMP in pancreatic cancer

Purpose: Membrane type-1 matrix metalloproteinase (MT1-MMP) is often activated and expressed in tumor cells with significant invasive properties, and is associated with poor prognosis of patients. This could partly be due to deregulated expression of microRNAs (miRNAs) which regulates the expression of MT1-MMP and PTEN (Phosphatase and tensin homolog) contributing to tumor invasion and metastasis. Experimental Procedure: We initially compared the expression profile of miR-200 family, PTEN and MT1-MMP expression in six pancreatic cancer (PC) cell lines by qRT-PCR and western blot analysis. Based on our initial findings, we chose BxPC-3, MIAPaCa-2, and MIAPaCa-2-GR cells for further mechanistic studies. We assessed the effect of two separate novel agents CDF, (a synthetic analogue of curcumin) and BR-DIM (a natural agent) on PC cells. Results: We found loss of expression of miR-200a, b, and c in chemo-resistant PC cell lines, which was correlated with loss of PTEN and over-expression of MT1-MMP. The expression of miR-200 family and PTEN was significantly re-expressed whereas the expression of MT1-MMP was down-regulated by CDF and BR-DIM treatment. Forced over-expression or silencing of miR-200c, followed by either CDF or BR-DIM treatment of MIAPaCa-2 cells altered the morphology of cells, wound-healing capacity, colony formation, and the expression of MT1-MMP and PTEN. Conclusion: These results provide strong experimental evidence showing that the loss of miR-200 family and PTEN expression, and increased level of MT1-MMP leads to aggressive behavior of PC cells, which could be attenuated through re-expression of miR-200c by CDF and/or BR-DIM treatment, suggesting that these agents could be useful for treatment.
A regional perspective on the attitudes of fourth-year medical students toward the field of general surgery.

Background Despite the stabilization of match rates, negative perceptions toward general surgery are still rife among medical students. The aim of this study was to describe the attitudes of fourth-year medical students towards general surgery at a regional level. Method All fourth-year medical students in the state of Nebraska were invited to complete an online survey about their perceptions of the field of general surgery and the factors that influenced their residency choice. Results Of the 145 respondents, 10% were interested in general surgery; this result is slightly higher than the national average. The main reasons cited by those who are choosing general surgery were personal factors; the perceived adverse external factors did not influence their career choice. In contrast, students who chose nonsurgical careers did so because of external factors, such as poor lifestyle and perceptions of an unfriendly environment. Conclusions The results of this study suggested regional variations in the level of interest toward general surgery and that interest in the field among medical students in Nebraska may be higher than what has been reported nationally. Students who chose general surgery did so for personal reasons, which were independent of external factors. Recruitment efforts into the field should be focused on those students who choose non-general surgery careers and on rectifying the negative influences that steered them away from the field.
Congressional Trade Politics, 1985-1995

The foreign trade literature typically sees Congress abdicating its policymaking role to the executive. In addition to a presidential model of policymaking, three other models are identified (the joint participation, congressional, and bureaucratic models) and Congress's significant post-cold war foreign trade policymaking across these models is examined. Policy outputs are also categorized, as instances of congressional victories, presidential victories, partial victories for each side, and instances of policy agreement. The findings indicate that Congress plays an active policymaking role in 78 percent of the cases and gets part or all of its policy desires enacted in 84 percent of the cases. Thus the congressional role in post-cold war foreign trade policy-making seems substantially more significant than much of the literature suggests. Further, Congress in this period seems particularly responsive to bipartisan and interest group pressures, but the presence of presidential lobbying shows some variance...
Work in progress: A multi-strategy model for promoting high school students interest in STEM

In this paper we propose a new multi-strategy model for immersing students in STEM. Rooted in the current research and experiences, the new practices are being developed and implemented in a college-based hybrid STEM learning center that is geared to serve as a hub connecting high schools, higher education institutions, and industries bringing new and existing strategies together into one integral system with unique online features. The Hub model would serve as an educational research laboratory contributing to the knowledge base about STEM by investigating what strategies (or combination of what strategies) will best support student development for the STEM workforce. In addition, the model would illustrate the importance of interconnection between engineering education research and engineering education practice.
Diverse Pore Loops of the AAA+ ClpX Machine Mediate Unassisted and Adaptor-Dependent Recognition of ssrA-Tagged Substrates

ClpX, an archetypal proteolytic AAA+ unfoldase, must engage the ssrA tags of appropriate substrates prior to ATP-dependent unfolding and translocation of the denatured polypeptide into ClpP for degradation. Here, specificity-transplant and disulfide-crosslinking experiments reveal that the ssrA tag interacts with different loops that form the top, middle, and lower portions of the central channel of the ClpX hexamer. Our results support a two-step binding mechanism, in which the top loop serves as a specificity filter and the remaining loops form a binding site for the peptide tag relatively deep within the pore. Crosslinking experiments suggest a staggered arrangement of pore loops in the hexamer and nucleotide-dependent changes in pore-loop conformations. This mechanism of initial tag binding would allow ATP-dependent conformational changes in one or more pore loops to drive peptide translocation, force unfolding, and mediate threading of the denatured protein through the ClpX pore.
Multiphoton ionization of H 2 + in xuv laser pulses

We consider the ionization of the hydrogen molecular ion after one-, two-, and three-photon absorption over a large range of photon energies between 9 and 40 eV in the fixed-nuclei approximation. The temporal development of the system is obtained in a fully ab initio time-dependent grid-based approach in prolate spheroidal coordinates. The alignment dependence of the one-photon ionization amplitude is highlighted in the framework of time-dependent perturbation theory. For one-photon ionization as a function of the nuclear separation, the calculations reveal a significant minimum in the ionization probability. The suppressed ionization is attributed to a Cooper-type minimum, which is similar, but not identical, to the cancellation effect observed in photoionization cross sections of some noble-gas atoms. The effect of the nonspherical two-center Coulomb potential is analyzed. For two- and three-photon ionization, the angle-integrated cross sections clearly map out intermediate-state resonances, and the predictions of the current computations agree very well with those from time-independent calculations. The dominant emission modes for two-photon ionization are found to be very similar in both resonance and off-resonance regions.
Childhood sexual abuse and early menarche: the direction of their relationship and its implications.

Abstract Purpose A relationship between childhood sexual abuse (CSA) and early menarche previously has been proposed and psychobiological mechanisms for the association have been suggested. Because it has serious implications for many disciplines, we attempted to confirm that association and explore its direction, first with hypothesis 1: the negative relationship between pubertal age and CSA is based on victims' increased target gratifiability at ages of high target vulnerability, and then with hypothesis 2: CSA and circumstances surrounding it are related causally to early menarche. Methods African-American and multi-ethnic Caucasian women (N = 323) were interviewed at several women's clinics at Johns Hopkins Bayview Medical Center; 64 women reported premenarcheal abuse. We assessed (1) ages of CSA and menarche to determine their relationships, (2) household characteristics and their relationships with CSA, (3) variables associated with CSA, to determine the independent effect of CSA and explore potential dose response (i.e., effects of increased stress). Results CSA and menarcheal age are related negatively ( p Conclusions Hypothesis 1 may apply when CSA occurs within 2 years premenarche but, because hypothesis 2 is supported, continuing psychobiological effects and stress engendered by CSA are underscored. Mechanisms through which they impact the developing child require further exploration, and medical and psychological attention.
A multimodel simulation of pan-Arctic hydrology

[1] We compare the performance of five land surface models (Chameleon Surface Model (CHASM), Noah, Community Land Model (CLM), Variable Infiltration Capacity Model (VIC), European Centre for Medium Range Weather Forecasts (ECMWF)), in the simulation of hydrological processes across the terrestrial Arctic drainage system for the period 1980–2001. The models represent a wide range of model physics, particularly with respect to high-latitude processes, and are forced with surface meteorology derived from the ERA-40 reanalysis. Models offer great potential for enlightenment regarding large-scale hydrology in this poorly observed region; thus our objective is to assess the ability of the models to capture various aspects of pan-Arctic hydrology as well as identify those features that contain the largest uncertainty. Results reveal up to a 30% difference in annual partitioning of precipitation between evaporation and runoff with major Arctic watersheds such as the Lena. Capturing the correct base flow of the large rivers is a consistent problem. The model hydrographs are often out of phase, peaking too early in comparison to observations. However, allowing for a large uptake in soil moisture as well as moisture movement during frozen periods alleviates this discrepancy. A negative correlation exists between models and observations for annual runoff time series over the Yenesi basin, apparently mostly because of inconsistencies in the input data. Compared to station data, all models produce similar errors in snow water equivalent; yet they differ widely in their snow regimes in terms of snowfall quantity, estimated snow depths, and most importantly, sublimation rates. Additionally, model albedo is consistently higher than observations in the presence of snow. No single model is the best or worst performing when compared to a range of observations.
No-Tillage Corn and Grain Sorghum Response to Cover Crop and Nitrogen Fertilization

No-tillage cropping systems may benefit from the addition of winter annual cover crops through decreased soil erosion, accumulation of biologically fixed N, or increased crop yield. The objectives of this research were to assess the amount of cover provided by winter annual legumes and oat (Avena saliva L.) to quantify the fertilizer N equivalent value of each cover crop system and the effect of cover crop and N rate on corn (Zea mays L.) and grain sorghum [Sorghum bicolor (L.) Moench] grain yield. Two experiments, one in corn and one in sorghum, were conducted in 1997,1998, and 1999. In each experiment, the main-plot effect was cover crop treatment while the subplot effect was spring N rates of 0, 56, 112, and 168 kg ha -1 . The addition of oat to the legume cover crop treatments increased fall ground cover but decreased total spring dry matter yield. Maximum spring dry matter yield was greatest in the hairy vetch (Vicia villosa Roth)-alone treatment. Hairy vetch alone also produced the greatest mean fertilizer N equivalent value in the corn and sorghum experiments, 43.6 and 56.9 kg N ha -1 , respectfully. These values, however, were variable among years. Corn and sorghum grain yield were greatest in the Austrian winter pea (Pisum sativum L.) and hairy vetch full seeding rate treatments, 5.19 and 7.06 Mg ha -1 , respectfully. Our results indicate that winter annual cover crops provide several distinct benefits to no-tillage corn and sorghum production systems and that cover crops should be selected based on specific grower needs.
Pt−Co Bimetallic Catalyst Supported on Single-Walled Carbon Nanotubes: Effect of Alloy Formation and Oxygen Containing Groups†

Pt monometallic and Pt−Co bimetallic catalysts have been prepared on single-walled carbon nanotubes (SWNT) with and without HNO3 treatment. The HNO3 treatment introduced oxygen containing groups (O...
Nonneutral and quasi‐neutral diffusion of weakly ionized multiconstituent plasma

A theory is developed for quasi-neutral and nonneutral ambipolar diffusion in a weakly ionized multiconstituent plasma. Magnetic field effects are disregarded. The effects of negative ions and various positive and negative ion diffusion coefficients are identified. It is found that the presence of negative ions leads to enhanced electron diffusion and a retarded diffusion of positive ions. In some cases electrons may be forcibly propelled from the area of perturbations in ionic concentrations. The ambipolar electric field is observed to cause negative ions to flow in a countergradient fashion where the gradient is small. Electrons tend toward a more homogeneous spatial distribution in the nonneutral case than in the quasi-neutral case.
The relation between flux vector splitting and parabolized schemes

Abstract The relationship between PNS and thin layer Navier-Stokes algorithms is used to develop traditional as well as new PNS procedures. The use of characteristics-based flux vector splitting gives rise to a parabolized system that is based on the predominant physics of the flow, while pressure-gradient-based flux vector splitting is shown to give the traditional parabolized scheme of Vigneron. Comparisons with TLNS results show the characteristics-based PNS system gives results that are at least as accurate as the more traditional pressure-gradient-split PNS system. The use of a safety factor in the pressure-gradient splitting is shown to cause inaccuracies and should be avoided. The interpretation of PNS procedures as the first sweep of a TLNS ADI procedure also suggests an obvious global pressure iteration method that is mathematically well posed and, hence, leads to an efficient rapidly converging global iteration procedure.
POLYMER DELIVERY SYSTEMS FOR SITE-SPECIFIC GENOME EDITING

Triplex-forming peptide nucleic acids (PNAs) can be used to coordinate the recombination of short 50–60 bp “donor DNA” fragments into genomic DNA, resulting in site-specific correction of genetic mutations or the introduction of advantageous genetic modifications. Site-specific gene editing in hematopoietic stem and progenitor cells (HSPCs) could result in the treatment or cure of inherited disorders of the blood such as β-thalassemia or sickle cell anemia. Gene editing in HSPCs and differentiated T cells could also help combat HIV infection by modifying the HIV co-receptor CCR5, which is necessary for R5-tropic HIV entry. However, translation of genome modification technologies to clinical practice is limited by challenges in intracellular delivery, especially in difficult-to-transfect hematolymphoid cells. Here, we review the use of engineered biodegradable polymer nanoparticles for site-specific genome editing in human hematopoietic cells, which represent a promising approach for ex vivo and in vivo gene therapy.
Studies on the Mechanism of Phytohormone Damage by Ionizing Radiation. I. The Radiosensitivity of Indoleacetic Acid.

The phytohormone auxin is widely recognized as a regulator of growth and morphogenesis. Since retarded growth and altered developmental patterns in plants are known to follow exposure to ionizing radiation, Skoog (26) investigated the inactivation of auxin by xand ?-rays. His data indicated that both native auxin preparations and pure 3-indoleacetic acid (IAA) in solution were highly labile when irradiated. A marked reduction in auxin levels also occurred when plant tissues were given moderate doses of x-radiation. Auxin thus appeared to be radiosensitive in vitro and in vivo. Skoog pointed out the parallel effects of decreased auxin levels and low doses of radiation in growth and correlation phenomena. His results were used subsequently by other workers to interpret various radiation responses on the basis of auxin radiosensitivity (10, 16, 27). However, certain considerations discussed below cast doubt on the implied direct sensitivity of the auxin molecule, and prompted our reinvestigation of auxin radiosensitivity. Concomitantly, a more precise evaluation of IAA inactivation kinetics was obtained. The present work deals with the destruction of auxin in aqueous solution by ionizing radiation. Auxin sensitivity in the plant, and the biochemical mechanisms whereby auxin levels are lowered in vivo, will be treated in subsequent papers of this series.
Thoracoscopic evaluation and treatment of pulmonary disease.

The expectation for video-assisted thoracoscopic surgery (VATS) is that it decreases morbidity, mortality, length of hospital stay (LOS), and time to return to regular activities for patients after procedures that formerly required major incisions. Although the data have not conclusively proven these benefits, VATS has been incorporated into thoracic surgery. Thoracoscopic evaluation and treatment of pulmonary disease are evolving, but this article presents techniques for lung resection (i.e., wedge resection, lobectomy, and pneumonectomy) with VATS.
On the information expressed in enzyme structure: more lessons from ribonuclease A

Brownian computations were directed at Ribonuclease A (RNase A) and variants in folded states so as to quantify information of the statistical type at the atom/covalent bond level. This advanced the research reported in this journal last year on the information properties of enzyme primary structure. Brownian computation data are illustrated for a sixteen-member library. The results identify signature traits that distinguish the folded wild type (WT) molecule from variants. The distinctions are explainable in terms of correlated information and dispersion energy. The Brownian tools used for this study can be directed at other protein families (e.g., kinases, isomerases, etc.) in rapid screening, QSAR, and design applications.
Reduction of phenoxyl radicals of the antitumour agent etoposide (VP-16) by glutathione and protein sulfhydryls in human leukaemia cells: Implications for cytotoxicity.

Abstract Phenoxyl radicals are inevitable intermediates in the oxidative enzymatic metabolism of a phenolic antitumour drug, etoposide (VP-16), by peroxidases, cytochrome P-450, prostaglandin synthetase and tyrosinase, as well as in its interactions with oxygen and peroxyl radicals. It has been shown that one-electron reduction of the VP-16 phenoxyl radical by ascorbate and thiols prevents/delays its oxidative metabolism by tyrosinase both in model systems and in cell homogenates. To elucidate the role of endogenous thiols in the reduction of VP-16 phenoxyl radicals, K562 human leukaemia cells grown in Dulbecco's modified Eagle's medium which does not contain vitamin C (ascorbate) were used, thus excluding the ascorbate-dependent reduction of VP-16 phenoxyl radicals. VP-16 phenoxyl radicals were reduced by endogenous reductants in K562 cell homogenates, intracellular thiols mainly being responsible. Depletion of endogenous thiols by mersalyl acid resulted in almost complete inhibition of the ability of cell homogenates to reduce VP-16 phenoxyl radicals. Three systems were used to evaluate the contribution of thiol-dependent reduction of VP-16 phenoxyl radicals: (1) K562 cell homogenates depleted or supplemented with glutathione (GSH) in vitro; (2) homogenates derived from K562 cells with a decreased level of endogenous thiols and GSH (using a specific inhibitor of γ-glutamyl cysteine synthetase, buthionine-S,R-sulfoximine; BSO) and (3) homogenates derived from K562 cells with increased content of endogenous thiols as a result of treatment with cadmium chloride. Depletion of thiols in K562 cells or cell homogenates proportionally decreased the ability of homogenates to reduce VP-16 phenoxyl radicals. Similarly, depletion or supplementation of K562 cells or cell homogenates with GSH proportionally decreased or increased the ability to reduce VP-16 phenoxyl radicals. Reduction of VP-16 phenoxyl radicals by K562 cell homogenates was similar to that obtained from cell homogenates isolated from K/VP.5 cells, a VP-16 resistant cell line derived from K562 cells. Elevation of endogenous thiols by cadmium chloride increased the ability of homogenates to reduce VP-16 phenoxyl radicals but did not reveal any significant difference in the ability of the two types of cells to interact with VP-16 radicals. Finally, BSO treatment of K562 cells led to potentiation of VP-16-induced DNA damage and to an increase in VP-16-induced growth inhibition, suggesting that, in the absence of ascorbate, modulation of endogenous thiols may be an important factor determining the oxidative metabolism and cytotoxic activity of VP-16 in tumour cells.
Prediction of pKa Value of Zinc-Bound Water in Carbonic Anhydrase

The deprotonation of zinc-bound water in carbonic anhydrase II is the rate-limiting step in the catalytic reaction of CO2-bicarbonate conversion. In order to understand the factors determining the pKa of the zinc bound water at the active site, quantum chemistry calculation together with continuum model is carried out. The pka changes due to the active site mutation are well reproduced. Additionally, the structural analysis and charge/dipole examination provide evidence that the fluctuation of the active site structure and the redistribution of the electrostatics lead to the pKa shift. Also, the distinct pka value of the same type of mutation at different site results from asymmetric ligation and different electronic environment around the zinc ion. This study not only provides insight into the molecular mechanism of the enzyme but also helps design artificial material for CO2 sequestration.
Combined microsurgical and endovascular management of complex intracranial aneurysms.

Objective The disciplines of microneurosurgery and cranial base surgery have reached maturity, and technical advances in the surgical management of aneurysms are limited. Although most aneurysms can be clipped microsurgically or coiled endovascularly, a subset of patients may require a combined approach. A consecutive series of patients with aneurysms in one surgeon's cerebrovascular practice was reviewed retrospectively to analyze strategies for integrating microsurgical and endovascular techniques in the management of complex aneurysms. Methods Between 1997 and 2001, 596 aneurysms in 491 patients were treated microsurgically by the senior author (MTL) at the University of California, San Francisco, and 77 of these patients (96 aneurysms) were managed with a multimodality approach comprising a total of eight different combinations: selective revascularization and aneurysm occlusion (n = 23), endovascular and surgical trapping (n = 1), clipping of the aneurysm after attempted or incomplete coiling (n = 22), coiling after attempted or incomplete clipping (n = 5), clipping of recurrent aneurysm after coiling (n = 6), coiling of recurrent aneurysm after clipping (n = 1), clipping and coiling of multiple remote aneurysms (n = 13), and coiling after previous surgery (n = 6). Results A total of 96 aneurysms were treated with combined therapy, of which 43% were large or giant in size and 34% had fusiform or dolichoectatic morphology. Complete angiographic obliteration was achieved in 91 aneurysms (95%). Overall, 66 patients (86%) had good outcomes (Glasgow Outcome Scale score of 4 or 5; mean follow-up, 9 mo). The treatment mortality rate was 9.1% (seven patients), and permanent treatment-associated neurological morbidity rate was 5.2% (four patients). Conclusion Evolving endovascular technologies need to be integrated into the microsurgical management of aneurysms. Multimodality approaches are best used with complex aneurysms in which conventional therapy with a single modality has failed. Revascularization remains a unique surgical contribution to the overall management of aneurysms with which current endovascular techniques cannot be used. Multimodality management should be considered an elegant addition to the therapeutic armamentarium that, through simplification and increased safety, improves the treatment of complex aneurysms beyond what is achievable by performing clipping or coiling alone.
Protein composition of white skeletal muscle from mesopelagic fishes having different water and protein contents

The consequences for white skeletal muscle of the whole body variation in water and protein content were examined in 11 mesopelagic fishes taken off the coast of Oregon, USA, in 1983. For such muscles, water content varied from 71 to 91% of muscle wet weight, and protein content ranged from 56 to 141 mg g-1 muscle wet weight, depending on the species. Dilution by increased water content did not account for the decrease in protein content. Total muscle protein was partitioned into soluble (myogen or sarcoplasmic) and insoluble (myofibrillar) components. Both the myogen and myofibrillar components are reduced in muscle with decreased protein content. The activities (units g-1 wet wt) of white muscle L-lactate dehydrogenase and L-malate dehydrogenase are higher in fishes undergoing diel vertical migration to surface waters than in fishes that either do not migrate or do not migrate to surface waters. The differences in enzyme activities are not due to a general dilution of muscle protein. The actin content of white skeletal muscle was maintained at a relatively constant level in all 11 species examined and was similar to actin levels observed previously in the white skeletal muscle of scombrids and demersal fishes. This conservation of actin content requires species with a reduced muscle protein content to maintain a significant fraction of their total protein as actin. The specific activities of the myofibrillar Mg2+−Ca2+-activated adenosine triphosphatases of the mesopelagic species are similar in all 11 species studied. Thus, the ratios of proteins in the isolated myofibrils are probably similar. These results suggest that, in species with decreased muscle protein, there is an increase in the non-myofibrillar form of actin.
Synthesis of Coumarin–Polyamine-Based Molecular Probe for the Detection of Hydroxyl Radicals Generated by Gamma Radiation

Abstract Singh, A., Chen, K., Adelstein, S. J. and Kassis, A. I. Synthesis of Coumarin–Polyamine-Based Molecular Probe for the Detection of Hydroxyl Radicals Generated by Gamma Radiation. Radiat. Res. 168, 233–242 (2007). To develop a molecular probe for detection of hydroxyl radicals in the vicinity of DNA, the coumarin–polyamine complexes, N1,N12-bis[2-oxo-2H-chromene-3-carbonyl]-1,12-diamine-4,9-diazadodecane (5) and tris[2-(2-oxo-2H-chromene-3-carboxamido)ethyl]amine (7), and their hydroxylated derivatives, N1,N12-bis[7-hydroxy-2-oxo-2H-chromene-3-carbonyl]-1,12-diamine-4,9-diazadodecane (6) and tris[2-(7-hydroxy-2-oxo-2H-chromene-3-carboxamido)ethyl]amine (8), have been synthesized. Using computer-generated molecular modeling, the derivatives have been docked onto DNA dodecamer d(CGCGAATTCGCG)2, the ligand–DNA complexes have been minimized, and the free binding energies (ΔGbinding) and inhibition constants (Ki) have been calculated. Compound 7 is not water-soluble at the concentrations required for t...
The JmjN Domain of Jhd2 Is Important for Its Protein Stability, and the Plant Homeodomain (PHD) Finger Mediates Its Chromatin Association Independent of H3K4 Methylation

Histone lysine methylation is a dynamic process that plays an important role in regulating chromatin structure and gene expression. Recent studies have identified Jhd2, a JmjC domain-containing protein, as an H3K4-specific demethylase in budding yeast. However, important questions regarding the regulation and functions of Jhd2 remain unanswered. In this study, we show that Jhd2 has intrinsic activity to remove all three states of H3K4 methylation in vivo and can dynamically associate with chromatin to modulate H3K4 methylation levels on both active and repressed genes and at the telomeric regions. We found that the plant homeodomain (PHD) finger of Jhd2 is important for its chromatin association in vivo. However, this association is not dependent on H3K4 methylation and the H3 N-terminal tail, suggesting the presence of an alternative mechanism by which Jhd2 binds nucleosomes. We also provide evidence that the JmjN domain and its interaction with the JmjC catalytic domain are important for Jhd2 function and that Not4 (an E3 ligase) monitors the structural integrity of this interdomain interaction to maintain the overall protein levels of Jhd2. We show that the S451R mutation in human SMCX (a homolog of Jhd2), which has been linked to mental retardation, and the homologous T359R mutation in Jhd2 affect the protein stability of both of these proteins. Therefore, our findings provide a mechanistic explanation for the observed defects in patients harboring this SMCX mutant and suggest the presence of a conserved pathway involving Not4 that modulates the protein stability of both yeast Jhd2 and human SMCX.
Gene regulation. One man's food.

Drugs can have unpredictable effects, especially if several are taken at once. A particular type of genetically engineered, 'humanized', mouse may shed light on the delicate balance between toxicity and therapy.
Common features of megakaryocytes and hematopoietic stem cells: What's the connection?

Megakaryocytes (Mks) are rare polyploid bone marrow cells whose function is to produce blood platelets. Since the purification and cloning of the major Mk cytokine, thrombopoietin, in 1994, considerable progress has been made in understanding the biology of Mk development. Remarkably, these advances have revealed a number of key features of Mks that are shared with hematopoietic stem cells (HSCs), such as common surface receptors, lineage-specific transcription factors, and specialized signaling pathways. Why there should be such a close connection between these two cell types remains unclear. In this Prospect article, we summarize the data supporting these shared features and speculate on possible teleological bases. In particular, we focus on common links involving developmental hierarchy, endothelial cells, and bone marrow niche interactions. This discussion highlights new data showing close ontologic relationship between HSCs and specialized "hemogenic" endothelial cells during development, and functional overlap between Mks/platelets and endothelial cells. Overall, these findings may be of relevance in the development of techniques for HSC ex vivo culture and/or possible generation of HSCs via somatic cell reprogramming.