cssi/SciSciGPT-SciSciNet huggingface dataset:
Potential Anti-SARS-CoV-2 Therapeutics That Target the Post-Entry Stages of the Viral Life Cycle: A Comprehensive Review

The coronavirus disease-2019 (COVID-19) pandemic continues to challenge health care systems around the world. Scientists and pharmaceutical companies have promptly responded by advancing potential therapeutics into clinical trials at an exponential rate. Initial encouraging results have been realized using remdesivir and dexamethasone. Yet, the research continues so as to identify better clinically relevant therapeutics that act either as prophylactics to prevent the infection or as treatments to limit the severity of COVID-19 and substantially decrease the mortality rate. Previously, we reviewed the potential therapeutics in clinical trials that block the early stage of the viral life cycle. In this review, we summarize potential anti-COVID-19 therapeutics that block/inhibit the post-entry stages of the viral life cycle. The review presents not only the chemical structures and mechanisms of the potential therapeutics under clinical investigation, i.e., listed in clinicaltrials.gov, but it also describes the relevant results of clinical trials. Their anti-inflammatory/immune-modulatory effects are also described. The reviewed therapeutics include small molecules, polypeptides, and monoclonal antibodies. At the molecular level, the therapeutics target viral proteins or processes that facilitate the post-entry stages of the viral infection. Frequent targets are the viral RNA-dependent RNA polymerase (RdRp) and the viral proteases such as papain-like protease (PLpro) and main protease (Mpro). Overall, we aim at presenting up-to-date details of anti-COVID-19 therapeutics so as to catalyze their potential effective use in fighting the pandemic.
Quantitative analysis of CMTM6 expression in tumor microenvironment in metastatic melanoma and association with outcome on immunotherapy.

Chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing 6 (CMTM6) modulates degradation of a number of proteins, including programmed death ligand-1 (PD-L1) by protecting it from u...
The role of metal patch testing in evaluating patients for metallic prosthetic joint failure.

Abstract Background Metal allergy may be an uncommon cause of prosthetic joint failure. There exist little data on patch testing to metals in this context and its impact on outcomes of joint revision in these patients. Objective To explore the use and indications for metal patch testing in the evaluation of patients suspected of having metal allergy as a cause of failed joint replacements and to clarify the outcomes of patients revised with alternative metallic joints because of positive patch testing result. Methods A retrospective analysis from January 2016 to April 2020 was completed on a patient cohort referred for evaluation of metal hypersensitivity. Charts were reviewed for age, biological sex, referring specialty, patch testing results, joint, revision status, and outcome measures. Biostatistical analysis and descriptive statistics were performed to determine patch testing performance and functional outcome trends among this patient cohort. Results The sensitivity and specificity of patch testing, in general, are limited when evaluating patients with metallic joint replacements. However, the predictive value of testing seemed to improve with strongly positive patch testing results. Functional outcomes in patients when positive results were used to guide revision prosthesis revealed clinical improvement. Conclusion The attribution of metal allergy or hypersensitivity as a cause of failure in metal prosthetic joint replacement remains unproven. Some patients with positive histories and patch testing results that were used to modify the implanted prosthesis had improved functional outcomes. These results suggest that patch testing may be useful in patients with history of metal sensitivity and prosthetic failure.
Acute Brain Injury in Postcardiotomy Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation.

Objective Acute brain injury (ABI) is common in venoarterial extracorporeal membrane oxygenation (VA-ECMO). One of the most common indications for use of VA-ECMO is postcardiotomy shock (PCS). The authors aimed to characterize the prevalence of ABI and its association with outcomes in this population. Design prospective observational. Setting Single-center tertiary care university hospital. Participants Fifty-two consecutive patients treated for PCS with VA-ECMO from November 2017 to March 2020. Interventions None. Measurements and Main Results The median age of patients was 64 (interquartile range 44-84), 62% were male. Of 52 PCS patients treated with extracorporeal membrane oxygenation, 38% (n = 20) experienced acute brain injury. Ischemic stroke was the most common (n = 13, 25%). Patients with central versus peripheral cannulation experienced more ischemic and hemorrhagic strokes (8% v 38%, p = 0.04). Patients with intracardiac thrombus experienced more brain injury (n = 4, 8% p = 0.02). The in-hospital mortality in patients with brain injury was 90% (n = 18/20) compared to 78% (n = 25/32) in patients without brain injury. Conclusions ABI is common in postcardiotomy VA-ECMO and associated with worse outcome. Patients with central recanalization experienced the majority of acute strokes. Intracardiac thrombus was significantly associated with acute brain injury.
Patterns of opioid and benzodiazepine use with gabapentin among disabled Medicare beneficiaries - A retrospective cohort study

BACKGROUND Our goal was to describe specific patterns associated with co-prescriptions of gabapentin, opioids, and benzodiazepines among disabled Medicare beneficiaries. METHODS Using 2013-2015 Medicare data, we conducted a retrospective cohort study among fee-for-service disabled beneficiaries continuously enrolled in Medicare Parts A, B, and D. The index date was defined as the earliest fill date for a gabapentin, opioid, or benzodiazepine prescription. Monotherapy, dual therapy, and tri-therapy were defined as utilization of one, two, and three medication classes, respectively. Augmentation was defined as a prescription for a different medication class in addition to prescription for initial medication; switching referred to a change in prescription for a different medication class with no subsequent fills of initial medication. We used descriptive statistics, Kaplan Meier analyses and Cox proportional hazards to examine the association between initial therapy and monotherapy, dual therapy, tri-therapy, switching and augmentation. RESULTS Among 151,552 disabled beneficiaries, gabapentin initiators were more likely to augment therapy (50.1%) when compared to opioid (28.7%) and benzodiazepine (38.7%) users. When compared to opioid initiators, the risk of augmentation (HR[95%CI]: 1.85[1.82-1.89]) and switching (1.62 [1.51-1.73]) was significantly higher among gabapentin initiators. Risk of augmentation was also significantly higher among beneficiaries with co-morbid pain and mental health conditions (p < 0.01). Overall, the majority of beneficiaries augmented and switched within 2-months and 4-months after initiating therapy, respectively. CONCLUSIONS Given safety concerns associated with gabapentin, opioids, and benzodiazepines, it is imperative that the benefits and risks of co-prescribing these medications be examined comprehensively, especially for those in vulnerable sub-groups.
Why No Respect? The Contractual Duties of Good Faith and Fair Dealing in Delaware

The thesis of this paper focuses on the statutory policy of "freedom of contract" in Delaware unincorporated entity law and the confusion of some courts in applying these contractarian principles in the face of, what would have been, traditional fiduciary duties. What has resulted is a muddle in the case law caused by the similarity in the terms good faith, in the context of the duty of good faith in contract law, and the term good faith as it is used in the law of business organizations to describe a fiduciary duty of care or the standard of conduct for a director in a corporation. Similarly, puzzlement results when litigators or courts mistakenly interchange the contract term fair dealing with the judicial standard of entire fairness traditionally reserved for the review of conduct by disloyal fiduciaries. In Delaware, it is time for corporate principles to remain in the realm of corporate law and the corpfuscation of unincorporated law to end.
Regulatory Competition and Anticorruption Law

This article considers whether the prospect of increased competition in the regulation of international bribery is desirable or not. It explores the factors that can determine whether this competition will augment or diminish global welfare. Its conclusion is optimistic. Based on what we know about the general dynamics of regulatory competition, the risk that multiple anticorruption regimes will lead to confusion, obstruction of valuable transactions, or a kind of arms race among states seeking to protect national champions is low. Conversely, the likelihood that multiple, often overlapping regimes will decrease the incidence of welfare-diminishing corruption is high. The article initially was presented at a conference organized by the Virginia Journal of International Law and the John Bassett Moore Society of International Law.
Max-Min Representation of Piecewise Linear Functions

It is shown that a piecewise linear function on a convex domain in R d can be represented as a boolean polynomial in terms of its linear components.
Grand unification and cosmology

Most recent breakthroughs in understanding the physics of elementary particle interactions have been based on the framework of spontaneously broken gauge symmetries. The historically very successful quantum field theory of electromagnetism is a gauge theory based on the group U(1), complex phase rotation. More recently, the Weinberg-Salam SU(2) × U(1) model has become the accepted theory of ‘electroweak’ interactions, and SU(3) ‘quantum chromodynamics’ is the popular theory of strong interactions. From here, a Grand Unification (GU) of all these forces into a theory with a single large symmetry group is a natural outgrowth.
Spectrum sharing between matrix completion based MIMO radars and a MIMO communication system

Recently proposed multiple input multiple output radars based on matrix completion (MIMO-MC) employ sparse sampling to reduce the amount of data forwarded to the radar fusion center, and as such enable savings in communication power and bandwidth. This paper proposes designs that optimize the sharing of spectrum between MIMO-MC radars and MIMO communication systems, so that the latter interferes minimally with the former. First, the communication system transmit covariance matrix is designed to minimize the effective interference power (EIP) at the radar receiver, while maintaining certain average capacity and transmit power for the communication system. Two approaches are proposed, namely a noncooperative and a cooperative approach, with the latter being applicable when the radar sampling scheme is known at the communication system. Second, a joint design of the communication transmit covariance matrix and the MIMO-MC radar sampling scheme is proposed, which achieves even further EIP reduction.
Ironies of Social Control and the Criminalization of Immigrants

As moral panic over immigrants spreadduring the early 1990s, immigrationpolicies became increasingly criminalized in the wake of the bombingsof the World Trade Center in 1993 and ofthe Murrah Federal Building in OklahomaCity in 1995. In response to the threat ofterrorism at home, Congress enacted theIllegal Immigration Reform andImmigration Responsibility Act along withthe Anti-Terrorism and Effective DeathPenalty Act in 1996. Since then severalkey provisions of those statutes haveproduced numerous violations of civilliberties and immigrants' rights. Drawingon a conceptual framework developed bysociologist Gary T. Marx (1981), thisarticle examines critically thecontradictions and ironies of immigrationcontrol, specifically the mostcontroversial aspects of the 1996 laws:court-stripping provisions, use of secretevidence, and growing register ofdeportable crimes. In light of theterrorist attacks on September 11th, 2001,the article expresses concerns over thegovernment's current campaign to fightterrorism, especially the use of racialprofiling and mass detention shrouded insecrecy.
Utility and Safety of Axillo‐subclavian Venous Imaging with Carbon Dioxide (CO2) Prior to Chronic Lead System Revisions

Background: Prior to attempting placement of one or more electrodes to revise existing rhythm control devices, patency of the central veins should be documented, in view of a high incidence of significant chronic occlusions. Since iodinated contrast venography may be contraindicated in select situations, imaging of the axillo-subclavian venous system with gaseous carbon dioxide (CO2) was evaluated prospectively in 23 consecutive individuals who were considered for revision of previously implanted pacemaker or automatic cardioverter defibrillator lead systems. Methods: Approximately 20 mL of CO2 were manually infused via CO2 primed injection tubing into a vein at or above the level of the antecubital fossa ipsilateral to the side of prior lead placements. Digital subtraction imaging over the axillo-subclavian region, lower neck, and mediastinum was performed. Formal interpretation was obtained from one of three interventional radiologists and at least one electrophysiologist. Results: Significant venous occlusions were identified in five (22%) patients. Vascular access utilized for the subsequent 18 revisions performed included the imaged patent ipsilateral vein in 14 patients and the contralateral, right-sided subclavian venous system in three patients. One patient required epicardial left ventricular lead placement. There were no complications from venography. Conclusions: Axillo-subclavian venography with gaseous CO2 in patients undergoing pacemaker or implantable cardioverter defibrillator lead revisions is feasible and safe when use of iodinated dye is contraindicated. This technique should be employed in patients with azotemia, dye contrast allergies, or significant inflammation in the vicinity of the intravenous line insertion. (PACE 2010; 790–794)
Compressive sensing as a paradigm for building physics models

The widely accepted intuition that the important properties of solids are determined by a few key variables underpins many methods in physics. Though this reductionist paradigm is applicable in many physical problems, its utility can be limited because the intuition for identifying the key variables often does not exist or is difficult to develop. Machine learning algorithms (genetic programming, neural networks, Bayesian methods, etc.) attempt to eliminate the ap riorineed for such intuition but often do so with increased computational burden and human time. A recently developed technique in the field of signal processing, compressive sensing (CS), provides a simple, general, and efficient way of finding the key descriptive variables. CS is a powerful paradigm for model building; we show that its models are more physical and predict more accurately than current state-of-the-art approaches and can be constructed at a fraction of the computational cost and user effort.
Regulation of biosynthesis of aminoacyl-tRNA synthetases and of tRNA in Escherichia coli. III. Biochemical characterization of regulatory mutants affecting leucyl-tRNA synthetase levels.

We have investigated the consequences of two mutations, leu X and leu Y, which affect the level of leucyl-tRNA synthetase on the amount of tRNA and other aminoacyl-tRNA synthetases and on the expression of the ilv and leu operons in Escherichia coli . Neither mutation appears to alter the cellular concentrations of other aminoacyl-tRNA synthetases or tRNA isoacceptor families. It was shown that leucyl-tRNA rather than leucyl-tRNA synthetase is the defective control element responsible for derepression of the leu and ilv operon in leu S31 strains. Steady-state levels of leucine, isoleucine, valine, ppGpp, pppGpp and leucyl-tRNA, and the rate of protein synthesis have been measured in leu S + , leu S − , leu S − leu X − , and leu S − leu Y − strains. The levels of magic spot compounds appear to correlate with the extent that protein synthesis is arrested rather than the concentration of limiting leucyl-tRNA.
Conditional deletion of Dicer in vascular smooth muscle cells leads to the developmental delay and embryonic mortality

Dicer is a RNAase III enzyme that cleaves double stranded RNA and generates small interfering RNA (siRNA) and microRNA (miRNA). The goal of this study is to examine the role of Dicer and miRNAs in vascular smooth muscle cells (VSMCs). We deleted Dicer in VSMCs of mice, which caused a developmental delay that manifested as early as embryonic day E12.5, leading to embryonic death between E14.5 and E15.5 due to extensive hemorrhage in the liver, brain, and skin. Dicer KO embryos showed dilated blood vessels and a disarray of vascular architecture between E14.5 and E15.5. VSMC proliferation was significantly inhibited in Dicer KOs. The expression of VSMC marker genes were significantly downregulated in Dicer cKO embryos. The vascular structure of the yolk sac and embryo in Dicer KOs was lost to an extent that no blood vessels could be identified after E15.5. Expression of most miRNAs examined was compromised in VSMCs of Dicer KO. Our results indicate that Dicer is required for vascular development and regulates vascular remodeling by modulating VSMC proliferation and differentiation.
Rain Reevaporation, Boundary Layer Convection Interactions, and Pacific Rainfall Patterns in an AGCM

Sensitivity experiments with an atmospheric general circulation model (AGCM) show that parameterized rain re-evaporation has a large impact on simulated precipitation patterns in the tropical Pacific, especially on the configuration of the model s intertropical convergence zone (ITCZ). Weak re-evaporation leads t o the formation of a "double ITCZ" during the northern warm season. The double ITCZ is accompanied by strong coupling between precipitation and high-frequency vertical motion in the planetary boundary layer (PBL). Strong reevaporation leads to a better overall agreement of simulated precipitation with observations. The model s double ITCZ bias is reduced. At the same time, correlation between high-frequency vertical motion in the PBL and precipitation is reduced. Experiments with modified physics suggest that evaporative cooling by rain near the PBL top weakens the coupling between precipitation and vertical motion. This may reduce the model s tendency to form double ITCZs. The strength of high-frequency vertical motions in the PBL was also reduced directly through the introduction of a diffusive cumulus momentum transport (DCMT) parameterization. The DCMT had a visible impact on simulated precipitation in the tropics, but did not reduce the model s double bias in all cases.
The structure of psychotropic drugs (including theoretical prediction of a new class of effective neuroleptics)

A brief introductory review is presented of the etiology of affective disorders, the neuropsychopharma-cological modalities used in treating these states, and the mechanisms by which these therapies act. The topological and topographical requisites for effective neuroleptic (antipsychotic) drugs (the major tranquillizers) are outlined. Quantum chemical results, both CNDO/2 and INDO, are presented for promazine, perazine, and their CI and CF3 derivatives. Application of the topographical postulates led us to perform quantum chemical calculations on a series of hitherto unsynthesized and untested compounds, N-piperdinopromazines. We predicted these would be effective neuroleptics. In the interim a compound of this type was synthesized and tested and it is, indeed, a major tranquillizer. The subtle differences in geometrical conformation between tricyclic neuroleptics (which are postsynaptic dopamine blockers) and the closely related tricyclic antidepressants (which inhibit reuptake of norepinephrine and serotonin back into the the presynapse) are indicated. In the area of hallucinogens or psychotomimetic agents, it is emphasized that even though compounds like LSD and mescaline exhibit cross tolerance, they apparently do not act by the same mechanism. Thus the commonalities in structures between these two groups previously invoked by other authors merit reexamination and a sharpening of focus. Quantum chemical results, CNDO/2 and PCILO, are presented for a few of these compounds whose crystal structures have been determined recently. Our interest in these psychotomimetics was twofold; first, because of their intrinsic interest in the hierarchy of psychotropic drugs and second, to gain insight into why many narcotic antagonists are undesirably psychotomimetic.
Possible orders for the stabilizer of a set of M.O.L.S.

Abstract Let A = { a 1 , a 2 ,…, a k } be a k -set of mutually orthogonal tables and let ( u, v ) be a pair of orthogonal tables. Then B = { b 1 , b 2 ,…, b k } where b i ( x , y ) = a i ( u ( x , y ), v ( x , y )), for i = 1, 2, …, k , is a k -set of mutually orthogonal tables called a conjugate of A . The set of all conjugates equal to the original set forms a group. This group is isomorphic to a subgroup of S k which we call the array stabilizer. It is shown that if a subgroup H of S k acts as the array stabilizer for a k -set of mutually orthogonal tables, then the order of H is a divisor of k ( k −1). In the case where the set of mutually orthogonal tables contains five tables the necessary conditions are shown to be also sufficient.
Copper-Promoted Sulfenylation of sp2 C–H Bonds

An auxiliary-assisted, copper catalyzed or promoted sulfenylation of benzoic acid derivative β-C–H bonds and benzylamine derivative γ-C–H bonds has been developed. The method employs disulfide reagents, copper(II) acetate, and DMSO solvent at 90–130 °C. Application of this methodology to the direct trifluoromethylsulfenylation of C–H bonds was demonstrated.
Community Attitudes Toward the Homeless.

The question of community attitudes toward the homeless has received little systematic attention. Media accounts suggest a paradoxical situation, involving general communitywide support for program...
Techniques for measuring neutron scattering cross sections with a beam swinger

Abstract Techniques have been developed for measuring neutron elastic and inelastic scattering cross sections using a beam swinger based time-of-flight system. The use of a beam swinger has significant advantages at high neutron energies because of the simplification of shielding arrangements and the convenient use of long flight paths to obtain high resolution. Applications have been made to neutron scattering at 30.3 and 40 MeV.
Urban development, collective consumption and the politics of metropolitan fragmentation

Abstract The territorial partition of the metropolis is a theme central to discussions of urban problems in the US. Metropolitan political fragmentation per se is far from understood, however. Theories of metropolitan political fragmentation have tended to emphasize interests in consumption to the neglect of matters of production. Moreover, the role of state managers tends to be marginalized in such theories. This paper situates an actual politics of metropolitan fragmentation in relation to the two dominant discourses of contemporary urban theory: the politics of local economic development and the politics of collective consumption. Consideration is paid to pressures for territorial organization emanating from coalitional forces that span the state-civil society boundary. These conceptual themes are examined concretely through a detailed study of post-war patterns of territorial organization in metropolitan Columbus, Ohio. While integration of the metropolitan area in terms of the provision of water and sewerage for local economic development projects has been a project of the metropolitan growth coalitions and the city of Columbus, that integration has only been possible to the extent that interests in collective consumption or, more specifically, in education, have been politically neutralized.
Comparison of the results obtained with different models for the simulation of preparative chromatography

Abstract We examine the theoretical similarities and differences between three calculation procedures used for the simulation of band propagation in non-linear chromatography. All three approaches are implementations of the finite difference method of integration of the partial diiterential equations which state the mass balances of the sample components. The elution profiles calculated with these three procedures agree quite well when applied to reasonably efficient columns (over 1000 theoretical plates), at moderate and high sample loads as long as the displacement effect predominates. These profiles also agree well with experimental results. Significant differences appear, however, when the concentration of the second component in the feed is smaller than that of the first one. The origin and extent of these differences are discussed in detail and the range of deviations to be expected in practical cases is illustrated.
Muscle-like nicotinic receptor accessory molecules in sensory hair cells of the inner ear.

Nothing is known about the regulation of nicotinic acetylcholine receptors (nAChRs) in hair cells of the inner ear. MuSK, rapsyn and RIC-3 are accessory molecules associated with muscle and brain nAChR function. We demonstrate that these accessory molecules are expressed in the inner ear raising the possibility of a muscle-like mechanism for clustering and assembly of nAChRs in hair cells. We focused our investigations on rapsyn and RIC-3. Rapsyn interacts with the cytoplasmic loop of nAChR α9 subunits but not nAChR α10 subunits. Although rapsyn and RIC-3 increase nAChR α9 expression, rapsyn plays a greater role in receptor clustering while RIC-3 is important for acetylcholine-induced calcium responses. Our data suggest that RIC-3 facilitates receptor function, while rapsyn enhances receptor clustering at the cell surface.
Effects of acute hyperprolactinemia on LH pulsatile secretion in hypogonadal and early follicular phase women

Abstract To investigate the effects of acute hyperprolactinemia on the 24 h LH pulsatile pattern, 11 women in the early follicular phase (EF, days 3 and 4) and 8 postmenopausal women (PMW) were studied before and during administration of metoclopramide, a dopamine receptor antagonist. Sequential 24 h infusions of either metoclopramide (MCP, 30 μg/kg/h) or normal saline were conducted and pulsatile LH activity assessed for 48 hrs. In both EF women and PMW, a prompt (within 90 min, p 45 μg/L, p
Drill Pipe Buckling in Inclined Holes

Etude theorique montrant que les tiges de forage peuvent supporter des charges de compression sans flambage dans les forages a forte inclinaison
Expression of a truncated keratin 5 may contribute to severe palmar--plantar hyperkeratosis in epidermolysis bullosa simplex patients.

Epidermolysis bullosa simplex are dominant disorders of skin fragility characterized by intraepidermal blistering upon mild mechanical trauma. Skin fragility is caused by expression of either an abnormal keratin 5 or an abnormal keratin 14 protein, which compromises the structure and function of the keratin cytoskeleton of basal cells. We report an epidermolysis bullosa simplex patient with a novel single base substitution (A→T1414) that changes the lysine residue at amino acid 472 to a non-sense codon (K472X). This change predicts the synthesis of a truncated keratin 5, missing 119 amino acids, including the entire tail domain and the highly conserved KLLEGE motif at the carboxy terminus of the 2B domain of the central rod. Expression of an altered keratin 5, of predicted mass and pI for the product of the K472X allele, was documented by one- and two-dimensional western blots of protein extracts from patient skin. Ultrastructural analysis of the patient's nonhyperkeratotic skin was remarkable for basal keratinocytes with dense and irregular keratin filaments proximal to the basement membrane. Keratinocytes, transfected with a cDNA carrying the A→T1414 non-sense mutation, overexpressed a truncated keratin 5, and showed a disorganized and collapsed keratin filament cytoskeleton. This is the second epidermolysis bullosa simplex patient reported with a premature termination mutation in the KLLEGE motif. The remarkable occurrence of severe palmar–plantar hyperkeratosis in both patients suggests that the keratin 5 tail domain may have unrecognized, but important, normal functions in palmar–plantar tissues.
A DECONVOLUTION TECHNIQUE FOR HUBBLE SPACE TELESCOPE FGS FRINGE ANALYSIS

A technique has been developed for directly transforming interferometer fringe visibility functions ('S curves') from the Hubble Space Telescope (HST) fine guidance sensors (FGSs) into intensity profiles of the program object. In a process analogous to Fourier transform image deconvolution, an S curve from a double star yields a pair of narrow profiles containing information on the separation (in one coordinate), and relative brightness of the two stars. The procedure has yielded high internal precision for the separation and relative brightness in tests with HST data. Simulations indicate that it can also deconvolve S curves from multiple stars or continuous intensity distributions such as resolvable stellar or extragalactic objects. Similar deconvolution analyses may be useful in other types of interferometry.
Lipoprotein augmentation of human chorionic gonadotropin and prolactin stimulated progesterone synthesis by rat luteal cells

Abstract A collagenase dispersed cell suspension from PMSG-hCG primed immature rats responded to exogenously added hCG, cholera enteroxin, prolactin, and 8-Bromocyclic-AMP with increase in progesterone production in a dose dependent manner, and this stimulation was augmented by the plasma lipoprotein fractions hHDL and hLDL. The responsiveness to low doses of prolactin was not apparent when lipoprotein fractions were not included in the assay mixture. When the incubation mixture contained either LDL or HDL, the stimulatory effect of prolactin on progesterone production was evident at 5 and 10 μg prolactin/ml of the incubation mixture. Progesterone production, both basal and hormone stimulated, was maximum on day 7 of pseudopregnancy. Although the extent of hCG and prolactin stimulation of progesterone production and its potentiation by lipoprotein fractions was observed to be higher on days 3 and 5 than that seen on day 7, the net amount of progesterone produced was highest on day 7. The basal as well as hormone and lipoprotein stimulated progesterone production started to decline after day 7, reaching a nadir on day 14. These experiments show that prolactin is effective in stimulating progesterone production by rat luteal cells in vitro and that lipoprotein fractions, LDL and HDL further potentiate this response. This study further suggests that it is important to include LDL or HDL as a source of cholesterol for in vitro experiments in which the steroidogenic response of luteal cells to exogenous stimuli is tested.
Systematics of crack controlled mechanical properties for a suite of Conway granites from the White Mountains, New Hampshire

Abstract The Conway granite of New Hampshire is a highly radioactive intrusive into which a 1-km deep borehole was drilled and continuously cored. The formation is composed of two major granitic units, the Osceola and the Conway; and it is cut by three lamprophyre dikes. The suite of rocks used in this paper contained eight granitic and two lamprophyre samples on which acoustic and strain measurements were performed over the pressure range of 1 atm. to 0.4 GPa. The V p data were subjected to cluster analyses to determine what, if any, similarities in pressure-dependence existed among the samples. Three distinct similarity groupings were found: the lamprophyre dike rocks and two groups each of which contains samples from both granitic units. These groupings by V p behavior were also found to correlate exactly with sample similarity groupings formed by dynamic and static moduli data, crack spectra, and rock texture. Such sample similarities in the functional forms of the pressure-dependence were found not to correlate with mineral modes nor with original in situ depth, but rather with grain size and the degree to which the mineral phases were homogeneously mixed. A consideration of the results suggests that for these rocks, grain size and mineral phase homogeneity exerted a dominant influence on crack population formation. Further, it appears that the exhumation and coring of these samples may have intensified the amount of cracking over that in situ but it did not necessarily introduce any individual distinct crack populations.
Modeling of Heterogeneous Propellant Combustion: A Survey

H ETEROGENEOUS solid energetic materials are widely used in the aerospace and defense industries in rockets, explosives, and diverse pyrotechnic devices. Their basic microstructure consists of oxidizer particles embedded in a polymeric binder. Two important classes of energeticmaterials are solid propellants and plastic bonded explosives. A typical composite solid propellant is composed ammonium perchlorate (AP) particles embedded in a polymer such as hydroxyl-terminated polybutadiene (HTPB) or polybutadiene acrylonitrile. A common variation is the addition of metal particles (e.g., aluminum) to raise the combustion temperature. Plastic bonded explosives consist of a heterogeneous mixture of high-explosive crystals (such as cyclotetramethylenetetranitramine or cyclotrimethylenetrinitramine) and a polymeric binder. Here, the discussion is restricted to composite solid propellants. The intent of the present survey is to provide a highlighted discussion of relevant work on the multidimensional computational simulation of heterogeneous solid propellant combustion. Routine numerical simulations are now being carried out, in which many of the physical characteristics of real propellants are mimicked, including random packing of oxidizer particles in a fuel binder, unsteady three-dimensional heat conduction within the solid, unsteady regressionof thenonplanar propellant surface, andcoupling with an unsteady three-dimensional combustion field sustained by reactantfluxes from the surface. Such computations require the use of massively parallel supercomputers, and even then there are limitations onwhat physics can be included. The ultimate goal is to develop a truly predictive simulation tool that can assist in design and optimization of propellant microstructures and propellant grain designs for internal solid rocket motors. Modeling and simulation of composite propellants will remain a vital task because solid rocket motors are critical to national defense, communications, space exploration, and eventually space tourism. The value of computational combustion is eloquently presented in a recent review paper [1]. II. Modeling
Care for the caregiver: benefits of expressive writing for nurses in the United States

AbstractThis paper introduces expressive writing as a new tool to build psychological resilience in nurses by helping them to reduce the negative impact of the primary sources of stress in their jobs. Delivering care to patients exposes nurses to intense stressors including staffing and workload problems, communication breakdowns, death, bereavement, and medical error. Not surprisingly, these conditions contribute to job dissatisfaction and burnout which are primary causes of nurse turnover. There is an acute need for low cost and simple interventions that enhance nurses' coping with problems leading up to burnout and turnover. We found almost 2 out of 3 RNs reported trouble sleeping, almost half reported feeling burned out, and 1 out of 4 were depressed. Expressive writing has been widely used and is well validated in many non-nursing populations in helping people cope more effectively with job-related stress and traumatic events. Writing improves health in several ways. One way is through exposure, the ...
On the partition function as a functional integral over the eigenspace of an elliptic operator

Abstract Using a particular scalar product in the functional measure, a general form is derived for the partition function of systems whose action functionals are of a certain form. Applications to one-and higher-dimensional cases are discussed.
5-propynylpyrimidine nucleoside derivatives: rationally designed mechanism-based inactivators of thymidylate synthase

A novel series of 5-propynyl-dUMP derivatives, with a variety of leaving groups on the side-chain, was designed as potential mechanism-based inhibitors of thymidylate synthase (TS), and synthesized from 5-iodo-2'-deoxyuridine by Pd(0)-catalyzed coupling, followed by direct phosphorylation with POCl3. All members of the series inhibited TS competitively with Ki-values of 0.015-18 microM. Analogs with fluorine or imidazole-based leaving groups caused rapid, irreversible inactivation of TS.
Polyamine Transport Inhibitors: Design, Synthesis, and Combination Therapies with Difluoromethylornithine

The development of polyamine transport inhibitors (PTIs), in combination with the polyamine biosynthesis inhibitor difluoromethylornithine (DFMO), provides a method to target cancers with high polyamine requirements. The DFMO+PTI combination therapy results in sustained intracellular polyamine depletion and cell death. A series of substituted benzene derivatives were evaluated for their ability to inhibit the import of spermidine in DFMO-treated Chinese hamster ovary (CHO) and L3.6pl human pancreatic cancer cells. Several design features were discovered which strongly influenced PTI potency, sensitivity to amine oxidases, and cytotoxicity. These included changes in (a) the number of polyamine chains appended to the ring system, (b) the polyamine sequence, (c) the attachment linkage of the polyamine to the aryl core, and (d) the presence of a terminal N-methyl group. Of the series tested, the optimal design was N1,N1′,N1″-(benzene-1,3,5-triyltris(methylene))tris(N4-(4-(methylamino)butyl)butane-1,4-diamine,...
Computational and Bioinformatics Frameworks for Next-Generation Whole Exome and Genome Sequencing

It has become increasingly apparent that one of the major hurdles in the genomic age will be the bioinformatics challenges of next-generation sequencing. We provide an overview of a general framework of bioinformatics analysis. For each of the three stages of (1) alignment, (2) variant calling, and (3) filtering and annotation, we describe the analysis required and survey the different software packages that are used. Furthermore, we discuss possible future developments as data sources grow and highlight opportunities for new bioinformatics tools to be developed.
Variation in rates of nitrogen fixation in termites: response to dietary nitrogen in the field and laboratory

. Termites contribute nitrogen to their habitat through the nitrogenase activity of their bacterial symbionts. Previous studies indicate that high levels of dietary nitrogen suppress nitrogen fixation in termites. We examined the effects of dietary nitrogen on fixation rates in termites in both field and laboratory experiments. Ten field cplonies of Reticulitermes were collected and assayed for nitrogenase activity in July 1993, October 1993, January 1994, and April 1994. The nitrogen content of the wood collected with each colony was determined. There was no correlation between termite nitrogen fixation rates and the amount of nitrogen in their food for any of the four collection periods. In laboratory experiments, nitrogen fixation rates decreased when termites were fed filter paper treated with 2% and 5% ammonium nitrate or a 5% mixture of the amino acids proline, tryptophan and leucine, compared to water-treated controls. By contrast, the nitrogenase activity of termites fed filter paper treated with 2% and 5% ammonium phosphate, a mixture of the amino acids histidine, serine and aspartic acid, or 2% and 5% urea did not differ from the controls. However, nitrogenase activity increased when termites were fed with 2% uric acid. No clear association exists between termite nitrogen fixation and the nitrogen content of their food.
“That Sounded Good!”: Using Whole-Class Choral Reading to Improve Fluency

Whole-class choral reading (WCCR) is an oral reading fluency strategy that can help older elementary students in need of fluency development. Implementation is simple and requires only a few minutes per day. WCCR can be easily adapted for use with narrative and expository texts and allows all students the opportunity to practice within an environment that provides monitored reader support.
Resistance to QoI Fungicides in Ascochyta rabiei from Chickpea in the Northern Great Plains.

ABSTRACT Ascochyta blight, caused by Ascochyta rabiei (teleomorph: Didymella rabiei), is an important fungal disease of chickpea (Cicer arietinum). A monitoring program was established in 2005 to d...
Synchrotron SAXS and Laser Light Scattering Studies of Aggregation Behavior of Poly(1,1-dihydroperfluorooctyl acrylate-b-vinyl acetate) Diblock Copolymer in Supercritical Carbon Dioxide

The aggregation behavior of dilute poly(1,1-dihydroperfluorooctyl acrylate-b-vinyl acetate) diblock copolymer in supercritical carbon dioxide (SCCO2) has been studied by using synchrotron small-angle X-ray scattering (SAXS) for the following two processes: an isothermal process with changes in pressure and a cooling process at a constant pressure. The above two processes also made it possible to compare the phase behavior of the solution at a constant SCCO2 density. The SAXS study, together with some light scattering experiments, shows that the phase behavior of the copolymer changes dramatically with experimental conditions in the SCCO2 solvent. The soluble solution was obtained at a low pressure of 180 bar with a corresponding SCCO2 density ρ ∼ 0.65 g/cm3 and at a high pressure at 450 bar with ρ ∼ 0.90 g/cm3 for the isothermal process at 65 °C. In the isothermal process, large aggregates exhibiting domain-packing structures were formed in the pressure range from 190 to 226 bar. Block copolymer micelles...
Activation of rat-liver microsomal glucose 6-phosphatase, inorganic pyrophosphatase and inorganic pyrophosphate-glucose phosphotransferase by hydroxyl ion.

Abstract 1. 1. OH- has been shown to produce a 2- to 3-fold increase in the apparent activity in vitro of rat-liver microsomal glucose 6-phosphatase (EC 3.1.3.9) and the related enzymatic activities, inorganic pyrophosphatase, inorganic pyrophosphate-glucose phosphotransferase and adenosine-5′-triphosphate-glucose phosphotransferase. 2. 2. Optimal activation is achieved by pre-treatment of liver microsomes with ammonium or amino acid buffers at pH 9.5–9.8. Inactivation is observed above pH 10. 3. 3. This activation is as great or greater than that produced by deoxycholate or Triton X-100 treatment and the thermal instability introduced by these reagents is avoided. 4. 4. Alteration of the microsomal membranes by treatment with base is accompanied by a decrease in turbidity but does not result in a solubilization of the enzyme. The essential protein-lipid binding is apparently retained and the enzyme, so treated, is relatively stable at 30°. 5. 5. NH4OH pretreatment of microsomes results in a lowering of the apparent Michaelis constant for glucose 6-phosphatase, similar to that caused by digitonin, deoxycholate and Triton X-100.
The thermal near-field: Coherence, spectroscopy, heat-transfer, and optical forces

Abstract One of the most universal physical processes shared by all matter at finite temperature is the emission of thermal radiation. The experimental characterization and theoretical description of far-field black-body radiation was a cornerstone in the development of modern physics with the groundbreaking contributions from Gustav Kirchhoff and Max Planck. With its origin in thermally driven fluctuations of the charge carriers, thermal radiation reflects the resonant and non-resonant dielectric properties of media, which is the basis for far-field thermal emission spectroscopy. However, associated with the underlying fluctuating optical source polarization are fundamentally distinct spectral, spatial, resonant, and coherence properties of the evanescent thermal near-field. These properties have been recently predicted theoretically and characterized experimentally for systems with thermally excited molecular, surface plasmon polariton (SPP), and surface phonon polariton (SPhP) resonances. We review, starting with the early historical developments, the emergence of theoretical models, and the description of the thermal near-field based on the fluctuation–dissipation theory and in terms of the electromagnetic local density of states (EM-LDOS). We discuss the optical and spectroscopic characterization of distance dependence, magnitude, spectral distribution, and coherence of evanescent thermal fields. Scattering scanning near-field microscopy proved instrumental as an enabling technique for the investigations of several of these fundamental thermal near-field properties. We then discuss the role of thermal fields in nano-scale heat transfer and optical forces, and the correlation to the van der Waals, Casimir, and Casimir–Polder forces. We conclude with an outlook on the possibility of intrinsic and extrinsic resonant manipulation of optical forces, control of nano-scale radiative heat transfer with optical antennas and metamaterials, and the use of thermal infrared near-field spectroscopy (TINS) for broadband chemical nano-spectroscopic imaging, where the thermally driven vibrational optical dipoles provide their own intrinsic light source.
The Histone Deacetylase Inhibitor Valproic Acid Lessens NK Cell Action against Oncolytic Virus-Infected Glioblastoma Cells by Inhibition of STAT5/T-BET Signaling and Generation of Gamma Interferon

Tumor virotherapy has been and continues to be used in clinical trials. One barrier to effective viral oncolysis, consisting of the interferon (IFN) response induced by viral infection, is inhibited by valproic acid (VPA) and other histone deacetylase inhibitors (HDACi). Innate immune cell recruitment and activation have been shown to be deleterious to the efficacy of oncolytic herpes simplex virus (oHSV) infection, and in this report we demonstrate that VPA limits this deleterious response. VPA, administered prior to oHSV inoculation in an orthotopic glioblastoma mouse model, resulted in a decline in NK and macrophage recruitment into tumor-bearing brains at 6 and 24 h post-oHSV infection. Interestingly, there was a robust rebound of recruitment of these cells at 72 h post-oHSV infection. The observed initial decline in immune cell recruitment was accompanied by a reduction in their activation status. VPA was also found to have a profound immunosuppressive effect on human NK cells in vitro. NK cytotoxicity was abrogated following exposure to VPA, consistent with downmodulation of cytotoxic gene expression of granzyme B and perforin at the mRNA and protein levels. In addition, suppression of gamma IFN (IFN-γ) production by VPA was associated with decreased STAT5 phosphorylation and dampened T-BET expression. Despite VPA-mediated immune suppression, mice were not at significantly increased risk for HSV encephalitis. These findings indicate that one of the avenues by which VPA enhances oHSV efficacy is through initial suppression of immune cell recruitment and inhibition of inflammatory cell pathways within NK cells.
Surprising synapses deep in the brain.

Two independent groups in this issue report synaptic communication between callosal axons and the NG2-positive glial precursors in the brain. Activity-dependent vesicular glutamate release from axon collaterals triggers AMPA-type currents in the precursors. This phenomenon might be involved in regulation of oligodendrocyte differentiation or remyelination.