cssi/SciSciGPT-SciSciNet huggingface dataset:
Comparative study on the inhibition of plasmin and delta-plasmin via benzamidine derivatives

The potent fibrinolytic enzyme, plasmin has numerous clinical applications for recannulizing vessels obstructed by thrombus. Despite its diminutive size, 91 kDa, success in the recombinant expression of this serine protease has been limited. For this reason, a truncated non-glycosylated plasmin variant was developed capable of being expressed and purified from E. coli. This mutated plasmin, known as δ-plasmin, eliminates four of the five kringle domains present on native plasmin, retaining only kringle 1 fused directly to the unmodified catalytic domain of plasmin. This study demonstrates that δ-plasmin exhibits similar kinetic characteristics to full length plasmin despite its heavily mutated form; KM = 268.78 ± 19.12, 324.90 ± 8.43 μM and Kcat = 770.48 ± 41.73, 778.21 ± 1.51 1/min for plasmin and δ-plasmin, respectively. A comparative analysis was also carried out to investigate the inhibitory effects of a range of benzamidine based small molecule inhibitors: benzamidine, p-aminobenzamidine, 4-carboxybenzamidine, 4-aminomethyl benzamidine, and pentamidine. All of the small molecule inhibitors, with the exception of unmodified benzamidine, demonstrated comparable competitive inhibition constants (Ki) for both plasmin and δ-plasmin ranging from Ki 1000 μM in the case of aminomethyl benzamidine. This result further supports that δ-plasmin retains much of the same functionality as native plasmin despite its greatly reduced size and complexity. This study serves the purpose of demonstrating the tunable inhibition of plasmin and δ-plasmin with potential applications for the improved clinical delivery of δ-plasmin to treat various thrombi.
Reflectivity of the atmosphere-inhomogeneous surfaces system Laboratory simulation

Theoretical two- and three-dimensional solutions of the radiative transfer equation have been applied to the earth-atmosphere system. Such solutions have not been verified experimentally. A laboratory experiment simulates such a system to test the theory. The atmosphere was simulated by latex spheres suspended in water and the ground by a nonuniform surface, half white and half black. A stable radiation source provided uniform illumination over the hydrosol. The upward radiance along a line orthogonal to the boundary of the two-halves field was recorded for different amounts of the hydrosol. The simulation is a well-defined radiative transfer experiment to test radiative transfer models involving nonuniform surfaces. Good agreement is obtained between the measured and theoretical results.
Numerical Study of Polarization-Dependent Focusing for a Bilayer Planar FSS Reflective Lens at Millimeter Wavelengths

In this paper, we numerically analyze the polarization-dependent focusing properties of a planar reflective lens formed by two parallel layers of nonuniform “gangbuster” surfaces (GSs) above a ground plane. Since these GSs consist of superdense arrays of thin finite-length parallel metallic wires, the desired phase patterns on such a lens surface are achieved by adjusting the lengths of these metallic wires for appropriate polarization components. In our analysis, we use the method of moments (MoM) and the transmission-lines analogy, along with the surface-equivalence theorem, to estimate the field intensity in the focal plane. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 40: 361–365, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.11382
Plasma cortisol levels in patients with septic shock

To investigate the endogenous adrenocortical response to sepsis, plasma cortisol concentrations were measured in 37 patients (53 +/- 3 yr of age) with septic shock. Patients were studied 11 +/- 2 h after shock commenced. Vasopressor therapy was required in 35 of 37 patients (median dopamine infusion rate of 11 micrograms/kg.min, range 3 to 74). Plasma cortisol concentrations were increased markedly (median 50.7 micrograms/dl, range 15.6 to 400) above normal values (10 to 20 micrograms/dl) in patients with septic shock. Neither patients who reversed their shock nor those who survived to hospital discharge had significantly different plasma cortisol concentrations from those who did not. Patients with Gram-positive infections had increased cortisol levels compared with those who had Gram-negative infections (median 83 micrograms/dl, range 32 to 400 vs. median 44 micrograms/dl, range 16 to 81, respectively; p less than .05). The source of infection, amount of vasopressors infused, and severity of shock were not associated with differences in cortisol concentrations. The length of time in shock before collection of the blood sample for measurements of cortisol and mean arterial pressure at the time of blood collection had significant but weak negative correlations with cortisol concentrations (p less than .05, rs = .37 and p less than .05, rs = -.40, respectively). We conclude that plasma cortisol concentrations are increased in patients with septic shock, but that the degree of increase is variable. This variability may, in part, be related to type of infection, length of time in shock, and BP at the time of blood sampling.(ABSTRACT TRUNCATED AT 250 WORDS)
Atmospheric pressure photoionization proton transfer for complex organic mixtures investigated by fourier transform ion cyclotron resonance mass spectrometry

To further clarify the role of dopant solvent in proton transfer in atmospheric pressure photoionization (APPI), we employ ultrahigh-resolution FT-ICR mass analysis to identify M+•, [M+H]+, [M-H]−, and [M+D]+ species in toluene or perdeuterotoluene for an equimolar mixture of five pyrrolic and pyridinic nitrogen heterocyclic model compounds, as well as for a complex organic mixture (Canadian Athabasca bitumen middle distillate). In the petroleum sample, the protons in the [M+H]+ species originate primarily from other components of the mixture itself, rather than from the toluene dopant. In contrast to electrospray ionization, in which basic (e.g., pyridinic) species protonate to form [M+H]+ positive ions and acidic (e.g., pyrrolic) species deprotonate to form [M-H]− negative ions, APPI generates ions from both basic and acidic species in a single positive-ion mass spectrum. Ultrahigh-resolution mass analysis (in this work, m/Δm50%=500,000, in which Δm50% is the mass spectral peak full width at half-maximum peak height) is needed to distinguish various close mass doublets: 13C versus 12CH (4.5 mDa), 13CH versus 12CD (2.9 mDa), and H2 versus D (1.5 mDa).
Use of Rorschach tests at the Nuremberg war crimes trial: A forgotten chapter in history of medicine

Seventy years ago, psychiatrists and psychologists had unusual access to the Nazi leaders awaiting trial by the International Military Tribunal in Nuremberg. Early leaders in the field of psychosomatic medicine were instrumental in facilitating these interviews as well as arranging for the administration of psychological testing with the Rorschach inkblot test. These observations were kept under wraps for decades and there remains controversy even now about what these Rorschachs revealed-demonic psychopaths or just morally corrupt individuals.
Low-Temperature Specific Heats of Zr-Ti, Zr-Hf, and Zr-Sc Alloys

The specific heats of hexagonal Zr-Ti, Zr-Hf, and Zr-Sc alloys were measured at 1.1 to 4.2\ifmmode^\circ\else\textdegree\fi{}K. Maxima in both the electronic specific-heat coefficient $\ensuremath{\gamma}$ and the superconducting transition temperature ${T}_{c}$ were observed at 60 at.% Ti in the Zr-Ti system. No superconductivity was found in the Zr-Sc system, although $\ensuremath{\gamma}$ rose to high values for pure scandium, and a minimum in $\ensuremath{\gamma}$ occurred near 10 at.% Sc. In the Zr-Hf system $\ensuremath{\gamma}$ was nearly linear between pure element values. The Debye temperatures ${\ensuremath{\Theta}}_{D}$, after correction for atomic mass and volume, deviate negatively near 60 at.% Ti in Ti-Zr, positively near hafnium in Zr-Hf, and in an S-type manner in Zr-Sc. The effects of scandium in depressing $\ensuremath{\gamma}$ in the zirconium-rich region are in qualitative agreement with dependence on electron/atom ratio indicated by earlier $B$-subgroup solute effects in zirconium-rich alloys. The $\ensuremath{\gamma}$ for Zr-Sc alloys, after a correction for phonon enhancement and with the assumption of a rigid band in the alloys, correlates fairly well with the electronic density of states for pure zirconium, calculated by Loucks. The rigid-band approximation, on the other hand, cannot explain the maxima in $\ensuremath{\gamma}$ and ${T}_{c}$ in Zr-Ti alloys, which involve no change of electron/atom ratio. Rather the maximum may arise from differences in the relative energies of the third and fourth bands in titanium and zirconium, with a crossing of these bands in the alloys. The $\ensuremath{\gamma}$ and ${T}_{c}$ are related to both the density of states and the electron-electron interactions, and although a clear separation of the two factors is not possible, a reasonable interpretation can be made, assuming that the electron-phonon interaction is nearly constant.
The effect of the location of an in-line tube bundle on orifice flowmeter performance

Abstract The Gas Research Institute has sponsored many significant flow measurement studies at the National Institute of Standards and Technology. The main thrust of the 1988 research project was to determine the effect of the location of an in-line tube bundle flow conditioner on the orifice discharge coefficient. An in-line bundle was place at four locations-7, 12, 17 and 17 pipe diameters upstream of the orifice plate in a 100 mm (4 inch) orifice meter. This research has determined that if the in-line tube bundle is placed at 7 pipe diameters, the minimum distance specified in the flow measurement standards for a 0.75 beta ratio plate, as much as 1% error in the discharge coefficient occurs. At 17 pipe diameters, the discharge coefficients of all the beta ratios are statistically the same as would be determined in ‘ideal’ conditions. These new experimental data will help to improve the current flow measurement standards and suggest the direction of future reserach.
Transcriptome meta-analysis reveals a central role for sex steroids in the degeneration of hippocampal neurons in Alzheimer’s disease

Alzheimer’s disease is the most prevalent form of dementia. While a number of transcriptomic studies have been performed on the brains of Alzheimer’s specimens, no clear picture has emerged on the basis of neuronal transcriptional alterations linked to the disease. Therefore we performed a meta-analysis of studies comparing hippocampal neurons in Alzheimer’s disease to controls. Homeostatic processes, encompassing control of gene expression, apoptosis, and protein synthesis, were identified as disrupted during Alzheimer’s disease. Focusing on the genes carrying out these functions, a protein-protein interaction network was produced for graph theory and cluster exploration. This approach identified the androgen and estrogen receptors as key components and regulators of the disrupted homeostatic processes. Our systems biology approach was able to identify the importance of the androgen and estrogen receptors in not only homeostatic cellular processes but also the role of other highly central genes in Alzheimer’s neuronal dysfunction. This is important due to the controversies and current work concerning hormone replacement therapy in postmenopausal women, and possibly men, as preventative approaches to ward off this neurodegenerative disorder.
MCC-555-induced NAG-1 expression is mediated in part by KLF4.

Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a central role in cell differentiation, metabolism and tumorigenesis. We have investigated the therapeutic properties of 5-[[6-[(2-fluorophenyl)-methoxy]-2-napthalenyl]-methyl]-2,4-thiazolidinedione (MCC-555) a PPARgamma agonist in human colorectal cancer cells. To elucidate the molecular mechanism(s), by which MCC-555 exerts its effects on the human colorectal cancer cells, we have analyzed the expression of two pro-apoptotic proteins, Kruppel-like factor 4 (KLF4) and nonsteroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1). MCC-555-induced expression of the transcription factor, KLF-4 was blocked by a PPARgamma specific antagonist GW9662 in PPARgamma-dependent manner in HCT-116 cells. We further identified a new KLF4 target gene NAG-1, which shows a pro-apoptotic activity. We confirmed that PPARgamma agonists-induced NAG-1 expression was abolished using KLF4 siRNA in HCT-116 cells. Subsequently, KLF4 expression enhances the NAG-1 promoter activity in HCT-116 cells, and functional KLF4 binding sites in the NAG-1 promoter were also identified. MCC-555, a PPARgamma agonist induced the expression of Klf4 mRNA and protein in murine intestinal tumors from MCC-555-treated mice, as assessed by RT-PCR and immunohistochemistry. This study shows that PPARgamma agonists up-regulate KLF4 expression in receptor-dependent manner, and KLF4 was identified as a novel transcription factor that controls NAG-1 promoter activity in human and mouse colorectal cancers.
Intracerebral Hemorrhages Associated With Neurointerventional Procedures Using a Combination of Antithrombotic Agents Including Abciximab

Background— We report the occurrence of fatal intracerebral hemorrhage associated with using a combination of antithrombotic agents, including abciximab, in patients undergoing neurointerventional procedures. Summary of Report— Seven patients (average age 60, range 46 to 73 years) developed fatal intracerebral hemorrhages associated with neurointerventional procedures and the use of intravenous abciximab. The procedures included angioplasty and stent placement in the cervical internal carotid artery (n=4), angioplasty of the intracranial internal carotid artery (n=1), and angioplasty of the middle cerebral artery (n=2). Clinical deterioration was observed within 1 hour of the procedure in 5 patients and 7 and 8 hours after the procedure, respectively, in the remaining 2 patients. All patients had received heparin and clopidogrel; 6 had also received aspirin. Conclusions— Intracerebral hemorrhages can occur after neurointerventional procedures in patients with recent cerebral ischemic events, particularly ...
New solitons and kink solutions for the Gardner equation

Abstract The Gardner equation, also called combined KdV–mKdV equation, is studied. New hyperbolic ansatze are proposed to derive solitons solutions. The tanh method is used as well to obtain kink solutions.
Social Work Practice in the Addictions, by Michael G. Vaughn and Brian E. Perron (Eds.)

Addiction intersects nearly every social work practice arena; consequences of drug and alcohol abuse are pervasive among populations involved with child welfare, mental health, and criminal justice...
Injuriousness of bordeaux mixture

Although Bordeaux mixture was known to reduce potato yields in the absence of pests, it has been demonstrated that the yields are also reduced where pests are serious. In such cases the dwarfing effect is masked by pest control.
"Activated"-RecA protein affinity chromatography of LexA repressor and other SOS-regulated proteins.

Abstract We have developed an affinity column to study the interaction of LexA repressor and other substrates with the activated form of RecA protein. Nucleoprotein complexes of RecA protein, (dT)25-30, and adenosine 5'-[gamma-S]thio-triphosphate were formed in solution and bound to RecA protein-agarose columns. These "activated"-RecA nucleoprotein complexes were retained by strong hydrophobic interactions. Purified LexA protein bound tightly to these activated RecA columns, whereas the LexA protein bound poorly to RecA-agarose alone. Once bound, LexA protein underwent specific proteolysis, and the fragments were released from the complex. The mutant LexA protein, LexA-SA119, which cannot carry out self-cleavage or RecA-mediated cleavage in solution, bound efficiently to the activated RecA column but was not cleaved, indicating that these columns can be used to identify residues involved in RecA-LexA binding. As an example of this use, nucleoprotein complexes were prepared using the RecA430 protein. In vivo the recA430 mutation blocks induction of the SOS response. LexA protein was not efficiently retained on the immobilized RecA430 complexes, suggesting that Gly-204 is required for efficient repressor binding. These results show that activated RecA affinity columns can be used to investigate the binding and cleaving properties of mutationally altered RecA and LexA proteins. Additionally, these activated RecA columns have been used to investigate binding interactions of phage lambda repressor, as well as the UmuC protein, which is required for chemical mutagenesis.
Composite anomalies in supergravity

Abstract It is argued that the vectors of N -extended supergravity theories should be thought of as self-dual tensor fields, and that they contribute to the anomalies of the (S)U( N ) currents Some implications of these anomalies are discussed. The total anomaly is found to vanish for N > 4, so the composite gauging scenario is consistent in these cases.
Book review of "The Ethics of Coercion in Mass Casualty Medicine" by Griffin Trotter MD, PhD

Public health ethics is neither taught widely in medical schools or schools of public health in the US or around the world. It is not surprising that health care professionals are particularly challenged when faced with ethical questions which extend beyond safeguarding the interests of their individual patients to matters that affect overall public good. The perceived threat of terror after September 11 2007, the anthrax attacks and the Katrina debacle are recent circumstances which may result in coercion. These have piqued the interest of medical professionals and the general public on public health ethics. The Ethics of Coercion in Mass Casualty Medicine written by Griffin Trotter MD, PhD attempts to fill a timely void in this area by examining the ethics of coercion in times of public health disasters.
Extending mathematical principles of reinforcement into the domain of behavioral pharmacology.

Abstract Mathematical principles of reinforcement (MPR) attempts to integrate the empirical laws of reinforcement schedules that have accumulated over the decades. MPR is based on three principles: incentives excite behavior; there are temporal constraints on responding; and coupling of responses to reinforcers strengthens behavior [Behav. Brain Sci. 17 (1994) 105]. In the present paper MPR is extended into the domain of behavioral pharmacology, specifically to model the effects of d -amphetamine on operant behavior. In Experiment 1a, a five-component multiple fixed-ratio schedule was designed to generate behavioral baselines that were subsequently used to assess drug effect. In Experiments 1b and 1c, the quality and quantity of reinforcer were manipulated. The data generated by the three experiments were consistent with MPR. In Experiment 2, MPR was used to model the effects of d -amphetamine on rats responding under the five-component multiple fixed-ratio schedule. According to the model, the rate-decreasing effects of d -amphetamine were due primarily to motor disruption and secondarily to increased impulsivity; at the highest dosages, d -amphetamine also may have decreased the incentive value of food.
State of Water in Hydrating Tricalcium Silicate and Portland Cement Pastes as Measured by Quasi-Elastic Neutron Scattering

Quasi-elastic neutron scattering (QENS) was used to monitor the state of water in portland cement and tricalcium silicate pastes during the first 2 days of hydration at three different temperatures. By applying a double-Lorentzian rather than a single-Lorentzian fitting function, the QENS signal from water at a given hydration time was divided into three separate populations arising from liquid water, chemically bound water, and constrained water. The constrained water population consisted of water adsorbed on surfaces and contained in very small (<10 nm) pores, and could be associated primarily with the calcium-silicate-hydrate (C-S-H) phase. The rate of increase in the chemically bound water population closely followed the exothermic heat output, while the constrained water population increased more rapidly during the first several hours of hydration and then leveled off.
Effect of Salt Shock on Stability of λimm434 Lysogens

The affinities of the bacteriophage 434 repressor for its various binding sites depend on the type and/or concentration of monovalent cations. The ability of bacteriophage 434 repressor to govern the lysis-lysogeny decision depends on the DNA binding activities of the phage's cI repressor protein. We wished to determine whether changes in the intracellular ionic environment influence the lysis-lysogeny decision of the bacteriophage lambda(imm434). Our findings show that the ionic composition within bacterial cells varies with the cation concentration in the growth media. When lambda(imm434) lysogens were grown to mid-log or stationary phase and subsequently incubated in media with increasing monovalent salt concentrations, we observed a salt concentration-dependent increase in the frequency of bacteriophage spontaneous induction. We also found that the frequency of spontaneous induction varied with the type of monovalent cation in the medium. The salt-dependent increase in phage production was unaffected by a recA mutation. These findings indicate that the salt-dependent increase in phage production is not caused by activation of the SOS pathway. Instead, our evidence suggests that salt stress induces this lysogenic bacteriophage by interfering with 434 repressor-DNA interactions. We speculate that the salt-dependent increase in spontaneous induction is due to a direct effect on the repressor's affinity for DNA. Regardless of the precise mechanism, our findings demonstrate that salt stress can regulate the phage lysis-lysogeny switch.
Within-group social bonds in white-faced saki monkeys (Pithecia pithecia) display male-female pair preference.

White-faced saki monkeys (Pithecia pithecia) lack most of the behavioral and physical traits typical of primate monogamy [Fuentes, 1999]. In order to determine if social bonds in this species reflect patterns displayed by pair-bonded groups or larger multimale–multifemale groups, we draw on 17 months of data collected on wild white-faced sakis at Brownsberg Nature Park, Suriname. We analyzed within-group social bonds for three habituated groups (one two-adult and two multiadult groups) by measuring grooming, proximity, and approach/leave patterns between adult and subadult group members. We found that both two-adult and multiadult groups showed significantly stronger social bonds between a single male–female dyad within each group (deemed “primary dyads”). In all three groups, primary dyads were composed of the oldest adult male and a breeding female. These pairs had significantly higher levels of grooming than other within-group dyads and were also in close proximity (<1 m) more often than nonprimary dyads. Grooming in primary dyads was nonreciprocal, and consistently biased toward female investment. Grooming patterns in nonprimary dyads varied, but were often more reciprocal. Grooming and proximity of the primary dyad also changed in relation to infant development. Our results suggest that while white-faced sakis do not show behavioral and physical traits typical of monogamy or pair-bonding, social bonds are strongest between a single male–female pair. Pitheciine social systems range from small group monogamy in Callicebus to large multimale–multifemale groups in Chiropotes and Cacajao. As the middle taxon in this platyrrhine radiation, behavioral strategies of white-faced sakis provide a model for how social bonds and affiliation could be influenced by and affect the evolution of larger group size in primates. Am. J. Primatol. 73:1051–1061, 2011. © 2011 Wiley-Liss, Inc.
PSYCHOLOGY AND THE STUDY OF MARITAL PROCESSES

▪ Abstract The divorce rate in the United States is extremely high. It is estimated that between 50% and 67% of first marriages end in divorce. For second marriages, failure rates are even higher. There are strong negative consequences to separation and divorce on the mental and physical health of both spouses, including increased risk for psychopathology, increased rates of automobile accidents, and increased incidence of physical illness, suicide, violence, homicide, significant immunosuppression, and mortality from diseases. In children, marital distress, conflict, and disruption are associated with depression, withdrawal, poor social competence, health problems, poor academic performance, and a variety of conduct-related difficulties. Though intervention techniques might be expected to reduce these grim statistics, our best scholars have concluded that marital therapy is at a practical and theoretical impasse. This article discusses the progress of research on the study of marriage.
Lessons learned from pesticide drift: a call to bring production agriculture, farm labor, and social justice back into agrifood research and activism

I use the case of pesticide drift to discuss the neoliberal shift in agrifood activism and its implications for public health and social justice. I argue that the benefits of this shift have been achieved at the cost of privileging certain bodies and spaces over others and absolving the state of its responsibility to ensure the conditions of social justice. I use this critical intervention as a means of introducing several opportunities for strengthening agrifood research and advocacy. First, I call for increased critical attention to production agriculture and the regulatory arena. Second, I call for increased attention to ‘social justice’ within the food system, emphasizing the need to rekindle research on the immigrant farm labor force.
Rapid diversification of the cotton genus (Gossypium: Malvaceae) revealed by analysis of sixteen nuclear and chloroplast genes.

formation of the genus. Maximum likelihood analysis of nuclear synonymous sites shows that this radiation occurred within a time span equivalent to 17% of the time since the separation of Gossypium from its nearest extant relatives in the genera Kokia and Gossypioides. Chloroplast and nuclear phylogenies differ significantly with respect to resolution of the basal divergence in the genus and to interrelationships among African cottons. This incongruence is due to limited character evolution in cpDNA and either previously unsuspected hybridization or unreliable phylogenetic performance of the cpDNA characters. This study highlights the necessity of using multiple, independent data sets for resolving phylogenetic relationships of rapidly diverged lineages.
Efficiency of III-V compound electro-optic phase modulators

The efficiency of electro-optic phase modulators built in the form of multilayer slab waveguides depends on the waveguide design. Analytical expressions have been developed for the effectiveness of such PIN and metal-IN phase-modulator waveguides as functions of design parameters.
Assessment of Delaware and Groningen effects on dual-laterolog measurements with a self-adaptive hp finite-element method

Wedescribenumericalsimulationsofanomalousdual-laterolog DLL borehole measurements, including Delaware and Groningen effects. Both effects give rise to abnormally high readings of DLL measurements under extreme logging conditions. Specifically, a low resistive bed below a highly resistivelayercauseselectricalcurrentstoconcentratewithin the borehole, which generates a negative potential at the referenceelectrodeand,consequently,anabnormallyhighreading in DLL measurements. These effects are exacerbated by thepresenceofcasingand/oratnonzerofrequencies.Simulationsareperformedwitha2Dgoal-oriented,high-order,selfadaptive hp finite-element method together with an embedded postprocessing method. Results indicate that the presence of electrodesB andN is critical for proper simulation of Delaware effects on DLL measurements. Delaware effects onDLLlogsdecreaseasthecurrentreturnelectrodeismoved farther away from either the logging point or the borehole. The frequency of operation also affects deep laterolog measurements,generatingtheso-calledGroningeneffect.
Picosecond measurements by free-running electro-optic sampling

Timing jitter in passively mode-locked lasers is an important limit in electro-optic measurements. We demonstrate picosecond resolution electro-optic sampling measurements in the presence of nanosecond-scale timing jitter. Timing-jitter distortion is eliminated by scanning at a large offset frequency and triggering on the resulting waveform. Frequency jitter and the effects of triggering on a noisy signal are analyzed. Using this method, 1.5 ps fall times are measured on electronically generated shock waveforms. >
IL-10 Inhibits Mature Fibrotic Granuloma Formation during Mycobacterium tuberculosis Infection

Protective immunity and latent Mycobacterium tuberculosis infection in humans are associated with the formation of mature protective granulomas within the lung. Unfortunately, understanding the importance of such structures has been hindered by the lack of small-animal models that can develop mature granulomas. In this article, we describe for the first time, to our knowledge, the formation of mature, fibrotic M. tuberculosis-containing pulmonary granulomas in a mouse model of IL-10 deficiency (CBA/J IL-10(-/-)). Long-term control of M. tuberculosis infection in the absence of IL-10 was also associated with an early and enhanced capacity for Ag presentation and a significant increase in the generation of multifunctional T cells. Although IL-10 deficiency is known to enhance Th1 immune responses in general, we demonstrate in this study using transient anti-IL-10R treatment that it is the presence of IL-10 in vivo during the first month of M. tuberculosis infection that plays a definitive role in the inhibition of optimum protective immunity that can establish the environment for mature granuloma formation. Although the importance of IL-10 during M. tuberculosis infection has been debated, our data demonstrate that in CBA/J mice, IL-10 plays a significant early inhibitory role in preventing the development of protective immunity associated with containment of M. tuberculosis infection.
Wind-driven surficial oxygen transfer and dinitrogen gas emission from treatment lagoons.

Surficial oxygen transfer plays an important role, when analyzing the complex biochemical and physical processes responsible for ammonia and dinitrogen gas emission in animal waste treatment lagoons. This paper analyzes if currently known nitrogen biochemical pathways can explain the enigmatic dinitrogen gas emissions recently observed from the treatment lagoons, based on the amount of wind-driven oxygen that can be transferred through the air-water interface. The stoichiometric amounts of the maximum dinitrogen gas production potential per unit mass of O2 transferred were calculated according to three most likely biochemical pathways for ammonia removal in the treatment lagoons—classical nitrification-denitrification, partial nitrification-denitrification, and partial nitrification-Anammox. Partial nitrification-Anammox pathway would produce the largest N2 emission, followed by partial nitrification-denitrification pathway, then by classical nitrification-denitrification pathway. In order to estimate sto...
MMP28 promotes macrophage polarization toward M2 cells and augments pulmonary fibrosis

Members of the MMP family function in various processes of innate immunity, particularly in controlling important steps in leukocyte trafficking and activation. MMP28 (epilysin) is a member of this family of proteinases, and we have found that MMP28 is expressed by macrophages and regulates their recruitment to the lung. We hypothesized that MMP28 regulates other key macrophage responses, such as macrophage polarization. Furthermore, we hypothesized that these MMP28-dependent changes in macrophage polarization would alter fibrotic responses in the lung. We examined the gene expression changes in WT and Mmp28-/- BMDMs, stimulated with LPS or IL-4/IL-13 to promote M1 and M2 cells, respectively. We also collected macrophages from the lungs of Pseudomonas aeruginosa-exposed WT and Mmp28-/- mice to evaluate changes in macrophage polarization. Lastly, we evaluated the macrophage polarization phenotypes during bleomycin-induced pulmonary fibrosis in WT and Mmp28-/- mice and assessed mice for differences in weight loss and total collagen levels. We found that MMP28 dampens proinflammatory macrophage function and promots M2 programming. In both in vivo models, we found deficits in M2 polarization in Mmp28-/- mice. In bleomycin-induced lung injury, these changes were associated with reduced fibrosis. MMP28 is an important regulator of macrophage polarization, promoting M2 function. Loss of MMP28 results in reduced M2 polarization and protection from bleomycin-induced fibrosis. These findings highlight a novel role for MMP28 in macrophage biology and pulmonary disease.
Deficiency of IL-17A, but not the prototypical Th17 transcription factor RORγt, decreases murine spontaneous intestinal tumorigenesis

While inflammation has been associated with the development and progression of colorectal cancer, the exact role of the inflammatory Th17 pathway remains unclear. In this study, we aimed to determine the relative importance of IL-17A and the master regulator of the Th17 pathway, the transcription factor RORγt, in the sporadic intestinal neoplasia of APC(MIN/+) mice and in human colorectal cancer. We show that levels of IL-17A are increased in human colon cancer as compared to adjacent uninvolved colon. Similarly, naive helper T cells from colorectal cancer patients are more inducible into the Th17 pathway. Furthermore, IL-17A, IL-21, IL-22, and IL-23 are all demonstrated to be directly mitogenic to human colorectal cancer cell lines. Nevertheless, deficiency of IL-17A but not RORγt is associated with decreased spontaneous intestinal tumorigenesis in the APC(MIN/+) mouse model, despite the fact that helper T cells from RORγt-deficient APC(MIN/+) mice do not secrete IL-17A when subjected to Th17-polarizing conditions and that Il17a expression is decreased in the intestine of RORγt-deficient APC(MIN/+) mice. Differential expression of Th17-associated cytokines between IL-17A-deficient and RORγt-deficient APC(MIN/+) mice may explain the difference in adenoma development.
Using deductive knowledge to improve cryptographic protocol verification

An effective representation of principals' knowledge can greatly improve the efficiency of cryptographic protocol analysis. In this paper, we propose a mechanism to represent the deductive knowledge contained in a set of terms. Using Dolev-Yao model as an example, we design two algorithms to generate the knowledge representation and derive terms, respectively. We prove that using our knowledge representation, a principal can derive a term by using only constructive operations. To demonstrate the advantages of the proposed approach, we integrate it with Athena to build a new protocol verifier. The new approach will drastically reduce the number of states that are generated and analyzed during protocol verification. Experiments on several cryptographic protocols widely used for evaluating protocol verifiers demonstrate the improvements.
Stability analysis of power systems by Lyapunov's direct method

The Lyapunov direct method is on the verge of being implemented for assessment of online dynamic security. The main bottleneck has been in the proper characterization of the stability boundary and defining the fault-dependent region of attraction locally around the controlling unstable equilibrium points. Now there is a better understanding of this issue, and hence, a number of algorithms have been proposed. Improved generating-unit models and transmission-network models are now being included in the technique. An overview is presented of the theory, practical implementation, and future research. >
Speech enhancement using a frequency-specific composite Wiener function

This paper introduces a new speech enhancement approach based on the design of a frequency-specific composite gain function for Wiener filtering. Motivated by the recently established finding that the acoustic cues at low frequencies can improve speech recognition in noise by the combined electric and acoustic stimulation technique, a less aggressive gain function is applied to replace the Wiener filter's conventional rigid gain function at low frequencies. With this modification, the proposed approach is able to recover more low frequency (LF) components and enhance the speech quality in noisy environments. An adaptive procedure is utilized to determine the low frequency boundary. Objective evaluation, based on the PESQ measure, revealed that the proposed approach with adaptive LF boundary improved significantly the PESQ scores compared to the scores obtained with the conventional Wiener filter in steady-state noise, white noise and babble interference conditions. Speech quality was also found to be significantly enhanced in the car noise conditions when the less aggressive gain function was selectively applied only to the consonants.
Chronic AT1 receptor blockade normalizes NMDA-mediated changes in renal sympathetic nerve activity and NR1 expression within the PVN in rats with heart failure

Exercise training normalizes enhanced glutamatergic mechanisms within the paraventricular nucleus (PVN) concomitant with the normalization of increased plasma ANG II levels in rats with heart failu...
Sparse decomposition of transformation-invariant signals with continuous basis pursuit

Consider the decomposition of a signal into features that undergo transformations drawn from a continuous family. Current methods discretely sample the transformations and apply sparse recovery methods to the resulting finite dictionary. These methods do not exploit the underlying continuous structure, thereby limiting the ability to produce sparse solutions. Instead, we employ interpolation functions which linearly approximate the manifold of scaled and transformed features. Coefficients are interpreted as interpolation weights, and we formulate a convex optimization problem for obtaining them, enforcing both reconstruction accuracy and sparsity. We compare our method, which we call continuous basis pursuit (CBP) with the standard basis pursuit approach on a sparse deconvolution task. CBP yields substantially sparser solutions without sacrificing accuracy, and does so with a smaller dictionary. We conclude that for signals generated by transformation-invariant processes, a representation that explicitly accommodates the transformation(s) can yield sparser and more interpretable decompositions.
PAST INSIGHTS, FUTURE PROMISES Race and Health in the Twenty-first Century

Over one hundred years ago, W. E. B. Du Bois ~1899! documented large, pervasive, and persistent racial inequities in health. While the current demography of racial groups in the United States is radically different compared to the times when Du Bois first discussed issues of race and health, many of the significant developments in research on racial differences in health in the last century can be traced to his seminal work ~Williams and Sternthal, 2010!. Du Bois recognized that the limited access to economic resources and the social marginalization of some racial groups could have dire social, physical, and psychological consequences for them. Current research studies continue to document that racial groups with a long history characterized by economic exploitation and geographic marginalization—Blacks or African Americans, American Indians, and Native Hawaiians and other Pacific Islanders—have markedly poor health outcomes compared to the dominant White population. Immigrant Asians and Hispanics tend to have better health than the U.S. average, but their health tends to worsen over time and across subsequent generations. Despite Du Bois’s prescience and the advances made by contemporary researchers, there are many substantive theoretical and methodological challenges confronting scholars who study the health of diverse racial and ethnic groups. This special issue of the Du Bois Review provides a state-of-the-art overview of some of these unanswered questions and critical research directions for the study of racial inequality in health. We have organized the papers in this volume into five sections. The first section provides an overview of the current status of research on the uneven distribution of health and illness in society and identifies some key issues that need to be addressed to accurately portray the patterns of racial inequality. Hummer and Chin
Reduced-reference image quality assessment using a wavelet-domain natural image statistic model

Reduced-reference (RR) image quality measures aim to predict the visual quality of distorted images with only partial information about the reference images. In this paper, we propose an RR quality assessment method based on a natural image statistic model in the wavelet transform domain. In particular, we observe that the marginal distribution of wavelet coefficients changes in different ways for different types of image distortions. To quantify such changes, we estimate the Kullback-Leibler distance between the marginal distributions of wavelet coefficients of the reference and distorted images. A generalized Gaussian model is employed to summarize the marginal distribution of wavelet coefficients of the reference image, so that only a relatively small number of RR features are needed for the evaluation of image quality. The proposed method is easy to implement and computationally efficient. In addition, we find that many well-known types of image distortion lead to significant changes in wavelet coefficient histograms, and thus are readily detectable by our measure. The algorithm is tested with subjective ratings of a large image database that contains images corrupted with a wide variety of distortion types.
Measuring MPI send and receive overhead and application availability in high performance network interfaces

In evaluating new high-speed network interfaces, the usual metrics of latency and bandwidth are commonly measured and reported. There are numerous other message passing characteristics that can have a dramatic effect on application performance that should be analyzed when evaluating a new interconnect. One such metric is overhead, which dictates the networks ability to allow the application to perform non-message passing work while a transfer is taking place. A method for measuring overhead, and hence calculating application availability, is presented. Results for several next-generation network interfaces are also presented.
Patient Satisfaction, Chronic Pain, and Functional Status following Laparoscopic Ventral Hernia Repair

Background Ventral hernia repairs are one of the most common surgeries performed. Symptoms are the most common motivation for repair. Unfortunately, outcomes of repair are typically measured in recurrence and infection rather than patient focused results. We correlated factors associated with decreased patient satisfaction, chronic pain, and diminished functional status following laparoscopic ventral hernia repair (LVHR)
Anatomical retro-apical technique of synchronous (posterior and anterior) urethral transection: a novel approach for ameliorating apical margin positivity during robotic radical prostatectomy.

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To describe a novel synchronous approach to apical dissection during robotic-assisted radical prostatectomy (RARP) which augments circumferential visual appreciation of the prostatic apex and membranous urethra anatomy, and assess its effect on apical margin positivity. PATIENTS AND METHODS Positive surgical margins (PSM) during RP predispose to earlier biochemical recurrence, and occur most frequently at the prostatic apex. Conventional apical transection after early ligation of the dorsal venous complex (DVC) remains suboptimal, as this approach obscures visualization of the intersection between prostatic apex and membranous urethra, leading to inadvertent apical capsulotomy and eventual margin positivity. A synchronous urethral transection commenced via a retro-apical approach was adopted in 209 consecutive patients undergoing RARP by one surgeon (A.T.) between April to September 2009. The apical margin rates for this group were compared with those of 1665 previous patients who received conventional urethral transection via an anterior approach after DVC ligation. Outcomes were adjusted for differences in clinicopathological variables. All RP specimens were processed according to institutional protocols, and examined by dedicated genitourinary pathologists. The location of PSMs was identified as apex, posterior, posterolateral, bladder neck, anterior, base, or multifocal. RESULTS Patients receiving synchronous urethral transection had significantly lower apical PSM rates than the control group (1.4% vs 4.4%, P= 0.04). This marked improvement in the retro-apical group occurred despite a significantly higher incidence of aggressive cancer (≥pT3a) documented on final specimen pathology (16% vs 10%, P= 0.027).Technical difficulty was encountered in three of 209 study patients, in whom urethral transection had to be completed using the classic anterior approach. CONCLUSION Improved circumferential visualization of the prostatic apex, membranous urethra and their anatomical intersection facilitates precise dissection of the apex and its surrounding neural scaffold, and optimizes membranous urethral preservation. This has significantly ameliorated apical PSM rates in patients undergoing RARP, despite having to deal with more aggressive cancer on final specimen pathology.
S-Nitrosylation in Organs of Mice Exposed to Low or High Doses of γ-Rays: The Modulating Effect of Iodine Contrast Agent at a Low Radiation Dose.

The covalent addition of nitric oxide (NO•) onto cysteine thiols, or S-nitrosylation, modulates the activity of key signaling proteins. The dysregulation of normal S-nitrosylation contributes to degenerative conditions and to cancer. To gain insight into the biochemical changes induced by low-dose ionizing radiation, we determined global S-nitrosylation by the “biotin switch” assay coupled with mass spectrometry analyses in organs of C57BL/6J mice exposed to acute 0.1 Gy of 137Cs γ-rays. The dose of radiation was delivered to the whole body in the presence or absence of iopamidol, an iodinated contrast agent used during radiological examinations. To investigate whether similar or distinct nitrosylation patterns are induced following high-dose irradiation, mice were exposed in parallel to acute 4 Gy of 137Cs γ rays. Analysis of modulated S-nitrosothiols (SNO-proteins) in freshly-harvested organs of animals sacrificed 13 days after irradiation revealed radiation dose- and contrast agent-dependent changes. The major results were as follows: (i) iopamidol alone had significant effects on S-nitrosylation in brain, lung and liver; (ii) relative to the control, exposure to 0.1 Gy without iopamidol resulted in statistically-significant SNO changes in proteins that differ in molecular weight in liver, lung, brain and blood plasma; (iii) iopamidol enhanced the decrease in S-nitrosylation induced by 0.1 Gy in brain; (iv) whereas a decrease in S-nitrosylation occurred at 0.1 Gy for proteins of ~50 kDa in brain and for proteins of ~37 kDa in liver, an increase was detected at 4 Gy in both organs; (v) mass spectrometry analyses of nitrosylated proteins in brain revealed differential modulation of SNO proteins (e.g., sodium/potassium-transporting ATPase subunit beta-1; beta tubulins; ADP-ribosylation factor 5) by low- and high-dose irradiation; and (vi) ingenuity pathway analysis identified major signaling networks to be modulated, in particular the neuronal nitric oxide synthase signaling pathway was differentially modulated by low- and high-dose γ-irradiation.
Enteral infusions of elemental diets stimulate pancreatic enzyme secretion in normal subjects but not in patients with acute pancreatitis

Enteral infusions of elemental diets stimulate pancreatic enzyme secretion in normal subjects but not in patients with acute pancreatitis