cssi/SciSciGPT-SciSciNet huggingface dataset:
Proteasome Inhibition Attenuates Infarct Size and Preserves Cardiac Function in a Murine Model of Myocardial Ischemia-Reperfusion Injury

Background Despite improvements in protection, myocardial ischemia-reperfusion remains an important cause of cardiac dysfunction. Multiple strategies exist experimentally; few are clinically accessible. Nuclear factor kappa-B (NF-κB) is a transcription factor central to the inflammatory response and is implicated in reperfusion injury. Its activation relies on the degradation of its inhibitory molecule, IκB, by the 20S proteasome. We hypothesized that proteasome inhibition would decrease the extent of infarction after temporary coronary occlusion. Methods C57Bl6 mice received a specific proteasome inhibitor (PS-519) and were subjected to 30 minutes of transient occlusion of the left anterior descending artery. After 24 hours of reperfusion, echocardiography was performed to evaluate ventricular function and hearts were excised and analyzed for infarct size, areas at risk, and molecular markers of injury and NF-κB activation. Results Compared with controls, PS-519 delivered before left anterior descending (coronary artery) ligation reduced the area of infarct without a change in the area at risk. Similar results were seen with PS-519 delivered at reperfusion. Echocardiography demonstrated a relative reduction in fractional shortening in the vehicle group of 9.8% versus only 2.7% in the PS-519 group. Markers of myocardial stress and injury were accordingly suppressed with PS-519. These physiologic findings were associated with PS-519 decreasing p65 and TNF expression while preserving IκBα expression. Conclusions In this murine infarct model PS-519 significantly preserved regional myocardial function, reduced the size of infarction, and attenuated expression of myocardial inflammatory response genes. These data demonstrate that a currently available and well-tolerated inhibitor of NF-κB can decrease the risk of myocardial injury associated with ischemia-reperfusion.
Optische Spaltung des 5-Hydroxy-DL-Tryptophans

A novel method for the resolution of 5-hydroxy-DL-tryptophan is described. Successive treatment of N-Benzyloxycarbonyl-5-benzyloxy-DL-tryptophan with the stereoisomeric bases quinidine and quinine precipitates directly the corresponding salts of the L- and D-antipodes.
Effects of Soaking Treatments and Cooking Upon Selected B-Vitamins and the Quality of Blackeyed Peas

Commercially harvested blackeyed peas (cultivar Crimson) were divided into lots soaked 3 hr in 3 buffers (citrate, phosphate, bicarbonate) at 4 pH's (4.5, 5.5, 7.0, 8.5) with and without added ethylenediaminetetracetate (EDTA). Soaked peas were cooked by boiling and steaming. Vitamins, including pantothenic acid, niacin, and folacin, were more consistently stable to bicarbonate buffer, and were not affected by EDTA. None of the buffers showed a consistently negative effect on all vitamins lost. Soaking in phosphate and citrate buffers, especially at pH 4.5, decreased discoloration. Steam cooking retained more B-vitamins in peas, while boiling resulted in more tender peas. Soaking peas in buffers prior to pre-cooking reduced the time required for cooking.
Improving Spelling Performance By Imitating A Child's Errors

Various self-correction procedures have been used to improve spelling performance oflearning handicapped students, but few studies have been concerned with qualitative changes in spelling attempts during intervention. This study focused on both the qualitative and quantitative changes in spelling performance of a learning disabled student whe a contingent imitation and modeling procedure was used. Sufficient number of trials were allowed to assure learning. Results indicated significant improvement in the number of correctly spelled words. On a test for transfer, using orthographically and phonetically similar words, performance was slightly improved over pretest performance on the training list. However, analysis of error quality revealed substantial improvement in ability. Effectiveness of the imitation and modeling procedures was replicated. The data also extended previous work by providing a basis for explaining effectiveness of these procedures for spelling instruction. The usefulness of a problem-so...
Application of multiplex ligation-dependent probe amplification to screen for β-globin cluster deletions: detection of two novel deletions in a multi ethnic population.

Hereditary persistence of fetal hemoglobin (HPFH) and δβ-thalassemia (δβ-thal) are heterogeneous disorders caused by deletions within the β-globin gene cluster. When combined with other β-thal mutations or structural hemoglobin (Hb) variants, these deletions give rise to clinical phenotypes ranging from an asymptomatic condition to β-thal major (β-TM). Overlap in hematological parameters and variability in expression of Hbs A2 and F make molecular testing necessary to distinguish clinically relevant deletions. Multiplex ligation-dependent probe amplification (MLPA) was used to screen for β-globin gene cluster deletions in 49 unresolved samples referred for a suspected β-thal anomaly. The 1.39 kb Black β0, 3.5 kb Thai β0, 118 kb Filipino β0, 11.8 kb Black (δβ)0, 13.4 kb Sicilian (δβ)0, 35.8 kb Black (Aγδβ)0, Hb Lepore-Boston-Washington (Hb LBW) and HPFH-2 deletions, and two novel deletions, a 61.7 kb Pakistani β0 deletion and an (Aγδβ)0 deletion, were identified in 15 cases. Detection of both known and unk...
The 15-kDa selenoprotein (Sep15): functional analysis and role in cancer

The 15-kDa selenoprotein (Sep15) was identified several years ago as a protein of unknown function. In recent years, several lines of evidence implicated Sep15 in the effect of dietary selenium in cancer prevention. These lines of evidence include: 1) protein expression patterns in normal and malignant cells; 2) identification of polymorphic sites that regulate Sep15 levels and differentially respond to selenium supplementation; 3) location of the Sep15 gene in the human genome; and 4) correlation between Sep 15 haplotype and susceptibility to cancer. Functional analyses revealed a specific interaction between Sep15 and a protein folding sensor in the endoplasmic reticulum of mammalian cells and identified Sep15 as a novel thioredoxin-like fold redox regulator. Sep15 defines a new protein family that occurs in several organisms from green algae to mammals and also contains selenoprotein M (Se1M) and a recently identified fish-specific selenoprotein Fep15.
CLOCK deubiquitylation by USP8 inhibits CLK/CYC transcription in Drosophila

A conserved transcriptional feedback loop underlies animal circadian rhythms. In Drosophila, the transcription factors CLOCK (CLK) and CYCLE (CYC) activate the transcription of direct target genes like period (per) and timeless (tim). They encode the proteins PER and TIM, respectively, which repress CLK/CYC activity. Previous work indicates that repression is due to a direct PER-CLK/CYC interaction as well as CLK/CYC phosphorylation. We describe here the role of ubiquitin-specific protease 8 (USP8) in circadian transcriptional repression as well as the importance of CLK ubiquitylation in CLK/CYC transcription activity. usp8 loss of function (RNAi) or expression of a dominant-negative form of the protein (USP8-DN) enhances CLK/CYC transcriptional activity and alters fly locomotor activity rhythms. Clock protein and mRNA molecular oscillations are virtually absent within circadian neurons of USP8-DN flies. Furthermore, CLK ubiquitylation cycles robustly in wild-type flies and peaks coincident with maximal CLK/CYC transcription. As USP8 interacts with CLK and expression of USP8-DN increases CLK ubiquitylation, the data indicate that USP8 deubiquitylates CLK, which down-regulates CLK/CYC transcriptional activity. Taken together with the facts that usp8 mRNA cycles and that its transcription is activated directly by CLK/CYC, USP8, like PER and TIM, contributes to the transcriptional feedback loop cycle that underlies circadian rhythms.
Detection of sub-ppm traces of aqueous heavy-metal ions using micro-electro-mechanical beam resonators

Capacitive silicon micro-mechanical resonators have been utilized in this work as ultra-sensitive mass sensors for the detection of trace amounts of copper ions in water samples. The approach is based on the reduction of aqueous metal ions by the silicon in a resonant structure and consequently deposition of a very thin metal layer on the resonator surface changing its resonant frequency. Measurements demonstrate successful detection of sub-ppm concentrations of copper(II) ions in water. Relatively large frequency shifts (hundreds of ppm) have been measured for resonators exposed to copper concentrations as low as 4 μM (0.26 ppm). An analytical model for the resonant frequency of the resulting complex beams has been derived and used to calculate the thickness of the deposited copper layer based on the measured frequency shifts. The model shows that the measured frequency shifts correspond to only a few atomic layers of copper (as thin as ∼7 ˚ A) deposited on the resonator surfaces. This corresponds to a mass sensitivity of more than 4000 Hz μg −1 cm −2 which is much larger than the highest mass sensitivities measured for quartz crystal microbalances. (Some figures in this article are in colour only in the electronic version)
Analogue VLSI morphological image processing circuit

An analogue VLSI circuit that performs morphological image processing operations on the focal plane is presented. The circuit has been fabricated using a standard digital CMOS process. We exploit the parallelism of morphological image processing operations by using the massively parallel architecture of analogue VLSI arrays, achieving both high-speed and low-power computation. The analogue circuit presented computes the grey-scale morphological operation of dilation. This system also allows for programmability of the structuring element used in the dilation operation.
Mechanisms of active cell death in isolated hepatocytes

Active (or programmed) cell death is a generic term for “suicide-like” cell death. Its critical feature is the dependency on vital cell functions and inherent genetic programming. It occurs in the context of a broad range of physiological functions, including homeostatic regulation of tissue mass, removal of unwanted or harmful cells in immune systems, removal of (pre)neoplastic tissues, and morphogenesis during early development [1–3]. “Apoptosis” is the principal form of active cell death and is generally defined by its characteristic morphological and biochemical changes: nuclear condensation and fragmentation, formation of apoptotic bodies and internucleosomal DNA fragmentation [4,5]. At present, there are growing numbers of reports dealing with the molecular mechanisms of apoptosis (for detailed reviews, see [6–10]). Briefly, stimuli that induce apoptosis vary widely, but their respective signalling pathways frequently converge on one mechanism, in which a few common protein families play important roles: among them are the caspase (previously called the ICE/Ced-3 family) [10,11] and the Bcl-2/Ced-9 [10,12] families. Recent data suggest that mitochondria and cytochrome c play key roles in the regulation of caspases [6,7,9]. In addition, other mechanisms including non-caspase proteases [e.g. 13–18], protein phosphorylation [5,19], redox regulation [20], and Ca2+ signaling [21], may also participate in the process of apoptosis. Other forms of caspase-independent apoptosis [22–25] as well as non-apoptotic forms of active cell death [26–30] have also been reported.
Effects of hemolysis on serum electrolyte values.

The correction of serum potassium and phosphate values for erythrocyte contribution arising from hemolysis during blood collection may be made with a fair degree of confidence by evaluating the cellular potassium and phosphorus from the serum hemoglobin. The correction for potassium is appreciable, about 3.3 mEq./L. for each gram of liberated hemoglobin; the correction for phosphorus in fresh specimens is about one tenth as great, and may ordinarily be neglected.
Wear-Resistant and Antismudge Superoleophobic Coating on Polyethylene Terephthalate Substrate Using SiO2 Nanoparticles

It is of interest to create superoleophobic surfaces that exhibit high oil contact angle, low contact angle hysteresis, high wear resistance, antismudge properties, and optical transparency for industrial applications. In the superoleophobic surfaces developed to date, the mechanical durability data is lacking. By dip-coating polyethylene terephthalate substrate with hydrophobic SiO2 nanoparticles and methylphenyl silicone resin, followed by O2 plasma treatment and vapor deposition of 1H,1H,2H,2H-perfluorooctyltrichlorosilane, a durable superoleophobic surface was fabricated. The degree of superoleophobicity was found to be dependent on the particle-to-binder ratio. The coatings were found to exhibit wear resistance on microscale and macroscale, antismudge properties, and transparency.
Improving microRNA target prediction by modeling with unambiguously identified microRNA-target pairs from CLIP-ligation studies

MOTIVATION MicroRNAs (miRNAs) are small non-coding RNAs that are extensively involved in many physiological and disease processes. One major challenge in miRNA studies is the identification of genes targeted by miRNAs. Currently, most researchers rely on computational programs to initially identify target candidates for subsequent validation. Although considerable progress has been made in recent years for computational target prediction, there is still significant room for algorithmic improvement. RESULTS Here, we present an improved target prediction algorithm, which was developed by modeling high-throughput profiling data from recent CLIPL (crosslinking and immunoprecipitation followed by RNA ligation) sequencing studies. In these CLIPL-seq studies, the RNA sequences in each miRNA-target pair were covalently linked and unambiguously determined experimentally. By analyzing the CLIPL data, many known and novel features relevant to target recognition were identified and then used to build a computational model for target prediction. Comparative analysis showed that the new algorithm had improved performance over existing algorithms when applied to independent experimental data. AVAILABILITY AND IMPLEMENTATION All the target prediction data as well as the prediction tool can be accessed at miRDB (http://mirdb.org). CONTACT xwang@radonc.wustl.edu.
Clustering, cosmology and a new era of black hole demographics– I. The conditional luminosity function of active galactic nuclei

Deep X-ray surveys have provided a comprehensive and largely unbiased view of active galactic nuclei (AGN) evolution stretching back to $z \sim 5$. However, it has been challenging to use the survey results to connect this evolution to the cosmological environment that AGNs inhabit. Exploring this connection will be crucial to understanding the triggering mechanisms of AGNs and how these processes manifest in observations at all wavelengths. In anticipation of upcoming wide-field X-ray surveys that will allow quantitative analysis of AGN environments, this paper presents a method to observationally constrain the Conditional Luminosity Function (CLF) of AGNs at a specific $z$. Once measured, the CLF allows the calculation of the AGN bias, mean dark matter halo mass, AGN lifetime, halo occupation number, and AGN correlation function -- all as a function of luminosity. The CLF can be constrained using a measurement of the X-ray luminosity function and the correlation length at different luminosities. The method is illustrated at $z \approx 0$ and $0.9$ using the limited data that is currently available, and a clear luminosity dependence in the AGN bias and mean halo mass is predicted at both $z$, supporting the idea that there are at least two different modes of AGN triggering. In addition, the CLF predicts that $z\approx 0.9$ quasars may be commonly hosted by haloes with $M_{\mathrm{h}} \sim 10^{14}$ M$_{\odot}$. These `young cluster' environments may provide the necessary interactions between gas-rich galaxies to fuel luminous accretion. The results derived from this method will be useful to populate AGNs of different luminosities in cosmological simulations.
56 PLASMINOGEN ACTIVATOR INHIBITOR ACTIVITY DURING PREGNANCY IN 43 WOMEN WITH POLYCYSTIC OVARY SYNDROME, 21 WITH LIVE BIRTHS, 22 WITH MISCARRIAGES

We hypothesized that diet-metformin (MET) promote successful live births in women with polycystic ovary syndrome (PCOS) by lowering hypofibrinolytic plasminogen activator inhibitor (PAI-Fx) during the 1st two trimesters of pregnancy. We studied 43 women with PCOS, 21 with live births, 22 with 1st trimester miscarriages. Women with BMI 0.1) at pre-treatment (pre-Rx) study entry by median age (28 vs 30 years), BMI (33.6 vs 34.9), serum insulin (24 vs 20 μU/mL), HOMA insulin resistance (IR) (5.07 vs 4.42), HOMA insulin secretion (342 vs 240), PAI-Fx (18.8 vs 11.7 u/mL), or race (95% vs 100% white). At pre-Rx baseline, in the 21 live birth pregnancies, median PAI-Fx was 18.8 u/mL, fell on MET-diet to 11.4 at the last pre-conception visit, fell to 8.6 at the end of the 1st trimester, and was 11.7 at the end of the 2nd trimester (p .05). In the live birth group, on diet-MET for 12 months pre-conception, PAI-Fx fell 54% (p =.051) from pre-Rx baseline to the last pre-conception visit. In the miscarriage group, on diet-MET for 9 months pre-conception, PAI-Fx rose 19% from pre-Rx baseline to the last pre-conception visit, differing from the live birth group (p = .01). From pre-Rx baseline to the 1st trimester, live birth and miscarriage groups both lost weight (9.7% [p
Policy innovations for private forest management and conservation in Costa Rica

Costa Rica is a leader in innovative forest conservation and management policies, including a program of direct payments to private forest landowners for environmental services. This approach is widely advocated but rarely implemented, and thus the Costa Rican experience constitutes a valuable real-world policy experiment. We discuss the motivation for this program, its domestic and international funding sources, and the structure of contracts with landowners. The successes and challenges facing the Costa Rican program offer insights for other countries-both developed and developing-regarding policies for private forest management.
On Moral Alchemy: A Critical Examination of Post-9/11 U.S. Military Policy

There is a growing consensus, even within the United States, that the decision to attack Iraq was morally unjustifiable and strategically disastrous. But there has been relatively little public scrutiny of two fundamental shifts in U.S. foreign policy and military doctrine that accompanied the war and that threaten to have a long-term impact on the use of the world’ s most powerful military force. Half a year before attacking Iraq, the U.S. Department of State attempted to prepare the legal and moral basis for the war by issuing a new National Security Strategy that broke decisively with prior limitations on the self-defensive use of military violence, declaring that the United States would attack other nations to defuse long-term threats to its security even when those nations had no imminent plans to attack the United States or its allies. Two years after invading Iraq, the U.S. Army and Marine Corps made an equally fundamental change in their strategic doctrine—a change aimed at improving its capacity to suppress the sort of resistance movement that has arisen in Iraq and that might confront its operations in other foreign nations. I believe that both of these fundamental changes in war policy are strategically unwise, but I will not pursue that matter here. My aim is to show that they are both morally indefensible. The doctrine of preventive self-defense could be counted as moral only on the exceedingly implausible supposition that when a group of individuals forms a state, this gives them a newly enhanced right to kill their fellow human beings. The new counterinsurgency doctrine would be morally benign only if put into practice by an army of angels. Applied to an army of human beings it is a recipe for brutality and oppression, and it will often result in the violent death of many innocent human beings.
Male parental care and extrapair copulations in the indigo bunting

-Levels of parental care by male Indigo Buntings (Passerina cyanea) were predicted to be lower and the tendency to pursue extrapair matings greater when (1) the opportunity of additional matings (extrapair copulations) was high, (2) the male was cuckolded, and (3) the clutch or brood size was small. Observations of male care revealed that approximately 10% of all males fed nestlings at least once, whereas more than 30% fed fledglings. Males in their first breeding season were never seen feeding young. Males made more trips off their territories when females were fertilizable on nearby territories, but other measures of parental care (feeding young and time spent within 10 m of nest) were not affected. Cuckolded males (known through genetic analyses of parents and offspring) tended to feed young less often, but forayed off their territories significantly less than apparently uncuckolded males. Finally, males with small clutches or broods gave slightly, but not significantly, less care than males with large clutches or broods. These results suggest that the relationship between mating effort and parental effort is complicated by the presence of extrapair copulations as a type of mating effort, and that factors not included in current theory on parental care might influence a male's parental care. Received 18 June 1987, accepted 19 October 1987. WHEN an individual spends time and energy to help raise its offspring, it potentially sacrifices opportunities to pursue additional reproduction (Trivers 1972, Maynard Smith 1977). In other words, reproductive effort can be divided into two components, mating effort and parental effort (Low 1978). Because energy spent on one component often reduces the energy available to spend on the other component, parenting behavior can be thought of as a reproductive strategy in competition with other strategies. Maynard Smith (1977) quantified the tradeoff between the gain in reproduction from additional matings and the gain from parental care. In this model, deserting a mate with young will be favored if
Finding Tie-sets with the Minimal Number of Total Elements for Effective Failure Recovery

This paper introduces the failure recovery method using ring structures called tie-sets and proposes an algorithm to search a set of tie-sets which generate a shorter detour path in the case of a link failure. The idea of tie-sets, which is defined in the graph theory, is to divide a mesh network into logical loops and manage a failure with them. The tie-set recovery method works on a mesh network in the same manner as ring based protection schemes. When applying this method, it is necessary to consider how the tie-sets cover an entire network since the length of a detour path is determined by the size of a tie-set. Experimental results illustrate that obtained tie-sets generate a short detour path compared with the shortest path algorithm.
Post-Concussive Syndrome: a Focus on Post-Traumatic Headache and Related Cognitive, Psychiatric, and Sleep Issues

Post-traumatic headache (PTH) is a secondary headache disorder following traumatic brain injury. We sought to examine the recent literature on PTH and associated cognitive, psychiatric, and sleep conditions to understand the latest findings about the associated conditions and available screening tools, and to understand the available treatment options for PTH. Up to one third of PTH patients may have depression and about one quarter may have insomnia. Anxiety and cognitive issues are also common. While there are few studies examining abortive medications for PTH, recent studies of preventive medications examine the efficacy of topiramate, and topiramate may be better than other oral preventive medications. Other currently investigated treatments include nerve blocks, onabotulinum toxin A, transmagnetic stimulation, and behavioral therapy (biofeedback). Due to an expanded focus on and knowledge of concussion and PTH, comorbid psychiatric, cognitive, and sleep issues have become more widely acknowledged and studied. However, more high-quality studies must be conducted to examine the underlying pathophysiology of PTH and associated symptoms and to determine the most effective abortive and preventive treatment options.
High efficiency radiofrequency power amplifier module for parallel transmit arrays at 3 Tesla.

Purpose The purpose of this study is to develop an in-bore radiofrequency (RF) power amplifier (RFPA) module with high power efficiency and density for use in parallel transmit (pTX) arrays at 3 Tesla. Methods The modules use a combination of current mode class D, class S, and class E amplifiers based on enhancement-mode gallium nitride-on-silicon field-effect transistors. Together the amplifiers implement envelope elimination and restoration to achieve amplitude modulation with high efficiency over a wide operating range. The static nonlinearity and power efficiency of the module were measured using pulsed RF measurements over a 37 dB dynamic range. Thermal performance was also measured with and without forced convection cooling. Results The modules produces peak RF power up to 130 W with an overall efficiency of 85%. When producing 100 W RF pulses at a duty cycle of 10%, maximum junction temperatures did not exceed 80 °C, even without the use of heatsinks or forced convection. Conclusion The small size and low cost of the modules promise lower cost implementation of pTX systems compared with linear RFPAs located remotely. Further work must be done on control of the RF output in the presence of nonlinearities and coupling. Magn Reson Med 78:1589–1598, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
Structural and Functional Characterization of the NHR2 and Runt Domains of AML1/ETO.

AML1/ETO is the chimeric fusion protein resulting from the t(8;21) found in AML of the M2 subtype. It contains the N-terminal 177 amino acids of RUNX1 and virtually all (575aa) of ETO. The RUNX1 component includes the Runt domain, which mediates both DNA binding and heterodimerization with CBFβ, but lacks the more C-terminal sequences required for transactivation. AML1/ETO occupies RUNX target genes in vivo and is associated with a repressive chromatin structure characterized by reduced levels of acetylated histone H3. AML1/ETO is thought to repress transcription by recruiting a SMRT (N-CoR)/Sin3A/HDAC complex to chromatin via sequences in ETO. ETO is the human homologue of the Drosophila Nervy protein and shares 4 regions of homology with Nervy called Nervy Homology Regions (NHR) 1–4. Deletion studies have shown that three of the AML1/ETO domains essential for its repressive function are the Runt domain, NHR2, and NHR4. The NHR2 domain is a hydrophobic heptad repeat that mediates oligomerization of AML1/ETO, interaction with ETO family members, and also with mSin3A and HDACs. We recently solved an x-ray structure of the NHR2 domain and found it to be an alpha-helical tetramer. Based on this structure we have introduced amino acid substitutions into the NHR2 domain that disrupt tetramer formation but not AML1/ETO stability. These mutations impair the ability of AML1/ETO to inhibit the differentiation of GR−1+/Mac−1+ cells following retroviral transduction into primary mouse bone marrow cells, and also inhibit the serial replating ability of AML1/ETO expressing bone marrow cells in vitro. We also assessed the outcome of disrupting oligomerization on a variety of previously described protein-protein interactions, and found that neither deleting the NHR2 domain nor disrupting oligomerization affected the ability of HDAC1, HDAC2, HDAC3, N-CoR, SMRT, PKA RIIα, PLZF, or HEB, to co-immunoprecipitate AML1/ETO from cell extracts. Deletion of the NHR2 domain reduced binding of mSin3a as shown previously, but disruption of oligomerization did not. To investigate the contribution of oligomerization to AML1/ETO-mediated transcriptional modulation, we amplified RNA from retrovirally-transduced, lineage depleted primary mouse bone marrow cells and performed Real Time Quantitative PCR of genes whose expression is known to be regulated by AML1/ETO or RUNX1. We show that the requirement for oligomerization is target gene dependent, with several classes of genes resulting from our study. We also introduced mutations in the Runt domain of AML1/ETO that disrupt CBFβ binding by defined amounts (40-fold, 200-fold, 500-fold), and demonstrated that CBFβ binding by AML1/ETO is essential for its dominant negative activity. The latter results suggest that small molecules designed to selectively impair heterodimerization of AML1/ETO with CBFβ could potentially block AML1/ETO’s dominant negative activity.
Productivity and Efficiency

Often productivity is correlated to profitability, which signifies a company’s ability to generate revenues in comparison to expenses of inputs. However, for a given company, a high rate of profitability does not mean a high rate of productivity. A production process with low productivity can still generate high profits if a favorable market exists. Conversely, a production process with high productivity may still result in a decrease in profit if market conditions do not comply. Many factors contribute to the improvement of productivity. Such factors include the quality of materials, versatility and capability of equipment, skill of employees, design of production systems, and management approach. When all these factors work synchronously, improvement in productivity can be achieved. Such improvements, in turn, will improve the quality of produced goods and will result in a lower cost of production, which will contribute to an increase in profitability.
Glomerular Lesions in Proteinuric Miniature Schnauzer Dogs

Miniature Schnauzer dogs are predisposed to idiopathic hypertriglyerceridemia, which increases risk for diseases such as pancreatitis and gallbladder mucocele. Recently, elevated triglyceride concentrations have been associated with proteinuria in this breed, although it is difficult to determine which abnormality is primary. Retrospective review of renal tissue from 27 proteinuric Miniature Schnauzers revealed that 20 dogs had ultrastructural evidence of osmophilic globules consistent with lipid in glomerular tufts. Seven of these dogs had lipid thromboemboli in glomerular capillary loops that distorted their shape and compressed circulating erythrocytes. Triglyceride concentrations were reported in 6 of these 7 dogs, and all were hypertriglyceridemic. In addition, glomerular lipidosis (defined as accumulation of foam cells within peripheral capillary loops) was identified in a single dog. The remaining 12 dogs had smaller amounts of lipid that could only be identified ultrastructurally. Neither signalment data nor clinicopathologic parameters (serum albumin, serum creatinine, urine protein-to-creatinine ratio, and blood pressure) differed among the various types of lipid lesions. During the time course of this study, all dogs diagnosed with glomerular lipid thromboemboli were Miniature Schnauzers, underscoring the importance of recognizing these clear spaces within capillary loops as lipid.
Pain Management and Acupuncture After Vertebral Fractures

Osteoporosis is a significant cause of morbidity in the elderly as well as in certain populations of non-elderly. Vertebral compression fractures caused by osteoporosis are a significant cause of decreased function as well as pain. Care of this population sometimes requires a multimodal approach including referrals to pain clinics. Pain management strategies are varied; in addition to the usual pharmacologic approach (including oral and topical medications), non-pharmacologic approaches can be very useful. Spine injections, bracing, exercise, and vertebral augmentation as well as less conventional therapies including acupuncture can also be used as valuable adjuncts for pain management or as a safe alternative to oral medication use. Acupuncture has gained in popularity as a valid treatment option for many different types of pain conditions including back pain.
Clinical implications of donor age: A single-institution analysis spanning 3 decades.

Abstract Background We sought to clarify the effect of donor age as a continuous variable on morbidity and mortality in a single-institution experience. Methods From 1986 to 2016, 882 adult lung transplants were performed, including 396 in the lung allocation score era. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate the association of donor age with overall survival and bronchiolitis obliterans syndrome (BOS) score ≥1-free survival. Logistic regression was used to evaluate the association with primary graft dysfunction grade 3. Natural cubic splines were used to explore donor age in a continuous fashion to allow for nonlinear relationships. Results In the lung allocation score era, unadjusted 5-year survival was not significantly different between 3 a priori–defined donor age groups: age P = .8). Unadjusted 5-year freedom from BOS ≥1 was not significantly different (34%, 20%, and 33%, respectively, P = .1). After we adjusted for comorbidities, cubic spline analysis demonstrated no effect between donor age as a continuous variable and hazard for mortality at 5 years. Similarly, no interaction was seen between donor age and risk of BOS or primary graft dysfunction 3. Adjusted analysis of all 882 transplants pre- and postinception of the lung allocation score also showed no effect of age on 10-year survival. Conclusions Long-term survival of lung transplant recipients was not affected by the age of the donor. These findings support the notion that donor age could be relaxed.
Effect of Growth Hormone on Carbohydrate and Lipid Metabolism: An Overview

Approximately 60 years ago, Houssay and his colleagues described hypersensitivity to insulin in hypophysectomized (hypox) animals (1). Further work documented a primary effect of growth hormone (GH) in this phenomenon (1). Over the ensuing years, numerous investigators have sought to define the role of GH in carbohydrate and lipid metabolism. Unfortunately, no unified picture has emerged. Both “insulin-like” and “anti-insulin-like” effects have been documented although the physiological significance of the former is uncertain. Major controversies surround the relationship between structure and function of the GH molecule. Indeed, some believe that most of the reported effects of GH are due to contaminants in the hormone preparation. With two exceptions (2,3), reviews in this area (4–10) have focused mainly on the author–s own work in a circumscribed field, e.g., in vivo effects after GH administration (6,7,9), tissue effects in vitro (5,7), or effects on lipolysis (4,8,10). Furthermore, these reviews were published more than 10 years ago.
Chapter 25 – Astrocytes as Pharmacological Targets in the Treatment of Schizophrenia: Focus on Kynurenic Acid

Abstract The levels of the tryptophan metabolite kynurenic acid (KYNA) are elevated in the brain and cerebrospinal fluid of individuals with schizophrenia and may be causally involved in pathophysiology. This view is based on the ability of KYNA to antagonize the function of α7 nicotinic and N-methyl- d -aspartate receptors, both of which are critical to normal brain development and cognitive processes, and are impaired in schizophrenia. Further support of the “KYNA hypothesis” comes from studies in experimental animals in which even relatively moderate increases in brain KYNA result in a spectrum of biochemical and cognitive abnormalities reminiscent of schizophrenia. Interventions leading to a reduction of cerebral KYNA formation may therefore have therapeutic benefits. Most efforts in this regard have focused on inhibiting the astrocytic enzyme kynurenine aminotransferase II, a major route of KYNA neosynthesis in the brain. Promising preclinical results using specific kynurenine aminotransferase II inhibitors have been obtained recently.
Imagining the Parish in Late Medieval England. By Ellen K. Rentz. (Columbus, OH: The Ohio State University Press, 2015. Pp. xiii, 183. $62.95.)

In an era when religion and ethnic/local ties often dominate concepts of self‐identity, this new interdisciplinary study is most welcome. The English parish church was the most important communal s...
Formative work in the development of a physical activity smartphone app targeted for patients with alcohol use disorders

Abstract Objectives Alcohol use disorders (AUDs) are associated with significant physical and mental health concerns. Interventions focused on increasing physical activity (PA) in this population may improve overall physical and mental health associated with AUDs. Given how ubiquitous smartphones have become, PA apps may be a feasible, acceptable, and potentially scalable approach to integrating PA in alcohol recovery. To date, there are no PA apps targeted specifically for this population. Design The current study describes 2 formative phases in the development of Fit&Sober, a theory-informed smartphone app designed to increase PA in patients with alcohol dependence. Methods Phase 1 consisted of questionnaires and focus groups (3 groups with total N = 23) conducted with patients in current AUD treatment regarding their preferences and feedback on the proposed app design and components. Phase 2 consisted of individual usability sessions (N = 10) conducted with a different set of patients with AUD, in which feedback was provided on the look, usability, and functionality of the Fit&Sober app prototype. Results Phase 1 evaluated key components of a physical activity app designed especially for increasing PA in early recovery and refined app features such as the logo, graphical display of data, and specific physical activity-relevant affect words to be used in the app. Phase 2 usability studies provided support for usability, attractiveness, and potential usefulness in the target population. Conclusions Through the iterative 2-phase process, a prototype of the Fit&Sober app was created and readied for pilot testing in patients with AUD.
The Role of the Constant Region in Antibody-Antigen Interactions: Redefining the Modular Model of Immunoglobulin Structure

Abstract Immunological canon traditionally divides immunoglobulin molecules into a functionally distinct antigen-binding variable region and a constant region that interacts with downstream components of the immune system. Recent research, along with a reexamination of earlier studies, shows that this modular model of antibody structure is incomplete. Biochemical, structural, and computational studies over the past five decades with many different antibodies illustrate an allosteric antibody model, where conformational changes in the variable region are propagated to the constant region and vice versa. The immunoglobulin constant region is now thought to play a major role in antibody-antigen interactions and can be viewed as another mechanism by which the immune system generates antibody diversity. While a precise structural mechanism is unclear and likely varies by the particular antibody or antibody family, the allosteric antibody model has many implications for the immune response, autoimmunity, vaccine development, and antibody engineering.
Marijuana Initiatives Versus Legislation and Public Health

An editorial is presented which addresses various marijuana-related initiatives and legislation in America as of 2018, and it mentions U.S. public health issues, public policies in American states, and the classification of marijuana as a Schedule I drug under the nation's Controlled Substances Act. An article about a normative regulatory framework for the retail sales of marijuana, which appears in the same issue of the journal, is examined.
Accounting Documentation Software: An Overview of Options and Results from a Lucidchart Software Evaluation

Accounting practitioners use documentation diagrams to plan audits, train employees, and consult on accounting information systems development. Accounting educators instruct students in diagram development with various software tools as preparation for industry requirements. This paper presents a review of documentation diagrams identified by practice and major textbooks, a summary of software tool options, and an examination of cloud-based documentation software. We suggest software adoption criteria and propose Lucidchart as a cloud-software solution for developing accounting documentation diagrams. Finally, we present the results from a Lucidchart software evaluation study. The practical contribution is two-fold for educators responsible for teaching accounting documentation topics: (a) a documentation software resource; and (b) an initial usage assessment of Lucidchart software.
Nonlinear Diffusion for Community Detection and Semi-Supervised Learning

Diffusions, such as the heat kernel diffusion and the PageRank vector, and their relatives are widely used graph mining primitives that have been successful in a variety of contexts including community detection and semi-supervised learning. The majority of existing methods and methodology involves linear diffusions, which then yield simple algorithms involving repeated matrix-vector operations. Recent work, however, has shown that sophisticated and complicated techniques based on network embeddings and neural networks can give empirical results superior to those based on linear diffusions. In this paper, we illustrate a class of nonlinear graph diffusions that are competitive with state of the art embedding techniques and outperform classic diffusions. Our new methods enjoy much of the simplicity underlying classic diffusion methods as well. Formally, they are based on nonlinear dynamical systems that can be realized with an implementation akin to applying a nonlinear function after each matrix-vector product in a classic diffusion. This framework also enables us to easily integrate results from multiple data representations in a principled fashion. Furthermore, we have some theoretical relationships that suggest choices of the nonlinear term. We demonstrate the benefits of these techniques on a variety of synthetic and real-world data.
Abstract 4339: Critical role of Dnmt3b catalytic activity in prevention of oncogene-induced leukemias and lymphomas

Cytosine methylation is involved in a variety of biological processes, including development, X-chromosome inactivation, imprinting, and suppressing unwanted transcription. DNA methylation in mammalian cells is catalyzed by several DNA methyltransferases, including DNMT1, DNMT3A and DNMT3B. In addition to DNA methylation catalysis, these enzymes interact with a number of repressive proteins including HDACs, thereby repressing transcription in methylation-independent manner. The extent to which methylation-dependent and independent activities play roles in biological processes remains poorly understood. Here we examined the role of methyltransferase (MT) activity of Dnmt3b in normal mouse embryogenesis and in prevention of hematologic malignancies. Loss of Dnmt3b in mice is embryonically lethal between 10.5-12.5 dpc. Dnmt3b was also identified as tumor suppressor in murine models of lymphoid and myeloid malignancies. To address whether Dnmt3b’s catalytic activity is important for mouse embryogenesis and prevention of hematologic malignancies, we generated mice bearing a conventional Dnmt3bCI allele using CRISPR/Cas9 system. This catalytically inactive allele of Dnmt3b (Dnmt3bCI) was generated by a double amino acid substitution in enzyme active center (P656V and C657D) abolishing its ability to perform transfer of methyl group onto cytosine. Surprisingly, Dnmt3bCI/CI mice were born at similar ratios as wild-type littermates and lived over 12 months suggesting that Dnmt3b is dispensable for both pre- and post-natal development. Importantly, MYC-induced T-cell lymphomagenesis was accelerated in the absence of Dnmt3b’s methyltransferase activity in MYC;Dnmt3bCI/CI mice. Global gene expression and methylation profiling revealed a number of deregulated events specific for MYC;Dnmt3bCI/CI, resulting in activation of Pak, Fgfr and Igf2 signaling and downregulation of tumor suppressors (e.g. Lrp12, Dusp6 and Marcks). The lack of Dnmt3b catalytic activity also accelerated a development of acute myeloid leukemia induced by MLL-AF9 overexpression in mice. Altogether, our data suggest that Dnmt3b’s MT activity is dispensable for mouse development but critical to prevent hematologic malignancies. Citation Format: Katarina Lopusna, Pawel Nowialis, Staci L. Haney, Ajay Abraham, Jana Opavska, Rene Opavsky. Critical role of Dnmt3b catalytic activity in prevention of oncogene-induced leukemias and lymphomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4339.
Du « Délire à deux » : une lecture de Macbeth

Resume Objectifs L’objectif de notre etude est d’apporter une lecture originale sur Macbeth, sur les circonstances qui declencherent la folie meurtriere de Macbeth (parricide et crimes en cascade), mais aussi et surtout sur le caractere tres singulier du couple Macbeth, qui a notre sens peut etre saisi sous l’angle d’un « delire a deux ». Methodologie La revue selective de la litterature permet d’apprehender au fil du temps la dimension « pathologique » de Macbeth et le role fondamental, central, que joue Lady Macbeth dans la tragedie. Suite a cette revue de la litterature, nous envisageons le deroulement logique des evenements, une approche historique de ce que l’on nomme « folie », ou « delire a deux » (Ch. Lasegue, J. Falret), et les elements qui permettent d’avancer cette hypothese du delire a deux pour le couple Macbeth. Les references de la psychiatrie classique, mais aussi les references a S. Freud, a J. Lacan, et a d’autres auteurs et/ou critiques, nous permettent de l’envisager de la sorte. Resultats La lecture que nous faisons de Macbeth permet de rendre compte des elements declencheurs de la folie de Macbeth, elements necessaires a la decompensation du heros eponyme, mais non suffisants. Le role que joue ici son epouse, Lady Macbeth, apparait alors comme determinant, car c’est elle qui le « pousse-au-crime ». Le couple Macbeth n’est pas un couple commun, ni meme un couple simplement complice dans le crime, comme les faits-divers en temoignent parfois. La seule ambition, la seule quete du pouvoir, ne peuvent expliquer Macbeth. Les deux protagonistes de ce couple criminel ne vont pas l’un sans l’autre. Il semble bien que l’on ne peut les separer, qu’on ne peut penser l’un sans l’autre, que les deux font Un, ce qui permettrait d’ecrire ce couple comme Un-possible. L’hypothese du « delire a deux » nous semble ainsi eclairer – en partie seulement, sans doute – le fonctionnement de ce couple tout comme que le deroule logique de la tragedie. Discussion L’article permet de revenir sur la notion de « delire a deux », avec la distinction eventuelle d’avec le delire dit « simultane » (E. Regis). La discussion porte egalement sur ce qui a pu faire « tenir » Macbeth jusqu’a la rencontre fatidique avec les trois sœurs Sorcieres. On s’interessera alors a cette identification-compensation imaginaire du guerrier vaillant, courageux, heroique au champ de bataille, a tout ce qui peut donner une valeur phallique chez un Macbeth sterile, dont l’epouse n’a de cesse de lui repeter qu’il n’est pas un homme. Conclusion Bien que la plus courte des tragedies de Shakespeare, bien que simple – en apparence – dans le deroule des evenements ou dans sa thematique, Macbeth est une piece fort complexe. L’hypothese du « delire a deux » nous semble apporter quelques eclairages sur cette tragedie noire, sanglante, dont le brouillard envahit aussi bien la scene que l’âme de ses heros.