cssi/SciSciGPT-SciSciNet huggingface dataset:
Acetylcholinesterase of the sand fly, Phlebotomus papatasi (Scopoli): construction, expression and biochemical properties of the G119S orthologous mutant

Phlebotomus papatasi vectors zoonotic cutaneous leishmaniasis. Previous expression of recombinant P. papatasi acetylcholinesterase (PpAChE1) revealed 85% amino acid sequence identity to mosquito AChE and identified synthetic carbamates that effectively inhibited PpAChE1 with improved specificity for arthropod AChEs compared to mammalian AChEs. We hypothesized that the G119S mutation causing high level resistance to organophosphate insecticides in mosquitoes may occur in PpAChE1 and may reduce sensitivity to inhibition. We report construction, expression, and biochemical properties of rPpAChE1 containing the G119S orthologous mutation. Targeted mutagenesis introduced the G119S orthologous substitution in PpAChE1 cDNA. Recombinant PpAChE1 enzymes containing or lacking the G119S mutation were expressed in the baculoviral system. Biochemical assays were conducted to determine altered catalytic properties and inhibitor sensitivity resulting from the G119S substitution. A molecular homology model was constructed to examine the modeled structural interference with docking of inhibitors of different classes. Genetic tests were conducted to determine if the G119S orthologous codon existed in polymorphic form in a laboratory colony of P. papatasi. Recombinant PpAChE1 containing the G119S substitution exhibited altered biochemical properties, and reduced inhibition by compounds that bind to the acylation site on the enzyme (with the exception of eserine). Less resistance was directed against bivalent or peripheral site inhibitors, in good agreement with modeled inhibitor docking. Eserine appeared to be a special case capable of inhibition in the absence of covalent binding at the acylation site. Genetic tests did not detect the G119S mutation in a laboratory colony of P. papatasi but did reveal that the G119S codon existed in polymorphic form (GGA + GGC). The finding of G119S codon polymorphism in a laboratory colony of P. papatasi suggests that a single nucleotide transversion (GGC → AGC) may readily occur, causing rapid development of resistance to organophosphate and phenyl-substituted carbamate insecticides under strong selection. Careful management of pesticide use in IPM programs is important to prevent or mitigate development and fixation of the G119S mutation in susceptible pest populations. Availability of recombinant AChEs enables identification of novel inhibitory ligands with improved efficacy and specificity for AChEs of arthropod pests.
Thermal conductivity of carbon nanotubes

As the sizes of electronic and mechanical devices are decreased to the micron and nanometre level, it becomes particularly important to predict the thermal transport properties of the components. Using molecular level theories, such predictions are particularly important for modelling nano-electronic devices where scaling laws may change substantially but it is most difficult to accurately measure the properties. Hence, using the empirical bond order dependent force field, we have studied here the thermal conductivity of nanotubes' dependence on structure, defects and vacancies. The anisotropic character of the thermal conductivity of the graphite crystal is naturally reflected in the carbon nanotubes. We found that the carbon nanotubes have very high thermal conductivity comparable to diamond crystal and in-plane graphite sheet. In addition, nanotube bundles show very similar properties as graphite crystal in which dramatic difference in thermal conductivities along different crystal axis.
Labial root torque: Effect on the maxilla and incisor root apex

This study was designed to determine the effectiveness of labial root torque on anterior nasomaxillary development. Quantification was made of the angular and linear changes in Downs' point A (representing midsagittal basal bone) and incisor point A (representing the dentoalveolar bone) and any concomitant incisor root resorption. The study was divided into two parts: part 1--to determine the anatomic configuration of the premaxillary region by use of laminagraphy on skulls, and part 2--to use the morphologic landmarks found in part 1 to assess the development of the nasomaxillary complex in maxillary retrusive patients. The clinical study involved 17 maxillary retrusive patients, aged 8.0 to 15.7 years, who had been treated for a period between 0.31 and 3.70 years with edgewise advancing mechanics. Clinical results indicate that during the first phase of orthodontic treatment with labial root torque, encompassing a 0.63-year mean treatment period, a greater rate of advancement of Downs' point A was produced when compared with normal growth. The skeletal convexity increased, whereas normal growth straightened the profile. Incisor point A advanced at a greater rate than Downs' point A, suggesting that treatment caused a larger dentoalveolar effect than the effect on midsagittal basal bone. When treatment was extended to 1.57 years, similar changes were found but at a reduced rate. Overall apical root resorption was 12.7%/year. Sex and age were not found to have any correlation to the amount of apical root loss.
Estimating service capacity using nonhomogeneous work arrivals

We explore experimental procedures for comparing the capabilities of complex discrete event service systems. Instead of measuring system capability by an analyzing or simulating the system with a constant rate of arriving work, system capability is measured as the maximum rate of work arrival for which the system has a steady state. Hence, we seek the arrival rate which causes the system to be at full capacity. This rate is arguably the best indication of the service system's capability.
Lessons learned from the bevacizumab experience.

Background: Bevacizumab is an important agent in the oncologic armamentarium, with activity in a broad spectrum of solid tumors. It has been approved in the management of metastatic colorectal cancer, non–small cell lung cancer, renal cancers, and recurrent glioblastoma multiforme. Methods: We reviewed the published literature and briefi ng documents of the US Food and Drug Administration that provided the data leading to approval or change in approval status. Results: Bevacizumab initially received accelerated approval for the treatment of advanced breast cancer. However, lack of confi rmatory data from additional clinical trials resulted in the loss of that indication. Both the expected and unexpected toxicities reported from clinical trials using bevacizumab have helped us to understand the drug’s mechanism of action and to identify who are most likely to benefi t from this important agent. Conclusions: The side effects of treatment may provide important information about drug mechanism and effi cacy. Bevacizumab is clearly an important agent in oncology and is likely to become more signifi cant once a clinical or pathological marker to predict its effi cacy has been identifi ed.
Private Monitoring and Communication in the Repeated Prisoner’s Dilemma

This paper provides a model of the repeated prisoner’s dilemma in which cheap-talk communication is necessary in order to achieve cooperative outcomes in a long-term relationship. The model is one of complete information. I consider a continuous time repeated prisoner’s dilemma game where informative signals about another player’s past actions arrive following a Poisson process; actions have to be held fixed for a certain time. I assume that signals are privately observed by players. I consider an environment where signals are noisy, and the correlation of signals is higher if both players cooperate. We show that, provided that players can change their actions arbitrary frequently, there exists an equilibrium with communication that strictly Pareto-dominates all equilibria without communication.
Low energy CID and action IRMPD provide insights into a minor subpopulation of the gas-phase conformers of triply charged bradykinin

Abstract Unique fragmentation of the IMS-resolved conformers of triply charged bradykinin is shown to occur at very low collision energies by quadrupole CID. For the major C conformation of bradykinin, the unique fragmentation appears to result from a subpopulation that has a different average CCS than the dominant C population that has been previously identified as TTC (trans, trans, cis at the three Pro residues). The three major gas-phase isomers exhibit minimal differences in fragmentation at collision energies greater than 12 eV, presumably because the amide bonds of the proline residues isomerize prior to dissociation at these higher energies. The differences in fragmentation observed in the low collision energy regime (
Observations of an aeolian landscape: From surface to orbit in Gale Crater

Abstract Landscapes derived solely from aeolian processes are rare on Earth because of the dominance of subaqueous processes. In contrast, aeolian-derived landscapes should typify Mars because of the absence of liquid water, the long exposure times of surfaces, and the presence of wind as the default geomorphic agent. Using the full range of available orbital and Mars Science Laboratory rover Curiosity images, wind-formed features in Gale Crater were cataloged and analyzed in order to characterize the aeolian landscape and to derive the evolution of the crater wind regime over time. Inferred wind directions show a dominance of regional northerly winds over geologic time-scales, but a dominance of topography-driven katabatic winds in modern times. Landscapes in Gale Crater show a preponderance of aeolian features at all spatial scales. Interpreted processes forming these features include first-cycle aeolian abrasion of bedrock, pervasive deflation, organization of available sand into bedforms, abundant cratering, and gravity-driven wasting, all of which occur over a background of slow physical weathering. The observed landscapes are proposed to represent a spectrum of progressive surface denudation from fractured bedrock, to retreating bedrock-capped mesas, to remnant hills capped by bedrock rubble, to desert pavement plains. This model of landscape evolution provides the mechanism by which northerly winds acting over ∼3 Ga excavated tens of thousands of cubic kilometers of material from the once sediment-filled crater, thus carving the intra-crater moat and exhuming Mount Sharp (Aeolis Mons). The current crater surface is relatively sand-starved, indicating that potential sediment deflation from the crater is greater than sediment production, and that most exhumation of Mount Sharp occurred in the ancient geologic past.
Lawrence, Mill, and Same-Sex Relationships: On Values, Valuing, and the Constitution

Some commentators suggest that Lawrence v. Texas is best understood as incorporating John Stuart Mill's harm principle from "On Liberty." These commentators are incorrect in two different respects: (1) they misconstrue Mill's principle by making it less robust than it actually is, and (2) they misrepresent Lawrence by characterizing it as merely standing for this watered-down version of the harm principle. Lawrence is not merely about the freedom from state interference, since it goes out of its way to affirm the positive worth of same-sex relationships. While we will not know what Lawrence means for years to come, we can be confident that some of the interpretations of it that are currently offered simply cannot be right.
Body in Transit, Body in Transition: Resignifying Colonial Wounds in Roch Carrier’s La Guerre, Yes Sir!

Quebec’s status as a potentially colonial space that underwent a process akin to decolonization during the Revolution tranquille has generated much critical attention in recent years, as scholars consider how Quebec’s liberatory struggles resonate with other narratives of decolonization around the globe. Roch Carrier’s first and most renowned novel, La Guerre, Yes Sir! (1968), deserves particular attention as a literary work that interrogates Quebec’s colonial dynamics. While scholars have emphasized the images of the body in Carrier’s work, with particular consideration of La Guerre, Yes Sir!’s carnivalesque elements, no study thus far has focused on how shifting depictions of individual bodies over time and space allegorize transformations of an imagined national body. In this article, I argue that La Guerre, Yes Sir! dramatizes Quebec’s struggle to regain possession of and define its national body, as represented by the villagers’ desire to recover physical and symbolic possession of the corpse of the ...
The Filling and Emptying of the Uterovaginal Sperm-Host Glands in the Domestic Hen

In a series of three replicated experiments, dwarf hens were inseminated with semen of one phenotype (normal or dwarf) and then reinseminated 4 hr later with semen of the other phenotype. All eggs were pedigree-hatched for two weeks following the inseminations. Subsequent phenotypic determinations of the progeny demonstrated a preponderance of offspring from the latter insemination. The results suggested that spermatozoa sequentially filled the uterovaginal sperm-host glands which produced a permanent stratification of sperm cells, and mixing did not occur within a gland. Emptying of the host-glands appeared to follow a pattern of slow superficial leakage where spermatozoa from the second insemination were the first spermatozoa released, giving rise to the large number of progeny phenotypes from the second insemination. In addition, progeny phenotypes from the second insemination were predominant throughout the fertility period suggesting that the storage capacity of the uterovaginal sperm-host glands can exceed the functional life span of stored spermatozoa following a normal insemination.
Micrognathism corrected by vertical osteotomy of ascending ramus and iliac bone graft: a new technique.

Abstract The method of open vertical osteotomy of the ascending ramus with iliac bone graft is presented as a surgical procedure in the correction of micrognathia. A case treated by this method is presented. As no conclusions can be drawn from one case, this patient will be examined from time to time for a follow-up of this preliminary report.
Role of the Stringent Stress Response in the Antibiotic Resistance Phenotype of Methicillin-Resistant Staphylococcus aureus

Resistance to beta-lactam antibiotics in methicillin-resistantStaphylococcus aureus(MRSA) requires the presence of an acquired genetic determinant,mecAormecC, which encode penicillin-binding protein PBP2A or PBP2A', respectively. Although all MRSA strains share a mechanism of resistance, the phenotypic expression of beta-lactam resistance shows considerable strain-to-strain variation. The stringent stress response, a stress response that results from nutrient limitation, was shown to play a key role in determining the resistance level of an MRSA strain. In the present study, we validated the impact of the stringent stress response on transcription and translation ofmecAin the MRSA clinical isolate strain N315, which also carries known regulatory genes (mecI/mecR1/mecR2andblaI/blaR1) formecAtranscription. We showed that the impact of the stringent stress response on the resistance level may be restricted to beta-lactam resistance based on a "foreign" determinant such asmecA, as opposed to resistance based on mutations in the nativeS. aureusdeterminantpbpB(encoding PBP2). Our observations demonstrate that high-level resistance mediated by the stringent stress response follows the current model of beta-lactam resistance in which the native PBP2 protein is also essential for expression of the resistance phenotype. We also show that theStaphylococcus sciuri pbpDgene (also calledmecAI), the putative evolutionary precursor ofmecA, confers oxacillin resistance in anS. aureusstrain, generating a heterogeneous phenotype that can be converted to high and homogenous resistance by induction of the stringent stress response in the bacteria.
A Hybrid Integrated Laboratory and Inquiry-Based Research Experience: Replacing Traditional Laboratory Instruction with a Sustainable Student-Led Research Project

The Department of Chemistry at American University has replaced its junior- and senior-level laboratory curriculum with two, two-semester long, student-led research projects as part of the department’s American Chemical Society-accredited program. In the first semester of each sequence, a faculty instructor leads the students through a set of previously performed experiments and introduces the students to a research project, specific laboratory techniques, and instrumentation. As such, the first (fall) semester takes the form of a control experiment. During the second (spring) semester, students design and carry out experiments of their own choosing that are based on their research interests and that build upon the first semester’s work. In the subsequent academic year, the research is continued by a new set of students. The research from the previous academic year’s second semester becomes the control experiments of the current academic year’s first semester. In this way, the research project continually...
Lesbian, Gay, or Bisexual (LGB): Caring with Quality and Compassion

Lesbian, gay, and bisexual patients are ubiquitous in medicine. However, patients who identify as such, and those who engage in same-sex sexual behavior, encounter important challenges often different than those in the sexual majority. Education, additional research, and an environment of inclusion are necessary to remove barriers and provide equitable health care. This chapter explores societal stigmas, barriers, and unique health care disparities common to men who have sex with men (MSM), and women who have sex with women (WSW).
Pre-service teachers’ conceptions of effective teacher talk: their critical reflections on a sample teacher-student dialogue

This study aimed to explore pre-service elementary teachers’ (PSTs’) conceptions of effective teacher talk in mathematics instruction, which were interpreted primarily based on the concept of communicative approach. This was accomplished through a task that involves analyzing and evaluating a sample teacher-student dialogue. This study specifically investigated: (a) aspects of the sample dialogue that PSTs attended to in critiquing the teacher talk, (b) PSTs’ espoused conceptions of effective teacher talk in an authoritative-dialogic approach framework, and (c) comparison between PSTs’ interpretations and the researchers’ interpretation. Forty-six elementary PSTs engaged in the task and their responses were analyzed using the inductive content analysis approach. Findings showed that PSTs attended to various features of effective teacher-student dialogue; however, they paid more attention to the form of teacher talk than the function of it in context. PSTs’ justifications used in evaluating the sample teacher-student dialogue showed some glaring differences from researchers’ evaluations in regards to how the presented teacher talk would function in terms of the dialogic-authoritative spectrum. PSTs underscored affective support and clarity of teacher talk at its surface level, while showing strong resistance to the intentional vagueness within teacher talk, which might accommodate more dialogic engagement. This study suggests that initial teacher training programs should include more specific investment in PSTs’ insights into effective use of classroom dialogue for learning.
Sublimation therapy: Helping reason get back to a solid footing

ABSTRACTThis article responds to Professor Tumolo’s “A Sublimed Experience of the Rhetoric of Plato’s Republic.” He selects passages from Plato’s Republic in order to illustrate Plato’s explicit use of rhetoric as a subliminal tool for political control. He finds the Myth of Metals establishes through “public memory” a caste system ensuring that only the golden people, the philosophers, will be considered able rulers. They are the only ones able to see the Truth outside the Cave. Philosophy publically opposes rhetoric because it privately manipulates it for its own power. I respond that Tumolo’s conclusions are too broad for the limited passages that he considers, too literal when considering a dramatic and dialogic text like the Republic, and too committed to a preconceived mind-set that Plato (and philosophy) is opposed to rhetoric and wishes to avoid it. Philosophy and rhetoric do basically differ that one needs to reveal itself for examination and the other to conceal for most effective persuasion, bu...
p66Shc regulates renal vascular tone in hypertension-induced nephropathy

Renal preglomerular arterioles regulate vascular tone to ensure a large pressure gradient over short distances, a function that is extremely important for maintaining renal microcirculation. Regulation of renal microvascular tone is impaired in salt-sensitive (SS) hypertension-induced nephropathy, but the molecular mechanisms contributing to this impairment remain elusive. Here, we assessed the contribution of the SH2 adaptor protein p66Shc (encoded by Shc1) in regulating renal vascular tone and the development of renal vascular dysfunction associated with hypertension-induced nephropathy. We generated a panel of mutant rat strains in which specific modifications of Shc1 were introduced into the Dahl SS rats. In SS rats, overexpression of p66Shc was linked to increased renal damage. Conversely, deletion of p66Shc from these rats restored the myogenic responsiveness of renal preglomerular arterioles ex vivo and promoted cellular contraction in primary vascular smooth muscle cells (SMCs) that were isolated from renal vessels. In primary SMCs, p66Shc restricted the activation of transient receptor potential cation channels to attenuate cytosolic Ca2+ influx, implicating a mechanism by which overexpression of p66Shc impairs renal vascular reactivity. These results establish the adaptor protein p66Shc as a regulator of renal vascular tone and a driver of impaired renal vascular function in hypertension-induced nephropathy.
From superdeformation to extreme deformation and clusterization in the N ≈ Z nuclei of the A ≈ 40 mass region

A systematic search for extremely deformed structures in the N~Z nuclei of the A~40 mass region has been performed for the first time in the framework of covariant density functional theory. At spin zero such structures are located at high excitation energies which prevents their experimental observation. The rotation acts as a tool to bring these exotic shapes to the yrast line or its vicinity so that their observation could become possible with future generation of $\gamma-$tracking (or similar) detectors such as GRETA and AGATA. The major physical observables of such structures (such as transition quadrupole moments as well as kinematic and dynamic moments of inertia), the underlying single-particle structure and the spins at which they become yrast or near yrast are defined. The search for the fingerprints of clusterization and molecular structures is performed and the configurations with such features are discussed. The best candidates for observation of extremely deformed structures are identified. For several nuclei in this study (such as $^{36}$Ar), the addition of several spin units above currently measured maximum spin of $16\hbar$ will inevitably trigger the transition to hyper- and megadeformed nuclear shapes.
Plane Geometry, Archimedean

context: no traces of ancient sources providing a context of similar problems, but: connection to non-trivial theorems/methodological devices with “potential” for future mathematical theories: (i) Diameters in configuration of tangent circles, theorem of Menelaus (→ points of similarity (projective geometry)) (ii) Arithmetical progression (→ complete induction) (iii) Capture infinity using a quasi-mapping onto natural number progression
Efficacy and Safety of Long-term RN-1 Treatment to Increase HbF in Baboons

To the editor: Elevated levels of fetal hemoglobin (HbF; α2γ2) lessen the severity of symptoms and increase the life span of patients with sickle cell disease (SCD).[1][1],[2][2] Hydroxyurea, the only approved drug for the treatment of SCD, is ineffective in a large proportion of patients, and
Dose-dependent progression of parkinsonism in manganese-exposed welders.

Objective: To determine whether the parkinsonian phenotype prevalent in welders is progressive, and whether progression is related to degree of exposure to manganese (Mn)-containing welding fume. Methods: This was a trade union–based longitudinal cohort study of 886 American welding-exposed workers with 1,492 examinations by a movement disorders specialist, including 398 workers with 606 follow-up examinations up to 9.9 years after baseline. We performed linear mixed model regression with cumulative Mn exposure as the independent variable and annual change in Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) as the primary outcome, and subcategories of the UPDRS3 as secondary outcomes. The primary exposure metric was cumulative Mn exposure in mg Mn/m3-year estimated from detailed work histories. Results: Progression of parkinsonism increased with cumulative Mn exposure. Specifically, we observed an annual change in UPDRS3 of 0.24 (95% confidence interval 0.10–0.38) for each mg Mn/m3-year of exposure. Exposure was most strongly associated with progression of upper limb bradykinesia, upper and lower limb rigidity, and impairment of speech and facial expression. The association between welding exposure and progression appeared particularly marked in welders who did flux core arc welding in a confined space or workers whose baseline examination was within 5 years of first welding exposure. Conclusions: Exposure to Mn-containing welding fume may cause a dose-dependent progression of parkinsonism, especially upper limb bradykinesia, limb rigidity, and impairment of speech and facial expression.
Association of tissue factor expression in squamous cell head and neck carcinomas with well-differentiated tumors.

e16022 Background: Tissue factor (TF) is a glycoprotein that initiates coagulation when complexed with factor VIIa. High levels of TF expression have been found in many cancers and correlated with tumor aggressiveness. TF has been shown to be expressed in head and neck squamous cell carcinomas (HNSCC) but the role of TF on cell function and prognosis are not known. The epidermal growth factor receptor (EGFR) is overexpressed in many HNSCC and EGFR and TF expression are highly correlated in some tumor types. Our goal was to correlate the expression of TF and EGFR in HNSCC with tumor cell differentiation and prognosis. Methods: Twenty biopsy specimens of squamous cell head and neck carcinomas were studied. Immunohistochemistry for TF, EGFR, and p16 was performed. Cases were scored based upon the staining intensity of tumor cells using a semiquantitative scale as negative, weakly (+), moderately (++) or strongly (+++) positive. Results: The tumor stages ranged from T1N0 to T4N3. Of the 20 specimens, 5 were w...
GPS or travel diary: Comparing spatial and temporal characteristics of visits to fast food restaurants and supermarkets

To assess differences between GPS and self-reported measures of location, we examined visits to fast food restaurants and supermarkets using a spatiotemporal framework. Data came from 446 participants who responded to a survey, filled out travel diaries of places visited, and wore a GPS receiver for seven consecutive days. Provided by Public Health Seattle King County, addresses from food permit data were matched to King County tax assessor parcels in a GIS. A three-step process was used to verify travel-diary reported visits using GPS records: (1) GPS records were temporally matched if their timestamps were within the time window created by the arrival and departure times reported in the travel diary; (2) the temporally matched GPS records were then spatially matched if they were located in a food establishment parcel of the same type reported in the diary; (3) the travel diary visit was then GPS-sensed if the name of food establishment in the parcel matched the one reported in the travel diary. To account for errors in reporting arrival and departure times, GPS records were temporally matched to three time windows: the exact time, +/- 10 minutes, and +/- 30 minutes. One third of the participants reported 273 visits to fast food restaurants; 88% reported 1,102 visits to supermarkets. Of these, 77.3 percent of the fast food and 78.6 percent supermarket visits were GPS-sensed using the +/-10-minute time window. At this time window, the mean travel-diary reported fast food visit duration was 14.5 minutes (SD 20.2), 1.7 minutes longer than the GPS-sensed visit. For supermarkets, the reported visit duration was 23.7 minutes (SD 18.9), 3.4 minutes longer than the GPS-sensed visit. Travel diaries provide reasonably accurate information on the locations and brand names of fast food restaurants and supermarkets participants report visiting.
Oxidants and Antioxidants

Oxidants are an important source of injury to cells and tissues. The lung is exposed to significantly more oxidants than are most other organs. The lung is unique because of its large epithelial surface area that is directly exposed to high levels of oxygen tension, that is, oxygen pressure in inhaled air is 20 kPa (150 mm Hg). Ambient air contains additional oxidants, including cigarette smoke, asbestos fibers, mineral dust, and environmental carcinogens. A common component in most lung disease is activation of the inflammatory response, which leads to the generation of a relatively large quantity of oxidants. Even some therapeutic interventions, such as ventilation and oxygen therapy in the treatment of prematurely born neonates and acute respiratory distress syndrome, or chemotherapeutic agents, including bleomycin, carmustine, and anthracyclines, enhance oxidant burden to lung tissue.1 Thus, the lung represents a unique tissue exposed not only directly to external environmental oxidants under nor mal conditions but also to inflammation- and therapy-associated oxidants in disease state.
Direct depth distribution measurement of deuterium in bulk tungsten exposed to high-flux plasma

Understanding tritium retention and permeation in plasma-facing components is critical for fusion safety and fuel cycle control. Glow discharge optical emission spectroscopy (GD-OES) is shown to be an effective tool to reveal the depth profile of deuterium in tungsten. Results confirm the detection of deuterium. A ∼46 μm depth profile revealed that the deuterium content decreased precipitously in the first 7 μm, and detectable amounts were observed to depths in excess of 20 μm. The large probing depth of GD-OES (up to 100s of μm) enables studies not previously accessible to the more conventional techniques for investigating deuterium retention. Of particular applicability is the use of GD-OES to measure the depth profile for experiments where high deuterium concentration in the bulk material is expected: deuterium retention in neutron irradiated materials, and ultra-high deuterium fluences in burning plasma environment.
Dopamine reduces cell surface Na+/H+ exchanger-3 protein by decreasing NHE3 exocytosis and cell membrane recycling.

The intrarenal autocrine-paracrine dopamine (DA) system mediates a significant fraction of the natriuresis in response to a salt load. DA inhibits a number of Na+ transporters to effect sodium excretion, including the proximal tubule Na+/H+ exchanger-3 (NHE3). DA represent a single hormone that regulates NHE3 at multiple levels, including translation, degradation, endocytosis, and protein phosphorylation. Because cell surface NHE3 protein is determined by the balance between exocytotic insertion and endocytotic retrieval, we examined whether DA acutely affects the rate of NHE3 exocytosis in a cell culture model. DA inhibited NHE3 exocytosis at a dose-dependent manner with a half maximal around 10-6 M. The DA effect on NHE3 exocytosis was blocked by inhibition of protein kinase A and by brefeldin A, which inhibits endoplasmic reticulum-to-Golgi transport. NHE3 directly interacts with the e-subunit of coatomer protein based on yeast-two-hybrid and coimmunoprecipitation. Because NHE3 has been shown to be recycled back to the cell membrane after endocytosis, we measured NHE3 recycling using a biochemical reinsertion assay and showed that reinsertion of NHE3 back to the membrane is also inhibited by DA. In conclusion, among the many mechanisms by which DA reduces apical membrane NHE3 and induces proximal tubule natriuresis, one additional mechanism is inhibition of exocytotic insertion and reinsertion of NHE3 in the apical cell surface.
Designing Mixed Detergent Micelles for Uniform Neutron Contrast

Micelle-forming detergents provide an amphipathic environment that mimics lipid bilayers and are important tools used to solubilize and stabilize membrane proteins in solution for in vitro structural investigations. Small-angle neutron scattering (SANS) at the neutron contrast match point of detergent molecules allows observing the signal from membrane proteins unobstructed by contributions from the detergent. However, we show that even for a perfectly average-contrast matched detergent there arises significant core-shell scattering from the contrast difference between aliphatic detergent tails and hydrophilic head groups. This residual signal interferes with interpreting structural data of membrane proteins. This complication is often made worse by the presence of excess empty (protein-free) micelles. We present an approach for the rational design of mixed micelles containing a deuterated detergent analog, which eliminates neutron contrast between core and shell, and allows the micelle scattering to be f...
Management of Anaphylaxis

Anaphylaxis is a severe systemic reaction that can be managed appropriately with expedient diagnosis and treatment. Intramuscular epinephrine continues to be the mainstay of treatment of anaphylaxis; however, it is still underused in the community and in the medical setting. Further education and counseling of patients and health care providers is required to prevent and manage anaphylaxis successfully. In-office management of anaphylaxis includes training of staff, preparedness with the necessary supplies and medication, and an effective action plan.
The Multifaceted Role of the Ventromedial Prefrontal Cortex in Emotion, Decision Making, Social Cognition, and Psychopathology.

The ventromedial prefrontal cortex (vmPFC) has been implicated in a variety of social, cognitive, and affective functions that are commonly disrupted in mental illness. In this review, we summarize data from a diverse array of human and animal studies demonstrating that the vmPFC is a key node of cortical and subcortical networks that subserve at least three broad domains of psychological function linked to psychopathology. One track of research indicates that the vmPFC is critical for the representation of reward- and value-based decision making, through interactions with the ventral striatum and amygdala. A second track of research demonstrates that the vmPFC is critical for the generation and regulation of negative emotion, through its interactions with the amygdala, bed nucleus of the stria terminalis, periaqueductal gray, hippocampus, and dorsal anterior cingulate cortex. A third track of research shows the importance of the vmPFC in multiple aspects of social cognition, such as facial emotion recognition, theory-of-mind ability, and processing self-relevant information, through its interactions with the posterior cingulate cortex, precuneus, dorsomedial PFC, and amygdala. We then present meta-analytic data revealing distinct subregions within the vmPFC that correspond to each of these three functions, as well as the associations between these subregions and specific psychiatric disorders (depression, posttraumatic stress disorder, addiction, social anxiety disorder, bipolar disorder, schizophrenia, and attention-deficit/hyperactivity disorder). We conclude by describing several translational possibilities for clinical studies of vmPFC-based circuits, including neuropsychological assessment of transdiagnostic functions, anatomical targets for intervention, predictors of treatment response, markers of treatment efficacy, and subtyping within disorders.
Impact of economic factors and a political conflict on international tourism demand in Nepal: a vector error correction model

A vector error correction model (VECM) was used to determine short- and long-term relationships of the number of international tourists visiting Nepal during 1962–2012 with gross domestic product (GDP) per capita in China, India, Nepal, Sri Lanka, the UK, and the USA; exchange rate of Nepalese rupee (NPR) to the US dollar (USD); and Maoist insurgency. Three foreign economies, India, Sri Lanka, and the USA, had a short-term associations with the annual international tourist arrivals in Nepal. In the long-term, economic growth in Nepal, Sri Lanka, and the USA was associated with international arrivals in Nepal, whereas the economic growth in China, India, and the UK had no long-term associations. The Maoist insurgency had a negative association with international tourist arrivals in the short term, but the relationship was ambiguous in the long term. Nepal's short-term tourism policies should focus on a strategic marketing in regional countries such as China, India, and Sri Lanka, whereas long-term policies should focus on improving Nepal's safety perception and marketing efforts in all countries with a substantial economic growth.
Qualitative Information and Entropy Structures

Information theory deals with the mathematical properties of communication models, which are usually defined in terms of concepts like channel, source, information, entropy, capacity, code, and which satisfy certain conditions and axioms.
Variance and Standard Deviation

In Chapter 12, we show that the mean value µX = E[X] of a random variable locates the center of mass of the induced probability distribution. As the center of mass, the mean value provides important information about the distribution, hence about the values likely to be taken on by the random variable. However, this location of the center of mass is not a sufficient characterization of the distribution for most purposes. Quite different probability distributions may share the same mean value. For example, the random variable X uniformly distributed on the interval (-0.1,0.1) and the random variable Y uniformly distributed on the interval (-100,100) both have zero mean value. But there is far less uncertainty about where to look for an observed value of X than there there is for Y. The difference is the spread of probability mass (hence possible values) about the mean. It is highly desirable to have an appropriate measure of this spread or variation.
THE DESOXYRIBONUCLEIC ACID CONTENT OF ISOLATED NUCLEI OF TUMOR CELLS

In a recent communication Koller (1) has stated his belief that the nucleic acid content of chromosomes rises to abnormally high values in tumor cells. Apparently he believes that this increased content of nucleic acid is related to the cause of malignancy, as he makes the following statement. “Since the amount of nucleic acid and the rate of its production determine the frequency of division, the excess amount of nucleic acid present in the tumour must be considered as the fundamental cause of increased division rate and malignancy.” In this paper we should like to report the results of analyses for desoxyribonucleic acid in nuclei isolated from the cells of the two types of rat tumor, and to compare these results with the total desoxyribonucleic acid content of cell nuclei of normal rat liver. Also, in order to show that other types of cell nuclei may have a much higher desoxyribonucleic acid content than either the cell nuclei of normal liver or the nuclei of the two tumor cells studied, we have included analyses for the desoxyribonucleic acid content of the nuclei of fish spermatozoa and bird eryt,hrocytes.
Abstract 5881: Novel inhibitors of the epigenetic reader protein MBD2

DNA hypermethylation can trigger silencing of tumor suppressor genes during cancer development and progression, partly through binding by methylated-DNA binding proteins (MBD), such as MBD2, that function as “epigenetic readers” and recruit co-repressor complexes to promote gene repression. Inhibiting MBD2-mediated repression represents an attractive cancer therapeutic strategy. Here, we used a cell-based screen to identify small molecules capable of reactivating hypermethylated promoter sequences. We used biochemical, molecular biologic, and pharmacologic approaches to characterize mechanism of action of identified MBD2 inhibitors. A subset of these compounds represent a new class of inhibitors capable of selectively antagonizing interactions between MBD2 and methylated DNA, leading to reactivation of the hypermethylated gene GSTP1 and the epigenetically silenced retinoic acid signaling pathway. Combinations of one of the newly identified MBD2 inhibitors, KCC-08, with the retinoic acid receptor agonist, isotretinoin, significantly reduced cancer cell growth/survival in vitro and in vivo. These novel MBD2 inhibitors are thus positioned for further pharmacologic lead development for use as probes to interrogate epigenetic gene silencing mechanisms and as cancer therapeutics. Citation Format: Hugh Giovinazzo, Zachary R. Reichert, Andries Bergman, Xiaohui Lin, Nicolas Wyhs, David Esopi, Ajay Vaghasia, Jianyong Liu, Yash Jain, Akshay Bhamidipati, Ruchama Steinberg, Traci Speed, Matthew Vaughn, Yonggang Zhang, Nate Brennen, Theodore Deweese, Srinivasan Yegnasubramanian, William G. Nelson. Novel inhibitors of the epigenetic reader protein MBD2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5881.
Practical Design Considerations for Broadband Cognitive Radio Systems: Co-existence

The two main challenges for Cognitive Radio systems are the identification of available bands for opportunistic communication and the co-existence of Cognitive Radio users; these challenges are revisited in this paper. Availability of two potential bands is analyzed based on spectrum sensing results. A mixed signal IC technique is proposed to improve co-existence of Cognitive Radio systems. It is shown that the co-existence of Cognitive Radio systems is improved through spread spectrum technique, at the expenses of major system complexity and limited bandwidth efficiency.
Prevalence of mental health conditions and pain in adults with skeletal dysplasia

We sought to examine the prevalence of depression and anxiety in adults with skeletal dysplasias, and to assess any correlations with pain. Participation was via an anonymous REDCap survey, which consisted of sociodemographic questions followed by the brief pain inventory-short form (BPI-SF), patient health questionnaire-8 (PHQ-8), and generalized anxiety disorder-7 (GAD-7) questionnaires. These assessed pain, depression, and anxiety respectively. Of the 336 usable responses, 16.1% scored 10 or greater on the PHQ-8 consistent with current depression while 17.3% scored 10 or greater on the GAD-7 consistent with current anxiety. The majority of participants (76.2%) experienced pain, which was significantly associated with prior mental health diagnoses (p < 0.05). A total of 34% reported either a prior diagnosis of depression or scored 10 or greater on the PHQ-8, and 31% reported either a prior diagnosis of anxiety or scored 10 or greater on the GAD-7. This study identified a substantial percentage of individuals with mental health concerns as well as pain in the adult skeletal dysplasia population. Further research is warranted to investigate barriers to service or treatment of mental health disorders as well as pain management.
Monolithic-3D Integration with 2D Materials: Toward Ultimate Vertically-Scaled 3D-ICs

This paper evaluates the merits of incorporating two-dimensional (2D) materials into monolithic threedimensional integrated circuits (M3D-IC), in terms of overcoming the major drawbacks of current 3D-ICs, including low thermal process budget, inter-tier signal delay and chip overheating problems. Our analysis reveals for the first time that the 2D-based M3D integration can offer $ > 10 -$folds higher integration density compared with through-silicon-via (TSV)based 3D integration, and $ > 150$% integration density improvement w.r.t conventional M3D integration. Therefore, 2D materials provide a better platform, with respect to bulk materials (such as Si, Ge, etc.), for realizing ultra-high-density M3D-ICs for next-generation electronics.
Childhood abuse predicts affective symptoms via HPA reactivity during mother-infant stress.

Abstract Despite extensive literature positing the hypothalamic-pituitary-adrenal (HPA) axis as a mechanism in the association between early childhood maltreatment and later adult psychopathology, empirical support for this full pathway is lacking. We tested indirect effects of childhood maltreatment on women’s later affective symptomatology via HPA axis responding to a stressor involving their own infant. Women (n = 47) in a larger longitudinal study were assessed following the birth of their infant from 3 to 18 months postnatal. They reported childhood maltreatment history at 3 months and participated in a dyadic stress task with their infant at 12 months, at which time four salivary cortisol samples were collected to assess HPA response. Depression and anxiety symptoms at 18 months (controlling for symptom levels reported at 12 months) served as the primary outcome. Multilevel modeling was used to estimate both levels and dynamics of women’s cortisol response trajectories. Tests of indirect effects revealed a significant effect of total Childhood Trauma Questionnaire (CTQ) scores on anxiety symptoms and a marginally significant effect on depression symptoms. Follow-up analyses with CTQ subscales revealed significant indirect effects of emotional and physical abuse on women’s ongoing anxiety symptoms via more pronounced cortisol reactivity curves during the mother-infant stressor. We discuss methodological choices that may have allowed these effects to be detected in the present study and implications for stress-related risk and intervention.
Cross-sectional associations of tau-PET signal with cognition in cognitively unimpaired adults

Objective To assess cross-sectional associations of neurofibrillary tangles, measured by tau-PET, with cognitive performance in cognitively unimpaired (CU) adults. Methods Tau- and amyloid-PET were performed in 579 CU participants aged 50–98 from the population-based Mayo Clinic Study of Aging. Associations between tau-PET signal in 43 brain regions and cognitive test scores were assessed using penalized linear regression. In additional models, participants were classified by normal/abnormal global amyloid-PET (A+/A−) and normal/abnormal regional tau-PET (T+/T−). Regional tau-PET cutpoints were defined as standardized uptake value ratio (SUVR) greater than the 95th percentile of tau-PET SUVR in that region among 117 CU participants aged 30–49. Results Higher tau-PET signal was associated with poorer memory performance in all medial temporal lobe (MTL) regions and also in the middle temporal pole and frontal olfactory regions. The largest association with tau-PET and memory z scores was seen in the entorhinal cortex; this association was independent of tau-PET signal in other brain regions. Tau-PET in the entorhinal cortex was also associated with poorer global and language performance. In the entorhinal cortex, T+ was associated with lower memory performance among both A− and A+. Conclusions Tau deposition in MTL regions, as reflected by tau-PET signal, was associated with poorer performance on memory tests in CU participants. The association with entorhinal cortex tau-PET was independent of tau-PET signal in other brain regions. Longitudinal studies are needed to understand the fate of CU participants with elevated medial temporal tau-PET signal.