cssi/SciSciGPT-SciSciNet huggingface dataset:
Protein phosphorylation in intact bovine epididymal spermatozoa: identification of the type II regulatory subunit of cyclic adenosine 3',5'-monophosphate-dependent protein kinase as an endogenous phosphoprotein.

An obstacle to the study of protein phosphorylation in mammalian spermatozoa has been the inability to incorporate sufficient amounts of 32P1 into cellular adenosine triphosphate (ATP) (Babcock et a!., 1975). We report conditions under which 32P1 is effectively incorporated into the ATP of intact bovine spermatozoa. In the presence of a bicarbonate-buffered medium containing glucose, spermatozoa incorporated 32P into intracellular ATP in a time-dependent manner; after 2 h of incubation, the specific activity of [y-32PJATP (2.3 x i#{252}� cpm/nmol ATP) was estimated to be 50-65% of the specific activity of the intracellular phosphate pooi. In the absence of glucose or other added substrates, the specific activity of [7�32 P]ATP was 1025% that of the specific activity observed in the presence of glucose. Washed spermatozoa incubated in carrier-free 32P1 for 2 h at 37#{176}C, and solubilized in a solution containing final concentrations of 6.8 M urea, 6% NP4 0, and 5% 13-mercaptoethanol contained in excess of 40 32P�labeled proteins as assessed by two-dimensional polyac,ylamide gel electrophoresis. Major phosphoproteins had approximate molecular weights of 93,000, 40,000, and 22,000. A different two-dimensional gel pattern was observed when cells were extracted with a solution containing 38.5mM 2[N-cyclohexylaminoJ ethanesulfonic acid (CHES), pH 9.5/1.5% sodium dodecyl sulphate (SDS) at 100#{176} C. In contrast to the urea/Nonidet P-40 (NP4O)43-mercaptoethanol extract, a 56,000 Mr phosphoprotein represented a major component while the 40,000 Mr and several of the 22,000 Mr polypeptides were markedly reduced in radioactive intensity. The 56,000 Mr species present in the CHES/SDS extract comigrated with the purified, phosphoiylated regulatory subunit (Rfl) of cyclic adenosine 3’, 5’-monophosphate-dependent protein kinase from bovine heart. Antibodies to RH immunoprecipitated a 56,000 Mr, 32P-labeled polypeptide from the CHES/SDS extract that comigrated with purified, 132 P1 Rjj after two-dimensional electrophoresis. Rjj, then, appears to represent one of the endogenous phosphoproteins of intact bovine epididymal spermatozoa.
Analysis of the peroxiredoxin family: using active-site structure and sequence information for global classification and residue analysis.

Peroxiredoxins (Prxs) are a widespread and highly expressed family of cysteine-based peroxidases that react very rapidly with H2O2, organic peroxides, and peroxynitrite. Correct subfamily classification has been problematic since Prx subfamilies are frequently not correlated with phylogenetic distribution and diverge in their preferred reductant, oligomerization state, and tendency towards overoxidation. We have developed a method that uses the Deacon Active Site Profiler (DASP) tool to extract functional site profiles from structurally characterized proteins, to computationally define subfamilies, and to identify new Prx subfamily members from GenBank(nr). For the 58 literature-defined Prx test proteins, 57 were correctly assigned and none were assigned to the incorrect subfamily. The >3500 putative Prx sequences identified were then used to analyze residue conservation in the active site of each Prx subfamily. Our results indicate that the existence and location of the resolving cysteine varies in some subfamilies (e.g. Prx5) to a greater degree than previously appreciated and that interactions at the A interface (common to Prx5, Tpx and higher order AhpC/Prx1 structures) are important for stabilization of the correct active site geometry. Interestingly, this method also allows us to further divide the AhpC/Prx1 into four groups that are correlated with functional characteristics. The DASP method provides more accurate subfamily classification than PSI-BLAST for members of the Prx family and can now readily be applied to other large protein families.
THE EFFECT OF CYTOTOXIC AGENTS ON THE PASSIVE TRANSFER OF CELL-MEDIATED IMMUNITY

A system involving the passive transfer of committed lymphoid cells from Listeria-immune donors has been used to study the phases of the immune response which are sensitive to the immunosuppressive action of various cytotoxic agents. The agents investigated included cyclophosphamide, vinblastine, methotrexate, azathioprine, and X-irradiation. Complete suppression of passive immunization was obtained by the administration of cyclophosphamide or vinblastine to recipients at the time of cell transfer or by prior X-irradiation of recipients a day before cell transfer. Methotrexate was only partially suppressive, whereas azathioprine had no effect at all. The donor cell responsible for the transfer of immunity to recipients was shown to be a resting cell which is sensitive to the action of cyclophosphamide but not to vinblastine. The results of this investigation suggest that the donor cells undergo multiplication in the tissues of the recipient, presumably in response to specific stimulation by Listeria antigens. This in turn results in the activation of host macrophages. The immunosuppressive action of cyclophosphamide, vinblastine, and irradiation in the cell-transfer system has been discussed in relation to a direct cytotoxic action on the immune lymphoid cells of the donor and specific interference with their proliferation in the recipient, as well as impairment of macrophage production on the part of the recipient itself.
On linear predictors for MIMO channels and related blind identification and equalization

The existence of finite-length one-step linear predictors plays a key role in several existing algorithms for blind identification and equalization of multiple-input multiple-output (MIMO) systems. An upper bound on the length of the predictor is known for the case when the underlying MIMO transfer function is irreducible and column-reduced. When the MIMO transfer function is irreducible but not necessarily column-reduced, it is known that a finite-length linear predictor exists; however, its length has not been specified in the literature. An upper bound on the length of a linear predictor for MIMO systems with irreducible transfer functions is derived.
Death Domain Mutagenesis of KILLER/DR5 Reveals Residues Critical for Apoptotic Signaling

Abstract The Fas/tumor necrosis factor (TNF)/TRAIL receptors signal death through a cytoplasmic death domain (DD) containing six α-helices with positively charged helix 2 interacting with negatively charged helix 3 of another DD. DD mutation occurs in head/neck and lung cancer (TRAIL receptor KILLER/DR5) and inlpr mice (Fas). We examined the apoptotic potential of known KILLER/DR5 lung tumor-derived mutants (n = 6) and DD mutants (n = 18) generated based on conservation with DR4, Fas, Fas-associated death domain (FADD), and tumor necrosis factor receptor 1 (TNFR1). With the exception of Arg-330 required in Fas or FADD for aggregation or for TNFR1 cytotoxicity, surprisingly major loss-of-function KILLER/DR5 alleles (W325A, L334A (lpr-like), I339A, and W360A) contained hydrophobic residues. Loss-of-function of I339A (highly conserved) has not been reported in DDs. Charged residue mutagenesis revealed the following points. 1) E326A, conserved in DR4, is dispensable for death; the homologous residue is positively charged in Fas, TNFR1, and FADD and is critical for DD interactions. 2) K331A, D336A, E338A, K340A, K343A, and D351A have partial loss-of-function suggesting multiple charges stabilize receptor-adapter interactions. Analysis of the tumor-derived KILLER/DR5 mutants revealed the following. 1) L334F has partial loss-of-function versus L334A, whereas E338K has major loss-of-function versus E338A, examples where alanine and tumor-specific substitutions have divergent phenotypes. 2) Unexpectedly, S324F, E326K, K386N, and D407Y have no loss-of-function with tumor-specific or alanine substitutions. Loss-of-function KILLER/DR5 mutants were deficient in recruitment of FADD and caspase 8 to TRAIL death-inducing signaling complexes. The results reveal determinants within KILLER/DR5 for death signaling and drug design.
the fitness consequences of P element insertion in Drosophila melanogaster

In this study we estimate the frequency at which P-element insertion events, as identified by in situ hybridization, generate lethal and mild viability mutations. The frequency of lethal mutations generated per insertion event was 0·004. Viability dropped an average of 1% per insertion event. Our results indicate that it is deletions and rearrangements resulting from the mobilization of P elements already in place and not the insertions per se that cause the drastic effects on viability and fitness observed in most studies of P–M dysgenesis-derived mutations. Elements of five other families (I, copia, 412, B104, and gypsy) were not mobilized in these crosses. Finally, we contrast the density of P elements on the X chromosome with the density on the four autosomal arms in a collection of thirty genomes from an African population. The relative number of P elements on the X chromosome is too high to be explained by either a hemizygous selection or a neutrality model. The possible reasons for the failure to detect selection are discussed.
Learning query intent from regularized click graphs

This work presents the use of click graphs in improving query intent classifiers, which are critical if vertical search and general-purpose search services are to be offered in a unified user interface. Previous works on query classification have primarily focused on improving feature representation of queries, e.g., by augmenting queries with search engine results. In this work, we investigate a completely orthogonal approach --- instead of enriching feature representation, we aim at drastically increasing the amounts of training data by semi-supervised learning with click graphs. Specifically, we infer class memberships of unlabeled queries from those of labeled ones according to their proximities in a click graph. Moreover, we regularize the learning with click graphs by content-based classification to avoid propagating erroneous labels. We demonstrate the effectiveness of our algorithms in two different applications, product intent and job intent classification. In both cases, we expand the training data with automatically labeled queries by over two orders of magnitude, leading to significant improvements in classification performance. An additional finding is that with a large amount of training data obtained in this fashion, classifiers using only query words/phrases as features can work remarkably well.
Some Geographical and Political Aspects to Relations between Egypt and Nubia in C-Group and Kerma Times, ca. 2500 – 1500 B.C.

New evidence illuminates several problems in the historical geography of Nubia and its political relations with Egypt. At Gebel Uweinat, an inscription naming the country of Yam has changed what we know of the political and cultural geography of the peoples south of Egypt in the late Third Millennium. Regions of Northeastern Africa have been explored, such as the southern Atbai and the Fourth Cataract of the Nile, which is now fairly well known. Connections between these areas and lower Nubia help to understand the development of the archaeological culture known as the Pan Graves. The discovery of a new inscription in Upper Egypt and at Gebel Uweinat have challenged our assumptions about the scale of the Kushite state and its geography in the Second Intermediate Period. The changes are substantial, but they can be integrated with earlier evidence to produce a credible picture of Nubian-Egyptian relations. DOI:10.2458/azu_jaei_v06i1_williams
Damping in Discrete Linear Elastic Systems

Analysis shows that if the viscous damping in a linear elastic system can be represented in the form C = Σ β i (BS) i in which S and B represent the stiffness and universe of the mass matrix, respectively, and the β i are scalar constants, then the mode shapes for damped and undamped vibration are identical. The assumption of small damping is not imposed. It is shown how the damping matrix can be constructed when the damping ratios in the normal modes of vibration are known.
A balancing act: manipulating reactivity of shape-controlled metal nanocatalysts through bimetallic architecture

Manipulating the electronic structure of metal nanocrystals is one way of altering their catalytic activities. This ability is demonstrated here by introducing a Au interior to shape-controlled Pd nanocrystals, producing core@shell Au@Pd nanoparticles with varying shell thicknesses. As revealed by X-ray photoelectron spectroscopy, the electronic structure of the Pd shell depends on its thickness. These core@shell nanocrystals were used to catalyze two model reactions: selective hydrogenation of 2-hexyne and oxidation of formic acid, where different reactivities were found also as a function of shell thickness. The comparison of particles with varying bimetallic architecture but identical geometric features provides insight into how electronic regulation in a catalytic reaction can be achieved. It is concluded that a balance in binding interaction between the molecular substrate and catalyst surface is necessary to design an efficient catalyst and can be achieved with shape-controlled core@shell nanocrystals.
Mammography: review of the controversy, health disparities, and impact on young african american women.

Background Ongoing debate about mammography screening for women in their 40s has brought awareness to the opportunities and challenges for achieving optimal breast health in young African American women and in battling health inequities that place them at greater risk for mortality from breast cancer. Despite the screening controversy, a need exists to understand the complex issues related to mammography knowledge, attitudes, and behaviors of young minority women, while empowering them to take an active role in their breast health care. Objectives The purpose of this article is to describe the complicated issues related to screening in young African American women within the context of the uncertainty about the evidence surrounding screening practices. Methods Literature was reviewed to garner a comprehensive update of the mammography screening controversy and its impact on mammography practices. Findings Nurses should be aware of the mammography screening controversy and breast cancer risk assessment and how they affect young women's participation in mammography screening. Mammography screening should be a shared decision between the patient and healthcare provider. A better understanding of breast health and its effect on young minority women is needed. Nurses have a prominent role to advocate for, empower, and educate patients as they face the task of deciding whether to begin or continue mammography in their 40s.
Expression of T cell antigens by cells in mouse and human primary and secondary follicles.

Peripheral lymphoid organs are divided into predominantly B cell domains (primary and secondary follicles) and T cell domains (lymph node paracortex in spleen periarteriolar sheath). Occasional T cells have been described within these B cell regions (Gutman and Weissman, 1972). Since these regions are potential sites for T and B cell collaboration, we have studied the phenotype of T cells in the follicles of mouse and human lymphoid organs.
Paul Zweifel, pioneer fetal physiologist. A centennary tribute.

The demonstration by Paul Zweifel a hundred years ago (1876) that the fetus in utero consumes oxygen marks the beginning of the modern era of research on foetal physiology. The circumstances which led to the demonstration are reviewed, and its importance acknowledged anew as a tribute to Zweifel's many contributions to obstetrics and gynecoloy.
Developmental Lung Disease

The development of the male and female mature human lungs is a highly regulated process controlled by genetic, epigenetic, hormonal, and environmental factors. Depending on the stage of lung development these come into play, they may have a different effect in male and female lung health. Normal lung development and growth varies in males and females, and it is differentially affected by risk factors that can result in reduced lung function, and persistent physiological effects that can predispose individuals to lung disease. In this chapter, we discuss major sex differences identified at the various stages of lung development, from embryonic to adult life, in terms of lung morphology, gene expression, hormonal regulation, epigenetic control, and the influence of environmental exposures.
Recalling basal cell carcinoma patients. A regional survey.

background. Patients with a basal cell carcinoma (BCC) are at increased risk for developing further BCCs, and long-term follow-up has been recommended to detect new cancers at an earlier, more easily treatable stage. The majority of BCCs are treated by dermatologists in their offices; we do not know to what extent they perform long-term follow up on their patients. objective. To determine how practicing dermatologists follow up their BCC patients. methods. A mailed questionnaire survey of 166 practicing members of a regional dermatologic society (the San Francisco Dermatological Society), to which 142 (85%) replied. results. Two thirds of the respondents recalled BCC patients for screening examinations; of these, 58% followed up non-responders. Recall efforts were hampered by inefficient, unwieldy, and time-consuming techniques. conclusion. Practicing dermatologists are motivated to recall BCC patients for examination, but guidelines and techniques for effective and efficient computerized recalling of skin cancer patients are needed. It is suggested that the American Academy of Dermatology set up a task force to develop guidelines and criteria for effective recall software.
On the effectiveness of labeled latent dirichlet allocation in automatic bug-report categorization

Bug-reports are valuable sources of information. However, study of the bug-reports' content written in natural language demands tedious human efforts for manual interpretation. This difficulty limits the scale of empirical studies, which rely on interpretation and categorization of bug-reports. In this work, we investigate the effectiveness of Labeled Latent Dirichlet Allocation (LLDA) in automatic classification of bug-reports into a predefined set of categories.
Migration Policy and Autocratic Power

Throughout history, control over the movement of citizens has been a central source of autocratic power. Yet modern autocracies vary considerably in how much they limit the freedom to emigrate. Although mass exit can threaten autocratic leaders, emigration can also stabilize regimes by expelling dissidents and encouraging remittances. We disentangle these effects by analyzing the interaction between migration flows, democratic change, and regimes' strategic choices of emigration policy, something that has been neglected in the literature. Despite globalization, we show that emigration freedom has been steadily declining in autocracies since 1980. Using a half-century of bilateral migration data, we calculate the level and targets of expected emigration given exogenous geographic and socioeconomic characteristics. We find that when citizens are more likely to emigrate to democracies, autocracies lower emigration freedom in response. Nevertheless, these countries remain more likely to democratize. Surprisingly, total expected emigration, which tracks the feasibility of exit, predicts autocratic stability and greater emigration freedom.
Testing Molecular Homogeneity at the Nanoscale with Massive Cluster Secondary Ion Mass Spectrometry.

This study deals with assessing the homogeneity of a mixture of ultrasmall nanoparticles differing only by their respective functionalization. While measuring the relative abundance of nanoparticles with specific functionalization is feasible with mass spectrometry, the determination of mixed or segregated moieties is beyond current capabilities. Our approach is based on SIMS with massive projectiles, specifically Au400+4. A distinct feature of bombardment with Au400+4 is abundant emission of multiple secondary ions from one projectile impact. Their analysis allows for examination of coemitted and thus colocalized molecules within the emission area of a single impact (∼10–15 nm in diameter). It is possible to collect the mass spectrum from each projectile impact, which probes individual nanodomains, allowing for examination of molecular homogeneity at the nanoscale.
The Group IA and IIA Metals

The elements that constitute Groups IA and IIA of the periodic table are the active metals known as the alkali metals and alkaline earths, respectively. Because of their reactivity, none of these elements is found free in nature. Moreover, because they are difficult to reduce, equation ( 7.1 ) Group IA M + +e − →M Group IA M + + e − → M equation ( 7.2 ) Group IIA M2++2 e − →M Group IIA M 2 + + 2 e − → M they were not easy enough to reduce by the chemical means available to the ancients. Therefore, the uncombined elements were not obtained until comparatively recently. Most of the metals were obtained by electrochemical means in the early 1800s. However, several compounds of the Group IA and IIA metals have been known since the earliest times. Salt (NaCl), limestone (CaCO 3 ), and sodium carbonate (Na 2 CO 3 ) have had important uses throughout history.
Distributed Iteratively Quantized Kalman Filtering for Wireless Sensor Networks

Estimation and tracking of generally nonstationary Markov processes is of paramount importance for applications such as localization and navigation. In this context, ad hoc wireless sensor networks (WSNs) offer distributed Kalman filtering (KF) based algorithms with documented merits over centralized alternatives. Adhering to the limited power and bandwidth resources WSNs must operate with, this paper introduces a novel distributed KF estimator based on quantized measurement innovations. The quantized observations and the distributed nature of the iteratively quantized KF algorithm are amenable to the resource constraints of the ad hoc WSNs. Analysis and simulations show that KF-like tracking based on to bits of iteratively quantized innovations communicated among sensors exhibits MSE performance identical to a KF based on analog-amplitude observations applied to an observation model with noise variance increased by a factor of [1 - (1 - 2/pi)m] -1. With minimal communication overhead, the mean-square error (MSE) of the distributed KF-like tracker based on 2-3 bits is almost indistinguishable from that of the clairvoyant KF.
Improving module temperature measurements using averaging resistive temperature devices

Determination of module temperature coefficients for voltage, current and power requires measuring the average of cell temperatures. Conventional practice is to place thermocouples or resistive temperature devices (RTDs) at a few locations on a module's back surface and to average the readings, which may not accurately represent the average temperature over all cells. We investigate the suitability of averaging RTDs, which measure average temperature along a 1m length, to accurately measure the average cell temperature when determining temperature coefficients outdoors.
I-Monoaryl-polyenes

The stereo chemical relationships in the extended class of mono-aryl-polyenes will be illustrated by two very different substances: I-Phenylbutadiene is a lower molecular weight, volatile liquid; hence, the separation of its spatial forms has been carried out mainly by distillation and by treatment with maleic anhydride (cf. 6); in contrast, the separation of the higher molecular weight, non-volatile polyene, I-phenyl-undecapentaenal set has required chromatographic methods.
Diagnostic accuracy of cardiac positron emission tomography versus single photon emission computed tomography for coronary artery disease: a bivariate meta-analysis.

Background—Positron emission tomography (PET) myocardial perfusion imaging (MPI) offers technical benefits compared with single photon emission computed tomography (SPECT) MPI, but there has been no systematic comparison of their diagnostic accuracy for coronary artery disease. We performed a bivariate meta-analysis of the published literature to compare the sensitivity and specificity of PET versus SPECT stress MPI for ≥50% stenosis of any epicardial coronary artery in patients with known or suspected coronary artery disease. Methods and Results—We searched MEDLINE and EMBASE from inception through January 2012 and the references of identified studies for prospective, English language studies that evaluated the sensitivity and specificity of PET and/or SPECT MPI with coronary angiography as the reference standard and reported sufficient data to calculate patient-level true and false positives and negatives. Two investigators independently extracted patient and study characteristics; a third investigator resolved any disagreements. We identified 117 studies, including 108 evaluating SPECT MPI, 4 evaluating PET MPI, and 5 evaluating both modalities. Bivariate meta-analysis demonstrated a significantly higher pooled mean sensitivity with PET (92.6% [95% Confidence Interval, 88.3% to 95.5%]) compared with SPECT (88.3% [95% confidence interval, 86.4% to 90.0%]) (P=0.035). No significant difference in specificity was observed between PET (81.3% [95% confidence interval, 66.6% to 90.4%]) and SPECT (75.8% [95% confidence interval, 72.1% to 79.1%]) (P=0.39). Few studies investigated coronary angiography with PET. Only 5 studies directly compared SPECT and PET. Conclusions—In a meta-analysis of 11,862 patients, PET MPI demonstrated a higher sensitivity for coronary artery disease than SPECT MPI. No difference in specificity was detected in the pooled analysis of PET and SPECT MPI. (Circ Cardiovasc Imaging. 2012;5:700-707.)
Micromechanical Analysis of Strength of Polymer Networks with Polydisperse Structures

The effect of network chain distribution on the mechanical behavior of elastomers is one of the long-standing problems in rubber mechanics. The classical theory of rubber elasticity is built upon the assumption of entropic elasticity of networks whose constitutive strands are of uniform length. The kinetic theories for vulcanization, computer simulations, and indirect experimental measurements all indicate that the microstructure of vulcanizates is made of polymer strands with a random distribution of length. The polydispersity in strand length is expected to control the mechanical strength of rubber as the overloaded short strands break at small deformations and transfer the load to the longer strands. The purpose of the contributions presented in this thesis is to present simple theories of rubber mechanics that take into account the length distribution of strands and its effect on elasticity and the onset of bulk failure in unfilled and filled elastomers. In unfilled system, the population of short chains is identified as the culprits for damage initiation. Upon deformation of a polydisperse network, shorter strands break at considerably smaller stretches compared to the longer ones. The network alteration continues concurrent with increasing deformation and controls the onset of mechanical failure. In the filled networks, the degradation in network mechanical behavior is assumed to be controlled by the adhesive failure of the short strands adsorbed onto the filler surface. The finite extensibility of the short adsorbed strands is a key determinant of mechanical strength.
Abstract 1122: ATR inhibitors synergize with PARP inhibitors in killing glioblastoma stem cells and treating glioblastoma

PARP inhibitors (PARPi) have been used alone or in combination with other agents for the treatment of tumors with homologous repair (HR) deficiencies. However, challenges remain for the treatment of tumors that are PARPi-resistant or HR-proficient. Glioblastoma (GBM) is an invariably lethal tumor that is not associated with HR deficiencies. GBM stem cells (GSCs), thought to be critical for tumor growth and resistance to therapy, can be isolated from GBM specimens and are representative of the patient9s tumors. GSCs exhibit variable PARPi sensitivity, with at least half being resistant. In order to enhance the antitumor efficacy of PARPi for GBM, we examined the combination of PARPi with inhibitors of oncogenic or DNA damage pathways, including inhibitors of PTEN, PI3K, ATM, ATR, and temozolomide, some of which have been reported to sensitize cancer cells to PARPi. Only inhibitors of ATR (VE821, VE822, AZ20) synergized with PARPi in killing GSCs in vitro. VE822 inhibited ATR activity both in vitro and in vivo, and modestly, but significantly, extended survival in mice bearing GSC-derived tumors. However, ATR inhibitor (ATRi) in combination with PARPi further prolonged survival, compared to each drug alone, even in mice bearing PARPi-resistant GSC-derived tumors. This is the first report that ATRi alone or in combination with PARPi is effective in treating GBM and provides a rationale for clinical trials for GBM. Citation Format: Jianfang Ning, Hiroaki Wakimoto, Robert L. Martuza, Samuel D. Rabkin. ATR inhibitors synergize with PARP inhibitors in killing glioblastoma stem cells and treating glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1122. doi:10.1158/1538-7445.AM2017-1122
Teaching user centered design and content through image tweets: a social constructivist approach

By designing image based social media, students can gain rapid, hands-on understanding of user experience design and content principles. This paper provides an overview of a pedagogical research project on using image tweets in a freshman design class taught in a journalism school, with the goal of introducing students to principles of user experience design and content.
Engineering chemical interactions in microbial communities

Microbes living within host-associated microbial communities (microbiotas) rely on chemical communication to interact with surrounding organisms. These interactions serve many purposes, from supplying the multicellular host with nutrients to antagonizing invading pathogens, and breakdown of chemical signaling has potentially negative consequences for both the host and microbiota. Efforts to engineer microbes to take part in chemical interactions represent a promising strategy for modulating chemical signaling within these complex communities. In this review, we discuss prominent examples of chemical interactions found within host-associated microbial communities, with an emphasis on the plant-root microbiota and the intestinal microbiota of animals. We then highlight how an understanding of such interactions has guided efforts to engineer microbes to participate in chemical signaling in these habitats. We discuss engineering efforts in the context of chemical interactions that enable host colonization, promote host health, and exclude pathogens. Finally, we describe prominent challenges facing this field and propose new directions for future engineering efforts.
Perplexed in Translation: Bringing a Language Disorder to College

Speech and language disorders significantly impact a youth’s quality of life and education status. Mild to moderate language impairments can be subtle and difficult to detect. Youth with Learning Disabilities transitioning to adulthood often have impact in the areas of post-secondary education, social communication and ultimate employment. The practicing clinician has an important role to play in facilitating collaboration among the student with learning challenges, the family, and the special education staff at the high school to ensure a realistic and solid understanding of the student’s learning challenges and strengths. Transition preparation and planning involves more than arranging for services at the post-secondary institution. It involves helping the student develop skills and strategies to manage learning issues, practicing self-advocacy skills, and working with the student to create a portable learning plan that can be taken to college.
Biomedical and Behavioral Outcomes of Keep It Up!: An eHealth HIV Prevention Program RCT

Introduction HIV diagnoses among young men who have sex with men are increasing, but few effective HIV prevention interventions exist for this population. An RCT was conducted of the online Keep It Up! intervention to determine if it significantly reduced condomless anal sex and sexually transmitted infections compared with an HIV knowledge condition. Study design From May 2013 to March 2017, a total of 901 participants were enrolled in a double-blinded RCT of Keep It Up! with 1-year follow-up. After completing baseline surveys and sexually transmitted infection testing, participants were randomized by an eHealth platform to the intervention or control condition. Setting/participants HIV-negative men who have sex with men reporting condomless anal sex, aged 18–29 years, were recruited through advertising and from HIV testing sites and outreach in Atlanta, Georgia; Chicago, Illinois; and New York, New York. Intervention Multimedia was used to address HIV knowledge and motivate safer behaviors. The control condition reflected existing online HIV information. Main outcome measures Primary outcomes were incident gonorrhea or chlamydia at 12-month follow-up and self-reported condomless anal sex with casual partners at 3-, 6-, and 12-month follow-up. Results In 2017, data were analyzed from 445 (49%) participants randomized to the intervention and 456 (51%) to the control. Participants were primarily racial/ethnic minorities (63%). Sexually transmitted infections at Month 12 was 40% lower for intervention participants (risk ratio=0.60, 95% CI=0.38, 0.95, p=0.01). For the primary behavioral outcome, both arms showed reductions over time with 44% of control and 37% of intervention participants reporting condomless anal sex at Month 12 (prevalence ratio=0.83, 95% CI=0.70, 0.99, p=0.04). Conclusions The Keep It Up! intervention resulted in significantly lower sexually transmitted infection incidence and a small but significant decrease in condomless anal sex 12 months post-intervention relative to an online HIV knowledge condition. In addition, this study demonstrated the feasibility and acceptability of at-home sexually transmitted infection testing as part of an eHealth intervention. Trial registration This study is registered at www.clinicaltrials.gov NCT01836445.
Ras-associating domain proteins: a new class of cyclic nucleotide-gated channel modulators.

The Ras is a protein subfamily of small GTPases that are involved in cellular signal transduction. Members of Ras family are all related in structure and regulate diverse cell behaviors. Ras-associating/binding (RA/RBD) domain-containing proteins perform several different functions ranging from tumor suppression to being oncoproteins. Their role in different biological processes may be unclear and highly divergent but what is clear is that they convergently function by interacting with Ras proteins through their RA/RBD subdomains directly or indirectly. Apart from interacting with Ras proteins, there is no perceptible relationship between these proteins or their highly unrelated protein bodies. The heterogeneity among these RA domains allows them to interact with Ras proteins of different types as well as several other proteins which contain similar motifs. Very recently, we have demonstrated that growth factor receptor bound protein 14 (Grb14) RA domain binds to photoreceptor cyclic nucleotide-gated channel (CNG) and inhibits its activity in vivo. In this study, we have examined two other RA domain-containing protein phosphates expressed in retina, PHLPP1, and PHLPP2 on CNG channel activity. Our data indicate that not all RA domain proteins are modulators of CNG channel, suggesting the existence of heterogeneity among several RA domain proteins.
Automatic Code Generation: Model-Code Semantic Consistency.

Automatic translation or code generation of software models to code may help alleviate problems associated with manual coding effort. This paper emphasizes the importance of attaining a high level of assurance that the process of automatically translating model to code is correct. It illustrates modeling experiments performed using Statemate (iLogix) to establish a correspondence between model elements and code constructs. The research is a step towards achieving assurance of semantic consistency between model and generated code.
Diversity of Structures, Catalytic Mechanisms and Processes of Cofactor Biosynthesis of Tryptophylquinone-Bearing Enzymes

Tryptophyquinone-bearing enzymes contain protein-derived cofactors formed by posttranslational modifications of Trp residues. Tryptophan tryptophylquinone (TTQ) is comprised of a di-oxygenated Trp residue, which is cross-linked to another Trp residue. Cysteine tryptophylquinone (CTQ) is comprised of a di-oxygenated Trp residue, which is cross-linked to a Cys residue. Despite the similarity of these cofactors, it has become evident in recent years that the overall structures of the enzymes that possess these cofactors vary, and that the gene clusters that encode the enzymes are quite diverse. While it had been long assumed that all tryptophylquinone enzymes were dehydrogenases, recently discovered classes of these enzymes are oxidases. A common feature of enzymes that have these cofactors is that the posttranslational modifications that form the mature cofactors are catalyzed by a modifying enzyme. However, it is now clear that modifying enzymes are different for different tryptophylquinone enzymes. For methylamine dehydrogenase a di-heme enzyme, MauG, is needed to catalyze TTQ biosynthesis. However, no gene similar to mauG is present in the gene clusters that encode the other enzymes, and the recently characterized family of CTQ-dependent oxidases, termed LodA-like proteins, require a flavoenzyme for cofactor biosynthesis.
Infections Complicating Orthopedic Surgery and Implants

Given the frequent utilization of devices and implants to provide stability and/or correct deformity, infections complicating orthopedic surgery in children can present management challenges. In these cases it is necessary to ensure both the eradication of infection and the successful healing of the initial orthopedic intervention. This requires a balance between thorough debridement of infected tissue and avoidance of unnecessary surgical procedures and attendant complications. Furthermore, in the skeletally immature child, consideration must be given to ensuring continued optimal growth. Such infections are best managed through a multidisciplinary approach including the orthopedic surgeon, infectious disease specialist, and generalist guided by laboratory data, clinical assessment, and risks/benefits of implant removal.
Cancer: Context Is Key for E-cadherin in Invasion and Metastasis

A recent paper demonstrates how tissue context impacts the breast cancer cell phenotype. Loss of the E-cadherin tumor suppressor protein enhanced cell invasion, but inhibited multiple steps in metastatic spread due to the accumulation of reactive oxygen species and induction of apoptosis.
Faculty Acceptance of the Peer Assessment Collaboration Evaluation Tool: A Quantitative Study.

The problem this study sought to address was faculty reluctance to use new online peer-assessment tools. The purpose of this study was to examine the motivational factors that influence the acceptance of the Peer Assessment Collaboration Evaluation (PACE) Tool among faculty employed at a mid-sized university in the Southeastern United States. This study used Davis’s (1986) technology acceptance model (TAM) and motivational constructs “attitude toward using, perceived usefulness and perceived ease of use” (p. 44). The researcher used simple linear regression and standard multiple regression to determine if there was a significant relationship, if any, between the motivational constructs. The results of the linear regressions denoted positive, significant relationships between perceived ease of use of the PACE Tool and attitude toward using the PACE Tool, perceived usefulness of the PACE Tool and attitude toward using the PACE Tool; and perceived ease of use of the PACE Tool and perceived usefulness of the PACE Tool. The results of the multiple regression indicated that both perceived ease of use and perceived usefulness of the PACE Tool were positively, significantly related to attitude toward using the PACE Tool. Through faculty members’ speculations, the researcher was able to measure their motivation to use the PACE Tool. The results of this study demonstrated faculty members are motivated to use the PACE Tool, which indicates high acceptability and potential usage in the future. By understanding how faculty members perceive the PACE Tool, designers may be able to develop online peer-assessment tools that are more acceptable.
Evaluation of Cell Harvesting Techniques to Optimize Lipidomic Analysis from Human Meibomian Gland Epithelial Cells in Culture

The lipidomic analysis of immortalized human meibomian gland epithelial cells (HMGECs) has been proposed as a preclinical model to study meibomian gland dysfunction. An in vitro study was conducted to evaluate neutral lipid recovery following three harvesting techniques and to identify candidate lipid biomarkers of HMGECs. HMGECs were cultured in serum-containing media for two days to promote lipid production. Cells were either harvested by 0.25% trypsin–ethylenediaminetetraacetic acid (EDTA), harvested by 10 mM EDTA, or simultaneously harvested and extracted by 2:1 chloroform–methanol (CM). After extraction by a modified Folch technique, the nonpolar phase was processed and infused into a TripleTOF 5600 mass spectrometer (Sciex, Framingham, MA, USA) with electrospray ionization. MS and MS/MSall spectra were acquired. Nonpolar cholesteryl esters (CEs) were consistently detected in all samples, while wax esters were not. Only small differences in two out of twenty CEs were detected between harvesting methods. CM yielded less CE18:1 than the other methods but greater CE20:4 than the trypsin–EDTA method (p < 0.05 for all). Similar to human meibum, very long-chain CEs with carbon number (nc) ≥ 24 were detected in all samples and may serve as HMGEC lipid biomarkers. Further work is needed to address the absence of wax esters. Overall, the three harvesting methods are reasonably equivalent, though CM promotes much better efficiency and is recommended for higher throughput.
Insight Into the Movement Behaviors of Nursing Home Residents Living With Obesity: A Report of Two Cases.

Obesity (body mass index [BMI] ≥30 kg/m2) can have a profound influence on the likelihood of developing a pressure injury (PrI); little is known about the movement behaviors (movement frequency, body position frequency, and position duration) of obese individuals. Purpose This report examines 2 cases of obese nursing home residents and their movement behaviors in relation to their potential influence on overall PrI risk. Methods Resident movements were monitored 24 hours/day using a wearable sensor, and repositioning events were observed as part of a larger study examining repositioning intervals. Braden Pressure Ulcer Risk Assessment was conducted weekly. Results Both residents (BMI 39 kg/m2 and 50 kg/m2) had limitations in movement with prolonged periods spent in a single body position. Each resident addressed movement challenges unique to their desire to remain mobile and level of dependency on nursing staff. Conclusion Presence of obesity is a factor affecting resident movement and creates environmental and psychosocial barriers to health. Nurses can play a key role in PrI prevention by addressing these barriers and encouraging positive, long-term behavior changes that mitigate risk. Future research should guide tailored PrI prevention protocols and national/ international guidelines for obese residents.
Frailty after lung transplantation is associated with impaired health-related quality of life and mortality

Background Lung transplantation and related medications are associated with pathobiological changes that can induce frailty, a state of decreased physiological reserve. Causes of persistent or emergent frailty after lung transplantation, and whether such transplant-related frailty is associated with key outcomes, are unknown. Methods Frailty and health-related quality of life (HRQL) were prospectively measured repeatedly for up to 3 years after lung transplantation. Frailty, quantified by the Short Physical Performance Battery (SPPB), was tested as a time-dependent binary and continuous predictor. The association of transplant-related frailty with HRQL and mortality was evaluated using mixed effects and Cox regression models, respectively, adjusting for age, sex, ethnicity, diagnosis, and for body mass index and lung function as time-dependent covariates. We tested the association between measures of body composition, malnutrition, renal dysfunction and immunosuppressants on the development of frailty using mixed effects models with time-dependent predictors and lagged frailty outcomes. Results Among 259 adults (56% male; mean age 55.9±12.3 years), transplant-related frailty was associated with lower HRQL. Frailty was also associated with a 2.5-fold higher mortality risk (HR 2.51; 95% CI 1.21 to 5.23). Further, each 1-point worsening in SPPB was associated, on average, with a 13% higher mortality risk (HR 1.13; 95% CI 1.04 to 1.23). Secondarily, we found that sarcopenia, underweight and obesity, malnutrition, and renal dysfunction were associated with the development of frailty after transplant. Conclusions Transplant-related frailty is associated with lower HRQL and higher mortality in lung recipients. Abnormal body composition, malnutrition and renal dysfunction may contribute to the development of frailty after transplant. Confirming the role of these potential contributors and developing interventions to mitigate frailty may improve lung transplant success.
Guidelines for gastrostomy tube placement and enteral nutrition in patients with severe, refractory hypoglycemia after gastric bypass.

Abstract Background Postbariatric hypoglycemia (PBH) affects up to 38% of Roux-en-Y gastric bypass (RYGB) patients. Severe cases are refractory to diet and medications. Surgical treatments including bypass reversal and pancreatectomy are highly morbid and hypoglycemia often recurs. We have developed a highly effective method of treatment by which enteral nutrition administered through a gastrostomy (G) tube placed in the remnant stomach replaces oral diet: if done correctly this reverses hyperinsulinemia and hypoglycemia, yielding substantial health and quality of life benefits for severely affected patients. Objectives To provide clinical guidelines for placement of a G-tube to treat postRYGB hypoglycemia, including candidate selection, preoperative evaluation, surgical considerations, and post-RYGB management. Setting Stanford University Hospital and Clinics. Methods Based on our relatively large experience with placing and managing G-tubes for PBH treatment, an interdisciplinary task force developed guidelines for practitioners. Results A team approach (endocrinologist, dietitian, surgeon, psychologist) is recommended. Appropriate candidates have a history of RYGB, severe hypoglycemia refractory to medical-nutrition therapy, and significantly affected quality of life. Preoperative requirements include education and expectation setting, determination of initial enteral feeding program, and establishing service with a home enteral provider. Close postoperative follow-up is needed to ensure success and may require adjustments in formula and mode/rate of delivery to optimize tolerance and meet nutritional goals. G-tube nutrition must fully replace oral nutrition to prevent hypoglycemia. Conclusions G-tube placement in the remnant stomach represents a relatively well-tolerated and effective treatment for severe, refractory hypoglycemia after RYGB.