cssi/SciSciGPT-SciSciNet huggingface dataset:
Imaging of Peripheral Blood Mononuclear Cells (PBMC) Trafficking in Patients with Non-Hodgkin’s Lymphoma (NHL) Prior to and Following Therapy.

Antibody-dependent cellular cytotoxicity (ADCC) mediated by PBMC’s is believed to play an important role in the anti-tumor effects of rituximab in patients (pts) with NHL but little is known about the trafficking of PBMC’s into the involved nodes. The primary objective of this pilot study is to demonstrate the feasibility of imaging PBMC trafficking in pts with NHL prior to and following various forms of therapy, including rituximab. To date, autologous PBMC’s were harvested in 9 pts (7M, 2F, age 49–83 y) using 100 ml of peripheral blood and Ficoll-Paque density gradient for cell separation and then radiolabeled with 400–450 mCi of 111 In-oxine. Total number of leukocytes in the final product ranged from 1.5–12x10 7 (mean=5.5x10 7 ) with %PBMC’s ranging from 40–98 (mean= 75). The radiolabeling efficiency ranged from 53 to 87% (mean = 71) Viability of PBMC’s by trypan blue exclusion was 99–100%. Eight patients were imaged at baseline and six of these also following 2 cycles of rituximab (n=5) or one cycle of R-CHOP (n=1). Imaging was performed at approximately 4, 24, and 48 h after injection of 165–300 mCi of 111 In-PBMCs. No significant adverse events were observed. All 8 pts showed the expected biodistribution of PBMC’s in normal organs, such as lung (primarily at 4h) and liver and spleen (at all timepoints). There was no evidence of PBMC localization in normal lymph nodes prior to or posttherapy. In contrast, PBMC localization was seen prior to therapy in ≥ 1 known tumor lesion per pt in all 8 pts and in the 6 pts imaged posttherapy, similar or greater PBMC tumor accumulation was observed. In conclusion, our initial results demonstrate the feasibility of imaging PBMC trafficking in pts with NHL prior to and following therapy with promising initial imaging findings. Our studies could eventually help better understand the role that PBMC play in the anti-tumor effect of rituximab and prove useful in the development of combination treatments such as the use of moAbs and cytokines.
A11 Longitudinal assessment of a nonhuman primate model of huntington’s disease

An animal model with clinical features paralleling human conditions that recapitulates disease progression is an integral component for advancing biomedical research and the development of novel therapeutics. We have developed a transgenic nonhuman primate model of Huntington’s disease (HD monkeys) and longitudinal assessment using clinical measurements such as MR imaging, cognitive behavioural assessment and neuropathology reveal progressive development of HD similar to human HD patients suggesting that HD monkeys could be used as an animal model for studying HD pathogenesis and the development of biomarkers. Additionally, HD monkeys can be used as a large preclinical animal model for the development of novel treatment and therapeutics. In summary, HD monkeys is a unique animal model for studying disease pathogenesis, progression and preclinical studies, which can make unprecedented contributions toward unravelling the molecular, cellular and clinical basis of inherited neurodegenerative diseases. Support Office of Research and Infrastructure Program (ORIP)/NIH OD010930
Parental Leave Equality and Subjective Well-Being

This study uses data from Sweden to investigate the proportional distribution of parental leave days between parents and to analyze how this “parental leave equality” may be related to the parents’ subjective well-being. Three results are presented. First, there is no linear relationship between the total share of leave days taken by an individual and that individual’s subjective well-being; in other words, more parental leave is not unequivocally better. Second, and by contrast, there seems to be a significant relationship between parental leave equality and subjective well-being, which implies that parents who share the responsibility for childrearing more equally tend to be more satisfied with their lives. Third, a very simple and tentative analysis of a Swedish parental leave reform suggests that incentivizing parents to share leave days more equally potentially could have improved their subjective well-being.
Crises de legitimidade e corrupção

Without doubt, pervasive corruption may undermine a government’s legitimacy. Citizens may lose faith in political and legal institutions and become cynical or rebel. Ultimately, the very survival of the polity may be at stake. This paper deals with these issues, but at a rather specific conceptual level. In particular, it explores the notion of a legitimation crisis and its implications for the issue of corruption in Latin America. This exercise will make it possible to appreciate how corrupt practices debilitate the state’s claim to justification. Indeed, the notion of a legitimation crisis helps to illuminate the problem of governmental dishonesty in Latin America. If properly reinterpreted, it enables one to grasp corruption as an endemic threat to the normative identity of the national communities. The concept may describe a situation in which these collectivities must, at the outset, transition from an instrumental to a reflexive construction of legitimacy norms, such as autonomy, legality, and equality, in order effectively to regenerate a corrupt bureaucracy and, thereafter, struggle to recognize themselves after the changeover. Accordingly, one should not respond to the challenge exclusively in a technical manner, such as with the enactment of tougher laws or with the implementation of more drastic enforcement mechanisms. Nor should one take a merely motivational approach, in the sense of U.S. psychologist David McClelland, rather than that of Habermas. In other words, one should not solely seek to change the attitude or the prevailing professional culture in civil service. Instead, Latin American societies must embark upon an unlikely radical crusade to transform the way in which they understand themselves, particularly the premises of their social integration. Against all odds, they must genuinely commit to and identify with democracy, the rule of law, and solidarity.
Responses to Trust Violation: A Theoretical Framework

Much has been said about the need for trust, and much has been implied about the consequences of violating trust. There is little empirical evidence of the consequences of trust violation, with the recent exception of Pavlou and Gefen [40]. In this article, we provide a theoretical framework for the study of responses to trust violation. Within this framework, we have outlined five models, each focusing on a different dependent variable. The models also indicate some important covariates that need to be considered when studying the responses to trust violation. The proposed theoretical framework provides a good starting point for the study of trust violation.
ABM Clinical Protocol #22: Guidelines for Management of Jaundice in the Breastfeeding Infant 35 Weeks or More of Gestation-Revised 2017.

A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols free from commercial interest or influence for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient.
Human papillomavirus infection and its role in the pathogenesis of anal cancer

Abstract The incidence of anal cancer has been increasing among both men and women in the general population since the 1970s, and is more common among women than men. Like cervical cancer, anal cancer is associated with human papillomavirus (HPV) infection and is preceded by a precursor lesion, anal high-grade squamous intraepithelial lesions (HSIL) that may take decades to progress to anal cancer. Groups at particularly high risk of anal cancer include immunosuppressed individuals, particularly those with HIV infection, men who have sex with men (MSM), and women with a history of cervical or vulvar HSIL or cancer. HIV-infected MSM constitute the group at highest risk. Once established, HPV may transform the anal epithelium by causing genomic instability, manifest histologically as HSIL. The events associated with progression from HSIL to cancer are poorly understood. Studies are currently in progress to determine whether treatment of anal HSIL reduces the risk of cancer among HIV-infected men and women, and to define the molecular events associated with progression from HSIL to cancer.
Novel markers of inflammation and their relevance to depression: The unique relation of the Neutrophil: Lymphocyte Ratio (NLR) and the Cortisol:C-reactive protein (CORT/CRP) ratio to an intermediate phenotype of Major Depressive Disorders (MDD)

We have shown that low CORT/CRP ratio values, suggestive of enhanced inflammation with attenuated CORT release, predict negative affect (NA) reactivity to stress but only among adults with elevated depressive symptoms. The NLR is another ratio measure of inflammation associated with MDD. In these analyses we evaluated the relative contributions of NLR and CORT/CRP ratio to NA responses to the Anger Recall Interview (ARI) as a function of depressive symptom severity in 196 adults. NA was assessed prior to and after the ARI. Depressive symptom severity was measured using the Hamilton Depression (HAMD). In univariate analysis, the CORT/CRP ratio was associated with NLR (r = −0.20, p
Brain Large Artery Lymphocytic Inflammation and Human Immunodeficiency Virus-Related Brain Arterial Remodeling

The pathogenesis of increased stroke risk in human immunodeficiency virus (HIV) remains unclear. Our study investigated the relationship between adventitial and intimal CD3+ T cells and brain arterial remodeling that potentially contributes to HIV-related vasculopathy and stroke. Large brain arteries from 84 HIV+ cases and 78 HIV- cases were analyzed to determine interadventitial and luminal diameters, intimal and wall thickness, percent stenosis, and the presence of atherosclerosis. Immunohistochemical analysis was performed to detect and visually score CD3, a pan-T-cell marker, in the intima and adventitia. Our study showed that numbers of adventitial CD3+ T cells are lower among persons with HIV than among those without HIV, especially if CD4 counts are 200 or HIV- controls, intimal CD3+ T cells were associated with hypertrophic inward remodeling. We conclude that intimal lymphocytic inflammation is involved in brain arterial remodeling that may contribute to HIV-related cerebrovascular pathology.IMPORTANCE Although mortality from human immunodeficiency virus (HIV) has decreased with the use of combination antiretroviral therapies, there is now an increased risk of cardiovascular and cerebrovascular disease associated with HIV. Thus, there is a need to understand the pathogenesis of stroke in HIV infection. Our study examines how lymphocytic inflammation in brain arteries may contribute to increased cerebral vasculopathy. With this understanding, our study can potentially help direct future therapies to target and prevent brain arterial remodeling processes associated with HIV.
Evaluation of mandibular anterior alveolus in different skeletal patterns

The boundaries for orthodontic tooth movement are set by the bony support of the dentition. This study compares the mandibular anterior alveolar housing in individuals with low, average, and high mandibular plane angles before orthodontic treatment and measures alveolar bone loss and root resorption after orthodontic treatment. Pretreatment cone-beam computed tomography (CBCT) images of 75 non-growing individuals, 25 in three groups: low-angle (sella-nasion to mandibular plane ≤28°), average-angle (30°–37°), and high-angle (≥39°), were analyzed. Buccolingual bone thickness was measured at the root apex, mid-root, and alveolar crest of the mandibular right central incisor. Pre- and posttreatment CBCT images of 11 low-angle, 20 average-angle, and 27 high-angle patients were compared to determine changes in the alveolus and mandibular incisor root after orthodontic treatment. The pretreatment anterior alveolar bone widths were significantly different, wider in low-angle than in average- and high-angle individuals (p value = 0.000). High-angle individuals also had greater posttreatment external root resorption, even though the bony housing changed minimally. Negative sequelae of orthodontic treatment are more frequently found in individuals with high mandibular plane angles and could be linked to their thin pre-existing alveolar housing.
Dispelling the myths of exercise and asthma

A 16-year-old boy comes into your office and says he needs inhaled albuterol. He wants to play soccer but becomes short of breath when he is out on the soccer field. He currently uses the drug once a week during exercise, and he tells you that his albuterol keeps him from being so short of breath. When you listen to his chest, it is clear. His history includes no complaints of wheeze or cough; he has had no emergency department visits, hospital visits, or even sick days related to asthma. How would you proceed with this patient? With the paradigm of adolescence revolving around sports, it is not unusual for children to come into a primary care office with shortness of breath related to exercise. Right now, 20% of all children enrolled in the Dallas Independent School District have a history of asthma or current symptoms. Yet it is important to clarify the role of exercise in asthma and to dispel some commonly held misconceptions about exercise and asthma. This article deals with 3 such myths: that asthma stops patients in their tracks, that patients are “allergic” to exercise, and that managing exercise-triggered asthma requires specialized help.
Fracture Analysis of Interlaminar Cracking

Abstract This article details a method for treating interlaminar cracking (delamination) in polymer-based fiber-reinforced composite laminates. The method is developed on the basis of observing the physical characteristics of delamination on the phenomenological scale, interpret the visual findings and model the initiation and propagation mechanisms within the concepts of the classical fracture mechanics. The method is then incorporated into a finite-element simulation procedure for actual delamination processes in specific laminate situations. Thus, this article consists of discussions on three main parts: one part on the physical characteristics as they are observed in actual experiments, one part on the logical formulation of the analysis method and one part on the simulation of some specific laminates with numerical results and experimental correlations. The finite-element procedure used in the simulation is discussed in the appendix at the end of this article for ready reference.
Development of a personalized diagnostic model for kidney stone disease tailored to acute care by integrating large clinical, demographics and laboratory data: the diagnostic acute care algorithm - kidney stones (DACA-KS).

Kidney stone (KS) disease has high, increasing prevalence in the United States and poses a massive economic burden. Diagnostics algorithms of KS only use a few variables with a limited sensitivity and specificity. In this study, we tested a big data approach to infer and validate a ‘multi-domain’ personalized diagnostic acute care algorithm for KS (DACA-KS), merging demographic, vital signs, clinical, and laboratory information. We utilized a large, single-center database of patients admitted to acute care units in a large tertiary care hospital. Patients diagnosed with KS were compared to groups of patients with acute abdominal/flank/groin pain, genitourinary diseases, and other conditions. We analyzed multiple information domains (several thousands of variables) using a collection of statistical and machine learning models with feature selectors. We compared sensitivity, specificity and area under the receiver operating characteristic (AUROC) of our approach with the STONE score, using cross-validation. Thirty eight thousand five hundred and ninety-seven distinct adult patients were admitted to critical care between 2001 and 2012, of which 217 were diagnosed with KS, and 7446 with acute pain (non-KS). The multi-domain approach using logistic regression yielded an AUROC of 0.86 and a sensitivity/specificity of 0.81/0.82 in cross-validation. Increase in performance was obtained by fitting a super-learner, at the price of lower interpretability. We discussed in detail comorbidity and lab marker variables independently associated with KS (e.g. blood chloride, candidiasis, sleep disorders). Although external validation is warranted, DACA-KS could be integrated into electronic health systems; the algorithm has the potential used as an effective tool to help nurses and healthcare personnel during triage or clinicians making a diagnosis, streamlining patients’ management in acute care.
Acute ultraviolet radiation exposure attenuates nitric oxide-mediated vasodilation in the cutaneous microvasculature of healthy humans.

Endothelial-derived nitric oxide (NO) contributes to normal healthy function of the human cutaneous microvasculature. Bioavailability of 5-methyltetrahydrofolate (5-MTHF) is important for the produ...
Gender Nonconformity Is Perceived Differently for Cisgender and Transgender Targets

The present research examined the role gender non-conformity plays in attitudes toward transgender people. Study 1 with 232 U.S college students focused on attitudes toward female targets; Study 2 with 217 U.S. college students focused on male targets; and Study 3 with 462 mTurk workers directly compared attitudes toward female and male targets. In all three studies, participants read a vignette depicting either a transgender or cisgender target who presents as either gender conforming or gender nonconforming. In all three studies, we found that gender nonconforming targets and transgender targets were perceived as more threatening to the distinction between men and women, and in two of the studies, we found that gender conforming transgender targets were more threatening than conforming cisgender targets. We also found that anti-transgender prejudice, traditional gender role beliefs (Studies 1 and 2), and biological gender essentialism (Study 3) moderated these effects. Transgender targets who conform to the traditional binary gender role associated with their gender expression are perceived as transgressing distinct binary gender boundaries, which may be threatening because “passing” transgender individuals are harder to detect as transgressors and because their “passing” challenges the belief that gender is biologically essential and immutable. Furthermore, as anti-transgender prejudice, traditional gender role beliefs, and gender essentialist beliefs increase, liking decreased and threat increased for transgender and gender nonconforming targets. Working to alter gender essentialist beliefs may be a route to reducing anti-transgender prejudice.
Assessing Historical Thinking and Understanding: Innovative Designs for New Standards

Assessing Historical Thinking and Understanding advocates for a fundamental change in how educators think about making sense of learners’ developing cognition and understanding in history. Author Bruce VanSledright argues that traditional and typical standardized testing approaches are seldom up to the task of measuring the more complex understandings students are asked to attain, as they cannot fully assess what the student knows. Rather, he points forward along a path toward changes in learning, teaching, and assessing that closely aligns with the Common Core State Standards. He delves into the types of history knowledge the standards require, illustrates how they can be applied in-use in history learning contexts, and theorizes how the standards might fit together cognitively to produce deep historical understandings among students in teaching-learning contexts. By providing a variety of assessment strategies and items that align with the standards, and identifying rich, useful assessment rubrics applicable to the different types of assessments, he offers an important resource for social studies teachers and curriculum writers alike.
Deep Visual Teach and Repeat on Path Networks

We propose an approach for solving Visual Teach and Repeat tasks for routes that consist of discrete directions along path networks using deep learning. Visual paths are specified by a single monocular image sequence and our approach does not query frames or image features during inference, but instead is composed of classifiers trained on each path. Our method is efficient for both storing or following paths and enables sharing of visual path specifications between parties without sharing visual data explicitly. We evaluate our approach in a simulated environment, and present qualitative results on real data captured with a smartphone.
Transgenerational Effects of Endocrine-Disrupting Chemicals on Male and Female Reproduction

Endocrine-disrupting chemicals are known to interfere with normal reproductive function and hormone signaling. Phthalates, bisphenol A, pesticides, and environmental contaminants such as polychlorinated biphenyls and dioxins are known endocrine-disrupting chemicals that have been shown to negatively affect both male and female reproduction. Exposure to these chemicals occurs on a daily basis owing to these compounds being found in plastics, personal care products, and pesticides. Recently, studies have shown that these chemicals may cause transgenerational effects on reproduction in both males and females. This is of concern because exposure to these chemicals prenatally or during adult life can negatively impact the reproductive health of future generations. This mini-review summarizes the endocrine-disrupting chemicals that humans are exposed to on a daily basis and what is known about the transgenerational effects that these chemicals may have on male and female reproduction.
Data visualization heuristics for the physical sciences

Abstract Data visualization – that is, the graphical representation of numerical information – is foundational to the scientific enterprise. A broad literature base is available providing rules, guidelines, and heuristics for authors of scientific literature to assist in the production of scientific graphics that are readable and intuitive. However, most of the available recent publications are in the bio-, psycho-, or climate sciences literature. In this paper, we address this deficiency and provide data visualization heuristics tuned to the specific needs of the physical sciences, and particularly materials sciences, community. We enumerate six general rules and provide examples of bad and improved data graphics, and provide source code to illustrate the generation of the improved figures. The six rules we enumerate are: (1) Generate figures programmatically; (2) Multivariate data calls for multivariate representation; (3) Showing the data beats mean ± standard deviation; (4) Choose colormaps that match the nature of the data; (5) Use small multiples; and (6) Don't use vendor exports naively.
Distributed Energy Optimization in MAS-based Microgrids using Asynchronous ADMM

This paper proposes a scalable distributed energy management system for multi-agent system (MAS)-based microgrids under communication delay. In the proposed approach, the centralized convex optimization problem of a microgrid with distributed energy resources is decomposed into sub-problems solved iteratively by the respective agents in a distributive manner using privacy-preserving asynchronous alternating direction method of multipliers (ADMM) algorithm. In this algorithm, each agent accumulates the sub-system updates from local controllers and only shares partial information with the adjacent agents while minimizing the aggregated operational cost of the microgrid in a cooperative mode. The numerical result shows that the algorithm can reach the convergence very fast under various conditions. The optimality of this algorithm was analyzed briefly and its effectiveness was compared with the synchronous ADMM algorithm.
Paying attention to attention in depression

Attention is the gate through which sensory information enters our conscious experiences. Oftentimes, patients with major depressive disorder (MDD) complain of concentration difficulties that negatively impact their day-to-day function, and these attention problems are not alleviated by current first-line treatments. In spite of attention’s influence on many aspects of cognitive and emotional functioning, and the inclusion of concentration difficulties in the diagnostic criteria for MDD, the focus of depression as a disease is typically on mood features, with attentional features considered less of an imperative for investigation. Here, we summarize the breadth and depth of findings from the cognitive neurosciences regarding the neural mechanisms supporting goal-directed attention in order to better understand how these might go awry in depression. First, we characterize behavioral impairments in selective, sustained, and divided attention in depressed individuals. We then discuss interactions between goal-directed attention and other aspects of cognition (cognitive control, perception, and decision-making) and emotional functioning (negative biases, internally-focused attention, and interactions of mood and attention). We then review evidence for neurobiological mechanisms supporting attention, including the organization of large-scale neural networks and electrophysiological synchrony. Finally, we discuss the failure of current first-line treatments to alleviate attention impairments in MDD and review evidence for more targeted pharmacological, brain stimulation, and behavioral interventions. By synthesizing findings across disciplines and delineating avenues for future research, we aim to provide a clearer outline of how attention impairments may arise in the context of MDD and how, mechanistically, they may negatively impact daily functioning across various domains.
Evaluation of Xie et al.: Sphingolipid Modulation Activates Proteostasis Programs to Govern Human Hematopoietic Stem Cell Self-Renewal

This article shows an example of the peer review process for "Sphingolipid Modulation Activates Proteostasis Programs to Govern Human Hematopoietic Stem Cell Self-Renewal" (Xie et al., 2019).
EXTH-08. REPLACEMENT OF MICROGLIA BY BRAIN-ENGRAFTED MACROPHAGES PREVENTS MEMORY DEFICITS AFTER THERAPEUTIC WHOLE-BRAIN IRRADIATION

Author(s): Feng, Xi; Gupta, Sonali; Chen, David; Boosalis, Zoe; Liu, Sharon; Gupta, Nalin; Rosi, Susanna | Abstract: Abstract Microglia have a distinct origin compared to blood circulating myeloid cells. Under normal physiological conditions, microglia are maintained by self-renewal, independent of hematopoietic progenitors. Following genetic or pharmacologic depletion, newborn microglia derive from the local residual pool and quickly repopulate the entire brain. The depletion of brain resident microglia during therapeutic whole-brain irradiation fully prevents irradiation-induced synaptic loss and recognition memory deficits but the mechanisms driving these protective effects are unknown. Here, we demonstrate that after CSF-1R inhibitor-mediated microglia depletion and therapeutic whole-brain irradiation, circulating monocytes engraft into the brain and replace the microglia pool. These monocyte-derived brain-engrafted macrophages have reduced phagocytic activity compared to microglia from irradiated brains, but similar to locally repopulated microglia without brain irradiation. Transcriptome comparisons reveal that brain-engrafted macrophages have both monocyte and embryonic microglia signatures. These results suggest that monocyte-derived brain-engrafted macrophages represent a novel therapeutic avenue for the treatment of brain radiotherapy-induced cognitive deficits.
Identification of Major Road Influence Area Using NDS Data

Crashes at rural intersection make up almost one-third of rural crashes. Many studies have focused on the minor stream driver since they are typically the ones who initiate the sequence of events leading to a crash, such as failure to yield to traffic control. However, the actions of the mainline road driver can influence crash outcome and severity. For instance, an alert major street driver can take the necessary maneuvers to avoid a crash or lessen the severity.This study used NDS data to assess the number of major approach drivers who demonstrate a measureable response to an upcoming intersection. A binary model was developed to relate response point to roadway, driver, and environmental characteristics. The result from this study showed that about 32% of mainline drivers at the high speed rural minor street stop controlled intersections showed a measurable response. The majority of drivers responded 80 to 240 meters upstream of the intersection. The relationship between other characteristics and response was also modeled.Results can be used to indicate where drivers react to an upcoming minor street intersection which can inform sign and countermeasure placement. Additionally it demonstrates a method to which could be used to assess rural intersection countermeasures. For instance, a number of agencies in the US are utilizing intelligent transportation system countermeasures such as intersection collision warning systems. Understanding where drivers are likely to respond can help in placing these types of countermeasures.Results also have implications for connected and autonomous vehicles. If application developers understand how a mainline driver reacts to the presence of an intersection, it can guide warning systems for the minor approach vehicle. For instance, detecting a change in speed of the major approach driver could signify the mainline driver is aware of the minor street vehicle while lack of response could trigger an alert for the minor street driver. This is particularly helpful in assessing on-coming vehicle speed and gap selection are problematic for drivers at minor stop-controlled approach.
Bioengineering an in situ ovary (ISO) for fertility preservation

Female cancer patients who have undergone chemotherapy have an elevated risk of developing premature ovarian failure (POF) and infertility. Experimental approaches to treat iatrogenic infertility are evolving rapidly; however, there remain challenges and risks that have hindered clinical translation. To address these concerns, we developed an ovarian-specific extracellular matrix hydrogel to facilitate follicle delivery and establish an in situ ovary (ISO). We demonstrate sustainable engraftment, natural pregnancy and the birth of healthy pups after intraovarian microinjection of isolated exogenous follicles in a chemotherapy-induced POF mouse model. Our results suggest that the methods described could offer a minimally invasive alternative for the restoration of the ovarian reserve post-chemotherapy.
Engineering natural and noncanonical nicotinamide cofactor-dependent enzymes: design principles and technology development

Nicotinamide cofactors enable oxidoreductases to catalyze a myriad of important reactions in biomanufacturing. Decades of research has focused on optimizing enzymes which utilize natural nicotinamide cofactors, namely nicotinamide adenine dinucleotide (phosphate) (NAD(P)+). Recent findings reignite the interest in engineering enzymes to utilize noncanonical cofactors, the mimetics of NAD+ (mNADs), which exhibit superior industrial properties in vitro and enable specific electron delivery in vivo. We compare recent advances in engineering natural versus noncanonical cofactor-utilizing enzymes, discuss design principles discovered, and survey emerging high-throughput platforms beyond the traditional 96-well plate-based methods. Obtaining mNAD-dependent enzymes remains challenging with a limited toolkit. To this end, we highlight design principles and technologies which can potentially be translated from engineering natural to noncanonical cofactor-dependent enzymes.
Lumen and mucosa-associated Lactobacillus rhamnosus from the intestinal tract of organ donors

Knowledge of the intra-individual spatial and regional distribution of intestinal microbial populations is essential to understand gut host–microbial interactions. In this study, we performed a compositional analysis of luminal and mucosal samples from the small and large intestine of four organ donors by 16S rRNA amplicon sequencing and high-throughput quantitative polymerase chain reaction. Since the human microbiota is subject to selection pressure at lower taxonomic levels, we isolated over 400 bacterial strains and investigated strain-level variation of 11 Lactobacillus rhamnosus from different intestinal regions. Results substantiate reported inter-individual variability as well as intra-individual differences along the gastrointestinal tract. Although the luminal and mucosal-associated communities were similar within individuals, relative abundance reflected the donors’ demographic and potential pathologies. The total bacterial load of all donors increased from small intestine to colon, while Bifidobacterium was in greater abundance in the small intestine. Comparative genomic analysis of L. rhamnosus showed the strains segregated into two distinct clusters and identified no features specific to location. Analysis revealed genetic differences for exopolysaccharide production, carbohydrate utilization, pilus formation and vitamin K biosynthesis between clusters. This study contributes to the understanding of niche-specific microbial communities, encouraging subsequent studies to better understand microbial signatures at lower taxonomic levels.
Taxanes Sensitize Prostate Cancer Cells to TRAIL-Induced Apoptotic Synergy via Endoplasmic Reticulum Stress

Docetaxel (DTX) and cabazitaxel (CBZ) are guideline-chemotherapy treatments for metastatic castration-resistant prostate cancer (mCRPC), which comprises the majority of prostate cancer (PCa) deaths. TNF-related apoptosis inducing ligand (TRAIL) is an anti-cancer agent that is selectively cytotoxic to cancer cells; however, many human cancers are resistant to TRAIL. In this study, we sensitized androgen-independent and TRAIL-resistant PCa cells to TRAIL-mediated apoptosis via taxane therapy and examined the mechanism of sensitization. DU145 and PC3 cells displayed no significant reduction in cell viability when treated with soluble TRAIL, DTX, or CBZ alone indicating that both cell lines are resistant to TRAIL and taxanes individually. Taxane and TRAIL combination synergistically amplified apoptosis strongly suggesting that taxanes sensitize prostate cancer cells to TRAIL. A Jun N-terminal kinases (JNK) inhibitor inhibited apoptosis in treated cells and significantly reduced death receptor expression indicating JNK activation by ER stress sensitizes PCa cells to TRAIL-induced apoptosis by upregulating DR4/DR5 expression. In addition, suppression of C/EBP homologous protein (CHOP) reduced TRAIL sensitization in both cell lines indicating that ER stress-related apoptosis is mediated, in part by CHOP. Cytochrome c knockdown showed a significant decrease in sensitivity in PC3 cells, but not in Bax-deficient DU145 cells. A computational model was used to simulate apoptosis for cells treated with taxane and TRAIL therapy as demonstrated in in vitro experiments. Pretreatment with taxanes sensitized cells to apoptosis induced by TRAIL-mediated apoptosis, demonstrating that combining TRAIL with ER stress inducers is a promising therapy to reverse TRAIL resistance to treat mCRPC.
Being before: three Deleuzian becomings in teacher education

In this article, I use data from interviews with three social studies teachers to consider teachers’ identity development. I point to how their narratives challenge traditional linear notions of pr...
Campus Carry Attitudes Revisited: Variations within the University Campus Community.

This study examined attitudes toward campus carry – a policy that would permit individuals to carry concealed firearms on a university’s grounds if they possess a permit. Survey data were collected...
Winning ugly: Profit maximizing marketing strategies for ugly foods

Abstract Ugly foods meet nutritional and safety benchmarks but deviate from cosmetic and size standards. The marketability of ugly food is a major factor that frustrates field-level food rescue efforts. We investigate opportunities to promote ugly foods in a way that converts uniform negative preferences towards ugly food to more diverse and horizontally differentiated preferences where some consumers prefer ugly food to standard offerings and pay a premium. We conduct an online discrete choice experiment and find a portfolio of marketing strategies that significantly enhance respondent willingness to pay for ugly carrots. Dual messages that simultaneously (1) link the purchase of ugly food to reductions in food waste and (2) suggest ugly food is natural and authentic significantly improve willingness to pay. We also find respondents tolerate some level of mixing of ugly with standard carrots. We find the most profitable strategy is to form bunches that include 40% ugly and 60% standard carrots and to sell the bunches with green leaves attached at farmers markets where consumers receive dual marketing messages. Profit simulations confirm that, in the absence of such marketing strategies, farmers rationally create waste by discontinuing harvest when the percentage of remaining carrots that are ugly is high.
Validation of 31 of the most commonly used immunohistochemical antibodies in cytology prepared using the cellient® automated cell block system

The Cellient® cell block system has become available as an alternative, partially automated method to create cell blocks in cytology. We sought to show a validation method for immunohistochemical (IHC) staining on the Cellient cell block system (CCB) in comparison with the formalin fixed paraffin embedded traditional cell block (TCB). Immunohistochemical staining was performed using 31 antibodies on 38 patient samples for a total of 326 slides. Split samples were processed using both methods by following the Cellient® manufacturer's recommendations for the Cellient cell block (CCB) and the Histogel method for preparing the traditional cell block (TCB). Interpretation was performed by three pathologists and two cytotechnologists. Immunohistochemical stains were scored as: 0/1+ (negative) and 2/3+ (positive). Inter-rater agreement for each antibody was evaluated for CCB and TCB, as well as the intra-rater agreement between TCB and CCB between observers. Interobserver staining concordance for the TCB was obtained with statistical significance (P < 0.05) in 24 of 31 antibodies. Interobserver staining concordance for the CCB was obtained with statistical significance in 27 of 31 antibodies. Intra-observer staining concordance between TCB and CCB was obtained with statistical significance in 24 of 31 antibodies tested. In conclusions, immunohistochemical stains on cytologic specimens processed by the Cellient system are reliable and concordant with stains performed on the same split samples processed via a formalin fixed-paraffin embedded (FFPE) block. The Cellient system is a welcome adjunct to cytology work-flow by producing cell block material of sufficient quality to allow the use of routine IHC. Diagn. Cytopathol. 2014;42:1024–1033. © 2014 Wiley Periodicals, Inc.
An Experimental and Modeling Investigation on High‐Rate Formability of Aluminum

This work describes the integrated experimental and modeling effort at PNNL to enhance the room-temperature formability of aluminum alloys by taking advantage of formability improvements generally associated with high-strain-rate forming. Al alloy AA5182-O sheets were deformed in near plane-strain conditions at strain-rates exceeding 1000 /s using the electrohydraulic forming (EHF) technique, and at quasi-static strain-rates via a bulge test. A novel capability, combining highspeed imaging with digital image correlation technique, was developed to quantify the deformation history during high-rate forming. Sheet deformation under high rates was modeled in Abaqus and validated with experimentally determined deformation data. The experimental results show a ~2.5x increase in formability at high rates, relative to quasi-static rates, under a proportional loading path that was verified by the experimental data. The model shows good correlation with the experimentally determined strain path. It is anticipated that such integrated experimental and modeling work will enable room-temperature forming of Al and industrial implementation of high-rate forming processes.
On the possibility of the existence of fractional charges 1/2

Arguments are advanced against a recently proposed scheme for producing excitations with the fractional charge 1/2 in liquid helium.
Immunological Probes of Gastrointestinal Secretion

The sections in this article are: 1 Antibodies As Probes 1.1 Polyclonal Antisera 1.2 Monoclonal Antibodies 1.3 Immunocytochemistry 1.4 Immunoassay 1.5 Immunoblotting 1.6 Immunoprecipitation 1.7 Immunoaffinity Chromatography 2 Salivary Secretion 3 Gastric Secretion 3.1 Hydrochloric Acid 3.2 Pepsinogen 3.3 Intrinsic Factor 4 Pancreatic Secretion 5 Hepatobiliary Secretion 6 Colonic Secretion 7 Future Directions 7.1 Anti-idiotypes 7.2 Immunodissection 7.3 Reverse Hemolytic Plaque Assay 7.4 Antibodies and Molecular Biology
Association Between High‐Sensitivity C‐Reactive Protein and Total Stroke by Hypertensive Status Among Men

Background High‐sensitivity C‐reactive protein (hsCRP), a marker of systemic inflammation, may promote atherosclerosis, particularly among adults with elevated blood pressure; however, data are sparse. We examined the association between hsCRP concentrations and risk of total stroke by hypertension status (normotension, prehypertension, and hypertension) among men in the Physicians’ Health Study (PHS). Methods and Results Blood samples were collected (1996–1997) and assayed for hsCRP among 10 456 initially healthy men from PHS I and PHS II and followed from 1997 to 2012. Self‐reported hypertension status, cardiovascular risk factors, lifestyle, and alcohol consumption were obtained from the baseline questionnaire prior to randomization in PHS II. Strokes were updated approximately annually and confirmed by medical records according to the National Survey of Stroke criteria. Multivariable Cox models were used. We observed 395 incident total strokes over 115 791 person‐years. In analyses adjusted for potential confounders and stroke risk factors, clinically elevated hsCRP (>3 mg/L) was associated with a 40% significantly greater hazard of total stroke compared with hsCRP <1 mg/L (hazard ratio 1.40, 95% CI 1.06 to 1.8 7 ; P trend=0.01). Additional adjustment for blood pressure and biomarkers associated with cardiovascular risk marginally attenuated the estimates. Results were similar by hypertension status, although not statistically significant among normotensive and prehypertensive participants due to limited events. Conclusions Elevated hsCRP levels were associated with a greater risk of total stroke, even after adjustment for potential confounders and cardiovascular risk factors. Risk of total stroke was significantly higher among hypertensive men with elevated hsCRP compared with normotensive men with low hsCRP.
Graduate student cognition during information retrieval using the World Wide Web: a pilot study

Abstract The intensity of Internet use in higher education, particularly the World Wide Web, has stimulated concern regarding the ways in which students acquire necessary skills for managing, filtering, and storing vast amounts of information. Research is beginning to focus on how students think about an Internet search and how they use cognitive strategies for information retrieval. The purpose of this study was to describe and interpret the cognition of a graduate student during information retrieval using the World Wide Web. The participant was a doctoral student in psychology with little experience using the Internet, particularly fewer experiences with the World Wide Web. The student performed an open search of her dissertation topic (i.e., child temperament), followed by a pre-arranged task requiring the student to answer several questions regarding the American Civil War using only the Web to obtain the information. Three qualitative sources of data were collected involving student cognition: observation, think aloud protocols, and an in-depth interview. A core category derived from the qualitative analysis indicated that the student’s thoughts and perceptions centered on information overload. A systematic approach outlined two major dimensions of this core category: knowledge and personal characteristics. Within each dimension several subcategories were identified. The results are interpreted within a theory of information processing. Implications for continuing this line of research are provided.
Chinese hamster ovary cell lines selected for resistance to ebolavirus glycoprotein mediated infection are defective for NPC1 expression

Ebolavirus causes severe hemorrhagic fever in humans and non-human primates. Entry of ebolavirus is mediated by the viral glycoprotein, GP; however, the required host factors have not been fully elucidated. A screen utilizing a recombinant Vesicular Stomatitis Virus (VSV) encoding Zaire ebolavirus GP identified four Chinese Hamster Ovary (CHO) cell lines resistant to GP-mediated viral entry. Susceptibility to vectors carrying SARS coronavirus S or VSV-G glycoproteins suggests that endocytic and processing pathways utilized by other viruses are intact in these cells. A cathepsin-activated form of the ebolaviral glycoprotein did not overcome the entry restriction, nor did expression of several host factors previously described as important for ebolavirus entry. Conversely, expression of the recently described ebolavirus host entry factor Niemann-Pick Type C1 (NPC1) restored infection. Resistant cells encode distinct mutations in the NPC1 gene, resulting in loss of protein expression. These studies reinforce the importance of NPC1 for ebolavirus entry.
A review of workplace aerosol sampling procedures and their relevance to the assessment of beryllium exposures

Standardized conventions governing the fractions of airborne particles that can penetrate the human head airways, the thoracic airways and the alveolar spaces have been internationally (although not universally) adopted. Several agencies involved in setting limit values for occupational exposure concentrations have taken these conventions into account when considering the appropriate standard for specific chemicals, in order to ensure the standards are biologically relevant. A convention is selected based on the characteristic health effects, and forms the basis of measurement against the limiting concentration value. In order to assess exposure for comparison to this metric or any other purposes, it is necessary to choose a sampler whose performance matches the convention, and protocols have been developed and used to test sampler performance. Several aerosol sampling devices are available, nominally at least, for each of the conventions. Some considerations important to the sampling of airborne particles containing beryllium with regard to the sampling conventions, the test protocols and sampler performance are discussed.
VT-DRIFTS : a two-dimensional infrared thermal analysis method

Thermal analysis by using variable-temperature diffuse reflectance infrared spectroscopy (VT-DRIFTS) is described. Techniques for extracting spectral information from VT-DRIFTS data regarding temperature-dependent solid-state structure changes are discussed. The use of VT-DRIFTS for investigating the thermal degradation mechanisms of calcium oxalate monohydrate and poly(vinyl alcohol) and for profiling the Lewis and Bronsted acid strength distributions for an HZSM-5 zeolite by monitoring pyridine desorption as a function of temperature is described.