cssi/SciSciGPT-SciSciNet huggingface dataset:
Tuning Hydrogel Properties to Promote the Assembly of Salivary Gland Spheroids in 3D

Current treatments for chronic xerostomia, or “dry mouth”, do not offer long-term therapeutic benefits for head and neck cancer survivors previously treated with curative radiation. Toward the goal of creating tissue-engineered constructs for the restoration of salivary gland functions, we developed new hyaluronic acid (HA)-based hydrogels using thiolated HA (HA-SH) and acrylated HA (HA-AES) with a significant molecular weight mismatch. Four hydrogel formulations with varying HA concentration (1–2.4 wt %), thiol/acrylate ratios (2/1 to 36/1) and elastic moduli (G′: 35 to 1897 Pa, 2 h post-mixing) were investigated. In our system, the thiol/acrylate reaction was initiated rapidly upon mixing of HA-SH/HA-AES to establish thioether cross-links with neighboring ester groups, and spontaneous sulfhydryl oxidation occurred slowly over several days to install a secondary network. The concurrent reactions cooperatively create a cell-permissive network to allow for cell expansion and aggregation. Multicellular sphe...
Impact of Swift and Certain Sanctions

Research Summary In the wake of the mass incarceration movement, many states must now manage the rebound of decarceration. Thermodynamic forces of the justice system, however, have pushed former fiscal pressures of institutions onto that of community corrections. Encouraged by the positive findings of recently piloted innovations, several jurisdictions have taken great interest in the implementation of deterrence-based sanctioning models when dealing with supervision violations. Among the first to implement a statewide turn to this style of sanctioning, Washington State's swift-and-certain (SAC) policy was implemented in June 2012. The intent of SAC was to expand the model found in Hawaii's Opportunity Probation and Enforcement (HOPE) to a wider criminal justice population, while emphasizing the reduction of confinement costs. This study focused on the impact of SAC with regard to supervision outcomes for participants. By using a quasi-experimental design, we examined confinement, recidivism, treatment, violation, and costs outcomes of SAC participants. Findings reveal that SAC participants were found to incur fewer sanctioned incarceration days after a violation, reduced odds of recidivism, possessed greater treatment program utilization, reduced their propensity of committing violations over time, and as a result, imposed lower correctional and associated costs. The SAC model provides noteworthy positive effects and no appreciable negative impacts on public safety. Policy Implications We further discuss the impact of SAC in the context of deterrence-based sanctioning. Specifically, we explain how practices such as SAC may impact the future of sanctioning community supervision conditions. Although many policies that emphasize deterrence demonstrate inconsistent findings, immediate advantages of SAC take the form of fiscal savings, indicating that these novel methods provide a form of justice reinvestment. Additionally, connecting deterrence-based supervision methods to reductions in most recidivism measures suggests that proportionality and quality assurance may increase the effectiveness of these policies. We recommend ways that such nuanced implementation may be fruitful, as well as suggest ways of conceptualizing the theory of deterrence. Policy makers can appropriately work its components into supervision practice without depreciating the importance of treatment and addressing criminogenic needs.
An institutional comparison of total abdominal colectomy and diverting loop ileostomy and colonic lavage in the treatment of severe, complicated Clostridium difficile infections.

Abstract Background Total abdominal colectomy (TAC) is the standard surgical treatment of Clostridium difficile infection (CDI). An alternative therapy, loop ileostomy and colonic lavage (IL), was described in 2011, but the results have never been validated. Methods Patients treated surgically for CDI between April 2011 and June 2015 were included. Bivariable analysis was used to compare 30-day mortality, 1-year mortality, CDI recurrence, colon preservation and ileostomy reversal. Results Ten IL patients and thirteen TAC patients were identified. 30-day mortality (30% vs 23%, p = 1.0) and 1-year mortality (40% vs 46%, p = 1.0) were similar. Four IL and three TAC patients (57% vs 30%, p = 0.35) experienced recurrent CDI. All six surviving IL patients had successful colon preservation; five underwent ileostomy reversal compared to three in the TAC group (83% vs 43%, p = 0.27). Conclusions Although IL allowed colon preservation and return of intestinal continuity in most patients, IL did not decrease mortality or recurrent CDI when compared to TAC.
Variations in Developmental Patterns across Pragmatic Features.

Drawing on the findings of longitudinal studies in uninstructed contexts over the last two decades, this synthesis explores variations in developmental patterns across second language (L2) pragmatic features. Two synthesis questions were addressed: (a) What are the variations in developmental patterns across pragmatic features?, and (b) What are the potential explanations for the variations? In response to the first question, previous studies showed that L2 pragmatic development is a non-linear, dynamic process, with developmental paces varying across pragmatic features (Ortactepe, 2013; Taguchi, 2010, 2011, 2012; Warga & Scholmberger, 2007). These studies revealed that some aspects of pragmatic features (e.g., semantic strategies of speech acts) develop faster than others (e.g., lexical features such as mitigators). In response to the second question, three potential explanations were identified to account for the developmental variations: (a) language-related, (b) situation-dependent, and (c) learner-related explanations, with three subcategories for the language-related explanation: (a) the functions of pragmatic features, (b) the frequency of availability of target features, and (c) the similarity and difference between languages with respect to the target feature.
Single Nucleotide Polymorphisms Influence the Phenotype of Mutations P618A and R1336W found in the ADAMTS13 Gene of Congenital TTP Patients.

ADAMTS13 cleaves plasmatic von Willebrand factor (VWF) between Tyr 1605 and Met 1606 and regulates thereby the hemostatic activity of VWF. Mutations in the ADAMTS13 gene leading to severe ADAMTS13 deficiency have been found in patients with congenital thrombotic thrombocytopenic purpura (TTP). We have analyzed the ADAMTS13 gene defects in two brothers with hereditary TTP [Antoine et al, Brit. J. Hematol., 2003] where we detected a total of six nucleotide exchanges causing point mutations. On the maternal allele we found an accumulation of five amino acid substitutions (R7W, Q448E, P618A, A732V, R1336W) and on the paternal allele a stop mutation (Q44X) leading to premature protein termination in the propeptide region. Both brothers were double heterozygotes with
Dynamic prediction of drivers' personal routes through machine learning

Personal route prediction (PRP) has attracted much research interest recently because of its technical challenges and broad applications in intelligent vehicle and transportation systems. Traditional navigation systems generate a route for a given origin and destination based on either shortest or fastest route schemes. In practice, different people may very likely take different routes from the same origin to the same destination. Personal route prediction attempts to predict a driver's route based on the knowledge of driver's preferences. In this paper we present an intelligent personal route prediction system, I_PRP, which is built based upon a knowledge base of personal route preference learned from driver's historical trips. The I_PRP contains an intelligent route prediction algorithm based on the first order Markov chain model to predict a driver's intended route for a given pair of origin and destination, and a dynamic route prediction algorithm that has the capability of predicting driver's new route after the driver departs from the predicted route.
Sex-Specific Epigenetics: Implications for Environmental Studies of Brain and Behavior

This review discusses the current state of knowledge on sex differences in the epigenetic regulation in the brain and highlights its relevance for the environmental studies of brain and behavior. Recent evidence shows that epigenetic mechanisms are involved in the control of brain sexual differentiation and in memory-enhancing effects of estradiol in females. In addition, several studies have implicated epigenetic dysregulation as an underlying mechanism for sex-specific neurobehavioral effects of environmental exposures. The area of sex-specific neurepigenetics has a great potential to improve our understanding of brain function in health and disease. Future neuropigenetic studies will require the inclusion of males and females and would ideally account for the fluctuating hormonal status in females which is likely to affect the epigenome. The implementation of cutting-edge methods that include epigenomic characterization of specific cell types using latest next-generation sequencing approaches will further advance the area.
Defining and discovering interactive causes

The problem of learning causal influences from passive data has attracted a good deal of attention in the past 30 years, and techniques have been developed and tested. These techniques assume the composition property, which entails that they cannot in general learn interactive causes with little marginal effects. However, such interactions are fairly commonplace. One notable example is genetic epistasis, which is the interaction of two or more genetic loci to affect phenotype. Often the genes exhibit little marginal effects. Another important example is the interaction of a treatment with patient features to affect outcomes. Even though efforts have recently been made towards developing new algorithms that discover such interactions from data, to our knowledge no definition of a discrete causal interaction has been forwarded. Using information theory, we develop a fuzzy definition of a discrete causal action, called Interaction Strength (IS). The IS is bounded above by 1 and equals 1 if the causes in the interaction exhibit no marginal effects. Using the IS and BN scoring, we develop an exhaustive search algorithm, Exhaustive-IGain, which learns interactions from low-dimension datasets, and a heuristic search algorithm, called MBS-IGain, which learns interactions from high-dimensional datasets. Using simulated high-dimensional datasets, based on models of genetic epistasis, we compare MBS-IGain to 7 algorithms that learn genetic epistasis from high-dimensional datasets, and show that MBS-IGain’s discovery performance is notably better than the other methods. We apply MBS-IGain to a real LOAD dataset, and obtain results substantiating previous research and new results. Using low-dimensional simulated datasets, we show Exhaustive-IGain can learn 4-cause interactions with no marginal effects. We apply Exhaustive-Gain to a real clinical breast cancer datasets, and learn interactions that agree with the judgements of a breast cancer oncologist. Our algorithms are only directly applicable to problems where we have a specified target and its candidate causes. However, our algorithms could be used for general causal learning by being a front end to a standard causal learning algorithm.
Cell Types Contributing to the Biosynthesis of sIgA

Almost a decade ago different isotypes of immunoglobulin were found, by immunohistochemical analysis, to be localized in different plasma cells and it was inferred that circulating IgA was synthesized by the unique class of plasma cells which contained this protein (1,2). Thus it seemed particularly encouraging to efforts to locate the sites of synthesis of secretory IgA (sIgA) when Tomasi and his colleagues found many IgA containing lymphoid cells in the interstitial tissue between acini of human salivary glands (3) and Heremans and coworkers found copious numbers of IgA immunocytes (400,000/mm3) in the lamina propria of human intestine (4). Our analysis of the rabbit ileum by double fluorescent antibody staining confirmed the abundance of IgA lymphoid cells in the lamina propria and revealed the skewed distribution of IgA containing lymphoid cells in favor of intestinal mucosa compared with spleen and peripheral lymph nodes (5). The IgA immunocytes comprise 80–90% of the total population of plasma cells in the rabbit intestinal mucosa but they only make up about 5% of the total in spleen and peripheral lymph nodes. A possible explanation for the preponderance of IgA containing cells in secretory tissue in contrast to their relative scarcity elsewhere is that there are “central” lymphoid tissues which give rise to IgA plasma cell precursors uniquely able to selectively populate gut lamina propria and the interstitia of exocrine glands. Alternatively, each locale may contain a mixed population of lymphocytes which include some that are pre-committed to give rise to IgA-producing daughters and that are selectively stimulated. If, however, lymphocytes are not necessarily committed to the synthesis of a particular Ig class before antigenic stimulation, it may be that the secretory tissue environment can somehow influence plasma cell precursors to generate cells producing IgA.
Cannabinoid Hyperemesis Syndrome: Pathophysiology and Treatment in the Emergency Department.

Abstract Background Cannabinoid hyperemesis syndrome (CHS) is a challenging clinical disorder. CHS patients frequently present to the emergency department and may require treatment for intractable emesis, dehydration, and electrolyte abnormalities. Thought to be a variant of cyclic vomiting syndrome, CHS has become more prevalent with increasing cannabis potency and use, as enabled by various states having legalized the recreational use of cannabis. Objective This aim of this review is to investigate the pathophysiology of CHS and evaluate the published literature on pharmacologic treatment in the emergency department. This information may be helpful in providing evidence-based, efficacious antiemetic treatment grounded in knowledge of antiemetic medications’ mechanisms of action, potentially precluding unnecessary tests, and reducing duration of stay. Discussion The endocannabinoid system is a complex and important regulator of stress response and allostasis, and it is occasionally overwhelmed from excessive cannabis use. Acute episodes of CHS may be precipitated by stress or fasting in chronic cannabis users who may have pre-existing abnormal hypothalamic–pituitary–adrenal axis feedback and sympathetic nervous system response. The reasons for this may lie in the physiology of the endocannabinoid system, the pathophysiology of CHS, and the pharmacologic properties of specific classes of antiemetics and sedatives. Treatment failure with standard antiemetics is common, necessitating the use of mechanistically logical sedating agents such as benzodiazepines and antipsychotics. Conclusion Despite the increasing prevalence of CHS, there is a limited body of high-quality research. Benzodiazepines and antipsychotics represent logical choices for treatment of CHS because of their powerful sedating effects. Topical capsaicin holds promise based on a totally different pharmacologic mechanism. Discontinuation of cannabis use is the only assured cure for CHS.
Antibody Immunodominance: The Key to Understanding Influenza Virus Antigenic Drift

Abstract Influenza A virus (IAV) imposes a significant socioeconomic burden on humanity. Vaccination is effective in only 60% of individuals, even under optimal circumstances. The difficulty stems from the remarkable ability of IAV to evade existing immunity. IAV's error prone polymerase enables the rapid antigenic evolution of the two virion surface glycoproteins, neuraminidase and hemagglutinin (HA). Since the most potent antibodies (Abs) at neutralizing viral infectivity are directed the head of the HA, amino acid substitutions in this region enable IAV to evade Ab-based immunity. Here, we review recent progress in understanding how immunodominance, the tendency of the immune system to respond to foreign immunogens in a hierarchical manner, shapes IAV evolution.
Fluid Composition, Infusion Rate, and Brain Injury in Diabetic Ketoacidosis.

Diabetic ketoacidosis constitutes a profound metabolic disturbance of energy homeostasis with a distinct biochemical profile that is characterized by hyperglycemia, ketonemia, metabolic acidosis, a...
Impact origin of large intracratonic basins, the stationary Proterozoic crust, and the transition to modern plate tectonics

Impacts of large meteorites or comets into Proterozoic continental crust may have opened basins as much as hundreds of kilometers in diameter. We suggest that basalt magma generated through pressure-relief, partial melting flooded the craters to form lava lakes, which evolved into lopoliths capped with flood-basalt flows.
Strategies for Maintaining Sanity and Success

The number of women enrolled in graduate programs in the U.S. exceeds that of men (Snyder, 2009). Nevertheless, women have not advanced through the academic ranks at the same rate as their male counterparts (Mason & Goulden, 2004).
Self-destructive dermatoses.

This article outlines the important psychodynamic and biologic connections between mental illness and skin disturbances. The possible relationships in skin disease, depression, and psychosis are discussed with particular emphasis on two self-mutilative conditions: neurotic excoriations and dermatitis artefacta. The authors also provide guidelines for pharmacotherapy, psychotherapy, and prognosis.
The Contrast Between Causal (Explanatory) and Experiential (Normative) Understanding and Its Ramifications

As the medieval schoolmen already recognized, two rather different issues arise according as we concern ourselves with the relationships of the world’s things to one another among themselves (quoad se) or with how they make an impact upon us (quoad nos). In our endeavors to come to cognitive terms with the world about us we correspondingly have at our disposal two very different modes of understanding, based on two very different cognitive perspectives — the explanatorily causal and the affectively experiential.
Does Opioid Tapering in Chronic Pain Patients Result in Improved Pain or Same Pain vs Increased Pain at Taper Completion? A Structured Evidence-Based Systematic Review.

Objective To support or refute the hypothesis that opioid tapering in chronic pain patients (CPPs) improves pain or maintains the same pain level by taper completion but does not increase pain. Methods Of 364 references, 20 fulfilled inclusion/exclusion criteria. These studies were type 3 and 4 (not controlled) but reported pre/post-taper pain levels. Characteristics of the studies were abstracted into tabular form for numerical analysis. Studies were rated independently by two reviewers for quality. The percentage of studies supporting the above hypothesis was determined. Results No studies had a rejection quality score. Combining all studies, 2,109 CPPs were tapered. Eighty percent of the studies reported that by taper completion pain had improved. Of these, 81.25% demonstrated this statistically. In 15% of the studies, pain was the same by taper completion. One study reported that by taper completion, 97% of the CPPs had improved or the same pain, but CPPs had worse pain in 3%. As such, 100% of the studies supported the hypothesis. Applying the Agency for Health Care Policy and Research Levels of Evidence Guidelines to this result produced an A consistency rating. Conclusions There is consistent type 3 and 4 study evidence that opioid tapering in CPPs reduces pain or maintains the same level of pain. However, these studies represented lower levels of evidence and were not designed to test the hypothesis, with the evidence being marginal in quality with large amounts of missing data. These results then primarily reveal the need for controlled studies (type 2) to address this hypothesis.
16 Family Therapy

Family therapy is a set of treatment methods based in a systemic understanding of mutual influence in family systems, and which typically involve the presence of more than one family member in treatment. Research finds the effect sizes of couple and family therapy to be approximately the same as in individual therapy, with 70% of clients showing significant improvement. The first major schools of family therapy included structural family therapy, strategic therapy, Bowen therapy, and experiential, cognitive, and psychoanalytic therapies. Ideas and intervention strategies from each of these schools have influenced present practice. Today, many major forms of family therapy are largely integrative, including multidimensional, multi-systemic, and functional family therapies and integrative behavioral and emotionally focused couple therapies. Understandings of culture and gender are crucial foundations of today's family therapies. Keywords: family therapy; family systems; couple therapy
Electrical resistivity as a binary classifier for bridge scour evaluation

Abstract Scour is responsible for approximately 60% of all bridge collapses in the United States. Evaluating scour using empirical equations has proven inaccurate, particularly in fine-grained soils. Furthermore, evaluating scour potential based on site specific erosion testing can be uneconomic as erosion testing is time consuming. Many soil characteristics that affect soil erosion also influence soil electrical resistivity (ER) which can be measured in the field or in the laboratory. The objectives of this study were to assess if field and laboratory ER measurements can be used interchangeably for characterizing soil erodibility and the impact of saturation as expected during a flood event, on the ER based soil erodibility model. Twenty-one bridge sites were used for in situ electrical resistivity tomography (ERT) surveys and erosion testing. Supplementary ER measurements at varying degrees of saturation were also conducted using a soil box in the laboratory. It was found that ER values do not differ significantly when ERT is conducted on streambanks as opposed to fully saturated conditions. A receiver operating characteristic curve and probability density function (PDF) were used to determine that soils with ER over 50 Ωm had an 87% probability of classifying as highly erodible based on this data set. Statistical tests also suggested that laboratory ER can be used as an alternative to field ERT surveys. While in situ ERT provides more information in terms of spatial variation in the subsurface, laboratory ER measurements on retrieved samples will allow transportation agencies to utilize the developed erodibility classifier model without the capital investment of an ERT system. Given the large number of bridges with scour susceptible foundations in the National Bridge Inventory, ER can be used to rapidly prioritize them for additional testing to measure the erosion potential or to characterize the soil erosion at proposed bridge sites.
Recognition and significance of Upper Devonian fluvial, estuarine, and mixed siliciclastic-carbonate nearshore marine facies in the San Juan Mountains (southwestern Colorado, USA): Multiple incised valleys backfilled by lowstand and transgressive systems tracts

Geosphere, October 2019, v. 15, no. 5, 1479–1507, doi:10.1130/GES02085.1, Supplemental Materials. Petrology data; detrital zircon U/Pb geochronology data.
Abstract 038: The Arg16 / Gln27 Diplotype of the Beta-2 Adrenergic Receptor: Cardiovascular Insights from a Novel Transgenic Mouse Model

The beta-2 adrenergic receptor (B2AR) is an established regulator of vascular tone and cardiac contractility. Two polymorphisms of the B2AR (Gly16Arg and Glu27Gln) have been associated with cardiov...
The Underappreciated Influence of Elisabeth Kübler-Ross on the Development of Palliative Care for Children.

In the history of palliative care, all roads lead back to Dame Cicely Saunders, a remarkable social worker/nurse/physician who promoted the concept of total pain and founded the first modern hospic...
How Not to Deal with the Tragic Dilemma

Race is often epistemically relevant, but encoding racial stereotypes can lead to implicitly biased behavior. Thus, given the way race structures society, it seems to be impossible to be both epist...
Proposing rapid source pulsing for improved super-resolution in digital breast tomosynthesis

Our previous work showed that digital breast tomosynthesis (DBT) systems are capable of super-resolution, or subpixel resolution relative to the detector. Using a bar pattern phantom, it is possible to demonstrate that there are anisotropies in super-resolution throughout the reconstruction. These anisotropies are lessened in acquisition geometries with narrow spacing between source positions. This paper demonstrates that by re-arranging the source positions in the scan, the anisotropies can be minimized even further. To this end, a theoretical model of the reconstruction of a high-frequency sinusoidal test object was developed from first principles. We modeled the effect of clustering additional source positions around each conventional source position in fine increments (submillimeter). This design can be implemented by rapidly pulsing the source during a continuous sweep of the x-ray tube. It is shown that it is not possible to eliminate the anisotropies in a conventional DBT system with uniformly-spaced source positions, even if the increments of spacing are narrower than those used clinically. However, super-resolution can be achieved everywhere if the source positions are re-arranged in clusters with submillimeter spacing. Our previous work investigated a different approach for optimizing super-resolution through the use of detector motion perpendicular to the breast support. The advantage of introducing rapid source pulsing is that detector motion is no longer required; this mitigates the need for a thick detector housing, which may be cumbersome for patient positioning.
Unusual responses to PCSK9 inhibitors in a clinical cohort utilizing a structured follow-up protocol.

Abstract Objective To characterize unusual responses to PCSK9 inhibitor (PCSK9i) therapy in a real-world setting, given their extremely low prevalence in clinical trials. Methods A retrospective study of patients seen in a structured academic PCSK9i clinic who had LDL-C measurements before and after initiation of PCSK9i (up to 12 months). Unusual response was defined as: (1) no response: no changes in LDL-C level at all time points; (2) delayed response: Results Of the 411 patients meeting inclusion criteria, 54 were initially classified as unusual responders. After excluding those not adherent to prescribed interventions, 31 patients (7.5%) were classified as true unusual responders. These included: 2 with no response, 12 with delayed response, 3 with reduced response, 6 with delayed or reduced response, 4 with lost response, and 4 with delayed and lost response. Response to PCSK9i therapy at all time points revealed higher on-treatment LDL-C values (94–100 vs. 47–51 ​mg/dL, p ​ ​0.05), suggesting that unusual responses were not due to insufficient plasma PCSK9 blockade. Multiple logistic regression analysis identified clinical FH (OR 2.9, 95% CI 1.27-7.24) and no ezetimibe therapy (OR 0.334, 95% CI 0.150-0.728) as factors related to true unusual response. Conclusions Unusual responses to PCSK9i in a clinical cohort are more common than reported in clinical trials. Of the suspected unusual responders, nearly half were the result of adherence issues, and thus careful medication reconciliation should be the first step in diagnosing an unusual response.
Chapter 7 – Machine Learning

Publisher Summary Machine learning (ML) refers to a system's ability to acquire, and integrate knowledge through large-scale observations, and to improve, and extend itself by learning new knowledge rather than by being programmed with that knowledge. ML techniques are used in intelligent tutors to acquire new knowledge about students, identify their skills, and learn new teaching approaches. They improve teaching by repeatedly observing how students react and generalize rules about the domain or student. The role of ML techniques in a tutor is to independently observe and evaluate the tutor's actions. ML tutors customize their teaching by reasoning about large groups of students, and tutor-student interactions, generated through several components. A performance element is responsible for making improvements in the tutor, using perceptions of tutor/student interactions, and knowledge about the student's reaction to decide how to modify the tutor to perform better in the future. ML techniques are used to identify student learning strategies, such as, which activities do students select most frequently and in which order. Analysis of student behavior leads to greater student learning outcome by providing tutors with useful diagnostic information for generating feedback.
Effects of inter-alpha inhibitor proteins on brain injury after exposure of neonatal rats to severe hypoxia-ischemia

Abstract Hypoxic-ischemic (HI) brain injury is one of the most common neurological problems occurring in premature and full-term infants after perinatal complications. Hypothermia is the only treatment approved for HI encephalopathy in newborns. However, this treatment is only partially protective, cannot be used to treat premature infants, and has limited efficacy to treat severe HI encephalopathy. Inflammation contributes to the evolution of HI brain injury in neonates. Inter-alpha Inhibitor Proteins (IAIPs) are immunomodulatory proteins that have neuroprotective properties after exposure to moderate HI in neonatal rats. The objective of the current study was to determine the neuroprotective efficacy of treatment with IAIPs starting immediately after or with a delay of one hour after exposure to severe HI of 120 min duration. One hundred and forty-six 7-day-old rat pups were randomized to sham control, HI and immediate treatment with IAIPs (60 mg/kg) or placebo (PL), and sham, HI and delayed treatment with IAIPs or PL. IAIPs or PL were given at zero, 24, and 48 h after HI or 1, 24 and 48 h after HI. Total brain infarct volume was determined 72 h after exposure to HI. Treatment with IAIPs immediately after HI decreased (P
The paradox of framing water as a human right in the United States: An analysis of power and resistance

Many communities across the US struggle to access clean and affordable water. We examine civil society responses relying on “water as a human right” through case studies in California, Michigan, an...
The Mediator Subunit, Med23 Is Required for Embryonic Survival and Regulation of Canonical WNT Signaling During Cranial Ganglia Development.

Development of the vertebrate head is a complex and dynamic process, which requires integration of all three germ layers and their derivatives. Of special importance are ectoderm-derived cells that form the cranial placodes, which then differentiate into the cranial ganglia and sensory organs. Critical to a fully functioning head, defects in cranial placode and sensory organ development can result in congenital craniofacial anomalies. In a forward genetic screen aimed at identifying novel regulators of craniofacial development, we discovered an embryonically lethal mouse mutant, snouty, which exhibits malformation of the facial prominences, cranial nerves and vasculature. The snouty mutation was mapped to a single nucleotide change in a ubiquitously expressed gene, Med23, which encodes a subunit of the global transcription co-factor complex, Mediator. Phenotypic analyses revealed that the craniofacial anomalies, particularly of the cranial ganglia, were caused by a failure in the proper specification of cranial placode neuronal precursors. Molecular analyses determined that defects in cranial placode neuronal differentiation in Med23sn/sn mutants were associated with elevated WNT/β-catenin signaling, which can be partially rescued through combined Lrp6 and Wise loss-of-function. Our work therefore reveals a surprisingly tissue specific role for the ubiquitously expressed mediator complex protein Med23 in placode differentiation during cranial ganglia development. This highlights the importance of coupling general transcription to the regulation of WNT signaling during embryogenesis.
Surveillance in Older Women With Incidental Ovarian Cysts: Maximal Projected Benefits by Age and Comorbidity Level

Abstract Purpose The aim of this study was to estimate effects on life expectancy (LE) of imaging-based ovarian surveillance after detection of incidental postmenopausal ovarian cysts, under different assumptions of patient age, comorbidity level, and cancer risk and detection. Methods A decision-analytic Markov model was developed to estimate LE benefits. Hypothetical cohorts of postmenopausal women with simple ovarian cysts were evaluated, with varied age (66-80 years) and comorbidity level (none, mild, moderate, severe). For each cohort, imaging “follow-up” (2 years) and “no-follow-up” strategies were compared. Consistent with current evidence, increased cancer risk in patients with cysts was not assumed; however, incident ovarian cancers could be detected during follow-up. To estimate theoretical maximal LE gains from follow-up, perfect ovarian cancer detection and treatment during follow-up were assumed. This and other key assumptions were varied in sensitivity analysis. Results Projected LE gains from follow-up were limited. For 66-, 70-, 75-, and 80-year-old women with no comorbidities, LE gains were 5.1, 5.1, 4.5, and 3.7 days; with severe comorbidities, they were 3.5, 3.2, 2.7, and 2.1 days. With sensitivity of 50% for cancer detection, they were 3.7 days for 66-year-old women with no comorbidities and 1.3 days for 80-year-old women with severe comorbidities. When cancer risk for women with cysts was assumed to be elevated (1.1 times average risk), LE gains increased only modestly (5.6 and 2.3 days for analogous cohorts). Conclusions Even in the circumstance of perfect ovarian cancer detection and treatment, surveillance of postmenopausal women (≥66 years of age) with simple cysts affords limited benefits, particularly in women with advanced age and comorbidities.
Introduction: The Existential Crisis of Motherhood

The experience of motherhood is paradoxical; it evokes powerful emotions which are often contradictory. It is also a time of crisis as mothers undergo many changes both physical and emotional. This chapter explores how the crisis that a mother faces is an existential crisis as she becomes aware of the entirety of existence, of life and death and of the many choices she must make without any certainty of their outcome. This has the effect of making women feel umheimlich, or ‘not-at-home’ in their lives, where everything is transformed, and mothers have to rethink and re-evaluate their lives. In the same way that women are born psychologically when they become mothers, they also undergo an existential re-birth, as they confront the reality of their existence.
Synthetic training of machine learning algorithms for holographic cell imaging

In this work we seek to demonstrate acceptable classification performance for classifiers trained using augmented training data of synthetic cells imaged by simulated holography and evaluated using experimentally collected holographic data. In particular, we utilize experimentally collected DHM phase maps derived from the MDA-MB-231 breast cancer cell and immortalized human gingival fibroblast (GIE) cell lines. Automated segmentation was performed using a floodfill clustering approach and experimental feature distributions were used to generate statistically random synthetic cell realizations for each class.
Exploring the Role of Antinuclear Antibody Positivity in the Diagnosis, Treatment, and Health Outcomes of Patients With Rheumatoid Arthritis.

Objective The objective of this study was to describe differences in the clinical course of patients with rheumatoid arthritis (RA) who are antinuclear antibody (ANA)-positive compared with those who are ANA-negative. Methods This was a retrospective population-based cohort study of residents in Olmsted County, Minnesota, who first fulfilled 1987 American College of Rheumatology criteria for RA in 2009-2014. Data were collected on first documentation of joint swelling. Data on rheumatoid factor or anti-cyclic citrullinated peptide antibody testing and the ANA level were also collected. Comparisons between groups were performed by using χ2 and rank sum tests. Results In this cohort, 64% of patients were tested for ANA within ±90 days of RA criteria fulfillment. In the161 patients with ANA testing, 25% were ANA-positive. Patients who were ANA-positive were younger, female, and less likely to be current smokers. ANA positivity did not differ between patients with RA who were seropositive and seronegative. In seropositive patients who were ANA-positive, there was an increased time to fulfillment of RA criteria, increased time to treatment with disease-modifying antirheumatic drugs (DMARDs), and increased likelihood of being treated with hydroxychloroquine as opposed to methotrexate. Other outcomes, including disease activity and mortality, did not differ significantly between groups. Conclusion In patients with RA, important differences exist between those who are ANA-positive and ANA-negative in terms of time to fulfillment of RA criteria and time to DMARD initiation as well as choice of initial pharmacotherapy. These findings could indicate a difference in clinical presentation or perception of patients with RA who are ANA-positive. Further research is needed to study the long-term outcomes of patients with RA who are ANA-positive.
Direction-of-Arrival Estimation With A Vector Sensor Using Deep Neural Networks

A vector sensor is a type of sensor array with six collocated antennas that measures all electromagnetic field components of incident waves. The vector sensor has been shown to be advantageous in estimating both the angle of arrival and polarization of the incident sources. While direction-of-arrival (DOA) estimation with machine learning for linear arrays has been well studied, there has not been a similar solution for the vector sensor. In this paper, we propose a neural network that is capable of determining the number of the sources and estimating the DOA of each source based on the covariance matrix extracted from the received data. Additionally, a solution is proposed to associate the estimated DOAs to their sources, and a customized training loss function to address the field-of-view limit problem. Simulation results show that neural networks can achieve a reasonably accurate DOA estimation measured by the RMSE for up to five sources.
Site-directed mutagenesis studies on the recombinant thioesterase domain of chicken fatty acid synthase expressed in Escherichia coli.

Abstract The animal fatty acid synthase is a multifunctional protein with a subunit molecular weight of 260,000. We recently reported the expression and characterization of the acyl carrier protein and thioesterase domains of the chicken liver fatty acid synthase in Escherichia coli. In order to gain insight into the mechanism of action of the thioesterase domain, we have replaced the putative active site serine 101 with alanine and cysteine and the conserved histidine 274 with alanine by site-directed mutagenesis. While both the Ser101----Ala and His274----Ala mutant proteins were inactive, the Ser101----Cys mutant enzyme (thiol-thioesterase) retained considerable activity, but the properties of the enzyme were changed from an active serine esterase to an active cysteine esterase, providing strong evidence for the role of Ser101 as the active site nucleophile. In order to further probe into the role of His274, a double mutant was constructed containing both the Ser101----Cys and the His274----Ala mutations. The double-mutant protein was inactive and exhibited diminished reactivity of the Cys-SH to iodoacetamide as compared to that of the Ser101----Cys-thioesterase, suggesting a role of His274 as a general base in withdrawing the proton from the Cys-SH in the thiol-thioesterase or Ser101 in the wild-type enzyme. Incubation of the recombinant thioesterases with [1-14C] palmitoyl-CoA resulted in the incorporation of [1-14C] palmitoyl into the enzyme only in the double mutant, suggesting that Cys-SH of the double mutant is reactive enough to form the palmitoyl-S-enzyme intermediate. This intermediate is not hydrolyzed because of the lack of His274, which is required for the attack of H2O on the acyl enzyme. These results suggest that the catalytic mechanism of the thioesterases may be similar to that of the serine proteases and lipases, which employ a serine-histidine-aspartic acid catalytic triad as part of their catalytic mechanism.
Loss of CHFR in human mammary epithelial cells causes genomic instability by disrupting the mitotic spindle assembly checkpoint.

CHFR is an E3 ubiquitin ligase and an early mitotic checkpoint protein implicated in many cancers and in the maintenance of genomic stability. To analyze the role of CHFR in genomic stability, by siRNA, we decreased its expression in genomically stable MCF10A cells. Lowered CHFR expression quickly led to increased aneuploidy due to many mitotic defects. First, we confirmed that CHFR interacts with the mitotic kinase Aurora A to regulate its expression. Furthermore, we found that decreased CHFR led to disorganized multipolar mitotic spindles. This was supported by the finding that CHFR interacts with α-tubulin and can regulate its ubiquitination in response to nocodazole and the amount of acetylated α-tubulin, a component of the mitotic spindle. Finally, we found a novel CHFR interacting protein, the spindle checkpoint protein MAD2. Decreased CHFR expression resulted in the mislocalization of both MAD2 and BUBR1 during mitosis and impaired MAD2/CDC20 complex formation. Further evidence of a compromised spindle checkpoint was the presence of misaligned metaphase chromosomes, lagging anaphase chromosomes, and defective cytokinesis in CHFR knockdown cells. Importantly, our results suggest a novel role for CHFR regulating chromosome segregation where decreased expression, as seen in cancer cells, contributes to genomic instability by impairing the spindle assembly checkpoint.
Childhood Obesity: A Global Public Health Crisis

Introduction: Childhood obesity is a major public health crisis nationally and internationally. The prevalence of childhood obesity has increased over few years. It is caused by imbalance between calorie intake and calories utilized. One or more factors (genetic, behavioral, and environmental) cause obesity in children. Physical, psychological, and social health problems are caused due to childhood obesity. Hence, effective intervention strategies are being used to prevent and control obesity in children. The purpose of this manuscript is to address various factors influencing childhood obesity, a variety of interventions and governmental actions addressing obesity and the challenges ahead for managing this epidemic. Methods: In order to collect materials for this review a detailed search of CINAHL, MEDLINE, ERIC, Academic Search Premier databases was carried out for the time period 1999‑2011. Results: Some of the interventions used were family based, school based, community based, play based, and hospital based. The effective school‑based interventions were seen targeting physical activity along with healthy diet education. The major challenges faced by these intervention programs are financial, along with stigmatization of obese children. Governments along with other health care organizations are taking effective actions like policy changing and environmentally safe interventions for children to improve physical activity. Conclusions: In conclusion, childhood obesity can be tackled at the population level by education, prevention and sustainable interventions related to healthy nutrition practices and physical activity promotion.
Recent Rocket Observations of the Ultraviolet Spectrum of the Zodiacal Light

Observations of the spectrum of the zodiacal light in the wavelength range 1800–3000 A have been obtained in two recent sounding rocket experiments. The September 1979 observation was made close to the ecliptic plane at elongation angles of 20° and 28° and with a spectral resolution of 25 A, while in April 1981 the elongation was 125° (inclination 60°), and the spectral resolution 50 A. Both observations confirm the slight reddening in the ultraviolet reported previously and show the same dependence on elongation as in the visible. There appears to be some structure in the ultraviolet albedo of the dust grains near 2800 A but the exact nature of this structure cannot be determined at the low spectral resolution of the present observations. Detailed descriptions of the two observations has been given by Cebula and Feldman (1982) and Tennyson (1983), respectively.
Alterations in white matter pathways in Angelman syndrome.

Aim Angelman syndrome is a neurogenetic disorder characterized by severe intellectual disability, absent speech, seizures, and outbursts of laughter. The aim of this study was to utilize diffusion tensor imaging (DTI) to examine alterations in white matter pathways in Angelman syndrome, with an emphasis on correlations with clinical severity. Method DTI was used to examine the arcuate fasciculus (AF), uncinate fasciculus (UF), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and the corpus callosum (CC). We enrolled 14 children aged 8 to 17 years (mean age 10y 8mo; SD 2y 7mo) with Angelman syndrome (seven male; seven female) and 13 typically developing children, aged 8 to 17 years, for comparison (five male; eight female; mean age 12y; SD 2y 9mo). Individuals with Angelman syndrome were assessed using standardized measures of development, language, and behaviour. Results The children with Angelman syndrome exhibited lower fractional anisotropy and increased radial diffusivity values than the comparison group for the AF, UF, ILF, and CC (p<0.006 corrected for multiple comparisons). They also had lower fractional anisotropy values for the IFOF and higher radial diffusivity values for the left IFOF (p<0.006). Additionally, children with Angelman syndrome had significantly higher apparent diffusion coefficient values in the AF, CC, ILF, and the left IFOF (p<0.006). Significant correlations were noted between DTI parameters and some of the clinical assessment outcomes (e.g. language, socialization, cognition) for three of the temporal pathways (AF, UF, ILF; p<0.05). Interpretation Changes in DTI parameters in individuals with Angelman syndrome suggest decreased/delayed myelination, decreased axonal density or diameter, or aberrant axonal organization. Our findings suggest a generalized white matter alteration throughout the brain in those with Angelman syndrome; however, only the alterations in temporal white matter pathways were associated with language and cognitive and social functioning.
The Character of Discrimination Law: The Incompatibility of Rule 404 and Employment Discrimination Suits

This Note illustrates how violations of Rule 404 of the Federal Rules of Evidence (which prohibits litigants from relying on certain propensity proofs) occur routinely. It demonstrates that the ineffectiveness of the ban in the context of discrimination suits cannot be blamed on clever lawyers or negligent judges, but rather is a predictable consequence of the dearth of evidence available to discrimination plaintiffs. This Note concludes by arguing that this subtle but problematic incongruity justifies a reform of the Rule.