cssi/SciSciGPT-SciSciNet huggingface dataset:
Binding of Pseudomonas aeruginosa AlgZ to Sites Upstream of the algZ Promoter Leads to Repression of Transcription

Mucoid variants of the opportunistic pathogen Pseudomonas aeruginosa produce the exopolysaccharide alginate and colonize the respiratory tracts of cystic fibrosis patients. The genes encoding the alginate biosynthetic enzymes are clustered in a single operon, which is under tight transcriptional control. One essential activator of the alginate operon is AlgZ, a proposed ribbon-helix-helix DNA binding protein that shares 30% amino acid identity with the Mnt repressor of Salmonella enterica serovar Typhimurium bacteriophage P22. In the current study, we examined the role of AlgZ as an autoregulator. Using single-copy algZ-lacZ transcription fusions, an increase in algZ transcription was observed in an algZ mutant compared to the isogenic wild-type strain, suggesting that AlgZ may have an additional role as a repressor. To identify the AlgZ binding site, overlapping regions upstream of algZ were incubated with AlgZ and analyzed by electrophoretic mobility shift assays. Specific binding activity was localized to a region spanning from 66 to 185 base pairs upstream of the algZ transcriptional start site. Two AlgZ binding sites were defined using copper-phenanthroline footprinting and deletion analyses, with one site centered at 93 base pairs and the other centered at 161 base pairs upstream of the algZ promoter. Deletion of both binding sites resulted in the loss of AlgZ binding. These results indicate that AlgZ represses algZ transcription, and this activity is mediated by multiple AlgZ-DNA interactions.
Ironic insult added to copper injury.

Several clinical studies have suggested that excess hepatic iron accumulation is a progressive factor in some liver diseases including chronic viral hepatitis and hemochromatosis. However, it is not known whether iron-induced hepatotoxicity may be directly involved in hepatitis, cirrhosis, and liver cancer. The Long-Evans Cinnamon (LEC) rat, which accumulates excess copper in the liver as in patients with Wilson's disease, is of a mutant strain displaying spontaneous hemolysis, hepatitis, and liver cancer. We found previously that LEC rats harbored an additional abnormality: accumulation of as much iron as copper in the liver. In the present study, we compared the occurrence of hepatitis and liver cancer in LEC rats fed an iron-deficient diet (ID) with those in rats fed a regular diet (RD). The RD group showed rapid increments of hepatic iron concentrations as the result of hemolysis, characteristics of fulminant hepatitis showing apoptosis, and a 53% mortality rate. However, no rats in the ID group died of fulminant hepatitis. Hepatic iron, especially “free” iron concentration and the extent of hepatic fibrosis in the ID group were far less than those of the RD group. At week 65, all rats in the RD group developed liver cancer, whereas none did in the ID group. These results suggest that the accumulation of iron, possibly by virtue of synergistic radical formation with copper, plays an essential role in the development of fulminant hepatitis, hepatic fibrosis, and subsequent hepatocarcinogenesis in LEC rats.
NMDA Receptor Blockade Alters Stress-Induced Dendritic Remodeling in Medial Prefrontal Cortex

The development and relapse of many psychopathologies can be linked to both stress and prefrontal cortex dysfunction. Glucocorticoid stress hormones target medial prefrontal cortex (mPFC) and either chronic stress or chronic administration of glucocorticoids produces dendritic remodeling in prefrontal pyramidal neurons. Exposure to stress also causes an increase in the release of the excitatory amino acid glutamate, which binds to N-methyl-D-aspartate (NMDA) receptors, which are plentiful in mPFC. NMDA receptor activation is crucial for producing hippocampal dendritic remodeling due to stress and for dendritic reorganization in frontal cortex after cholinergic deafferentation. Thus, NMDA receptors could mediate stress-induced dendritic retraction in mPFC. To test this hypothesis, dendritic morphology of pyramidal cells in mPFC was assessed after blocking NMDA receptors with the competitive NMDA antagonist ±3-(2-carboxypiperazin-4yl)propyl-1-phosphonic acid (CPP) during restraint stress. Administration of CPP prevented stress-induced dendritic atrophy. Instead, CPP-injected stressed rats showed hypertrophy of apical dendrites compared with controls. These results suggest that NMDA activation is crucial for stress-induced dendritic atrophy in mPFC. Furthermore, NMDA receptor blockade uncovers a new pattern of stress-induced dendritic changes, suggesting that other neurohormonal changes in concert with NMDA receptor activation underlie the net dendritic retraction seen after chronic stress.
Resetting of ventricular tachycardia: Implications for localizing the area of slow conduction

Analysis of local endocardial electrograms recorded during reentrant ventricular tachycardia does not provide direct information as to the participation of the recording site in the tachycardia circuit. To determine if programmed electrical stimulation at the recording site can assist in localizing areas of slow conduction that are participating in the tachycardia circuit, seven patients with sustained monomorphic ventricular tachycardia were studied. The cardiac cycle was scanned with single stimuli delivered during ventricular tachycardia at multiple endocardial sites. In four patients, an endocardial site was identified at which stimuli advanced the tachycardia with marked conduction delay and without alteration of the ventricular activation sequence, as indicated by a lack of change in the configuration of the QRS complex and endocardial electrograms distant from the stimulation site. This finding was seen only during stimulation at sites displaying abnormal electrograms and is consistent with premature depolarization of an area of slow conduction within the tachycardia focus by stimuli delivered at or near that area. Attempted endocardial catheter ablation at or adjacent to these sites in three patients was followed by persistent noninducibility of ventricular tachycardia in one patient, marked modification of the configuration and cycle length of inducible tachycardia in one patient and transient noninducibility of tachycardia in one patient. Programmed electrical stimulation during ventricular tachycardia at sites with abnormal electrograms may provide information about the proximity of the stimulation site to the tachycardia circuit.
Filming Nabokov: On the Visual Poetics of the Text

(2004). Filming Nabokov : On the Visual Poetics of the Text. Russian Studies in Literature: Vol. 40, No. 3, pp. 6-31.
Incorporating Archaeology Into Local Government Historic Preservation and Planning: A Review of Current Practice

Problem, research strategy, and findings: The fate of archaeological sites in cities, towns, and county jurisdictions are greatly affected by the decisions of local governments and planning departments, which usually operate with little formal guidance regarding archaeological site stewardship. What strategies do local governments use to effectively manage archaeological sites in their jurisdictions? Which ones work best? To address these questions, we carried out an exploratory study of mechanisms used by local government planners for archaeological resource protection in 24 states between 2008 and 2015, obtaining information from 69 local governments. We use questionnaires and interviews with local government staff, Tribal Historic Preservation Officers (THPOs), and State Historic Preservation Officers (SHPOs), identifying the range of practices employed. Within the jurisdictions we studied, the most elaborate programs a) have local ordinances protecting archaeology, on-staff archaeologists, and use spe...
Therapy assessment of locally advanced pancreatic adenocarcinoma: Hopkins criteria and FDG-PET/CT quantitative parameters.

640 Objectives This study aims to evaluate the predictive value of Hopkins criteria and quantitative PET/CT parameters for therapy response assessment in patients with locally advanced pancreatic adenocarcinoma (LAPC). Methods Forty-two patients (median age 66 years) with LAPC were retrospectively included. PET/CT performed at a median of 4.6 weeks following completion of chemotherapy ± radiotherapy to assess therapy response. PET was interpreted visually using a structured qualitative five-point scale (Hopkins criteria for therapy assessment) and was dichotomized to negative (score 1-3) and positive (score 4 and 5) result. Quantitative PET/CT parameters including SUVmax, SUVpeak, Tumor lesion glycolysis (TLG), and metabolic tumor volume (MTV) were also measured using gradient segmentation method. Univariate and multivariate Cox regression analysis was performed using death as an endpoint and Kaplan Meir curves were generated with median and optimum cut points. Results All patients, except 7, were followed until death. The median survivals were 14.6 vs. 8.7 months in patients with negative vs. positive PET scan (p=0.04). Positive Hopkins criteria was associated with increased hazard of death within 1-year (HR=3.32, p=0.03). In quantitative analysis, SUVmax (cut point 3.62; HR=5, p=0.001), SUVpeak (cut point 2.69; HR=4.18, p=0.002), TLG (cut point 57.92g; HR=2.82, p=0.01), and MTV (cut point 37.41ml; HR=3.6, p=0.003) were significantly predict death within 1-year following the therapy assessment PET scan. In multivariate cox-regression analysis, the median SUVpeak 2.64 (HR=6.15, p=0.006), TLG 43.98g (HR=2.97, p=0.01), and MTV 24.69ml (HR=2.69, p=0.03) were significant predictors of overall survival even after adjustment for age, sex, race, and serum level of post-treatment CA19-9. Conclusions PET-based structured qualitative therapy assessment (Hopkins Criteria) and volumetric parameters can predict survival outcomes of patients with LAPC.
Wall Deformation, Wall Shear Stress and Atherosclerosis Around the Intercostal Ostia of C57 Mice

Dorsal surfaces and upstream regions around ostia of aortic branches are favored sites of atherosclerosis. Both asymmetrical stresses in branch walls and disturbed flow patterns have been suggested as contributing to this localization. In the present study, fluorescence images of the thoracic aortic tree of C57 mice were obtained using quantum dot (Qdot) bioconjugate markers for vascular cell adhesion molecule-1 (VCAM-1) and two-photon excitation laser scanning microscopy. The images show that dorsal surfaces and upstream regions of intercostal ostia have a higher intensity of VCAM-1 than the downstream region. We also investigated blood flow patterns and wall shear stress (WSS) in the descending aorta and proximal intercostal branches of C57 mice using micro-CT imaging and ultrasound velocity measurements, combined with computational fluid dynamics (CFD). The latter investigation showed that dynamical wall deformation caused by pulsatile pressure around the ostia induces blood flow patterns which create lower and oscillating WSS in the upstream region and dorsal surface than in the distal region. Comparisons of the Qdot marker and CFD studies demonstrate that the distribution of greater expression of VCAM-1 corresponds with lower and oscillating WSS around the branch ostia. Thus, local wall deformation may contribute to disturbed flow patterns that are known to be associated with increased VCAM-1 expression.© 2007 ASME
Quantile inference based on clustered data

One-sample sign test is one of the common procedures to develop distribution-free inference for a quantile of a population. A basic requirement of this test is that the observations in a sample must be independent. This assumption is violated in certain settings, such as clustered data, grouped data and longitudinal studies. Failure to account for dependence structure leads to erroneous statistical inferences. In this study, we have developed statistical inference for a population quantile of order p in either balanced or unbalanced designs by incorporating dependence structure when the distribution of within-cluster observations is exchangeable. We provide a point estimate, develop a testing procedure and construct confidence intervals for a population quantile of order p. Simulation studies are performed to demonstrate that the confidence intervals achieve their nominal coverage probabilities. We finally apply the proposed procedure to Academic Performance Index data.
Ten rules for keeping the art of medicine alive in daily practice.

A physician presents ten rules for maintaining the art of healing in daily medical practice. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.
Some Questions on Microecological

Objective:To discusse some questions and sol ve method on microecological in the market at present, to uppraised the form and p harmacologic effect. Methods:To gather the directions rel ated to content for clinical often to used preparations. Results:It hasn't unitary standard and expression on every microecological, the effect is close related to the form. The importance of pharmacologic effect is h ealth care and regalating. Conclusion:It must have a qual ity standard and expression on microecological.
Prevention of Multiple Systems Failure

Multiple organ failure is not only a syndrome but a concept in the care and study of injured patients. This concept provides a framework for clinical problem solving which should be an important activity for all surgeons.
Negative urgency, mood induction, and alcohol seeking behaviors.

Abstract Background Negative urgency, defined as impulsive risk-taking during extreme negative emotional states, is the most important impulsivity-related trait for alcohol-related problems and alcohol dependence. However, how negative urgency imparts risk for alcohol-related problems is not yet well understood. Therefore, the goal of the current study was to examine how negative urgency relates to separable aspects of the emotional experience and alcohol-seeking behaviors. Methods A total of 34 (19 women) community-dwelling, alcohol-using adults aged 21–32 (mean age = 24.86, SD = 3.40, 74.3% Caucasian) completed two counterbalanced intravenous alcohol self-administration sessions: one during a neutral mood condition and one during a negative mood condition. Results Negative urgency was associated with 1) greater mood change following negative mood induction (F = 4.38, df = 15, p = 0.002, η2 = 0.87), but was unrelated to changes in craving or cortisol release in response to mood induction; 2) greater alcohol craving prior to and after an alcohol prime (F = 3.27, p = 0.02, η2 = 0.86), but only in the negative and not the neutral mood condition; and 3) higher peak BrAC (F = 2.13, df = 42, p = 0.02, η2 = 0.48), continuing to increase intoxication level over a longer period (F = 3.77, df = 42, p Conclusions These results highlight the importance of assessing behavioral indicators of negative urgency under mood condition, and suggest that negative urgency may amplify alcohol self-administration through increased negative emotional reactivity to mood events and increased alcohol craving after initial alcohol exposure, leading to maintenance of alcohol related behavior.
Lack of Agreement With What We Think Is Right Does Not Necessarily Equal an Ethical Problem: Respecting Patients' Goals of Care.

Implantable cardioverter defibrillators (ICDs) have proven effective in preventing sudden cardiac death for appropriately selected patients, and are implanted under guidelines that recommend them f...
To Break or Not To Break: Sex Chromosome Hemizygosity During Meiosis in Caenorhabditis.

Meiotic recombination establishes connections between homologous chromosomes to promote segregation. Hemizygous regions of sex chromosomes have no homologous chromosome to recombine with, yet must be transmitted through meiosis. An extreme case of hemizygosity exists in the genus Caenorhabditis, where males have a single X chromosome that completely lacks a homologous partner. To determine whether similar strategies have evolved to accommodate hemizygosity of the X during male meiosis in Caenorhabditis with distinct modes of sexual reproduction, we examined induction and processing of meiotic double strand breaks (DSBs) in androdioecious (hermaphrodite/male) Caenorhabditis elegans and C. briggsae, and gonochoristic (female/male) C. remanei and C. brenneri. Analysis of the recombinase RAD-51 suggests more meiotic DSBs are induced in gonochoristic vs. androdioecious species. However, in late prophase in all species, chromosome pairs are restructured into bivalents around a single axis, suggesting that the holocentric nature of Caenorhabditis chromosomes dictates a single crossover per bivalent regardless of the number of DSBs induced. Interestingly, RAD-51 foci were readily observed on the X chromosome of androdioecious male germ cells, while very few were detected in gonochoristic male germ cells. As in C. elegans, the X chromosome in C. briggsae male germ cells undergoes transient pseudosynapsis and flexibility in DSB repair pathway choice. In contrast, in C. remanei and C. brenneri male germ cells, the X chromosome does not undergo pseudosynapsis and appears refractory to SPO-11-induced breaks. Together our results suggest that distinct strategies have evolved to accommodate sex chromosome hemizygosity during meiosis in closely related Caenorhabditis species.
Diagnostics of non-equilibrium atmosperic plasma jets for cancer therapy

Plasma medicine is a relatively new field that outgrew from research in application of low-temperature (or cold) non-equilibrium atmospheric plasmas in bioengineering. One of the most promising applications of cold atmospheric plasma (CAP) is the cancer therapy. Convincing evidence of CAP selectivity towards the cancel cells has been accumulated.
Wrist Motions in Industry: Variance between Jobs and Subjects

Ergonomists assume that they can design out injurious postures and motions with engineering controls by guiding the worker to use the preferred, less injurious motions. The variance between workers...
PatterNet: a system to learn compact physical design pattern representations for pattern-based analytics

This research considers the problem of generating compact vector representations of physical design patterns for analytics purposes in semiconductor patterning domain. PatterNet uses a deep artificial neural network to learn mapping of physical design patterns to a compact Euclidean hyperspace. Distances among mapped patterns in this space correspond to dissimilarities among patterns defined at the time of the network training. Once the mapping network has been trained, PatterNet embeddings can be used as feature vectors with standard machine learning algorithms, and pattern search, comparison, and clustering become trivial problems. PatterNet is inspired by the concepts developed within the framework of generative adversarial networks as well as the FaceNet. Our method facilitates a deep neural network (DNN) to learn directly the compact representation by supplying it with pairs of design patterns and dissimilarity among these patterns defined by a user. In the simplest case, the dissimilarity is represented by an area of the XOR of two patterns. Important to realize that our PatterNet approach is very different to the methods developed for deep learning on image data. In contrast to “conventional” pictures, the patterns in the CAD world are the lists of polygon vertex coordinates. The method solely relies on the promise of deep learning to discover internal structure of the incoming data and learn its hierarchical representations. Artificial intelligence arising from the combination of PatterNet and clustering analysis very precisely follows intuition of patterning/optical proximity correction experts paving the way toward human-like and human-friendly engineering tools.
Aberrant expression of redox regulatory proteins in patients with concomitant primary Sclerosing cholangitis/inflammatory bowel disease.

Abstract Objective Primary Sclerosing Cholangitis (PSC) is a severe cholestatic liver disease characterized by progressive peri-biliary tract inflammation, elevated oxidative stress and hepatocellular injury. A hallmark of PSC patients is the concurrent diagnosis of Inflammatory Bowel Disease occurring in approximately 70%–80% of PSC patients (PSC/IBD). We previously reported dysregulation of key anti-oxidant pathways in PSC/IBD. The objective of this study was to expand previous data by examining the abundance of thioredoxins (Trx) in PSC/IBD. Methods Using hepatic tissue and whole cell extracts isolated from age-matched healthy humans and patients diagnosed with end stage PSC/IBD, the protein abundance of thioredoxin, thioredoxin reductase (TrxR1), and their downstream substrates peroxiredoxins was assessed. Results Western blot analyses of thioredoxin and peroxiredoxin abundance revealed significant increases in abundance of Trx1 and TrxR1 whereas expression of thioredoxin-interacting protein was significantly decreased in PSC/IBD. Concurrently, abundance of cytosolic peroxiredoxins was not significantly impacted. The abundance of mitochondrial Trx2, along with peroxiredoxins 3, 5 and 6 were significantly decreased by concurrent PSC/IBD. Histological staining of Trx1/TrxR1 revealed elevated nuclear Trx1 and TrxR1 staining within cholangiocytes as well as an overall periportal increase in expression in PSC/IBD. An examination of additional anti-oxidant responses reveal suppression of gamma-glutamylcysteine synthetase and heme oxygenase (HO-1) whereas expression of the protein chaperone glucose regulated protein 78 increased suggesting elevated cellular stress in PSC/IBD. Conclusions Results herein suggest that in addition to severe dysregulation of anti-oxidant responses, cholestasis impacts both cytosolic/nuclear (Trx1) as well as mitochondrial (Trx2) redox signaling and control pathways.
Basic Definitions and Criteria for the Management and Assurance of Quality in Health Care

Although health care quality has been defined in many different ways, it is probably fair to say that none has clearly captured all the elements involved. One of the more comprehensive definitions, developed for the Department of Veterans’ Affairs, states that “quality health care is care that is needed and delivered in a manner that is competent, caring, cost effective and timely and that minimizes risk and achieves achievable benefits” (Barbour, 1996). This definition, though adequate, has all the grace usually found in the products of committees, of which it clearly is an example. Translated from committee jargon, the definition can be summed up as “quality health care is doing the right thing, at the right time, and in the right way.” To provide health care of high quality, then, we have to know what is the right action, seize the right time, and single-mindedly pursue the right way—a tall order, indeed.
Factors that predict the need for intubation in patients with smoke inhalation injury

Early identification of smoke inhalation patients who will require intubation is crucial. We conducted a retrospective chart review to identify predictors of respiratory distress in patients who present with smoke inhalation injury. Our study involved 41 patients who had been treated in the emergency room at a regional burn center. Eight of these patients required intubation. Intubation was positively correlated with physical examination findings of soot in the oral cavity (p < 0.001), facial burns (p = 0.025), and body burns (p = 0.025). The need for intubation was also predicted by fiberoptic laryngoscopic findings of edema of either the true vocal folds (p < 0.001) or the false vocal folds (p < 0.01). No statistically significant correlation was found between intubation and any of the classic symptoms of smoke inhalation: stridor, hoarseness, drooling, and dysphagia (all p = 1.0). Also, multivariate analysis revealed that facial burns correlated significantly with edema of the true vocal folds (p = 0.01) and body burns correlated significantly with edema of both the true (p = 0.047) and false (p = 0.003) vocal folds. We conclude that patients with soot in the oral cavity, facial burns, and/or body burns should be monitored closely because these findings indicate a higher likelihood of laryngeal edema and the need for intubation.
Sensitivity analysis of hydraulic conductivity and Manning's n parameters lead to new method to scale effective hydraulic conductivity across model resolutions

Hydrological modelling is an important tool for research, policy, and management, but uncertainty remains about parameters transferability from field observations made at small scale to models at the catchment scale and larger. This uncertainty compels the need to develop parameter relationships that are translatable across scale. In this study, we compare the changes to modelled processes as resolution is coarsened from 100‐m to 1‐km in a topographically complex, 255‐km² Colorado River headwater catchment. We conducted a sensitivity analysis for hydraulic conductivity (K) and Manning's n parameters across four orders of magnitude. Results showed that K acts as a moderator between surface and subsurface contributions to streamflow, whereas n moderates the duration of high intensity, infiltration‐excess flow. The parametric sensitivity analysis informed development of a new method to scale effective hydraulic conductivity across modelling resolutions in order to compensate for the loss of topographic gradients as resolution is coarsened. A similar mathematical relationship between n and lateral resolution changes was not found, possibly because n is also sensitive to time discretization. This research provides an approach to translate hydraulic conductivity parameters from a calibrated coarse model to higher resolutions where the number of simulations are limited by computational demand.
Der künstlich erzeugte Leberinfarkt zur Behandlung örtlich beschränkten Lebercarcinoms

Es wird eine Methode zur kunstlichen Infarzierung von Leberabschnitten beschrieben, welche innerhalb gewisser Grenzen von Laboratoriumssaugetieren gut vertragen wird. Anwendung dieser Methode zur Zerstorung in die Kaninchenleber implantierten V 2-Carcinoms verlangerte die durchschnittliche Uberlebenszeit behandelter Tiere gegenuber nichtbehandelten Kontrolltieren.
Nishida’s Bow: Evaluating Nishida’s Wartime Actions

ABSTRACTThis paper examines Nishida’s later work on the historical world and religious transformation in an effort to clarify his political writings during the Pacific War. It sheds new light on th...
Systematic determination of the relationship between nanoparticle core diameter and toxicity for a series of structurally analogous gold nanoparticles in zebrafish

AbstractPredictive models for the impact of nanomaterials on biological systems remain elusive. Although there is agreement that physicochemical properties (particle diameter, shape, surface chemis...
Harm Reduction Process for Severe Hoarding

The primary goal of the harm reduction (HR) process is to create a plan to minimize the risks associated with severe hoarding. A HR plan identifies what must be done to the living environment to bring it to a minimum level of safety; who will do the work and how they will go about doing this; how long will the process take; and, who will monitor adherence with the plan and how. This chapter describes the HR process applied to severe hoarding in detail. This chapter begins with a description of the initial and ongoing phases of the HR process, including the rationale and objectives of these phases. This chapter then describes the primary features of the HR process and guidelines for conducting full and modified cleanouts. This chapter then describes the role of the clinician and the role of the legal system in the HR process, a topic of growing importance to municipalities looking for ways to manage the problem of severe hoarding in their communities.
Challenges to and strategies for recruiting chronic care dyads into intervention research.

ObjectivesRecruiting and enrolling appropriate participants into research trials for chronic illness populations can be challenging and time intensive. Successful recruitment requires a variety of ...
Randomized Clinical Trial Examining Cognitive Behavioral Therapy for Individuals With a First-Time DUI Offense

BACKGROUND Driving under the influence (DUI) programs are a unique setting to reduce disparities in treatment access to those who may not otherwise access treatment. Providing evidence-based therapy in these programs may help prevent DUI recidivism. METHODS We conducted a randomized clinical trial of 312 participants enrolled in 1 of 3 DUI programs in California. Participants were 21 and older with a first-time DUI offense who screened positive for at-risk drinking in the past year. Participants were randomly assigned to a 12-session manualized cognitive behavioral therapy (CBT) or usual care (UC) group and then surveyed 4 and 10 months later. We conducted intent-to-treat analyses to test the hypothesis that participants receiving CBT would report reduced impaired driving, alcohol consumption (drinks per week, abstinence, and binge drinking), and alcohol-related negative consequences. We also explored whether race/ethnicity and gender moderated CBT findings. RESULTS Participants were 72.3% male and 51.7% Hispanic, with an average age of 33.2 (SD = 12.4). Relative to UC, participants receiving CBT had lower odds of driving after drinking at the 4- and 10-month follow-ups compared to participants receiving UC (odds ratio [OR] = 0.37, p = 0.032, and OR = 0.29, p = 0.065, respectively). This intervention effect was more pronounced for females at 10-month follow-up. The remaining 4 outcomes did not significantly differ between UC versus CBT at 4- and 10-month follow-ups. Participants in both UC and CBT reported significant within-group reductions in 2 of 5 outcomes, binge drinking and alcohol-related consequences, at 10-month follow-up (p < 0.001). CONCLUSIONS In the short-term, individuals receiving CBT reported significantly lower rates of repeated DUI than individuals receiving UC, which may suggest that learning cognitive behavioral strategies to prevent impaired driving may be useful in achieving short-term reductions in impaired driving.
Neural adaptation to accented speech: prefrontal cortex aids attunement in auditory cortices

Speech is a complex and ambiguous acoustic signal that varies significantly within and across speakers. A prevalent and ubiquitous example of such variation is accented speech, to which humans adapt extremely rapidly. The goal of this study is to uncover the neurobiological bases of the attunement process that enables such fluent comprehension. Twenty-four native English participants listened to words spoken by an unaccented "canonical" American talker and two "accented" talkers, and performed a word-picture matching task, while magnetoencephalography (MEG) was recorded. Accented speech was created by including systematic phonological substitutions within the word (e.g. [s] -> [sh]). Activity in the auditory cortex (superior temporal gyrus) was greater for accented speech, but, critically, this was not attenuated by exposure. By contrast, prefrontal regions showed an interaction between the presence of an accent and amount of exposure: while activity decreased for canonical speech over time, responses to accented speech remained consistently elevated. Grainger causality analyses further revealed that prefrontal responses serve to modulate activity in auditory regions, suggesting the recruitment of top-down processing to decode accented signal. In sum, our results show that accented speech does not elicit the same prefrontal reduction in amplitude over time that unaccented speech does, and points to a dynamic exchange of information between the prefrontal and auditory cortices in order to recalculate phonetic classification and subsequent identification of lexical items.
Dally-like protein sequesters multiple Wnt ligands in the Drosophila germarium.

Abstract Cells in multicellular organisms rely on secreted ligands for development and morphogenesis. Several mechanisms modulate the availability and distribution of secreted ligands, determining their ability to signal locally and at long range from their source. One of these mechanisms is Dally-like protein (Dlp), a cell-surface glypican that exhibits biphasic functions in Drosophila wing discs, promoting Wg signaling at long-range from Wg source cells and inhibiting Wg signaling near source cells. In the germarium at the tip of the ovary, Dlp promotes long-range distribution of Wg from cap cells to follicle stem cells. However, the germarium also expresses other Wnts - Wnt2, Wnt4, and Wnt6 - that function locally in escort cells to promote oogenesis. Whether and how local functions of these Wnts are regulated remains unknown. Here we show that the dlp overexpression phenotype is multifaceted and phenocopies multiple Wnt loss-of-function phenotypes. Each aspect of dlp overexpression phenotype is suppressed by co-expression of individual Wnts, and the suppression pattern exhibited by each Wnt suggests that Wnts have functional specificity in the germarium. Further, dlp knockdown phenocopies Wnt gain-of-function phenotypes. Together these data show that Dlp inhibits the functions of each Wnt. All four Wnts co-immunoprecipitate with Dlp in S2R+ ​cells, suggesting that in the germarium, Dlp sequesters Wnts to inhibit local paracrine Wnt signaling. Our results indicate that Dlp modulates the availability of multiple extracellular Wnts for local paracrine Wnt signaling in the germarium.
When Are Search Completion Suggestions Problematic

Problematic web search query completion suggestions-perceived as biased, offensive, or in some other way harmful-can reinforce existing stereotypes and misbeliefs, and even nudge users towards undesirable patterns of behavior. Locating such suggestions is difficult, not only due to the long-tailed nature of web search, but also due to differences in how people assess potential harms. Grounding our study in web search query logs, we explore when system-provided suggestions might be perceived as problematic through a series of crowd-experiments where we systematically manipulate: the search query fragments provided by users, possible user search intents, and the list of query completion suggestions. To examine why query suggestions might be perceived as problematic, we contrast them to an inventory of known types of problematic suggestions. We report our observations around differences in the prevalence of a) suggestions that are problematic on their own versus b) suggestions that are problematic for the query fragment provided by a user, for both common informational needs and in the presence of web search voids-topics searched by few to no users. Our experiments surface a rich array of scenarios where suggestions are considered problematic, including due to the context in which they were surfaced. Compounded by the elusive nature of many such scenarios, the prevalence of suggestions perceived as problematic only for certain user inputs, raises concerns about blind spots due to data annotation practices that may lead to some types of problematic suggestions being overlooked.
Changes in Body Mass Index Are Related to Faster Cognitive Decline Among African American Older Adults

Background/objectives The purpose of this study was to: (1) examine relationships between body mass index (BMI) stability and cognitive decline in older African Americans; and (2) investigate differences in the relationships between women and men. Design The present study is a secondary data analysis of the Minority Aging Research Study, which is a longitudinal, cohort study of risk factors for cognitive decline and Alzheimer's disease among older African Americans living in the Chicago, IL, area. The study entails annual clinical evaluations, including measures of 19 neuropsychological tests that represent five cognitive domains, including episodic, semantic, and working memory, perceptual speed, and visuospatial ability. Participants Participants (n = 671; mean age = 73.5 years; standard deviation = 6.2 years) were included in the present analysis if they were dementia free at baseline and completed at least two clinical evaluations, on average 1 year apart, that included valid cognitive and BMI assessments. Results Mixed-effects models showed higher baseline BMI was related to slower global cognitive decline, whereas changes in BMI (instability) were related to faster global cognitive decline. These effects were the same for four of five cognitive domains and remained after controlling for various health characteristics. However, women and men did not differ in any of the relationships. Conclusion Higher BMI is related to slower cognitive decline in older African Americans, but greater BMI instability is related to faster decline. Stability of BMI should be considered in the cognitive aging of African Americans.
A pattern transfer from semiconductors, and more: Nikon’s large-size photomask blanks for flat panel display

In this presentation we introduce photolithography for Flat Panel Display. The conventional problem for large-size photomask blanks is uniformity. For a large area, it is really difficult to improve substrate flatness and PSM transmittance/phase shifting angle uniformity. In this presentation we introduce our “Super Flat Mask (SFM) series” that have excellent flatness over G10 area. We also introduce our Att-Phase Shift film over G10 area. These films have uniform optical characteristics and nearly orthogonal cross section after etching. Along with very flat substrates, these films contribute well to production of high resolution panels.
Demonstration of the EMPATHIC Framework for Task Learning from Implicit Human Feedback

Reactions such as gestures, facial expressions, and vocalizations are an abundant, naturally occurring channel of information that humans provide during interactions. An agent could leverage an understanding of such implicit human feedback to improve its task performance at no cost to the human. This approach contrasts with common agent teaching methods based on demonstrations, critiques, or other guidance that need to be attentively and intentionally provided. In this work, we demonstrate a novel data-driven framework for learning from implicit human feedback, EMPATHIC. This two-stage method consists of (1) mapping implicit human feedback to relevant task statistics such as reward, optimality, and advantage; and (2) using such a mapping to learn a task. We instantiate the first stage and three second-stage evaluations of the learned mapping. To do so, we collect a dataset of human facial reactions while participants observe an agent execute a sub-optimal policy for a prescribed training task. We train a deep neural network on this data and demonstrate its ability to (1) infer relative reward ranking of events in the training task from prerecorded human facial reactions; (2) improve the policy of an agent in the training task using live human facial reactions; and (3) transfer to a novel domain in which it evaluates robot manipulation trajectories. In the video, we focus on demonstrating the online learning capability of our instantiation of EMPATHIC.
Study on the Effect of Two Different Transfusion Methods in Neonates with Hyperbilirubinemia Induced by Non-Blood-Group Antibodies.

Purpose The study aimed to analyse the clinical effect of homotype ET method and compatible ET method in neonates with hyperbilirubinemia caused by non-blood-group antibodies (non-blood-group antibodies refers to due to cause other than blood-group antibodies) as well as to provide relevant reference materials for clinical diagnosis and treatment in Fuzhou city. Patients and Methods Between January 2011 and December 2020, a total of 125 neonates, who were admitted to the Sentinel hospital of Fuzhou city, Fujian Provincial Maternity and Children's Hospital for hyperbilirubinemia and treated with ET therapy were selected. They were divided into homotype ET (n=32) and compatibility ET (n=93) treatment groups. We analysed changes in serum total bilirubin (STB), serum indirect bilirubin (SIB), and platelet count before and after ET; retrospectively analysed the neonates' clinical data; and compared findings between the 2 groups. Results The homotype ET group and the compatible ET group showed higher STB, SIB, and platelet levels before ET and decreased levels of the same after ET; the difference was statistically significant (P 0.05). Conclusion ET therapy is the most timely and effective treatment method for severe hyperbilirubinemia in neonates clinically, and the effects of homotype and compatible ET are similar.
Viscoplasticity and large-scale chain relaxation in glassy-polymeric strain hardening.

Developing a microscopic analytic theory of glassypolymeric mechanical response has been a long-standing challenge. Plasticity in amorphous materials is almost always viscoplasticity, i.e., plasticity with rate dependence. Many recent studies have focused on plasticity in metallic or colloidal glasses. Relative to these systems, polymer glasses possess a wider range of characteristic length and time scales because of the connectivity, uncrossability, and randomwalk-like structure of the constituent chains. These alter the mechanical properties significantly 1; for example, a uniquely polymeric feature of plastic response is massive strain hardening beyond yield. The relationships between polymeric relaxation times on different spatial scales are fairly well understood for melts 2 but much less so for glasses. Recent experiments 3–5, simulations 5–7, and theories 8,9 have all shown that local segment-level relaxation times in polymer glasses decrease dramatically under active deformation especially at yield and increase when deformation is ceased. Analysis of these phenomena has focused on stress-assisted thermal activation of the local relaxation processes, but it is likely that other structural relaxation processes at larger scales or of different e.g., strain-activated character are also important in determining the mechanical response. Improved understanding of the concomitant scale-dependent relaxation is necessary to better understand polymeric plasticity and material failure. However, theoretical prediction of large-scale relaxation in deformed polymer glasses is still in its infancy; most treatments evaluate mechanical response “neglecting the effect of the ongoing structural relaxation during the experiment” 10.
Recent advances in genome editing and creation of genetically modified pigs

The field of xenotransplantation is benefiting greatly from recent advances in genetic engineering. The efficiency and pace with which new model animals are being created has dramatically sped progress towards clinical relevance. Endonuclease-driven genome editing now allows for the efficient generation of targeted genetic alterations. Herein we review the available methods of genetic engineering that have been successfully employed to create genetically modified pigs.
Directly Measuring the Adhesive and Elastic Properties of Bacteria using a Surface Force Apparatus

Bacteria are increasingly being employed as components in biosensors and biofilm reactors. It is important to understand the material properties of bacteria in dry conditions for these applications. For a decade, Atomic Force Microscopy (AFM) has been the primary tool used to study the adhesion and elastic properties of individual bacteria. In this work we show it is possible to use a Surface Forces Apparatus (SFA) to measure elastic and adhesive properties of small collections of surface bound bacteria. The measurements are conducted with submonolayer, patterned bacterial films and we have developed a protocol to image the contact area with AFM after the experiment. Using the SFA, we measured the force profile between a Pseudomonas aeruginosa PAO1 film and a bare mica surface. Pseudomonas aeruginosa PAO1 is a ubiquitous gram-negative soil bacterium and is also an opportunistic pathogen. We repeated the measurement in the same contact position for a number of days to determine the effect of desiccation on the film material properties.
The Current Status of Liver Transplantation

I would like to cover the experience which we have had with liver transplantation and to try to indicate where I think developments in this field will be going. There has been some interesting administrative movement in the United States which may have relevance to the objectives of workers in Europe and the Middle East.
The Future of Federal-State Land Exchanges

Today, the land ownership map of the West in many places resembles a crazy quilt, without reason or coherent pattern. Often no single owner (states, private entities, or the Federal government) owns enough contiguous land to allow effective management of land holdings, and fragmented ownership patterns generate a plethora of disputes over access and similar problems. While this paper focuses on examples from Utah, the challenges posed by a fragmented landscape and conflicting management objectives are much broader. Across the 11 contiguous Western states, state trust lands account for twice the acreage of National Parks and trust lands are often interspersed with protected or sensitive lands. Inholdings within National Forests, for example, total 14.3 million acres. While many inholdings are owned by private parties rather than state trust land agencies, the fact that National Forest inholdings in the 11 contiguous Western states account for more land than all of Maryland and Vermont combined indicates the scope of the problem.
Improving the Department of Defense's Small Business Innovation Research Program

Abstract : This document presents the statement of Bruce Held, Senior Policy Researcher at the RAND Corporation, before the Committee on Science and Technology, Subcommittee on Technology and Innovation, United States House of Representatives on April 26, 2007. The testimony draws primarily on research that Mr. Held led in 2004 for the Department of Defense's Small Business Technology and Industrial Base Office (SBTIBO). The purpose of that research was to provide DoD with insights into the current status of its Small Business Innovation Research (SBIR) program in terms of the department's transformational technology priorities, innovation, and the small-business defense industrial base. Following that initial assessment, the project's objective became the recommendation of policy options for making the DoD SBIR program more responsive to the needs of the department. In his invitation to testify, Mr. Held was asked to address the following questions: (1) How could program effectiveness be improved?; (2) What are appropriate award levels?; (3) How should administration costs be funded?; (4) How can the programs increase the participation of innovative small businesses in federal RD and (5) What program enhancements are recommended to address the financing and commercialization assistance needs of participants?
Inheritance of osteosarcoma and Paget's disease of bone: a familial loss of heterozygosity study.

Pagetoid osteosarcoma is a complication of Paget's disease of bone. Sarcomatous transformation is most often seen in severe, long-standing Paget's disease. Familial clustering of Paget's disease has been described with apparent autosomal dominant inheritance with high penetrance by the sixth decade. Although definitive proof of the specific gene involved remains elusive, some researchers have shown loss of heterozygosity in a region of chromosome 18q in a relatively high percentage of studied patients affected with either Paget's disease alone, in Pagetoid osteosarcoma, and in uncomplicated osteosarcoma. Our patient was diagnosed with Pagetoid osteosarcoma and had a first-degree relative with history of the same. We hypothesized that our patient's tumor samples might contain a similar genetic abnormality. Our analysis of several polymorphic markers from the chromosome 18q21–22 region showed loss of maternally inherited alleles throughout the region. This finding is similar to those described previously4 and provides further evidence of a susceptibility region relating to this disease. This report describes a father and son, their young ages at diagnosis of Pagetoid sarcoma, the identical sites of disease involvement, and a loss of heterozygosity study illustrating the inheritance of the presumed defective gene.