cssi/SciSciGPT-SciSciNet huggingface dataset:
CtIP mediates replication fork recovery in a FANCD2-regulated manner

Fanconi anemia (FA) is a chromosome instability syndrome characterized by increased cancer predisposition. Within the FA pathway, an upstream FA core complex mediates monoubiquitination and recruitment of the central FANCD2 protein to sites of stalled replication forks. Once recruited, FANCD2 fulfills a dual role towards replication fork recovery: (i) it cooperates with BRCA2 and RAD51 to protect forks from nucleolytic degradation and (ii) it recruits the BLM helicase to promote replication fork restart while suppressing new origin firing. Intriguingly, FANCD2 and its interaction partners are also involved in homologous recombination (HR) repair of DNA double-strand breaks, hinting that FANCD2 utilizes HR proteins to mediate replication fork recovery. One such candidate is CtIP (CtBP-interacting protein), a key HR repair factor that functions in complex with BRCA1 and MRE11, but has not been investigated as putative player in the replication stress response. Here, we identify CtIP as a novel interaction partner of FANCD2. CtIP binds and stabilizes FANCD2 in a DNA damage- and FA core complex-independent manner, suggesting that FANCD2 monoubiquitination is dispensable for its interaction with CtIP. Following cellular treatment with a replication inhibitor, aphidicolin, FANCD2 recruits CtIP to transiently stalled, as well as collapsed, replication forks on chromatin. At stalled forks, CtIP cooperates with FANCD2 to promote fork restart and the suppression of new origin firing. Both functions are dependent on BRCA1 that controls the step-wise recruitment of MRE11, FANCD2 and finally CtIP to stalled replication forks, followed by their concerted actions to promote fork recovery.
Decreased uptake and release of D-aspartate in the guinea pig spinal cord after partial cordotomy.

: This study attempts to determine if L-glutamate and/or L-aspartate may be transmitters of neural tracts descending from the brain to the spinal cord. The uptake and electrically evoked release of D-[3H]aspartate, a putative marker for L-glutamate and L-aspartate, were measured in the cervical enlargement of the guinea pig spinal cord. These activities were compared using unlesioned animals and others with a lesion on the right side of the spinal cord. Partial cordotomy (segment C5) produced a heavy loss of descending fibers, a small loss of primary sensory fibers, and a depression of the uptake and the Ca2+-dependent, electrically evoked release of D-aspartate ipsilateral and caudal to the lesion. Contralaterally, there was a moderate loss of corticospinal fibers, some loss of other descending axons, and a depression of D-aspartate release. Dorsal rhizotomy (segments C4–T1) produced a heavy loss of primary sensory fibers ipsilateral to the lesion. Ipsilaterally, but not contralaterally, the uptake and release of D-aspartate were depressed. Degeneration after partial cordotomy in combination with dorsal rhizotomy was assumed to be the sum of that produced by each lesion separately. This combined lesion depressed D-aspartate uptake ipsilaterally and depressed D-aspartate release on both sides of the cervical enlargement. None of the lesions altered the up-take and the evoked release of [3H]GABA. These findings support the hypothesis that the synaptic endings of one or more neural tracts descending from the brain to the spinal cord mediate the uptake and release of D-aspartate and, therefore, may use L-glutamate or L-aspartate as a transmitter.
The Need to Treat Maternal Pain in the Breastfeeding Mother: Are Opioids Safe?

Do we have an ethical imperative to treat pain in women who are breastfeeding? In essence, there are two patient entities to be considered: the mother and the breastfed infant. The drugs used in the treatment of maternal pain may have potentially deleterious effects on the breastfed infant. Safety of the infant is paramount, but inadequate treatment of maternal pain seems unethical. In fact, under treatment of pain in a breastfeeding woman may make it difficult for the woman to breast feed the baby, and may contribute to maternal depression ⇓. The American Academy of Pediatrics recommends that infants be exclusively breastfed up to 6 months, followed by continuation of breastfeeding (along with complementary foods) up to the first year of life or even longer depending on the mother and the child ⇓. However, one of the factors affecting the decision to breast feed may …
Complex dynamics in a 4D Peano-Hilbert space

The work outlines a scenario for a dynamic system to possess strange nonchaotic behaviour in the presence of quasi-periodic forcing. Implications for ergodicity and turbulence are also discussed in connection with Serpenski and Peano-Hilbert spaces in 4D. Relation to quantum space-time is also touched upon.
Estimating High-Resolution Atmospheric Phase Screens From Radar Interferometry Data

Radar interferometry (InSAR) deformation measurements are afflicted by artifacts associated with the atmosphere and errors in removing the topographic phase contribution. We present a new time series algorithm that eliminates high-spatial-frequency atmospheric effects (bubbles) not removed with existing advanced InSAR approaches applied to measurements of smoothly varying deformation through time. Our High-Resolution Atmospheric Phase Screen (APS) (HiRAPS) algorithm initially uses a connected set of short-period interferograms, each spanning no more than three satellite-orbit repeat cycles. We estimate height error differences between a pixel and its neighbors within a radius chosen to be significantly smaller than a bubble. The height errors are unwrapped and removed from those pixels with high values of a newly defined multi-interferogram phase correlation. We then create a deformation time series for the pixels using singular value decomposition. The high-resolution APS are estimated from a dense set of pixels using spatiotemporal filtering. We evaluate the HiRAPS algorithm on simulated data consisting of realistic time-linear and nonlinear deformation, height errors, and bubbles. The root mean square error between all simulated and estimated APS pixels is 0.26 rad with the HiRAPS algorithm and 0.39 rad with a persistent scatterer (PS) algorithm. We also apply the HiRAPS algorithm to 66 Radarsat-1 images of Phoenix, AZ. Our HiRAPS approach results in an 18-fold increase in APS pixel density over PS processing. After removing the HiRAPS and PS APS from PS interferograms, we find that HiRAPS provides an 18% increase in the number of final PS detected.
Complications associated with anterior cervical surgery

Abstract Fortunately, the incidence of major complications associated with anterior cervical spine surgery is low. Surgeons should remain cognizant of the possible intraoperative and postoperative complications, along with methods of prevention and treatment. This review briefly discusses the complications of esophageal, vertebral, and neurological injury, along with spinal fluid leak and hematoma. In general, anterior cervical spine procedures are highly successful with infrequent complications. However, the range of associated morbidity (and mortality) can be broad with each potential complication. Knowledge of potential complications is essential, including associated risk factors, methods of prevention, and treatment. This review briefly discusses intraoperative and immediate postoperative complications.
Molecular Principles Underlying the Ames Salmonella/Microsome Test: Elements and Design of Short-Term Mutagenesis Tests

The drug resistance plasmid pKM101 has played a critical role in the success of the Ames Salmonella tester strains in detecting carcinogens as mutagens. pKM101 increases the susceptibility of bacterial cells to both point and frameshift mutagenesis by a variety of chemical mutagens and makes them more resistant to killing by ultraviolet light. It does so in a recA + lexA +-dependent fashion and suppresses the mutagenesis and repair deficiencies of Escherichia coli umuC mutants, suggesting that the plasmid codes for protein(s) which participate in the process of “error-prone repair.” In the absence of pKM101, Salmonella typhimurium appears to be less proficient than Escherichia coli in its capacity to carry out “error-prone repair”; but if pKM101 is present, both have similar capacities. In addition, much of this capacity to process chemical damage and give mutations is constitutively expressed in pKM101-containing cells. pKM101 is able to increase the frequencies of both transitions and transversions in response to chemical mutagens. Point mutants of pKM101 have been isolated which have concomitantly lost the ability to increase base-pair substitution and frameshift mutagenesis and to protect cells against killing by UV. Recently, we have isolated pKM101 mutants with similar properties by insertion of the translocatable drug resistance element Tn5. All such insertions were shown to map within a ca. 1500 bp region of pKM101. Genetic experiments suggest that at least two pKM101-coded functions are involved in the enhancement of chemical mutagenesis.
Roles for p53 in growth arrest and apoptosis: putting on the brakes after genotoxic stress

The tumor suppressor gene p53 plays a major role in regulation of the mammalian cellular stress response, in part through the transcriptional activation of genes involved in cell cycle control, DNA repair, and apoptosis. Many factors contribute to control of the activation of p53, and the downstream response to its activation may also vary depending on the cellular enviroment or other modifying factors in the cell. The complexity of the p53 response makes this an ideal system for application of newly emerging rapid throughput analysis techniques and informatics analysis
Krylov Integration Factor Method on Sparse Grids for High Spatial Dimension Convection---Diffusion Equations

Krylov implicit integration factor (IIF) methods were developed in Chen and Zhang (J Comput Phys 230:4336---4352, 2011) for solving stiff reaction---diffusion equations on high dimensional unstructured meshes. The methods were further extended to solve stiff advection---diffusion---reaction equations in Jiang and Zhang (J Comput Phys 253:368---388, 2013). Recently we studied the computational power of Krylov subspace approximations on dealing with high dimensional problems. It was shown that the Krylov integration factor methods have linear computational complexity and are especially efficient for high dimensional convection---diffusion problems with anisotropic diffusions. In this paper, we combine the Krylov integration factor methods with sparse grid combination techniques and solve high spatial dimension convection---diffusion equations such as Fokker---Planck equations on sparse grids. Numerical examples are presented to show that significant computational times are saved by applying the Krylov integration factor methods on sparse grids.
Self-reported gadolinium toxicity: A survey of patients with chronic symptoms

Abstract Purpose This study aims to describe the self-reporting symptoms experienced by individuals with self-reported normal renal function after gadolinium based contrast agent (GBCA) administration. Materials and methods This HIPAA-compliant, IRB-approved study consisted of an anonymous online survey of patients who believe that they suffer from gadolinium toxicity. 50 respondents completed the nine-question survey. Results Fifty (100%) of the subjects ascribed their complaints to gadolinium exposure. Thirty-three (66%) described the onset immediately following GBCA administration and 16 (32%) within 6 weeks. The most common symptoms included bone/joint pain and head/neck symptoms including headache, vision change, and hearing change (77.6% each). Other symptoms occurred with lesser incidence. Conclusions This survey represents an initial description of patients with normal renal function who self-described toxicity related to GBCA administration. Bone and joint complaints and skin changes are two of the most common complaints.
Saccular Aneurysms of the Transverse Aortic Arch: Treatment Options Available in the Endovascular Era

Saccular aneurysms of the aortic arch, whether single or multiple, are uncommon. The choice of repair technique is influenced by patients' comorbidities and age. Repairing saccular aneurysms with traditional open techniques can be technically demanding; therefore, endovascular technology and a variety of hybrid approaches have been developed to facilitate such repairs and, potentially, to improve clinical outcomes, especially in high-risk patients. There have been no large, randomized studies to compare the outcomes of these different treatment options in patients with single or multiple saccular aneurysms of the arch. In this review, we outline the etiology and common locations of these aneurysms, the different open, completely endovascular, and hybrid techniques used to treat them, and the treatment selection process.
Degradation of Bovine Factor VIII by Plasmin and Trypsin

The degradation of bovine Factor VIII by plasmin, trypsin, and thrombin was monitored with polyacrylamide gel electrophoresis in a urea-acetic acid system. The sequences of plasmic and tryptic proteolysis were very similar, proceeding via several intermediate, enzyme-sensitive products to smaller derivatives which were relatively resistant to further degradation. The intermediate degradation products were similar for both enzymes, although prolonged digestion with trypsin produced final products which were smaller than those observed with plasmin. Stages of digestion which reflect the degree of completeness of proteolysis were defined on the basis of the presence or absence of these distinct components in the electrophoretic profiles. Thrombin treatment of Factor VIII caused a loss of coagulant activity but did not yield products small enough to be characterized in this electrophoretic system. During the course of plasmic and tryptic digestion, there was a rapid loss of all coagulant activity without the generation of anticoagulant activity. Agarose chromatography of a 24-hr plasmic digest revealed three major protein peaks, which corresponded to individual electrophoretic bands on polyacrylamide gel electrophoresis in a nondenaturing system at pH 8.8. Upon polyacrylamide gel electrophoresis in the urea-acetic acid system, the components of the first two of these peaks dissociated into two and three separate fragments, respectively. Immunoelectrophoresis demonstrated two major distinct antigenic determinants in these first two elution peaks.
Predictors of Intractable Epilepsy

Risk factors for intractable epilepsy at the time of initial diagnosis were determined in a case-control study at Yale University, New Haven, CT.
Frequency of and Significance of Physical Frailty in Patients With Heart Failure

Physical frailty is an important prognostic indicator in heart failure (HF); however, few studies have examined the relation between physical frailty and invasive hemodynamics among adults with HF. The purpose of this study was to characterize physical frailty in HF in relation to invasive hemodynamics. We enrolled 49 patients with New York Heart Association class II to IV HF when participants were scheduled for a right-sided cardiac heart catheterization procedure. Physical frailty was measured according to the "frailty phenotype": shrinking, weakness, slowness, physical exhaustion, and low physical activity. Markers of invasive hemodynamics were derived from a formal review of right-sided cardiac catheterization tracings, and projected survival was calculated using the Seattle HF model. The mean age of the sample (n = 49) was 57.4 ± 9.7 years, 67% were men, 92% had New York Heart Association class III/IV HF, and 67% had nonischemic HF. Physical frailty was identified in 24 participants (49%) and was associated with worse Seattle HF model 1-year projected survival (p = 0.007). After adjusting for projected survival, physically frail participants had lower cardiac index (by both thermodilution and the Fick equation) and higher heart rates compared with those not physically frail (all p
The effects of circadian rhythms on Toll-like receptor responses in murine macrophages (INM7P.357)

Circadian rhythms refer to the endogenous oscillations of biological processes with 24-hour periodicity in response to environmental cues. On a molecular level, circadian rhythms are accomplished through positive and negative feedback loops among the core Clock genes: Clock, Period , Cryptochrome and Bmal . These oscillations in gene expression regulate a myriad of cellular functions and activities. Recently, circadian rhythms have been found to promote comparable oscillations in components of the innate and adaptive immune system. Synchronization of the circadian clock can be induced in vitro via a process known as serum shock. Here, we took advantage of this model to investigate the effects of circadian oscillations on Toll-like receptor (TLR) responses in murine macrophages. Serum shock induced a 24h oscillation in mRNA expression for the clock gene Period 2 , as well as for a period2-luciferase fusion reporter gene, confirming synchronization of the circadian clock. Serum-shocked cells were then stimulated with a panel of TLR agonists and cytokine secretion was quantified over time to investigate the impact of circadian rhythms on TLR responses. Our findings suggest circadian oscillation with regard to interleukin (IL)-12p40 production upon stimulation of TLR2 and TLR7. Suggestive oscillations were also observed with regard to IL-6 production upon stimulation of TLR2. These data suggest that circadian rhythms control TLR responses at the cellular level.
Imaging in the TEM

We’ve already mentioned back in Chapters 2–4 that TEM image contrast arises because of the scattering of the incident beam by the specimen. The electron wave can change both its amplitude and its phase as it traverses the specimen and both these kinds of change can give rise to image contrast. Thus a fundamental distinction we make in the TEM is between amplitude contrast and phase contrast. In most situations, both types of contrast actually contribute to an image, although one will tend to dominate. In this chapter we’ll discuss only amplitude contrast and we’ll see that there are two principal types, namely mass-thickness contrast and diffraction contrast. This kind of contrast is observed in both TEM and STEM BF and DF images and we’ll discuss the important differences between the images formed in each of these two modes of operation. We’ll then go on to discuss the principles of diffraction contrast, which are sufficiently complex that it takes Chapters 23–26 to show you how this form of contrast is used to identify and distinguish different crystal defects. Diffraction-contrast imaging came into prominence in about 1956, when it was realized that the intensity in a diffracted beam depends strongly on the deviation parameter, s, and that crystal defects distort the diffracting planes. Therefore, the diffraction contrast from regions close to the defect would depend on the properties (in particular, the strain field) of the defect. We’ll then consider phase contrast and how it can be used to image atomic level detail in Chapters 27–30. Other forms of TEM imaging and variations on these major types of contrast are gathered in the catch-all Chapter 31.
Comprehensive approach to reestablishing form and function after radical parotidectomy.

Abstract Introduction The reconstructive goals following radical parotidectomy include restoration of symmetry, reanimation of the face, and reestablishment of oral competence. We present our experience utilizing the anterolateral thigh (ALT) free flap, orthodromic temporalis tendon transfer (OTTT), and facial nerve cable grafting to reestablish form and function. Material and methods From 2010 to 2016, 17 patients underwent radical parotidectomy followed by immediate reconstruction. An ALT was harvested to accommodate the volume and skin defect. Additional fascia lata and motor nerve to vastus lateralis (MNVL) were obtained. Anastomosis of the ALT to recipient vessels was performed, most commonly using the facial artery and internal jugular vein. OTTT was performed by securing the medial tendon of the temporalis to orbicularis oris through a nasolabial incision. Fascia lata was tunneled through the lower lip, then secured laterally to the temporalis tendon. The MNVL was cable grafted from either the proximal facial nerve or masseteric nerve to the distal facial nerve branches. ALT fascia was suspended to the superficial muscular aponeurotic system. Results Average follow up was 19 months. Only one patient failed to achieve symmetry attributed to dehiscence of OTTT. All patients achieved oral competence and dynamic smile with OTTT activation. Facial nerve recovery was seen in 8 patients. 5 reached a House Brackman Score of 3. Two donor site seromas and two wound infections occurred. Conclusion Simultaneous ALT, OTTT, and facial nerve cable grafting provides early reestablishment of facial symmetry, facial reanimation, and oral competence with minimal morbidity.
Images of Water and the Sea in Tristan L’ Hermite’s “La Mer” and in Painting

Seascapes and water in baroque poetry and painting often portray disquiet and portend disruption, disaster, and chaos. Skepticism and pessimism characterize this outlook in which man no longer exists as the highlight and center of a closed universe leading to eternal salvation. As late as the mid-seventeenth century, Pascal, in Les Pensees, states that man cannot acquire certain knowledge outside his own experiences. He describes man as existing in an incommensurable infinity of eternal silence. According to Pascal, man bases his uncertain certainty on uncertainty.1 Sponde’s Sonnet XI “Et quel bien de la mort” emphasizes the poet’s recognition of the illogical pattern of life. The poet’s voice is divided between resignation and rebellion as he questions: “C’est benediction que de vivre, pourquoy nous fais-tu mourir?” The query’s basic contradiction is overcome only by an act of faith in God and the belief in the reward of eternal salvation which bypasses reason and exists as an uncertain certainty.2 Baroque creative artists juxtapose the ephemerality of human existence with the eternal presence of the four elements: land, air, fire, and water.
Purification and characterization of the recombinant CMP-sialic acid synthetase from Neisseria meningitidis

CMP-Sialic acid synthetase from Neisseria meningitidis 406Y was expressed in Escherichia coli K113 pLysS and produced at 360 U/L. The purified CMP-sialic acid synthetase used both N-acetyl-neuraminic acid (Km = 0.34 mM) and N-glycolyl-neuraminic acid (Km = 2.6 mM) as substrates. The recombinant synthetase could be used in a coupled reaction with an β-2,3-sialyltransferase to sialylate a lactose derivative in a one-reactor synthesis.
Give Me More Feedback: Annotating Argument Persuasiveness and Related Attributes in Student Essays

While argument persuasiveness is one of the most important dimensions of argumentative essay quality, it is relatively little studied in automated essay scoring research. Progress on scoring argument persuasiveness is hindered in part by the scarcity of annotated corpora. We present the first corpus of essays that are simultaneously annotated with argument components, argument persuasiveness scores, and attributes of argument components that impact an argument’s persuasiveness. This corpus could trigger the development of novel computational models concerning argument persuasiveness that provide useful feedback to students on why their arguments are (un)persuasive in addition to how persuasive they are.
S-CHIRP: Securing Communications in Lightweight Peer-to-Peer Networks in the IoT

Although you may think of our technological world as a giant web of elegantly interconnected devices, the reality is a collection of messy overlapping networks, all communicating simultaneously on disparate infrastructural backbones. To communicate within the chaos today, specific components may be forced to share space on dedicated local networks, or, in many cases, they must rely on complex switching and routing methods to transfer information.
‘apparent’: a simple and flexible R package for accurate SNP-based parentage analysis in the absence of guiding information

The accurate determination of parent-progeny relationships within both in situ natural populations and ex situ genetic resource collections can greatly enhance plant breeding/domestication efforts and support plant genetic resource conservation strategies. Although a range of parentage analysis tools are available, none are designed to infer such relationships using genome-wide single nucleotide polymorphism (SNP) data in the complete absence of guiding information, such as generational groups, partial pedigrees, or genders. The R package (‘apparent’) developed and presented here addresses this gap. ‘apparent’ adopts a novel strategy of parentage analysis based on a test of genetic identity between a theoretically expected progeny (EPij), whose genotypic state can be inferred at all homozygous loci for a pair of putative parents (i and j), and all potential offspring (POk), represented by the k individuals of a given germplasm collection. Using the Gower Dissimilarity metric (GD), genetic identity between EPij and POk is taken as evidence that individuals i and j are the true parents of offspring k. Significance of a given triad (parental pairij + offspringk) is evaluated relative to the distribution of all GDij|k values for the population. With no guiding information provided, ‘apparent’ correctly identified the parental pairs of 15 lines of known pedigree within a test population of 77 accessions of Actinidia arguta, a performance unmatched by five other commonly used parentage analysis tools. In the case of an inconclusive triad analysis due to the absence of one parent from the test population, ‘apparent’ can perform a subsequent dyad analysis to identify a likely single parent for a given offspring. Average dyad analysis accuracy was 73.3% in the complete absence of pedigree information but increased to 100% when minimal generational information (adults vs. progeny) was provided. The ‘apparent’ R package is a fast and accurate parentage analysis tool that uses genome-wide SNP data to identify parent-progeny relationships within populations for which no a priori knowledge of family structure exists.
Adversarial Speaker Adaptation

We propose a novel adversarial speaker adaptation (ASA) scheme, in which adversarial learning is applied to regularize the distribution of deep hidden features in a speaker-dependent (SD) deep neural network (DNN) acoustic model to be close to that of a fixed speaker-independent (SI) DNN acoustic model during adaptation. An additional discriminator network is introduced to distinguish the deep features generated by the SD model from those produced by the SI model. In ASA, with a fixed SI model as the reference, an SD model is jointly optimized with the discriminator network to minimize the senone classification loss, and simultaneously to mini-maximize the SI/SD discrimination loss on the adaptation data. With ASA, a senone-discriminative deep feature is learned in the SD model with a similar distribution to that of the SI model. With such a regularized and adapted deep feature, the SD model can perform improved automatic speech recognition on the target speaker’s speech. Evaluated on the Microsoft short message dictation dataset, ASA achieves 14.4% and 7.9% relative word error rate improvements for supervised and unsupervised adaptation, respectively, over an SI model trained from 2600 hours data, with 200 adaptation utterances per speaker.
An ethnography of the safety professional’s dilemma: Safety work or the safety of work?

Abstract The safety profession has grown and evolved over recent decades, and despite the prominence of the role within organisations, there is limited research about the current state of safety professional practice. The objective of a safety professional’s role is often stated as ‘preventing incidents and harm to people', although the existing research fails to demonstrate a compelling link between safety professional practice and worker safety. More recently, a model of safety work in organisations proposed that safety activities fulfill broader social and political needs, in addition to the physical reduction of safety risk. In this paper, we report a study that investigated the underlying objectives of individual safety professional tasks, then performed thematic analysis to explore the contemporary role of safety professionals in organisations. 12 mid-level and senior-level safety professionals were interviewed at monthly intervals for six months regarding their work activities, in addition to an embedded researcher performing more than 240 h of field observations. Four categories of safety work in organisations – demonstrated, social, administrative, and physical – were used as priori themes to deductively analyze the data. The findings demonstrate strength of alignment between the safety professional role and line management, the increasing institutionalization of safety professional work, an absence of safety professional work directed at reducing safety risks to workers, and the lack of a clear connection between safety professional practice and safety science research.
An aryl isonitrile compound with an improved physicochemical profile that is effective in two mouse models of multidrug-resistant Staphylococcus aureus infection

Abstract Objectives The aim of this study was to investigate the antibacterial activity of a synthetic aryl isonitrile compound (35) that was developed as part of a compound library to identify new antibacterial agents effective against methicillin-resistant Staphylococcus aureus (MRSA). Methods Compound 35 was evaluated against MRSA isolates by the broth microdilution assay and for toxicity to mammalian keratinocytes using the MTS assay. A multistep resistance selection assay was conducted to investigate MRSA resistance development to 35. A Caco-2 bidirectional permeability assay was employed to evaluate the ability of 35 to permeate across the gastrointestinal tract, and compound 35 was incubated with human liver microsomes to determine susceptibility to hepatic metabolism. Finally, compound 35 was evaluated in an uncomplicated MRSA skin infection mouse model and an MRSA neutropenic thigh infection mouse model. Results Compound 35 inhibited the growth of MRSA clinical isolates at 2–4 μM and was non-toxic to human keratinocytes. No resistance formation was observed with MRSA against compound 35 after 10 serial passages. In a murine skin wound model, compound 35 significantly reduced the burden of MRSA, similar to the antibiotic fusidic acid. Compound 35 exhibited a marked improvement both in permeability and stability to hepatic metabolism (half-life >11 h) relative to the first-generation lead compound. In a neutropenic thigh infection mouse model, compound 35 successfully reduced the burden of MRSA in immunocompromised mice. Conclusion In summary, compound 35 was identified as a new lead aryl isonitrile compound that warrants further investigation as a novel antibacterial agent.
Seasonal incidence of biopsy-proven giant cell arteritis: a 20-year retrospective study of the University of California Davis Medical System.

OBJECTIVES Giant cell arteritis (GCA) is a vasculitis that affects large and medium sized arteries. The aetiology of GCA is unknown and numerous risk factors have been proposed. In this article, we evaluate the incidence of biopsy-positive GCA in Northern California and assess for seasonal variation. METHODS We performed a retrospective review based on billing codes of temporal artery biopsies performed at the University of California, Davis from 2003 to 2014. RESULTS We identified 174 biopsies (119 female, 55 male). Of these, 21 positive biopsies were female while 8 were male. Although three times as many women had a positive biopsy compared to men, twice as many biopsies were performed on women. Women were not found to have a significantly higher risk of developing GCA over men. Patients with a positive biopsy averaged 76.4±8.9 years of age. The odds of having a positive biopsy increased significantly with age. Positive biopsies were significantly more likely to occur in the months of May through July than the rest of the year (p<0.028). CONCLUSIONS Our retrospective study is the first report of the seasonal incidence of biopsy-proven GCA in California. Our data suggest that increased age and summer months are risk factors for developing biopsy-proven GCA in our region.
PHENOPROFILING CARDIOGENIC SHOCK: A REPORT FROM THE CARDIOGENIC SHOCK WORKING GROUP

Cardiogenic shock (CS) mortality remains unacceptably high. Predicting in-hospital mortality is a critical barrier. Using clinical variables, we applied a machine learning approach to improve the assessment of risk for in-hospital mortality among patients with CS. The Cardiogenic Shock Working
Experimental evolutionary simulations of learning, memory and life history.

Humans possess an unusual combination of traits, including our cognition, life history, demographics and geographical distribution. Many theories propose that these traits have coevolved. Such hypo...
Multi-physics modeling of thermoacoustic pulse generation and propagation during pulsed microwave ablation of tissue

Microwave-induced thermoacoustic (TA) imaging is a potential alternative to conventional real-time imaging methods for monitoring microwave ablation (MWA). In this study, we develop a multi-physics model for the generation and propagation of microwave-induced TA signals during pulsed MWA. Our model couples electromagnetics, heat transfer, and acoustics physics. We compare simulation and experimental results for a pulsed MWA system wherein a coaxial MWA antenna is used to heat water. The simulated and experimentally measured TA signals for this configuration are in good qualitative agreement. This multi-physics modeling tool is valuable for understanding the fundamentals of TA signal generation and propagation from within an evolving ablation zone.
Instafame: Graffiti and Street Art in the Instagram Era

Instafame: Graffiti and Street Art in the Instagram Era by Lachlan MacDowall examines the production, display and promotion of the two art forms on the popular social media platform.
Comparing cost and print time estimates for six commercially-available 3D printers obtained through slicing software for clinically relevant anatomical models

3D printed patient-specific anatomical models have been applied clinically to orthopaedic care for surgical planning and patient education. The estimated cost and print time per model for 3D printers have not yet been compared with clinically representative models across multiple printing technologies. This study investigates six commercially-available 3D printers: Prusa i3 MK3S, Formlabs Form 2, Formlabs Form 3, LulzBot TAZ 6, Stratasys F370, and Stratasys J750 Digital Anatomy. Seven representative orthopaedic standard tessellation models derived from CT scans were imported into the respective slicing software for each 3D printer. For each printer and corresponding print setting, the slicing software provides a print time and material use estimate. Material quantity was used to calculate estimated model cost. Print settings investigated were infill percentage, layer height, and model orientation on the print bed. The slicing software investigated are Cura LulzBot Edition 3.6.20, GrabCAD Print 1.43, PreForm 3.4.6, and PrusaSlicer 2.2.0. The effect of changing infill between 15% and 20% on estimated print time and material use was negligible. Orientation of the model has considerable impact on time and cost with worst-case differences being as much as 39.30% added print time and 34.56% added costs. Averaged across all investigated settings, horizontal model orientation on the print bed minimizes estimated print time for all 3D printers, while vertical model orientation minimizes cost with the exception of Stratasys J750 Digital Anatomy, in which horizontal orientation also minimized cost. Decreasing layer height for all investigated printers increased estimated print time and decreased estimated cost with the exception of Stratasys F370, in which cost increased. The difference in material cost was two orders of magnitude between the least and most-expensive printers. The difference in build rate (cm3/min) was one order of magnitude between the fastest and slowest printers. All investigated 3D printers in this study have the potential for clinical utility. Print time and print cost are dependent on orientation of anatomy and the printers and settings selected. Cost-effective clinical 3D printing of anatomic models should consider an appropriate printer for the complexity of the anatomy and the experience of the printer technicians.
Anesthetic Management of a Child With Propionic Acidemia Complicated by Bacteremia and Severe Acute Respiratory Syndrome Coronavirus 2

Propionic acidemia (PA) is a rare, multi-systemic inborn error of metabolism. PA results from an impaired activity of the mitochondrial enzyme, propionyl-CoA carboxylase (PCC). PCC holds an essential role in the catabolic pathways for odd-chain fatty acids, cholesterol side-chains and branched-chain amino acids. Errors in these pathways result in the accumulation of toxic metabolites that may advance into end-organ damage and dysfunction. Clinical manifestations of PA include relapsing courses of severe metabolic acidosis, concurrent viral or bacterial infection, episodic vomiting, gastroesophageal reflux disease (GERD), seizures, developmental delay, hypotonia, hyperammonemia, osteopenia, pancreatitis and cardiomyopathy. This case describes a 3-year-old boy with PA who presented with an acute metabolic crisis, precipitated by Staphylococcus epidermidis (S. epidermidis) bacteremia and severe acute respiratory syndrome due to coronavirus 2 (SARS-CoV-2) co-infection. He required anesthetic management for surgical removal of an infected central venous port. Anesthetic care for this patient presented the unique challenges of metabolic decompensation amidst infection with SARS-CoV-2. Options for anesthetic care for patients with PA have been elucidated in the literature. However, to our knowledge, this is the first case to describe anesthetic management in a PA patient with SARS-CoV-2.
Cutaneous segmental hemangioma of the face

This is a picture of a one year old female toddler who presented to our clinic at two and half months of age with complain of bright red rash on the face two weeks …
Abstract 176: Detecting neoepitopes from tumor RNA sequencing datasets

Epitopes are peptides that present on the surface of the cell and can be recognized by immune cells to initiate the immune response. Identification of neoepitopes – tumor-specific, MHC-bound epitopes recognized specifically by T-cells – is valuable for predicting response to immunotherapies, including checkpoint blockade therapies. Tumors with more neoepitopes tend to be more responsive to immune checkpoint therapies compared to tumors with fewer neoepitopes. ProTECT is a previously published computational method that uses Illumina whole genome and transcriptome sequencing data from tumor and matched normal tissues to identify neoepitopes. Tumor and normal whole genome sequencing data are used to infer a patient9s HLA haplotypes, as well as annotate variants as either somatic or germline. While whole genome sequencing is comprehensive, it is quite costly and not available for many samples. Here we adapt ProTECT to use only tumor RNA sequencing data and HLA haplotype information available to the clinician to identify neoepitopes in a tumor sample. Prior to running ProTECT, we use the computational tools Opossum and Platypus for variant calling instead of Radia (which is designed for variant calling using both RNA and DNA sequencing data as input). To determine which variants are somatic and therefore could represent tumor neoepitopes, variants found in RNA are compared to a panel of normals, for example the Genome Aggregation Database (gnomAD; containing variants from 125,748 exome sequences and 15,708 whole-genome sequences). With the resulting somatic variants and the HLA type, ProTECT proceeds as usual, with translation of variants into proteins, MHC:Peptide binding predictions and neoepitope ranking. We find that high quality neoepitopes are identifiable using an RNA-only approach, when genomic data is absent. Future work will validate the sensitivity of our method by benchmarking it against the original ProTECT predictions in the TCGA Prostate Adenocarcinoma cohort. Citation Format: Drew Thompson, Olena M. Vaske, Arjun Rao, Holly C. Beale. Detecting neoepitopes from tumor RNA sequencing datasets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 176.
P75 Disaggregating Nutrition Education Evaluation Data to Assess Racial Equity in Program Outcomes

Background A legacy of structural discrimination has contributed to increased rates of poverty, food insecurity, and obesity among African American Americans compared to White Americans. Supplemental Nutrition Assistance Program - Education (SNAP-Ed) is intended to ameliorate food insecurity and obesity and must consider whether it meets the needs of African Americans at increased risk of those conditions. Objective To assess whether educational outcomes from participation in the Louisiana State University SNAP-Ed program were equivalent for African American participants compared to White participants. Study Design, Settings, Participants Change in eating behaviors following SNAP-Ed participation were evaluated with pre/post surveys. Outcomes measured included change in frequency of consuming fruits, vegetables, whole grain and dairy products, and sugar sweetened beverages after SNAP-Ed participation. Data from 2 prior evaluations were combined and stratified by race (n = 434, 66% African American). Paired t tests for change in dietary behaviors were conducted across race categories using Stata 16.1. Results Outcomes did not differ between African American and White participants for most behaviors. However, frequency of fruit juice consumption increased significantly among African Americans (mean increase 0.27 on a Likert scale of 1-5, P = 0.005), but not among White participants (0.12 increase, P = 0.191). Frequency of low-fat milk (0.24, P = 0.053) and whole grain pasta consumption (0.33, P = 0.001) increased among White participants with marginal significance, but not among African American participants (mean increase 0.11, P = 0.247 and 0.16, P = 0.102, respectively). Conclusion SNAP-Ed must consider whether it adequately serves African Americans given the historical structural discrimination they have faced. Though most outcomes from LSU SNAP-Ed participation were not significantly different between African American and White participants, the consumption of fruit juice, low fat milk, and whole grain pasta changed differently in African American participants. This study serves as an example for future equity-focused evaluations. Further research should assess what may contribute to racial differences in behavior change outcomes of SNAP-Ed participation.
Electrically or chemically tunable photodetector with ultra high responsivity using graphene/InN nanowire based mixed dimensional barristors.

In this work, an electrically/chemically tunable highly sensitive photodetector based on mixed dimensional heterojunction of graphene and planar InN nanowires (NW) is presented. Controlled partial oxidation of InN has been employed to effectively reduce the high surface carrier concentration of InN, which normally prevents it from forming good rectifying contact with graphene. The resulting surface modified InN NWs have been found to form excellent Schottky junction with graphene, with an increase in effective Schottky barrier height (SBH) by over 1.1 eV and a ratio of forward and reverse bias currents exceeding 4 orders of magnitude. Moreover, very strong barristor (gate tunable heterojunction) action has been observed, withIon/Ioff ≈ 4 orders of magnitude, and SBH increase by >0.3 eV. The barristor has been demonstrated to be highly sensitive to light, especially in the ultra-voilet, visible and near IR spectra. Responsivity was found to be widely tunable by gate voltage, with the highest value exceeding 1000 A W-1. Rise and fall times being in the range of hundreds of ms are indicative of photoconductive gain, which can be attributed to the ultra high responsivity. A method of semi-permanent molecular doping has been demonstrated to realize a two-terminal version of the photodetector, where the desired responsivity can still be achieved without requiring a back gate terminal, enabling the device to be realized on insulating substrates. The effect of encapsulation has been studied as a function of time, which has showed the long term stability of the dopant-induced enhancement and ultra high responsivity of the barristor photodetector.
Chipscale Piezo-Magnetostrictive Interfaces - A new simplified and microminiaturized telemetry paradigm for Medical Device Packages

Miniaturized 3D package integration with piezo-magnetostrictive telemetry is analyzed towards advanced wireless medical systems. The paper is composed of three aspects. The first is to analyze telemetry using a multiferroic or piezo-magnetostrictive power interface. Parametric analysis was performed to estimate the impact of material, geometry and input magnetic fields. The second aspect is the process integration of devices and telemetry interfaces in 3D embedded packages for smallest form-factors. The telemetric interface and sensor devices are packaged in a flexible substrate with 3D interconnections, leading to miniaturized solutions. The sensor-communication and the power source flex layers are separately fabricated and connected with via-fill layers that are flex-compatible. Flex integration allows the devices to be functional on curved surfaces. In the final part, coupled magnetostrictive and piezoelectric films were considered to power devices in neural recording, neurostimulation and biophotonic systems. Power analysis requirements and piezo-magnetostrictive solutions for these specific scenarios is shown to illustrate the geometric compatibility towards emerging needs.