cssi/SciSciGPT-SciSciNet huggingface dataset:
Declines of the California red-legged frog: Climate, UV-B, habitat, and pesticides hypotheses

The federally threatened California red-legged frog (Rana aurora draytonii) has disappeared from much of its range for unknown reasons. We mapped 237 historic locations for the species and determined their current population status. Using a geographic information system (GIS), we determined latitude, elevation, and land use attributes for all sites and analyzed the spatial pattern of declines. We then compared the observed patterns of decline to those predicted by the climate change, UV-B radiation, pesticides, and habitat alteration hypotheses for amphibian decline. Declines were not consistent with the climate change hypothesis but showed a strong positive association with elevation, percentage upwind agricultural land use, and local urbanization. These results apply to patterns of decline across the entire range of R. a. draytonii in California, as well as within geographic subregions. The elevational gradient in declines is consistent with the UV-B hypothesis, although the UV-B hypothesis also predicts a north-to-south gradient in declines, which we did not observe. The association of declines with the amount of upwind agricultural land use strongly suggests that wind-borne agrochemicals may be an important factor in declines. This association was most pronounced within the Central Valley-Sierra region, where other studies have documented both transport and deposition of pesticides to the Sierra Nevada and the presence of pesticide residues in the bodies of congeneric (Rana muscosa) and more distantly related (Hyla regilla) frog species.
Investigating Public Health Surveillance using Twitter

Microblog services such as Twitter are an attractive source of data for public health surveillance, as they avoid the legal and technical obstacles to accessing the more obvious and targeted sources of health information. Only a tiny fraction of tweets may contain useful public health information but in Twitter this is oset by the sheer volume of tweets posted. We present a system which can identify medical named entities in a real-time stream of Twitter posts and determine their geographic locations, as well as preliminary experiments in using this information for health surveillance purposes.
On mobile positioning via Cellular Synchronization Assisted Refinement (CeSAR) in LTE and GSM networks

Inferring user equipment (UE) location in cellular networks via uplink timing management presents attractive possibilities in an increasingly mobile-connected world. Power constrained mobile devices with ever more common applications that rely on location-based services demand an alternate solution to positioning than a Global Navigation Satellite System (GNSS) and its derivatives. In this paper we provide analysis of mobile positioning via timing advance (TA), an LTE parameter also accounted for in legacy network deployments. Specifically, we provide analysis for a TA-based method Cellular Synchronization Assisted Refinement (CeSAR). We demonstrate through analysis and simulation how CeSAR can increase accuracy in timing advance-based positioning by several hundreds of meters with no impact to radio link level traffic. CeSAR is shown to be robust to situations where unassisted TA-based positioning can provide poor positioning accuracy.
Abstract 5477: Engineered toxin body demonstrating CD20-specific binding and cell kill in B-cell non-Hodgkin's lymphoma cells.

Non-Hodgkin9s lymphoma (NHL) offers an attractive area for therapeutic biologics. The most successful example of this targeted approach is rituximab, which is approved for front and second line therapy of NHL. Rituximab targets the CD20 antigen expressed on 90% of B-cell NHL cells. However, rituximab has limited direct cell-kill effects, acting instead primarily through indirect immune responses induced by antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC). Direct-cell kill approaches to CD20 have been limited to radioimmunotherapy because CD20 does not efficiently internalize. Despite improved clinical efficacy seen over Rituximab with both 131 tositumomab and ibritumomab tiuxetan, challenges around the administration of radioimmunotherapies have severely curtailed therapeutic use. We have developed an engineered toxin body (ETB) comprising a CD20 scFv and a modified Shiga-like Toxin A (3F7) capable of specifically recognizing and killing CD20 expressing cells. Utilizing a flow cytometry based binding affinity assay, 3F7 demonstrated selective binding to CD20 positive Raji cells whereas no significant binding was observed in CD20 negative BC-1 cells. Further, direct competition of 3F7 binding to Raji cells was observed in the presence of rituximab or the parent monoclonal antibody. 3F7 demonstrated CD20-specific direct cell kill of Raji, Daudi and Ramos cells with minimal cell kill of CD20 negative BC-1 or Jurkat cells. Initial dose finding studies in mice found that a therapeutic dosing schedule was well tolerated. Raji xenograft studies in mice are ongoing. 3F7 is a novel therapeutic approach with direct cell-kill activity against CD20-expressing cells which could expand treatment options for B-cell lymphoma. Citation Format: Rachel Wirth, Sangeetha Rajagopalan, Erin Willert, William Null, Jennifer Erdman, Jen-Sing Liu, Jack P. Higgins. Engineered toxin body demonstrating CD20-specific binding and cell kill in B-cell non-Hodgkin9s lymphoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5477. doi:10.1158/1538-7445.AM2013-5477
Systematics and Acoustic Behavior of United States Crickets of the Genus Cyrtoxipha (Orthoptera: Gryllidae)

Six species of Orocharis (Gryllidae: Entopterinae) occur in the United States. O. saltator Uhler and luteolira , n. sp., are widespread in the southeastern States, while gryllodes (Pallas), tricornis , n. sp., diplastes , n. sp., and nigrifrons , n. sp., are limited to coastal peninsular Florida. The distinctive calling songs of all species are described from analyses of field and laboratory tape recordings. The high wing-stroke rate of gryllodes (150–280/sec) suggests asynchronous, fibrillar muscles. O. saltator and luteolira cannot be distinguished morphologically. They have different seasonal life histories and distinctive calling songs but overlap in geographic distribution and habitat.
Vernal Pool Inventory and Classification at Pictured Rocks National Lakeshore, Michigan, USA

ABSTRACT: Vernal pools occur in the glaciated forests of northeastern North America and provide critical breeding and foraging habitat for amphibian and mammal species. Protection for these ephemeral wetlands is not federally mandated, placing them at risk for habitat fragmentation and making them more vulnerable to impacts of climate change. Unlike the northeastern United States, limited information about vernal pools exists for the Great Lakes region, and there is a lack of information about techniques to identify and classify vernal pools using remote sensing and field surveys. At Pictured Rocks National Lakeshore, Michigan, USA, our objectives were to locate vernal pools using true-color, spring leaf-off aerial photography at the 1:12,000 scale, classify vernal pools using modified geomorphological classification systems, and determine landscape associations with soil series and cover type GIS datasets. From the 214 water features identified and categorized via aerial photography, two (water with cano...
Genetic Variation in the IL-6 and HLA-DQB1 Genes Is Associated with Spontaneous Clearance of Hepatitis C Virus Infection

Background. Millions of people are infected with hepatitis C virus (HCV) worldwide and 30% spontaneously clear the infection. Reasons for HCV clearance without antiviral treatment are not well understood. Methods. Blood was collected for DNA analysis from patients with chronic HCV infection or evidence of spontaneous clearance. To overcome anticipated limitations of small sample size, primary analyses consisted of a candidate gene analysis of 12 preselected genes based on known association with host immunologic response to HCV infection. To further reduce the impact of multiple testing on power, a single likelihood ratio test was conducted for each gene using all associated SNPs assayed on the Illumina Quad 610/660W chip. Step-down permutation methods were used to adjust for multiple testing in all analyses. Results. Ninety-five and 62 patients with HCV chronic infection or spontaneous clearance, respectively, were included for analysis. HLA-DQB1 (p = 1.76⁎10(-5)) and IL-6 (p = 0.0007) genes were significantly associated with spontaneous HCV clearance. IL-28B was not significantly associated with spontaneous clearance (p = 0.17). Conclusion. Our whole-gene analytic strategy identified a previously unreported association of IL-6 with spontaneous clearance of HCV infection. We also confirmed the finding that HLA-DQB1 is associated with spontaneous resolution of HCV infection.
Testing the evidence effect of Additive Cues Model (ACM)

Abstract Since Aristotle, evidence provides a means of support to justify the acceptance of a conclusion. Textbooks used to teach persuasion in courses like public speaking often note the independent importance of speaker credibility, message evidence, and reasoning without necessarily considering the additive persuasive impact of the elements. Advice on how to persuade others requires consistent updating with empirical testing. The current study tests the Additive Cues Model (ACM; Kim et al., 2012 , Kim et al., 2014a ) to examine whether increasing the amount of evidence contributes to message persuasiveness in the context of global warming. Contrary to prediction offered by the ACM, the current data show that anti-global warming beliefs do not necessarily increase as anti-global warming evidence increases. Instead, the results present preliminary evidence that the ACM may be used to predict a persuasive boomerang for individuals with high issue involvement on the topic.
Total synthesis of a key series of vinblastines modified at C4 that define the importance and surprising trends in activity

The total synthesis and evaluation of a key systematic series of vinblastines that incorporate the first deep-seated changes to the substituent at C4 are detailed. The synthetic approach features an expanded and redefined scope of a 1,3,4-oxadiazole [4 + 2]/[3 + 2] cycloaddition cascade in which electronically mismatched electron-deficient trisubstituted alkenes and unactivated trisubstituted alkenes were found to productively initiate the cycloaddition cascade with tethered electron-deficient 1,3,4-oxadiazoles. Such cycloaddition cascades were used to directly introduce altered C4 substituents, providing the basis for concise total syntheses of a series of C4 modified vindolines and their subsequent single-step incorporation into the corresponding synthetic vinblastines in routes as short as 8–12 steps. Evaluation of the synthetic vinblastines revealed a surprisingly large impact and role of the C4 substituent on activity even though it was previously not thought to intimately interact with the biological target tubulin. Only the introduction of a C4 methyl ester, a constitutional isomer of vinblastine in which the carbonyl carbon and ester oxygen of the C4 acetate are transposed, provided a synthetic vinblastine that matched the potency of the natural product. In contrast, even introduction of a C4 acetamide or N-methyl carboxamide, which incorporate single heavy atom exchanges (amide NH for ester oxygen) in vinblastine or the C4 methyl ester, provided compounds that were ≥10-fold less active than vinblastine. Other C4 acetate replacements, including a C4 amine, carboxylic acid, hydroxymethyl or acetoxymethyl group, led to even greater reductions in potency. Even replacement of the C4 acetoxy group or its equally active C4 methyl ester with an ethyl or isopropyl ester led to 10-fold or more reductions in activity. These remarkable trends in activity, which correlate with relative tubulin binding affinities, retrospectively may be ascribed to the role the substituent serves as a H-bond acceptor for α-tubulin Lys336 and Asn329 side chains at a site less tolerant of a H-bond donor, placing the methyl group of the C4 acetate or C4 methyl ester in a spatially restricted and well-defined hydrophobic half pocket created by a surrounding well-ordered loop. This remarkable impact of the C4 substituent, its stringency, and even the magnitude of its effect are extraordinary, and indicate that its presence was selected in Nature to enhance the effects of vinblastine and related natural products.
Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation

Purpose There is growing evidence that inflammation is a central and reversible mechanism through which obesity promotes cancer risk and progression. Methods We review recent findings regarding obesity-associated alterations in the microenvironment and the local and systemic mechanisms through which these changes support tumor growth. Results Locally, hyperadiposity is associated with altered adipose tissue function, adipocyte death, and chronic low-grade inflammation. Most individuals who are obese harbor inflamed adipose tissue, which resembles chronically injured tissue, with immune cell infiltration and remodeling. Within this distinctly altered local environment, several pathophysiologic changes are found that may promote breast and other cancers. Consistently, adipose tissue inflammation is associated with a worse prognosis in patients with breast and tongue cancers. Systemically, the metabolic syndrome, including dyslipidemia and insulin resistance, occurs in the setting of adipose inflammation and operates in concert with local mechanisms to sustain the inflamed microenvironment and promote tumor growth. Importantly, adipose inflammation and its protumor consequences can be found in some individuals who are not considered to be obese or overweight by body mass index. Conclusion The tumor-promoting effects of obesity occur at the local level via adipose inflammation and associated alterations in the microenvironment, as well as systemically via circulating metabolic and inflammatory mediators associated with adipose inflammation. Accurately characterizing the obese state and identifying patients at increased risk for cancer development and progression will likely require more precise assessments than body mass index alone. Biomarkers of adipose tissue inflammation would help to identify high-risk populations. Moreover, adipose inflammation is a reversible process and represents a novel therapeutic target that warrants further study to break the obesity-cancer link.
Resonant Magnetotunneling in Type II Heterostructures

We review the experimental effects of a magnetic field on the current-voltage characteristics of type II resonant-tunneling structures, mainly GaSb-AlSb-InAs-AlSb-GaSb. Their behavior under field, found to be very different from that of type I structures, is a consequence of the peculiar conduction-valence band alignment of the InAs-GaSb system.
Export Awareness, Attitude, and Behavior of American Award-Winning Exporters

A select group of American companies and organizations are awarded each year the coveted “E Star” award for excellence in exporting by the US Department of Commerce. A question, however, is whether...
The use of Twitter to facilitate engagement and reflection in a constructionist learning environment

Abstract Objectives Determine students' self-reported use of Twitter in a health systems course and gauge their perceptions of its value and utility for self-guided supplementation of course material, and evaluate the quality of students' reflections from information they found on Twitter. Methods Students in a health systems course create a Twitter account to remain abreast of current developments in pharmacy and health systems. They were afforded the autonomy to follow organizations/individuals they chose and write reflective mini-papers on selected tweets from their Twitter feed prior to each course session. A self-administered survey solicited students' favor toward various aspects of the Twitter reflection assignment. An examination of students' reflections as the course progressed was also undertaken. Results Approximately 2/3 of the students enrolled in the course responded to the survey. Student perceptions of the Twitter assignment were quite favorable, with highest favor related to facets regarding the construction of their own learning and continuation of engagement throughout the course. Responses to open-ended questions corroborated students’ perceptions of their own learning, as did the content and quality of their reflections during progression of the course. Conclusions The course design reinforced previous claims outside of pharmacy that Twitter can be a useful tool to reinforce or create new learning paradigms, but especially under the auspices of established theory, such as a constructivist environment employing constructionism pedagogy. A course like health systems in programs of academic pharmacy might especially benefit from use of Twitter and such course design.
Preclinical Efficacy Testing of Baxter's Recombinant ADAMTS13 in a Mouse Model of TTP.

Abstract 2216 Baxter is currently developing a recombinant ADAMTS13 (rADAMTS13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) product for potential prophylaxis and treatment of thrombotic thrombocytopenic purpura (TTP). We established a disease model in ADAMTS13 ko mice (B6.129-ADAMTS13 tm1Dgi ), in which the animals simultaneously and consistently develop TTP-like symptoms by challenge with a high dose of human recombinant von Willebrand factor (rVWF) containing ultra-large VWF multimers. To test the prophylactic efficacy of Baxter9s rADAMTS13, groups of 10 ADAMTS13 ko mice received single doses of rADAMTS13 (1, 5, 40, 80 or 200U/kg) before challenge with rVWF. Doses of 1 and 5mL/kg fresh frozen plasma corresponding to 1 and 5U/kg ADAMTS13 served as positive controls. In a second study, the prophylactic and therapeutic efficacy of Baxter9s rADAMTS13 was tested over time. Groups of 10 ADAMTS13 ko mice received a single dose of 200 FRETS-U/kg rADAMTS13 5min-120h before, or 15–180min after challenge with rVWF. In both studies, buffer was used as a negative control. Efficacy was defined as the degree of prevention of platelet drop and LDH increase. Schistocytosis and organ damage were also assessed. Morbidity in negative controls was 100%: all animals receiving rVWF containing ultra-large VWF multimers were severely thrombocytopenic, showed increased LDH levels, schistocytosis and organ damage. Prophylactic treatment with rADAMTS13 prevented LDH increase (p Efficacy of rADAMTS13 was treatment interval-dependent in both studies. Platelet count at termination of all rADAMTS13-treated animals was statistically higher than that of buffer-treated controls (p≤0.0001). However, animals receiving prophylactic treatment 120h before administration of rVWF showed severe thrombocytopenia; clinically relevant protection was only seen with treatment intervals ≤72h. Therapeutic treatment with rADAMTS13 stabilized platelet count and prevented further thrombocytopenia. LDH, schistocytosis and organ damage confirmed the treatment interval-dependent improvement in platelet count. In summary, Baxter9s rADAMTS13 was effective in an rVWF-induced animal model closely mimicking the situation in patients with hereditary TTP. Comparison with FFP, the current standard of treatment of TTP, showed Baxter9s rADAMTS13 to have similar or slightly improved efficacy. Disclosures: Schiviz: Baxter Innovations GmbH: Employment. Resch: Baxter Innovations GmbH: Employment. Farnleitner: Baxter Innovations GmbH: Employment. Rottensteiner: Baxter Innovations GmbH: Employment. Schwarz: Baxter Innovations GmbH: Employment. Hoellriegl: Baxter Innovations GmbH: Employment. Muchitsch: Baxter Innovations GmbH: Employment.
Effects of dose reduction on gemcitabine-based neoadjuvant chemoradiotherapy for localized pancreatic cancer.

e15262 Background: Patients receiving gemcitabine-based neoadjuvant chemoradiotherapy for non-metastatic pancreatic cancer often have difficulty tolerating full treatment courses. Providers are thu...
Accuracy of Substrate Selection by Enzymes Is Controlled by Kinetic Discrimination

Enzymes have the remarkable ability to select the correct substrate from the pool of chemically similar molecules. The accuracy of such a selection is determined by differences in the free-energy profiles for the right and wrong reaction pathways. Here, we investigate which features of the free-energy landscape govern the variation and minimization of selectivity error. It is generally believed that minimal error is affected by both kinetic (activation barrier heights) and thermodynamic (binding stability) factors. In contrast, using first-passage theoretical analysis, we show that the steady-state selectivity error is determined only by the differences in transition-state energies between the pathways and is independent of the energies of the stable complexes. The results are illustrated for two common catalytic mechanisms: (i) the Michaelis–Menten scheme and (ii) an error-correcting kinetic proofreading scheme with tRNA selection and DNA replication as guiding biological examples. Our theoretical analys...
Synaptic up-scaling preserves motor circuit output after chronic, natural inactivity

Neurons in the brain communicate using chemical signals that they send and receive across junctions called synapses. To maintain normal behavior over time, circuits of neurons must reliably process these signals. A variety of nervous system disorders may result if they are unable to do so, as may occur when neural activity changes as a result of disease or injury. The processes underlying the stability of a neuron’s synapses is referred to as “homeostatic” synaptic plasticity because the changes made by the neuron directly oppose the altered level of activity. In one form of homeostatic plasticity, known as synaptic scaling, neurons modify the strength of all of their synapses in response to changes in neural activity. There is substantial experimental evidence to show that in young animals, neurons that communicate using a chemical called glutamate undergo synaptic scaling in response to artificial changes in activity. It had not been directly shown that synaptic scaling protects the neural activity of adult animals in their natural environments, in part, because neural activity in most healthy animals generally only goes through small changes. However, the neurons in the brain that cause the breathing muscles of bullfrogs to contract are ideal for studying homeostatic plasticity because they are naturally inactive for several months when frogs hibernate in ponds during the winter. During this time, the bullfrogs do not need to use their lungs to breathe because enough oxygen passes through their skin to keep them alive. Santin et al. have now observed synaptic scaling of glutamate synapses in individual bullfrog neurons that had been inactive for two months. Further experiments that examined the activity of the breathing control circuit in the brainstem provided evidence that synaptic scaling leads to sufficient amounts of neural activity that would activate the breathing muscles when frogs emerge from hibernation. Therefore neural activity after prolonged, natural inactivity relies on synaptic scaling to preserve life-sustaining behavior in frogs. These results open up new questions: mainly, how do synaptic scaling and other forms of homeostatic plasticity operate in animals as they experience normal variations in neural activity? Determining how homeostatic plasticity works normally in an animal will help us to understand what happens when plasticity mechanisms go wrong, as is thought to occur in several human nervous system diseases including nervous system injury, Alzheimer’s disease, and epilepsy.
Polyhydramnios Affecting a Recipient-like Twin: Risk of Progression to Twin-Twin Transfusion Syndrome and Outcomes.

Objective The significance of polyhydramnios of one twin in the absence of oligohydramnios of the cotwin in monochorionic diamniotic (MCDA) twin pregnancies (polyhydramnios affecting a recipient-like twin [PART]) is unknown. Our aim is to assess the risk of progression to twin–twin transfusion syndrome (TTTS) with PART, progression to ≥ stage II TTTS, and neonatal survival. Study Design This study was a retrospective cohort study of MCDA twin pregnancies with PART evaluated at a referral center from 2008 to 2015. Results Sixty-four MCDA twin pregnancies with PART were identified. Fifteen (23.4%) progressed to TTTS, including 10 (15.6%) who progressed to ≥ stage II TTTS. Three pregnancies were terminated and one underwent selective reduction by radiofrequency ablation. Overall survival was 113 out of 128 (88.3%). Of those who remained stable, 91.8% (N = 45) had survival of both neonates. In multivariate analysis, the presence of arterioarterial (A-A) anastomosis by in utero Doppler ultrasound was associated with decreased risk of progression to TTTS (odds ratio: 0.12, p = 0.03, 95% confidence interval: 0.02–0.78). Conclusion Most MCDA twin pregnancies with PART do not progress to TTTS and have a favorable prognosis. Progression rates are higher than observed in uncomplicated MCDA twins; however, so close surveillance is warranted. The presence of an A-A anastomosis appears to confer decreased risk of progression to TTTS.
Morphology and deformational history of Tellus Regio, Venus: Evidence for assembly and collision

Abstract Tessera terrain is the oldest stratigraphic unit on Venus, but its origin and evolution are inadequately understood. Here we have performed detailed mapping of Tellus Regio, the third largest tessera plateau on Venus. Tellus Regio is shown to have distinct marginal and interior facies. The east and west margins of Tellus rise up to 2 km above the interior and include ridges and troughs ∼5–20 km across, oriented parallel to the present plains-tessera boundary. Structures characteristic of the interior of Tellus are found within the eastern and western margins and are deformed by the margin-parallel ridges indicating their presence during the time of the formation of the current margins. These relationships suggest that the margins formed by the application of external horizontal compressional stresses at the edges of an already-existing tessera interior. Structural and stratigraphic relationships in southwest Tellus show the assembly of three structurally distinct tessera regions and intervening plains that are consistent with the collision of the southwest margin into the plateau interior. This requires that tessera terrain was formed regionally and collected into the present day Tellus plateau. The latest stages of activity in Tellus include volcanism and pervasive, distributed, 1–2 km wide graben, which may have been formed due to large-scale gravitational relaxation of the plateau topography. A large intratessera plains unit may have formed via crustal delamination. The collisional oroclinal deformation of the margins are most consistent with models that invoke mantle downwelling for the origin of Tellus Regio and other tessera plateaus with similar structural relationships.
Preoperative Chemotherapy and Surgical Resection for Squamous Cell Carcinoma of the Esophagus

In an attempt to increase the long-term survival rate of patients with squamous cell carcinoma of the esophagus, we developed a treatment protocol consisting of a combination of preoperative chemotherapy, surgical resection, and in selected patients postoperative radiation and/or chemotherapy [1]. Our intent is to use a reasonably simple and brief preoperative regimen with low toxicity, followed by a standard transthoracic esophageal resection. Then based on the patient’s response to chemotherapy, the pathologic findings in the resected esophageal specimen, and the patient’s postoperative nutritional status, selectively to administer postoperative therapy. We elected to use the chemotherapy regimen proposed by Leichman et al. [2], consisting of 5-fluorouracil and Cisplatin, and carried out radiologic, endoscopic, and surgical evaluation of the effects of the chemotherapy. We omitted the preoperative radiotherapy proposed by Leichman et al. [2] in order to simplify the regimen and perhaps to decrease the high hospital mortality rate cited in their report.
Do Newts Avoid Conspecific Alarm Substances: The Predation Hypothesis Revisited

Predator detection and avoidance are important for prey survival. Upon noticing a predator, most prey will decrease activity, move into refugia, or flee (Lima, 1998). Many prey rely on visual cues to reveal threats, but dense vegetation and turbidity often make vision unreliable in aquatic environments (Kats and Dill, 1998). Therefore, aquatic prey may benefit more from using chemical cues than visual cues to detect predators (Dodson et al., 1994). Numerous studies have demonstrated that aquatic animals use their chemical senses to identify predators and release antipredatory behaviors (Kats and Dill, 1998). In fact, Stauffer and Semlitsch (1993) demonstrated that predators’ chemical cues amplified antipredatory behaviors in Rana lessonae and Rana esculenta tadpoles, but visual cues did not.
Antibiotic Lethality and Membrane Bioenergetics.

Abstract A growing body of research suggests bacterial metabolism and membrane bioenergetics affect the lethality of a broad spectrum of antibiotics. Electrochemical gradients spanning energy-transducing membranes are the foundation of the chemiosmotic hypothesis and are essential for life; accordingly, their dysfunction appears to be a critical factor in bacterial death. Proton flux across energy-transducing membranes is central for cellular homeostasis as vectorial proton translocation generates a proton motive force used for ATP synthesis, pH homeostasis, and maintenance of solute gradients. Our recent investigations indicate that maintenance of pH homeostasis is a critical factor in antibiotic killing and suggest an imbalance in proton flux initiates disruptions in chemiosmotic gradients that lead to cell death. The complex and interconnected relationships between electron transport systems, central carbon metabolism, oxidative stress generation, pH homeostasis, and electrochemical gradients provide challenging obstacles to deciphering the roles for each of these processes in antibiotic lethality. In this chapter, we will present evidence for the pH homeostasis hypothesis of antibiotic lethality that bactericidal activity flows from disruption of cellular energetics and loss of chemiosmotic homeostasis. A holistic understanding of the interconnection of energetic processes and antibiotic activity may direct future research toward the development of more effective therapeutic interventions.
A Simple Correction for Nonadditive Dispersion within Extended Symmetry-Adapted Perturbation Theory (XSAPT).

Extended symmetry-adapted perturbation theory (XSAPT), in conjunction with empirical “+aiD” potentials fit to ab initio dispersion data, is a low-scaling approach to compute intermolecular interaction energies in noncovalent clusters. One shortcoming is that the aiD atom–atom dispersion potentials are independent of the chemical environment of the atoms in question and therefore neglect nonadditive dispersion effects. These can be significant in large systems, so to account for them we test a simple correction to XSAPT(KS)+aiD, where “KS” indicates the use of Kohn–Sham orbitals. This correction, which can be evaluated at fourth-order cost using double-ζ basis sets, is based on comparing second-order SAPT dispersion with and without a self-consistent charge embedding for the monomer wave functions. The correction amounts to ∼1.4 kcal/mol in (H2O)6 but ∼5.5 kcal/mol in (H2O)20. With the nonadditive dispersion correction, XSAPT(KS)+aiD affords errors of ∼1 kcal/mol for isomers of F–(H2O)10 and (H2O)20, where...
Marijuana use motives mediate the association between experiences of childhood abuse and marijuana use outcomes among emerging adults

Abstract Introduction Experiences of childhood sexual abuse (CSA) and childhood physical abuse (CPA) are associated with poor mental health outcomes including substance use in subsequent years. Marijuana use motives (i.e., coping with negative affect, enhancing positive affect, or improving social interactions) may influence problematic substance use among young adults. Specifically, motives may be associated with severity of marijuana use outcomes among individuals who have experienced CSA or CPA. This study investigated the indirect effect of marijuana use motives between experiences of CSA or CPA and marijuana use and problems among emerging adults. Method Participants were 397 young adults (50.1% male, 66.2% White) between ages 18–25 years, who reported 15.85 (SD = 11.66) days of marijuana use in the past month. Participants reported on history of childhood abuse, marijuana use days, problems, and motives for use. Results Findings suggest a significant indirect effect of coping motives in the association between CPA and marijuana use days and marijuana problems. Further, both coping motives and marijuana use days indicated a significant indirect effect between CPA and problems. Motives of socializing or enhancement did not have a significant indirect effect between CPA and marijuana use or problems. There were no significant findings with CSA and marijuana use outcomes. Discussion Coping motives might be an important potential target for future marijuana interventions in persons with childhood physical abuse.
Outcomes in Combined Heart-Liver Transplantation: A Single-Center Experience

Purpose Combined heart and liver transplantation is an uncommon operation. Given the rarity of this procedure, outcomes data have been limited to case reports and several single-institution series. To better define this patient population and augment the existing data, we report our combined heart and liver transplant experience. Methods An institutional database was queried to identify all patients undergoing combined heart-liver transplantation between 1998 and 2018. A retrospective review of baseline patient characteristics and outcomes was performed. Results Sixteen patients (age 51.4 ± 16, male 69%) underwent combined heart-liver transplantation between 1998 and 2018. The majority (81.3%) of patients were afflicted with non-ischemic cardiomyopathies (idiopathic: 25.0%, congenital: 18.8%, infectious: 12.5%, restrictive: 12.5%, autoimmune: 6.5%), while only 18.8% of patients presented with ischemic cardiomyopathy. Median ejection fraction was 20% [18.3-37.3], and mechanical assist devices or intra-aortic balloon pumps were employed in 25.0% and 18.8%, respectively. Concurrent with cardiac pathology, patients presented with cardiac cirrhosis (43.8%), hepatitis C cirrhosis (25%), primary biliary cirrhosis (6.3%), NASH (6.3%), autoimmune (6.3%) and amyloid (6.3%) liver disease. The median MELD score was 17.5 [12.0-21.3], and 62.5% of patients exhibited ascites. Patients underwent simultaneous transplantation, with median cardiac and hepatic graft ischemia times of 189.0 min and 486.5 min, respectively. Mild cardiac rejection (ACR 1R, AMR 1, DSA:DQ8) occurred in 18.8%, while hepatic rejection occurred in 12.5% of patients. Median intensive care unit and total hospital length of stay were 7.0 [5.0-9.0] and 65.5 [40.8-97.8] days, respectively. In hospital mortality occurred in one patient, with 30-day and 1-year survival rates of 93.8% and 92.8%, respectively. Conclusion This single institution experience with combined heart-liver transplantation augments the available data for this rare procedure, and demonstrates that it can be performed with excellent outcomes.
Negligence and AI's Human Users

Negligence law is often asked to adapt to new technologies. So it is with artificial intelligence (AI). But AI is different. Drawing on examples in medicine, financial advice, data security, and driving in semi-autonomous vehicles, this Article argues that AI poses serious challenges for negligence law. By inserting a layer of inscrutable, unintuitive, and statistically-derived code in between a human decisionmaker and the consequences of that decision, AI disrupts our typical understanding of responsibility for choices gone wrong. The Article argues that AI’s unique nature introduces four complications into negligence: 1) unforeseeability of specific errors that AI will make; 2) capacity limitations when humans interact with AI; 3) introducing AI-specific software vulnerabilities into decisions not previously mediated by software; and 4) distributional concerns based on AI’s statistical nature and potential for bias. Tort scholars have mostly overlooked these challenges. This is understandable because they have been focused on autonomous robots, especially autonomous vehicles, which can easily kill, maim, or injure people. But this focus has neglected to consider the full range of what AI is. Outside of robots, AI technologies are not autonomous. Rather, they are primarily decision-assistance tools that aim to improve on the inefficiency, arbitrariness, and bias of human decisions. By focusing on a technology that eliminates users, tort scholars have concerned themselves with product liability and innovation, and as a result, have missed the implications for negligence law, the governing regime when harm comes from users of AI. The Article also situates these observations in broader themes of negligence law: the relationship between bounded rationality and foreseeability, the need to update reasonableness conceptions based on new technology, and the difficulties of merging statistical facts with individual determinations, such as fault. This analysis suggests that though there might be a way to create systems of regulatory support to allow negligence law to operate as intended, an approach to oversight that it not based in individual fault is likely to be a more fruitful approach.
Modeling series compensation effect on the bus impedance matrix for online applications

Abstract This paper derives new expressions for updating Bus Impedance Matrix (Zbus) elements to account for the modification of the series impedance of a line connected between two existing buses. Such kind of modification is not accounted for in Brown's method and requires building Zbus all over again which is time-consuming, and redundant. Afterwards, we show that a modified form of Sherman–Morisson identity is the generalization of our work. We test our modeling approach with seven systems of different sizes. Results show very minor errors between the predictions of our techniques and Brown's method. Further, speed comparison shows that our method substantially improves calculation speed from a few minutes with Brown and Bus Admittance Matrix (Ybus) inversion methods to seconds (1.35s and 2.9s for 2383 and 3120 bus systems, respectively) making it more suitable for online applications.
Mobilizing historical knowledge through transcultural play: a multi-sited ethnographic case study of an immigrant child

ABSTRACTThis multi-sited ethnographic case study documents a second-generation Korean immigrant child who engages in regular border-crossing experiences between the U.S. and South Korea, his father...
Exposing Worry's Deceit: Percentage of Untrue Worries in Generalized Anxiety Disorder Treatment

Theories of cognitive therapy have long proposed that those with generalized anxiety disorder (GAD) have inaccurate expectations. By challenging them with objective evidence, symptoms are thought to decrease. To test these premises, this study used ecological momentary assessment (EMA) during the Worry Outcome Journal (WOJ) treatment to determine the percentage of GAD worries that did not come true. We then analyzed the association between participants' untrue worry percentages and GAD symptom change across treatment. Twenty-nine participants with GAD recorded worries when prompted for 10 days, reviewed them online nightly, and tracked their worry outcomes across 30 days. These recordings were then coded by independent raters. Analyses applied bias-correct bootstrapping path analysis on slopes extracted from longitudinal linear mixed models. Primary results revealed that 91.4% of worry predictions did not come true. Higher percentages of untrue worries significantly predicted lower GAD symptoms after treatment, as well as a greater slope of symptom reduction from pre- to post-trial. Participants' average expected likelihoods of worries coming true were much greater than actual observed likelihoods. The most common percentage of untrue worries per person was 100%. Thus, worries in those with GAD were mostly inaccurate. Greater evidence of this inaccuracy predicted greater improvement in treatment. As theorized, disconfirming false expectations may significantly contribute to treatment's effect.
A 640 pW 22 pJ/sample Gate Leakage-Based Digital CMOS Temperature Sensor with 0.25°C Resolution

This work presents a 640 pW, 22 pJ/conversion gate leakage-powered temperature sensor with 0.25°C resolution and -2.7/1.8°C worst-case inaccuracy from - 20 °C to 100°C. Gate leakage currents drive both the sensing and sampling elements to provide compact but reliable operation that balances low power and low energy for flexible application use. This low-power, low-energy performance enables continuous sub-nW temperature sensing for the Internet of Things.
Screening of microbial volatile organic compounds for detection of disease in cattle: development of lab-scale method.

The primary hurdle for diagnosis of some diseases is the long incubation required to culture and confirm the presence of bacteria. The concept of using microbial VOCs as “signature markers” could provide a faster and noninvasive diagnosis. Finding biomarkers is challenging due to the specificity required in complex matrices. The objectives of this study were to (1) build/test a lab-scale platform for screening of microbial VOCs and (2) apply it to Mycobacterium avium paratuberculosis; the vaccine strain of M. bovis Bacillus Calmette-Guerin; and M. kansasii to demonstrate detection times greater those typically required for culture. SPME-GC-MS was used for sampling, sample preparation, and analyses. For objective (1), a testing platform was built for headspace sampling of bacterial cultures grown in standard culture flasks via a biosecure closed-loop circulating airflow system. For (2), results show that the suites of VOCs produced by Mycobacteria ssp. change over time and that individual strains produce different VOCs. The developed method was successful in discriminating between strains using a pooled multi-group analysis, and in timepoint-specific multi- and pair-wise comparisons. The developed testing platform can be useful for minimally invasive and biosecure collection of biomarkers associated with human, wildlife and livestock diseases for development of diagnostic point-of-care and field surveillance.
Jamf is A Verb, Have you been Jamfed?

A cross-functional team at Lehigh University Library and Technology Services (LTS) implemented a management system for Apple devices. This presentation will cover the steps to collaboratively implement an Apple device management system, the security features it provides, training, machine enrollment, creating documentation, communicating to the campus, and future management features. We will focus on the development and design of the Jamf Pro Cloud service for Lehigh University's use case, while emphasizing the security goals of this project which include, strong password requirements, enforcing encryptions, and inventory device management.This presentation will focus on why it vital to implement Jamf. It will also focus on the best solution for the design in Jamf Pro Cloud for our university and its benefits for further implementation and enhancement. There will be a demonstration from start to finish the interface of enrolling machines, and design processes. Improving the security to apple users is vital and was unaddressed. It was important to also document and communicate Jamf to make the transition for faculty and staff. There are continuous enhancements of Jamf at Lehigh for the following year becoming a more valuable component of the Lehigh University device management process.
Streamlining Radiologist Workflow for Multidisciplinary Conferences: A Web-Based System to Represent Radiology.

Radiologists are an integral component in patient care and provide valuable information at multidisciplinary tumor boards. However, the radiologists’ role at such meetings can be compromised by technical and workflow limitations, typically including the need for complex software such as picture archiving and communication system (PACS) applications which are difficult to install and manage in disparate locations with increasing security and network limitations. Our purpose was to develop a web-based system for easy retrieval of images and notes for presentation during multidisciplinary conferences and tumor boards. Our system allows images to be viewed from any computer with a web browser and does not require a stand-alone PACS software installation. The tool is launched by the radiologist marking the exam in PACS. It stores relevant text-based information in a MySQL server and is indexed to the conference for which it is to be used. The exams are then viewed through a web browser, via the hospital intranet or virtual private network (VPN). A web-based viewing platform, provided by our PACS vendor, is used for image display. In the 28 months following implementation, our web-based conference system was well-received by our radiologists and is now fully integrated into daily practice. Our method streamlines radiologist workflow in preparing and presenting medical imaging at multidisciplinary conferences and overcomes many previous technical obstacles. In addition to its primary role for interdepartmental conferences, our system also functions as a teaching file, fostering radiologist education within our department.
Neuroimaging of Brain Metastases

Magnetic resonance imaging (MRI) with gadolinium contrast is the most useful imaging modality to visualize brain metastases. Metastases typically occur at the gray/white matter junction and can occur in any region of the brain. They may exert mass effect on surrounding structures that can produce clinical signs and symptoms, including hydrocephalus. While T1 and T2-weighted images are most commonly used in evaluating brain metastases, spoiled gradient recall echo and susceptibility-weighted imaging are also useful tools to evaluate brain metastases that are not contrast-enhancing, and perfusion imaging is useful for differentiating radiation necrosis. Metastatic disease to the meninges includes leptomeningeal and pachymeningeal disease, which is typically a poor prognostic sign. The 3D characteristics of post-contrast MRI and the various special sequences of MRI should all be used in the diagnosis and delineation of brain metastases.
An Empty Frame: Thinking about Art Crime 'Thoughts on the Leonardo Trial'

That makes a recent jury verdict in Edinburgh in which five defendants were cleared of wrongdoing all the more troubling. In 2003 two men appearing to be tourists removed the 16th century work, Madonna of the Yarnwinder from the Duke of Buccleuch’s estate in August. The men pulled the work off the wall, setting off alarms, before escaping through a window and leaving the estate. The theft was one of the most audacious in recent memory.
Geriatrics workforce enhancement program: educational outcomes of community-based dementia caregiver conferences

Providing educational interventions to informal dementia caregivers has been shown to have numerous positive outcomes including improving general well-being and quality of life as well as reducing ...