Transactional Economics: Victor Goldberg\u27s \u3ci\u3eFraming Contract Law\u3c/i\u3e

Professor Mark Gergen: Thank you. It is an honor to speak to this group and to be on a panel with Stewart Macaulay, Keith Rowley, and Victor Goldberg. I have an enormous amount of respect for the three. Keith had the misfortune of being a student of mine in Federal Income Tax. Framing Contract Law offers a wealth of information about familiar cases. Victor argues that in construing contracts, courts should be attentive to how people engineer contracts to minimize transaction costs. He shows that courts often err in this regard, imposing unnecessary costs. To make his case, Victor delves deeply into the background of cases, many that will be familiar to anyone who has taught contracts, and turns up much that is new and interesting. I am going to follow Victor\u27s lead by focusing on two cases that he discusses. I will briefly summarize what he says about the cases. I will then use the cases as a springboard to make my points, which are different from Victor\u27s points

Improving Student Learning Through Use of an In-class Material Processing Design Project

At Marquette University, hybrid project-based learning has been implemented in an undergraduate mechanical engineering course on materials processing and forming using a team-based approach. The goals of the project are to 1) introduce more active and student-centered activities to improve student engagement and mastery of core concepts, 2) increase students\u27 confidence in their ability to apply what they learned in the course to solving real-world problems, 3) enable students to gain experience using engineering software as part of the learning process and in applications context. While use of process modeling software in materials processing and manufacturing courses is not entirely new, the project has students actively developing a model around a realistic process, rather than passive users running canned models and reviewing the output. This paper presents details of the project and discusses preliminary results regarding its impact on student learning and confidence related to application of the course concepts. Recommendations for improving and expanding this in-class project are presented, along with a description of the assessment methods used to measure the impact on students

Methodological considerations for epidemiological studies of air pollution and the sars and COVID-19 coronavirus outbreaks

BACKGROUND: Studies have reported that ambient air pollution is associated with an increased risk of developing or dying from coronavirus-2 (COVID-19). Methodological approaches to investigate the health impacts of air pollution on epidemics should differ from those used for chronic dis-eases, but the methods used in these studies have not been appraised critically. OBJECTIVES: Our study aimed to identify and critique the methodological approaches of studies of air pollution on infections and mortality due to COVID-19 and to identify and critique the methodological approaches of similar studies concerning severe acute respiratory syndrome (SARS). METHODS: Published and unpublished papers of associations between air pollution and developing or dying from COVID-19 or SARS that were reported as of 10 May 2020 were identified through electronic databases, internet searches, and other sources. RESULTS: All six COVID-19 studies and two of three SARS studies reported positive associations. Two were time series studies that estimated associations between daily changes in air pollution, one was a cohort that assessed associations between air pollution and the secondary spread of SARS, and six were ecological studies that used area-wide exposures and outcomes. Common shortcomings included possible cross-level bias in ecological studies, underreporting of health outcomes, using grouped data, the lack of highly spatially resolved air pollution measures, inadequate control for confounding and evaluation of effect modification, not accounting for regional variations in the timing of outbreaks’ temporal changes in at-risk popu-lations, and not accounting for nonindependence of outcomes. DISCUSSION: Studies of air pollution and novel coronaviruses have relied mainly on ecological measures of exposures and outcomes and are suscepti-ble to important sources of bias. Although longitudinal studies with individual-level data may be imperfect, they are needed to adequately address this topic. The complexities involved in these types of studies underscore the need for careful design and for peer review

Leucine Zipper-Bearing Kinase Is a Critical Regulator of Astrocyte Reactivity in the Adult Mammalian CNS.

Reactive astrocytes influence post-injury recovery, repair, and pathogenesis of the mammalian CNS. Much of the regulation of astrocyte reactivity, however, remains to be understood. Using genetic loss and gain-of-function analyses in vivo, we show that the conserved MAP3K13 (also known as leucine zipper-bearing kinase [LZK]) promotes astrocyte reactivity and glial scar formation after CNS injury. Inducible LZK gene deletion in astrocytes of adult mice reduced astrogliosis and impaired glial scar formation, resulting in increased lesion size after spinal cord injury. Conversely, LZK overexpression in astrocytes enhanced astrogliosis and reduced lesion size. Remarkably, in the absence of injury, LZK overexpression alone induced widespread astrogliosis in the CNS and upregulated astrogliosis activators pSTAT3 and SOX9. The identification of LZK as a critical cell-intrinsic regulator of astrocyte reactivity expands our understanding of the multicellular response to CNS injury and disease, with broad translational implications for neural repair

Complete Genome Sequence and Comparative Metabolic Profiling of the Prototypical Enteroaggregative Escherichia coli Strain 042

Background \ud Escherichia coli can experience a multifaceted life, in some cases acting as a commensal while in other cases causing intestinal and/or extraintestinal disease. Several studies suggest enteroaggregative E. coli are the predominant cause of E. coli-mediated diarrhea in the developed world and are second only to Campylobacter sp. as a cause of bacterial-mediated diarrhea. Furthermore, enteroaggregative E. coli are a predominant cause of persistent diarrhea in the developing world where infection has been associated with malnourishment and growth retardation. \ud \ud Methods \ud In this study we determined the complete genomic sequence of E. coli 042, the prototypical member of the enteroaggregative E. coli, which has been shown to cause disease in volunteer studies. We performed genomic and phylogenetic comparisons with other E. coli strains revealing previously uncharacterised virulence factors including a variety of secreted proteins and a capsular polysaccharide biosynthetic locus. In addition, by using Biolog™ Phenotype Microarrays we have provided a full metabolic profiling of E. coli 042 and the non-pathogenic lab strain E. coli K-12. We have highlighted the genetic basis for many of the metabolic differences between E. coli 042 and E. coli K-12. \ud \ud Conclusion \ud This study provides a genetic context for the vast amount of experimental and epidemiological data published thus far and provides a template for future diagnostic and intervention strategies

Concert/C: A language for distributed programming

Concert/C is a new language for distributed C programming that extends ANSI C to support distribution and process dynamics. Concert/C provides the ability to create and terminate processes, connect them together, and communicate among them. It supports transparent remote function calls (RPC) and asynchronous messages. Interprocess communications interfaces are typed in Concert/C, and type correctness is checked at compile time wherever possible, otherwise at runtime. All C data types, including complex data structures containing pointers and aliases, can be transmitted in RPCs. Concert/C programs run on a heterogeneous set of machine architectures and operating systems and communicate over multiple RPC and messaging protocols. The current Concert/C implementation runs on AIX 3.2 1, SunOS 4.1, Solaris 2.2 and OS/2 2.1, and communicates over Sun RPC, OSF/DCE and UDP multicast. Several groups inside and outside IBM are actively using Concert/C, and it is available via anonymous ftp from software.watson.ibm.com:/pub/concert.

Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study.

BackgroundInternal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia.MethodsIn this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment. Patients were enrolled into one of seven dose-escalation or dose-expansion cohorts assigned to receive once-daily doses of oral gilteritinib (20 mg, 40 mg, 80 mg, 120 mg, 200 mg, 300 mg, or 450 mg). Cohort expansion was based on safety and tolerability, FLT3 inhibition in correlative assays, and antileukaemic activity. Although the presence of an FLT3 mutation was not an inclusion criterion, we required ten or more patients with locally confirmed FLT3 mutations (FLT3mut+) to be enrolled in expansion cohorts at each dose level. On the basis of emerging findings, we further expanded the 120 mg and 200 mg dose cohorts to include FLT3mut+ patients only. The primary endpoints were the safety, tolerability, and pharmacokinetics of gilteritinib. Safety and tolerability were assessed in the safety analysis set (all patients who received at least one dose of gilteritinib). Responses were assessed in the full analysis set (all patients who received at least one dose of study drug and who had at least one datapoint post-treatment). Pharmacokinetics were assessed in a subset of the safety analysis set for which sufficient data for concentrations of gilteritinib in plasma were available to enable derivation of one or more pharmacokinetic variables. This study is registered with ClinicalTrials.gov, number NCT02014558, and is ongoing.FindingsBetween Oct 15, 2013, and Aug 27, 2015, 252 adults with relapsed or refractory acute myeloid leukaemia received oral gilteritinib once daily in one of seven dose-escalation (n=23) or dose-expansion (n=229) cohorts. Gilteritinib was well tolerated; the maximum tolerated dose was established as 300 mg/day when two of three patients enrolled in the 450 mg dose-escalation cohort had two dose-limiting toxicities (grade 3 diarrhoea and grade 3 elevated aspartate aminotransferase). The most common grade 3-4 adverse events irrespective of relation to treatment were febrile neutropenia (97 [39%] of 252), anaemia (61 [24%]), thrombocytopenia (33 [13%]), sepsis (28 [11%]), and pneumonia (27 [11%]). Commonly reported treatment-related adverse events were diarrhoea (92 [37%] of 252]), anaemia (86 [34%]), fatigue (83 [33%]), elevated aspartate aminotransferase (65 [26%]), and increased alanine aminotransferase (47 [19%]). Serious adverse events occurring in 5% or more of patients were febrile neutropenia (98 [39%] of 252; five related to treatment), progressive disease (43 [17%]), sepsis (36 [14%]; two related to treatment), pneumonia (27 [11%]), acute renal failure (25 [10%]; five related to treatment), pyrexia (21 [8%]; three related to treatment), bacteraemia (14 [6%]; one related to treatment), and respiratory failure (14 [6%]). 95 people died in the safety analysis set, of which seven deaths were judged possibly or probably related to treatment (pulmonary embolism [200 mg/day], respiratory failure [120 mg/day], haemoptysis [80 mg/day], intracranial haemorrhage [20 mg/day], ventricular fibrillation [120 mg/day], septic shock [80 mg/day], and neutropenia [120 mg/day]). An exposure-related increase in inhibition of FLT3 phosphorylation was noted with increasing concentrations in plasma of gilteritinib. In-vivo inhibition of FLT3 phosphorylation occurred at all dose levels. At least 90% of FLT3 phosphorylation inhibition was seen by day 8 in most patients receiving a daily dose of 80 mg or higher. 100 (40%) of 249 patients in the full analysis set achieved a response, with 19 (8%) achieving complete remission, ten (4%) complete remission with incomplete platelet recovery, 46 (18%) complete remission with incomplete haematological recovery, and 25 (10%) partial remission INTERPRETATION: Gilteritinib had a favourable safety profile and showed consistent FLT3 inhibition in patients with relapsed or refractory acute myeloid leukaemia. These findings confirm that FLT3 is a high-value target for treatment of relapsed or refractory acute myeloid leukaemia; based on activity data, gilteritinib at 120 mg/day is being tested in phase 3 trials.FundingAstellas Pharma, National Cancer Institute (Leukemia Specialized Program of Research Excellence grant), Associazione Italiana Ricerca sul Cancro

Potentiometric ion- and bioselective electrodes based on asymmetric polyurethane membranes

The potentiometric ion responses of ammonium- and proton-selective electrodes prepared by incorporating appropriate neutral carriers within novel asymmetric polyurethane membranes are reported. The membranes are formed by first casting a plasticized polyurethane(PU)/terpoly(vinyl chloride/vinyl acetate/vinyl alcohol) (PVA)-based ion-selective membrane and then applying a thin second layer of a more hydrophilic polyurethane (HPU) containing polylysine. The resulting asymmetric membranes function equivalently to normal PU/PVA membranes and conventional poly(vinyl chloride) type membranes in terms of potentiometric ion selectivity and dynamic response properties. The large amount of amine functional groups from the polylysine within the outer hydrophilic layer can be further activated for direct enzyme immobilization. As examples, adenosine deaminase and urease are immobilized on ammonium- and proton-selective membranes, respectively, to yield adenosine and urea electrodes with good dynamic responses and sensitivities. Advantageous use of this new membrane system for preparation of solid-state microfabricated enzyme-based sensors is also described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30916/1/0000586.pd

Screen printing: a technology for the batch fabrication of integrated chemical-sensor arrays

The commercialization of integrated chemical sensor has been slowed by the difficulty of device encapsulation and membrane application. For reasons of both cost and reproducibility, the sensor-specific structures should be mass fabricated, as are the microelectronics. The challenge lies in merging the standard semiconductor process sequence with the non-standard steps used to form the transducers. We demonstrate that screen printing can be used to partition the fabrication into two distinct sequences, semiconductor processing and sensor-specific steps. This simplifies process development and evolution, and makes semiconductor foundry services available for manufacturing sensors. After conventional semiconductor processing, our wafers have silver epoxy contacts screen printed on the aluminum sensor pads; the silver forms a stable chemical interface to the membranes, and the epoxy makes a strong physical bond to them. Next, the polymeric membranes are applied and patterned with screen printing. Membranes of different compositions can be deposited on the various sites of a multisensor chip by simply repeating the screen print/cure cycle. We show that the electrochemical performance of mass-fabricated passive and active sensor arrays is comparable to that of conventional liquid-junction ion-selective electrodes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31350/1/0000261.pd