Can disclosure regulation impede innovation?

I investigate whether mandating transparent patent disclosure fosters or harms incentives to innovate. While transparent patent disclosure reveals proprietary information to competitors and reduces a firm’s lead time and competitive advantage, a firm stands to benefit from knowledge spill-ins from competitors either through reduced uncertainty or improved efficiency. I exploit the implementation of the American Inventors Protection Act (“AIPA”) in 2001, which accelerates the dissemination of patent information, as a shock to the transparency of patent disclosure. The results suggest the AIPA reduces firm incentives to innovate. I find that firms allocate fewer resources to R&D after the law change and that smaller firms reduce R&D intensity more than large firms. Furthermore, smaller firms produce fewer patents per dollar of R&D stock and receive fewer forward patent citations than large firms even as large firms experience an increase in R&D profitability and market share. However, there is some evidence firms adapt their patenting strategies in response. Specifically, the law increases foreign patent filings among smaller firms and increases the use of voluntary patent publication requests for all firms, perhaps to better take advantage of licensing opportunities. Results are robust to a variety of alternatives and do not appear to be attributable to the dot com bubble. Taken together, my evidence corroborates concerns raised by critics of the AIPA even as it suggests some achievement of international harmonization goals. I also inform academics interested in the role of patent disclosure and the real effects of disclosure regulation.Accountin

Punishing the \u27other\u27 : race, ethnicity, and the American justice system.

This thesis is an examination of the relationship between race and ethnicity and the American justice system. It is a comparative case study of the racial dimensions of the War on Drugs in the domestic criminal justice system and the ethnic dimensions of the War on Terror through an examination of the prison and prisoners at Guantanamo Bay. This thesis is about building bridges between domestic and international conceptions of justice with a focus on human rights. Central to this project is an exploration of similar process of white fear, racialization, and dehumanization black and Arab/Muslim men experience under the American justice system. Finally, this thesis explores the political ramifications of wars on ideas (the War on Drugs and the War on Terror) and how that effects punishment

Strategic Scientific Disclosure – Evidence from the Leahy-Smith America Invents Act

We examine the impact of technological competition on voluntary innovation disclosure using changes scientific publications around the enactment of Leahy-Smith America Invents Act of 2011 (AIA). The AIA changes the patent system from first-to-invent to first-inventor-to-file system and induces a patent “race” that increases technological competition. Firms with resource constraints tend to be slow in filing a patent and are disadvantaged in this race. Using a difference-in-differences design, we show that financially constrained firms strategically increase scientific publications in an attempt to block competitors from obtaining a patent and extend the patent race after the enactment of AIA. This effect is more pronounced among firms (1) that are less capital intensive, and whose competitors have a lower cost of entry; (2) that face more patent competition; and (3) whose patents have longer lifecycles. The findings suggest that technological competition is a key determinant of firms’ scientific publications. The positive effect of the AIA on corporate scientific publications is consistent with the policy makers’ goal to promote knowledge spillover in society

Mythology and the Movies, Vol. 1

In this course, Mythology and the Movies, students were assigned the creation of a four page comic book. Many of the students were unfamiliar with comic books but learned in the class how the visual sequence of images in a comic is very much like that in a movie. The project had to use either the Harry Potter movies or the Twilight movies as the basis for an original myth that investigated a mythological theme: chaos, creation, time, the quest, metamorphosis, difference, or the Other . Each comic was an exercise in rethinking these universes and using the characters and setting in a new, mythological context.https://repository.upenn.edu/showcase_comics/1023/thumbnail.jp

Structure-based design of a highly stable, covalently-linked SARS-CoV-2 spike trimer with improved structural properties and immunogenicity

The continued threat of SARS-CoV-2 to global health necessitates development of improved research tools and vaccines. We present an improved SARS-CoV-2 spike ectodomain, “VFLIP”, bearing five proline substitutions, a flexible cleavage site linker, and an inter-protomer disulfide bond. VFLIP displays significantly improved stability, high-yield production and retains its trimeric state without exogenous trimerization motifs. High-resolution cryo-EM and glycan profiling reveal that the VFLIP quaternary structure and glycosylation mimic the native spike on the viral surface. Further, VFLIP has enhanced affinity and binding kinetics relative to other stabilized spike proteins for antibodies in the Coronavirus Immunotherapeutic Consortium (CoVIC), and mice immunized with VFLIP exhibit potent neutralizing antibody responses against wild-type and B.1.351 live SARS-CoV-2. Taken together, VFLIP represents an improved tool for diagnostics, structural biology, antibody discovery, and vaccine design.Competing Interest StatementThe authors have declared no competing interest

Epigenetic mechanisms, T-cell activation, and CCR5 genetics interact to regulate T-cell expression of CCR5, the major HIV-1 coreceptor.

CAPRISA, 2015.Abstract available in pdf

Models of classroom assessment for course-based research experiences

Course-based research pedagogy involves positioning students as contributors to authentic research projects as part of an engaging educational experience that promotes their learning and persistence in science. To develop a model for assessing and grading students engaged in this type of learning experience, the assessment aims and practices of a community of experienced course-based research instructors were collected and analyzed. This approach defines four aims of course-based research assessment—(1) Assessing Laboratory Work and Scientific Thinking; (2) Evaluating Mastery of Concepts, Quantitative Thinking and Skills; (3) Appraising Forms of Scientific Communication; and (4) Metacognition of Learning—along with a set of practices for each aim. These aims and practices of assessment were then integrated with previously developed models of course-based research instruction to reveal an assessment program in which instructors provide extensive feedback to support productive student engagement in research while grading those aspects of research that are necessary for the student to succeed. Assessment conducted in this way delicately balances the need to facilitate students’ ongoing research with the requirement of a final grade without undercutting the important aims of a CRE education

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Pathogenic follicular CD8 T cells promote autoimmune disease.

The contribution of CD8 T cells to autoimmune disease remains in debate. We show autoimmune CD8 T cells which induce antibody class switching and plasma cell differentiation act synergistically with CD4 T cells in promoting germinal center reactions. We have identified CXCR5+PD-1+ CD8 effector T (CD8 T follicular; Tfc) cells, within the germinal center, that expand during late autoimmune disease progression. We show that CD8 Tfc cells transcriptionally and phenotypically resemble CD4 T follicular helper (Tfh) cells in multiple models of spontaneous autoantibody-mediated disease including IL-2 deficient (IL-2-KO), scurfy and MRL/MpJ-FASlpr mice. CD8 Tfc cells maintain the capacity to produce significant amounts of cytotoxic proteins granzyme B, CD107a and TNFα, and helper-associated cytokines IL-21, IFNγ and IL-4. Functionally, CD8 Tfc cells promote cytokine-mediated antibody class switch using mechanisms largely independent of IFNγ or IL-21. When adoptively transferred CD8 Tfc cells in combination with CD4 Tfh cell promote autoantibody production. Our results indicate that CD8 Tfc cells contribute to autoimmune disease synergistically with CD4 Tfh cells to induce B cell class switching and autoantibodies during disease progression. Autoimmune disease is a novel immune setting during which CXCR5+ CD8 T cells develop beyond situations of chronic viral infection and cancer. Thus, pathogenic CD8 T cells influence germinal center reactions and promote autoimmune responses