Judicial Mistakes in Discovery

A recent wave of scholarship argues that judges often fail to comply with binding rules or precedent and sometimes apply overturned laws. Scholars have hypothesized that the cause of this “judicial noncompliance” may be flawed litigant briefing that introduces mistakes into judicial decisions—an idea this Essay calls the “Litigant Hypothesis.” The Essay presents a preliminary study aimed at exploring ways of testing the validity of the Litigant Hypothesis. Employing an empirical analysis that exploits recent amendments to Federal Discovery Rule 26, this Essay finds that the strongest predictor of noncompliance in a dataset of discovery decisions is indeed faulty briefs. This study concludes that the Litigant Hypothesis of noncompliance may have explanatory value

Judicial Mistakes in Discovery

A recent wave of scholarship argues that judges often fail to comply with binding rules or precedent and sometimes apply overturned laws. Scholars have hypothesized that the cause of this “judicial noncompliance” may be flawed litigant briefing that introduces mistakes into judicial decisions—an idea this Essay calls the “Litigant Hypothesis.” The Essay presents a preliminary study aimed at exploring ways of testing the validity of the Litigant Hypothesis. Employing an empirical analysis that exploits recent amendments to Federal Discovery Rule 26, this Essay finds that the strongest predictor of noncompliance in a dataset of discovery decisions is indeed faulty briefs. This study concludes that the Litigant Hypothesis of noncompliance may have explanatory value

Discovery as Regulation

This article develops an approach to discovery that is grounded in regulatory theory and administrative subpoena power. The conventional judicial and scholarly view about discovery is that it promotes fair and accurate outcomes and nudges the parties toward settlement. While commonly held, however, this belief is increasingly outdated and suffers from limitations. Among them, it has generated endless controversy about the problem of discovery costs. Indeed, a growing chorus of scholars and courts has offered an avalanche of reforms, from cost shifting and bespoke discovery contracts to outright elimination. Recently, Judge Thomas Hardiman quipped that if he had absolute power, he would abolish discovery for cases involving less than $500,000. These debates, however, are at a standstill, and existing scholarship offers incomplete treatment of discovery theory that might move debates forward. The core insight of the project is that in the private-enforcement context—where Congress deliberately employs private litigants as the main method of statutory enforcement—there is a surprisingly strong case that our current discovery system should be understood in part as serving regulatory goals analogous to administrative subpoena power. That is, discovery here can be seen as an extension of the subpoena power that agencies like the SEC, FTC, and EPA possess and is the lynchpin of a system that depends on private litigants to enforce our most important statutes. By forcing parties to disclose large amounts of information, discovery deters harm and, most importantly, shapes industry-wide practices and the primary behavior of regulated entities. This approach has a vast array of implications for the scope of discovery as well as the debate over costs. Scholars and courts should thus grapple with the consequences of what I call “regulatory discovery” for the entire legal system

The philosophy of order trough der Ring des Nibelunguen of Wagner. (Part I: “Das Rheingold”)

La presente contribución analiza el pensamiento filosófico de Richard Wagner desde una propuesta politológica propia en la que muestra el conflicto que existe entre el amor y el poder, dos pasiones que determinan nuestra condición egoísta y las decisiones personales y sociales. La fundamentación teórica se basa en la función política de la estética que es capaz de describir el imaginario social y una forma de ordenar y normar la vida en común.This contribution analyses the thought of the philosopher Richard Wagner from a political proposal where he shows the conflict between the power and love, two natural passions of selfish condition and personal and social choices. The theoretical foundation it’s based on the political function of esthetic, who has the ability to describe the social imaginary as a way to give order to the community

Induction of DNA double-strand breaks and cellular senescence by human respiratory syncytial virus

Human respiratory syncytial virus (HRSV) accounts for the majority of lower respiratory tract infections during infancy and childhood and is associated with significant morbidity and mortality. HRSV provokes a proliferation arrest and characteristic syncytia in cellular systems such as immortalized epithelial cells. We show here that HRSV induces the expression of DNA damage markers and proliferation arrest such as P-TP53, P-ATM, CDKN1A and γH2AFX in cultured cells secondary to the production of mitochondrial reactive oxygen species (ROS). The DNA damage foci contained γH2AFX and TP53BP1, indicative of double-strand breaks (DSBs) and could be reversed by antioxidant treatments such as N-Acetylcysteine (NAC) or reduced glutathione ethyl ester (GSHee). The damage observed is associated with the accumulation of senescent cells, displaying a canonical senescent phenotype in both mononuclear cells and syncytia. In addition, we show signs of DNA damage and aging such as γH2AFX and CDKN2A expression in the respiratory epithelia of infected mice long after viral clearance. Altogether, these results show that HRSV triggers a DNA damage-mediated cellular senescence program probably mediated by oxidative stress. The results also suggest that this program might contribute to the physiopathology of the infection, tissue remodeling and aging, and might be associated to long-term consequences of HRSV infections.This work was supported by Grants MPY-1038/14 to Alberto Zambrano, PI 11/00590 to Isidoro Martínez and RD12/0036/0030 to Ana Aranda from FIS (Instituto de Salud Carlos III) and Grant BFU2011-28958, from Ministerio de Economía y Competitividad to Ana Aranda. The authors have no conflicting financial interests

Fludarabine inhibits KV1.3 currents in human B lymphocytes

Fludarabine (F-ara-A) is a purine analog commonly used in the treatment of indolent B cell malignancies that interferes with different aspects of DNA and RNA synthesis. KV1.3 K+ channels are membrane proteins involved in the maintenance of K+ homeostasis and the resting potential of the cell, thus controlling signaling events, proliferation and apoptosis in lymphocytes. Here we show that F-ara-A inhibits KV currents in human B lymphocytes. Our data indicate that KV1.3 is expressed in both BL2 and Dana B cell lines, although total KV1.3 levels were higher in BL2 than in Dana cells. However, KV currents in the plasma membrane were similar in both cell lines and were abrogated by the specific KV1.3 channel inhibitor PAP-1, indicating that KV1.3 accounts for most of the KV currents in these cell lines. F-ara-A, at a concentration (3.5 μM) similar to that achieved in the plasma of fludarabine phosphate-treated patients (3 μM), inhibited KV1.3 currents by 61 ± 6.3% and 52.3 ± 6.3% in BL2 and Dana B cells, respectively. The inhibitory effect of F-ara-A was concentration-dependent and showed an IC50 value of 0.36 ± 0.04 μM and a nH value of 1.07 ± 0.15 in BL2 cells and 0.34 ± 0.13 μM (IC50) and 0.77 ± 0.11 (nH) in Dana cells. F-ara-A inhibition of plasma membrane KV1.3 was observed irrespective of its cytotoxic effect on the cells, BL2 cells being sensitive and Dana cells resistant to F-ara-A cytotoxicity. Interestingly, PAP-1, at concentrations as high as 10 μM, did not affect the viability of BL2 and Dana cells, indicating that blockage of KV1.3 in these cells is not toxic. Finally, F-ara-A had no effect on ectopically expressed KV1.3 channels, suggesting an indirect mechanism of current inhibition. In summary, our results describe the inhibitory effect of F-ara-A on the activity of KV1.3 channel. Although KV1.3 inhibition is not sufficient to induce cell death, further research is needed to determine whether it might still contribute to F-ara-A cytotoxicity in sensitive cells or be accountable for some of the clinical side effects of the drug.This study was supported by MINECO (SAF2013-45800-R, SAF2016-75021-R, RD12/0042/0019, CB/11/00222) and ISCIII (PI12/01135 and PI16/00895). The cost of this publication was paid in part by funds from the European Fund for Economic and Regional Development (FEDER). TG is supported by the Ramón y Cajal Program.Peer reviewedPeer Reviewe

Use of Biofertilizers in Agricultural Production

Most of agricultural production in Latin America consists of smallholder farmers who need the development of sustainable technologies, with costs according to their economic condition. Biofertilizers composed of free-living bacteria promote plant’s growth, improve productivity through the strengthening of its roots, and reduce the amount of synthetic fertilizer applied to the crops. The aims of this chapter are to highlight the microorganisms commonly used in agriculture as biofertilizers and the main researches carried out in several countries of Latin America, and to describe the development of an experimental biofertilizer for maize, based on strains of Azospirillum spp. and Pseudomonas fluorescens, in the highlands (Sierra Region) of Ecuador. Seven phylum and 95 genera o microorganism used as biofertilizers or Plant Growth-Promoting Rhizobacteria (PGPR) are summarized, along with the benefits, challenges and future prospect of their use. The effectiveness of the experimental biofertilizer developed in Ecuador was demonstrated through several experiments at the green house and field, in which it was evident the increase of root’s size, the amount of crocket, the percentage of dry matter, and the crops´ yield. The evaluations, accomplished on farmers’ fields showed 30% of increase in yield and 21% of decrease in the cost of production per kilogram; as a consequence of the use of biofertilizer plus 50% of the recommended chemical fertilization, in comparison with standard farming techniques. Farmers can reduce the application of synthetic fertilizers and sustainably increase crop yield through the use of this technology

Identification of a critical binding site for local anaesthetics in the side pockets of Kv1 channels

© 2021 The Authors.[Background and Purpose]: Local anaesthetics block sodium and a variety of potassium channels. Although previous studies identified a residue in the pore signature sequence together with three residues in the S6 segment as a putative binding site, the precise molecular basis of inhibition of Kv channels by local anaesthetics remained unknown. Crystal structures of Kv channels predict that some of these residues point away from the central cavity and face into a drug binding site called side pockets. Thus, the question arises whether the binding site of local anaesthetics is exclusively located in the central cavity or also involves the side pockets. [Experimental Approach]: A systematic functional alanine mutagenesis approach, scanning 58 mutants, together with in silico docking experiments and molecular dynamics simulations was utilized to elucidate the binding site of bupivacaine and ropivacaine. [Key Results]: Inhibition of Kv1.5 channels by local anaesthetics requires binding to the central cavity and the side pockets, and the latter requires interactions with residues of the S5 and the back of the S6 segments. Mutations in the side pockets remove stereoselectivity of inhibition of Kv1.5 channels by bupivacaine. Although binding to the side pockets is conserved for different local anaesthetics, the binding mode in the central cavity and the side pockets shows considerable variations. [Conclusion and Implications]: Local anaesthetics bind to the central cavity and the side pockets, which provide a crucial key to the molecular understanding of their Kv channel affinity and stereoselectivity, as well as their spectrum of side effects.The study was supported by the Ministerio de Ciencia e Innovación (MICINN, Spain) Grants SAF2016-75021-R and PID2019-104366RB-C21 (to C.V. and T.G.); the European Regional Development Fund (Fondo Europeo de Desarrollo Regional [FEDER]) and the Instituto de Salud Carlos III CIBERCV programme CB/11/00222 (to C.V. and T.G.); the Consejo Superior de Investigaciones Científicas (CSIC) Grants PIE201820E104 and 2019AEP148 (to C.V.); the Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT) 1191133 and the Fondo de Equipamiento Científico y Tecnológico (FONDEQUIP) 160063 grants from ANID (to W.G.); and the Deutsche Forschungsgemeinschaft (DFG) Grant DE1482-4/1 to N.D

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

LegalBench: A Collaboratively Built Benchmark for Measuring Legal Reasoning in Large Language Models

The advent of large language models (LLMs) and their adoption by the legal community has given rise to the question: what types of legal reasoning can LLMs perform? To enable greater study of this question, we present LegalBench: a collaboratively constructed legal reasoning benchmark consisting of 162 tasks covering six different types of legal reasoning. LegalBench was built through an interdisciplinary process, in which we collected tasks designed and hand-crafted by legal professionals. Because these subject matter experts took a leading role in construction, tasks either measure legal reasoning capabilities that are practically useful, or measure reasoning skills that lawyers find interesting. To enable cross-disciplinary conversations about LLMs in the law, we additionally show how popular legal frameworks for describing legal reasoning—which distinguish between its many forms—correspond to LegalBench tasks, thus giving lawyers and LLM developers a common vocabulary. This paper describes LegalBench, presents an empirical evaluation of 20 open-source and commercial LLMs, and illustrates the types of research explorations LegalBench enables