The Law Against Family Separation

Most commentators assume that, except for the few restrictions expressly mentioned in the U.S. Constitution, the President\u27s pardon power is unlimited. This Paper suggests that this common view is mistaken in at least one unexpected way. Presidential pardons must satisfy a modest procedural rule: they must list the specific crimes covered by the pardon. The specificity requirement means that vague and broadly worded pardons are invalid. This claim bears a significant burden of persuasion, since it runs so counter to accepted opinion. Nonetheless, that burden can be met. This Paper\u27s argument rests on an originalist understanding of the constitutional text, an approach that the Supreme Court has repeatedly endorsed as the appropriate method for interpreting the Pardon Clause. That approach leaves little doubt that a specificity requirement is a binding limitation on the President\u27s pardon power. The final part of this Paper examines the ramifications of the specificity requirement for federal criminal investigations, particularly investigations into Russia\u27s interference in the 2016 presidential election. The specificity requirement may prove surprisingly significant in this latter context, since it both raises the political costs, and narrows the legal scope, of any pardon the President might grant to former campaign advisors. In effect, the requirement strengthens the hand of investigators, increasing the likelihood that defendants will cooperate with the prosecution. In so doing, the specificity requirement serves as an unexpected ally in the fight for political accountability and in defense of the rule of law

Ex Vivo Recapitulation of Trauma-Induced Coagulopathy and Preliminary Assessment of Trauma Patient Platelet Function Under Flow Using Microfluidic Technology

Background: Relevant to trauma induced coagulopathy (TIC) diagnostics, microfluidic assays allow controlled hemodynamics for testing of platelet and coagulation function using whole blood.Methods: Hemodilution or hyperfibrinolysis was studied under flow with modified healthy whole blood. Furthermore, platelet function was also measured using whole blood from trauma patients admitted to a Level 1 Trauma center. Platelet deposition was measured with PPACK-inhibited blood perfused over collagen surfaces at a wall shear rate of 200 s-1, while platelet/fibrin deposition was measured with corn trypsin inhibitor (CTI)-treated blood perfused over TF/collagen.Results: In hemodilution studies, PPACK-treated blood displayed almost no platelet deposition when diluted to 10% Hct with saline, platelet poor plasma (PPP), or platelet rich plasma (PRP). Using similar dilutions, platelet/fibrin deposition was essentially absent for CTI-treated blood perfused over TF/collagen. To mimic hyperfibrinolysis during trauma, exogenous tPA (50 nM) was added to blood prior to perfusion over TF/collagen. At both venous and arterial flows, the generation and subsequent lysis of fibrin was detectable within 6 min, with lysis blocked by addition of the plasmin inhibitor, [epsilon]-aminocaproic acid. Microfluidic assay of PPACK-inhibited whole blood from trauma patients revealed striking defects in collagen response and secondary platelet aggregation in 14 of 21 patients, while platelet hyperfunction was detected in 3 of 20 patients.Conclusions: Rapid microfluidic detection of (i) hemodilution-dependent impairment of clotting, (ii) clot instability due to lysis, (iii) blockade of fibrinolysis, or (iv) platelet dysfunction during trauma may provide novel diagnostic opportunities to predict TIC risk.Level of Evidence: Level IVStudy type: Diagnostic Tes

LILAC and Citation Project Workshop

The LILAC Project (Learning Information Literacy across the Curriculum) is a multi-institutional study of student information-seeking behaviors (lilac-group.blogspot.com). This year we join forces with the Citation Project, a study of how students use the information they find (CitationProject.net), to consider what both studies may have to tell us about students’ information literacy “habits of mind.” Participants will gain hands-on experience with the research-aloud protocol (RAP) video captures used as part of this study and identifying and coding subject behaviors. We will demonstrate coding and analysis of information-seeking behaviors of both native speakers of English and multilingual writers in composition courses, share preliminary findings of a project examining the information literacy of multilingual writers, and discuss its relevance in composition classes, ESL academic writing classes, and content courses in different disciplines. In both large- and small-group discussions, we will consider what we are learning from results of these studies and what we can do with the information, sharing our experience in data analysis and results interpretation, and inviting participants to discuss how to consider the framing of LILAC projects from different disciplinary perspectives. The addition of citation context analysis like that done by the Citation Project allows participants to explore both the research process and the products of that research. The triangulation of data made possible by this combined research provides deeper and more nuanced understanding of information literacy in general and use and misuse of sources in particular

GPER1 stimulation alters posttranslational modification of RGSz1 and induces desensitization of 5-HT1A receptor signaling in the rat hypothalamus

The final, published version of this article is available at http://www.karger.com/?doi=10.1159/000369467.Hyperactivity of the hypothalamic-pituitary-adrenal axis is a consistent biological characteristic of depression and response normalization coincides with clinical responsiveness to antidepressant medications. Desensitization of serotonin 1A receptor (5-HT1AR) signaling in the hypothalamic paraventricular nucleus (PVN) follows selective serotonin reuptake inhibitor (SSRI) antidepressant treatment and contributes to the antidepressant response. Estradiol alone produces a partial desensitization of 5-HT1AR signaling, and synergizes with SSRIs to result in a complete and more rapid desensitization than with SSRIs alone as measured by a decrease in the oxytocin and adrenocorticotrophic hormone(ACTH) responses to 5-HT1AR stimulation. G protein-coupled estrogen receptor1 (GPER1) is necessary for estradiol-induced desensitization of 5-HT1AR signaling, although the underlying mechanisms are still unclear. We now find that stimulation of GPER1 with the selective agonist G-1 and non-selective stimulation of estrogen receptors dramatically alter isoform expression of a key component of the 5-HT1AR signaling pathway, RGSz1, a GTPase activating protein selective for Gαz, the Gα subunit necessary for 5-HT1AR-mediated hormone release. RGSz1 isoforms are differentially glycosylated, SUMOylated, and phosphorylated, and differentially distributed in subcellular organelles. High molecular weight RGSz1 is SUMOylated and glycosylated, localized to the detergent-resistant microdomain (DRM) of the cell membrane, and increased by estradiol and G-1 treatment. Because activated Gαz also localizes to the DRM, increased DRM-localized RGSz1 by estradiol and G-1could reduce Gαz activity, functionally uncoupling 5-HT1AR signaling. Peripheral G-1 treatment produced partial reduction in oxytocin and ACTH responses to 5-HT1AR-stimulation similar to direct injections into the PVN. Together, these results identify GPER1 and RGSz1 as novel targets for the treatment of depression

Inducible ablation of CD11c+ cells to determine their role in skin wound repair

Wound healing in healthy skin requires a complex interplay between immune and non‐immune cells. In addition to their roles in infection control and cell debridement, leukocytes secrete factors to orchestrate the timing of the repair process via cross‐talk with epithelia. This critical role in wound timing is vital as failure to induce wound closure leads to debilitating chronic wounds susceptible to further infection and patient sepsis

GPR30 is necessary for estradiol-induced desensitization of 5- HT1A receptor signaling in the paraventricular nucleus of the rat hypothalamus

Estrogen therapy used in combination with selective serotonin reuptake inhibitor (SSRI) treatment improves SSRI efficacy for the treatment of mood disorders. Desensitization of serotonin 1A (5-HT1A) receptors, which takes one to two weeks to develop in animals, is necessary for SSRI therapeutic efficacy. Estradiol modifies 5-HT1A receptor signaling and induces a partial desensitization in the paraventricular nucleus (PVN) of the rat within two days, but the mechanisms underlying this effect are currently unknown. The purpose of this study was to identify the estrogen receptor necessary for estradiol-induced 5-HT1A receptor desensitization. We previously showed that estrogen receptor β is not necessary for 5-HT1A receptor desensitization and that selective activation of estrogen receptor GPR30 mimics the effects of estradiol in rat PVN. Here, we used a recombinant adenovirus containing GPR30 siRNAs to decrease GPR30 expression in the PVN. Reduction of GPR30 prevented estradiol-induced desensitization of 5-HT1A receptor as measured by hormonal responses to the selective 5-HT1A receptor agonist, (+)8-OH-DPAT. To determine the possible mechanisms underlying these effects, we investigated protein and mRNA levels of 5-HT1A receptor signaling components including 5-HT1A receptor, Gαz, and RGSz1. We found that two days of estradiol increased protein and mRNA expression of RGSz1, and decreased 5-HT1A receptor protein but increased 5-HT1A mRNA; GPR30 knockdown prevented the estradiol-induced changes in 5-HT1A receptor protein in the PVN. Taken together, these data demonstrate that GPR30 is necessary for estradiol-induced changes in the 5-HT1A receptor signaling pathway and desensitization of 5-HT1A receptor signaling

A general protease digestion procedure for optimal protein sequence coverage and PTM analysis of recombinant glycoproteins: Application to the characterization of hLOXL2 glycosylation

Using recombinant DNA technology for expression of protein therapeutics is a maturing field of pharmaceutical research and development. As recombinant proteins are increasingly utilized as biotherapeutics, improved methodologies ensuring the characterization of post-translational modifications (PTMs) are needed. Typically, proteins prepared for PTM analysis are proteolytically digested and analyzed by mass spectrometry. To assure full coverage of the PTMs on a given protein, one must obtain complete sequence coverage of the protein, which is often quite challenging. The objective of the research described here is to design a protocol that maximizes protein sequence coverage and enables detection of post-translational modifications, specifically N-linked glycosylation. To achieve this objective, a highly efficient proteolytic digest protocol using trypsin was designed by comparing the relative merits of denaturing agents (urea and Rapigest™ SF), reducing agents (dithiothreitol, DTT, and tris(2-carboxyethyl)phophine, TCEP), and various concentrations of alkylating agent (iodoacetamide, IAM). After analysis of human apo-transferrin using various protease digestion protocols, ideal conditions were determined to contain 6 M urea for denaturation, 5 mM TCEP for reduction, 10 mM IAM for alkylation, and 10 mM DTT, to quench excess IAM before the addition of trypsin. This method was successfully applied to a novel recombinant protein, human lysyl oxidase-like 2 (hLOXL2). Furthermore, the glycosylation PTMs were readily detected at two glycosylation sites in the protein. These digestion conditions were specifically designed for PTM analysis of recombinant proteins and biotherapeutics, and the work described herein fills an unmet need in the growing field of biopharmaceutical analysis

Developing soft skills: exploring the feasibility of an Australian well-being program for health managers and leaders in Timor-Leste

The article aims to describe the Family Wellbeing Program (FWB), a program that sets out to facilitate the enhancement of soft skills and to explore the relevance and acceptability of the FWB in the context of health managers and leaders in Timor-Leste. This article presents the fundamental principles of the FWB approach to facilitating soft skills in the context of trauma-informed training for managers and leaders. It describes how a participatory social learning approach advances deep, transformative, and long-lasting impacts. An exploratory mixed-methods design was adopted. Qualitative data were gathered from workshop participants through an evaluation form with open-ended questions allowing participants to provide comments on the program and how it could be enhanced. In addition, attendees participated in an online survey, which sought to capture data relating to demographics, soft skills for managers/leaders, personal well-being, and program satisfaction. Overall, the results show that the FWB program is both relevant and acceptable. The findings indicate that participants’ understanding of concepts of management and well-being, particularly as it is applied to the workplace, was improved. This outcome is important because it highlights how the FWB program can contribute to the development of more accomplished managers and leaders in the future. The results of this exploratory study will be useful in informing future management and leadership training for the Timorese health workforce

County development and sustainability in China: a systematic scoping of the literature

Despite the importance of research and innovation in facilitating sustainable county development in China, little evidence is available concerning the output and characteristics of that research. This scoping review assesses key features or characteristics of the research output, the extent to which researchers engage with concepts of sustainability and the potential impact of the research. Publications were identified and classified using a process consistent with Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). The R programming packages igraph and wordcloud respectively were used to analyse and graphically depict the strength of authorship networks and keyword frequency. Findings revealed that this field of research is an evolving one with a widely-dispersed network of researchers increasingly using new keywords. The implications of the review findings for improving the value and impact of sustainable county development research are explored

Alterations in AMPA Receptor Subunits and Tarps in the Rat Nucleus Accumbens Related to the Formation of Ca2+-Permeable AMPA Receptors During the Incubation of Cocaine Craving

Cue-induced cocaine seeking intensifies or incubates after withdrawal from extended access cocaine self-administration, a phenomenon termed incubation of cocaine craving. The expression of incubated craving is mediated by Ca²⁺-permeable AMPA receptors (CP-AMPARs) in the nucleus accumbens (NAc). Thus, CP-AMPARs are a potential target for therapeutic intervention, making it important to understand mechanisms that govern their accumulation. Here we used subcellular fractionation and biotinylation of NAc tissue to examine the abundance and distribution of AMPAR subunits, and GluA1 phosphorylation, in the incubation model. We also studied two transmembrane AMPA receptor regulatory proteins (TARPs), γ-2 and γ-4. Our results, together with earlier findings, suggest that some of the new CP-AMPARs are synaptic. These are probably associated with γ-2, but they are loosely tethered to the PSD. Levels of GluA1 phosphorylated at serine 845 (pS845 GluA1) were significantly increased in biotinylated tissue and in an extrasynaptic membrane-enriched fraction. These results suggest that increased synaptic levels of CP-AMPARs may result in part from an increase in pS845 GluA1 in extrasynaptic membranes, given that S845 phosphorylation primes GluA1-containing AMPARs for synaptic insertion and extrasynaptic AMPARs supply the synapse. Some of the new extrasynaptic CP-AMPARs are likely associated with γ-4, rather than γ-2. The maintenance of CP-AMPARs in NAc synapses during withdrawal is accompanied by activation of CaMKII and ERK2 but not CaMKI. Overall, AMPAR plasticity in the incubation model shares some features with better described forms of synaptic plasticity, although the timing of the phenomenon and the persistence of related neuroadaptations are significantly different