MARK TWAIN\u27S USES OF SUFFERING IN THE WRITER-CHARACTER-READER TRIAD

This thesis studies Mark Twain’s uses of suffering in the writer character reader triad. In the book Huckleberry Finn, Twain himself seems to identify more closely with Huck than he does with Tom, as evidenced by the first person narrative in Finn and the more serious, more carefully developed autobiographical incidents in that book. Perhaps because Twain’s later life was so bleak and unhappy, he poured all of his self-defeat and pessimism into his thoughts for Huck’s old age

\u3cem\u3eNoriega v. Pastrana\u3c/em\u3e: The Supreme Court Takes a Step Back from the Table

The Military Commissions Act of 2006 expressly removed the Geneva Conventions as a source of rights for any person litigating against the United States or its agents. For General Manuel Noriega, the Geneva Conventions provided him with his sole opportunity for relief from what is, in his opinion, a grave injustice; without it, he has no hope of returning to his home country any time in the near future. Thus, Noriega petitioned the Supreme Court and asked the Court to find this restriction to be an unconstitutional suspension of the writ of habeas corpus. To perform this analysis, the Supreme Court would have had to delve into territory previously unexplored and narrowly avoided. Ultimately, the Court declined to accept certiorari, over a strong objection by Justice Thomas, joined by Justice Scalia. This Comment argues that the Supreme Court has avoided the issue long enough, and should have settled the matter once and for all by accepting General Noriega’s challenge

Fed-batch control based upon the measurement of intracellular NADH

A series of experiments demonstrating that on-line measurements of intracellular NADH by culture fluorescence can be used to monitor and control the fermentation process are described. A distinct advantage of intercellular NADH measurements over other monitoring techniques such as pH and dissolved oxygen is that it directly measures real time events occurring within the cell rather than changes in the environment. When coupled with other measurement parameters, it can provide a finer degree of sophistication in process control

Flourishing Through Contemplative Practices

Our project involves outlining walking, running, and biking routes inside and around Farmville that people can use to not only get more active physically but mentally as well. How this might work is that people can pick up a brochure at the gym, along with possibly a bike, and then choose a route and a contemplative prompt to think about while going along that route. Additionally, we plan to mark good places to stop along the routes to read or just to take a break and continue contemplating the prompt. We will also encourage people to try to do this without their devices so that they are free of distractions and can focus their attention on contemplation. Our goal in doing this is to contribute to the individual flourishing of people within the Farmville community which might cause Farmville as a whole to flourish just a bit more

Protective Effects of Human and Mouse Soluble Scavenger-Like CD6 Lymphocyte Receptor in a Lethal Model of Polymicrobial Sepsis

Sepsis still constitutes an unmet clinical need, which could benefit from novel adjunctive strategies to conventional antibiotic therapy. The soluble form of the scavenger-like human CD6 lymphocyte receptor (shCD6) binds to key pathogenic components from Gram-positive and -negative bacteria and shows time- and dose-dependent efficacy in mouse models of monobacterial sepsis. The objective of the present work was to demonstrate the effectiveness of infusing mouse and human sCD6 by different systemic routes, either alone or as adjunctive therapy to gold standard antibiotics, in a lethal model of polymicrobial sepsis. To this end, C57BL/6 mice undergoing high-grade septic shock induced by cecal ligation and puncture (CLP; ≥90% lethality) were infused via the intraperitoneal (i.p.) or intravenous (i.v.) route with shCD6 at different doses and time points, either alone or in combination with imipenem/cilastatin (I/C) at a dose of 33 mg/kg of body weight every 8 h. Significantly reduced mortality and proinflammatory cytokine levels were observed by i.p. infusion of a single shCD6 dose (1.25 mg/kg) 1 h pre- or post-CLP. When using the i.v. route, mice survival was significantly extended by starting shCD6 infusion at later time points post-CLP (up to 6 h after CLP). Significant adjunctive effects on mouse survival were observed by i.p. or i.v. infusion of shCD6 in combination with i.p. I/C post-CLP. Similar results were obtained in mice expressing high sustained levels (5 to 10 μg/ml) of mouse sCD6 in serum by means of transduction with hepatotropic adeno-associated virus (AAV). Taken together, the data support the conserved antibacterial effects of human and mouse sCD6 and their use as adjunctive therapy in experimental models of complex and severe polymicrobial sepsis.Ministerio de Economía y Competitividad (España) SAF2013-46151-R PCIN-2015-070Instituto de Salud Carlos III RD12/0015/0018European Development Regional Fund RD12/0015/0018Fundació La Marató TV3 201319-30-3

Closed-loop control of continuous piperacillin delivery: an in silico study

Background and objective: Sub-therapeutic dosing of piperacillin-tazobactam in critically-ill patients is associated with poor clinical outcomes and may promote the emergence of drug-resistant infections. In this paper, an in silico investigation of whether closed-loop control can improve pharmacokinetic-pharmacodynamic (PK-PD) target attainment is described. Method: An in silico platform was developed using PK data from 20 critically-ill patients receiving piperacillin-tazobactam where serum and tissue interstitial fluid (ISF) PK were defined. Intra-day variability on renal clearance, ISF sensor error, and infusion constraints were taken into account. Proportional-integral-derivative (PID) control was selected for drug delivery modulation. Dose adjustment was made based on ISF sensor data with a 30-minute sampling period, targeting a serum piperacillin concentration between 32-64 mg/L. A single tuning parameter set was employed across the virtual population. The PID controller was compared to standard therapy, including bolus and continuous infusion of piperacillin-tazobactam. Results: Despite significant inter-subject and simulated intra-day PK variability and sensor error, PID demonstrated a significant improvement in target attainment compared to traditional bolus and continuous infusion approaches. Conclusion: A PID controller driven by ISF drug concentration measurements has the potential to precisely deliver piperacillin-tazobactam in critically-ill patients undergoing treatment for sepsis

Safety and efficacy of an adaptive bolus calculator for Type 1 diabetes: a randomised control cross over study

Background The Advanced Bolus Calculator for Type 1 Diabetes (ABC4D) is a decision support system employing the artificial intelligence technique of case-based reasoning to adapt and personalise insulin bolus doses. The integrated system comprises a smartphone application and clinical web portal. We aimed to assess safety and efficacy of the ABC4D (intervention) compared to a non-adaptive bolus calculator (control). Methods This was a prospective randomised controlled crossover study. Following a 2-week run-in period, participants were randomised to ABC4D or control for 12 weeks. After a 6-week washout period, participants crossed over for 12 weeks. The primary outcome was difference in percentage (%) time in range (TIR) (3.9-10.0 mmol/L (70-180mg/dL)) change during the daytime (07:00-22:00) between groups. Results 37 adults with type 1 diabetes on multiple daily injections of insulin were randomised, median (IQR) age 44.7 (28.2-55.2) years, diabetes duration 15.0 (9.5-29.0) years, HbA1C 61.0 (58.0-67.0) mmol/mol (7.7 (7.5-8.3)%). Data from 33 participants were analysed. There was no significant difference in daytime %TIR change with ABC4D compared to control (median (IQR) +0.1 (-2.6 to + 4.0)% versus +1.9 (-3.8 to + 10.1)%; p = 0.53). Participants accepted fewer meal dose recommendations in the intervention compared to control (78.7 (55.8-97.6)% versus 93.5 (73.8-100)%; p = 0.009) with a greater reduction in insulin dosage from that recommended. Conclusion The ABC4D is safe for adapting insulin bolus doses and provided the same level of glycaemic control as the non-adaptive bolus calculator. Results suggest that participants did not follow ABC4D recommendations as frequently as control, impacting its effectiveness

The ectodomains of the lymphocyte scavenger receptors CD5 and CD6 interact with tegumental antigens from Echinococcus granulosus sensu lato and protect mice against secondary cystic echinococcosis

Background: Scavenger Receptors (SRs) from the host's innate immune system are known to bind multiple ligands to promote the removal of non-self or altered-self targets. CD5 and CD6 are two highly homologous class I SRs mainly expressed on all T cells and the B1a cell subset, and involved in the fine tuning of activation and differentiation signals delivered by the antigen-specific receptors (TCR and BCR, respectively), to which they physically associate. Additionally, CD5 and CD6 have been shown to interact with and sense the presence of conserved pathogen-associated structures from bacteria, fungi and/or viruses. Methodology/Principal findings: We report herein the interaction of CD5 and CD6 lymphocyte surface receptors with Echinococcus granulosus sensu lato (s.l.). Binding studies show that both soluble and membrane-bound forms of CD5 and CD6 bind to intact viable protoscoleces from E. granulosus s.l. through recognition of metaperiodate-resistant tegumental components. Proteomic analyses allowed identification of thioredoxin peroxidase for CD5, and peptidyl-prolyl cis-trans isomerase (cyclophilin) and endophilin B1 (antigen P-29) for CD6, as their potential interactors. Further in vitro assays demonstrate that membrane-bound or soluble CD5 and CD6 forms differentially modulate the pro- and anti-inflammatory cytokine release induced following peritoneal cells exposure to E. granulosus s.l. tegumental components. Importantly, prophylactic infusion of soluble CD5 or CD6 significantly ameliorated the infection outcome in the mouse model of secondary cystic echinococcosis. Conclusions/Significance Taken together, the results expand the pathogen binding properties of CD5 and CD6 and provide novel evidence for their therapeutic potential in human cystic echinococcosis. Author summary: Scavenger Receptors (SRs) are constituents of host's innate immune system able to sense and remove altered-self and/or pathogen components. Data on their interaction with helminth parasites is scarce. In this work, we describe that CD5 and CD6 -two lymphoid SRs previously reported to interact with conserved structures from bacteria, fungi and viruses- recognize tegumental components in the cestode parasite Echinococcus granulosus sensu lato (s.l.). Moreover, both receptors differentially modulate the cytokine release by host cells exposed to E. granulosus s.l. tegumental components. Importantly, the infusion of soluble forms of CD5 or CD6 improve infection outcomes in a murine model of secondary cystic echinococcosis. In summary, our results expand the pathogen binding properties of CD5 and CD6 and suggest their therapeutic potential against helminth infections

Conceptual design of a two stage to orbit spacecraft

This project, undertaken through the Advanced Space Design Program, developed a 'Conceptual Design of a Two Stage To Orbit Spacecraft (TSTO).' The design developed utilizes a combination of air breathing and rocket propulsion systems and is fully reusable, with horizontal takeoff and landing capability. The orbiter is carried in an aerodynamically designed bay in the aft section of the booster vehicle to the staging altitude. This TSTO Spacecraft design meets the requirements of replacing the aging Space Shuttle system with a more easily maintained vehicle with more flexible mission capability