Miracle-dz/UniFAR-FTUs huggingface dataset:
β‐Lactam pharmacokinetics and pharmacodynamics in critically ill patients and strategies for dose optimization: A structured review

Infections and related sepsis are two of the most prevalent issues in the care of critically ill patients, with mortality as high as 70%. Appropriate antibiotic selection, as well as adequate dosing, is important to improve the clinical outcome for these patients. β‐Lactams are the most common antibiotic class used in critically ill sepsis patients because of their broad spectrum of activity and high tolerability. β‐Lactams exhibit time‐dependent antibacterial activity. Therefore, concentrations need to be maintained above the minimum inhibitory concentration (MIC) of pathogenic bacteria. β‐Lactams are hydrophilic antibiotics with small distribution volumes similar to extracellular water and are predominantly excreted through the renal system. Critically ill patients experience a myriad of physiological changes that result in changes in the pharmacokinetics (PK) of hydrophilic drugs such as β‐lactams. A different approach to dosing with β‐lactams may increase the likelihood of positive outcomes considering the pharmacodynamics (PD) of β‐lactams, as well as the changes in PK in critically ill patients. The present review describes the strategies for dose optimization of β‐lactams in critically ill patients in line with the PK and PD of these drugs.
Neurological conditions and disability in adolescents

A number of neurological conditions can cause a wide range of functional impairments and disability in adolescents. Depending on the specific condition and neurological deficits, these can have significant implications for the normal progression of adolescent growth and development as well as social participation. Some of the major neurological conditions that can cause functional impairments and disability include epilepsy, traumatic brain injury, complications of infections, cerebrovascular accidents, brain neoplasms, neuromuscular diseases, neurodegenerative diseases, movement disorders, and various neurobehavioral disorders. The major functional domains affected include motor, sensory, cognitive, and psychosocial. Relevant aspects of epilepsy, Tourette syndrome, and cerebral palsy are reviewed briefly to highlight some these issues.
Maternal, paternal, & child predictors of externalizing behaviors: Parental externalizing, parenting behaviors, and child self-regulation

Maternal, Paternal, & Child Predictors of Externalizing Behaviors: Parental Externalizing, Parenting Behaviors and Child Self-Regulation Amber Fitzpatrick Predictors for externalizing behavior were investigated in a high-risk sample of males. Parental antisocial histories, parental behaviors and child self-regulation were considered in relation to boys’ externalizing problems during the transition to adolescence. Participants included 201 families (n = 105 with mom only data and n = 96 with dad and mom data). The males were between the ages of 10 and 12 from inner city Pittsburgh, Pennsylvania, and were part of a larger longitudinal study aimed at identifying risk factors for developing antisocial behavior. Multi-rater questionnaires were used to assess study constructs, along with observational measures of parental behaviors. There was no relationship between parental externalizing histories and subsequent child behaviors. There were significant contributions of parental antagonism and maternal regulatory support, as well as child self regulation and boys’ prior externalizing to their subsequent externalizing problems. Findings confirm that parents’ exacerbation was associated with elevations in children’s behavior problems, while the child’s self-regulatory system was linked to fewer behavior problems. Overall, prior externalizing is the best predictor of future externalizing difficulties above and beyond parenting behaviors and self-regulation. ACKNOWLEDGEMENTS I would like to thank my committee chair, Dr. Moilanen, for getting me through this challenging process. Without you this would not have come to fruition. I am grateful for your direction and patience as well as your insight into this study. I also want to extend a thank you to my remaining committee members for their participation, suggestions, and insight they shared with me in this journey. This all would not have been possible without my mother and my partner Tom; a special thanks also goes out to them for supporting my decision to take on this endeavor. And last but not least, the music of Pink Floyd and Bob Marley for their lyrical and rhythmical masterpieces that contributed to the creative atmosphere that helped me create this masterpiece.
Phosphatidylserine Externalization during CD95-induced Apoptosis of Cells and Cytoplasts Requires ICE/CED-3 Protease Activity*

Phosphatidylserine (PS), a lipid normally confined to the inner leaflet of the plasma membrane, is exported to the outer plasma membrane leaflet during apoptosis to serve as a trigger for recognition of apoptotic cells by phagocytes. The mechanism of PS export during apoptosis is not known nor is it clear whether the nuclear changes that typify apoptosis contribute in any way to this event. Here, we demonstrate that ligation of the CD95 (Fas/APO-1) molecule on Jurkat cytoplasts induces dramatic PS externalization similar to that observed during apoptosis of intact cells. Apoptosis of both cells and cytoplasts was associated with proteolytic processing of CPP32, a member of the interleukin-1β converting enzyme (ICE)/CED-3 protease family, to its active form. Fodrin, a component of the cortical cytoskeleton, also underwent proteolytic cleavage during apoptosis of both cytoplasts and intact cells. Strikingly, CPP32 activation, fodrin proteolysis, and PS externalization were all inhibited in the presence of peptide inhibitors of ICE/CED-3 family proteases. These data provide strong support for the notion that the cell death machinery is extranuclear and is likely to be comprised of one or more members of the ICE/CED-3 family and that activation of this machinery does not require nuclear participation.
Storing Shared Data on the Cloud via Security-Mediator

Nowadays, many organizations outsource data storage to the cloud such that a member (owner) of an organization can easily share data with other members (users). Due to the existence of security concerns in the cloud, both owners and users are suggested to verify the integrity of cloud data with Provable Data Possession (PDP) before further utilization on data. However, previous methods either unnecessarily reveal the identity of a data owner to the untrusted cloud or any public verifiers, or introduce significant overheads on verification metadata to preserve anonymity. In this paper, we propose a simple and efficient publicly verifiable approach to ensure cloud data integrity without sacrificing the anonymity of data owners nor requiring significant verification metadata. Specifically, we introduce a security-mediator (SEM), which is able to generate verification metadata (i.e., signatures) on outsourced data for data owners. Our approach decouples the anonymity protection mechanism from the PDP. Thus, an organization can employ its own anonymous authentication mechanism, and the cloud is oblivious to that since it only deals with typical PDP-metadata, Consequently, there is no extra storage overhead when compared with existing non-anonymous PDP solutions. The distinctive features of our scheme also include data privacy, such that the SEM does not learn anything about the data to be uploaded to the cloud at all, which is able to minimize the requirement of trust on the SEM. In addition, we can also extend our scheme to work with the multi-SEM model, which can avoid the potential single point of failure existing in the single-SEM scenario. Security analyses prove our scheme is secure, and experiment results demonstrate our scheme is efficient.
Enabling Confidentiality of Data Delivery in an Overlay Broadcasting System

Most prior work on the use of key management algorithms to enable confidentiality of video delivery has been conducted in the context of IP Multicast. In this paper, we consider the unique challenges and opportunities of integrating key management algorithms in an overlay multicast system. We conduct a systematic and extensive performance evaluation of strategies for key dissemination in the context of an operational overlay broadcasting system on the Planetlab testbed using real traces of join/leave dynamics. We show that leveraging TCP in each hop of the overlay dissemination structure can significantly simplify reliable key dissemination. The performance can be further enhanced if convergence properties of overlays are considered. We show that using two specialized dissemination structures, one for data and one for keys, potentially achieves low overhead for key dissemination without sacrificing application performance. To our knowledge, this is the first paper to study key management schemes in an overlay context using real implementation and Internet experiments and the first to consider issues in resilient key dissemination with overlays.
Racism in the Gay Community and Homophobia in the Black Community: Negotiating the Gay Black Male Experience

This research posed the question “How does racism in the gay community and homophobia in the Black community restrict gay Black male’s life chances and life opportunities? ” Previous research has uncovered racist attitudes within the lesbian, gay, bisexual, and transgender (LGBT) community as well as homophobic attitudes within the Black community. Because of conflicting social identifiers (Is it possible for one to be both homosexual and Black? ) and the invisibility of a gay Black voice, it is imperative to deconstruct the relationship between gay Black men and the communities they are a part of. I utilized qualitative in-depth interviewing techniques interviewing 15 Black men aged 18 and older who identified themselves as homosexual. The questions revolved around three primary questions designed to center the researcher.How do gay Black men describe their lives, How do gay Black men describe what their lives ought to be, and What obstacles do gay Black men see effecting their opportunity to live the lives they feel they ought to be living. The gay Black male research participants disclosed that because of Black stereotypes, gay stereotypes, acceptance with stipulations in the gay community and the black community, racism in the gay community, homophobia in the Black community, and perceptions of blackness and masculinity’s affect on gay Black men.gay Black men live their lives with various restrictions. In other words, gay Black men do not appear to be living their lives the way they feel they ought to be living it. This work is important because a majority of the participants stated they wished to live restriction free lives. They are not able to fully be themselves in their daily lives and often have to assimilate to be accepted.
Oral Administration of Lactobacillus plantarum Strain AYA Enhances IgA Secretion and Provides Survival Protection against Influenza Virus Infection in Mice

The mucosal immune system provides the first line of defense against inhaled and ingested pathogenic microbacteria and viruses. This defense system, to a large extent, is mediated by the actions of secretory IgA. In this study, we screened 140 strains of lactic acid bacteria for induction of IgA production by murine Peyer’s patch cells. We selected one strain and named it Lactobacillus plantarum AYA. We found that L. plantarum AYA-induced production of IL-6 in Peyer’s patch dendritic cells, with this production promoting IgA+ B cells to differentiate into IgA-secreting plasma cells. We also observed that oral administration of L. plantarum AYA in mice caused an increase in IgA production in the small intestine and lung. This production of IgA correlated strongly with protective ability, with the treated mice surviving longer than the control mice after lethal influenza virus infection. Our data therefore reveals a novel immunoregulatory role of the L. plantarum AYA strain which enhances mucosal IgA production and provides protection against respiratory influenza virus infection.
Accelerating drug discovery Although the evolution of ‘-omics ’ methodologies is still in its infancy , both the pharmaceutical industry and patients could benefit from their implementation in the drug development process

Drug development, from initial discovery of a promising target to the final medication, is an expensive, lengthy and incremental process. The ultimate goal is to identify a molecule with the desired effect in the human body and to establish its quality, safety and efficacy for treating patients. The latter requirements ensure that the approved medication improves patients’ quality of life, not only by curing their illness, but also by making sure that the cure does not become the cause of other problems, namely side effects (Snodin, 2002). It also means that this is a particularly costly and prolonged process. At present, bringing a single new drug to market costs around US$800 million, an amount that doubles every five years. According to the US Food and Drug Administration (FDA), it takes, on average, 12 years for an experimental drug to progress from bench to market. Annually, the North American and European pharmaceutical industries invest more than US$20 billion to identify and develop new drugs, about 22% of which is spent on screening assays and toxicity testing (Michelson & Joho, 2000). In addition to costs, administrative hurdles have become problematic, which contributes to the high failure rate of new drug candidates. Of 5,000 compounds that enter pre-clinical testing, only five, on average, are tested in human trials, and only one of these five receives approval for therapeutic use (Fig 1). It is not surprising that, while development costs have increased, the absolute number of newly approved drugs has constantly decreased for several years. These trends—increasing costs for drug development and testing and greater scrutiny of the approval process— create a growing problem both for the drug industry and for patients who are desperately waiting for new drugs to treat their illnesses. It is therefore timely to consider how new technologies, namely functional genomics, proteomics and the related field of toxicogenomics, can help to speed up drug development and make it more efficient. The current process of identifying a new drug and bringing it to market involves several lengthy steps (Fig 2). It starts with the synthesis of small molecules to target specific proteins or enzymatic activities in living cells. The next step is to identify those compounds that have the best chance of survival in clinical trials. These drug candidates are then subjected to a battery of in vitro tests to investigate potential classand compound-specific toxicity; it is in these early stages that most candidates fail. Compounds that make it through this stage are then subjected to acute and short-term in vivo toxicology studies. All information gathered in these preclinical stages is then used as a guide for subsequent clinical trials in human volunteers and patients. It is on these pre-clinical and clinical tests that new technologies could have the largest impact.
Staphylococcal SSL5 Binding to Human Leukemia Cells Inhibits Cell Adhesion to Endothelial Cells and Platelets

Bacterial proteins provide promising tools for novel anticancer therapies. Staphylococcal superantigen-like 5 (SSL5) was recently described to bind P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes and to inhibit neutrophil rolling on a P-selectin surface. As leukocytes and tumor cells share many characteristics in migration and dissemination, we explored the potential of SSL5 as an antagonist of malignant cell behavior. Previously, it was demonstrated that rolling of human HL-60 leukemia cells on activated endothelial cells was mediated by P-selectin. In this study, we show that SSL5 targets HL-60 cells. Binding of SSL5 was rapid and without observed toxicity. Competition of SSL5 with the binding of three anti-PSGL-1 antibodies and P-selectin to HL-60 cells identified PSGL-1 as the ligand on HL-60 cells. Presence of sialyl Lewis x epitopes on PSGL-1 was crucial for its interaction with SSL5. Importantly, SSL5 not only inhibited the interaction of HL-60 cells with activated endothelial cells but also with platelets, which both play an important role in growth and metastasis of cancers. These data support the concept that SSL5 could be a lead in the search for novel strategies against hematological malignancies.
Application of multiple model adaptive control to upper limb stroke rehabilitation

Impaired arm function has a significant impact on the quality of life of stroke sufferers. Research has shown that the application of functional electrical stimulation (FES) to assist their movement over repeated attempts at a task is effective in restoring function. However, current FES control systems lack robustness to changes in plant dynamics caused by fatigue and spasticity. This paper details the application of a multiple model adaptive control algorithm that has the potential to overcome this problem. It is shown in an experimental setting that an adaptive estimation mechanism is able to detect changes in the true plant through optimal disturbance estimation. Finally, the performance of the algorithm is compared with that of fixed optimal controllers. These initial results suggest that the application of estimation-based multiple model switched adaptive control (EMMSAC) can increase the potential of FES-based rehabilitation through improved controller accuracy.
Inhibition of the intestinal glucose transporter GLUT2 by flavonoids

We tested whether the dominant intestinal sugar transporter GLUT2 was inhibited by intestinal luminal compounds that are inefficiently absorbed and naturally present in foods. Because of their abundance in fruits and vegetables, flavonoids were selected as model compounds. Robust inhibition of glucose and fructose transport by GLUT2 expressed in Xenopus laevis oocytes was produced by the flavonols myricetin, fisetin, the widely consumed flavonoid quercetin, and its glucoside precursor isoquercitrin. IC50s for quercetin, myricetin, and isoquercitrin were ∼200‐ to 1000‐fold less than glucose or fructose concentrations, and noncompetitive inhibition was observed. The two other major intestinal sugar transporters, GLUT5 and SGLT1, were unaffected by flavonoids. Sugar transport by GLUT2 overexpressed in pituitary cells and naturally present in Caco‐2E intestinal cells was similarly inhibited by quercetin. GLUT2 was detected on the apical side of Caco‐2E cells, indicating that GLUT2 was in the correct orientation to be inhibited by luminal compounds. Quercetin itself was not transported by the three major intestinal glucose transporters. Because the flavonoid quercetin, a food component with an excellent pharmacology safety profile, might act as a potent luminal inhibitor of sugar absorption independent of its own transport, flavonols show promise as new pharmacologic agents in the obesity epidemic. —Kwon, O. , Eck, P., Chen, S. , Corpe, C. P., Lee, J‐H. , Kruhlak, M. , Levine, M. Inhibition of the intestinal glucose transporter GLUT2 by flavonoids. FASEB J. 21, 366–377 (2007)
Panoramic Audio and Video: Towards an Immersive Learning Experience

Historically, learning has been seen as part of the human process to achieve a status, income and a better future. Traditionally students travel to attend lectures or participate in brainstorming and training sessions benefiting from the interaction afforded by the physical learning environment, the classroom, and the wider University facilities. However, financial pressures arising from national and global competition are putting pressure on Universities to find more cost-effective ways of delivering education. While distant learning has been always there, it is clear that this approach needs substantial improvements in order to deliver a similar learning experience to physically attending a university. To these end, this paper presents a novel immersive telepresence system that allows remote or distant students to customize their virtual presence at seminars and lectures based on a 360° panoramic video projected onto a 180° curved projected screen (an immersive shell). Audio is also collected with 3D information in order to be reproduced more naturally at the remote location. The arrangement is intended to provide online learners with a more faithful replication of human perception, akin to what they would experience in a real learning environment. Technically, to do this we use a 360° mirror to capture the lecture room scene and transmit it to remote locations where it is reconstructed the original image from spherical to Cartesian coordinates providing a novel but natural immersive experience. This paper describes the motivation, model, computational architecture and our main findings.
The Pre-Tenure Years: Survive, Succeed, and Thrive

Pre-tenure faculty members often find it stressful and difficult to determine the best path to academic success in their new institution. This article offers an assessment, advice, and a perspective on the early stages of an academic career. Although there are variations in the types of institutions, programs, and departments, there are also similarities. Academic administrators and colleagues may be somewhat vague in their description of the expectations that they have for new hires. Nonetheless, engaging in research and publishing, good teaching, and relevant service are important. While sensitivity to the environment can help junior faculty develop an appropriate strategy, a commitment to research is essential.
Antidepressant-Like Effect of Ilex paraguariensis in Rats

In this study, we investigated the possible antidepressant-like effect of I. paraguariensis in rats. Rats were treated for four weeks with an aqueous extract of I. paraguariensis in drinking water, following the traditional preparation of this beverage. After the period of treatment, behavioral (elevated plus-maze, open field test, and forced swimming test) and biochemical parameters (lipid peroxidation assay, thiol content, vitamin C levels, and monoamine oxidase activity) were evaluated. Animals were also analyzed on forced swimming test after 24 hours of I. paraguariensis intake. An additional group was injected with selegiline 24 hours and 30 minutes before forced swimming test as positive control. HPLC analysis revealed the profile of I. paraguariensis extract. I. paraguariensis reduced the immobility time on forced swimming test without significant changes in locomotor activity in the open field test. Any anxiolytic/anxiogenic effect of I. paraguariensis was observed in rats through the elevated plus-maze test. The antidepressant-like effect of I. paraguariensis was not accompanied by inhibitory effect on monoamine oxidase activity. There were no significant alterations on lipid peroxidation, thiol content, and vitamin C levels among the groups. In conclusion, aqueous extract of I. paraguariensis decreases the time of immobility in rats suggesting an antidepressant-like effect.