Novel Neuroprotective Agents to Treat Neonatal Hypoxic-Ischemic Encephalopathy: Inter-Alpha Inhibitor Proteins

Perinatal hypoxia-ischemia (HI) is a major cause of brain injury and mortality in neonates. Hypoxic-ischemic encephalopathy (HIE) predisposes infants to long-term cognitive deficits that influence their quality of life and place a large burden on society. The only approved treatment to protect the brain after HI is therapeutic hypothermia, which has limited effectiveness, a narrow therapeutic time window, and is not considered safe for treatment of premature infants. Alternative or adjunctive therapies are needed to improve outcomes of full-term and premature infants after exposure to HI. Inter-alpha inhibitor proteins (IAIPs) are immunomodulatory molecules that are proposed to limit the progression of neonatal inflammatory conditions, such as sepsis. Inflammation exacerbates neonatal HIE and suggests that IAIPs could attenuate HI-related brain injury and improve cognitive outcomes associated with HIE. Recent studies have shown that intraperitoneal treatment with IAIPs can decrease neuronal and non-neuronal cell death, attenuate glial responses and leukocyte invasion, and provide long-term behavioral benefits in neonatal rat models of HI-related brain injury. The present review summarizes these findings and outlines the remaining experimental analyses necessary to determine the clinical applicability of this promising neuroprotective treatment for neonatal HI-related brain injury.     

Structure of a 16 kDa integral membrane protein that has identity to the putative proton channel of the vacuolar H+-ATPase

A 16 kDa protein has been isolated in a homogeneous form asthe major component of a paracrystalline paired membrane structureclosely resembling the gap junction. The primary structure ofthis protein from arthropod and vertebrate species has beendetermined by protein and cDNA sequencing. The amino acid sequencesare highly conserved and virtually identical to the amino acidsequence of the proteolipid subunit of the vacuolar H⁺-ATPases.The disposition of the protein in the membrane has been studiedusing proteases and the N,N'-dicyclohexylcarbodiimide reactivesite identified. These data, together with secondary structurepredictions, suggest that the 16 kDa protein is for the mostpart buried in the membrane, arranged in a bundle of four hydrophobicß-helices. Using computer graphics, a model has beenconstructed based on this arrangement and on the electron microscopicimages of the paracrystalline arrays     

Video-assisted thoracoscopic surgery for pneumothorax

A 28-year-old Japanese woman who suffered from mononeuritis multiplex was admitted to our hospital. Serological study revealed cryoglobulinemia (type III), hypocomplementemia, high titers of rheumatoid factor (RF), and positive antihepatitis C virus (HCV) antibody. Nerve conduction velocities were slower in sensory nerves than in motor nerves. Biopsied sural nerve showed a marked decrease of myelinated fibers but no evidence of angitis. She received plasma exchange and cryoglobulinpheresis over a period of 2 months with approximately 2.0 L (40 ml/kg) of plasma replaced in each procedure. Both plasma exchange and cryoglobulinpheresis alleviated clinical symptoms, and nerve conduction velocities were improved in several nerves. The serum cryoglobulin level was markedly reduced after the treatment together with the recovery of the C4 level. Thus, complements appeared to be consumed in large quantities in the presence of cryoglobulinemia in this patient. Efficacy of cryoglobulinpheresis indicates the possibility that cryoglobulins produced in association with HCV infection played a role in damaging the nerve directly through the activation of the complement system.     

A pilgrim's progress: From cognitive science to cooperative design

This paper provides a glimpse of some different theoretical frameworks and empirical methods in the author's search for theories and practices that might improve the utility and usability of computer artifacts. The essay touches on some problematic aspects of currently accepted theories and techniques in the cognitive sciences, especially in their application to the field of human-computer interaction, and mentions some alternative conceptions based on a cultural-historical approach. The intent is to widen the nature of the debate about appropriate frameworks for discussing human activities especially when we discuss design activities in the context of computer systems development. The paper concludes with some suggestions for more fruitful research directions that involve the active participation of those for whom the research is ostensibly being done, and a greater emphasis on understanding how artifact design and use are inextricably intertwined.This paper originated from a talk entitled From Cognitive Science to Cooperative Design that later appeared in rough paper form in Finnemann, N. O. (Ed.) Proceedings from the Symposium Theories and Technologies of the Information Society (Centre for Cultural Research, Aarhus University, Denmark, Sept. 1989). Some of the ideas and material in the present paper first appeared in Bannon & Bødker (in press) and Bannon (in press).     

Planetary LakeLander—A Robotic Sentinel to Monitor Remote Lakes

This field report describes the design and operations of the Planetary LakeLander (PLL) probe and its ground data systems. LakeLander's primary mission is to characterize the physical, chemical, and biological processes occurring in a high‐altitude lake, and how they are being impacted by rapid deglaciation. LakeLander's secondary purpose is to test operation concepts for future exploration of Titan's lakes. The LakeLander probe is a permanently anchored buoy that measures both surface meteorology and water quality parameters in the top 40 m of the water column. The concept of operations calls for the probe to continue collecting and downlinking data through the Andean winter, when the lake is inaccessible; this drives the power system design and forces a strong focus on system reliability, analogous to a space mission. The PLL ground data system provides the central archive of downlinked data. They are structured around a unified data‐sharing web site that includes tools for mapping, data visualization, documentation, and numerical analysis. The web site provides a hub for engaging the science team and enables interdisciplinary collaboration. This report concludes with lessons learned during field deployment and several months of remote operations on the lake. Among the conclusions: (1) the choice to use an off‐the‐shelf profiling system has proven wise; (2) effective maintenance of a long‐lived remote system requires extensive measurement, logging, and display of as many system variables as possible; and (3) the visualization sandbox component of the data‐sharing web site has made numerical analysis of probe data much easier and more accessible to the entire interdisciplinary science team.     

Cement Formulations in the Calcium Phosphate H2O–H3PO4–H4P2O7 System

Despite numerous reports of calcium phosphate cement materials, a calcium cement that sets to form a matrix consisting of a pyrophosphate phase has not been reported. The formulation of such a material from the mixture of α-tricalcium phosphate (TCP), β-TCP, or tetracalcium phosphate with a solution containing pyro- and orthophosphoric acid is reported in this study. The effects of liquid and solid compositions on the setting times, compressive strengths and phase compositions of the resultant cements were investigated. It was found that cements could be produced that set to form up to 28 wt% dicalcium pyrophosphate, which appeared by comparison with Rietveld refinement and chemical methods to be entirely amorphous in nature. The solubilities of the different solid components were shown to have a marked effect on the composition of the cements. The strongest cement formulations exhibited compressive strengths comparable with those previously reported in the literature for brushite cements and set within clinically relevant time scales. This class of cement would appear to demonstrate potential as a bone replacement material.     

A fuzzy-decision-tree approach for manufacturing technology selection exploiting experience-based information

Manufacturing technology selection is traditionally a human-driven approach where the trade-off of alternative manufacturing investments is steered by a group of experts. The problem is a semi-structured and subjective-based decision practice influenced by the experience and intuitive feeling of the decision-makers involved. This paper presents a distinct experience-based decision support system that uses factual information of historical decisions to calculate confidence factors for the successful adoption of potential technologies for a given set of requirements. A fuzzy-decision-tree algorithm is applied to provide a more objective approach given the evidence of previous manufacturing technology implementation cases. The model uses the information relationship of key technology decision variables, project requirements of an implemented technology case and the success outcome of a project to support decision problems. An empirical study was conducted at an aircraft manufacturer to support their technology decision for a typical medium complexity assembly investment project. The experimental analysis demonstrated encouraging results and practical viability of the approach.     

Mobile agent approach to networked robots

Mobile agents provide the functionality of all other distributed computing paradigms in a unified environment and enables a natural design philosophy for distributed computing systems. These properties can provide multiple-robot system developers with a wide range of options for initial development and future extension of their systems, and an intuitive and robust design environment. In this paper, we present two examples to show how, by taking advantage of these properties, the adaptability and fault-tolerance of a multiple-robot architecture (the ALLIANCE architecture) can be extended in multiple networked robots.     

Acute Hypoxia Alters Extracellular Vesicle Signatures and the Brain Citrullinome of Naked Mole-Rats (Heterocephalus glaber)

Peptidylarginine deiminases (PADs) and extracellular vesicles (EVs) may be indicative biomarkers of physiological and pathological status and adaptive responses, including to diseases and disorders of the central nervous system (CNS) and related to hypoxia. While these markers have been studied in hypoxia-intolerant mammals, in vivo investigations in hypoxia-tolerant species are lacking. Naked mole-rats (NMR) are among the most hypoxia-tolerant mammals and are thus a good model organism for understanding natural and beneficial adaptations to hypoxia. Thus, we aimed to reveal CNS related roles for PADs in hypoxia tolerance and identify whether circulating EV signatures may reveal a fingerprint for adaptive whole-body hypoxia responses in this species. We found that following in vivo acute hypoxia, NMR: (1) plasma-EVs were remodelled, (2) whole proteome EV cargo contained more protein hits (including citrullinated proteins) and a higher number of associated KEGG pathways relating to the total proteome of plasma-EVs Also, (3) brains had a trend for elevation in PAD1, PAD3 and PAD6 protein expression, while PAD2 and PAD4 were reduced, while (4) the brain citrullinome had a considerable increase in deiminated protein hits with hypoxia (1222 vs. 852 hits in normoxia). Our findings indicate that circulating EV signatures are modified and proteomic content is reduced in hypoxic conditions in naked mole-rats, including the circulating EV citrullinome, while the brain citrullinome is elevated and modulated in response to hypoxia. This was further reflected in elevation of some PADs in the brain tissue following acute hypoxia treatment. These findings indicate a possible selective role for PAD-isozymes in hypoxia response and tolerance.     

Machine Learning‐Enabled Correlation and Modeling of Multimodal Response of Thin Film to Environment on Macro and Nanoscale Using “Lab‐on‐a‐Crystal”

To close the feedback loop between artificial intellegence‐controlled materials synthesis and characterization, material functionality must be rapidly tested. A platform for high‐throughput multifunctional materials characterization is developed using a quartz crystal microbalance with auxiliary in‐plane electrodes and a custom gas/vapor flow cell, enabling simultaneous scanning probe microscopy and electrical, optical, gravimetric, and viscoelastic characterization on the same film under controlled environment. The lab‐on‐a‐crystal in situ multifunctional output allows direct correlations between the gravimetric/viscoelastic, electrical, and optical responses of polymer film in response to environment. When multiple film properties are used to augment the training set for machine learning regression, prediction of material response to the environment improves by a factor of 13 when <5% of the total dataset is used for model training.