Mapping the Alzheimer’s Brain with Connectomics

Alzheimer’s disease (AD) is the most common form of dementia. As an incurable, progressive, and neurodegenerative disease, it causes cognitive and memory deficits. However, the biological mechanisms underlying the disease are not thoroughly understood. In recent years, non-invasive neuroimaging and neurophysiological techniques [e.g., structural magnetic resonance imaging (MRI), diffusion MRI, functional MRI, and EEG/MEG] and graph theory based network analysis have provided a new perspective on structural and functional connectivity patterns of the human brain (i.e., the human connectome) in health and disease. Using these powerful approaches, several recent studies of patients with AD exhibited abnormal topological organization in both global and regional properties of neuronal networks, indicating that AD not only affects specific brain regions, but also alters the structural and functional associations between distinct brain regions. Specifically, disruptive organization in the whole-brain networks in AD is involved in the loss of small-world characters and the re-organization of hub distributions. These aberrant neuronal connectivity patterns were associated with cognitive deficits in patients with AD, even with genetic factors in healthy aging. These studies provide empirical evidence to support the existence of an aberrant connectome of AD. In this review we will summarize recent advances discovered in large-scale brain network studies of AD, mainly focusing on graph theoretical analysis of brain connectivity abnormalities. These studies provide novel insights into the pathophysiological mechanisms of AD and could be helpful in developing imaging biomarkers for disease diagnosis and monitoring

Escherichia coli K1 RS218 Interacts with Human Brain Microvascular Endothelial Cells via Type 1 Fimbria Bacteria in the Fimbriated State

Escherichia coli K1 is a major gram-negative organism causing neonatal meningitis. E. coli K1 binding to and invasion of human brain microvascular endothelial cells (HBMEC) are a prerequisite for E. coli penetration into the central nervous system in vivo. In the present study, we showed using DNA microarray analysis that E. coli K1 associated with HBMEC expressed significantly higher levels of the fim genes compared to nonassociated bacteria. We also showed that E. coli K1 binding to and invasion of HBMEC were significantly decreased with its fimH deletion mutant and type 1 fimbria locked-off mutant, while they were significantly increased with its type 1 fimbria locked-on mutant. E. coli K1 strains associated with HBMEC were predominantly type 1 fimbria phase-on (i.e., fimbriated) bacteria. Taken together, we showed for the first time that type 1 fimbriae play an important role in E. coli K1 binding to and invasion of HBMEC and that type 1 fimbria phase-on E. coli is the major population interacting with HBMEC

EPOCA House: The Implementation Strategy

This capstone report provides a written strategic implementation plan for EPOCA House. EPOCA, Ex-Prisoners and Prisoners Organizing for Community Advancement, is a non-profit dedicated to creating better resources and opportunities for prisoners and ex-prisoners in Worcester. The organization’s most recent initiative, EPOCA House, is a transitional facility that will provide reentry services and temporary housing to ex-offenders in and around the Worcester area. Recently, Massachusetts passed a comprehensive criminal justice reform bill that will dramatically reduce the number of people being incarcerated; however, little attention is focused on what will happen to individuals after they leave prison. At the same time, funding for halfway houses and reentry programs have decreased across the country and there are very few adequate services offered for ex-offenders in the city. To address this need, Yoshada Kwaning, the Community Outreach Director at EPOCA came up with the idea for EPOCA House Inc. While EPOCA staff members have extensive knowledge about the needs of prison population, they lacked the time and resources to create a strategic action plan to implement their vision. This report employs a secondary data analysis methodology to compare ex-prisoner reentry programs across four specialization areas: education programming, vocational training, wellness programs, and sustainability initiatives. This report also draws on advice from experts and local practitioners in the field, who provide valuable insight into criminal justice issues in Worcester. Transcripts of these interviews can be found in the appendices

Control of astrocyte progenitor specification, migration and maturation by Nkx6.1 homeodomain transcription factor.

Although astrocytes are the most abundant cell type in the central nervous system (CNS), little is known about their molecular specification and differentiation. It has previously been reported that transcription factor Nkx6.1 is expressed in neuroepithelial cells that give rise to astrocyte precursors in the ventral spinal cord. In the present study, we systematically investigated the function of Nkx6.1 in astrocyte development using both conventional and conditional Nkx6.1 mutant mice. At early postnatal stages, Nkx6.1 was expressed in a subpopulation of astrocytes in the ventral spinal cord. In the conventional Nkx6.1KO spinal cord, the initial specification of astrocyte progenitors was affected by the mutation, and subsequent migration and differentiation were disrupted in newborn mice. In addition, the development of VA2 subtype astrocytes was also inhibited in the white matter. Further studies with Nkx6.1 conditional mutants revealed significantly delayed differentiation and disorganized arrangement of fibrous astrocytes in the ventral white matter. Together, our studies indicate that Nkx6.1 plays a vital role in astrocyte specification and differentiation in the ventral spinal cord

A Cyber-Secured Operation for Water-Energy Nexus

The wide implementation of information and communication technologies (ICT) cause power system operations exposed to cyber-attacks. Meanwhile, the tendency of integrated multi energy vectors has worsened this issue with multiple energy coupled. This paper proposes a two-stage risk-averse mitigation strategy for water-energy systems (WESs), incorporating power, natural gas and water systems against false data injection attacks (FDIA) under water-energy nexus. The FDIA on individual sub-systems is modelled through hampering false data integrity to the systems. An innovative two-stage risk-averse distributionally robust optimization (RA-DRO) is proposed to mitigate uneconomic operation and provides a coordinated optimal load shedding scheme for the nexus system security. A coherent risk measure, Conditional Value-at-Risk is incorporated into the RA-DRO to model risk. A Benders decomposition method is used to solve the original NP-hard RA-DRO problem. Case studies are demonstrated on a WES under water-energy nexus and results show that the effectiveness of the method to mitigate risks from potential FDIA and renewable uncertainties. This research provides WES operators an economic system operation tool by optimally coordinating energy infrastructures and implementing reasonable load shedding to enhance cybersecurity

Bis(chloro­acetato-κ2 O,O′)bis­(2-fluoro­benzyl-κC 1)tin(IV)

In the title complex, [Sn(C2H2ClO2)2(C7H6F)2], the SnIV atom is located on a twofold rotation axis and forms a strongly distorted trans-octa­hedral geometry. The equatorial plane is defined by two chelating chloro­acetate ligands with asymmetrical Sn—O bond lengths, while the axial positions are occupied by the C atoms of two 2-fluoro­benzyl groups. In the crystal, infinite chains in the [010] direction are formed through inter­molecular Sn⋯O inter­actions [Sn⋯O separation = 3.682 (3) Å]

A Cyber-Secured Operation for Water-Energy Nexus

The wide implementation of information and communication technologies (ICT) cause power system operations exposed to cyber-attacks. Meanwhile, the tendency of integrated multi energy vectors has worsened this issue with multiple energy coupled. This paper proposes a two-stage risk-averse mitigation strategy for water-energy systems (WESs), incorporating power, natural gas and water systems against false data injection attacks (FDIA) under water-energy nexus. The FDIA on individual sub-systems is modelled through hampering false data integrity to the systems. An innovative two-stage risk-averse distributionally robust optimization (RA-DRO) is proposed to mitigate uneconomic operation and provides a coordinated optimal load shedding scheme for the nexus system security. A coherent risk measure, Conditional Value-at-Risk is incorporated into the RA-DRO to model risk. A Benders decomposition method is used to solve the original NP-hard RA-DRO problem. Case studies are demonstrated on a WES under water-energy nexus and results show that the effectiveness of the method to mitigate risks from potential FDIA and renewable uncertainties. This research provides WES operators an economic system operation tool by optimally coordinating energy infrastructures and implementing reasonable load shedding to enhance cybersecurity