Multi-Layer Cyber-Physical Security and Resilience for Smart Grid

The smart grid is a large-scale complex system that integrates communication technologies with the physical layer operation of the energy systems. Security and resilience mechanisms by design are important to provide guarantee operations for the system. This chapter provides a layered perspective of the smart grid security and discusses game and decision theory as a tool to model the interactions among system components and the interaction between attackers and the system. We discuss game-theoretic applications and challenges in the design of cross-layer robust and resilient controller, secure network routing protocol at the data communication and networking layers, and the challenges of the information security at the management layer of the grid. The chapter will discuss the future directions of using game-theoretic tools in addressing multi-layer security issues in the smart grid.Comment: 16 page

Phencyclidine Disrupts the Auditory Steady State Response in Rats

The Auditory Steady-State Response (ASSR) in the electroencephalogram (EEG) is usually reduced in schizophrenia (SZ), particularly to 40 Hz stimulation. The gamma frequency ASSR deficit has been attributed to N-methyl-D-aspartate receptor (NMDAR) hypofunction. We tested whether the NMDAR antagonist, phencyclidine (PCP), produced similar ASSR deficits in rats. EEG was recorded from awake rats via intracranial electrodes overlaying the auditory cortex and at the vertex of the skull. ASSRs to click trains were recorded at 10, 20, 30, 40, 50, and 55 Hz and measured by ASSR Mean Power (MP) and Phase Locking Factor (PLF). In Experiment 1, the effect of different subcutaneous doses of PCP (1.0, 2.5 and 4.0 mg/kg) on the ASSR in 12 rats was assessed. In Experiment 2, ASSRs were compared in PCP treated rats and control rats at baseline, after acute injection (5 mg/kg), following two weeks of subchronic, continuous administration (5 mg/kg/day), and one week after drug cessation. Acute administration of PCP increased PLF and MP at frequencies of stimulation below 50 Hz, and decreased responses at higher frequencies at the auditory cortex site. Acute administration had a less pronounced effect at the vertex site, with a reduction of either PLF or MP observed at frequencies above 20 Hz. Acute effects increased in magnitude with higher doses of PCP. Consistent effects were not observed after subchronic PCP administration. These data indicate that acute administration of PCP, a NMDAR antagonist, produces an increase in ASSR synchrony and power at low frequencies of stimulation and a reduction of high frequency (> 40 Hz) ASSR activity in rats. Subchronic, continuous administration of PCP, on the other hand, has little impact on ASSRs. Thus, while ASSRs are highly sensitive to NMDAR antagonists, their translational utility as a cross-species biomarker for NMDAR hypofunction in SZ and other disorders may be dependent on dose and schedule

Label-free electrochemical monitoring of DNA ligase activity

This study presents a simple, label-free electrochemical technique for the monitoring of DNA ligase activity. DNA ligases are enzymes that catalyze joining of breaks in the backbone of DNA and are of significant scientific interest due to their essential nature in DNA metabolism and their importance to a range of molecular biological methodologies. The electrochemical behavior of DNA at mercury and some amalgam electrodes is strongly influenced by its backbone structure, allowing a perfect discrimination between DNA molecules containing or lacking free ends. This variation in electrochemical behavior has been utilized previously for a sensitive detection of DNA damage involving the sugar-phosphate backbone breakage. Here we show that the same principle can be utilized for monitoring of a reverse process, i.e., the repair of strand breaks by action of the DNA ligases. We demonstrate applications of the electrochemical technique for a distinction between ligatable and unligatable breaks in plasmid DNA using T4 DNA ligase, as well as for studies of the DNA backbone-joining activity in recombinant fragments of E. coli DNA ligase

BRIT1/MCPH1 links chromatin remodelling to DNA damage response

To detect and repair damaged DNA, DNA damage response proteins need to overcome the barrier of condensed chromatin to gain access to DNA lesions1. ATP-dependent chromatin remodeling is one of the fundamental mechanisms used by cells to relax chromatin in DNA repair2–3. However, the mechanism mediating their recruitment to DNA lesions remains largely unknown. BRIT1 (also known as MCPH1) is an early DNA damage response protein that is mutated in human primary microcephaly4–8. We report here a previously unknown function of BRIT1 as a regulator of ATP-dependent chromatin remodeling complex SWI/SNF in DNA repair. Upon DNA damage, BRIT1 increases its interaction with SWI/SNF through the ATM/ATR-dependent phosphorylation on the BAF170 subunit. This increase of binding affinity provides a means by which SWI/SNF can be specifically recruited to and maintained at DNA lesions. Loss of BRIT1 causes impaired chromatin relaxation owing to reduced association of SWI/SNF with chromatin. This explains the decreased recruitment of repair proteins to DNA lesions and reduced efficiency of repair in BRIT1-deficient cells, resulting in impaired survival from DNA damage. Our findings, therefore, identify BRIT1 as a key molecule that links chromatin remodeling with DNA damage response in the control of DNA repair, and its dysfunction contributes to human disease

Dna2 in chromosome stability and cell survival—is it all about replication forks?

The conserved nuclease-helicase DNA2 has been linked to mitochondrial myopathy, Seckel syndrome, and cancer. Across species, the protein is indispensable for cell proliferation. On the molecular level, DNA2 has been implicated in DNA double-strand break (DSB) repair, checkpoint activation, Okazaki fragment processing (OFP), and telomere homeostasis. More recently, a critical contribution of DNA2 to the replication stress response and recovery of stalled DNA replication forks (RFs) has emerged. Here, we review the available functional and phenotypic data and propose that the major cellular defects associated with DNA2 dysfunction, and the links that exist with human disease, can be rationalized through the fundamental importance of DNA2-dependent RF recovery to genome duplication. Being a crucial player at stalled RFs, DNA2 is a promising target for anti-cancer therapy aimed at eliminating cancer cells by replication-stress overload

Rif1 S-acylation mediates DNA double-strand break repair at the inner nuclear membrane

Rif1 is involved in telomere homeostasis, DNA replication timing, and DNA double-strand break (DSB) repair pathway choice from yeast to human. The molecular mechanisms that enable Rif1 to fulfill its diverse roles remain to be determined. Here, we demonstrate that Rif1 is S-acylated within its conserved N-terminal domain at cysteine residues C466 and C473 by the DHHC family palmitoyl acyltransferase Pfa4. Rif1 S-acylation facilitates the accumulation of Rif1 at DSBs, the attenuation of DNA end-resection, and DSB repair by non-homologous end-joining (NHEJ). These findings identify S-acylation as a posttranslational modification regulating DNA repair. S-acylated Rif1 mounts a localized DNA-damage response proximal to the inner nuclear membrane, revealing a mechanism of compartmentalized DSB repair pathway choice by sequestration of a fatty acylated repair factor at the inner nuclear membrane

Myoglobin Unfolding and Protein Stability With TMG

Myoglobin, a widely studied protein in biophysics, is a small, helical, and highly soluble protein that has been investigated for decades. Its heme prosthetic group facilitates easy analysis of its folding state through absorbance spectroscopy. Ionic liquids (ILs), particularly room-temperature ionic liquids or molten salts, have gained significant attention in the past 15- 20 years for their potential use in electrochemical devices. Recently, their biocompatibility has become a focal point in research, given that certain IL species can either stabilize or destabilize biomolecular structures. This study employs absorbance and fluorescence spectroscopy to examine how amino acid-based ILs, specifically tetramethyl guanidine and choline as cations and serine, aspartic acid, and proline as anions, impact the unfolding of myoglobin. These amino acids were chosen based on previous findings indicating their varying effects on the protein azurin. The study evaluates the individual impacts of these amino acids and their collective ability to destabilize lysozyme when denatured with guanidinium HCl, monitored through absorbance spectroscopy and fluorescence signals from the heme group, Trp fluorescence, and Trp-heme interactions

Historical perspectives on pastoralism and land tenure transformation in Ngamiland, Botswana: What are the policy and institutional lessons?

Pastoral societies in dryland Africa continue to face changes to their pastoral systems. These systems are influenced by a range of historical factors but little use is made of this information to design policies that suit pastoralists’ landscapes. This article provides a synthesis of historical perspectives on pastoral land use and tenure transformations in Ngamiland, south of the Okavango Delta, Botswana. Little documentation of herders’ historical perspectives exists and less is known about how past experiences can be applied to sustainable pastoralism policies. In this article, current land use pressing issues are examined and analysed within the context of past experiences. We use a series of oral histories with key informants, focus group discussions, expert interviews and rangelands field observations. Ngamiland historical perspectives depict a pastoral landscape that has been shaped by a variety of factors; livestock diseases, Human-wildlife-conflicts, droughts, land tenure transformations associated with rangeland policies and the pastoral identity of the Ovaherero/Ovambanderu ethnic groups. Pastoralists have followed unique trajectories, specific to their rangeland conditions and socio-cultural context. Resilience to climate shocks and diseases has been weakened by inequitable patterns of control over rangeland resources. We recommend institutional diversity such that from experiences of the past, lessons can be drawn of the sort of processes and institutions required for pastoralism policies including targeted pastoralists’ adaptations. Using pastoralists to provide information, especially in the area of indigenous knowledge, strategies can be developed to link conservation of wildlife and rangelands with pastoral production by developing ecologically-sensitive low-volume tourism that pastoral communities can tap in to diversify their livelihoods

The genesis of cerebellar interneurons and the prevention of neural DNA damage require XRCC1

Defective responses to DNA single strand breaks underlie various neurodegenerative diseases. However, the exact role of this repair pathway during the development and maintenance of the nervous system is unclear. Using murine neural-specific inactivation of Xrcc1, a factor that is critical for the repair of DNA single strand breaks, we found a profound neuropathology that is characterized by the loss of cerebellar interneurons. This cell loss was linked to p53-dependent cell cycle arrest and occurred as interneuron progenitors commenced differentiation. Loss of Xrcc1 also led to the persistence of DNA strand breaks throughout the nervous system and abnormal hippocampal function. Collectively, these data detail the in vivo link between DNA single strand break repair and neurogenesis and highlight the diverse consequences of specific types of genotoxic stress in the nervous system