THE MARITIME OPERATIONAL THREAT RESPONSE PLAN: A MODEL FOR INTERAGENCY COOPERATION

History has shown that homeland security is a learning process and an evolution, whereby threats are identified and strategies and policies are developed and implemented. Those strategies and policies are occasionally tested in the real world and refined to adapt to the new threat landscape. The modern homeland security apparatus is characterized by overlapping and interconnecting legal and jurisdictional responsibilities that intertwine response agencies and require a whole-of-government response. A reorganization of the federal government in response to the terrorist attacks of September 11, 2001, created a plethora of new policies and procedures. This restructuring produced overlapping interests and responsibilities that required cross-disciplines, jurisdictions, and authorities to manage threats appropriately. To adapt, the federal government developed several strategies and frameworks for organizing these disparate departments and agencies. This thesis provides a comprehensive understanding of the Maritime Operational Threat Response (MOTR) Plan and how it successfully connects federal organizations to adapt and deal with threats in the unique environment of the maritime domain. Also, it identifies several elements that make the MOTR Plan successful, so the plan may be exported to other areas such as federal, state, or local governments and international partners interested in interagency collaboration.Lieutenant Commander, United States Coast GuardApproved for public release. Distribution is unlimited

Separable GPL: Decidable Model Checking with More Non-Determinism

Generalized Probabilistic Logic (GPL) is a temporal logic, based on the modal mu-calculus, for specifying properties of branching probabilistic systems. We consider GPL over branching systems that also exhibit internal non-determinism under linear-time semantics (which is resolved by schedulers), and focus on the problem of finding the capacity (supremum probability over all schedulers) of a fuzzy formula. Model checking GPL is undecidable, in general, over such systems, and existing GPL model checking algorithms are limited to systems without internal non-determinism, or to checking non-recursive formulae. We define a subclass, called separable GPL, which includes recursive formulae and for which model checking is decidable. A large class of interesting and decidable problems, such as termination of 1-exit Recursive MDPs, reachability of Branching MDPs, and LTL model checking of MDPs, whose decidability has been studied independently, can be reduced to model checking separable GPL. Thus, GPL is widely applicable and, with a suitable extension of its semantics, yields a uniform framework for studying problems involving systems with non-deterministic and probabilistic behaviors

Co3O4 Nanocrystals on Graphene as a Synergistic Catalyst for Oxygen Reduction Reaction

Catalysts for oxygen reduction and evolution reactions are at the heart of key renewable energy technologies including fuel cells and water splitting. Despite tremendous efforts, developing oxygen electrode catalysts with high activity at low costs remains a grand challenge. Here, we report a hybrid material of Co3O4 nanocrystals grown on reduced graphene oxide (GO) as a high-performance bi-functional catalyst for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). While Co3O4 or graphene oxide alone has little catalytic activity, their hybrid exhibits an unexpected, surprisingly high ORR activity that is further enhanced by nitrogen-doping of graphene. The Co3O4/N-doped graphene hybrid exhibits similar catalytic activity but superior stability to Pt in alkaline solutions. The same hybrid is also highly active for OER, making it a high performance non-precious metal based bi-catalyst for both ORR and OER. The unusual catalytic activity arises from synergetic chemical coupling effects between Co3O4 and graphene.Comment: published in Nature Material

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome

A homozygous mutational change in the Ataxia-Telangiectasia and RAD3 related (ATR) gene was previously reported in two related families displaying Seckel Syndrome (SS). Here, we provide the first identification of a Seckel Syndrome patient with mutations in ATRIP, the gene encoding ATR-Interacting Protein (ATRIP), the partner protein of ATR required for ATR stability and recruitment to the site of DNA damage. The patient has compound heterozygous mutations in ATRIP resulting in reduced ATRIP and ATR expression. A nonsense mutational change in one ATRIP allele results in a C-terminal truncated protein, which impairs ATR-ATRIP interaction; the other allele is abnormally spliced. We additionally describe two further unrelated patients native to the UK with the same novel, heterozygous mutations in ATR, which cause dramatically reduced ATR expression. All patient-derived cells showed defective DNA damage responses that can be attributed to impaired ATR-ATRIP function. Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS). The identification of an ATRIP-deficient patient provides a novel genetic defect for Seckel Syndrome. Coupled with the identification of further ATR-deficient patients, our findings allow a spectrum of clinical features that can be ascribed to the ATR-ATRIP deficient sub-class of Seckel Syndrome. ATR-ATRIP patients are characterised by extremely severe microcephaly and growth delay, microtia (small ears), micrognathia (small and receding chin), and dental crowding. While aberrant bone development was mild in the original ATR-SS patient, some of the patients described here display skeletal abnormalities including, in one patient, small patellae, a feature characteristically observed in Meier-Gorlin Syndrome. Collectively, our analysis exposes an overlapping clinical manifestation between the disorders but allows an expanded spectrum of clinical features for ATR-ATRIP Seckel Syndrome to be define

Association studies and direct DNA sequencing implicate some known genetic susceptibility loci in the etiology of nonsyndromic orofacial clefts in sub-Saharan African populations

Orofacial clefts (OFCs) are congenital dysmorphologies of the human face and oral cavity, with a global incidence of 1 per 700 live births. These anomalies exhibit multifactorial pattern of inheritance, with both genetic and environmental factors playing crucial roles. Many loci have been implicated in the aetiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in populations of Asian and European ancestries through genome-wide association studies (GWAS) and candidate gene studies. However, few populations of African descent have been studied to date. Here, we show evidence of association of some loci with NSCL/P and nonsyndromic cleft palate only (NSCPO) in cohorts from Africa (Ghana, Ethiopia and Nigeria). We genotyped 48 SNPs that were selected from previous GWAS and candidate gene studies. These markers were successfully genotyped on 701 NSCL/P and 163 NSCPO cases, 1070 unaffected relatives and 1078 unrelated controls. We also directly sequenced 7 genes in 184 nonsyndromic OFC (NSOFC) cases and 96 controls from Ghana. Population-specific associations were observed in the case-control analyses of the sub-populations, with West African subpopulations (Ghana and Nigeria) showing similar pattern of associations. In meta-analyses of the case-control cohort, PAX7 (rs742071, p=5.10×10-03), 8q24 (rs987525, p=1.22×10-03) and VAX1 (rs7078160, p=0.04) were nominally associated with NSCL/P; MSX1 (rs115200552, p=0.01), TULP4 (rs651333, p=0.04), CRISPLD2 (rs4783099, p=0.02) and NOG1 (rs17760296, p=0.04) were nominally associated with NSCPO. Moreover, 7 loci exhibited evidence of threshold over-transmission in NSOFC cases in both transmission disequilibrium test (TDT) and family-based association for disease traits (DFAM) analyses. Through DNA sequencing, we also identified two novel, rare, potentially pathogenic variants (p.Asn323Asp and p.Lys426IlefsTer6) in ARHGAP29. In conclusion, we have shown evidence of association of many loci with NSCL/P and NSCPO. To the best of our knowledge, our study is the first to demonstrate any of these association signals in any African population.<br/

A comparison of vestibular and auditory phenotypes in inbred mouse strains

The purposes of this research were to quantify gravity receptor function in inbred mouse strains and compare vestibular and auditory function for strain- and age-matched animals. Vestibular evoked potentials (VsEPs) were collected for 19 inbred strains at ages from 35 to 389 days old. On average, C57BL/6J (35 to 190 days), BALB/cByJ, C3H/HeSnJ, CBA/J, and young LP/J mice had VsEP thresholds comparable to normal. Elevated VsEP thresholds were found for elderly C57BL/ 6J, NOD.NONH2kb, BUB/BnJ, A/J, DBA/2J, NOD/LtJ, A/WySnJ, MRL/MpJ, A/HeJ, CAST/Ei, SJL/J, elderly LP/J, and CE/J. These results suggest that otolithic function varies among inbred strains and several strains displayed gravity receptor deficits by 90 days old. Auditory brainstem response (ABR) thresholds were compared to VsEP thresholds for 14 age-matched strains. C57BL/6J mice (up to 190 days) showed normal VsEPs with normal to mildly elevated ABR thresholds. Four strains (BUB/BnJ, NOD/LtJ, A/J, elderly LP/J) had significant hearing loss and elevated VsEP thresholds. Four strains (DBA/2J, A/WySnJ, NOD. NONH2kb, A/HeJ) had elevated VsEP thresholds (including absent VsEPs) with mild to moderate elevations in ABR thresholds. Three strains (MRL/MpJ, Ce/J, SJL/J) had significant vestibular loss with no concomitant hearing loss. These results suggest that functional change in one sensory system does not obligate change in the other. We hypothesize that genes responsible for early onset hearing loss may affect otolithic function, yet the time course of functional change may vary. In addition, some genetic mutations may produce primarily gravity receptor deficits. Potential genes responsible for selective gravity receptor impairment demonstrated herein remain to be identified. Originally published in Brain Research 1091(1), 2006

TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism.

DNA lesions encountered by replicative polymerases threaten genome stability and cell cycle progression. Here we report the identification of mutations in TRAIP, encoding an E3 RING ubiquitin ligase, in patients with microcephalic primordial dwarfism. We establish that TRAIP relocalizes to sites of DNA damage, where it is required for optimal phosphorylation of H2AX and RPA2 during S-phase in response to ultraviolet (UV) irradiation, as well as fork progression through UV-induced DNA lesions. TRAIP is necessary for efficient cell cycle progression and mutations in TRAIP therefore limit cellular proliferation, providing a potential mechanism for microcephaly and dwarfism phenotypes. Human genetics thus identifies TRAIP as a component of the DNA damage response to replication-blocking DNA lesions.This work was supported by funding from the Medical Research Council and the European Research Council (ERC, 281847) (A.P.J.), the Lister Institute for Preventative Medicine (A.P.J. and G.S.S.), Medical Research Scotland (L.S.B.), German Federal Ministry of Education and Research (BMBF, 01GM1404) and E-RARE network EuroMicro (B.W), Wellcome Trust (M. Hurles), CMMC (P.N.), Cancer Research UK (C17183/A13030) (G.S.S. and M.R.H), Swiss National Science Foundation (P2ZHP3_158709) (O.M.), AIRC (12710) and ERC/EU FP7 (CIG_303806) (S.S.), Cancer Research UK (C6/A11224) and ERC/EU FP7 (HEALTH-F2- 2010-259893) (A.N.B. and S.P.J.).This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.345