Explore the vast range of titles available.

This paper summarizes current high explosive pulsed power (HEPP) work in the U.S. Three categories are listed in the following text: computational, experimental, and university programs. The focus is on the type of work being done rather than the goals of each program. Most of the work mentioned is also represented elsewhere in the conference, and specific program goals are described in those papers. The programs are treated individually within each category. In reviewing the work, many papers are referenced in this conference (ITC) by principle author, but will not be compiled in a reference list due to space. The reader can find the author, hence the paper, in the index.

At Los Alamos, we investigate solid density materials under extreme conditions of high pressure or strain. To further these studies, we develop pulsed power techniques for driving high energy imploding liners. We have developed the Ranchero explosive-driven magnetic flux compression generator (FCG) system to perform such experiments at very high energy, in remote locations. Our first charter is to support the development of the Atlas capacitor bank [1] which, when completed in 2001, will deliver up to 30 MA to hydrodynamic liners. The basic unit of the Ranchero system is a 1.4 m long coaxial FCG that is simultaneously initiated along its axis and has an armature expansion ratio of 2:1. We performed initial system tests using 43 cm long [2,3] coaxial modules and are finalizing the design and development of our 1.4 m detonation system. This development, which met with unexpected difficulties, is the subject of another paper in this conference [4]. The 43cm module combined with the 2.4 MJ capacitor bank at our high explosive pulsed power facility has the capability of delivering ~40 MA to a load of ~5 nH. Coupled with a fuse opening switch (FOS), the system will generate a good approximation of Atlas waveforms with 5 nH in the load and transmission lines. This allows us to begin preliminary Atlas related tests before the 1.4 m module is completed. Herein is described our efforts to develop the capability and the design of our first imploding liner experiment.

Ranchero is an explosively driven magnetic flux-compression generator that has been developed over the last four years as a versatile power source for high energy density physics experiments. It is coaxial and comprises a 15 cm diameter armature and a 30 cm diameter stator, each made of aluminum. The length may be varied to suit the demands of each experiment. Thus far, lengths of 0.43 m and 1.4 m have been used. The armature is filled and driven by a high-performance cast explosive, and the ultimate performance of the device is limited by the smoothness of the armature expansion. The armature explosive is initiated on axis by PETN hemispheres spaced at intervals of between 18 mm and 24.5 mm. Each is simultaneously detonated by a slapper detonator system. Armature expansion calculations predicted ripples less than 0.2 mm, which was confirmed in early experiments. Yet, ripples approaching tens of millimeters were observed in some more recent experiments. We will discuss the possible origins of these large ripples and the methods we have used to correct them.

At Los Alamos, we have primarily applied Explosively Formed Fuse (EFF) techniques to high current systems. In these systems, the EFF has interrupted currents from 19-25 MA, thus diverting the current to low inductance loads. The transferred current magnitude is determined by the ratio of storage inductance to load inductance and, with dynamic loads, the current has ranged from 12-20 MA. In a system with 18 MJ stored energy, the switch operates at a power of up to 6 TW. We are now investigating the use of the EFF technique to apply high voltages to high impedance loads in systems that are more compact. In these systems we are exploring circuits with EFF lengths from 43-100 cm, which have storage inductances large enough to apply 300-500 kV across high impedance loads. Experimental results and design considerations are presented. Using cylindrical EFF switches of 10 cm diameter and 43 cm length, currents of approximately 3 MA were interrupted producing ~200 kV. This indicates the switch had an effective resistance of ~100 mΩ where 150-200 mΩ was expected. To understand the lower performance, several parameters were studied including electrical conduction through the explosive products; current density; explosive initiation; insulator type and conductor thickness. The results show a number of interesting features, most notably that the primary mechanism of switch operation is mechanical and not electrical fusing of the conductor. Switches opening on a 1-10 μs time scale with resistances starting at 50 μΩ and increasing to perhaps 1 Ω now seem possible to construct using explosive charges as small as a few pounds.

The Herth Hope Index (HHI) is a validated and reliable tool that measures hope and emotional wellbeing. Comparing the HHI with Edmonton Symptom Assessment Scale (ESAS) provides a means of comparison between symptom burden and hope. We assessed hope and its relationship to symptom burden in an inpatient palliative medicine unit as a pilot trial. Eligible patients verbally consented, participated in the study. Patients completed or were assisted in completing the HHI and ESAS. Correlation between the HHI and symptom burden will be estimated using a 95 % confidence interval once the study is completed. A correlation of>0.20 or <-0.20 would be considered clinically relevant. One hundred ninety-three patients will be needed to have 80 % power at a 5 % significance level based on pilot data. From pilot data of 25 patients, no correlation between hope and symptom burden was observed. Mean ESAS score is 35/90, mean Herth score is 35/ 48. The mean ESAS NRS scores for pain is 4/10, nausea 2/10, and tiredness 5/10. A large study powered to 196 patients for a correlation of <0.2 will be completed January 2014 with final analysis available for presentation. Comparison between symptom burden and hope is relevant to patient care. If a high correlation is found, symptom management may improve hope if no or low correlation is found additional services are needed. This ongoing study has potential to influence patient care and service delivery in an inpatient palliative medicine units.

Congenital deafness occurs in approximately 1 in 1000 live births, and 50 percent of these cases are hereditary. 1 Nonsyndromic recessive deafness, defined as lack of hearing with no other associated clinical features, accounts for approximately 80 percent of cases of hereditary deafness. 1 The existence of at least 20 genes that, if mutated, result in nonsyndromic recessive deafness has been demonstrated through genetic-linkage studies, although most of these genes have not yet been identified. 2 Population studies suggest that many more are likely to exist. 1 , 3 – 8 Recently, mutations in the GJB2 gene were shown to be among the causes of the . . .

The COVID-19 pandemic has highlighted how viral variants that escape monoclonal antibodies can limit options to control an outbreak. With the emergence of the SARS-CoV-2 Omicron variant, many clinically used antibody drug products lost in vitro and in vivo potency, including AZD7442 and its constituent, AZD1061. Rapidly modifying such antibodies to restore efficacy to emerging variants is a compelling mitigation strategy. We therefore sought to computationally design an antibody that restores neutralization of BA.1 and BA.1.1 while simultaneously maintaining efficacy against SARS-CoV-2 B.1.617.2 (Delta), beginning from COV2-2130, the progenitor of AZD1061. Here we describe COV2-2130 derivatives that achieve this goal and provide a proof-of-concept for rapid antibody adaptation addressing escape variants. Our best antibody achieves potent and broad neutralization of BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4, BA.5, and BA.5.5 Omicron subvariants, where the parental COV2-2130 suffers significant potency losses. This antibody also maintains potency against Delta and WA1/2020 strains and provides protection in vivo against the strains we tested, WA1/2020, BA.1.1, and BA.5. Because our design approach is computational - driven by high-performance computing-enabled simulation, machine learning, structural bioinformatics and multi-objective optimization algorithms - it can rapidly propose redesigned antibody candidates aiming to broadly target multiple escape variants and virus mutations known or predicted to enable escape. Competing Interest Statement M.S.D. is a consultant for Inbios, Vir Biotechnology, Senda Biosciences, Moderna and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. J.E.C. has served as a consultant for Luna Labs USA, Merck Sharp & Dohme Corporation, Emergent Biosolutions, and GlaxoSmithKline, is a member of the Scientific Advisory Board of Meissa Vaccines, a former member of the Scientific Advisory Board of Gigagen (Grifols) and is founder of IDBiologics. The laboratory of J.E.C. received unrelated sponsored research agreements from AstraZeneca, Takeda, and IDBiologics during the conduct of the study. Lawrence Livermore National Laboratory, Los Alamos National Laboratory, and Vanderbilt University have applied for patents for some of the antibodies in this paper, for which T.A.D, A.T.Z., E.Y.L., F.Z., A.M.L., R.H.C., J.E.C., and D.M.F. are inventors. Vanderbilt University has licensed certain rights to antibodies in this paper to Astra Zeneca.

The authors examined school discipline problems in relation to academic and interpersonal characteristics of students in a middle school of a rural low-income community. The sample comprised 259 students (83 boys, 176 girls)—all of whom were African American—and reflected the community's public school attendance. School records were examined, and students were identified as having no offenses, minor offenses, or major offenses. More than 50% of the girls had no offenses, and fewer than 20% had major offenses. Girls identified as having no offenses tended to be competent across the academic, behavioral, and social domains, whereas girls with major offenses tended to have multiple problems. For the boys, 37% had major offenses and 34% had no offenses. Involvement in aggression appeared to be the primary factor that differentiated among boys who were and were not referred for discipline problems. The authors discuss the results in terms of their implications for assessment and prevention.