Challenges and Opportunities in Implementation of the Future California Rail Network

The California High-Speed Rail Authority (CHSRA) adopted a "blended system" at the northern and southern termini of the planned first phase of its high-speed rail line. In this blended operation, the high-speed rail line will share track and other infrastructure with commuter, intercity, and freight rail. However, the lack of common infrastructure among rail modes and the financial and organizational challenges associated with building that common infrastructure and capacity allocation in California present challenges for the implementation of high-speed rail via a blended system in the state. This paper reviews the blended system and discusses the level of cooperation and coordination necessary between host railroads/agencies and the high-speed rail tenant operator. Sharing track comes with challenges for all participating railroad operators and often requires coordination between heterogeneous rail traffic. However, costs can be reduced compared to dedicated track. How blended service is carried out will impact state and local agencies, railroad owners and operators, and customers across the California rail network

Interacting multivalent molecules: affinity and valence impact the extent and symmetry of phase separation

Self-assembly by phase separation is emerging as a powerful and ubiquitous mechanism to organize and compartmentalize biomolecules in cells. Most of the proteins involved in phase separation have a fixed number of binding sites, i.e., fixed multivalency. Therefore, extending theories of phase separation to multivalent components with a fixed number of binding sites is an important challenge. In this work, we develop a simple lattice model for a three-component system composed of two multivalent proteins and the solvent. We show that interaction strength as well as valency of the protein components determine the extent of phase separation, whereas valency alone determines the symmetry of the phase diagram. Our theoretical predictions agree with experimental results on a synthetic system of proteins with tunable interaction strength and valency

Drugs and Criminal Responsibility

This Special Project has carried out three broad purposes.First, it has synthesized and organized materials concerning drugs and criminal responsibility into a useful guide for legal practitioners and others interested in the problems of the drug dependent defendant. Second, it has identified serious analytical flaws in many of the defenses available to the criminal defendant. Finally,it has responded to these deficiencies with proposals intended to protect not only the legal rights of the drug dependent defendant but also the rights of society pertaining to criminal justice. While these societal interests include the swift imposition of criminal penalties when warranted, they should not be allowed to diminish the concomitant rights of the criminal defendant. In fact, societal rights would be better served by a reexamination and reinterpretation of several traditional legal theories concerning drugs and criminal defendants. A recognition by courts and legislatures of the existing analytical flaws should lead to the development of more equitable theories and a search for alternative forms of treatment and rehabilitation for the drug dependent defendant. Rather than hiding behind the guise of legal history and moral judgment, courts and legislatures should respond to illogical and insufficient theories that fail to deal with the drug dependent defendant in an equitable and just manner

Genetic Variation in an Individual Human Exome

There is much interest in characterizing the variation in a human individual, because this may elucidate what contributes significantly to a person's phenotype, thereby enabling personalized genomics. We focus here on the variants in a person's ‘exome,’ which is the set of exons in a genome, because the exome is believed to harbor much of the functional variation. We provide an analysis of the ∼12,500 variants that affect the protein coding portion of an individual's genome. We identified ∼10,400 nonsynonymous single nucleotide polymorphisms (nsSNPs) in this individual, of which ∼15–20% are rare in the human population. We predict ∼1,500 nsSNPs affect protein function and these tend be heterozygous, rare, or novel. Of the ∼700 coding indels, approximately half tend to have lengths that are a multiple of three, which causes insertions/deletions of amino acids in the corresponding protein, rather than introducing frameshifts. Coding indels also occur frequently at the termini of genes, so even if an indel causes a frameshift, an alternative start or stop site in the gene can still be used to make a functional protein. In summary, we reduced the set of ∼12,500 nonsilent coding variants by ∼8-fold to a set of variants that are most likely to have major effects on their proteins' functions. This is our first glimpse of an individual's exome and a snapshot of the current state of personalized genomics. The majority of coding variants in this individual are common and appear to be functionally neutral. Our results also indicate that some variants can be used to improve the current NCBI human reference genome. As more genomes are sequenced, many rare variants and non-SNP variants will be discovered. We present an approach to analyze the coding variation in humans by proposing multiple bioinformatic methods to hone in on possible functional variation

Evaluation of next generation sequencing platforms for population targeted sequencing studies

Human sequence generated from three next-generation sequencing platforms reveals systematic variability in sequence coverage due to local sequence characteristics

Maria Auxiliadora Hospital in Lima, Peru as a model for neurosurgical outreach to international charity hospitals

A myriad of geopolitical and financial obstacles have kept modern neurosurgery from effectively reaching the citizens of the developing world. Targeted neurosurgical outreach by academic neurosurgeons to equip neurosurgical operating theaters and train local neurosurgeons is one method to efficiently and cost effectively improve sustainable care provided by international charity hospitals. The International Neurosurgical Children’s Association (INCA) effectively improved the available neurosurgical care in the Maria Auxiliadora Hospital of Lima, Peru through the advancement of local specialist education and training. Neurosurgical equipment and training were provided for the local neurosurgeons by a mission team from the University of California at San Diego. At the end of 3 years, with one intensive week trip per year, the host neurosurgeons were proficiently and independently applying microsurgical techniques to previously performed operations, and performing newly learned operations such as neuroendoscopy and minimally invasive neurosurgery. Our experiences may serve as a successful template for the execution of other small scale, sustainable neurosurgery missions worldwide