Abstract: In certain aspects, the present invention provides methods for inducing a stable gene modification of a target nucleic acid via homologous recombination in a primary cell, such as a primary blood cell and/or a primary mesenchymal cell. In certain other aspects, the present invention provides methods for enriching a population of genetically modified primary cells having targeted integration at a target nucleic acid. The methods of the present invention rely on the introduction of a DNA nuclease such as a Cas polypeptide and a homologous donor adeno-associated viral (AAV) vector into the primary cell to mediate targeted integration of the target nucleic acid. Also provided herein are methods for preventing or treating a disease in a subject in need thereof by administering to the subject any of the genetically modified primary cells or pharmaceutical compositions described herein to prevent the disease or ameliorate one or more symptoms of the disease.

Abstract: Enhanced shadow page table algorithms are presented for enhancing typical page table algorithms. In a virtual machine environment, where an operating system may be running within a partition, the operating system maintains it's own guest page tables. These page tables are not the real page tables that map to the real physical memory. Instead, the memory is mapped by shadow page tables maintained by a virtualing program, such as a hypervisor, that virtualizes the partition containing the operating system. Enhanced shadow page table algorithms provide efficient ways to harmonize the shadow page tables and the guest page tables. Specifically, by using tagged translation lookaside buffers, batched shadow page table population, lazy flags, and cross-processor shoot downs, the algorithms make sure that changes in the guest pages tables are reflected in the shadow page tables.

Abstract: A system and method for self-diagnosing a likely cause of a system crash is disclosed. A mechanism within an operating system checks for the existence of a stop code at startup of the machine. The existence of the stop code indicates that the system crashed during the previous session, and the type of system crash. The mechanism may read the stop code and implement a self-diagnostic procedure that corresponds to that stop code. In this manner, the mechanism may automate many of the tasks normally performed by humans, such as a system administrator, to self-diagnose the likely cause of the crash. If the crash occurs again, the mechanism, through the tracking procedures automatically implemented, may identify and report to a system administrator the likely cause of the crash, e.g. the particular faulty driver or configuration error.

Abstract: The present invention relates to a system and methodology to facilitate I/O access to a computer storage medium in a predictable and efficient manner. A scheduling system is provided that mitigates the problem of providing differing levels of performance guarantees for disk I/O in view of varying levels of data access requirements. In one aspect, the scheduling system includes an algorithm or component that provides high performance I/O updates while maintaining high throughput to the disk in a bounded or determined manner. This is achieved by dynamically balancing considerations of I/O access time and latency with considerations of data scheduling requirements. Also, the system provides latency boundaries for multimedia applications as well as managing accesses for other applications.

Abstract: Provided are optimizations to the memory virtualization model employed in a virtual machine environment. An opportunistic hypervisor page mapping process is used in order to utilize large memory pages in a virtual machine environment. Using these optimizations, physical memory is being virtualized for the virtual machine in a manner that allows the operating system (OS) running within the virtual machine to take real and full advantage of large physical memory pages.

Abstract: An operating system is described that is capable of ascertaining whether it is executing in a virtual machine environment and is further capable of modifying its behavior to operate more efficiently and provide optimal behavior in a virtual machine environment. An operating system is enlightened so that it is aware of VMMs or hypervisors, taking on behavior that is optimal to that environment. The VMM or hypervisor informs the operating system of the optimal behavior, and vice versa.

Abstract: Efficient power management of a system with virtual machines is disclosed. In particular, such efficient power management may enable coordination of system-wide power changes with virtual machines. Additionally, such efficient power management may enable coherent power changes in a system with a virtual machine monitor. Furthermore, such efficient power management may enable dynamic control and communication of power state changes.

Abstract: For failure management for multiple operating systems in a virtual environment, an external virtual machine or agent is provided that has been granted rights to full physical memory space to perform a crashdump for the machine. To avoid exposing secret information during a crashdump, private information for a virtual machine or partition is encrypted prior to generating a dump. The storing of crashdump information for virtual machines may avoid storing crashdump information for virtual machines that are stateless. Instead of having an (unstable) operating system running within a virtual machine perform a crashdump, the provision of an external agent, e.g., an external virtual machine, to perform the crashdump avoids many limitations associated with a normal dump when performed by a crashed operating system.

Abstract: Enhanced shadow page table algorithms are presented for enhancing typical page table algorithms. In a virtual machine environment, where an operating system may be running within a partition, the operating system maintains it's own guest page tables. These page tables are not the real page tables that map to the real physical memory. Instead, the memory is mapped by shadow page tables maintained by a virtualing program, such as a hypervisor, that virtualizes the partition containing the operating system. Enhanced shadow page table algorithms provide efficient ways to harmonize the shadow page tables and the guest page tables. Specifically, by using tagged translation lookaside buffers, batched shadow page table population, lazy flags, and cross-processor shoot downs, the algorithms make sure that changes in the guest pages tables are reflected in the shadow page tables.

Abstract: A method of sharing pages between virtual machines in a multiple virtual machine environment includes initially allocating a temporary guest physical address range of a first virtual machine for sharing pages with a second virtual machine. The temporary range is within a guest physical address space of the first virtual machine. An access request, such as with a DMA request, from a second virtual machine for pages available to the first virtual machine is received. A reference count of pending accesses to the pages is incremented to indicate a pending access and the ages are mapped into the temporary guest physical address range. The pages are accessed and the reference count is decremented. The mapping in the temporary guest physical address range is then removed if the reference count is zero.

Abstract: The present invention relates to a system and methodology to facilitate I/O access to a computer storage medium in a predictable and efficient manner. A scheduling system is provided that mitigates the problem of providing differing levels of performance guarantees for disk I/O in view of varying levels of data access requirements. In one aspect, the scheduling system includes an algorithm or component that provides high performance I/O updates while maintaining high throughput to the disk in a bounded or determined manner. This is achieved by dynamically balancing considerations of I/O access time and latency with considerations of data scheduling requirements. Also, the system provides latency boundaries for multimedia applications as well as managing accesses for other applications.