A spill code minimization algorithm for loops

Loops are the main source of parallelism in applications. The issue of finding an optimal register allocation to loops has been an open issue for some time. In this case optimal refers to the minimization of spills from registers to memory. In this paper we address this issue and present an optimal, but exponential algorithm which allocates registers to loop bodies such that the spill code is minimal. We also show heuristic modifications to the algorithm which perform in practice as well as the exponential approach. Finally, we examine this algorithm's feasibility in production compilers

Survey of switching techniques in high-speed networks and their performance

One of the most promising approaches for high speed networks for integrated service applications is fast packet switching, or ATM (Asynchronous Transfer Mode). ATM can be characterized by very high speed transmission links and simple, hard wired protocols within a network. To match the transmission speed of the network links, and to minimize the overhead due to the processing of network protocols, the switching of cells is done in hardware switching fabrics in ATM networks.A number of designs has been proposed for implementing ATM switches. While many differences exist among the proposals, the vast majority of them is based on self-routing multi-stage interconnection networks. This is because of the desirable features of multi-stage interconnection networks such as self-routing capability and suitability for VLSI implementation.Existing ATM switch architectures can be classified into two major classes: blocking switches, where blockings of cells may occur within a switch when more than one cell contends for the same internal link, and non-blocking switches, where no internal blocking occurs. A large number of techniques has also been proposed to improve the performance of blocking and nonblocking switches. In this paper, we present an extensive survey of the existing proposals for ATM switch architectures, focusing on their performance issues

HIV-Associated Neurocognitive Disorder: Pathogenesis and Therapeutic Opportunities

Human immunodeficiency virus type 1 (HIV) infection presently affects more that 40 million people worldwide, and is associated with central nervous system (CNS) disruption in at least 30% of infected individuals. The use of highly active antiretroviral therapy has lessened the incidence, but not the prevalence of mild impairment of higher cognitive and cortical functions (HIV-associated neurocognitive disorders) as well as substantially reduced a more severe form dementia (HIV-associated dementia). Furthermore, improving neurological outcomes will require novel, adjunctive therapies that are targeted towards mechanisms of HIV-induced neurodegeneration. Identifying such molecular and pharmacological targets requires an understanding of the events preceding irreversible neuronal damage in the CNS, such as actions of neurotoxins (HIV proteins and cellular factors), disruption of ion channel properties, synaptic damage, and loss of adult neurogenesis. By considering the specific mechanisms and consequences of HIV neuropathogenesis, unified approaches for neuroprotection will likely emerge using a tailored, combined, and non-invasive approach

A bone of contention: A dynamic ultrasound assessment of the role of the radial head in the arthrokinematics of the proximal radioulnar joint

INTRODUCTION: The arthrokinematics of the proximal radioulnar joint (PRUJ) are believed to follow the convex-concave rule, meaning that when the convex radial head articulates with the concave radial notch on the ulna, rolling and gliding occur in opposite directions during forearm pronation and supination. Previous research using helical computerized tomography (CT) identified that the sequence of joint actions is in contrast with this rule, which would indicate a posterior glide of the radius on the ulna during pronation movement and the converse during supination. OBJECTIVES: The aims of this study are to determine the arthrokinematics of the PRUJ while being assessed via ultrasound (US) imaging and to assess the impact the direction of joint mobilization has on active and passive range of motion (ROM) during forearm supination and pronation at the PRUJ. METHODS: A convenience sample of 53 healthy individuals were recruited. The arthrokinematics of the PRUJ were observed via US cine-loops. A linear US transducer was applied in the transverse plane and placed over the radial head during all testing conditions. A metronome standardized the rate of forearm pronation and supination at 1Hz (60 bpm) during US cine-loops acquisition. Radial head motion was assessed in two different elbow positions during US and joint range of motion assessment. The elbow was flexed to 90° with a neutral forearm position and fully extended with a neutral forearm position. The glenohumeral joint was stabilized during all testing conditions. A repeated measures design randomizing joint mobilization direction to the radial head was utilized to assess forearm pronation and supination via inclinometer data measured in degrees. Joint glides were applied to the radial head according to the convex-concave rule to facilitate forearm supination and pronation. An anteromedial glide to facilitate forearm supination and a posterolateral glide to facilitate forearm pronation. A metronome standardized the rate of joint mobilization at a rate 2Hz (120 bpm). A bubble inclinometer assessed active and passive PRUJ ROM at the wrist during all testing conditions. RESULTS:US imaging cine-loops showed the radial head rolled anteromedially during pronation and posterolaterally during supination, with no translation/gliding evident. Multivariate analysis revealed that the direction of joint mobilization had a significant impact on ROM F(1,47.0)= 6.964, p=.011, partial η2 =.129), with anterior mobilization increasing pronation and posterior mobilization increasing supination. Supination ROM was significantly increased F1(1, 47.0) = 78.03, p CONCLUSION: Our findings are in conflict with the convex-concave rule, which is frequently used by physical therapists to improve joint motion. Should we now reconsider applying this rule to improve joint ROM at the PRUJ

Examining virtual driving test performance and its relationship to individuals with HIV-associated neurocognitive disorders

SIGNIFICANCE: Existing screening tools for HIV-associated neurocognitive disorders (HAND) are often clinically impractical for detecting milder forms of impairment. The formal diagnosis of HAND requires an assessment of both cognition and impairment in activities of daily living (ADL). To address the critical need for identifying patients who may have disability associated with HAND, we implemented a low-cost screening tool, the Virtual Driving Test (VDT) platform, in a vulnerable cohort of people with HIV (PWH). The VDT presents an opportunity to cost-effectively screen for milder forms of impairment while providing practical guidance for a cognitively demanding ADL. OBJECTIVES: We aimed to: (1) evaluate whether VDT performance variables were associated with a HAND diagnosis and if so; (2) systematically identify a manageable subset of variables for use in a future screening model for HAND. As a secondary objective, we examined the relative associations of identified variables with impairment within the individual domains used to diagnose HAND. METHODS: In a cross-sectional design, 62 PWH were recruited from an established HIV cohort and completed a comprehensive neuropsychological assessment (CNPA), followed by a self-directed VDT. Dichotomized diagnoses of HAND-specific impairment and impairment within each of the seven CNPA domains were ascertained. A systematic variable selection process was used to reduce the large amount of VDT data generated, to a smaller subset of VDT variables, estimated to be associated with HAND. In addition, we examined associations between the identified variables and impairment within each of the CNPA domains. RESULTS: More than half of the participants ( CONCLUSION: We identified a subset of VDT performance variables that are associated with HAND and assess relevant functional abilities among individuals with HAND. Additional research is required to develop and validate a predictive HAND screening model incorporating this subset

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-1-Associated Neurocognitive Disorders

Antiretroviral therapy (ART) has reduced morbidity and mortality in HIV-1 infection; however HIV-1-associated neurocognitive disorders (HAND) persist despite treatment. The reasons for the limited efficacy of ART in the brain are unknown. Here we used functional genomics to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed genome-wide microarray analysis using Affymetrix U133 Plus 2.0 Arrays, real-time PCR, and immunohistochemistry in brain tissues from seven treated and eight untreated HAND patients and six uninfected controls. We also determined brain virus burdens by real-time PCR. Treated and untreated HAND brains had distinct gene expression profiles with ART transcriptomes clustering with HIV-1-negative controls. The molecular disease profile of untreated HAND showed dysregulated expression of 1470 genes at p<0.05, with activation of antiviral and immune responses and suppression of synaptic transmission and neurogenesis. The overall brain transcriptome changes in these patients were independent of histological manifestation of HIV-1 encephalitis and brain virus burdens. Depending on treatment compliance, brain transcriptomes from patients on ART had 83% to 93% fewer dysregulated genes and significantly lower dysregulation of biological pathways compared to untreated patients, with particular improvement indicated for nervous system functions. However a core of about 100 genes remained similarly dysregulated in both treated and untreated patient brain tissues. These genes participate in adaptive immune responses, and in interferon, cell cycle, and myelin pathways. Fluctuations of cellular gene expression in the brain correlated in Pearson's formula analysis with plasma but not brain virus burden. Our results define for the first time an aberrant genome-wide brain transcriptome of untreated HAND and they suggest that antiretroviral treatment can be broadly effective in reducing pathophysiological changes in the brain associated with HAND. Aberrantly expressed transcripts common to untreated and treated HAND may contribute to neurocognitive changes defying ART

Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease

Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the 'preclinical' stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI]) and 0.88 (0.81-0.94 CI), respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions

Register allocation issues in embedded code generation

In conventional compilation, register allocation—the mapping of program variables to the registers of the target architecture—plays an important role in the performance of application code. In particular, for load/store architectures, good register allocation is exceedingly important as all operands to instructions, in this type of architecture, must be contained within the register set.Typical processors selected as the core unit or core processor for an embedded system closely resemble the load/store or RISC-type of architecture, and, thus, conventional register allocation techniques are applicable in the generation of code for an embedded processor. However, architectural features of the core processor, features designed to reduce core size/cost and/or are specific to the target application area for improved performance—such as disjoint register files and/or requirements that operands to particular instructions reside in specialized registers—complicate the register allocation process. This, coupled with the time-sensitive nature of typical embedded applications necessitates high-quality register allocation.[...

A spill code minimization algorithm for loops

Loops are the main source of parallelism in applications. The issue of finding an optimal register allocation to loops has been an open issue for some time. In this case optimal refers to the minimization of spills from registers to memory. In this paper we address this issue and present an optimal, but exponential algorithm which allocates registers to loop bodies such that the spill code is minimal. We also show heuristic modifications to the algorithm which perform in practice as well as the exponential approach. Finally, we examine this algorithm's feasibility in production compilers