Selective Core Boosting: The Return of the Turbo Button

Several modern multi-core architectures support the dynamic control of the CPU's clock rate, allowing processor cores to temporarily operate at speeds exceeding the operational base frequency. Conversely, cores can operate at a lower speed or be disabled altogether to save power. Such facilities are notably provided by Intel's Turbo Boost and AMD's Turbo CORE technologies. Frequency control is typically driven by the operating system which requests changes to the performance state of the processor based on the current load of the system. In this paper, we investigate the use of dynamic frequency scaling from user space to speed up multi-threaded applications that must occasionally execute time-critical tasks or to solve problems that have heterogeneous computing requirements. We propose a general-purpose library that allows selective control of the frequency of the cores - subject to the limitations of the target architecture. We analyze the performance trade-offs and illustrate its benefits using several benchmarks and real-world workloads when temporarily boosting selected cores executing time-critical operations. While our study primarily focuses on AMD's architecture, we also provide a comparative evaluation of the features, limitations, and runtime overheads of both Turbo Boost and Turbo CORE technologies. Our results show that we can successful exploit these new hardware facilities to accelerate the execution of key sections of code (critical paths) improving overall performance of some multi-threaded applications. Unlike prior research, we focus on performance instead of power conservation. Our results further can give guidelines for the design of hardware power management facilities and the operating system interfaces to those facilities

Midbrain–hindbrain malformations in patients with malformations of cortical development and epilepsy: A series of 220 patients

SummaryMidbrain–hindbrain malformations (MHM) may coexist with malformations of cortical development (MCD). This study represents a first attempt to investigate the spectrum of MHM in a large series of patients with MCD and epilepsy. We aimed to explore specific associations between MCD and MHM and to compare two groups of patients: MCD with MHM (wMHM) and MCD without MHM (w/oMHM) with regard to clinical and imaging features.Two hundred and twenty patients (116 women/104 men, median age 28 years, interquartile range 20–44 years at the time of assessment) with MCD and epilepsy were identified at the Departments of Neurology and Pediatrics, Innsbruck Medical University, Austria. All underwent high-resolution MRIs (1.5-T) between 01.01.2002 and 31.12.2011. Midbrain–hindbrain structures were visually assessed by three independent raters.MHM were seen in 17% (38/220) of patients. The rate of patients wMHM and w/oMHM differed significantly (p=0.004) in three categories of MCD (category I – to abnormal neuronal proliferation; category II – to abnormal neuronal migration; and category III – due to abnormal neuronal late migration/organization): MCD due to abnormal neuronal migration (31%) and organization (23%) were more commonly associated with MHM compared to those with MCD due to abnormal neuronal proliferation (9%). Extensive bilateral MCD were seen more often in patients wMHM compared to those w/oMHM (63% vs. 36%; p=0.004). In wMHM group compared to w/oMHM group there were higher rates of callosal dysgenesis (26% vs. 4%; p<0.001) and hippocampal abnormalities (52% vs. 27%; p<0.001). Patients wMHM were younger (median 25 years vs. 30 years; p=0.010) at the time of assessment and had seizure onset at an earlier age (median 5 years vs. 12 years; p=0.043) compared to those w/oMHM. Patients wMHM had higher rates of learning disability (71% vs. 38%; p<0.001), delayed developmental milestones (68% vs. 35%; p<0.001) and neurological deficits (66% vs. 47%; p=0.049) compared to those w/oMHM.The groups (wMHM and w/oMHM) did not differ in their response to antiepileptic treatment, seizure outcome, seizure types, EEG abnormalities and rate of status epilepticus. Presence of MHM in patients with MCD and epilepsy is associated with severe morphological and clinical phenotypes

Распространенность болезни Помпе у пациентов с идиопатической гиперкреатинкиназемией и слабостью поясно-конечностных мышц (анализ 3076 случаев)*

.Проведен проспективный скрининг дефицита фермента кислой α-глюкозидазы (GAA) европейской когорты пациентов с гиперкреатинкиназемией (гиперКК) и / или слабостью поясно-конечностных мышц (СПКМ) неустановленной этиологии с помощью метода сухого пятна крови (dry blood spot, DBS).Материалы и методы. Образцы DBS были собраны у 3076 взрослых пациентов, проходивших обследование в 7 немецких и британских нервно-мышечных центрах. Все образцы были исследованы на дефицит GAA методом флуорометрии. При выявлении пониженной ферментативной активности определяли наличие мутации гена GAA.Результаты. Из 3076 образцов DBS в 232 (7,6 %) случаях обнаружена низкая ферментативная активность GAA. У 55 (24 %) из 232 пациентов наблюдали изолированную гиперКК, а у 176 (76 %) – гиперКК и СПКМ. При комбинации 2 признаков у 94 % больных активность GAA была снижена. Мутационный анализ выявил мутации гена GAA у 74 (2,4 %) пациентов, при этом 70 больных были гетерозиготными по распространенной мутации сайта сплайсинга гена GAA c.-32-13T&gt;G. У пациентов с подтвержденной болезнью Помпе основной симптомокомплекс состоял из СПКМ (85,3 %) в сочетании с дыхательной недостаточностью (61 %). У 12,0 % больных наблюдали изолированную гиперКК, а у 2,7 % – гиперКК и дыхательную недостаточность.Заключение. В большой когорте пациентов с гиперКК и / или СПКМ  распространенность болезни Помпе с поздним началом составляет 2,4 %, что требует проведения целевого скрининга активности GAA у пациентов с гиперКК и / или СПКМнеустановленной этиологии

Expression of human Kallikrein 14 (KLK14) in breast cancer is associated with higher tumour grades and positive nodal status

Human kallikrein 14 (KLK14) is a steroid hormone-regulated member of the tissue kallikrein family of serine proteases, for which a prognostic and diagnostic value in breast cancer has been suggested. To further characterise the value of KLK14 as a breast tumour marker, we have carefully analysed KLK14 expression in normal breast tissue and breast cancer both on the RNA level by real-time RT-PCR (n=39), and on the protein level (n=127) using a KLK14-specific antibody for immunohistochemistry. We correlated KLK14 protein expression data with available clinico-pathological parameters (mean follow-up time was 55 months) including patient prognosis. KLK14 RNA expression as quantified by real-time RT-PCR was significantly more abundant in breast tumours compared to normal breast tissue (P=0.027), an issue that had not been clarified recently. Concordantly with the RNA data, cytoplasmic KLK14 protein expression was significantly higher in invasive breast carcinomas compared to normal breast tissues (P=0.003). Furthermore, KLK14 protein expression was associated with higher tumour grade (P=0.041) and positive nodal status (P=0.045) but was not significantly associated with shortened disease-free or overall patient survival time in univariate analyses. We conclude that KLK14 is clearly overexpressed in breast cancer in comparison to normal breast tissues and is positively associated with conventional parameters of tumour aggressiveness, but due to a missing association with survival times, the use of KLK14 immunohistochemistry as a prognostic marker in breast cancer is questionable

Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies

Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders exclusively or predominantly affecting the sensory and autonomic neurons. Due to the rarity of the diseases and findings based mainly on single case reports or small case series, knowledge about these disorders is limited. Here, we describe the molecular workup of a large international cohort of CIP/HSAN patients including patients from normally under-represented countries. We identify 80 previously unreported pathogenic or likely pathogenic variants in a total of 73 families in the >20 known CIP/HSAN-associated genes. The data expand the spectrum of disease-relevant alterations in CIP/HSAN, including novel variants in previously rarely recognized entities such as ATL3-, FLVCR1- and NGF-associated neuropathies and previously under-recognized mutation types such as larger deletions. In silico predictions, heterologous expression studies, segregation analyses and metabolic tests helped to overcome limitations of current variant classification schemes that often fail to categorize a variant as disease-related or benign. The study sheds light on the genetic causes and disease-relevant changes within individual genes in CIP/HSAN. This is becoming increasingly important with emerging clinical trials investigating subtype or gene-specific treatment strategies