Adaptive runtime-assisted block prefetching on chip-multiprocessors

Memory stalls are a significant source of performance degradation in modern processors. Data prefetching is a widely adopted and well studied technique used to alleviate this problem. Prefetching can be performed by the hardware, or be initiated and controlled by software. Among software controlled prefetching we find a wide variety of schemes, including runtime-directed prefetching and more specifically runtime-directed block prefetching. This paper proposes a hybrid prefetching mechanism that integrates a software driven block prefetcher with existing hardware prefetching techniques. Our runtime-assisted software prefetcher brings large blocks of data on-chip with the support of a low cost hardware engine, and synergizes with existing hardware prefetchers that manage locality at a finer granularity. The runtime system that drives the prefetch engine dynamically selects which cache to prefetch to. Our evaluation on a set of scientific benchmarks obtains a maximum speed up of 32 and 10 % on average compared to a baseline with hardware prefetching only. As a result, we also achieve a reduction of up to 18 and 3 % on average in energy-to-solution.Peer ReviewedPostprint (author's final draft

LA EFICIENCIA DE LA DIMENSIÓN SALUD EN MÉXICO, 1990-2010: UN ESTUDIO DEA INCORPORANDO FACTORES NO CONTROLABLES

El documento tiene por objetivo abordar el estudio del uso eficiente de los recursos socioeconómicos en la dimensión salud del desarrollo humano, incorporando factores no controlables, en los 32 estados de México, durante el período 1990-2010. El desarrollo humano en México se caracteriza por un pobre desempeño en las tres dimensiones. Por lo que el establecimiento de mecanismos que mejoren la dinámica de las dimensiones del desarrollo humano le permitirá al país aspirar a mayores niveles de bienestar social. Para determinar qué tan eficientes fueron los estados mexicanos se hizo uso del Análisis Envolvente de Datos, considerando variables no controlables, y para conocer su evolución en el tiempo se calculó el índice Malmquist. Los resultados del modelo muestran que sólo 3 de las 32 unidades estudiadas fueron eficientes en la generación de bienestar en salud mientras que el resto deberá aumentar la esperanza de vida al nacer con los recursos socioeconómicos que poseen

ANTIMICROBIAL ACTIVITY OF MEDICINAL PLANTS FROM THE HUAUTLA SIERRA BIOSPHERE RESERVE IN MORELOS (MÉXICO)

Twenty-two extracts from nine Mexicanmedicinal plants of eight different familiesused for people neighbor to Huautla SierraBiosphere Reserve (REBIOSH) in differentinfectious diseases were assayed in vitro todetermine their antibacterial activity againstStaphylococcus aureus, Streptococcus faecalis; Escherichia coli; Proteus mirabilis;Salmonella typhi and the yeast Candidaalbicans. Most plants showed antibacterialactivity, while two plants showed activityagainst range 0.25 a 4 mg/mL almost onemicroorganism used. The extracts showedminimum inhibitory concentration (MIC)against S. aureus and S. faecalis, representsmicroorganisms Gram-positive were hexanic and acetonic extracts of Bursera copallifera and hexanic extract of B. grandifolia.The ethanol extract of Lippia graveolensshowed a MIC value of 1 mg/mL againstyeast Candida albicans.Se determinó la actividad antimicrobianade veintidós extractos orgánicos de nueveespecies vegetales medicinales de ochodiferentes familias, que son comúnmenteempleadas por los habitantes de las comunidades vecinas a la reserva de la biosferaSierra de Huautla (REBIOSH), Morelos,para tratar diferentes padecimientos infecciosos. Los microorganismos empleadosfueron: Staphylococcus aureus; Streptococcus faecalis; Escherichia coli; Proteusmirabilis; Salmonella typhi y la levaduraCandida albicans. La mayoría de los extractos de las plantas probadas inhibieronel crecimiento microbiano en un rango de0.25 a 4 mg/mL de al menos uno de losmicroorganismos utilizados. Los extractosque mostraron las menores concentracionesmínimas inhibitorias (CMI) frente a losmicroorganismos S. aureus y S. faecalis,representativos de Gram-positivos fueron el extracto hexánico y acetónico de Burseracopallifera y el hexánico de B. grandifolia.El extracto etanólico de Lippia graveolenslogró inhibir a C. albicans con una CMIde 1 mg/mL

Improved performance of perylenediimide-based lasers

The aim of this work was to improve the laser performance, in terms of threshold and operational lifetime, of lasers based on polymer films doped with perylenediimide (PDI) derivatives as active media. For such purpose, we first investigated the amplified spontaneous emission (ASE) properties of perylene orange (PDI-O), when doped into polystyrene (PS) films. Lower ASE thresholds and larger photostabilities than those of similar films containing another PDI derivative (PDI-C6), recently reported in the literature, have been measured. Results have been interpreted in terms of the photoluminescence efficiency of the films, which depends on the type of molecular arrangement, inferred with the help of nuclear magnetic resonance experiments. We also show that PS films have a better ASE performance, i.e. lower thresholds and larger photostabilities, than those based on poly(methyl methacrylate), which was recently highlighted as one of the best matrixes for PDI-O. Finally, a one-dimensional second-order distributed feedback laser using PS doped with PDI-O was fabricated and characterized. This device has shown a threshold significantly lower (by around one order of magnitude) than that of a similar laser based on PDI-C6-doped PS.We thank support from the Spanish Government (MECC) and the European Community (FEDER) through grants MAT2008-06648-C02 and MAT-2011-28167-C02, as well as from the University of Alicante. MGR and MM are supported respectively by a CSIC fellowship within the program JAE and by MEC through a FPI fellowship

A Mathematical Description of the Bone Marrow Dynamics during CAR T-Cell Therapy in B-Cell Childhood Acute Lymphoblastic Leukemia

Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients' experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T-cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells, and CAR T-cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T-cells, and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T-cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load, and leukemia burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model.This work was partially supported by the Fundacion Espanola para la Ciencia y la Tecnologia (UCA PR214), the Asociacion Pablo Ugarte (APU, Spain), Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000154), Ministry of Science and Technology, Spain (PID2019110895RB-I00), and Inversion Territorial Integrada de la Provincia de Cadiz (ITI-0038-2019)

Thermal-nanoimprint lithography for perylenediimide-based distributed feedback laser fabrication

In the present work thermal-nanoimprint lithography of various commercial thermoplastic resists as matrixes for perylenediimides (PDIs) has been studied. This fabrication method reduces the number of fabrication steps, and therefore, the cost of the obtained distributed feedback (DFB) lasers. The optical properties of these devices are analyzed, aiming to optimize their performance.Spanish Government (MINECO) and the European Community (FEDER) through grants MAT2008-06648-C02 and MAT-2011-28167-C02. Manuel G. Ramírez is supported by a CSIC fellowship within the program JAE

Vascular interstitial cells in retinal arteriolar annuli are altered during hypertension

The authors thank Veronica Melgarejo, Lorena Noya, and Angel Vazquez for technical assistance. Supported by grants from Instituto de Salud Carlos III (PI12/00605, PI16/00719, SAF2014-59945-R, and Red de Investigación Renal REDinREN 12/0021/0013), Spain; Fundação para a Ciência e a Tecnologia (SFRH/BPD/102573/2014, SFRH/BD/95330/2013), Ministerio da Educação e Ciência, Portugal; and Fondo Europeo de Desarrollo Regional (FEDER).Supported by grants from Instituto de Salud Carlos III (PI12/00605, PI16/00719, SAF2014-59945-R, and Red de Investigacion Renal REDinREN 12/0021/0013), Spain; Fundacao para a Ciencia e a Tecnologia (SFRH/BPD/102573/2014, SFRH/BD/95330/2013), Ministerio da Educacao e Ciencia, Portugal; and Fondo Europeo de Desarrollo Regional (FEDER).PURPOSE. It has been suggested that arteriolar annuli localized in retinal arterioles regulate retinal blood flow acting as sphincters. Here, the morphology and protein expression profile of arteriolar annuli have been analyzed under physiologic conditions in the retina of wildtype, β-actin-Egfp, and Nestin-gfp transgenic mice. Additionally, to study the effect of hypertension, the KAP transgenic mouse has been used. METHODS. Cellular architecture has been studied using digested whole mount retinas and transmission electron microscopy. The profile of protein expression has been analyzed on paraffin sections and whole mount retinas by immunofluorescence and histochemistry. RESULTS. The ultrastructural analysis of arteriolar annuli showed a different cell population found between endothelial and muscle cells that matched most of the morphologic criteria established to define interstitial Cajal cells. The profile of protein expression of these vascular interstitial cells (VICs) was similar to that of interstitial Cajal cells and different from the endothelial and smooth muscle cells, because they expressed b-actin, nestin, and CD44, but they did not express CD31 and a-SMA or scarcely express F-actin. Furthermore, VICs share with pericytes the expression of NG2 and platelet-derived growth factor receptor beta (PDGFR-β). The high expression of Ano1 and high activity of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase observed in VICs was diminished during hypertensive retinopathy suggesting that these cells might play a role on the motility of arteriolar annuli and that this function is altered during hypertension. CONCLUSIONS. A novel type of VICs has been described in the arteriolar annuli of mouse retina. Remarkably, these cells undergo important molecular modifications during hypertensive retinopathy and might thus be a therapeutic target against this disease

Surgical Infection Reduction Program of the Observatory of Surgical Infection (PRIQ-O): Delphi prioritization and consensus document on recommendations for the prevention of surgical site infection

La infección de localización quirúrgica es la complicación más frecuente y más evitable de la cirugía, pero las guías clínicas para su prevención tienen un seguimiento insuficiente. Presentamos los resultados de un consenso Delphi realizado por un panel de expertos de 17 sociedades científicas con revisión crítica de la evidencia científica y guías internacionales, para seleccionar las medidas con mayor grado de evidencia y facilitar su implementación. Se revisaron 40 medidas y se emitieron 53 recomendaciones. Se priorizan 10 medidas principales para su inclusión en bundles de prevención: ducha preoperatoria; correcta higiene quirúrgica de manos; no eliminación del vello del campo quirúrgico o eliminación con maquinilla eléctrica; profilaxis antibiótica sistémica adecuada; uso de abordajes mínimamente invasivos; descontaminación de la piel con soluciones alcohólicas; mantenimiento de la normotermia; protectores-retractores plásticos de herida; cambio de guantes intraoperatorio, y cambio de material quirúrgico y auxiliar antes del cierre de las heridasSurgical site infection is the most frequent and avoidable complication of surgery, but clinical guidelines for its prevention are insufficiently followed. We present the results of a Delphi consensus carried out by a panel of experts from 17 Scientific Societies with a critical review of the scientific evidence and international guidelines, to select the measures with the highest degree of evidence and facilitate their implementation. Forty measures were reviewed and 53 recommendations were issued. Ten main measures were prioritized for inclusion in prevention bundles: preoperative shower; correct surgical hand hygiene; no hair removal from the surgical field or removal with electric razors; adequate systemic antibiotic prophylaxis; use of minimally invasive approaches; skin decontamination with alcoholic solutions; maintenance of normothermia; plastic wound protectors-retractors; intraoperative glove change; and change of surgical and auxiliary material before wound closur

HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients.

To evaluate the impact of hepatitis C virus (HCV) elimination via interferon (IFN)-based therapy on gene expression profiles related to the immune system in HIV/HCV-coinfected patients. We conducted a prospective study in 28 HIV/HCV-coinfected patients receiving IFN-based therapy at baseline (HIV/HCV-b) and week 24 after sustained virological response (HIV/HCV-f). Twenty-seven HIV-monoinfected patients (HIV-mono) were included as a control. RNA-seq analysis was performed on peripheral blood mononuclear cells (PBMCs). Genes with a fold-change (FC) ≥ 1.5 (in either direction) and false discovery rate (FDR) ≤ 0.05 were identified as significantly differentially expressed (SDE). HIV/HCV-b showed six SDE genes compared to HIV-mono group, but no significantly enriched pathways were observed. For HIV/HCV-f vs. HIV/HCV-b, we found 58 SDE genes, 34 upregulated and 24 downregulated in the HIV/HCV-f group. Of these, the most overexpressed were CXCL2, PDCD6IP, ATP5B, IGSF9, RAB26, and CSRNP1, and the most downregulated were IFI44 and IFI44L. These 58 SDE genes revealed two significantly enriched pathways (FDR < 0.05), one linked to Epstein-Barr virus infection and another related to p53 signaling. For HIV/HCV-f vs. HIV-mono group, we found 44 SDE genes that revealed 31 enriched pathways (FDR < 0.05) related to inflammation, cancer/cell cycle alteration, viral and bacterial infection, and comorbidities associated with HIV/HCV-coinfection. Five genes were overrepresented in most pathways (JUN, NFKBIA, PIK3R2, CDC42, and STAT3). HIV/HCV-coinfected patients who eradicated hepatitis C with IFN-based therapy showed profound gene expression changes after achieving sustained virological response. The altered pathways were related to inflammation and liver-related complications, such as non-alcoholic fatty liver disease and hepatocellular carcinoma, underscoring the need for active surveillance for these patients.This study was supported by grants from Instituto de Salud Carlos III (ISCII; Grant Numbers PI20/00474 and PI17/00657 to JB, PI20/00507 and PI17/00903 to JGG, PI18CIII/00020 to AFR, and PI20CIII/00004 and PI17CIII/00003 to SR). The study was also funded by the RD16CIII/0002/0002 and RD16/0025/0017, and RD16/0025/0018 projects as part of the Plan Nacional R + D + I and co-funded by ISCIII- Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER). JB is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS), Ref. INT16/00100.S

Role of neurokinin B in the control of female puberty and Its modulation by metabolic status

[Abstract] Human genetic studies have revealed that neurokinin B (NKB) and its receptor, neurokinin-3 receptor (NK3R), are essential elements for normal reproduction; however, the precise role of NKB–NK3R signaling in the initiation of puberty remains unknown. We investigated here the regulation of Tac2 and Tacr3 mRNAs (encoding NKB and NK3R, respectively) in female rats and demonstrated that their hypothalamic expression is increased along postnatal maturation. At puberty, both genes were widely expressed throughout the brain, including the lateral hypothalamic area and the arcuate nucleus (ARC)/medial basal hypothalamus, where the expression of Tacr3 increased across pubertal transition. We showed that central administration of senktide (NK3R agonist) induced luteinizing hormone (LH) secretion in prepubertal and peripubertal females. Conversely, chronic infusion of an NK3R antagonist during puberty moderately delayed the timing of vaginal opening (VO) and tended to decrease LH levels. The expression of NKB and its receptor was sensitive to changes in metabolic status during puberty, as reflected by a reduction in Tacr3 (and, to a lesser extent, Tac2) expression in the ARC after a 48 h fast. Yet, acute LH responses to senktide in pubertal females were preserved, if not augmented, under fasting conditions, suggesting sensitization of the NKB–NK3R–gonadotropin-releasing hormone signaling pathway under metabolic distress. Moreover, repeated administration of senktide to female rats with pubertal arrest due to chronic undernutrition rescued VO (in ∼50% of animals) and potently elicited LH release. Altogether, our observations suggest that NKB–NK3R signaling plays a role in pubertal maturation and that its alterations may contribute to pubertal disorders linked to metabolic stress and negative energy balance.Ministerio de Ciencia e Innovación; BFU 2008-00984Ministerio de Ciencia e Innovación; BFU 2011-25021Andalucía. Junta, P08-CVI-0060