Pinpointing and repairing performance bottlenecks in concurrent programs

Developing concurrent software that is both correct and efficient is challenging. Past research has proposed various techniques that support developers in finding, understanding, and repairing concurrency-related correctness problems, such as missing or incorrect synchronization. In contrast, existing work provides little support for dealing with concurrency-related performance problems, such as unnecessary or inefficient synchronization. This paper presents SyncProf, a profiling approach that helps in identifying, localizing, and repairing performance bottlenecks in concurrent programs. The approach consists of a sequence of dynamic analyses that reason about relevant code locations with increasing precision while narrowing down performance problems and gathering data for avoiding them. A key novelty is a graph-based representation of relations between critical sections, which is the basis for computing the performance impact of a critical section and for identifying the root cause of a bottleneck. Once a bottleneck is identified, SyncProf searches for a suitable optimization strategy to avoid the problem, increasing the level of automation when repairing performance bottlenecks over a traditional, manual approach. We evaluate SyncProf on 25 versions of eleven C/C++ projects with both known and previously unknown synchronization bottlenecks. The results show that SyncProf effectively localizes the root causes of these bottlenecks with higher precision than a state of the art lock contention profiler, and that it suggests valuable strategies to repair the bottlenecks.     

Synthesis and Biological Evaluation of Papain‐Family Cathepsin L‐Like Cysteine Protease Inhibitors Containing a 1,4‐Benzodiazepine Scaffold as Antiprotozoal Agents

Novel papain‐family cathepsin L‐like cysteine protease inhibitors endowed with antitrypanosomal and antimalarial activity were developed, through an optimization study of previously developed inhibitors. In the present work, we studied the structure–activity relationships of these derivatives, with the aim to develop new analogues with a simplified and more synthetically accessible structure and with improved antiparasitic activity. The structure of the model compounds was significantly simplified by modifying or even eliminating the side chain appended at the C3 atom of the benzodiazepine scaffold. In addition, a simple methylene spacer of appropriate length was inserted between the benzodiazepine ring and the 3‐bromoisoxazoline moiety. Several rhodesain and falcipain‐2 inhibitors displaying single‐digit micromolar or sub‐micromolar antiparasitic activity against one or both parasites were identified, with activities that were one order of magnitude more potent than the model compounds.     

Control of ATP metabolism in Rhodopseudomonas spheroides

Growth kinetics and cell composition (RNA, protein, bacteriochlorophyll and adenosyl nucleotides phosphate) of Rhodopseudomonas spheroides in photosynthetic growing culture with continuous illumination and various intermittent light regimens have been examined. The results indicated that bacteriochlorophyll and RNA were controlled by ATP level and protein synthesis and growth by the ability of the cells to utilize intracellular ATP.     

Changes in terpene content in milk from pasture-fed cows

Changes of terpene content in milk from cows grazing natural diversified upland pasture were examined in this observational trial. A homogeneous plot divided into 2 subplots was used from May 31 to July 1, 2003 (first growth) and again from October 1 to October 7, 2003 (vegetative regrowth). Each subplot was grazed by 6 dairy cows in 2 ways: strip grazing (SG), with new allocations of pasture strips at 2-d intervals, and paddock grazing (PG). The PG subplot was divided into 3 paddocks and the cows were moved to a new paddock on June 13 and June 24, 2003. Milk from the 6 cows was collected twice a week, pooled, and used for terpene analyses by dynamic headspace gas chromatography-mass spectrometry system. Twenty mono- and 23 sesquiterpenes desorbing from the milk fat were separated. The most abundant monoterpenes were β-pinene, α-pinene, γ-terpinene, limonene, α-tujene, terpinolene, and α-phellandrene. The most abundant sesquiterpenes were β-caryophyllene, α-copaene, β-cedrene, transmuurola-4-(14)-5-diene, β-bisabolene, and δ-cadinene. Both mono- and sesquiterpenes in SG milk increased across time with an 8-fold increase in total terpenes in milk from the beginning to the end of June. In parallel, dicotyledons, including the main terpene-rich plants, increased from 17 to 31% of total biomass of the vegetation and the development of Dactylis glomerata progressed from boot to ripening stage. The terpenes in PG milk were equivalent to those in SG milk for the first paddock at the beginning of June and remained constant or doubled for the sum of mono- and sesquiterpenes, respectively. The lower variability of the PG milk terpene content could be related to the opportunity that PG cows had to choose ingested herbage, whereas the SG cows had limited choice within the smaller allocated pasture strips. Milk from cows grazing regrowth pastures in October contained low levels of terpenes, and values were similar for PG and SG milks. Change in the sum of monoterpenes is representative of changes for most monoterpenes (except for limonene) and, conversely, the change in the sum of sesquiterpenes mainly reflected changes in β-caryophyllene and α-copaene. In addition to effects of botanical composition of pasture, it appears that terpene content in milk may vary according to factors linked to grazing management that need more intensive study. Nevertheless, current results raise questions about the precision of terpenes as feed tracers.     

Ultraviolet-absorbing compounds in milk are related to forage polyphenols

The aim of this work was to characterize UV-absorbing compounds (UAC) in milk in relation to diet. In winter, 4 groups of cows each received a different diet: concentrate rich containing 35% cocksfoot hay (CCH), maize silage (MS), rye grass silage (RS), or rye grass hay (RH). In summer, 2 additional diets were given: mountain grassland hay (GH) and mountain grassland pasture (GP). Polyphenols were analyzed by HPLC and Folin reaction on forages and UAC were extracted from milks and analyzed by HPLC. In forages, the number of polyphenols was lowest in MS (57) and greatest in GP (85). Twenty-four peaks were identified, accounting for 28 to 47% peak area at 280 nm. Caffeoyl compounds and flavonoid glycosides were mainly found in RH, GH, and GP. Hydrolyzed compounds such as hydroxycinnamic acids and aglycones were found in MS and RS. Estimated amounts of polyphenols were lowest for MS (3.7 g/kg), roughly similar for CH, RS, and RH (about 15 g/kg), and greatest for GH and GP (21.6 and 35.3 g/kg, respectively). About 230 different peaks were separated in milks. Milks from RH and GP contained the lowest (87) and the greatest (127) numbers of peaks, respectively. Only 10 peaks were identified, accounting for 21 to 54% of the total spectra area. In addition to the major compound hippuric acid, phenylacetic acid, benzoic acid, 4-hydroxybenzoic acid benzaldehyde, catechol, and small amounts of ferulic acid were found in varying amounts depending on the diet. Flavonoids such as quercetin, luteolin, and apigenin were also present. Hippuric acid was clearly related to the presence of caffeoylquinic compounds in forages. Other identified UAC may originate essentially from forage simple polyphenols or from cell wall aromatics. Some of the several unknown compounds may also originate from the transformation of other nutrients. Estimated amounts of UAC were widely variable within each animal group. They were surprisingly high in CCH and roughly similar in all milks from preserved forages (about 3.6 mg/L), with generally greater values for GH milks, whereas the greatest amount was found in GP milks (13.3 mg/L). Hierarchical clustering clearly discriminated the 6 diets, showing that there were major differences in GP milks. Some UAC were specific to one or a group of diets. Ultraviolet-absorbing compounds are therefore a potential tool to distinguish between milks according to diet. In addition, they may have a bioactive effect on milk component conservation or on human health.     

Quaternary Ammonium Salts and Their Antimicrobial Potential: Targets or Nonspecific Interactions?

For more than 50 years dequalinium chloride has been used successfully as an antiseptic drug and disinfectant, particularly for clinical purposes. Given the success of dequalinium chloride, several series of mono- and bisquaternary ammonium compounds have been designed and reported to have improved antimicrobial activity. Furthermore, many of them exhibit high activity against mycobacteria and protozoa, especially against plasmodia. This review discusses the structure-activity relationships and the modes of action of the various series of (bis)quaternary ammonium compounds.