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1.
Accid Anal Prev ; 152: 105968, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33578217

ABSTRACT

Haptic shared control is used to manage the control authority allocation between a human and an autonomous agent in semi-autonomous driving. Existing haptic shared control schemes, however, do not take full consideration of the human agent. To fill this research gap, this study presents a haptic shared control scheme that adapts to a human operator's workload, eyes on road and input torque in real time. We conducted human-in-the-loop experiments with 24 participants. In the experiment, a human operator and an autonomy module for navigation shared the control of a simulated notional High Mobility Multipurpose Wheeled Vehicle (HMMWV) at a fixed speed. At the same time, the human operator performed a target detection task. The autonomy could be either adaptive or non-adaptive to the above-mentioned human factors. Results indicate that the adaptive haptic control scheme resulted in significantly lower workload, higher trust in autonomy, better driving task performance and smaller control effort.


Subject(s)
Automobile Driving , Workload , Accidents, Traffic , Adaptation, Physiological , Humans , Task Performance and Analysis
2.
Antimicrob Agents Chemother ; 54(12): 5337-43, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20837751

ABSTRACT

Staphylococcal resistance to linezolid (LZD) is mediated through ribosomal mutations (23S rRNA or ribosomal proteins L3 and L4) or through methylation of 23S rRNA by the horizontally transferred Cfr methyltransferase. To investigate the structural basis for oxazolidinone activity against LZD-resistant (LZD(r)) strains, we compared structurally diverse, clinically relevant oxazolidinones, including LZD, radezolid (RX-1741), TR-700 (torezolid), and a set of TR-700 analogs (including novel CD-rings and various A-ring C-5 substituents), against a panel of laboratory-derived and clinical LZD(r) Staphylococcus aureus strains possessing a variety of resistance mechanisms. Potency against all strains was correlated with optimization of C- and D-rings, which interact with more highly conserved regions of the peptidyl transferase center binding site. Activity against cfr strains was retained with either hydroxymethyl or 1,2,3-triazole C-5 groups but was reduced by 2- to 8-fold in compounds with acetamide substituents. LZD, which possesses a C-5 acetamide group and lacks a D-ring substituent, demonstrated the lowest potency against all strains tested, particularly against cfr strains. These data reveal key features contributing to oxazolidinone activity and highlight structural tradeoffs between potency against susceptible strains and potency against strains with various resistance mechanisms.


Subject(s)
Acetamides/pharmacology , Bacterial Proteins/genetics , Methyltransferases/genetics , Oxazolidinones/pharmacology , Ribosomes/genetics , Staphylococcus aureus/drug effects , Staphylococcus aureus/genetics , Anti-Bacterial Agents/pharmacology , Linezolid , Microbial Sensitivity Tests , Mutation , Staphylococcus aureus/enzymology , Structure-Activity Relationship
3.
Antimicrob Agents Chemother ; 54(12): 5352-5, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20837755

ABSTRACT

Resistance to linezolid (LZD) occurs through mutations in 23S rRNA and ribosomal proteins L3 and L4 or through methylation of 23S rRNA by Cfr. Here we report novel L3 mutations, ΔSer145/His146Tyr and ΔMet169-Gly174, co-occurring with cfr in LZD-resistant Staphylococcus aureus isolates recovered from a hospital outbreak in Madrid, Spain. LZD MIC values (16, 32, or 64 µg/ml) correlated with the presence and severity of the L3 mutation. All isolates had TR-700 (torezolid) MIC values of ≤ 2 µg/ml.


Subject(s)
Acetamides/pharmacology , Anti-Infective Agents/pharmacology , Bacterial Proteins/genetics , Drug Resistance, Bacterial/genetics , Methyltransferases/metabolism , Oxazolidinones/pharmacology , Ribosomal Proteins/genetics , Staphylococcus aureus/drug effects , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Linezolid , Methyltransferases/chemistry , Methyltransferases/genetics , Microbial Sensitivity Tests , Mutation , Ribosomal Protein L3 , Ribosomal Proteins/chemistry , Ribosomal Proteins/metabolism , Staphylococcus aureus/enzymology , Staphylococcus aureus/genetics
4.
Appl Environ Microbiol ; 69(9): 5070-8, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12957888

ABSTRACT

The deep-sea polychaete Alvinella pompejana colonizes tubes on the sides of black smoker chimneys along the East Pacific Rise. A diverse, yet phylogenetically constrained episymbiotic community is obligately associated with its dorsal surface. The morphologically and phylogenetically distinct dominant episymbionts have not yet been cultured, and there are no clearly defined roles for these bacteria in this symbiosis. A large insert fosmid library was screened for the presence of the two dominant phylotypes. Two fosmids, 35.2 and 38 kb, containing phylotype-specific 16S ribosomal DNA sequences were fully sequenced. Each fosmid had a gene encoding ATP citrate lyase, a key enzyme in the reverse tricarboxylic acid (rTCA) cycle, a CO(2) fixation pathway. A selection of episymbiont communities from various geographic locations and vent sites were screened for the presence, diversity, and expression (via reverse transcription-PCR) of the ATP citrate lyase gene. Our results indicate that the ATP citrate lyase gene is not only a consistent presence in these episymbiont communities but is also expressed. Phylogenetically distinct forms of ATP citrate lyase were also found associated with and expressed by bacteria extracted from the tubes of A. pompejana. Utilizing PCR with degenerate primers based on a second key enzyme in the rTCA cycle, 2-oxoglutarate:acceptor oxidoreductase, we also demonstrated the persistent presence and expression of this gene in the episymbiont community. Our results suggest that members of both the episymbiont and the surrounding free-living communities display a chemolithoautotrophic form of growth and therefore contribute fixed carbon to other organisms in the vent community.


Subject(s)
ATP Citrate (pro-S)-Lyase/genetics , Bacteria/isolation & purification , Citric Acid Cycle , Polychaeta/microbiology , Amino Acid Sequence , Animals , Bacteria/classification , Bacteria/genetics , Cosmids , DNA, Ribosomal/genetics , Gene Library , Hot Temperature , Molecular Sequence Data , Phylogeny , Polychaeta/classification , Polychaeta/genetics , RNA, Ribosomal, 16S/genetics , Sequence Alignment , Sequence Homology, Amino Acid
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