Academic literature on the topic 'RL-37'

ABSTRACT Rhesus monkey bone marrow expresses a cathelicidin whose C-terminal domain comprises a 37-residue alpha-helical peptide (RL-37) that resembles human LL-37. Like its human counterpart, RL-37 rapidly permeabilized the membranes of Escherichia coli ML-35p and lysed liposomes that simulated bacterial membranes. When tested in media whose NaCl concentrations approximated those of extracellular fluids, RL-37 was considerably more active than LL-37 against staphylococci. Whereas human LL-37 contains five acidic residues and has a net charge of +6, rhesus RL-37 has only two acidic residues and a net charge of +8. Speculating that the multiple acidic residues of human LL-37 reduced its efficacy against staphylococci, we made a peptide (LL-37 pentamide) in which each aspartic acid of LL-37 was replaced by an asparagine and each glutamic acid was replaced by a glutamine. LL-37 pentamide's antistaphylococcal activity was substantially greater than that of LL-37. Thus, although the precursor of LL-37 is induced in human skin keratinocytes by injury or inflammation, its insufficiently cationic antimicrobial domain may contribute to the success of staphylococci in colonizing and infecting human skin.

The human cathelicidin LL-37 displays both direct antibacterial activities and the capacity to modulate host-cell activities. These depend on structural characteristics that are subject to positive selection for variation, as observed in a previous analysis of the CAMP gene (encoding LL-37) in primates. The altered balance between cationic and anionic residues in different primate orthologues affects intramolecular salt-bridging and influences the stability of the helical conformation and tendency to aggregate in solution of the peptide. In the present study, we have analysed the effects of these structural variations on membrane interactions for human LL-37, rhesus RL-37 and orang-utan LL-37, using several complementary biophysical and biochemical methods. CD and ATR (attenuated total reflection)-FTIR (Fourier-transform IR) spectroscopy on model membranes indicate that RL-37, which is monomeric and unstructured in bulk solution [F-form (free form)], and human LL-37, which is partly structured and probably aggregated [A-form (aggregated form)], bind biological membranes in different manners. RL-37 may insert more deeply into the lipid bilayer than LL-37, which remains aggregated. AFM (atomic force microscopy) performed on the same supported bilayer as used for ATR-FTIR measurements suggests a carpet-like mode of permeabilization for RL37 and formation of more defined worm-holes for LL-37. Comparison of data from the biological activity on bacterial cells with permeabilization of model membranes indicates that the structure/aggregation state also affects the trajectory of the peptides from bulk solution through the outer cell-wall layers to the membrane. The results of the present study suggest that F-form cathelicidin orthologues may have evolved to have primarily a direct antimicrobial defensive capacity, whereas the A-forms have somewhat sacrificed this to gain host-cell modulating functions.

Campylobacter is a major cause of acute human diarrheal illness. Broiler chickens constitute a primary reservoir for C. jejuni leading to human infection. Consequently, there is a need for developing novel intervention methods. Antimicrobial peptides (AMP) are small proteins which have evolved in most lifeforms to provide defense against microbial infections. To date, over 3000 AMP have been discovered; however, few of them have been analyzed specifically for ability to kill campylobacters. We selected and evaluated a set of 11 unique chemically synthesized AMP for ability to inhibit growth of C. jejuni. Six of the AMP we tested produced zones of inhibition on lawns of C. jejuni. These AMP included: NRC-13, RL-37, Temporin L, Cecropin–Magainin, Dermaseptin, and C12K-2β12. In addition, MIC were determined for Cecropin–Magainin, RL-37 and C12K-2β12 against 15 isolates of Campylobacter representing the three most common pathogenic strains. MIC for campylobacters were approximately 3.1 µg/mL for AMP RL-37 and C12K-2β12. MIC were slightly higher for the Cecropin–Magainin AMP in the range of 12.5 to 100 µg/mL. These AMP are attractive subjects for future study and potential in vivo delivery to poultry to reduce Campylobacter spp. populations.

A clinical case of the presence of multiple aneurysms of segmental branches of the renal artery with a rupture of one of the aneurysms with the formation of a retroperitoneal hematoma. (For citation: Kazarov RL, Maslov PV, Vasilyev AV, et al. Multiple aneurysms of segmentary branches of renal arteries. Urologicheskie vedomosti. 2017;7(2):34-37. doi: 10.17816/uroved7234-37).

To investigate the evolution of the nocturnal boundary layer (NBL) and its impacts on the vertical distributions of pollutant particulates, a combination of in situ observations from a large tethered balloon, remote sensing instruments (aerosol lidar and Doppler wind lidar) and an atmospheric environment-monitoring vehicle were utilized. The observation site was approximately 100 km southwest of Beijing, the capital of China. Results show that a considerable proportion of pollutant particulates were still suspended in the residual layer (RL) (e.g., the nitrate concentration reached 30 μg m−3) after sunset. The NBL height calculated by the aerosol lidar was closer to the top of the RL before midnight because of the pollutants stored aloft in the RL and the shallow surface inversion layer; after midnight, the NBL height was more consistent with the top of the surface inversion layer. As the convective mixing layer gradually became established after sunrise the following day, the pollutants stored in the nocturnal RL of the preceding night were entrained downward into the mixing layer. The early morning PM2.5 concentration near 700 m in the RL on 20 December decreased by 83% compared with the concentration at 13:34 on 20 December at the same height. The nitrate concentration also decreased significantly in the RL, and the mixing down of nitrate from the RL could contribute about 37% to the nitrate in the mixing layer. Turbulence activities still existed in the RL with the bulk Richardson number (Rb) below the threshold value. The corresponding increase in PM2.5 was likely to be correlated with the weak turbulence in the RL in the early morning.

The main problematic background of the article is the nature, prospects and obligations associated with the borrowing of philosophical concepts and ideas by psychology. Reasons are expressed for introductory interventions in psychology from the side of philosophy. An exemplification of such an intervention is presented in the form of an analysis of psychological approaches to the interpretation of E. Husserl's concept of intentionality. R. May's interpretation of intentionality is considered in more detail. It is suggested that his version of the concept of intentionality uses the implicit connotations of the phenomenological interpretation of intentionality with Freud's theory of drive.

The main problematic background of the article is the nature, prospects and obligations associated with the borrowing of philosophical concepts and ideas by psychology. Reasons are expressed for introductory interventions in psychology from the side of philosophy. An exemplification of such an intervention is presented in the form of an analysis of psychological approaches to the interpretation of E. Husserl's concept of intentionality. R. May's interpretation of intentionality is considered in more detail. It is suggested that his version of the concept of intentionality uses the implicit connotations of the phenomenological interpretation of intentionality with Freud's theory of drive.

The ice cloud detection sensitivity of the millimeter cloud radar (MMCR) and the Ka-band Zenith radar (KAZR) is investigated using a collocated Raman lidar (RL) at the Atmospheric Radiation Measurement Program Southern Great Plains site. Only profiles that are transparent to the RL with ice clouds only are considered in this study. The MMCR underestimates the RL ice cloud optical depth (COD) by 20%. The MMCR detects no ice clouds in 37% of the profiles. These profiles where ice cloud goes undetected by the MMCR typically contain very optically thin clouds, with a mean RL ice COD of 0.03. Higher ice cloud detection sensitivity is found for the KAZR, which underestimates the RL ice COD by 15%. The decrease in the ice COD bias for the KAZR compared to the MMCR is largely due to a decrease in the ice COD bias for the situation where the transparent profiles with ice clouds are detected by both the RL and cloud radar. The climatic net ice cloud radiative effects (CREs) from the RL at the top of the atmosphere (TOA) and the surface are 3.2 W m−2 and −0.6 W m−2, respectively. The ice CREs at the TOA and surface are underestimated for the MMCR by 0.7 W m−2 and 0.16 W m−2 (21% and 29%) and underestimated for the KAZR by 0.6 W m−2 and 0.14 W m−2 (17% and 24%). The ice clouds undetected by the cloud radars led to underestimating the climatic net cloud heating rates below 150 hPa by about 0–0.04 K day−1.

High-band allocations in the millimeter-wave (mm-Wave) frequency spectrum offer high-capacity wireless information transmission as required by fifth generation (5G) communication standards. Among different beamforming structures, the Rotman lens (RL) is an attractive passive-microwave-lens-based beamforming network due to its low fabrication cost, reliability, design simplicity and wide-angle scanning capabilities. Conventionally, the RL is implemented using microstrip line (MSL) technology for which there are inherent radiation losses that become severe when operating in mm-Wave 5G frequency bands. In this context, a novel substrate-integrated coaxial line (SICL)-based RL is designed, fabricated and tested, for accurate beamforming with extremely low feed line insertion loss. This article presents a complete design, development and performance analysis of an SICL-based RL beamformer. By using an SICL, isolation of up to 15 dB is achieved between the input beam ports of the RL, while the mutual coupling is kept at less than 20 dB. The SICL design shows a −10 dB insertion loss between the array and beam ports when compared to the same RL developed using MSL technology having an insertion loss of −15 dB. Due to the use of low-loss SICL technology, a realized gain of up to 14.2 dBi is achieved with an excellent scanning capability of −30 to 30 degrees, verifying for the first time the beamforming capabilities associated with SICL technology. The operational frequency band is 20–45 GHz, while the center operating frequency is 26 GHz making it appropriate for above 6-GHz 5G New Radio (NR) operating bands n257 (26.5 GHz to 29.5 GHz), n258 (24.25 GHz to 27.5 GHz), n261 (27.5 GHz to 28.35 GHz) and n260 (37 GHz to 40 GHz). Owing to the low-loss and stable beamforming performance, the SICL RL is suitable for mm-Wave 5G and is extendable to B5G applications.

We have studied the effects of aerosolized substance P (SP) in guinea pigs with reference to lung resistance and dynamic compliance changes and their recovery after hyperinflation. In addition, we have examined the concomitant formation of airway microvascular leakage and lung edema. Increasing breaths of SP (1.5 mg/ml, 1.1 mM), methacholine (0.15 mg/ml, 0.76 mM), or 0.9% saline were administered to tracheostomized and mechanically ventilated guinea pigs. Lung resistance (RL) increased dose dependently with a maximum effect of 963 +/- 85% of baseline values (mean +/- SE) after SP (60 breaths) and 1,388 +/- 357% after methacholine (60 breaths). After repeated hyperinflations, methacholine-treated animals returned to baseline, but after SP, mean RL was still raised (292 +/- 37%; P less than 0.005). Airway microvascular leakage, measured by extravasation of Evans Blue dye, occurred in the brain bronchi and intrapulmonary airways after SP but not after methacholine. There was a significant correlation between RL after hyperinflation and Evans Blue dye extravasation in intrapulmonary airways (distal: r = 0.89, P less than 0.005; proximal: r = 0.85, P less than 0.01). Examination of frozen sections for peribronchial and perivascular cuffs of edema and for alveolar flooding showed significant degrees of pulmonary edema for animals treated with SP compared with those treated with methacholine or saline. We conclude that the inability of hyperinflation to fully reverse changes in RL after SP may be due to the formation of both airway and pulmonary edema, which may also contribute to the deterioration in RL.

2012/2013
The human peptide LL-37 is an important innate immune effector that contributes to defending the organism against infection in different scenarios, ranging from direct bacterial killing to the modulation of immune responses and acting as a signal molecule for different cell types involved in defence or healing. All these functions are possible despite its relatively simple structure, due to its capacity to interact with different types of biological membranes. This cationic peptide is able to switch from a random coil in aqueous solutions into an amphipathic helical structure in presence of salt ions or in the presence of membranes. Intra- and inter-molecular hydrophobic interactions in the hydrophobic sector of the amphipathic helix, together with ionic interactions in the polar sector, make LL-37 prone to self-association, which strongly affects its multiple biological roles, and these therefore need to be explored in detail. In this thesis I have investigated how folding occurs when LL-37 passes from bulk solution to the surface of membranes, and which structural features could be relevant for its in vitro antimicrobial and host cell modulating activities. For this reason comparative biophysical studies were performed on LL-37 and its structurally diverse orthologue in macaque, RL-37. Fluorescent analogues of LL-37 and RL-37, obtained from the systematic substitution of Phe residues with the non-invasive fluorescent probe, p-cyanophenylalanine, contributed to elucidate differential conformational variations in these peptides. Steady-state and time-resolved fluorescence studies confirmed that unlike RL-37, which is monomeric in physiological solution or in presence of neutral model membranes, LL-37 is in an oligomeric form in solution, with a hydrophobic core likely forming near the central region. Furthermore LL-37 appears to interact with both anionic and neutral membranes in an oligomeric form. Cytofluorimetric studies, performed on bacterial cells treated at toxic peptide concentrations, confirmed that the different conformations of LL- and RL-37 in solution give rise to quite different modes of bacterial permeabilization. Lesions of a larger size were observed for LL-37, consistent with a toroidal pore-forming mechanism, while smaller lesions were detected for RL-37 and may indicate an incipient detergent-like mechanism of bacterial inactivation. I further investigated how many molecules are involved in the self-associated form of LL-37, either in solution or in presence of membranes, replacing the Phe5 residue with an analogue bearing Benzoyl-phenylalanine on the side-chain, which is able to crosslink to adjacent molecules when irradiated with UV light. Photo-crosslinking studies revealed that LL-37 is in equilibrium between forms ranging from monomeric to hexameric in physiological solution, and dissociates to lower order oligomers in the presence of membranes, but does not become completely monomeric. The effects of oligomerization on the biological activities of LL-37 were further explored through testing its antiparallel and parallel covalently bound dimers, linked at either end, designed to mimic an obligatory dimeric form of the peptide. Both types of dimerization reduced the antibacterial potency of LL-37 and its capacity to permeabilize the bacterial membrane. Cytotoxic effect against the host cells was instead different for the three forms of dimers tested, and was related to the degree of freedom of the C- or N-terminal region. From the information obtained on the role of oligomerization on the antibacterial and cytotoxic activity of LL-37, I then rationally designed four different analogues of LL-37, which bear minimal primary structure alterations from the native peptide, such as the replacement of one, or exchange of two adjacent residues, in order to modify inter- and intra-molecular salt-bridging. I attempted in this way to transfer some of the RL-37 characteristics to LL-37 in order to improve its antimicrobial properties through reducing its propensity to self-assemble. I confirmed that variations in the equilibrium between attractions or repulsions in LL-37 significantly affect its antibacterial activity and mode of action.
Il peptide antimicrobico dell’uomo LL-37 è un componente importante del sistema immunitario che contribuisce a difendere l’organismo dalle infezioni, per via di diversi meccanismi, che possono variare dall'azione diretta battericida, alla modulazione della risposta immunitaria, agendo da molecola segnale per diversi tipi di cellule coinvolte nella difesa oppure nella guarigione dell'organismo ospite. Tutte queste attività sono dovute alla sua struttura relativamente semplice, ma capace di interagire con diversi tipi di membrane biologiche. Questo peptide carico positivamente è in grado di assumere una conformazione elicoidale in presenza di soluzioni saline oppure in presenza delle membrane. La presenza di interazioni idrofobiche, inter- e intra-molecolari, nel settore idrofobico dell’elica amfipatica insieme alle forze ioniche presenti nella regione polare causano aggregazione di LL-37. Questa caratteristica a sua volta influenza fortemente le diverse attività biologiche di LL-37 e perciò è un aspetto importante che necessita di essere studiato in modo approfondito. In questa tesi io ho investigato come avviene la strutturazione del peptide quando esso passa dalla soluzione alla superficie della membrana, e quali sono gli aspetti strutturali rilevante per l'attività antimicrobica in vitro e per la modulazione della risposta delle cellule dell’ospite. Per questo motivo sono stati usati vari metodi biofisici per confrontare la struttura di LL-37 con il suo ortologo nella scimmia RL-37. Sostituendo un residuo di fenilalanina con la sonda fluorescente non invasiva p-cyano-fenilalanina è stato possibile ottenere vari analoghi fluorescenti dei due peptide nativi, disegnati per ottenere maggior informazione a riguardo le variazioni conformazionali e per investigare il meccanismo d’azione di LL- e RL-37. Gli studi con gli analoghi fluorescenti hanno confermato che diversamente da RL-37, che è monomerico in soluzioni fisiologiche o in presenza di membrane neutre, LL-37 forma un oligomero in soluzione, con un nucleo idrofobico attorno alla regione centrale dell’elica. Inoltre, LL-37 interagisce con le membrane sia cariche positivamente che neutre nella forma oligomerica. Dagli studi fatti con il cyto-fluorimetro, trattando le cellule batteriche con concentrazioni tossiche di peptide, si è notato che i due peptidi con conformazione diversa in soluzione interagiscono e permeabilizzano le membrane in modo diverso. Le lesioni causate nei batteri dopo il trattamento con LL-37 erano regolari e di dimensioni tali da suggerire un meccanismo battericida per via di formazione dei pori di membrana, invece RL-37 causa danni di piccole dimensioni alla membrana batterica, compatibile con un meccanismo d’azione simile a quello di un detergente. Inoltre io ho indagato sul numero di molecole che partecipano alla formazione della forma oligomerica di LL-37, sia in soluzione che in presenza delle membrane. Questo è stato possible tramite la sostituzione di Phe5 con un residuo analogo benzoyl-fenilalanina, il quale permette di legare covalentemente molecole adiacenti, quando viene irradiato con raggi UV. Questi studi hanno dimostrato che LL-37 è in equilibrio tra la forma monomerica ed oligmerica, con estensione fino ad esamero in soluzioni fisiologiche, per poi dissociarsi a forme inferiori oligomeriche in presenza delle membrane. Gli effetti dell’oligomerizzazione del peptide LL-37 sulle sue attività biologiche sono stati ulteriormente investigati tramite lo studio svolto con i dimeri covalenti di LL-37, legati con un ponte di solfuro nella regione C-terminale oppure N-terminale. Questi dimeri, paralleli o antiparalelli sono stati ideati per mimare la fomra oligomerica di LL-37. Entrambi i tipi di dimerizzazione hanno mostrato che l’aggregazione di LL-37 porta ad una riduzione dell’attività antimicrobica e dell’efficienza del peptide a permeabilizzare le membrane batteriche. Invece la cito-tossicità verso le cellule dell’ospite è diversa per tutte e tre forme dimeriche ed è legata al grado di libertà della regione N-terminale del peptide. Date le informazioni ottenute sul ruolo dell’oligomerizzazione sull'attività antibatterica e citotossica di LL-37, io ho disegnato 4 analoghi di LL-37 ottenuti da una minima alterazione della struttura primaria rispetto al peptide nativo, come per esempio lo scambio della posizione di uno o più residui adiacenti in modo da alterare la rete di ponti saline tra le molecole e interamente la struttura del peptide. In questo modo si è voluto attribuire alcune caratteristiche di RL-37 al peptide dell’uomo LL-37, in modo da modificare la sua propensione ad assemblarsi per formare oligomeri. Con questi studi si è confermato che variazioni nel equilibrio delle forze attrattive o repulsive nella catena di LL-37 possono alterare significativamente la sua attività antibatterica e il modo d’azione.
XXVI Ciclo
1985

AbstractSchool improvement research is faced with a school teaching staff, which is not a simple homogeneous entity. The compositional attributes of the teaching staff – such as diversity – can have a crucial influence on school processes. Whether the teaching staff is highly fractured, consists of sharply dissociated subgroups, or has shared beliefs, affects the adoption of school improvement programs differently. However, school improvement research has not yet taken into account what different compositions of the teaching staff mean from a methodological viewpoint. It is true that the use of multilevel analysis is standard in school improvement research and that it considers nested school data. However, this method alone only takes averaged measures of teaching staffs into consideration but not their different compositions. In this contribution, we argue that school improvement research has to consider, theoretically and methodologically, how compositional attributes of the teaching staff can be conceptualized. We first discuss some advancements in the conceptualization of group composition from research on small groups and organizations. We then incorporate suggestions for different diversity typologies from small group research to describe the compositional attributes of the teaching staff. Additionally, we address how the composition of the teaching staff influences each teacher differently, depending on the specific position a teacher has within the teaching staff. We further suggest incorporating the Group Actor-Partner Interdependence Model (GAPIM; Kenny, DA, Garcia RL, Small Group Res 43:468–496, 2012) as a methodological approach for assessing these compositional influences. In addition to classic multilevel analysis, the GAPIM also considers the effects of the other teachers on staff and the similarity and dissimilarity of a teacher to the other members of the teaching staff. Finally, we illustrate the possibilities of the theoretical and methodological endorsements discussed by applying the GAPIM to a data set of 37 German upper secondary schools by way of example. We show that a teacher’s job satisfaction is not only influenced by their individual and collective teacher self-efficacy but also by positional effects: The similarity of a teacher to the other teachers on staff and the similarity among the other members of the teaching staff have additional influences on job satisfaction.

Recent research has confirmed the feasibility of backdoor attacks in deep reinforcement learning (RL) systems. However, the existing attacks require the ability to arbitrarily modify an agent's observation, constraining the application scope to simple RL systems such as Atari games. In this paper, we migrate backdoor attacks to more complex RL systems involving multiple agents and explore the possibility of triggering the backdoor without directly manipulating the agent's observation. As a proof of concept, we demonstrate that an adversary agent can trigger the backdoor of the victim agent with its own action in two-player competitive RL systems. We prototype and evaluate BackdooRL in four competitive environments. The results show that when the backdoor is activated, the winning rate of the victim drops by 17% to 37% compared to when not activated. The videos are hosted at https://github.com/wanglun1996/multi_agent_rl_backdoor_videos.