Post-concussion syndrome (PCS) can affect up to 20%–30% of patients with mild closed head injury (mCHI), comprising incomplete recovery and debilitating persistence of post-concussional symptoms. Eye ...movements relate closely to the functional integrity of the injured brain and eye movement function is impaired post-acutely in mCHI. Here, we examined whether PCS patients continue to show disparities in eye movement function at 3–5 months following mCHI compared with patients with good recovery. We hypothesized that eye movements might provide sensitive and objective functional markers of ongoing cerebral impairment in PCS. We compared 36 PCS participants (adapted World Health Organization guidelines) and 36 individually matched controls (i.e. mCHI patients of similar injury severity but good recovery) on reflexive, anti- and self-paced saccades, memory-guided sequences and smooth pursuit. All completed neuropsychological testing and health status questionnaires. Mean time post-injury was 140 days in the PCS group and 163 days in the control group. The PCS group performed worse on anti-saccades, self-paced saccades, memory-guided sequences and smooth pursuit, suggesting problems in response inhibition, short-term spatial memory, motor-sequence programming, visuospatial processing and visual attention. This poorer oculomotor performance included several measures beyond conscious control, indicating that subcortical functionality in the PCS group was poorer than expected after mCHI. The PCS group had poorer neuropsychological function (memory, complex attention and executive function). Analysis of covariance showed oculomotor differences to be practically unaffected by group disparities in depression and estimated intellectual ability. Compared with neuropsychological tests, eye movements were more likely to be markedly impaired in PCS cases with high symptom load. Poorer eye movement function, and particularly poorer subcortical oculomotor function, correlated more with post-concussive symptom load and problems on activities of daily living whilst poorer neuropsychological function exhibited slightly better correlations with measures of mental health. Our findings that eye movement function in PCS does not follow the normal recovery path of eye movements after mCHI are indicative of ongoing cerebral impairment. Whilst oculomotor and neuropsychological tests partially overlapped in identifying impairment, eye movements showed additional dysfunction in motor/visuospatial areas, response inhibition, visual attention and subcortical function. Poorer subconscious oculomotor function in the PCS group supports the notion that PCS is not merely a psychological entity, but also has a biological substrate. Measurement of oculomotor function may be of value in PCS cases with a high symptom load but an otherwise unremarkable assessment profile. Routine oculomotor testing should be feasible in centres with existing access to this technology.
Cilj. Svrha je članka, kao i motiv za provedbu ovoga istraživanja, utvrditi prikladnost strukture životopisa koji se unose u mrežni biografski leksikon Obrazi slovenskih pokrajin (Lica slovenskih ...pokrajina). Namjera je i ustanoviti kriterije ili strukturne elemente koji mogu pomoći pri odlučivanju koje će se osobe uključiti u mrežni biografski leksikon.
Pristup/metodologija/dizajn. Za analizu strukture zapisa koji se unose u mrežni biografski leksikon, kao i za utvrđivanje kriterija za odabir osoba za unos u mrežni biografski leksikon, korištena je metoda analize sadržaja.
Rezultati. Definirani su kriteriji za odabir osoba za upis u mrežni biografski leksikon Obrazi slovenskih pokrajin (OSP) i struktura životopisa na mrežnom biografskom leksikonu OSP. Zaključeno je i da je poželjno da redoslijed strukturnih elemenata bude nepromjenjiv. Također, zaključeno je da je za razvoj biografskih leksikona bitna i suradnja svih ustanova koje mogu pridonijeti kvaliteti biografskih leksikona.
Ograničenja. Ograničenje istraživanja predstavljala je činjenica da svaku osobu čiji se životopisi uključuju u mrežni biografski leksikon OSP povezuju biografski jedinstveni podatci, isključivo vezani za život te osobe, pa je teško odrediti jedinstvenu strukturu elemenata.
Također, prema našim saznanjima, nema istraživanja koja se bave strukturom životopisa u biografskim leksikonima.
Originalnost/vrijednost. Rezultati istraživanja mogu pridonijeti kvaliteti unosa u mrežni biografski leksikon OSP, ali i u druge mrežne biografske leksikone. Kvalitetnija struktura životopisa i stručni kriterij za odabir osoba koje će biti uključene u biografski leksikon morali
bi utjecati i na zadovoljstvo korisnika samim portalom. Ovaj je rad i poziv za daljnji istraživački rad na tom području.
In alphaproteobacteria, the two-component system (TCS) formed by the hybrid histidine kinase CckA, the phosphotransfer protein ChpT, and the response regulator CtrA is widely distributed. In these ...microorganisms, this system controls diverse functions such as motility, DNA repair, and cell division. In Caulobacterales and Rhizobiales, CckA is regulated by the pseudo- histidine kinase DivL, and the response regulator DivK. However, this regulatory circuit differs for other bacterial groups. For instance, in Rhodobacterales, DivK is absent and DivL consists of only the regulatory PAS domain. In this study, we report that, in Rhodobacter sphaeroides, the kinase activity of CckA is inhibited by Osp, a single domain response regulator (SDRR) protein that directly interacts with the transmitter domain of CckA. In vitro, the kinase activity of CckA was severely inhibited with an equimolar amount of Osp, whereas the phosphatase activity of CckA was not affected. We also found that the expression of osp is activated by CtrA creating a negative feedback loop. However, under growth conditions known to activate the TCS, the increased expression of osp does not parallel Osp accumulation, indicating a complex regulation. Phylogenetic analysis of selected species of Rhodobacterales revealed that Osp is widely distributed in several genera. For most of these species, we found a sequence highly similar to the CtrA-binding site in the control region of osp, suggesting that the TCS CckA/ChpT/CtrA is controlled by a novel regulatory circuit that includes Osp in these bacteria. IMPORTANCE The two-component systems (TCS) in bacteria in its simplest architecture consist of a histidine kinase (HK) and a response regulator (RR). In response to a specific stimulus, the HK is activated and drives phosphorylation of the RR, which is responsible of generating an adaptive response. These systems are ubiquitous among bacteria and are frequently controlled by accessory proteins. In alphaproteobacteria, the TCS formed by the HK CckA, the phosphotransferase ChpT, and the RR CtrA is widely distributed. Currently, most of the information of this system and its regulatory proteins comes from findings carried out in microorganisms where it is essential. However, this is not the case in many species, and studies of this TCS and its regulatory proteins are lacking. In this study, we found that Osp, a RR-like protein, inhibits the kinase activity of CckA in a negative feedback loop since osp expression is activated by CtrA. The inhibitory role of Osp and the similar action of the previously reported FixT protein, suggests the existence of a new group of RR-like proteins whose main function is to interact with the HK and prevent its phosphorylation.
Generally, the success of optimal sensor placement (OSP) method based on artificial intelligence highly depends on signals at all feasible placements, which may be unavailable or expensive. ...Therefore, the acoustic sensor placement optimization method is proposed based on adversarial transfer learning (ATL) and vibro-acoustic simulation. First, the vibro-acoustic simulation is applied to provide sufficient simulation signals for all feasible placements. To bridge the deviation of simulation and measured signals, the ATL-based conditional generative adversarial network (CGAN) is presented, which can transfer signals from limited measured placements to unmeasured placements. In addition, a multi objective optimization model is proposed to obtain the OSP from three aspects, and it is useful for structural health monitoring (SHM). The acoustic signals obtained from the experimental platform are utilized to explore the feasibility and effectiveness of the proposed method. It can accurately detect the fault with average accuracy of 98.35% under four working conditions. The comparison investigations demonstrate that the proposed method can obtain high-quality signals at all feasible placements, which can realize SHM with the optimal sensor placements and the least sensor cost.
Human
infections pose significant public health challenges globally, primarily due to low diagnostic yield of systemic infections, emerging and expanding antibiotic resistance of both the typhoidal ...and non-typhoidal
strains and the development of asymptomatic carrier state that functions as a reservoir of infection in the community. The limited long-term efficacy of the currently licensed typhoid vaccines, especially in smaller children and non-availability of vaccines against other
serovars necessitate active research towards developing a multivalent vaccine with wider coverage of protection against pathogenic
serovars. We had earlier reported immunogenicity and protective efficacy of a subunit vaccine containing a recombinant outer membrane protein (T2544) of
Typhi in a mouse model. This was achieved through the robust induction of serum IgG, mucosal secretory IgA and
-specific cytotoxic T cells as well as memory B and T cell response. Here, we report the development of a glycoconjugate vaccine, containing high molecular weight complexes of
Typhimurium O-specific polysaccharide (OSP) and recombinant T2544 that conferred simultaneous protection against
Typhi,
Paratyphi,
Typhimurium and cross-protection against
enteritidis in mice. Our findings corroborate with the published studies that suggested the potential of
OSP as a vaccine antigen. The role of serum antibodies in vaccine-mediated protection is suggested by rapid seroconversion with high titers of serum IgG and IgA, persistently elevated titers after primary immunization along with a strong antibody recall response with higher avidity serum IgG against both OSP and T2544 and significantly raised SBA titers of both primary and secondary antibodies against different
serovars. Elevated intestinal secretory IgA and bacterial motility inhibition by the secretory antibodies supported their role as well in vaccine-induced protection. Finally, robust induction of T effector memory response indicates long term efficacy of the candidate vaccine. The above findings coupled with protection of vaccinated animals against multiple clinical isolates confirm the suitability of OSP-rT2544 as a broad-spectrum candidate subunit vaccine against human infection due to typhoidal and non-typhoidal
serovars.
Although the low-rank and sparse matrix decomposition (LRaSMD)-based anomaly detectors can effectively extract the low-rank structure as the background component and the sparse structure as the ...anomaly component for anomaly detection (AD) while simultaneously considering the additive noise, the background interferences in the sparse component remain a serious problem that will increase the false alarm rate and influence the detection of real anomalies. To alleviate this issue, a novel LRaSMD with orthogonal subspace projection (OSP)-based background suppression and adaptive weighting for hyperspectral AD is proposed in this letter. Based on the fact that the background interferences in the sparse component are mainly some sparse objects with slight spectral differences from the main background, the OSP is employed to project the sparse component into the background orthogonal subspace that is estimated from the low-rank component to suppress the background interferences and highlight the anomalies. Furthermore, the low-rank component provides an effective estimation of the background statistics, which can be used to adaptively weigh the detection results. Experiments on both synthetic and real hyperspectral data sets demonstrate the effectiveness of the proposed algorithm.
We determine the Verma multiplicities of standard filtrations of projective modules in integral atypical blocks in the BGG category O for the orthosymplectic Lie superalgebras osp(3|4) by way of ...translation functors. We then explicitly determine the composition factor multiplicities of Verma modules using BGG reciprocity.
There is a need to develop cholera vaccines that are protective in young children under 5 years of age, which induce long-term immunity, and which can be incorporated into the Expanded Programme of ...Immunization (EPI) in cholera-endemic countries. The degree of protection afforded by currently available oral cholera vaccines (OCV) to young children is significantly lower than that induced by vaccination of older vaccine recipients. Immune responses that protect against cholera target the O-specific polysaccharide (OSP) of Vibrio cholerae, and young children have poor immunological responses to bacterial polysaccharides, which are T cell independent antigens. To overcome this, we have developed a cholera conjugate vaccine (CCV) containing the OSP of V. cholerae O1, the main cause of endemic and epidemic cholera. Here, we describe production of CCV through a scalable manufacturing process and preclinical evaluation of immunogenicity in the presence and absence of aluminum phosphate (alum) as an adjuvant. The vaccine displays V. cholerae O1 Inaba OSP in sun-burst display via single point attachment of core oligosaccharide to a recombinant tetanus toxoid heavy chain fragment (rTTHc). Two different pilot-scale production batches of non-GMP CCV were manufactured and characterized in terms of physico-chemical properties and immunogenicity. In preclinical testing, the vaccine induced OSP- and lipopolysaccharide (LPS)-specific IgG and IgM responses, vibriocidal responses, memory B cell responses, and protection in a V. cholerae O1 challenge model. The addition of alum to the administered vaccine increased OSP-specific immune responses. These results support evaluation of CCV in humans.
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