Toward a general theory of linking invariants

Let N_1, N_2, M be smooth manifolds with dim N_1 + dim N_2 +1 = dim M$ and let phi_i, for i=1,2, be smooth mappings of N_i to M with Im phi_1 and Im phi_2 disjoint. The classical linking number lk(phi_1,phi_2) is defined only when phi_1*[N_1] = phi_2*[N_2] = 0 in H_*(M). The affine linking invariant alk is a generalization of lk to the case where phi_1*[N_1] or phi_2*[N_2] are not zero-homologous. In arXiv:math.GT/0207219 we constructed the first examples of affine linking invariants of nonzero-homologous spheres in the spherical tangent bundle of a manifold, and showed that alk is intimately related to the causality relation of wave fronts on manifolds. In this paper we develop the general theory. The invariant alk appears to be a universal Vassiliev-Goussarov invariant of order < 2. In the case where phi_1*[N_1] and phi_2*[N_2] are 0 in homology it is a splitting of the classical linking number into a collection of independent invariants. To construct alk we introduce a new pairing mu on the bordism groups of spaces of mappings of N_1 and N_2 into M, not necessarily under the restriction dim N_1 + dim N_2 +1 = dim M. For the zero-dimensional bordism groups, mu can be related to the Hatcher-Quinn invariant. In the case N_1=N_2=S^1, it is related to the Chas-Sullivan string homology super Lie bracket, and to the Goldman Lie bracket of free loops on surfaces.Comment: Published by Geometry and Topology at http://www.maths.warwick.ac.uk/gt/GTVol9/paper42.abs.htm

Utilization of the wastes of vital activity

The recycling of wastes from the biological complex for use in life-support systems is discussed. Topics include laboratory equipment, heat treatment of waste materials, mineralization of waste products, methods for production of ammonium hydroxide and nitric acid, the extraction of sodium chloride from mineralized products, and the recovery of nutrient substances for plants from urine

Link Invariants of Finite Type and Perturbation Theory

The Vassiliev-Gusarov link invariants of finite type are known to be closely related to perturbation theory for Chern-Simons theory. In order to clarify the perturbative nature of such link invariants, we introduce an algebra V_infinity containing elements g_i satisfying the usual braid group relations and elements a_i satisfying g_i - g_i^{-1} = epsilon a_i, where epsilon is a formal variable that may be regarded as measuring the failure of g_i^2 to equal 1. Topologically, the elements a_i signify crossings. We show that a large class of link invariants of finite type are in one-to-one correspondence with homogeneous Markov traces on V_infinity. We sketch a possible application of link invariants of finite type to a manifestly diffeomorphism-invariant perturbation theory for quantum gravity in the loop representation.Comment: 11 page

Artesunate potentiates antibiotics by inactivating heme-harbouring bacterial nitric oxide synthase and catalase

<p>Abstract</p> <p>Background</p> <p>A current challenge of coping with bacterial infection is that bacterial pathogens are becoming less susceptible to or more tolerant of commonly used antibiotics. It is urgent to work out a practical solution to combat the multidrug resistant bacterial pathogens.</p> <p>Findings</p> <p>Oxidative stress-acclimatized bacteria thrive in rifampicin by generating antibiotic-detoxifying nitric oxide (NO), which can be repressed by artesunate or an inhibitor of nitric oxide synthase (NOS). Suppressed bacterial proliferation correlates with mitigated NO production upon the combined treatment of bacteria by artesunate with antibiotics. Detection of the heme-artesunate conjugate and accordingly declined activities of heme-harbouring bacterial NOS and catalase indicates that artesunate renders bacteria susceptible to antibiotics by alkylating the prosthetic heme group of hemo-enzymes.</p> <p>Conclusions</p> <p>By compromising NO-mediated protection from antibiotics and triggering harmful hydrogen peroxide burst, artesunate may serve as a promising antibiotic synergist for killing the multidrug resistant pathogenic bacteria.</p

Oligomerization of the E. coli Core RNA Polymerase: Formation of (α2ββ'ω)2–DNA Complexes and Regulation of the Oligomerization by Auxiliary Subunits

In this work, using multiple, dissimilar physico-chemical techniques, we demonstrate that the Escherichia coli RNA polymerase core enzyme obtained through a classic purification procedure forms stable (α2ββ'ω)2 complexes in the presence or absence of short DNA probes. Multiple control experiments indicate that this self-association is unlikely to be mediated by RNA polymerase-associated non-protein molecules. We show that the formation of (α2ββ'ω)2 complexes is subject to regulation by known RNA polymerase interactors, such as the auxiliary SWI/SNF subunit of RNA polymerase RapA, as well as NusA and σ70. We also demonstrate that the separation of the core RNA polymerase and RNA polymerase holoenzyme species during Mono Q chromatography is likely due to oligomerization of the core enzyme. We have analyzed the oligomeric state of the polymerase in the presence or absence of DNA, an aspect that was missing from previous studies. Importantly, our work demonstrates that RNA polymerase oligomerization is compatible with DNA binding. Through in vitro transcription and in vivo experiments (utilizing a RapAR599/Q602 mutant lacking transcription-stimulatory function), we demonstrate that the formation of tandem (α2ββ'ω)2–DNA complexes is likely functionally significant and beneficial for the transcriptional activity of the polymerase. Taken together, our findings suggest a novel structural aspect of the E. coli elongation complex. We hypothesize that transcription by tandem RNA polymerase complexes initiated at hypothetical bidirectional “origins of transcription” may explain recurring switches of the direction of transcription in bacterial genomes

Количественная оценка эффекта амнезии и глубины угнетения сознания при терапевтической ингаляции ксенон-кислородной смеси

The current literature lacks data on the incidence of intraoperative awakening during xenon anesthesia. This could be due to amnesia preventing memories of the intraoperative awakening.The objective: to determine the concentration of xenon in the xenon-oxygen mixture, which causes amnesia for events during inhalation in 100% of patients, and to make correlations with the depth of hypnosis as per Kugler scale.Subjects and Methods: 34 patients with chronic neurogenic pain who received 111 20-minute inhalations with concentration of xenon up to 50% were included in the study. Amnesia evaluation, EEG monitoring, and pain assessment on a visual analog scale (VAS) were performed.Results. Amnesic effect developed in 100% of patients at xenon concentration of 45%. On inhalation of xenon at concentrations of up to 50%, EEG changes did not exceed D1 grade on Kugler scale. The decrease in bispectral index (BIS) did not reach the level of deep sedation (Me 96.2%) at xenon concentration of 50%. The decrease in pain on VAS was approximately 60%.Conclusions. Xenon inhalations cause transient congradic amnesia at concentrations of 45% or more. The accuracy of the BIS monitoring readings may be reduced when using xenon in a monovariant. Inhalations of xenon-oxygen mixture in concentrations up to 50% showed good analgesic properties in the framework of combined therapy of chronic pain syndrome.Информация о частоте интранаркозного пробуждения во время анестезии ксеноном в литературе не встречается. Это может быть связано с амнезией, предупреждающей воспоминания у пациентов при наступлении эпизода интранаркозного пробуждения.Цель исследования: определить концентрацию ксенона в ксенон-кислородной смеси, при ингаляции которой у 100% пациентов развивается амнезия на события во время ингаляции, и сопоставить с глубиной угнетения сознания по шкале Kugler.Материалы и методы: включены 34 пациента с хроническим нейрогенным болевым синдромом, которым проведено 111 ингаляций по 20 мин с концентрацией ксенона до 50%. Проводили оценку амнезии, ЭЭГ-мониторинг, оценку боли по визуально-аналоговой шкале.Результаты. Амнестический эффект развивался у 100% пациентов при концентрации ксенона 45%. При ингаляции в концентрациях до 50% изменения ЭЭГ не превысили D1 по шкале Kugler. Снижение BIS не достигло уровня глубокой седации (Ме 96,2%) при концентрации ксенона 50%. Снижение боли по визуально-аналоговой шкале составило ≈ 60%.Выводы. Ингаляции ксеноном вызывают преходящую конградную амнезию при концентрации от 45%. Точность показаний BIS-мониторинга может быть снижена при использовании ксенона в моноварианте. Ингаляции ксенон-кислородной смеси в концентрации до 50% показали хорошие анальгетические свойства в рамках проведения сочетанной терапии хронического болевого синдрома

Nutrient Availability as a Mechanism for Selection of Antibiotic Tolerant Pseudomonas aeruginosa within the CF Airway

Microbes are subjected to selective pressures during chronic infections of host tissues. Pseudomonas aeruginosa isolates with inactivating mutations in the transcriptional regulator LasR are frequently selected within the airways of people with cystic fibrosis (CF), and infection with these isolates has been associated with poorer lung function outcomes. The mechanisms underlying selection for lasR mutation are unknown but have been postulated to involve the abundance of specific nutrients within CF airway secretions. We characterized lasR mutant P. aeruginosa strains and isolates to identify conditions found in CF airways that select for growth of lasR mutants. Relative to wild-type P. aeruginosa, lasR mutants exhibited a dramatic metabolic shift, including decreased oxygen consumption and increased nitrate utilization, that is predicted to confer increased fitness within the nutrient conditions known to occur in CF airways. This metabolic shift exhibited by lasR mutants conferred resistance to two antibiotics used frequently in CF care, tobramycin and ciprofloxacin, even under oxygen-dependent growth conditions, yet selection for these mutants in vitro did not require preceding antibiotic exposure. The selection for loss of LasR function in vivo, and the associated adverse clinical impact, could be due to increased bacterial growth in the oxygen-poor and nitrate-rich CF airway, and from the resulting resistance to therapeutic antibiotics. The metabolic similarities among diverse chronic infection-adapted bacteria suggest a common mode of adaptation and antibiotic resistance during chronic infection that is primarily driven by bacterial metabolic shifts in response to nutrient availability within host tissues

Nitric oxide production and antioxidant function during viral infection of the coccolithophore Emiliania huxleyi

Emiliania huxleyi is a globally important marine phytoplankton that is routinely infected by viruses. Understanding the controls on the growth and demise of E. huxleyi blooms is essential for predicting the biogeochemical fate of their organic carbon and nutrients. In this study, we show that the production of nitric oxide (NO), a gaseous, membrane-permeable free radical, is a hallmark of early-stage lytic infection in E. huxleyi by Coccolithoviruses, both in culture and in natural populations in the North Atlantic. Enhanced NO production was detected both intra- and extra-cellularly in laboratory cultures, and treatment of cells with an NO scavenger significantly reduced viral production. Pre-treatment of exponentially growing E. huxleyi cultures with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) prior to challenge with hydrogen peroxide (H2O2) led to greater cell survival, suggesting that NO may have a cellular antioxidant function. Indeed, cell lysates generated from cultures treated with SNAP and undergoing infection displayed enhanced ability to detoxify H2O2. Lastly, we show that fluorescent indicators of cellular ROS, NO, and death, in combination with classic DNA- and lipid-based biomarkers of infection, can function as real-time diagnostic tools to identify and contextualize viral infection in natural E. huxleyi blooms

Clinical and organizational factors associated with mortality during the peak of first COVID-19 wave: the global UNITE-COVID study

Purpose: To accommodate the unprecedented number of critically ill patients with pneumonia caused by coronavirus disease 2019 (COVID-19) expansion of the capacity of intensive care unit (ICU) to clinical areas not previously used for critical care was necessary. We describe the global burden of COVID-19 admissions and the clinical and organizational characteristics associated with outcomes in critically ill COVID-19 patients. Methods: Multicenter, international, point prevalence study, including adult patients with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) and a diagnosis of COVID-19 admitted to ICU between February 15th and May 15th, 2020. Results: 4994 patients from 280 ICUs in 46 countries were included. Included ICUs increased their total capacity from 4931 to 7630 beds, deploying personnel from other areas. Overall, 1986 (39.8%) patients were admitted to surge capacity beds. Invasive ventilation at admission was present in 2325 (46.5%) patients and was required during ICU stay in 85.8% of patients. 60-day mortality was 33.9% (IQR across units: 20%–50%) and ICU mortality 32.7%. Older age, invasive mechanical ventilation, and acute kidney injury (AKI) were associated with increased mortality. These associations were also confirmed specifically in mechanically ventilated patients. Admission to surge capacity beds was not associated with mortality, even after controlling for other factors. Conclusions: ICUs responded to the increase in COVID-19 patients by increasing bed availability and staff, admitting up to 40% of patients in surge capacity beds. Although mortality in this population was high, admission to a surge capacity bed was not associated with increased mortality. Older age, invasive mechanical ventilation, and AKI were identified as the strongest predictors of mortality