The Dynamic Role of Breathing and Cellular Membrane Potentials in the Experience of Consciousness

Understanding the mechanics of consciousness remains one of the most important challenges in modern cognitive science. One key step toward understanding consciousness is to associate unconscious physiological processes with subjective experiences of sensory, motor, and emotional contents. This article explores the role of various cellular membrane potential differences and how they give rise to the dynamic infrastructure of conscious experience. This article explains that consciousness is a body-wide, biological process not limited to individual organs because the mind and body are unified as one entity; therefore, no single location of consciousness can be pinpointed. Consciousness exists throughout the entire body, and unified consciousness is experienced and maintained through dynamic repolarization during inhalation and expiration. Extant knowledge is reviewed to provide insight into how differences in cellular membrane potential play a vital role in the triggering of neural and non-neural oscillations. The role of dynamic cellular membrane potentials in the activity of the central nervous system, peripheral nervous system, cardiorespiratory system, and various other tissues (such as muscles and sensory organs) in the physiology of consciousness is also explored. Inspiration and expiration are accompanied by oscillating membrane potentials throughout all cells and play a vital role in subconscious human perception of feelings and states of mind. In addition, the role of the brainstem, hypothalamus, and complete nervous system (central, peripheral, and autonomic)within the mind-body space combine to allow consciousness to emerge and to come alive. This concept departs from the notion that the brain is the only organ that gives rise to consciousness

Kinetochore alignment within the metaphase plate is regulated by centromere stiffness and microtubule depolymerases

During mitosis in most eukaryotic cells, chromosomes align and form a metaphase plate halfway between the spindle poles, about which they exhibit oscillatory movement. These movements are accompanied by changes in the distance between sister kinetochores, commonly referred to as breathing. We developed a live cell imaging assay combined with computational image analysis to quantify the properties and dynamics of sister kinetochores in three dimensions. We show that baseline oscillation and breathing speeds in late prometaphase and metaphase are set by microtubule depolymerases, whereas oscillation and breathing periods depend on the stiffness of the mechanical linkage between sisters. Metaphase plates become thinner as cells progress toward anaphase as a result of reduced oscillation speed at a relatively constant oscillation period. The progressive slowdown of oscillation speed and its coupling to plate thickness depend nonlinearly on the stiffness of the mechanical linkage between sisters. We propose that metaphase plate formation and thinning require tight control of the state of the mechanical linkage between sisters mediated by centromeric chromatin and cohesion

Understanding the mechanism stabilizing intermediate spin states in Fe(II)-Porphyrin

Spin fluctuations in Fe(II)-porphyrins are at the heart of heme-proteins functionality. Despite significant progress in porphyrin chemistry, the mechanisms that rule spin state stabilisation remain elusive. Here, it is demonstrated by using multiconfigurational quantum chemical approaches, including the novel Stochastic-CASSCF method, that electron delocalization between the metal centre and the pi system of the macrocycle differentially stabilises the triplet spin states over the quintet. This delocalisation takes place via charge-transfer excitations, involving the out-of-plane iron d orbitals, key linking orbitals between metal and macrocycle. Through a correlated breathing mechanism, the 3d electrons can make transitions towards the pi orbitals of the macrocycle. This guarantees a strong coupling between the on-site radial correlation on the metal and electron delocalization. Opposite-spin 3d electrons of the triplet can effectively reduce electron repulsion in this manner. Constraining the out-of-plane orbitals from breathing hinders delocalization and reverses the spin ordering. Our results find a qualitative analogue in Kekul\'e resonance structures involving also the metal centre

Single DNA conformations and biological function

From a nanoscience perspective, cellular processes and their reduced in vitro imitations provide extraordinary examples for highly robust few or single molecule reaction pathways. A prime example are biochemical reactions involving DNA molecules, and the coupling of these reactions to the physical conformations of DNA. In this review, we summarise recent results on the following phenomena: We investigate the biophysical properties of DNA-looping and the equilibrium configurations of DNA-knots, whose relevance to biological processes are increasingly appreciated. We discuss how random DNA-looping may be related to the efficiency of the target search process of proteins for their specific binding site on the DNA molecule. And we dwell on the spontaneous formation of intermittent DNA nanobubbles and their importance for biological processes, such as transcription initiation. The physical properties of DNA may indeed turn out to be particularly suitable for the use of DNA in nanosensing applications.Comment: 53 pages, 45 figures. Slightly revised version of a review article, that is going to appear in the J. Comput. Theoret. Nanoscience; some typos correcte

Magnetic resonance multitasking for motion-resolved quantitative cardiovascular imaging.

Quantitative cardiovascular magnetic resonance (CMR) imaging can be used to characterize fibrosis, oedema, ischaemia, inflammation and other disease conditions. However, the need to reduce artefacts arising from body motion through a combination of electrocardiography (ECG) control, respiration control, and contrast-weighting selection makes CMR exams lengthy. Here, we show that physiological motions and other dynamic processes can be conceptualized as multiple time dimensions that can be resolved via low-rank tensor imaging, allowing for motion-resolved quantitative imaging with up to four time dimensions. This continuous-acquisition approach, which we name cardiovascular MR multitasking, captures - rather than avoids - motion, relaxation and other dynamics to efficiently perform quantitative CMR without the use of ECG triggering or breath holds. We demonstrate that CMR multitasking allows for T1 mapping, T1-T2 mapping and time-resolved T1 mapping of myocardial perfusion without ECG information and/or in free-breathing conditions. CMR multitasking may provide a foundation for the development of setup-free CMR imaging for the quantitative evaluation of cardiovascular health

Air-breathing hypersonic vehicle guidance and control studies; An integrated trajectory/control analysis methodology: Phase 1

A tool which generates optimal trajectory/control histories in an integrated manner is generically adapted to the treatment of single-stage-to-orbit air-breathing hypersonic vehicles. The methodology is implemented as a two point boundary value problem solution technique. Its use permits an assessment of an entire near-minimum-fuel trajectory and desired control strategy from takeoff to orbit while satisfying physically derived inequality constraints and while achieving efficient propulsive mode phasing. A simpler analysis strategy that partitions the trajectory into several boundary condition matched segments is also included to construct preliminary trajectory and control history representations with less computational burden than is required for the overall flight profile assessment. A demonstration was accomplished using a tabulated example (winged-cone accelerator) vehicle model that is combined with a newly developed multidimensional cubic spline data smoothing routine. A constrained near-fuel-optimal trajectory, imposing a dynamic pressure limit of 1000 psf, was developed from horizontal takeoff to 20,000 ft/sec relative air speed while aiming for a polar orbit. Previously unspecified propulsive discontinuities were located. Flight regimes demanding rapid attitude changes were identified, dictating control effector and closed-loop controller authority was ascertained after evaluating effector use for vehicle trim. Also, inadequacies in vehicle model representations and specific subsystem models with insufficient fidelity were determined based on unusual control characteristics and/or excessive sensitivity to uncertainty

A phantom based evaluation on the effects of patient breathing motion on Stereotactic Body Radiotherapy treatment volumes

Aim: The aim of the study was to design an upper body phantom to mimic the movement of the lesion inside the lungs during a breathing cycle. Phantom design included an assessment of the motion observed for lung lesions, identification of suitable phantom materials as well as design of a motorized arm to mimic the movements observed inside the lung area of the phantom. Introduction: Expansion margins are added to clinical target volumes contoured by Oncologists in order to safeguard against under- or over-treatment of the target volume. They are designed to account for errors during setup, inaccuracies on the linear accelerator, and movement of targets inside the patient. If the margins are too small, there is a risk that the lesion/target may not receive the necessary dose, due to being partially missed. On the other hand, if the margins are too wide, the lesion will be covered, but normal tissue may receive unnecessary dose, resulting in additional side effects to the patient. Assessment of the impact of these margins is not possible in a static phantom and the availability of a low-cost motorized phantom would assist in the validation of these margins. Method: Previously treated patients' 4D CT scanning data were used to quantify the amount of movement seen for lesions within the lung. A phantom was then designed and built in an attempt to mimic both patient anatomy and movement. Materials were identified to replicate anatomical shape and densities of various organs in the thorax, as seen on CT scan data. Two treatment planning systems (Monaco, (Elekta) and Eclipse (Varian)) were used to determine the dosimetric characteristics of the materials. This was compared to actual dose as delivered by a linear accelerator (Elekta Synergy). Results: Paths were calculated from the breathing cycles during the 4D-CT scan sets and templates designed to mimic these movements. A thorax phantom was built with the appropriate materials suitable and matched densities to replicate a human thorax. Comparing transmission for these materials on a linear accelerator for 6MV and 10MV energy, the deviation from planned versus measured dose varied between 1.67% to 3.32% and 0.45% to 2.30%, respectively for the silicon material and between 0.77% to 3.22% and 0.17% to 2.57% for the 3D printed bone for 6MV and 10MV. iv Conclusion: The measurements done on the linear accelerator matched closely with the calculated values on the treatment planning system for transmission through the materials in the customised phantom. Various proposals were put forward to mimic the movement of the targets within the lung regions. However, it was not possible to manufacture a mechanically based working model due to the small movements observed (<5mm). It is recommended that a robotic solution be investigated as alternative to mimic these small movements

Клінічні аспекти та цитоморфофункціональні особливості слизової оболонки носа при хронічній патології внутрішньоносових структур та їх верифікація на основі даних комп’ютерної томографії

Background. Approximately 30% of the general human population suffers from chronic pathology of intranasal structures, the main manifestations of which are impaired nasal breathing and sense of smell. The main instrumental diagnostic methods for this pathology are X-ray computed tomography (CT), which allows obtaining data on the architecture of the anatomical structures of the upper respiratory tract, and rhinomanometry, based on the results of which it is possible to assess the functional capacity of the nasal cavity during breathing. Also, a thorough study of the cytological material of the mucous membrane of the upper respiratory tract is an important component in determining the functional state of the nasal cavity, clarifying the diagnosis and choosing a treatment method. This allows the doctor to determine the composition and number of cellular elements in the material, assess their condition (destruction, proliferation, dystrophy, necrosis, etc.), ascertain the intensity of the body’s reactive abilities, monitor the dynamics of tissue recovery or the healing process in them, and encourages researchers to study in more detail and comparing the materials of clinical, radiological and cytological studies with the aim of developing a pathogenetically directed complex treatment of patients with nasal breathing disorders. Therefore it is necessary to know aspects of correlation between the results of rhinocytography and CT data in typical pathological conditions with nasal congestion are considered. Purpose – is to study the clinical aspects and cytomorphological and functional features of the nasal mucosa in patients with pathology of intranasal structures with respiratory and olfactory disorders and research their independent verification based on the CT data. Materials and Methods. Clinical examination of patients included the study of complaints, anamnesis of the disease, examination of the ENT organs, rhinomanometry, endoscopic examination of the nasal cavity and nasopharynx, The CT of the paranasal sinuses using 3D cone beam tomography on the Vatech PaX-i3D device, as well as cytological examination of the nasal mucosa. The criteria for participation in the study were the absence of chronic diseases of the cardiovascular, respiratory, digestive, urinary systems, as well as heredity burdened by these diseases. Results. Formation of a different nature of the course and severity of disorders is associated with inflammatory, dyscirculatory and trophic disorders in the nasal mucosa, which weaken both mucociliary clearance and local immunity. This applies mainly to the I group of observations. The consequence of a decrease in local immunity factors in the nasal mucosa is microbial contamination, which is associated with a long-term nasal breathing disorder in the I and II groups of observations, up to five years and six months, respectively. The results of rhinocytography mostly correspond with the aerodynamic models data of nasal сavity from the CT datasets. Conclusions. Despite the reliability of the examinations carried out by us, the cytological examination of the nasal mucosa is only an additional analysis, the interpretation of which should be based on the clinical picture of a particular patient. Proposed aerodynamic model from CT-datasets actually provides an independent verification of the aerodynamic characteristics of the nasal cavity, obtained from rhinomanometry data, and may indicate a violation of nasal breathing according to changes in the internal anatomical configuration of the nasal chanel.Актуальність. Приблизно 30% загальної людської популяції страждає на хронічну патологію внутрішньоносових структур, основними проявами якої є порушення носового дихання та нюху. Основними інструментальними діагностичними методами для виявлення даної патології є рентгенівська комп’ютерна томографія, яка дозволяє отримати дані про архітектоніку анатомічних структур верхніх дихальних шляхів, та риноманометрія, за результами якої можливо оцінити функціональну спроможність носової порожнини при диханні. Досконале дослідження цитологічного матеріалу слизової оболонки верхніх дихальних шляхів також є важливою складовою у визначенні функціонального стану носової порожнини, уточненні діагнозу і вибору методу лікування. Це дозволяє лікарю визначати склад і кількість клітинних елементів у матеріалі, оцінювати їх стан (деструкцію, проліферацію, дистрофію, некроз та ін.), констатувати напруженість реактивних властивостей організму, відстежувати динаміку відновлення тканин чи процес загоєння в них, та спонукає дослідників до більш детального вивчення і зіставлення матеріалів клінічного, радіологічного та цитологічного досліджень з метою розробки патогенетично спрямованого комплексного лікування хворих із порушеннями носового дихання. Тому в роботі розглядаються аспекти кореляції між результатами риноцитографії та даними комп’ютерної томографії у разі типових патологічних станів з порушеннями носового дихання. Мета роботи – вивчення клінічних аспектів і цитоморфофункціональних особливостей слизової оболонки носа у хворих з патологією внутрішньоносових структур з респіраторно-ольфакторними порушеннями та проведення їх незалежної верифікації на основі даних комп’ютерної томографії. Матеріали та методи. Клінічне обстеження хворих включало вивчення скарг, анамнезу захворювання, огляд ЛОР-органів, проведення риноманометрії, ендоскопічне дослідження порожнини носа та носоглотки, комп’ютерної томографії (КТ) навколоносових пазух за допомогою конусно-променевої томографії в форматі 3D на апараті Vatech PaX-i3D, а також цитологічне дослідження слизової оболонки носа. Критеріями участі в дослідженні були відсутність хронічних захворювань серцевосудинної, дихальної, травної, сечовидільної систем, а також обтяженої за цими захворюваннями спадковості. Результати та їх обговорення. Формування різного характеру перебігу та тяжкості порушень пов’язане із запальними, дисциркуляторними та трофічними порушеннями слизової оболонки носа, які послаблюють як мукоциліарний кліренс, так і місцевий імунітет. Це стосується переважно I групи спостережень. Наслідком зниження факторів місцевого імунітету в слизовій оболонці носа є мікробна контамінація, що супроводжується тривалим порушенням носового дихання в І та ІІ групах спостереження до 5 і 6 місяців відповідно. Результати риноцитографії повністю кореспондуються на основі аеродинамічних моделей носової порожнини, які створені за даними комп’ютерної томографії. Висновки. Незважаючи на достовірність проведених нами досліджень, цитологічне дослідження слизової оболонки носа є лише додатковим аналізом, інтерпретація якого повинна базуватися на клінічній картині конкретного пацієнта. Запропонована аеродинамічна модель із КТ-даних фактично забезпечує незалежну верифікацію аеродинамічних характеристик порожнини носа, отриманих за даними риноманометрії, і може свідчити про порушення носового дихання відповідно до змін внутрішньої анатомічної конфігурації носового каналу

Tomo-PIV in a patient-specific model of human nasal cavities: a methodological approach

The human nose serves as the primary gateway for air entering the respiratory system and plays a vital role in breathing. Nasal breathing difficulties are a significant health concern, leading to substantial healthcare costs for patients. Understanding nasal airflow dynamics is crucial for comprehending respiratory mechanisms. This article presents a detailed study using tomo-Particle Image Velocimetry (PIV) to investigate nasal airflow dynamics while addressing its accuracy. Embedded in the OpenNose project, the work described aims to provide a validation basis for different numerical approaches to upper airway flow. The study includes the manufacturing of a transparent silicone model based on a clinical CT scan, refractive index matching to minimize optical distortions, and precise flow rate adjustments based on physiological breathing cycles. This method allows for spatial high-resolution investigations in different regions of interest within the nasopharynx during various phases of the breathing cycle. The results demonstrate the accuracy of the investigations, enabling detailed analysis of flow structures and gradients. This spatial high-resolution tomo-PIV approach provides valuable insights into the complex flow phenomena occurring during the physiological breathing cycle in the nasopharynx. The study’s findings contribute to advancements in non-free-of-sight experimental flow investigation of complex cavities under nearly realistic conditions. Furthermore, reliable and accurate experimental data is crucial for properly validating numerical approaches that compute this patient-specific flow for clinical purposes

Translational design for limited resource settings as demonstrated by Vent-Lock, a 3D-printed ventilator multiplexer

BACKGROUND: Mechanical ventilators are essential to patients who become critically ill with acute respiratory distress syndrome (ARDS), and shortages have been reported due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We utilized 3D printing (3DP) technology to rapidly prototype and test critical components for a novel ventilator multiplexer system, Vent-Lock, to split one ventilator or anesthesia gas machine between two patients. FloRest, a novel 3DP flow restrictor, provides clinicians control of tidal volumes and positive end expiratory pressure (PEEP), using the 3DP manometer adaptor to monitor pressures. We tested the ventilator splitter circuit in simulation centers between artificial lungs and used an anesthesia gas machine to successfully ventilate two swine. RESULTS: As one of the first studies to demonstrate splitting one anesthesia gas machine between two swine, we present proof-of-concept of a de novo, closed, multiplexing system, with flow restriction for potential individualized patient therapy. CONCLUSIONS: While possible, due to the complexity, need for experienced operators, and associated risks, ventilator multiplexing should only be reserved for urgent situations with no other alternatives. Our report underscores the initial design and engineering considerations required for rapid medical device prototyping via 3D printing in limited resource environments, including considerations for design, material selection, production, and distribution. We note that optimization of engineering may minimize 3D printing production risks but may not address the inherent risks of the device or change its indications. Thus, our case report provides insights to inform future rapid prototyping of medical devices