Crowd Control: Regulating the Spatial Organization of Biopolymers and Gene Expression by Macromolecular Crowding

The intracellular environment is crowded with macromolecules that can occupy a significant fraction of the cellular volume. This can give rise to attractive depletion interactions that impact the conformations and interactions of biopolymers, as well as their interactions with confining surfaces. We used computer simulations to study the effects of crowding on biologically-inspired models of polymers. We showed that crowding can lead to attractive interactions between two flexible ring polymers, and we further characterized the adsorption of both flexible and semiflexible polymers onto confining surfaces. These results indicate that crowding-induced depletion interactions could play a role in the spatial organization of biopolymers in cells, and they also suggest that macromolecular crowding could be used to alter the spatial organization of cell-free synthetic systems. A major limitation of cell-free expression systems, which are widely used to study gene expression, is the lack of means to achieve spatial control of gene expression components. With a coarse-grained model of DNA plasmids and crowders, we showed that plasmids were uniformly distributed at low levels of crowding but, due to depletion interactions, became strongly adsorbed to confining surfaces at high levels of crowding. These results were experimentally validated by our collaborators using DNA and crowders in cell-sized vesicles. We used kinetic Monte Carlo simulations to study the effect of crowding and confinement on gene expression dynamics and noise, giving insight into experiments. Our work provides insights into the role of crowding and confinement on the spatial organization and dynamics of gene expression in cellular and cell-free systems

A Compact UWB BPF with a Notch Band using Rectangular Resonator Sandwiched between Interdigital Structure

This paper presents a compact design of an ultra wide band bandpass filters with a notch band using interdigital structure. The aim of the design is to reduce the size of filter, reduce the complexity of the design, and improve the performance of filter response. The proposed filter comprises of a rectangular resonator sandwiched between Interdigital structures, with rectangular slot as defected microstrip structure at the input and output ports. This design has been used for the first time to achieve the above aim. The advantage with this design is that, it does not use any via or defected ground structure. The insertion loss of proposed filter, in passband between 3.1 GHz to 10.8 GHz, is less than 0.7dB, and for the notched band it is 21.5 dB centred at 7.9 GHz. The proposed filter is fabricated, tested and compared with simulated results. The proposed design was small in size with less complexity, and shows performance better than the other designs available in the literatures at this dimension

Design of Single Narrow Band Bandpass Filter using Cascaded Open Loop Triangular Ring Resonators Embedded with Rectangular Ring

This paper presents a compact single narrow band bandpass filter using two cascaded open loop triangular ring resonator embedded with rectangular ring for various application at 11.8 GHz in microwave communication systems. Coupled resonator theory was used for coupling parasitic resonance of multiple degenerate modes operating close to the fundamental mode in the proposed structure of filter. The frequency response has low insertion loss and good rejection performance of the proposed filter. The filter was easy to fabricate since there was no use of via or defected ground structure. Cascading and the embedded rectangular ring were used to improve the stop band performances by creating several attenuation poles. A wide stop band was obtained at both the sides of passband. The proposed filter was designed and simulated in Agilent Advance Design System. The simulated result and the measured results were in good agreement

Implementation and Applications of Various Feeding Techniques Using CST Microwave StudioÂ

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Suprasellar epidermoid cyst: a rare cause of painless progressive bilateral vision loss-case report with clinico-radiological correlation

Intracranial epidermoid cysts are relatively rare lesions. They result from inclusion of ectodermal elements during time of neural tube closure. This lesion could rarely be acquired due to post-surgical or post traumatic implantation of the ectodermal components. They typically present in middle age group patients with evidence of loco-regional mass effect on adjacent structures. We present a clinico-radiological case report of the 27-year-old female patient who presented with painless progressive bilateral vision loss for last 4 months

Intrathecal Fentanyl With a Paracervical Block Is Safe and Effective for Elective Termination of Pregnancy in a Patient With Primary Pulmonary Hypertension

Pulmonary hypertension (PH) in pregnancy, irrespective of etiology, is associated with significant maternal morbidity and mortality. This case describes a novel approach to providing anesthesia for a hemodynamically fragile patient. It demonstrates the careful planning and weighted decision-making that is required when approaching a parturient with severe pulmonary hypertension. The patient\u27s previous pulmonary artery catheterization showed right ventricular systolic pressure of 78 mmHg and pulmonary artery pressure of 78/20 mmHg. The patient presented with worsening dyspnea and a decision was made to proceed with the termination of pregnancy via dilatation and curettage (D&C). Anesthesia was conducted with combined intrathecal fentanyl with a paracervical block using lidocaine 2%. The patient had a complication of post-procedure hemorrhage secondary to uterine atony that required careful monitoring and judicious use of uterotonic medications. A decision was made to use oxytocin due to its favorable effect profile compared to other uterotonic medications. We hope this anesthesia technique will aid in the future management of these challenging cases

Curious case of corpus callosal hematoma in a normotensive post-partum female patient: a case report of reversible post-partum angiopathy with clinico-radiological correlation

Postpartum cerebral angiopathy (PCA) is a rare cause of stroke in the puerperium. It usually presents with episodes of headache, seizures and neurological deficits in early post-partum period in normotensive females. CT, MRI and catheter angiography may demonstrate segmental vasoconstriction that often resolves spontaneously. PPA is generally regarded as a benign, non-relapsing and reversible disease process. We present a clinico-radiological correlative case of isolated corpus callosal hematoma in a post-partum normotensive female with evidence of intracranial vascular spasm and luminal irregularity on CT and catheter angiography. Follow up MR angiography showed resolution of the vasospasm and luminal irregularity. Patient was managed conservatively and showed resolution of the symptoms in follow up visit on 8th week.

Computational methods for cell culture media optimization and product quality control

Biologics development leading to approval can take decades. Acceleration of this timeline is necessary to bring safe and efficacious drugs to patients as early as possible. One research focus to reduce development time is the cell culture process development and optimization. In this study, we will present two computational strategies that cover: (1) enhancing cell culture media by amino acid optimization using Orthogonal-Partial Least Squares (OPLS) regression, and (2) modulating protein glycosylation by altering small molecule compound concentrations based on the Concentration Impact Factor. Disproportionate nutrient balance in cell culture medium can have a negative impact on cell culture performance. In our study, OPLS regression was used to explain cell growth and monoclonal antibody (mAb) production dynamics from Chinese Hamster Ovary (CHO) cells as a function of amino acid (AA) stoichiometric balances. The OPLS model was trained on metabolic data from 24 concurrent 14-day fed-batch cultures. Metabolic fluxes and respective stoichiometric balances were then generated by calculating the difference between the theoretical biomass demand of each AA and the actual AA usage towards mAb production and experimental consumption. As a result, highly weighted stoichiometric balances represented those AA that could potentially enhance the previous feed medium and aim to achieve a higher intracellular catabolic activity. Accordingly, we used our computational model to generate varied amino acid additions to either a platform feed or a low nutrient feed by means of a 16-run mixture design. The experimental results showed that addition of model generated key AA resulted in a ~55% increase in peak cell density and ~90% increase in mAb production, respectively. Appropriately glycosylated therapeutic mAb are critical for the proper molecular folding, stability, and in-vivo efficacy of the expressed proteins. Cell culture process conditions and medium compositions have been demonstrated to affect the expression of various glycosylation species. In this study, we evaluated a set of selected small compound for their potential in modifying glycosylation levels in mAb expressed in three different proprietary CHO cell lines. These small molecule compounds were first tested on one cell line to establish a baseline. To quantitate the glycosylation modifications, we have developed a mathematical correlation of a dimensionless number, termed Concentration Impact factor (Cf), to describe the degree changes in glycosylation species. Using the Cf algorithm established for the 1st cell line, we subsequently tested with other two cell lines, and were able to modulate and confirmed the level of glycan expression. This indicates that Cf correlation may serve as a tool to provide early assessment of final glycosylation profiles and levels on therapeutic proteins due to small molecule supplementations. Overall, the two computational methods presented here are aimed to enhance biologics development speed as well as ensure product quality control

Intra-Plate Dynamics and Active Tectonic Zones of the Indian Plate

The tectonic framework of the Indian Plate started to evolve since the break-up of Gondwanaland in the Late Triassic. It evolved mainly during the time between its separation from the African plate in the Early-Cretaceous and its collision with the Eurasian plate on the north in Late-Middle Eocene and with the Burmese plate in the northeast in Late-Oligocene. Present active tectonic zones, responsible for earthquake generation, were created by the collision pattern and subsequent plate motion. Continued subduction and plate motion due to ridge push and slab pull are responsible for the activation of primordial faults in the inherent structural fabric of the craton depending on the related stress field. Major tectonic zones of the Indian continental plate are related to the collision fronts and the reactivated intra-cratonic faults along the resurgent paleo-sutures between the proto-cratons. Major Tectonic Zones (TZ) are Himalayan TZ, Assam-Arakan TZ, Baluchistan- Karakoram TZ, Andaman-Nicobar TZ, and Stable Continental Region (SCR) earthquake zone. The structure of the continental margins developed during the break-up of Gondwana continental fragments. Western margin evolved during the sequential separation of Africa, Madagascar, and Seychelles since the Late-Triassic to Late Cretaceous time. The Eastern margin structure evolved during the separation of Antarctica in Mid Cretaceous. The orogenic belt circumscribing the northern margin of Indian plate is highly tectonised as the subduction of the plate continues due to northerly push from the Carlsberg Ridge in the SW and slab-pull towards northeast and east along the orogenic and island arc fronts in the NE. This stress pattern induced an anticlockwise rotatory plate motion. The back thrust from the collision front in the direction opposite to the ridge push put the plate under an overall compressive stress. This stress pattern and the plate motion are responsible for the reactivation of the major intra-cratonic faults. While the tectonised orogenic belts are the zones for earthquake nucleation, the reactivated faults are also the strained mega shear zones across the plate for earthquake generation in SCR. These faults trending WNW-ESE are apparently the transform faults that extend across the continent from Carlsberg ridge in the west to the collision zones in the northeast. As such, they are described here as the ‘trans-continental transform faults’. Three such major fault zones from north to south are (i) North Kathiawar fault - Great Boundary fault (along the Aravalli belt) zone, (ii) South Saurashtra fault (extension of Narmada fault) – SONATA-Dauki-Naga fault zone, and (iii) Tellichery-Cauvery-Eastern Ghat-T3-Hail Hakalula-Naga thrust zone. All these trans-continental faults, which are mega-shear zones, are traceable from western offshore to the northeastern orogenic belts along mega tectonic lineaments across the continent. The neotectonic movements along these faults, their relative motion, and displacement are the architect of the present geomorphic pattern and shape of the Indian craton. The overall compressive stress is responsible for strain build-up within these fault zones and consequent earthquake nucleation. The mid-continental Sonata-Dauki shear zone follows the Central Indian Suture Zone between Bundelkhand Proto Continent (BPC) and Deccan Proto Continent (DPC). With the reactivation of this shear zone, the two proto-cratonic blocks are subjected to relative movement as the plate rotates anticlockwise. The kinematics of these movements and their implications are discussed here with a special reference to the recent 2001 Bhuj earthquake