3D Simulation of Internal Tablet Strength During Tableting

This study presents a new approach to model powder compression during tableting. The purpose of this study is to introduce a new discrete element simulation model for particle–particle bond formation during tablet compression. This model served as the basis for calculating tablet strength distribution during a compression cycle. Simulated results were compared with real tablets compressed from microcrystalline cellulose/theophylline pellets with various compression forces. Simulated and experimental compression forces increased similarly. Tablet-breaking forces increased with the calculated strengths obtained from the simulations. The calculated bond strength distribution inside the tablets showed features similar to those of the density and pressure distributions in the literature. However, the bond strength distributions at the center of the tablets varied considerably between individual tablets.     

Genetically-designed Neural Networks for Error Reduction in an Optimized Biomechanical Model of the Human Elbow Joint Complex

A real time dynamic biomechanical model of the human elbow joint has been used as the first step in the process of calculating time varying joint position from the electromyograms (EMGs) of eight muscles crossing the joint. Since calculation of position has a high sensitivity to errors in the model torque calculation, a genetic algorithm (GA) neural network (NN) has been developed for automatic error reduction in the dynamic model. Genetic algorithms are used to design many neural network structures during a preliminary trial effort, and then each network's performance is ranked to choose a trained network that represents the most accurate result. Experimental results from three subjects have shown model error reduction in 84.2% of the data sets from a subject on which the model had been trained, and 52.6% of the data sets from the subjects on which the model had not been trained. Furthermore, the GA networks reduced the error standard deviation across all subjects, showing that progress in error reduction was made evenly across all data sets.     

Estimation of Coupling Strength in Regenerated Lamprey Spinal Cords Based on a Stochastic Phase Model

We present a simple stochastic model of two coupled phase oscillators and a method of fitting the model to experimental spike-train data or to sequences of burst times. We apply the method to data from lesioned isolated lamprey spinal cords. The remaining tracts at the lesion site are either regenerated medial tracts, regenerated lateral tracts, control medial tracts, or control lateral tracts. We show that regenerated tracts on average provide significantly weaker coupling than control tracts. We compare our model-dependent estimate of coupling strength to a measure of coordination based on the size of deflections in the spike-train cross-correlation histogram (CCH). Using simulated data, we show that our estimates are able to detect changes in coupling strength that do not change the size of deflections in the CCH. Our estimates are also more resistant to changes in the level of dynamic noise and to changes in relative oscillator frequency than is the CCH. In simulations with high levels of dynamic noise and in one experimental preparation, we are able detect significant coupling strength although there are no significant deflections in the CCH.     

老年男性腹股沟疝与肌肉质量、肌力及腹内压的相关性

摘要 目的：探讨老年男性腹股沟疝与肌肉质量、肌力及腹内压力（IAP）的相关性。方法：选取2021年1月-2023年1月在眉山市人民医院普外一科就诊的 86例老年男性腹股沟疝患者作为研究组,选取同期100名老年体检者作为对照组,对两组研究对象的腹部肌肉质量、肌力及IAP进行检测,并探讨其与腹股沟疝发病风险的相关性。结果：研究组患者腹部骨骼肌肉面积值（SMA）、骨骼肌指数（SMI）水平及右手握力、左手握力均低于对照组,腹内脂肪面积、SMI异常比例及直立加压时腹内压（OVIAP）、直立加压前后腹内压差（OVIAPD）、平卧与直立加压时腹内压差（OSVIAPD）均高于对照组,差异均有统计学意义（P<0.05）。Logistic多元回归模型分析结果显示,老年腹股沟疝的发生与SMI水平、SMI异常、右手握力、OVIAPD、OSVIAPD具有相关性（P<0.05）。结论：老年男性腹股沟疝患者存在腹部肌肉质量和肌力的下降,患者在直立做加压动作时可出现IAP水平的升高,上述指标均与腹股沟疝的发生具有相关性,临床可采用针对性的综合干预措施以降低老年男性人群腹股沟疝的发病风险。     

Strength and conditioning practices in rowing

There is limited published research on the practices of strength and conditioning (S &C) coaches in Great Britain. Information about training program design would be useful in developing models of good practice and ecologically valid intervention studies. The aim of this research was to quantify the training practices of coaches responsible for the S&C of rowing athletes. A questionnaire was developed that consisted of 6 sections: (a) personal details, (b) physical testing, (c) strength and power development, (d) flexibility development, (e) unique aspects of the program, and (f) any further relevant comments regarding the athletes prescribed training program. Twenty-two rowing and 10 S&C coaches with an average of 10.5 ± 7.2 years' experience agreed to complete the questionnaire. Approximately, 34% coached rowers of Olympic standard, 34% coached national standard, 3% coached regional standard, 19% coached club standard, and 10% coached university standard rowers. All coaches agreed that strength training enhanced rowing performance and the majority (74%) indicated that athletes' strength trained 2-3 times a week. Almost all coaches (94%) reported their rowers performed strength training, with 81% using Olympic lifting, and 91% employing a periodized training model. The clean (63%) and squat (27%) were rated the most important prescribed exercises. Approximately 50% of coaches used plyometrics such as depth jumps, box drills, and standing jumps. Ninety-four percent indicated they conducted physical testing on their rowers, typically assessing cardiovascular endurance (80%), muscular power (70%), muscular strength (70%), and anaerobic capacity (57%). This research represents the only published survey to date on the S&C practices in rowing within Great Britain.     

Recovery Kinetics of Knee Flexor and Extensor Strength after a Football Match

We examined the temporal changes of isokinetic strength performance of knee flexor (KF) and extensor (KE) strength after a football match. Players were randomly assigned to a control (N = 14, participated only in measurements and practices) or an experimental group (N = 20, participated also in a football match). Participants trained daily during the two days after the match. Match and training overload was monitored with GPS devices. Venous blood was sampled and muscle damage was assessed pre-match, post-match and at 12h, 36h and 60h post-match. Isometric strength as well as eccentric and concentric peak torque of knee flexors and extensors in both limbs (dominant and non-dominant) were measured on an isokinetic dynamometer at baseline and at 12h, 36h and 60h after the match. Functional (KF_ecc/KE_con) and conventional (KF_con/KE_con) ratios were then calculated. Only eccentric peak torque of knee flexors declined at 60h after the match in the control group. In the experimental group: a) isometric strength of knee extensors and knee flexors declined (P<0.05) at 12h (both limbs) and 36h (dominant limb only), b) eccentric and concentric peak torque of knee extensors and flexors declined (P<0.05) in both limbs for 36h at 60°/s and for 60h at 180°/s with eccentric peak torque of knee flexors demonstrating a greater (P<0.05) reduction than concentric peak torque, c) strength deterioration was greater (P<0.05) at 180°/s and in dominant limb, d) the functional ratio was more sensitive to match-induced fatigue demonstrating a more prolonged decline. Discriminant and regression analysis revealed that strength deterioration and recovery may be related to the amount of eccentric actions performed during the match and athletes'' football-specific conditioning. Our data suggest that recovery kinetics of knee flexor and extensor strength after a football match demonstrate strength, limb and velocity specificity and may depend on match physical overload and players'' physical conditioning level.     

Appraising bacterial strains for rapid BOD sensing—an empirical test to identify bacterial strains capable of reliably predicting real effluent BODs

The measured response of rapid biochemical oxygen demand (BOD) biosensors is often not identical to those measured using the conventional 5-day BOD assay. This paper highlights the efficacy of using both glucose–glutamic acid (GGA) and Organisation for Economic Cooperation and Development (OECD) BOD standards as a rapid screen for microorganisms most likely to reliably predict real effluent BODs when used in rapid BOD devices. Using these two synthetic BOD standards, a microorganism was identified that produced comparable BOD response profiles for two assays, the MICREDOX® assay and the conventional 5-day BOD₅ test. A factorial experimental design systematically evaluated the impact of four factors (microbial strain, growth media composition, media strength, and microbial growth phase) on the BOD response profiles using GGA and OECD synthetic standard substrates. An outlier was identified that showed an improved correlation between the MICREDOX® BOD (BOD_sens) and BOD₅ assays for both the synthetic standards and for real wastewater samples. Microbial strain was the dominant factor influencing BOD_sens values, with Arthrobacter globiformis single cultures clearly demonstrating superior rapid BOD_sens response profiles for both synthetic and real waste samples. It was the only microorganism to approach the BOD₅ response for the OECD substrate (171 mg O₂?L^?1), and also reported BOD values for real waste samples that were comparable to those produced by the BOD₅ test, including discriminating between filtered and unfiltered samples.     

A flexible and high throughput liquid chromatography–tandem mass spectrometric assay for the quantitation of telcagepant in human plasma

Telcagepant (MK-0974) is a novel oral calcitonin gene-related peptide (CGRP) receptor antagonist and is currently under clinical development. Results from phases II and III clinical trials have suggested that telcagepant is effective for migraine treatment. A reliable and high throughput protein precipitation (PPT) method for determination of telcagepant in human plasma using liquid chromatography coupled with atmospheric pressure chemical ionization (APCI) tandem mass spectrometry has been developed. Clinical samples, internal standard (IS) and acetonitrile are transferred into 96-well plates using a robotic liquid handling system. An aliquot of 10 μL supernatant is directly injected into the LC–MS/MS system where separation is performed on a FluoPhase RP (150 × 2.1 mm, 5 μm) column with an isocratic mobile phase (60% acetonitrile with 0.1% formic acid and 40% water with 0.1% formic acid) at 0.2 mL/min. The interfering 3S-diastereomer of telcagepant, which is observed in clinical samples, is chromatographically resolved from telcagepant. The PPT procedure significantly reduces the time required for sample processing and the assay is sufficiently sensitive for detection using both API 4000 and API 3000 mass spectrometers. The linear calibration range is 5–5000 nM using 200 μL of plasma. Assay intraday validation was conducted using six calibration curves derived from six lots of human control plasma. Calibration standard accuracy did not deviate by more than 3% and 6% of nominal values, and precision did not exceed 4% coefficient of variation (CV) and 10% CV, respectively on the API 4000 and API 3000. Several clinical phases IIb and III studies have been successfully supported with this assay.     

Pump out the volume—The effect of tracheal and subelytral pressure pulses on convective gas exchange in a dung beetle, Circellium bacchus (Fabricus)

Many flightless beetles like the large apterous dung beetle Circellium bacchus, possess a subelytral cavity (SEC) providing an extra air space below the elytra which connects to the tracheal system (TS) via metathoracic and abdominal spiracles. By measuring subelytral and intratracheal pressure as well as body movements and gas exchange simultaneously in a flow-through setup, we investigated the contribution of convection on Circellium respiratory gas exchange.No constriction phase was observed. TS and SEC pressures were always around atmospheric values. During interburst phase open abdominal spiracles and a leaky SEC led to small CO₂-peaks on a continuous CO₂ baseline, driven by intermittent positive tracheal pressure peaks in anti-phase with small negative subelytral pressure peaks caused by dorso-ventral tergite action.Spiracle opening was accompanied by two types of body movements. Higher frequency telescoping body movements at the beginning of opening resulted in high amplitude SEC and TS pressure peaks. High frequency tergite movements caused subelytral pressure peaks and led to a saw tooth like CO₂ release pattern in a burst. We propose that during the burst open mesothoracic spiracles increase the compliance of the subelytral cavity allowing big volumes of tracheal air being pulled out by convection.     

High throughput flow cytometry

BACKGROUND: Conventional flow cytometry does not allow the rapid analysis of multiple samples. This has limited its uses in drug discovery, for which the standard for throughput is 100,000 samples per day. METHODS: We describe a simple method in which commercial peristaltic tubing is connected from a commercial autosampler to a flow cytometer. The samples are delivered via a peristaltic pump from source wells in a multiwell plate. The samples are separated by air bubbles. RESULTS: Throughput rates approach the limit of the autosampler (up to 100 wells per minute). Using optimal tubing and flow rates, particles remain within appropriate light scatter and fluorescence gates. The carryover between wells is typically less than 5% without and 1% with a wash step. The volumes of sample delivered are in the microliter scale. The approach has been validated with instruments from three manufacturers. CONCLUSIONS: Flow cytometry has potential throughput of 100,000 samples or more per day starting with the method described. The method is currently best suited to end-point assays. However, combined with high-speed sorting and single- cell assays, the number of assays could approach 1 billion per day.     

Flow kinetics of L-asparaginase attached to nylon tubing

L -Asparaginase has been attached by chemical means to the inner surface of nylon tubing. An experimental study has been carried out of the flow kinetics for such a system, asparagine solutions at various concentrations being passed through two lengths of tubing at various flow rates. Measurements were made of the concentration of the product ammonia at the tube exit, and of the rate of formation of ammonia, under the various conditions. Apparent Michaelis constants, K_m(app), were some three orders of magnitude higher than the K_m for the enzyme in free solution (～13 × 10^?6JM). The results were analyzed with respect to the theoretical treatment described in the preceding paper (Kobayashi and Laidler), three different methods being employed. It is concluded that at lower substrate concentrations and flow rates the reactions are largely diffusion-controlled, the enhanced K_m(app) values being largely if not entirely due to the diffusion control; ionic strength studies showed electrostatic repulsion effects to be unimportant. At high concentrations and high flow rates (when the diffusion layer is of negligible thickness) the diffusional effects are minimized, and K_m(app) approaches the true K_m value for the immobilized enzyme.     

减压AF系统内固定治疗胸腰椎爆裂性骨折伴脊髓损伤的疗效

目的:探讨减压AF系统内固定治疗胸腰椎爆裂性骨折伴脊髓损伤的疗效。方法:本研究选取了82例胸腰椎爆裂性骨折伴脊髓损伤的患者,年龄20-67岁,采用减压AF系统内固定方式治疗,对患者术前及术后6个月,12个月的伤椎椎体高度比,Cobb's角,Frankel标准分级,VAS评分,Oswestry功能障碍指数等指标进行检测,以评价减压AF系统内固定的疗效。结果:与术前相比,患者术后6个月,12个月的伤椎体高度比值明显升高,Cobb角值明显下降(P0.05)。术后6个月与12个月伤椎椎体高度比值和Cobb角值改善情况相比,差异没有统计学意义(P0.05)。神经功能恢复方面,16例恢复到了E级,术后A级有4例未恢复,Frankel分级为A的患者术后有效恢复率为90.2%;B级有2例未恢复,B级术后有效恢复率89.5%。C级和D级术后有效恢复率均为100%。患者术后6个月,12个月的VAS和ODI值均低于术前分值(P0.05),且术后12个月ODI值与术后6个月的相比,有显著性差异(P0.05)。结论:减压AF系统内固定法对胸腰椎爆裂性骨折及脊髓神经损伤情况具较好的治疗效果,患者术后痛觉感受明显降低,下腰功能恢复良好,治疗效果满意。     

Evaluation of silicone tubing toxicity using tobacco BY2 culture

Summary Silicone tubing is frequently used for gas exchange in cell culture systems, due to its biocompatibility and high permeability to CO₂ and O₂. In cell culture chambers, medium pH and oxygen levels are often maintained by gas exchange through a coil of silicone tubing. Culture medium is recirculated between the gas exchanger and the culture chamber which contains a suspension of cells. We report that the type of agent used for silicone vulcanization (peroxide or platinum) can markedly affect its biocompatibility, and that tobacco cell culture represents a particularly sensitive indicator of tubing cytotoxicity. Under the conditions studied (cell suspension maintained with forward-reverse flow and stirring), peroxide-cured silicone tubing was toxic to the tobacco BY2 cell culture, in contrast to the platinum-cured silicone tubing that was completely biocompatible. Upon further investigation by mass spectrometry, it was determined that a component with a molecular mass of 288 Da, possibly a tetrachlorinated biphenyl, was present in culture medium in contact with peroxide-cured tubing but not in medium in contact with platinum-cured tubing. Additional curing of peroxide-cured tubing resulted in cell morphology and viability comparable to controls. These data suggest that improperly cured silicone tubing can release catalytic byproducts which can be toxic to plant cells, and that the BY2 tobacco cells represent a suitable model system for studies of materials biocompatibility.     

Tunable Polyaniline‐Based Porous Carbon with Ultrahigh Surface Area for CO2 Capture at Elevated Pressure

Natural gas is the cleanest fossil fuel source. However, natural gas wells typically contain considerable amounts of CO₂, with on‐site CO₂ capture necessary. Solid sorbents are advantageous over traditional amine scrubbing due to their relatively low regeneration energies and non‐corrosive nature. However, it remains a challenge to improve the sorbent's CO₂ capacity at elevated pressures relevant to natural gas purification. Here, the synthesis of porous carbons derived from a 3D hierarchical nanostructured polymer hydrogel, with simple and effective tunability over the pore size distribution is reported. The optimized surface area reaches 4196 m² g^?1, which is among the highest of carbon‐based materials, with abundant micro‐ and narrow mesopores (2.03 cm³ g^?1 with d < 4 nm). This carbon exhibits a record‐high CO₂ capacity among reported carbons at elevated pressure (i.e., 28.3 mmol g^?1 total adsorption at 25 °C and 30 bar). This carbon also shows good CO₂/CH₄ selectivity and excellent cyclability. Molecular simulations suggest increased CO₂ density in micro‐ and narrow mesopores at high pressures. This is consistent with the observation that these pores are mainly responsible for the material's high‐pressure CO₂ capacity. This work provides insights into material design and further development for CO₂ capture from natural gas.     

A theory of membrane permeability: III. The effect of hydrostatic pressure

Using expressions derived in previous papers, the author investigates the behavior of a cell immersed in an infinite medium, under the influence of diffusion of a single solute and flow of water. The effect of hydrostatic pressure on the system is taken into account. It is found that, depending on the values of certain parameters, the cell can collapse, burst, reach a stationary stable state, or execute undamped oscillations; a cell must burst or collapse unless its volume is an increasing function of internal pressure, and it can execute stable oscillations only if its membrane acts as a “potential well” to the molecules of the solute.     

DONNAN EQUILIBRIUM AND THE PHYSICAL PROPERTIES OF PROTEINS : II. OSMOTIC PRESSURE.

1. It had been shown in previous publications that the osmotic pressure of a 1 per cent solution of a protein-acid salt varies in a characteristic way with the hydrogen ion concentration of the solution, the osmotic pressure having a minimum at the isoelectric point, rising steeply with a decrease in pH until a maximum is reached at pH of 3.4 or 3.5 (in the case of gelatin and crystalline egg albumin), this maximum being followed by a steep drop in the osmotic pressure with a further decrease in the pH of the gelatin or albumin solution. In this paper it is shown that (aside from two minor discrepancies) we can calculate this effect of the pH on the osmotic pressure of a protein-acid salt by assuming that the pH effect is due to that unequal distribution of crystalloidal ions (in particular free acid) on both sides of the membrane which Donnan''s theory of membrane equilibrium demands. 2. It had been shown in preceding papers that only the valency but not the nature of the ion (aside from its valency) with which a protein is in combination has any effect upon the osmotic pressure of the solution of the protein; and that the osmotic pressure of a gelatin-acid salt with a monovalent anion (e.g. Cl, NO₃, acetate, H₂PO₄, HC₂O₄, etc.) is about twice or perhaps a trifle more than twice as high as the osmotic pressure of gelatin sulfate where the anion is bivalent; assuming that the pH and gelatin concentrations of all the solutions are the same. It is shown in this paper that we can calculate with a fair degree of accuracy this valency effect on the assumption that it is due to the influence of the valency of the anion of a gelatin-acid salt on that relative distribution of the free acid on both sides of the membrane which Donnan''s theory of membrane equilibrium demands. 3. The curves of the observed values of the osmotic pressure show two constant minor deviations from the curves of the calculated osmotic pressure. One of these deviations consists in the fact that the values of the ascending branch of the calculated curves are lower than the corresponding values in the curves for the observed osmotic pressure, and the other deviation consists in the fact that the drop in the curves of calculated values occurs at a lower pH than the drop in the curves of the observed values.     

Mechanical Strength of 17 134 Model Proteins and Cysteine Slipknots

A new theoretical survey of proteins'' resistance to constant speed stretching is performed for a set of 17 134 proteins as described by a structure-based model. The proteins selected have no gaps in their structure determination and consist of no more than 250 amino acids. Our previous studies have dealt with 7510 proteins of no more than 150 amino acids. The proteins are ranked according to the strength of the resistance. Most of the predicted top-strength proteins have not yet been studied experimentally. Architectures and folds which are likely to yield large forces are identified. New types of potent force clamps are discovered. They involve disulphide bridges and, in particular, cysteine slipknots. An effective energy parameter of the model is estimated by comparing the theoretical data on characteristic forces to the corresponding experimental values combined with an extrapolation of the theoretical data to the experimental pulling speeds. These studies provide guidance for future experiments on single molecule manipulation and should lead to selection of proteins for applications. A new class of proteins, involving cystein slipknots, is identified as one that is expected to lead to the strongest force clamps known. This class is characterized through molecular dynamics simulations.     

American petroleum institute in situ air sparging database

An evaluation of data detailing in situ air sparging (IAS) systems at 59 sites has been assembled into an American Petroleum Institute in situ Air Sparging Database (API‐IAS Database). The database was developed to provide site managers insights concerning the state‐of‐the‐art of IAS system design, operation, and evaluation. The IAS radius of influence (ROI) is often evaluated based on changes in a number of physical, chemical, or biological monitoring parameters. Measurements of groundwater dissolved oxygen levels was the technique used most often to determine the ROI. Other parameters such as pressure changes in the vadose and saturated zones, groundwater mounding, air bubbling in wells and tracer gases were also used to aid in the determination of the IAS ROI. A review of 37 pilot studies revealed that the IAS ROI is generally between 10 to 26 ft. IAS technology is generally being applied in sandy soils. The application of IAS technology was deemed infeasible at seven sites where soils contained high levels of silts or clay. Analysis of design and operation data at 40 IAS sites revealed that a typical IAS well is 2 in. in diameter, with a 2‐ft screen, positioned 5 to 10 ft beneath the water table. The wells typically were operated at an overpressure (i.e., pressure in excess of that required to overcome the hydrostatic head) of less than 5 psi with a flow rate of less than 5 cfm. At several sites when IAS system pressures and flows were doubled, only slight increases in ROI resulted. Significant reductions of dissolved volatile organic hydrocarbon (VOCs) were observed at 12 sites as a result of IAS. However, long‐term water quality data following an IAS system shutdown was very limited.     

Sucrose Synthase in Wild Tomato, Lycopersicon chmielewskii, and Tomato Fruit Sink Strength

Here it is reported that sucrose synthase can be readily measured in growing wild tomato fruits (Lycopersicon chmielewskii) when suitable methods are adopted during fruit extraction. The enzyme also was present in fruit pericarp tissues, in seeds, and in flowers. To check for novel characteristics, the wild tomato fruit sucrose synthase was purified, by (NH₄)₂SO₄ fraction and chromatography with DE-32, Sephadex G-200, and PBA-60, to one major band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The following characteristics were obtained: native protein relative molecular weight 380,000; subunit relative molecular weight 89,000; K_m values with: sucrose 53 millimolar, UDP 18.9 micromolar, UDP-glucose 88 micromolar, fructose 8.4 millimolar; pH optima between 6.2 to 7.3 for sucrose breakdown and 7 to 9 for synthesis; and temperature optima near 50°C. The enzyme exhibited a high affinity and a preference for uridylates. The enzyme showed more sensitivity to divalent cations in the synthesis of sucrose than in its breakdown. Sink strength in tomato fruits also was investigated in regard to sucrose breakdown enzyme activities versus fruit weight gain. Sucrose synthase activity was consistently related to increases in fruit weight (sink strength) in both wild and commercial tomatoes. Acid and neutral invertases were not, because the published invertase activity values were too variable for quantitative analyses regarding the roles of invertases in tomato fruit development. In rapidly growing fruits of both wild and commercially developed tomato plants, the activity of sucrose synthase per growing fruit, i.e. sucrose synthase peak activity X fruit size, was linearly related to final fruit size; and the activity exceeded fruit growth and carbon import rates by at least 10-fold. In mature, nongrowing fruits, sucrose synthase activities approached nil values. Therefore, sucrose synthase can serve as an indicator of sink strength in growing tomato fruits.