Monday, March 18, 2024

Processing of Soybean Meal and Cake into Flour and Bran

 

Processing of Soybean Meal and Cake into Flour and Bran

Introduction

Soybeans are the most common leguminous crop in the world. It has long been cultivated in the countries of Southeast Asia: China, India, Japan, Korea, Vietnam, Indonesia. Due to its climatic stability, soybeans have been widely distributed outside their original range and are now cultivated in more than sixty countries. The increase in the production of soybean seeds in the world is mainly due to the expansion of the sown area and, to a lesser extent, by increasing yields [1-5].

Nutrition experts define soy as the ideal food for humans. It is assumed that in the middle of the 21st century, more than half of the total volume of soybean seeds produced will be used as raw materials for food production. Soy attracts everyone’s attention not only for its high concentration and usefulness of protein, but also for its economy [5-10]. Vegetable soy and animal proteins are interchangeable in both quantitative and qualitative amino acid composition, close to beef meat proteins. At the same time, the digestibility of soy proteins reaches about 70%. Soy is not only proteins, it contains minerals necessary for the human body: potassium, sodium, calcium, iron, zinc, as well as vitamins of group B and C. Soy products are characterized by the absence of cholesterol, semi-saturated fatty acids and low calorie content [10-14].

Soybean meal is a secondary product of the oil extraction industry in the production of oil from soybean seeds by chemical extraction. Soybean meal is the most popular type of meal in the world. Its production volume in the world reaches about 130 million tons. Soybean meal has found wide application as the main protein additive to the feed of farm animals and in the production of various food products. The purpose of this research is to develop a technology for processing soybean meal and cake into flour and bran by mechanical means.

Research Materials and Methods

In the studies conducted at the Department of Grains, Bakery and Confectionery Technologies of the Federal State Budgetary Educational Institution of Higher Education “MSUPP”, experiments were conducted on the separation into anatomical parts of the initial samples of soybean meal and soybean cake by mechanical means using a roller machine. The object of the study was two samples of soybean meal and two samples of soybean meal with different content of protein, fiber and fat, obtained from two different enterprises. Table 1 presents the chemical composition of the presented samples of soybean meal and cake as objects of study.

Grinding of the initial samples of soybean meal and soybean cake was carried out at the laboratory grinding mill MLP-4 with rifled rollers. The main mechanical and kinematic indicators of the mill MLP-4 are as follows: productivity - up to 100 kg / h, speed of fastrotating roller 5.0 m / s, differential 1.5, arrangement of grooves - back on the back, number of grooves on the 1st running centimeter - 8 pieces, slope of grooves 7%. The developed technological scheme for processing soybean meal and cake into flour and bran consists of only 3 grinding systems. Modes and parameters of grinding on roller machines for all samples of soybean meal and soybean meal remained unchanged. Sifting of intermediate products of soy meal and soybean meal grinding and flour sowing was carried out at the sieving of the MLP-4 mill, consisting of a set of 3 sieves, including 2 grits and one flour sieve.

The chemical and physicochemical parameters of the initial samples of soybean meal and cake, as well as the fractions of soybean flour and soybean bran obtained after grinding, were determined on the infrared grain and flour analyzer OF the INFRALUM® FT-12 (manufactured in Russia).

Results and Discussion

At the first stage of research, grinding of the initial samples of soybean meal and cake was carried out to obtain flour and bran at the MLP-4 laboratory grinding mill with rifled rollers to determine the potential flour milling properties. The data obtained are presented in tables 2-4. As can be seen from Table 2, the total yield of soy protein flour was 93.8%, and the yield of soy bran was 6.2%. The yield of the highest protein fraction of soybean flour was 64.6%, and the yield of the lowest protein fraction of soybean flour was 5.6%. As can be seen from Table 3, the total yield of soy protein flour was 95.6%, and the yield of soy bran was only 4.4%. The yield of the highest protein fraction of soybean flour was 70.1%, and the yield of the lowest protein fraction of soybean flour was 4.7%. As can be seen from Table 4, the total yield of soy protein flour was only 86.5%, and the yield of soy bran was 13.5%. The yield of the highest protein fraction of soybean flour was 54.8%, and the yield of the lowest protein fraction of soybean flour was 8.6%.

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Table 1: Chemical composition of initial samples soybean meal and soybean meal.

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Table 2: Yield and extraction of soybean flour for all technological systems in the processing of soybean meal No. 1.

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Table 3: Yield and extraction of soybean flour for all technological systems during the processing of soybean meal No. 2.

As can be seen from Table 4, the total yield of soy protein flour was 91.7%, and the yield of soy bran was 8.3%. The yield of the highest protein fraction of soybean flour was 65.1%, and the yield of the lowest protein fraction of soybean flour was 8.3%. At the second stage of research, the chemical composition of the initial samples of soybean meal and cake and the products of their processing obtained on a roller machine from all technological systems was determined (Tables 5-8). The chemical composition of the initial samples of soybean meal and cake, as well as those obtained from them as a result of mechanical processing of soybean flour and soybean bran, are presented in tables 6-9. As can be seen from Table 6, the protein content in the highest protein fraction of soybean flour was 47.53% with a yield of 64.6%, and the protein content in soybean bran was 16.16% with a yield of 6.2%. As can be seen from Table 7, the protein content in the highest protein fraction of soybean flour was 43.15% with a yield of 70.1%, and the protein content in soybean bran was 19.22% with a yield of 4.4%.

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Table 4: Output and extraction of soybean flour for all technological systems during processing of soybean cake No. 1.

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Table 5: Output and extraction of soybean flour for all technological systems during processing of soybean cake No. 2.

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Table 6: Chemical composition of the initial sample of high-protein soybean meal No. 1 and products of its processing.

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Table 7: Chemical composition of the initial sample of high-protein soybean meal No. 2 and products of its processing.

As can be seen from Table 8, the protein content in the highest protein fraction of soybean flour was 31.57% with a yield of 54.8%, and the protein content in soybean bran was 19.94% with a yield of 13.5%. As can be seen from Table 9, the protein content in the highest protein fraction of soybean flour was 36.04% with a yield of 65.1%, and the protein content in soybean bran was 15.87% with a yield of 8.3%. Analyzing the data obtained from Tables 6-9, it can be seen that the processing of soybean meal into flour and bran occurs with greater efficiency compared to the processing of soybean meal. This is due to the fact that the original soybean meal has an increased fat content of up to 13. %, which prevents the effective separation of the original cake into flour and bran.

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Table 8: Chemical composition of the initial soybean sample cake No. 1 and products of its processing.

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Table 9: Chemical composition of the initial soybean sample cake No. 2 and products of its processing.

Findings

Based on the results of the studies, it is possible to draw conclusions about the excellent flour milling properties of all the presented samples of soybean meal and cake. The yield of soy protein flour ranged from 86.5 to 95.6%. It is established that the processing of soybean meal into flour and bran occurs with greater efficiency compared to the processing of soybean meal. This circumstance is due to the fact that in the original soybean cake there is an increased fat content of up to 13%,” which prevents the effective separation into flour and bran during the processing of the original cake. It is worth noting that during the processing of soybean cake, clogging (salting) of the cuts of the grinding rollers occurs, which can lead after a short period of time to a decrease in the yield of flour, the productivity of the mill and a deterioration in the quality of the finished product. In addition, sieves are clogged (salting occurs) in the sieve when sieving intermediate products of soy cake grinding. It is necessary to clean the sieves after each system. Thus, the processing of soybean cake into flour and bran is impractical due to the increased oil content.


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Friday, March 15, 2024

Low Cost CPAP for the Developing World

 

Low Cost CPAP for the Developing World

Introduction

The application of Continuous Positive Airway Pressure (CPAP) to the spontaneously breathing infants is a recognised therapeutic intervention for respiratory distress of the newborn, as well as bronchiolitis and pneumonia in the infant. It has been shown to be safe and to reduce the need for mechanical ventilation [1]. It may be applied through intranasal prongs or a nasal mask, with pressure generated by an upstream mechanical ventilator, or by downstream immersion of an exiting tube under required depths of water (Figure 1). In either case, the gases are usually supplied from bottled containers and, therefore, the mixture is likely to be dry and cold. Inhalation of ‘dry’ gas reduces the flow of mucous in the airways by interfering with the function of cilia and by drying secretions [2]. Inflammation may follow, with reduction of lung capacity, compliance and oxygenation [3]. In adults, such interference with flow of secretions has been demonstrated within 10 minutes of application [4]. Inhalation of cold gas has long been known to reduce muco-ciliary action [5]. Within the airways, Inhaled gas is heated and humidified to equilibrium with surrounding tissue, but this process takes energy. Dawson et al suggest that 1-2% of the infant’s energy consumption on the first day of life could, per hour, be expended on cold and dry gas [6].

Furthermore, they emphasise that oxygen consumption increases with the temperature gradient between child and environment. Inhaled gases can be heated and humidified before application but the apparatus is expensive. For example, in Australian dollars the single-use unit which humidifies the inhaled gas costs around $120 but its permanent heating base costs around $3600. To these costs are added those of single-use nasal prongs ($24) and gas supply. A standard 10 L tank costs around $260. If gas flows at 6 L/min, it will be emptied by 6 hours costing about $12 per day (Figure 1). Though the cost of refilling would appear to be minimal, third world budgets are limited, and gas re-supply often not guaranteed. Therefore, the use of small pumps that can entrain air at room temperature and humidity and deliver it at a rate to generate sufficient CPAP may be of advantage in developing world hospitals. The basic gas would be room air and the CPAP, by itself, may increase oxygenation to desired levels (Figure 2). If added oxygen is needed, it can be entrained into the inspiratory side of the apparatus, at the level of the nasal prongs, or further back in the tubing. If desired, inspired gas can be warmed by immersing tubing in warmed water bathes before it enters the nares. Pressure within the tubing, and thus CPAP, would be generated by the ‘fish tank pump’, supplemented by hydrostatic pressure associated with the depth of immersion of the exiting tubing beneath water in a nearby container.

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Figure 1: CPAP.

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Figure 2: High Flow.

To reduce the loss of pressure at the nostrils though any gap surrounding the nasal prongs, the size of the gap was reduced by inserting the prongs through appropriately sized holes cut into non-damaging adhesive tape which was applied across the nostrils. In Bangladesh, we aimed to examine the usefulness of small pumps otherwise designed for aquaria, fitted with plastic tubing acquired from hardware shops, at a total cost of at a total cost of $26. CPAP was applied to noses with standard a Hudson Nasal Prong cannula, costing $24 each. Ethical approval was given by governance of Shishu Children’s Hospital, Mymensingh Community Hospital and Joyramkura Hospitals, Bangladesh. Parental approval was secured for each application of the apparatus.

Method

We employed Hailea ACO 6604 Air pumps with twin outlets each delivering approx. 4.5L/min, for a total of 9L/min. The prongs were applied through holes cut in underlying Duoderm to minimise escape of gas from the nares . The apparatus was held in place in front of the face by Velcro attachment to a knitted cap or a Canberra Hat (Figure 1). The exiting tube was submersed below water in a cheap container with depth measured by an affixed tape. Progress was monitored by recordings of Oxygen Saturations levels (SpO2), Heart Rate (HR) and Respiratory Rate (RR).

Results

21 infants with respiratory distress associated with bronchiolitis and pneumonia were recruited (Figure 3). The average weight was 2.900 Kg. Before the application of ‘fish tank CPAP’, respiratory support had comprised the application of supplemental oxygen via small bore nasal tubes. Overall, with CPAP between 6-7 cm/ H2O, there was a mean increase in SpO2 levels of 16.76%, a mean decrease in RR of 21.2 breaths per minute and a mean decrease in HR 17.52 per min (Table 1). The average time on CPAP was 16.76 hours. Reduction of RR was noted within several hours by some. No complications were noted. One child, however, succumbed to overwhelming sepsis.

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Figure 3: CPAP in use in Mymensingh Children’s Ward.

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Table 1: Neonate and Infant data collected from 3 Bangladeshi Hospitals.

Note: *Shishu Childrens Hospital, **Mymansingh Community Hospital, ***Joyramkura.

Conclusion

The ‘fish tank’ apparatus can support ventilation and improve oxygenation in infants with respiratory distress in resource poorsettings, dramatically reducing costs. We used expensive nasal prongs but Chisti et al have demonstrated, also in Bangladesh, that inexpensive ‘high flow’ tubing with In inbuilt nasal prongs can be modified to produce CPAP by immersing one limb of the tubing beneath water (Figure 2) [7]. We have not yet established how long the ‘fish tank’ pumps will continue to work but experience suggests continued function for many months. Costs of replacement would be reduced by bulk buying. Anecdotally, ‘fish tank’ pumps have been trialled by one of the authors in Papua New Guinea and Madagascar. Indications have included severe pneumonia, bronchiolitis, apnoea of prematurity, as well as neonatal respiratory distress. They have been demonstrated to be efficient but the busyness of the hospitals has, thus far, precluded sufficient documentation for publication. Our study is thus limited by lack of local resources including access to blood gas machines, as well as demands of service load. Nevertheless, in ‘fish tank’ or other small pumps would appear to offer the possibility of CPAP in resource poor settings.


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Thursday, March 14, 2024

Hesitancy in Administering Gelatin-Containing Vaccines to Alpha-Gal Sensitized Patients

 

Hesitancy in Administering Gelatin-Containing Vaccines to Alpha-Gal Sensitized Patients

Introduction

Alpha-gal syndrome is a recently discovered disorder of sensitization to the carbohydrate galactose-α-1,3-galactose (alphagal) following a bite from the Lone Star tick. This can result in an IgE-mediated hypersensitivity reaction to non-primate mammalian meat [2,3] typically developing 3-8 hours following red meat ingestion. Alpha-gal can also be found in gelatin products [1], which gives rise to the question of whether gelatin-containing vaccines, such as the MMR, Varivax, Zostavax, and some influenza (Table 1), can be safely administered to patients sensitized to alpha-gal. Primary care physicians have been observed to be hesitant to administer gelatin-based vaccines to patients with diagnosed alpha-gal meat allergy. Concerns for adverse reactions to vaccines, in general, have resulted in a disconcerting 30% of the US population who have refused vaccination for themselves or their family members.

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Table 1: Gelatin content of vaccines licensed in the United States, 2019.

Methods

Our own records were first studied. Both a search of the Vaccine Adverse Event Reporting System (VAERS) database and a physician survey in an area endemic to the Lone Star tick were employed to access the magnitude of the problem afterwards. The VAERS database was utilized to study the analyzable incidence of hypersensitivity reactions to the MMR, Varivax, and Zostavax vaccines in reference to geographic location from 2000-2020. Pediatricians from an endemic area of Long Island, NY area were questioned regarding the incidence of allergic reactions observed to the gelatin-containing vaccines observed in more than 650 patients known to be sensitized to alpha-gal.

Results

The VAERS results (Table 2) show more vaccine reactions in states endemic to the Lone Star tick, but insufficient information did not permit statistical analysis. Among pediatricians surveyed from the endemic area with a patient population of more than 650 patients sensitized to alpha-gal, there were no noted reactions to the vaccines in the sensitized patients other than the 2 following cases. An observation of an immediate IgE reaction to gelatin-containing vaccines was observed in two patients. The first patient was an adult male who gave a longstanding history of suspected allergic reactions to meat and dairy and required an MMR vaccine at 38 years of age. Within 40 minutes of vaccination, he developed acute onset of cough, chest and throat tightness, and difficulty breathing and speaking. He required emergency room management and 2 doses of epinephrine for resolution. His alpha-gal IgE was noted to be 57.4 kU/L. The second patient had a history of severe gastrointestinal symptoms with dairy and meat, dating back to around 5 years of age. While in the pediatrician’s office following vaccination with Varivax, she developed acute anaphylaxis requiring treatment with epinephrine. She was subsequently tested for alpha-gal allergy and her alpha-gal IgE level was noted to be 10.5 kU/L.

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Table 2: VAERS database reactions to vaccines in reference to geographic location (2000-2020).

Discussion

Data obtained in this study did not support a markedly increased risk of IgE-mediated hypersensitivity reactions in alphagal sensitized patients which is consistent with the observation that many such patients have received gelatin-based vaccines without incident [1]. There is often hesitancy to give gelatin-containing vaccines (Table 1) due to concern for allergic reactions, however the risk of not receiving a particular vaccine may outweigh the possible risk of allergic reaction which is amenable to mitigation. As the world is presented with the development of the COVID-19 vaccines, there is significant scrutiny on every individual aspect of the various vaccines. As more pharmaceutical companies formulate their own versions, some may contain gelatin and the question of whether it is safe to administer these vaccines in alpha-gal sensitized patients will likely arise. The risks of measles, influenza, and COVID-19 infection likely outweigh the possible risk of a controllable IgE-mediated hypersensitivity reaction to a gelatincontaining COVID-19 vaccine. Vaccines should be considered by their physicians in individuals at-risk or hesitant patients, with practiced precautionary measures taken when indicated [4].


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Tuesday, March 12, 2024

Human Experience Versus Rule Decision at Krones AG

 

Human Experience Versus Rule Decision at Krones AG

Introduction

At Krones AG, the world market leader in the beverage industry, orders with very large area requirements have to be produced. Despite very high investments in suitable halls, the available area is a major bottleneck. This is also the case for other companies. Despite the use of planners, at least 21% of orders at Krones have consistently been late in recent years. Delays result in significant penalties and undermine the goal of getting every plant up and running on time. For many orders, delays were only avoided because process accelerations were made in the mostly long production processes through measures such as overtime.
Krones now wanted to know more precisely:
- How good is the actual quality of planning?
- How good is planning that (primarily) follows due dates?
Due to the improvement of planning within the production execution, the production result are not representative of the planning quality in terms of meeting due dates. Therefore, these questions should be answered by a simulation study. This article is structured as follows. In section 2, the previous planning procedure at Krones is explained and section 3 contains the relevant literature. In section 4 the self-developed simulation tool is explained. Section 5 contains an analysis of the simulation results. Finally, in section 6, a summary is given and planned further work is described.

Production and Planning at Krones Ag

Krones AG, headquartered in Neutraubling, Germany, employs around 15,000 people worldwide. It has been producing components, lines and systems for beverages and liquid food since 1951. It is assigned to the machinery and plant engineering sector, and it is a leading manufacturer in packaging and filling technology. The company covers every step of the production process, from product and container manufacturing, through filling and packaging, to material flow and container recycling. One of the last steps is the final assembly of filling machines in plant hall 5. The following description of the assembly serves to illustrate the area requirements, which can increase and decrease over time. At the same time, it mentions technical restrictions due to which processing times are not known in advance and are constant. Only one machine at a time can enter or leave the plant hall through the plant gates. Before starting the final assembly of a machine, a final assembly station with sufficient area is determined depending on the machine size. For example, in Figure 1, three fillers are to be assembled. Such a hall allocation is representative for the entire plant. All subassembly parts and materials of all machines are delivered to the delivery spots (i.e., “delivery spot” in) (Figure 1).

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Figure 1: Detail of the factory layout of the final assembly of the filling technology.

Materials from different machines and assemblies can be mixed here; indicated by “Assembly” in (Figure 1). These outdoor delivery areas are limited but can be used by any type of machine and material. The sub-assemblies and materials are divided into two groups of master material types. The first group of assemblies, due to design and/or weight, can only be lifted into the factory facility with the main crane (in (Figure 1), materials with solid border lines). Mostly these parts are main machine parts. The second group of materials can be brought to their target material location by operators (in (Figure 1) materials with dashed border lines). These are assembly parts sorted in trolleys or bins. These parts can be lifted by auxiliary cranes to their final place in the machine and are assigned to a single machine in the inside material place. These indoor material spots are physically fixed according to the final assembly station and are individual for each machine with materials. Final assembly stations are physically fixed and are individual for each machine with materials. After completion of the final assembly process, the finished machine can only be transported out of the hall by the main crane. The main crane and the outrigger cranes operate at different levels so that blocking is not possible.
Support cranes are divided between the right and left sides of the plant and cannot pass each other on either side. Due to this area demand and the large dimensions of the assembled machines with diameters from 1.0 m to 7.2 m, plant hall 5 has an overall length of 105 m and a width of 30 m and the area usable for assembly consists of 2208 m². In 2020, 145 machines were assembled and a higher number is expected in the next few years. The processing time of the assembly orders varies between 6 weeks and 19 weeks with a mean value of 10.24 weeks and a deviation of 2.5 weeks. At the end of a week, the plants leave the hall. Planning is done, as is standard for companies, by configuring the SAP system specifically for Krones AG. Its main components are listed in (Figure 2). Its main service is ensuring the availability of materials. As analysed in the literature, e.g., [1], this planning provides insufficient results when taking into account the limited capacity. Just very simple procedures are used; which are listed in (Figure 2). As discussed in the literature, e.g., [1-5] scheduling is needed as an additional planning procedure between capacity planning and manufacturing execution.

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Figure 2: Planning at Krones AG via a SAP system.

In Principle, Scheduling of the Assembly Orders of the Hall at Krones is Currently Carried Out by Means of the Following Procedure

Planning is performed always at the beginning of a week. The worklist covers 12 weeks. This worklist is the result of the capacity planning by the SAP system, which is executed every day. At the beginning of each week, a machine can be allocated into the hall, provided that the necessary area is available, without having to reposition the machines already in the hall. A planner uses a printed layout of the plant hall in which the previously scheduled lines are drawn. The plant data, such as length, width, (customer) due date, are located in Krones’ SAP system. Due to planning by the SAP system, the worklist is already ordered. A planner schedules the machines into the hall according to this list, provided availability is assured. The SAP system provides an order list (or machine list) for each day. The SAP system does not determine a sequence between the orders of a single day. A planner orders the machines of such a day. For this, she/he prefers larger required area or processing time over smaller ones. This follows the assumption that smaller machines, in terms of space requirements and/or processing times, can be more easily planned into a partially occupied hall than larger ones.
According to the literature and the experience of planner in companies, there is a conflict of objectives between minimizing the unused area, minimizing the number of workers, and minimizing the tardiness; as seen in the scheduling trilemma; see also [4]. In the literature there are numerous works on scheduling as in [4] or [5] and on layout planning as in [6] or [7]. In combinations of both problems, either scheduling or layout planning dominates. An example is project planning for ships in [8,9] where well-used spatial layout is most important. The class of problem considered here consists not of projects, but of independent individual assembly orders. The proceedings of the annual winter simulation conferences contain many articles on simulation that are relevant to this work. Particularly relevant for this research work were [10] and the description of a process simulation as part of modelling in [11]. The real application operates in dynamic environments where real time events like station failure, tool breakage, arrival of new orders with high priority, changes of due dates etc., may turn a feasible schedule into an infeasible one; examples can be found in [4,5]. A feasible schedule of jobs is achieved by a priority rule like Earliest Due Date (EDD), because a priority rule orders a queue of jobs in front of a station quasi immediately; for its description and the one of other widely used priority rules see [3]. Thus, priority rules are still analysed in many studies on scheduling; one example of a recent one is [12,2].
In addition to this facts, priority rules are also a first choice in the case of complex scheduling problems; especially in industrial practice. Thus, in [13] for a complex scheduling problem the performance of priority rules is analysed. Another example is the application of priority rules for the dispatching of AGVs in flexible job shops in [14]. It might be that in the near future several such problems will be solved by more sophisticated heuristics as genetic algorithms for example.

Simulation Tool

For the simulation study, common commercially available simulation tools such as Plant Simulation from Siemens were first evaluated against a proprietary development. The tools allow extensive visualisations of the processes. However, they cannot significantly reduce the development effort required to control the scheduling of randomly arriving customer orders in the factory hall compared to an in-house development. A tool is developed to simulate and analyse various sequences of assembling filling machines in plant hall 5. It is implemented in Excel (in VBA) and one Excel sheet represents an allocation of plant hall 5. The hall is represented in Excel by a rectangle of cells, where each cell represents an area over 1m² in the plant hall. An assignment of 0 means an unused area (over 1m²) and a 1 means an allocation by a machine; other areas, such as those of passageways, office area, etc., are coded in Excel by 80. The total area required by a filling machine is then a rectangle of 1-s in an Excel sheet. A sequence simulation creates such a sheet for each week (period) of the simulation horizon. It ends if the last machine of a set of orders, called workload, which is known at the beginning of the simulation run, has been assembled.
For a sequence of orders elaborated by a planner or by the slack rule, the machines (orders) are iteratively assigned to plant hall 5 as follows.
For an order (i.e., machine), the production area is searched from left to right and then from top to bottom until a sufficiently large free area is found. This area must also be free in the coming periods, as scheduling sequences are usually not sorted by release date. In the positive case, the allocation takes place, as far left-up as possible. In the negative case, this allocation attempt is repeated as soon as a machine is assembled and has left the hall; this could just happen at the of a week (period). After a successful simulation run, for each order its tardiness (actual completion date minus due date) and for each period the occupied area (or free area) are calculated.

Results

The basis for the simulation experiments is the order data in 2020. The direct use of these data resulted in a very high standard deviation of mean tardiness and other key figures named below and used in the analysis. As a result, it was not possible to identify statistically significant results. In order to obtain meaningful results, the sequence of incoming orders over all weeks was examined more closely. It shows that there are periods in which the due dates can easily be met because the time available for processing (i.e., due date minus release date) is high compared to the net processing time. In contrast, in other periods this ratio (quotient) of available time and net processing time is closer to one or even less than one (and thus critical); note: in the first case this quotient is significantly higher than 1. On the basis of this analysis, two classes of workloads were created. Each consists of a high number of sets of orders. Each of them is planned by a planner and by the slack rule. The key figures shown in (Table 1) are calculated for all sets of orders. Both workloads have the same key figures for the due dates. Therefore, higher processing times for workload 2 result in a more critical due date situation. The results achieved by the planners and the slack rule result in the key figures given in (Table 2).

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Table 1: Key Figures for the Two Classes of Workloads.

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Table 2: Key Figures for the Simulation Runs for Workload WL 1.

As said earlier, a planner prefers larger required area or processing time over smaller ones. Meeting due dates is thus only implicitly relevant in the best case. A detailed analysis of the individual plans shows: Responsible for the differences is that a planner prefers area requirements over tardiness avoidance (Table 3). This is more likely to be the case with sets of orders causing high time pressure. Conversely, there are situations in which the planner achieves better results because she/he achieves faster processing of orders through better utilisation of plant hall 5. Note: the figures for the mean free area are based on makespan (Figure 3).

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Table 3: Key Figures for the Simulation Runs for Workload WL 2.

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Figure 3: Trilemma.

Conclusion

Scheduling in the literature mainly considers a bottleneck, such as the limited capacity of the machines. Requirements for the use of limited area for the assembly of machines is dealt with in other publications. Responsible for this are different approaches to these two problem classes. For the final assembly at Krones AG, both planning problems have to be considered simultaneously. Two experienced planners are used for this purpose. A simulation tool was developed to analyse the possibilities for improvements. The simulation experiments so far show that planners often find a good balance between using the limited area and avoiding tardiness. In situations with high time pressure, a preference for meeting due dates will already provide better results through the slack rule. The two planners are therefore encouraged to consider an allocation decision through slack. The two planners are therefore encouraged to consider an allocation decision through slack. The results so far show a significant difference in the use of free areas. Therefore, combinations of priority rules to meet due dates with rules to avoid unused areas are to be designed and simulatively investigated.


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Thursday, February 29, 2024

Role and Relevant Significance of Autonomic Nerves in Esophageal Tumors

 

Role and Relevant Significance of Autonomic Nerves in Esophageal Tumors

Introduction

Tumor cells continue to proliferate in human body which is a very complex environment. The impact of tumor microenvironment on the occurrence and development of tumors is also one of the key directions of tumor prevention and treatment, and the nervous system, especially the autonomic nervous system, is an important part of the tumor microenvironment. Many studies in recent years had shown that the human autonomic nervous system interacts with tumors and stromal cells to mediate the occurrence and development of a variety of malignant tumors. In addition, new evidence suggests that malignant tumors may reshape autonomic nerves states, thereby maintaining the growth and survival of tumor cells [1]. Therefore, exploring and clarifying the autonomic nerves state of the human body with different tumors is of great significance to the research of tumor diseases. This article will make an exploratory analysis and exposition of autonomic nerves states in esophageal cancer and find ways to slow down the development of the tumor.

The Relationship between the Vagus Nervous System and the Occurrence and Development of Esophageal Cancer

It is well known that the esophagus is innervated by the vagus nerve and the spinal nerve. AS the vagus nerve and the esophagus go together, and anatomical studies had also confirmed that the vagus nerve is the most densely distributed on the esophagus, we need to consider whether the vagus nerve plays a role in esophageal lesions. At the same time, there are phenomena indicating that the vagus nerve in the distal esophagus has low distribution density and small branches, and this area is the high incidence of esophageal cancer. Therefore, some people suspect that vagal denervation may promote the occurrence of esophageal cancer. Ai Qun Wu and some other scholars [2] found that local anastomotic adenosquamous carcinoma was the main cause of recurrent esophageal cancer after surgery, and Esophageal motility disorders such as delayed gastric emptying after surgery were important reasons for the recurrence of this cancer, which suggested that vagal nerve injury may be related to the recurrence of esophageal cancer.

At the same time, Ai Qun Wu et al. believed that the vagus nerve and its transmitter acetylcholine (ACh) can inhibit esophageal cancer by reducing the inflammatory response which leads to oxidative membrane damage and DNA damage. In subsequent cell experiments, acetylcholine and norepinephrine could upregulate DNA repair enzyme expression in the cells of esophageal cancer and promote cell differentiation, which suggested a close relationship between these two neurotransmitters and cancer cell transformation. Except for Ai Qun Wu’s discussion on the relationship between vagus nerve and esophageal cancer, we have not find any other papers on this aspect. This suggests that the decrease of vagus nerve excitation can promote the occurrence of esophageal cancer, which may be just a guess, but not been effectively proved.

The Relationship between the Sympathetic Nervous System and the Occurrence and Development of Esophageal Cancer

As for the relationship between sympathetic nerve and the occurrence and development of esophageal cancer, most of the current studies focus on β receptors. Liu, et al. [3] used β-receptor selectors to regulate esophageal cancer cells and found that β -receptor agonists could promote cell proliferation, while β-receptor blockers significantly inhibited cell proliferation, suggesting that β-adrenergic receptors of the sympathetic nervous system are related to the growth of esophageal cancer. However, β receptor is related to the proliferation of a variety of tumor cells, such as breast cancer, gastric cancer, pancreatic cancer, malignant melanoma, prostate cancer, etc. and studies had shown that the use of β-adrenergic receptor blockers did not improve survival in patients with common cancers [4]. Therefore, whether there is a clear relationship between sympathetic nerve and esophageal cancer still needs to be confirmed.

Relationship between the Occurrence and Development of Esophageal Cancer and Nitric Oxide (NO)

It can be seen from the above studies that the autonomic nervous system, which is mainly composed of the sympathetic nerve and vagus nerve, does not seem to have much influence on the occurrence and development of esophageal cancer. Is the growth of esophageal cancer not affected by the tumor microenvironment constructed by the autonomic nervous state? However, it is not likely to grow independently. Could there be a non-adrenergic, non-cholinergic nerve that plays a role in esophageal cancer? NO is the important inhibitory non-adrenergic, non-cholinergic neurotransmitter, it mainly exists in the tissues of the gastrointestinal tract and is responsible for regulating the movement of the gastrointestinal tract [5]. It is generally believed that the release of NO in gastrointestinal tract is related to nitric oxide synthase (nNOS) expressed on the neuroexpandable membrane of intestinal neurons [6].

There is a large literature showing that nitric oxide (NO) plays a role in the development of esophageal cancer. For example, in the 57 cases of human esophageal squamous cell carcinoma studied by Tanaka et al. [7], high expression of iNOS was detected in 50 cases (87.7%), while the expression of iNOS was weak in esophageal non-neoplastic diseases. McAdam, et al. [8] found that iNOS/NO can induce DNA damage and nuclear factor -κB (NF-κB) signal transduction in esophageal cells, leading to the occurrence of esophageal cancer. Chen, et al. [9] found that selective iNOS inhibitors can significantly inhibit the progression of esophageal cancer by reducing NO production. Chen, et al. [10] found that benzo (a) pyrene in tobacco can increase the expression of iNOS, leading to the occurrence of esophageal cancer. These studies indicate that NO, a non-adrenergic and non-cholinergic neurotransmitter, plays a definite role in the occurrence of esophageal cancer.

The Tumor Mostly Occurs in the Middle and Lower Esophagus, Which May be Related to the Release of NO

Studies have shown that the contraction and relaxation of the lower esophageal sphincter are mainly affected by the action of NO [11-13], so where is the main source of NO in the esophagus? Kuramoto, et al. [14] found that nitric oxide synthase (NOS) in the esophagus is mostly concentrated on Fos neurons, while the distribution of Fos neurons in the esophagus gradually increased from the oral cavity to the gastric end and was highest in the abdominal esophagus. This is consistent with the common clinical phenomenon that esophageal cancer occurs in the middle and lower segments. It was also found that when the esophageal vagus nerve was stimulated, NOS in Fos neurons first showed high expression. Thus, it could release a large amount of NO to inhibit esophageal movement, while Fos neurons only expressed a small amount of acetylcholine transferase [14,15]. Meanwhile, Vazquez, et al. [16] showed that nitric oxide synthase inhibitors can promote the release of acetylcholine in the brain. Leonard, et al. [17] showed that NO can regulate the release of ACh. This can reasonably explain why there may be a relationship between vagus nerve and esophageal cancer mentioned in this paper, but no further research has been conducted.

The Occurrence and Development of Esophageal Cancer is Closely Related to Inos/NO, Especially Squamous Cell Carcinoma

As a physiological messenger, NO is synthesized by three different gene-encoded NO synthases (NOS) in mammals: neuronal NOS (nNOS or NOS-1), inducible NOS (iNOS or NOS- 2) and endothelial,NOS (eNOS or NOS-3). NO regulates a variety of important phy-siological responses, including vasodilation, respiration, cell migration, immune response and apoptosis. All these features are relevant in cancer [18]. It may be related to concentration, location, targets, source and other factors, NO can plays a role in promoting as well as inhibiting tumors [19,20]. In esophageal cancer, a large number of studies have found that iNOS/NO is closely related to the occurrence and development. For example, Kumagai, et al. [21] showed that the expression intensity of iNOS is positively correlated with the depth of tumor invasion of the esophageal wall. This may be due to iNOS and COX- 2 from cancer cells induce angio-genesis from the early stage of esophageal squamous cell carcinoma (ESCC) progression, in which NO produced by iNOS has been reported to enhance the activity of COX-2 [22].

Bednarz-Misa’s research has shown that Esophageal squamous carcinoma might be locally characterized by upregulated expression of genes encoding glucose transporter 1 (GLUT1) as well as inducible nitric oxide synthase (iNOS) and ornithine decarboxylase (ODC) of the L-arginine/nitricoxide (NO)/polyamine pathway. Karakasheva, et al. [23] found that iNOS could induce CD38-expressing in myeloidderived Suppressor in a Murine model of oral-esophageal cancer, thereby promoting tumor Growth. In esophageal adenocarcinoma, the Reflux esophagitis causes Barrett’s metaplasia [24], an abnormal esophageal mucosa predisposed to adenocarcinoma; McAdam’s research has shown that the protein levels of iNOS in esophageal adenocarcinoma was increased and the activity of DNA damage induction and nuclear factor-kappa B (NF-κB) signalling was dependent on iNOS/NO. Vaninetti, et al. [25] found that the expression of iNOS mRNA is higher than induced esophagitis and Barrett’s in esophageal adenocarcinoma, while Ferguson, et al. [26] explored the association Between iNOS polymorphisms and risk of esophageal adenocarcinoma, Barrett’s esophagus, or reflux esophagitis, did not show a positive result in the experiments.

Therefore, the role of iNOS/NO in esophageal adenocarcinoma remains to be further explored. Takala, et al. [27] found that iNOS positivity was more com-monly seen in squamous cell carcinomas than adenocarcinomas in esophageal cancer patients. For other types of NOS, only Chandra, et al. [28] detected NOS-3 expression in tissue samples of 20 patients with esophageal adenocarcinoma. It can be seen from the above studies that the expression of iNOS is more closely related to esophageal squamous cell carcinoma, and we can intervene the development of ESCC by inhibiting the expression of iNOS/NO.

Screening Drugs for Esophageal Cancer through Inos/ NO Pathway, Traditional Chinese Medicine May be the Best Choice

The role of iNOS/NO in the occurrence of esophageal cancer has been found, so what is the effect of relevant inhibitory drug intervention based on this? A study found that L-748706, a selective COX-2 inhibitor, and S,S′-1,4-phenylene-bis(1,2-ethanediyl)bisisothiourea (PBIT), a selective iNOS inhibitor, significantly inhibit NMBA-induced rat esophageal tumorigenesis [9,29]. Chen, et al. [30,31] found lyophilized Strawberries significantly reduced the protein expression level of iNOS and were shown to be effective in the prevention and treatment of esophageal cancer. Many studies have found that traditional Chinese medicine can achieve different therapeutic effects by interfering iNOS/NO. Guo, et al. [32] quickly screened and identified iNOS inhibitors from Ophiopogon japonicus. Chen, et al. [33] screened effective anti-inflammatory drugs by measuring the iNOS/NO inhibitory effect of extracts of 81 Kinds of traditional Chinese medicines. Mei, et al. [34] found two new ingredients from Lonicera Macranthoides, exhibited inhibitory effects on iNOS. Tian, et al. [35] found Berberine attenuates Renovascular hypertension and Sympatholay via the iNOS Pathway.

Such as Viola Yedoensis Makiho [36], Illicium Difengpi [37], Plantanone C [38] and Tribulus Terrestris L [39] can downregulation the expression of iNOS. It can be concluded that screening drugs for the prevention and treatment of esophageal cancer from Chinese herbal medicine through iNOS/NO pathway has great advantages. Qigesan, Shashen Maidong Decoction and other traditional Chinese medicine prescriptions for the treatment of esophageal cancer, as a kind of empirical medicine, it is still used in clinical Chinese medicine and has shown good results. Our previous studies found that Qigesan significantly inhibited the migration and invasion of esophageal cancer cells in vitro [40], and Qigesan inhibits esophageal cancer cell invasion and migration by inhibiting Gas6/Axl-induced epithelial-mesenchymal transition and NF-κB expression [41,42]. In the next step, we can use the iNOS/NO pathway to more accurately screen the active ingredients of related drugs from traditional prescriptions.

Conclusion

In conclusion, during the occurrence and development of esophageal cancer, the human autonomic nervous system releases a large amount of NO and only expresses a small amount of ACh, thus promoting the progression of esophageal cancer. Therefore, we can also treat esophageal cancer by inhibiting NO and increasing ACh. In this respect, the relevant research and clinical experience of traditional Chinese medicine are worth our reference.


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