Difluoromethylation of arylidene Meldrum's acid derivatives
Fluorine-containing compounds gained significant attention during the past decade1. About 20% of novel pharmaceuticals and 40% of novel agrochemicals every year contain at least one fluorine atom in the molecule. For a long time the most frequently used was trifluoromethyl group, but nowadays the most promising is the chemistry of partially-fluorinated groups. For example, the difluoromethyl substituent (CHF2) exhibits unique pharmacoforic properties capable of serving as lipophilic hydrogen bond donor thus being bioisosteric to hydroxyl group2. There are several general approaches for the formation of a required fluorinated fragment, one of them is direct nucleophilic fluoroalkylation. This approach is well-developed for trifluoromethylation reactions, such as addition of CF3-anion equivalents to C=O, C=N and electron-deficient C=C bonds or metal-catalyzed substitution in haloarenes3. However the similar difluoromethylation processes are still quite challenging. Herein we present a novel and convenient protocol for the synthesis of β-CF2H functionalized carbonyl compounds and carbinols by nucleophilic difluoromethylation of electron-deficient olefines. The process is based on a 1,4-addition of in situ generated4 phosphorus ylide Ph3P=CF2 2 to the arylidene Meldrum's acid conjugates 1. The resulting phosphobetaines 3 are hydrolized/protodephosphorilated without isolation, giving β-CF2H substituted carboxylic acids 4. The latter may be easily transformed to the corresponding ethers 5 and alcohols 6 without preliminary purification.
H.E.L.P. Heart Empowers Lifelong Pacemaker
EXPERIMENT 1---The effect of NaCl and Glucose Concentration on the efficiency of the cell I. Introduction Experiment on different concentrations of standard glucose solution (ranged from 0.125 M to 1.000 M) and standard sodium chloride solution (ranged from 0.250 M to 4.000 M) were done. We investigated the full concentration effect, which included both concentration of glucose solution and sodium chloride solution on the fuel cell’s output voltage, current and power. II. Procedures 1. Add 25.0 cm3 of Glucose solution of the tested concentration to the beaker representing the anode, and add 25.0 cm3 of distilled water to the beaker representing the cathode. 2. Add 50.0 cm3 of 0.250 M NaCl (aq) to both beakers representatively. 3. Fold a piece of filter paper and soak in fully into NaCl (aq) at cathode. 4. Clean and place the silver wires into the beakers representatively, and connect the air pump to the cathode. 5. Connect the cell to two multi-meters, each acting as a voltmeter and an ammeter respectively 6. Take the readings of multi-meters after 30 seconds. 7. Repeat steps 1 to 6 twice for the second and third reading of the cell. 8. Take average value among three values as the final reading of the cell. 9. Repeat steps 1 to 8 by replacing the NaCl (aq) with concentrations of 0.000 M, 0.500 M, 1.000 M, 2.000 M and 4.000 M, and the standard glucose solution with concentrations of 0.000 M, 0.125 M, 0.250 M, 0.500 M, 0.750 M and 1.000 M. III. Result of Experiment 1 When glucose concentration is increased from 0.000 M to 0.250 M, the output power increases, it is found that power generated is maximized at glucose concentrations between 0.125 M and 0.250 M. However, with further increase in glucose concentration from 0.250 M to 1.000 M, the power generated decreases. This shows that high concentration of glucose inhibits the generation of electricity, while higher concentration of sodium chloride solution can increase the output. EXPERIMENT 2---The effect of temperature on the efficiency of the cell I. Introduction In this experiment, the second effect - temperature on the fuel cell’s output voltage, current and power was investigated. In order to get a significant result, the effect of temperature on these measures with fixed 0.250 M glucose solution and sodium chloride solution concentrations varied from 0.500 M to 4.000 M had been investigated. II. Procedures 1. Add 25.0 cm3 of Glucose solution of the tested concentration (0.25 M) to the beaker representing the anode, and add 25.0 cm3 of distilled water to the beaker representing the cathode. 2. Add 50.0 cm3 of 0.500 M NaCl (aq) to both beakers representatively. 3. Fold a piece of filter paper and soak in fully into NaCl (aq) at cathode. 4. Clean and place the silver wires into the beakers respectively, and connect the air pump to the cathode. 5. Connect the cell to two multi-meters, each acting as a voltmeter and an ammeter respectively 6. Take the readings of multi-meters after 30 seconds. 7. Repeat steps 1 to 6 twice for the second and third reading of the cell. 8. Take average value among three values as the final reading of the cell. 9. Repeat steps 1 to 8 by varying the temperature from 42℃ to 32℃. 10. Repeat steps 1 to 9 by replacing the NaCl solution of 0.000 M, 1.000 M, 2.000 M, and 4.000 M respectively. III. Result of Experiment 2 The results showed a consistent trend and relationship of the effect of temperature on the output current, voltage and power of the fuel cell for 4 different concentrations of sodium chloride solution with fixed 0.25 M glucose solution. Generally, the results showed that the output power increases with temperature. EXPERIMENT 3---The effect of dialysis tubing and Nafion 117 on the efficiency of the cell I. Introduction Semi-permeable membrane separating glucose and oxygen, ensure the glucose oxidation only occurs at the anode, and preventing glucose oxidation occurs at the cathode, responds to maximize power output. Experimental study on two kinds of membranes, dialysis membranes and Nafion 117 films were done, by studying their fuel cell output voltage, current and power effects. Previous experiments showed that the optimal output of the battery is at 0.250 M glucose solution, Therefore, experimental conditions for glucose concentration is fixed on 0.250 M and sodium chloride solution concentration varies from 0.500 to 4.000 M. II. Procedures The Effect of Dialysis Tubing on voltage and current of the fuel cell 1. Pour 50 cm3 1.000 M NaCl (aq) to each compartment of the beaker separated by dialysis tubing. 2. Pour 0.250 M Glucose Solution into the compartment representing anode. 3. Connect the cell to two multimeters, which act as a voltmeter and ammeter respectively 4. Take the reading of the multimeters after 30 seconds 5. Repeat steps 1 to 4 twice for the second and third reading of the cell. 6. Take average value among three values as the final reading of the cell. 7. Repeat steps 1 to 6 with NaCl (aq) with concentration of 0.000 M, 0.250 M, 0.500 M, 2.000 M and 4.000 M to obtain the remaining data. The Effect of Nafion 117 on voltage and current of the fuel cell 1. Add 50 cm3 1.000 M NaCl (aq) and 50 cm3 of 0.250 M of glucose solution to the beaker. 2. Add 1.000 M NaCl (aq) to the Nafion 117 membrane pouch, and silver plate was put inside to become the anode. 3. Connect the cell to two multimeters, which act as a voltmeter and ammeter respectively 4. Take the reading of the multimeters after 30 seconds 5. Repeat steps 1 to 4 twice for the second and third reading of the cell. 6. Take average value among three values as the final reading of the cell. 7. Repeat steps 1 to 6 with NaCl (aq) with concentration of 0.000 M, 0.250 M, 0.500 M, 2.000 M and 4.000 M to obtain the remaining data. III. Result of Experiment 3 The result had shown that when the solution does not contain glucose (i.e. Glucose concentration equals to 0.000 M), Nafion 117 Membrane Cells have similar power outputs compared to the dialysis tubing cells. However, in 0.250 M glucose solution, the output of Nafion 117 membrane cell is about 1 to 5 times more compared to that of dialysis tubing cell. According to the experiment results, it was found out that the power output was maximized when the concentration of glucose solution and NaCl (aq) are 0.250 M and 4.000 M respectively. Under this concentration, the out of Nafion 117 membrane cell was 1336.68 nW which was 5 times higher than that of dialysis tubing cell. Hence, adopting Nafion 117 as the selectively membrane can greatly enhance the output of cell. It is believed that the special structure of Nafion 117 has limited the movement of glucose molecules, and prevented their oxidation at cathode. This has enhanced the oxidation of glucose at anode, and thus increased the power output of the cell.
Novel Approach to Screening Mutations Causing Retinoblastoma, a Childhood Cancer of Retina
Retinoblastoma (RB) is a childhood retinal cancer caused by mutations in the RB1 gene. Molecular diagnosis is crucial for early detection and treatment. Current DNA diagnostic screening requires substantial amounts of tumour and blood samples. However current screening methods face the challenges of limited DNA templates from minute retinal tumours and too much blood samples drawn from young patients. In addition, the starting DNA template amount and quality are important to ensure confident detection of disease-causing mutations. As the majority of RB1 mutations are unique and distributed throughout the RB1 gene with no real hot spots, the entire gene needs to be thoroughly analysed. This investigation proposes to enrich DNA samples using a whole genome amplification (WGA) step prior to RB1 mutation screening by RB1 gene-specific PCR amplification as well as high resolution melt (HRM) analysis and sequencing. It also identifies RB1 mutations in two RB patients and explores whether WGA and saliva products can be a source of DNA templates for RB1 analysis. In addition, this study was conducted based on the hypotheses that RB1 mutations were the underlying cause of the disease in the two patients, and that the products from WGA could be used specifically for RB1 gene analysis to overcome the constraint of insufficient DNA samples. Two anonymised genomic DNA samples from two unrelated RB patients and five normal healthy DNA samples were used in this project. WGA kits were compared according to three criteria, namely amplification yield, product fragment size and whether DNA is amplifiable. Prior to and after amplification, the optical density of two normal samples was measured to determine the increase in DNA yield. The amplicons were subjected to gel electrophoresis to determine the product fragment size. Exons 6, 14 and 25 of the original and amplified samples undergone PCR, and were examined again using gel electrophoresis to ascertain that the amplicons were amplifiable. Mutation analysis using HRM was carried out with pre-existing primers for all 27 exons and the promoter of RB1. Samples from patients were analysed against 83 saliva DNAs extracted using Oragene•DNA (OG-500) Kit. REPLI-g was observed to produce higher yield and products of reliable fragment size. Single distinct bands were also seen for exons amplified using REPLI-g, indicating that REPLI-g is more accurate and suitable in the amplification of DNA. Abnormal melt profiles were obtained for exon 6 in RB477 and exon 14 in RB572 for HRM. These exons were sequenced to determine the exact mutation. Exon 6 was found to have a splice-site mutation g.607+1G>T, while a point mutation, g.1363C>T (p.Arg455X) was identified in exon 14. Both the uses of saliva as a non-invasive DNA source and the WGA approach for enriching DNA sample for application in RB1 gene analysis have never been reported for RB. Although HRM analysis has been used for other diseases, this is its first instance applied in work on RB1 gene. In short, this report offers novel and promising approaches which would contribute significantly to the molecular analysis of mutations in RB.
Geographic Belts for Hurricane Landfall Location Prediction
When predicting a hurricane’s landfall location, small improvements in accuracy result in large savings of lives, property, and money. The project’s purpose was to apply a breakthrough method that can predict the geographic location of a hurricane’s landfall with high accuracy. Researchers have known for a long time that there are strong correlations between a hurricane’s landfall location and the geographic regions its track passes through. However, no methods have been developed to mathematically and explicitly describe these correlations. Consequently, the correlations can only serve to meteorologists as vague guidelines for their guestimates and are not usable in making practical forecasts. By studying the correlations and performing numerical optimization on historical hurricane data, this research discovered a set of geographic belt regions in the Gulf of Mexico that can be used as landfall location predictors. When a hurricane passes through any one of these belt lines, a prediction can be made by extending the hurricane’s moving direction vector towards land – the intersection point of this extension line with the coastline is the predicted landfall location. This prediction method is simple and straightforward. It only uses basic measurements from meteorological satellites: the hurricane’s real-time locations and moving directions. In conclusion, when compared to existing methods, the predictive belt method (PBM) created in this research provides a landfall location forecast with higher accuracy. Verification with historical hurricane data demonstrated that the PBM’s average error is less than 50% of the National Hurricane Center models’ error.
Development of a compact, self-stabilizing handheld camera mount
My purpose of the Research was build a small, compact device for the GoPro, which minimizes shocks that are typically caused by running and makes the video stable. The device must fit into a backpack and must be designed for the GoPro. This scenario raised two central questions for me: Which laws of physics are used for the stabilization of the camera? How can those laws of physics constructively be transformed into a working device? I have built four prototypes. To know which prototype was the best, I compared them and gained data into diagrams. The result with the last prototype was very impressive and encouraging, whether your are walking, running or skiing, the videos were no longer shaky. My final prototype consisted of a hollow tube which extended vertically. My conclusions: First the handheld camera mount mustn't be too light, as the inertia of the device is too low. Second it mustn't be too heavy, because you normally have to hold it over a certain time interval. Inertia as well as lever principal were essential to produce a smooth video. The most difficult part to build was the fully gimbaled suspension because it requires as little friction as possible and it must be precise and solid.