**3. Study area and its characteristics**

*Rainfall - Extremes, Distribution and Properties*

Sea. In early winter the Mediterranean-borne maritime air increasingly disturbs the monsoonal air movement and displaces it in the low altitudes. These maritime depressions draw the tropical continental air masses into the warm sectors, and extreme weather conditions occur that are associated with the passage of a hot sector. Both (2) and (3) move toward the east and prevail in the winter season. During this season, the western region, particularly the coastal area, is characterized by its relatively low rate of rainfall [38], whereas, due to the topographic effects, the highlands receive a considerable amount of rainfall. In spring, the impact of the Mediterranean air movement diminishes, whereas the monsoon from the south takes its place, penetrating the southern part of the Kingdom. During summer, the cyclonic flow sweeps along the Mediterranean Sea from the west toward the east and continues moving over the northern and central regions of the country preventing the maritime air masses of the northeasterly monsoon from penetrating the north regions of the Kingdom. Due to

this, the summer season will be somewhat dry in the area considered.

and in the west, the valleys are steep and flowing towards the Red Sea.

The mean annual rainfall (from 1960 to 2018) over the KSA can be shown in **Figure 2**. The rainfall rate in the KSA (except for the Empty Quarter desert) is 109 mm per year. The southwestern region is characterized by a heavy rainfall compared with the rest of the Kingdom. Rainfall is more than 500 mm per year in some locations. The peaks of the Sarawat Mountains, which extend from the northern part of the Kingdom to the south, parallel to the Red Sea, are the dividing line for the distribution of surface water. The rains that fall in the east of this line take place in the valleys heading east,

Recently, there is a definite increasing trend in rainfall in frequency and intensity in the KSA. Many areas in the KSA have shown an increasing trend in the annual rainfall and flood events. Most of the rainfall in the KSA occurs during the monsoon. Monsoon is a term derived from the Arabic word "mausim," meaning season. It was used to describe the seasonal winds of the Arabian Sea. The Jeddah area is characterized by wet and dry seasons that generally occur from November to May and from June to October, respectively. One example is Jeddah city which has shown an increasing trend in the rainfall events. These events cause disasters that result in human, property, and economic loss.

*Average annual rainfall values for 270 rainfall stations distributed across the KSA area (from 1960 to 2018).*

**20**

**Figure 2.**

The study area, the Jeddah area, is located in the western region of the KSA covering an area of ~1731 km2 and lies between latitudes 21°15′ and 21°57′N and

**Figure 3.** *Study area and its meteorology station locations.*

longitudes 39°06′ and 39°31′E (**Figure 3**). From the latitude point of view, the Jeddah area is considered to be in the arid zone (Köppen's climate classification). The Jeddah area has different geomorphological features. It represents a part of the Red Sea coastal zone. Jeddah drainage system comes from the east (a series of hills) toward the city which is located to the west. The catchment areas have a variety of landforms such as low- and midsize hills and flattened foothills in some places followed to the west by the floodplain areas. The monthly average relative humidity ranges between ~85% from September to October and ~34% from April to June. The Jeddah area is characterized by scarce rainfalls with high variability, which occur most often in November–December–January (the winter season). Additionally, monsoonal rainstorms take place in March and April due to the moist air currents from the Indian Ocean and the Arabian Sea. The average annual precipitation is ~52.5 mm/year. The maximum rainfall was recorded in 1996, with ~284 mm/year. Recently these thunderstorms increased in their frequencies and intensities causing flash floods and inundation events within Jeddah city.


Fanel Scheaua

[11] European Commission, Rural Development Programme 2014–2020: Key facts & fig‐ ures, Lithuania, Version 1, September 2015, available at: https://enrd.ec.europa.eu/

Proceedings of the International Conference on Interdisciplinary Studies (ICIS 2016) - Interdisciplinarity and Creativity

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[14] Berger H., Moutos T., Managing the European Union Enlargement, The MIT Press,

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[16] Badea D. G., The role of Romania in a changing Europe, [pdf], Bucharest, 2006, avail‐

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at 08 March 2016.

in the Knowledge Society

110

Cambridge, 2004.

09 March 2016.

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/65418

### **Abstract**

The construction of bridges or viaduct structures represents major infrastructure works of vital importance for human communities, and therefore they must be made to with‐ stand both the traffic and the seismic events. Therefore, all necessary measures should be taken so that these structures can remain functional even after the action of earthquakes of considerable magnitude. A high level of safety for these structures can be ensured if within the resistance structure some special mechanical systems are mounted, which will be able to improve the building assembly behaviour when an earthquake occurs. This kind of mechanical system capable of ensuring a high level of safety for the isolated struc‐ ture is described in this paper. The isolation system assembly consists of a rolling pendu‐ lum device combined with elastomeric system. This system was built and experimentally tested at random vibrations. The experimental results are presented regarding motion pa‐ rameters recorded at the pier and superstructure level. The combination between effects of the two dissipating system types represents the optimum solution intended to achieve an improved response of the isolated structure when subjected at dynamic actions. There‐ fore, it represents a special system which can be successfully used in the endowment of bridge or viaduct structural type.

**Keywords:** Dissipation system, rolling friction, anti-seismic device, experimental model‐ ling


**4. Conclusions**

Until recently flow cytometry was considered a powerful technology dedicated to bespoke assays where just a few samples were to be measured. No medium throughput let alone high throughput screen could be run on this technology due to lack of plate handling features, time needed per sample and therefore cellular imaging was the preferred method for any high content screen. Increases of interest in phenotypic screening combined with a desire to access relevant cell models, often suspension cells, and development of plate-based sampling flow cytometers have led to the opportunity to use flow cytometry as a drug screening technology platform. The ability to perform multiplexing where different cells or particles labeled with distinct fluorophores are analyzed in parallel and multiple endpoints are measured leads to in-depth analysis of subpopulations within a sample. Such an approach results in increased productivity by decreasing timelines and cell requirements, two critical parameters for high throughput screening.

We chose to run a screen for Rac1 inhibitors on our iQue® Screener HD as it enabled us to miniaturize and run a simple and robust assay on one of our automation platforms.

We have run a successful 500,000 compound screen using the iQue® HD screener as summarized in **Figure 13**. By optimizing the protocol, we were able to retain high-quality data while decreasing read time per 1536 well plate to under 50 min. This allowed us to run the primary screen within 4 weeks. Although time is not the most critical criteria we consider it remains an important factor as we need to maintain the overall flow of projects through our portfolio and therefore we must decide on a suitable time frame for completion of each screen.

The screen we have described here would have not been possible a few years ago but, thanks to the development of high throughput capable instruments, flow cytometry has found its place within the drug discovery process and high throughput screening in AstraZeneca. Although we decided not to multiplex our concentration response assays, it should be noted that the use of flow cytometry technology does allow for such multiplexing and indeed has

High Throughput Screen for Inhibitors of Rac1 GTPase by Flow Cytometry

http://dx.doi.org/10.5772/intechopen.71074

59

The authors would like to thank Matthew Collier for his assistance during the high throughput

been described in the literature [12].

screen and Kim Luu for her technical support with the iQue®.

**Acknowledgements**

**Figure 13.** Screen summary.

High throughput screening is a key method for the identification of hit and lead compounds and remains at the start of most of our drug discovery programs. As we pursue a wide range of targets we also use a wide range of assays and technologies. We have invested into several iQue® Screener systems as we updated and replaced previous detection systems and to fill a capability gap for screening suspension cells or primary cells in small sample volumes. We have successfully used the iQue® Screener systems in a variety of applications from phenotypic screening to more complex multiplex profiling. The technology has enabled several projects due to the ability to reduce cell requirement, cost and timelines.

**Figure 13.** Screen summary.

screen were serially diluted 1:3 to construct a 10-point concentration response curve. Compound concentration curves are dispensed using acoustic dispensing into assay ready plates at 150 compound curves per plate. Wells are backfilled with DMSO to keep the DMSO concentration constant in all wells. The plates were sealed and stored in the controlled atmosphere and temperature working plate store before use as for primary screen

58 Multidimensional Flow Cytometry Techniques for Novel Highly Informative Assays

pounds were confirmed as active with 44 identified as Rac1 selective using a ≥10 fold ratio of Rac1 IC50 vs. RhoA and Cdc42 as a cutoff. These compounds encompass a variety of chemical structures. **Figure 12** shows representative curves of selective and non-selective compounds. Selected hits are being further characterized through a panel of cellular assays

Until recently flow cytometry was considered a powerful technology dedicated to bespoke assays where just a few samples were to be measured. No medium throughput let alone high throughput screen could be run on this technology due to lack of plate handling features, time needed per sample and therefore cellular imaging was the preferred method for any high content screen. Increases of interest in phenotypic screening combined with a desire to access relevant cell models, often suspension cells, and development of plate-based sampling flow cytometers have led to the opportunity to use flow cytometry as a drug screening technology platform. The ability to perform multiplexing where different cells or particles labeled with distinct fluorophores are analyzed in parallel and multiple endpoints are measured leads to in-depth analysis of subpopulations within a sample. Such an approach results in increased productivity by decreasing timelines and cell requirements, two critical parameters for high

We chose to run a screen for Rac1 inhibitors on our iQue® Screener HD as it enabled us to

We have run a successful 500,000 compound screen using the iQue® HD screener as summarized in **Figure 13**. By optimizing the protocol, we were able to retain high-quality data while decreasing read time per 1536 well plate to under 50 min. This allowed us to run the primary screen within 4 weeks. Although time is not the most critical criteria we consider it remains an important factor as we need to maintain the overall flow of projects through our portfolio and

High throughput screening is a key method for the identification of hit and lead compounds and remains at the start of most of our drug discovery programs. As we pursue a wide range of targets we also use a wide range of assays and technologies. We have invested into several iQue® Screener systems as we updated and replaced previous detection systems and to fill a capability gap for screening suspension cells or primary cells in small sample volumes. We have successfully used the iQue® Screener systems in a variety of applications from phenotypic screening to more complex multiplex profiling. The technology has enabled several

miniaturize and run a simple and robust assay on one of our automation platforms.

therefore we must decide on a suitable time frame for completion of each screen.

projects due to the ability to reduce cell requirement, cost and timelines.

was added to the buffer for the RhoA assay. 82% of the tested com-

plates. 1 mM MgCl2

by the team at INSERM.

**4. Conclusions**

throughput screening.

The screen we have described here would have not been possible a few years ago but, thanks to the development of high throughput capable instruments, flow cytometry has found its place within the drug discovery process and high throughput screening in AstraZeneca. Although we decided not to multiplex our concentration response assays, it should be noted that the use of flow cytometry technology does allow for such multiplexing and indeed has been described in the literature [12].