**2. Hepatitis B Virus, Classification, and Gene Products**

HBV is a hepatocyte-tropic virus and is assigned to the family of hepatitis DNA viruses, *Hepadnaviridae* [11–13]. HBV is divided into 10 main genotypes, A–J, which differ by more than 8% at the nucleotide level [14,15]. The HBV genome has a size of approximately 3.2 kilobases (kb), and is represented by a relaxed circular, partially double-stranded DNA (rcDNA), which is delivered to the nucleus of the host cell and converted into a covalently closed circular DNA (cccDNA) molecule [12]. The cccDNA represents a non-integrated stable episome and forms the template for all viral RNA transcripts. In the absence of an origin of replication site required for DNA-dependent DNA amplification, one of the viral transcripts, the pre-genomic RNA (pgRNA), serves as the template for replication to generate rcDNA via reverse transcription [12]. HBV contains four open reading frames (C, P, S, and X) and encodes seven proteins (polymerase, X protein, HBcAg, HBeAg, HBsAgL, HBsAgM, and HBsAgS). The polymerase is essential for several steps in the replication pathway through its reverse transcriptase, RNaseH, and priming activities. The X protein supports efficient infection and replication in vivo [11,12,16]. The core protein (HBcAg) constitutes the subunit of the viral capsid and is essential for the formation of virions. The e-antigen (HBeAg) is derived from the pre-core protein by proteolytic processing and is not part of the viral capsid. It is involved in modulating the host immune response against HBV and represents an important serological marker [11–13]. The virus encodes for three related surface (envelope) proteins (HBsAg) that share a common S-domain. They are translated from different in-frame start codons and hence are distinguished by their N-terminal extensions. The small HBsAg (HBsAgS) comprises only the S-domain with a size of 226 amino acids (aa), the middle HBsAg protein (HBsAgM) has an N-terminal extension of 55 aa (pre-S2 domain), and the large HBsAg (HBsAgL) has an additional extension of 108 or 119 aa (preS1-domain) depending on the genotype [17] (Figure 1A,B). In addition to the classification by genotypes, HBV is distinguished by four main serotypes based on the reactivity against HBsAg. All genotypes have a common serotypic reactivity against a major antigenic site called the "a"-determinant, but further express two mutually exclusive allelic antigenic determinants "d" or "y" and "w" or "r" [18–20]. The antigenic determinants of HBsAg are located in an exposed loop region of the S-domain. HBsAg and antibodies against HBsAg (anti-HBs) are important serological markers. The loss of HBsAg and seroconversion to anti-HBs antibodies are a sign of immunity and recovery from acute or chronic hepatitis B [13].

Characteristic of a HBV infection is the generation of a large quantity of HBsAg SVPs and filaments devoid of capsid and of the viral genome. SVPs exceed the presence of infectious virions in host sera by a factor between 102 and 105 [17,21–24]. SVPs are predominately composed of HBsAgS, and their presence in the sera does not seem to interfere with HBV particle entry into hepatocytes, suggesting that SVPs represent decoys by binding to virus-neutralizing antibodies [25]. HBsAgS SVPs share important immunological determinants with the mature virus, and therefore, SVPs derived from patient serum or recombinant SVPs represent effective immunogens for the induction of a protective immune response [26–28]. Vaccinated individuals develop antibodies targeting the "a"-determinant region, which provides protection against the infection of all HBV serotypes [20,29]. The discovery and characterization of "empty" genome-free virions containing HBsAg and capsid is reviewed by Hu and Liu, 2017 [30].

**Figure 1.** The surface (envelope) proteins (HBsAg) of hepatitis B virus (HBV): (**A**) The open reading frame encoding the complete hepatitis B surface antigen is depicted. The domain organization of preS1, preS2, and S, with the number of amino acids (aa) of the individual domains are specified. The four transmembrane regions (TM1–4) are indicated by the thick black lines. The function of the different domains in relation to their orientation towards the lumen of the endoplasmic reticulum (ER) or cytosol is indicated. (**B**) The individual HBsAg open reading frames for the small (HBsAgS), middle (HBsAgM), and large (HBsAgL) proteins, and their post-translational modifications are shown. The size of the HBsAgS protein is indicated by the number of amino acids. Arrows represent the utilized glycosylation sites. Red arrows mark asparagine 146 (N146) in the S-domain. Orange and purple arrows represent the N-4 and threonine 37 (T37) respectively, in the preS2 domain. The glycine residue at position 2 (G2) of the preS1 domain, indicated by a purple line, is myristolated. The observed molecular weights (MW) of the glycosylated (gp) and non-glycosylated proteins (p) separated under reducing conditions on a SDS-PAGE are indicated on the right. (**C**) Design of the RTS,S vaccine that is produced by co-expressing HBsAgS (aa 1–226) and the chimeric protein that is a fusion of the circumsporozoite polypeptide (210–398 aa) to the N-terminus of HBsAgS, including 4 aa from the preS2 domain.


**About the Special Issue Editors**

**Łukasz Dębowski** obtained his MS.c. degree in Theoretical Physics from Warsaw University in 1994, Ph.D. degree in Computer Science from the Polish Academy of Sciences in 2005, and Habilitation in Computer Science from the Polish Academy of Sciences in 2015. He visited the Institute of Formal and Applied Linguistics at Charles University in 2001, Santa Fe Institute in 2002, the School of Computer Science and Engineering at the University of New South Wales in 2006, the Centrum Wiskunde & Informatica from 2008 to 2009, and the Department of Advanced Information Technology at Kyushu University in 2015. He is currently an Associate Professor at the Institute of Computer Science of the Polish Academy of Sciences. His research interests include information theory, statistics, linguistics, and natural language engineering. He is a member of the International Quantitative Linguistics Association.

**Christian Bentz** holds a Ph.D. in Computation, Cognition and Language from the University of Cambridge. He is currently Assistant Professor (Akademischer Rat a. Z.) at the University of Tubingen. ¨ Prior to this appointment, he was a Postdoctoral Researcher at URPP Language and Space, University of Zurich, ¨ and a Research Fellow at the DFG Center for Advanced Studies "Words, Bones, Genes, Tools" at University of Tubingen. ¨ His research focuses on the application of information theory to natural languages and other symbolic systems.


**3. Effects of incision on capsulorhexis**

An ideal surgical incision is the fundamental prerequisite for successful capsulorhexis. In Europe and America, a temporal incision is preferred, while in Asia it is mostly performed at an 11 o' clock position. Regardless of the orientation, when the incision is made, the direction of the tunnel knife should be along the meridian of the cornea, as shown in **Figure 17**.

A meridional incision does not limit the movement of capsular forceps, which ensures that the anterior opening is centered and perfectly round. When the incision deviates from the meridian, the boundaries of the inner incision will limit the track for the capsulorhexis forceps as shown in **Figure 18**.

**11**

**Figure 19.**

*Continuous Curvilinear Capsulorhexis DOI: http://dx.doi.org/10.5772/intechopen.96556*

arrows in **Figure 19**.

**Figure 17.**

*incision (B).*

**Figure 18.**

*movement of capsulorhexis forceps as showed in B.*

*opening (red arrow) followed the non-ideal incision.*

In addition, if the incision is too close to the center of the cornea, the range will be affected, leading to a small and off-center capsulorhexis, as shown by the red

*The direction of incision should along meridian direction (C) from positioning (A) to the process of making the*

*Incision deviates from the meridian showed in A. the boundaries of deflective inner incision limit the*

*Incision (red box) is too close to the center of the cornea relative to the limbus (red circle). The irregular AC*

*Continuous Curvilinear Capsulorhexis DOI: http://dx.doi.org/10.5772/intechopen.96556*

In addition, if the incision is too close to the center of the cornea, the range will be affected, leading to a small and off-center capsulorhexis, as shown by the red arrows in **Figure 19**.

#### **Figure 17.**

*Current Cataract Surgical Techniques*

*Capsulorhexis path is clear with good red reflex (white arrow).*

*Coaxial light and paraxial lights on the operation microscope.*

placed varies according to the practitioner's habits.

track for the capsulorhexis forceps as shown in **Figure 18**.

**3. Effects of incision on capsulorhexis**

the cornea, as shown in **Figure 17**.

To avoid wrist dangling, the surgeon's hands or wrists should rest steadily against the patient's forehead. This will allow the surgeon's hands to move synchronously with the patient's head if the they move head abruptly. The angle at which the hands

An ideal surgical incision is the fundamental prerequisite for successful capsulorhexis. In Europe and America, a temporal incision is preferred, while in Asia it is mostly performed at an 11 o' clock position. Regardless of the orientation, when the incision is made, the direction of the tunnel knife should be along the meridian of

A meridional incision does not limit the movement of capsular forceps, which ensures that the anterior opening is centered and perfectly round. When the incision deviates from the meridian, the boundaries of the inner incision will limit the

**Figure 15.**

**Figure 16.**

**2.5 Hand position**

**10**

*The direction of incision should along meridian direction (C) from positioning (A) to the process of making the incision (B).*

#### **Figure 18.**

*Incision deviates from the meridian showed in A. the boundaries of deflective inner incision limit the movement of capsulorhexis forceps as showed in B.*

#### **Figure 19.**

*Incision (red box) is too close to the center of the cornea relative to the limbus (red circle). The irregular AC opening (red arrow) followed the non-ideal incision.*


*2.1. Study Area*

This study was conducted in the central Ethiopian highlands at two experimental sites: Affesa in Dangila district and Alefa in Bure district (Figure 1). Affesa (36.83◦ N, 11.25◦ E) and Alefa (37.06◦ N, 10.62◦ E) sites are located about 80 km and 150 km southwest of Bahir Dar, respectively. The elevation of Affesa site ranges from 2132 to 2219 m above MSL, whereas Alefa site elevation ranges from 1983 to 2033 m above MSL. Both Dangila and Bure districts are categorized under moist sub-tropical regions. Dangila has an average annual rainfall of 1578 mm and a mean annual temperature of 17 ◦C [42], whereas, the mean annual rainfall and temperature in Bure ranges from 1386 mm to 1757 mm and 14 ◦C to 24 ◦C, respectively [43]. Based on soil laboratory analysis, clay soil is the dominant soil texture in Affesa (46% clay and 36% silt) and the soil type in Alefa is dominated by loam soil (44% sand and 29% silt). The dominant rainfed crops in both Dangila and Bure districts include maize, millets (sorghum: *Sorghum bicolor* L., or pearl millet: *Panicum sp*.), barley (*Hordeum vulgare* L.), teff [*Eragrostis tef* (Zucc.) Trotter], and wheat (*Triticum aestivum* L.), [44]. While, onion, potato, cabbage, pepper, tomato, and garlic are the dominant irrigated vegetables in both Dangila and Bure district [22,45]. In the Affesa site, farmers used to practice irrigation using river sources, whereas groundwater use was limited to domestic purposes in both sites due to lack of access to affordable water-lifting technology.