Growth Axis Research Articles

Rho of Plants GTPases and Cytoskeletal Elements Control Nuclear Positioning and Asymmetric Cell Division during Physcomitrella patens Branching

Branching morphogenesis is a widely used mechanism for development [1, 2]. In plants, it is initiated by the emergence of a new growth axis, which is of particular importance for plants to explore space and access resources [1]. Branches can emerge either from a single cell or from a group of cells [3-5]. In both cases, the mother cells that initiate branching must undergo dynamic morphological changes and/or adopt oriented asymmetric cell divisions (ACDs) to establish the new growth direction. However, the underlying mechanisms are not fully understood. Here, using the bryophyte moss Physcomitrella patens as a model, we show that side-branch formation in P.patens protonemata requires coordinated polarized cell expansion, directional nuclear migration, and orientated ACD. By combining pharmacological experiments, long-term time-lapse imaging, and genetic analyses, we demonstrate that Rho of plants (ROP) GTPases and actin are essential for cell polarization and local cell expansion (bulging). The growing bulge acts as a prerequisite signal to guide long-distance microtubule (MT)-dependent nuclear migration, which determines the asymmetric positioning of the division plane. MTs play an essential role in nuclear migration but are less involved in bulge formation. Hence, cell polarity and cytoskeletal elements act cooperatively to modulate cell morphology and nuclear positioning during branch initiation. We propose that polarity-triggered nuclear positioning and ACD comprise a fundamental mechanism for increasing multicellularity and tissue complexity during plant morphogenesis.

FoxO1\u2013Dio2 signaling axis governs cardiomyocyte thyroid hormone metabolism and hypertrophic growth

Forkhead box O (FoxO) proteins and thyroid hormone (TH) have well established roles in cardiovascular morphogenesis and remodeling. However, specific role(s) of individual FoxO family members in stress-induced growth and remodeling of cardiomyocytes remains unknown. Here, we report that FoxO1, but not FoxO3, activity is essential for reciprocal regulation of types II and III iodothyronine deiodinases (Dio2 and Dio3, respectively), key enzymes involved in intracellular TH metabolism. We further show that Dio2 is a direct transcriptional target of FoxO1, and the FoxO1–Dio2 axis governs TH-induced hypertrophic growth of neonatal cardiomyocytes in vitro and in vivo. Utilizing transverse aortic constriction as a model of hemodynamic stress in wild-type and cardiomyocyte-restricted FoxO1 knockout mice, we unveil an essential role for the FoxO1–Dio2 axis in afterload-induced pathological cardiac remodeling and activation of TRα1. These findings demonstrate a previously unrecognized FoxO1–Dio2 signaling axis in stress-induced cardiomyocyte growth and remodeling and intracellular TH homeostasis.

Long Non-Coding RNA SLC25A21-AS1 Promotes Multidrug Resistance in Nasopharyngeal Carcinoma by Regulating miR-324-3p/IL-6 Axis.

BackgroundNasopharyngeal carcinoma (NPC), one of the most common types of head and neck tumor, occurred in the epithelial lining of the nasopharynx and is mainly prevalent in Southeast Asia and Southern China. However, the molecular mechanisms of NPC multidrug resistance still remained largely unclear.MethodsThe qRT-PCR assay was performed to examine SLC25A21-AS1, miR-324-3p and IL-6 expression in NPC tissues and cell. The CCK8 assay and colony formation assay were used to detect cell growth. In addition, CCK8 assay was performed to detect IC50 values of different drugs in NPC cell.ResultsIn this study, we found that SLC25A21-AS1 expression was increased in NPC tissues and cell line, and knockdown of SLC25A21-AS1 inhibited cell growth and MDR in NPC cell. Moreover, SLC25A21-AS1 acted as a ceRNA for miR-324-3p and facilitates NPC cell growth and MDR by regulating the miR-324-3p/IL-6 axis.ConclusionOur findings demonstrated the role of SLC25A21-AS1/miR-324-3p/IL-6 axis in cell growth and MDR in NPC, which might be a potential prognostic and diagnostic marker in NPC patients and provide new insight into the molecular mechanism of MDR in NPC chemotherapy.

The 3D Reconstruction of Pocillopora Colony Sheds Light on the Growth Pattern of This Reef-Building Coral

SummaryCoral reefs are formed by living polyps, and understanding the dynamic processes behind the reefs is crucial for marine ecosystem restoration. However, these processes are still unclear because the growth and budding patterns of living polyps are poorly known. Here, we investigate the growth pattern of a widely distributed reef-building coral Pocillopora damicornis from Xisha Islands using high-resolution computed tomography. We examine the corallites in a single corallum of the species in detail, to interpret the budding, growth, and distribution pattern of the polyps, to reconstruct the growth pattern of this important reef-building species. Our results reveal a three-stage growth pattern of P. damicornis, based on different growth bundles that are secreted by polyps along the dichotomous growth axes of the corallites. Our work on the three-dimensional reconstruction of calice and inter-septal space structure of P. damicornis sheds lights on its reef-building processes by reconstructing the budding patterns.

VHL-HIF-2α axis-induced SMYD3 upregulation drives renal cell carcinoma progression via direct trans-activation of EGFR.

It has been well established that the von Hippel-Lindau/hypoxia-inducible factor α (VHL-HIFα) axis and epidermal growth factor receptor (EGFR) signaling pathway play a critical role in the pathogenesis and progression of renal cell carcinoma (RCC). However, few studies have addressed the relationship between the two oncogenic drivers in RCC. SET and MYND domain-containing protein 3 (SMYD3) is a histone methyltransferase involved in gene transcription and oncogenesis, but its expression and function in RCC remain unclear. In the present study, we found that SMYD3 expression was significantly elevated in RCC tumors and correlated with advanced tumor stage, histological and nuclear grade, and shorter survival. Depletion of SMYD3 inhibited RCC cell proliferation, colony numbers, and xenograft tumor formation, while promoted apoptosis. Mechanistically, SMYD3 cooperates with SP1 to transcriptionally promote EGFR expression, amplifying its downstream signaling activity. TCGA data analyses revealed a significantly increased SMYD3 expression in primary RCC tumors carrying the loss-of-function VHL mutations. We further showed that HIF-2α can directly bind to the SMYD3 promoter and subsequently induced SMYD3 transcription and expression. Taken together, we identify the VHL/HIF-2α/SMYD3 signaling cascade-mediated EGFR hyperactivity through which SMYD3 promotes RCC progression. Our study suggests that SMYD3 is a potential therapeutic target and prognostic factor in RCC.

MiR‑181b‑p53 negative feedback axis regulates osteosarcoma cell proliferation and invasion.

Osteosarcoma (OS) is one of the most common malignant tumors in young adults and as a high distant metastasis rate. The p53 protein, a potent prognostic biomarker for patients with OS, is altered in ~50% of OS cases. p53 was reported to exert its effects through regulating the transcription of microRNAs (miRNAs/miRs) and other genes. In the present study, the expression of miR-181b, a critical OS oncomiR, was shown to be significantly upregulated whereas p53 expression was downregulated within OS tissues and cells; in tissue samples, miR-181b and p53 were negatively correlated. p53 inhibited the transcription of miR-181b via targeting its promoter region, whereas miR-181b bound the TP53 3′-untranslated region (UTR) to inhibit p53 expression. miR-181b silencing considerably increased p53, p21, and epithelial-Cadherin protein levels but decreased Cyclin D1 protein levels in OS cells. In addition, miR-181b inhibition reduced OS cell proliferation and invasion. In contrast, p53 knockdown had the opposite effects on these proteins and OS cell proliferation and invasion. Above all, p53 knockdown significantly attenuated the effects of miR-181b inhibition. Moreover, OS cell xenograft assays further confirmed the roles of the miR-181b/p53 axis in OS growth. In conclusion, miR-181b and p53 are negatively regulated by one another and therefore form a negative feedback axis that regulates the proliferation and invasion abilities of OS cells. Targeting miR-181b to inhibit its abnormal upregulation might be a potent strategy for OS treatment.

Microstructure and Mechanical Properties of Platinum Fiber Fabricated by Unidirectional Solidification

The microstructure and mechanical properties of platinum (Pt) fibers fabricated by unidirectional solidification using the alloy-micro-pulling-down (A-μ-PD) method were investigated using a Universal Testing Machine and Electron Backscattered Diffraction (EBSD). The Pt fiber fabricated at a growth rate of 10 mm/min was composed of relatively large grains with <100> crystal orientation along the growth direction. The crystal orientation was consistent with the easy axis of the crystal growth on the face-centered-cubic (f.c.c.) structure. On the other hand, the adjacent grains of the Pt fiber fabricated at 50 mm/min were randomly oriented owing to a faster growth rate. In tensile tests, the Pt fibers fabricated by the A-μ-PD method indicated extremely different stress–strain curves compared to the commercial Pt wire. The maximum tensile stress of the Pt fiber reached ~100 MPa, and the Pt fiber ruptured after 58% nominal strain.

Spatially-resolved luminescence and crystal structure of single core–shell nanowires measured in the as-grown geometry

We report on the direct correlation between the structural and optical properties of single, as-grown core-multi-shell GaAs/In0.15Ga0.85As/GaAs/AlAs/GaAs nanowires. Fabricated by molecular beam epitaxy on a pre-patterned Si(111) substrate, on a row of well separated nucleation sites, it was possible to access individual nanowires in the as-grown geometry. The polytype distribution along the growth axis of the nanowires was revealed by synchrotron-based nanoprobe x-ray diffraction techniques monitoring the axial 111 Bragg reflection. For the same nanowires, the spatially-resolved emission properties were obtained by cathodoluminescence hyperspectral linescans in a scanning electron microscope. Correlating both measurements, we reveal a blueshift of the shell quantum well emission energy combined with an increased emission intensity for segments exhibiting a mixed structure of alternating wurtzite and zincblende stacking compared with the pure crystal polytypes. The presence of this mixed structure was independently confirmed by cross-sectional transmission electron microscopy.

CircCBFB-mediated miR-28-5p facilitates abdominal aortic aneurysm via LYPD3 and GRIA4

Heading aimsAbdominal aortic aneurysm (AAA) is featured by the growth impediment and apoptosis surge of VSMCs (vascular smooth muscle cells). MicroRNAs (miRNAs) are suggested to affect cellular behaviors including cell growth and apoptosis. This study concentrated on unraveling the emerging role of miR-28-5p in abdominal aortic aneurysm. Materials and methodsPreviously, miR-28-5p was reported to be highly expressed in AAA. Functional assays were utilized to determine the role of miR-28-5p in VSMC apoptosis. To narrow down the downstream mRNAs, bioinformatics methods were utilized. The interaction between miR-28-5p and GRIA4 (glutamate ionotropic receptor AMPA type subunit 4) or LYPD3 (LY6/PLAUR domain containing 3) was explored. Candidate circRNAs (circular RNAs) of miR-28-5p were identified. Rescue analyses validated function of circCBFB (core-binding factor subunit beta)/miR-28-5p/GRIA4/LYPD3 axis in VSMC apoptosis and growth. Key findingsMiR-28-5p acted as an apoptosis driver while circCBFB, GRIA4 and LYPD3 exerted anti-apoptosis effects in VSMCs. Mechanically, GRIA4 and LYPD3 were suppressed by miR-28-5p. Moreover, circCBFB served as a sponge of miR-28-5p, releasing GRIA4 and LYPD3 from miR-28-5p suppression. Functionally, GRIA4, LYPD3 and miR-28-5p were required in circCBFB-mediated VSMC apoptosis. SignificanceThis work unveiled an innovative axis of circCBFB/miR-28-5p/GRIA4/LYPD3 in VSMC apoptosis, exerting its potential in providing new thoughts in AAA management.

Site-Specific and Temporal Effects of Apraglutide, a Novel Long-Acting Glucagon-Like Peptide-2 Receptor Agonist, on Intestinal Growth in Mice.

Long-acting glucagon-like peptide-2 receptor (GLP-2R) agonists are well-established to increase intestinal growth in rodents and, most notably, humans with short bowel syndrome. Most of the trophic effects of GLP-2R agonists are reported to be mediated through increased growth of the crypt-villus axis, resulting in enhanced mucosal mass and improved intestinal function. The present study examined the effects of apraglutide, a novel GLP-2R agonist, on the growth of the small intestine and colon after 3, 7, and 10 weeks of treatment in male and female mice. Apraglutide (3 mg/kg; three times per week) significantly increased small intestinal weight (P < 0.001) and length (P < 0.001) after 3 weeks of administration, with a further increase in effectiveness after 10 weeks (P < 0.01). Crypt depth and villus height were both markedly increased after 3 weeks of apraglutide administration (P < 0.001) but did not show any further increase with duration of treatment, whereas crypt number and intestinal circumference were increased after 7 and 10 weeks (P < 0.01) but not after 3 weeks of apraglutide treatment. Both the weight and the length of the colon were also enhanced by apraglutide treatment for 3 weeks (P < 0.001), and these effects were maintained but did not improve further with continued apraglutide administration. The results of this study demonstrate that the novel, long-acting GLP-2R agonist, apraglutide, demonstrates an unexpected marked ability to increase intestinal length as well as exert time- and location-dependent specificity in its intestinotrophic actions. SIGNIFICANCE STATEMENT: The novel long-acting glucagon-like peptide 2 receptor agonist, apraglutide, enhances intestinal weight as well as intestinal length in a time- and site-dependent fashion.

CircGNB1 Facilitates Triple-Negative Breast Cancer Progression by Regulating miR-141-5p-IGF1R Axis.

As an intriguing class of RNA, circular RNAs (circRNAs) are vital mediators of various diseases including cancers. However, the biological role and underlying mechanism of the majority of circRNAs are still ambiguous in the progression of triple-negative breast cancer (TNBC). In this study, we characterized and further investigated hsa_circ_0009362 (circGNB1) by reanalyzing the circRNA microarray profiling in our previous study. Validating by qRT-PCR, circGNB1 was overexpressed in TNBC cell lines and high expression of circGNB1 was associated with worse clinical features and survival outcomes. The expression of circGNB1 was positively correlated with tumor size and clinical stage, and high expression of circGNB1 was an independent risk factor for TNBC patients. Cell proliferation, colony formation, wound-healing and mouse xenograft assays were carried out to investigate the functions of circGNB1. Both in vitro and in vivo assays revealed that knockdown of circGNB1 significantly suppressed cell proliferation, migration and tumor growth. Subsequently, we performed luciferase reporter assays and RNA immunoprecipitation assays to elucidate the underlying molecular mechanism of circGNB1. The results showed that circGNB1 sponges miR-141-5p and facilitates TNBC progression by upregulating IGF1R. Altogether, our study demonstrated the pivotal role of circGNB1-miR-141-5p-IGF1R axis in TNBC growth and metastasis though the mechanism of competing endogenous RNAs. Therefore, circGNB1 may have the potential to be a therapeutic target and novel prognostic biomarker for TNBC.

Combining Immune Checkpoint Inhibitors with Anti-Angiogenic Agents.

Immunotherapy has recently emerged as a novel strategy for treating different types of solid tumors, with promising results. However, still a large fraction of patients do not primarily respond to such approaches, and even responders sooner or later develop resistance. Moreover, immunotherapy is a promising strategy for certain malignancies but not for others, with this discrepancy having been attributed to a more immunogenic microenvironment of some tumors. As abnormal and augmented tumor vessels often occur in cancerogenesis, anti-angiogenic drugs have already demonstrated their effectiveness both in preclinical and in clinical settings. By targeting abnormal formation of tumor vessels, anti-angiogenetic agents potentially result in an enhanced infiltration of immune effector cells. Moreover, crosstalks downstream of the immune checkpoint axis and vascular endothelial growth factor receptor (VEGFR) signaling may result in synergistic effects of combined treatment in tumor cells. In this review, we will describe and discuss the biological rationale of a combined therapy, underlying the modification in tumor microenvironment as well as in tumor cells after exposure to checkpoint inhibitors and anti-angiogenic drugs. Moreover, we will highlight this strategy as a possible way for overcoming drug resistance. By first discussing potential prognostic and predictive factors for combined treatment, we will then turn to clinical settings, focusing on clinical trials where this strategy is currently being investigated.

Microstructure and crystallography of the wall plates of the giant barnacle Austromegabalanus psittacus: a material organized by crystal growth.

In biomineralization, it is essential to know the microstructural and crystallographic organization of natural hard tissues. This knowledge is virtually absent in the case of barnacles. Here, we have examined the crystal morphology and orientation of the wall plates of the giant barnacle Austromegabalanus psittacus by means of optical and electron microscopy, and electron backscatter diffraction. The wall plates are made of calcite grains, which change in morphology from irregular to rhombohedral, except for the radii and alae, where fibrous calcite is produced. Both the grains and fibres arrange into bundles made of crystallographically co-oriented units, which grow onto each other epitaxially. We call these areas crystallographically coherent regions (CCRs). Each CCR elongates and disposes its c-axis perpendicularly or at a high angle to the growth surfaces, whereas the a-axes of adjacent CCRs differ in orientation. In the absence of obvious organic matrices, this pattern of organization is interpreted to be produced by purely crystallographic processes. In particular, due to crystal competition, CCRs orient their fastest growth axes perpendicular to the growth surface. Since each CCR is an aggregate of grains, the fastest growth axis is that along which crystals stack up more rapidly, that is, the crystallographic c-axis in granular calcite. In summary, the material forming the wall plates of the studied barnacles is under very little biological control and the main role of the mantle cells is to provide the construction materials to the growth front.

Microhardness study of Cd1-x ZnxTe1-ySey crystals for X-ray and gamma ray detectors

We performed a detailed Vickers microhardness study of quaternary material Cd1−x ZnxTe1−y Sey (CZTS), which is currently under investigation for applications in the detection of hard X-rays and gamma rays. In this frame, the Vickers microhardness method, resistivity mapping, low-temperature (4.2 K) photoluminescence, and Se energy dispersive X-ray spectroscopy (EDX) composition analysis were employed along the crystal growth axis. The microhardness values measured at 50 g load (HV 0.05), bandgap, and crystal composition along the crystal axis have been correlated. We also performed a comparative study of a set of CdTe, CdZnTe, and CdTeSe samples. We observed a significantly higher microhardness in CZTS crystals when compared to CdZnTe crystals. While in the CdZnTe crystals the microhardness increases by approx. 2.1 HV 0.05 per 1% of Zn + Se content, in CZTS crystals this value is 4.1 HV 0.05. This result indicates a possible additional strengthening of the effect when Zn and Se are mixed in the CdTe lattice.

Desi and kabuli chickpea cultivars had differential behaviour towards salinity stress tolerance.

Twenty chickpea cultivars were germinated under control and different levels of salt stress induced by sodium chloride and out of these, three desi (PDG 3, GL 12003, C 106) and two kabuli (FLIP-08-125-C and GLK 28127) cultivars were selected on the basis of embryonic axis growth, biomass, salinity stress tolerance index. Antioxidative enzymes, non-enzymatic antioxidants proline and proline metabolizing enzymes and free radical scavenging activities were estimated in embryonic axes of these selected cultivars under control and salt stressed conditions. Higher activities of catalase and Δ1-pyrroline-carboxylate synthetase (P5CS) and sustained activities of superoxide dismutase (SOD) and ascorbate peroxidase (APX) in embryonic axis along with higher SOD and glutathione reductase and maintained APX in cotyledons might be mediating salt stress tolerance in kabuli cultivar FLIP-08-125-C. Higher proline content, enhanced P5CS activity and decreased proline dehydrogenase activity in embryonic axis along with higher free radical scavenging activities both in cotyledons and embryonic axis in desi cultivar PDG 3 might be mediating salt stress tolerance by maintaining osmotic balance and reducing oxidative damage.

Signaling Through Ions is Essential for Chemotropism and Reproduction

Chemotropism is essential for many cell types which must orient growth in complex biological spaces, such as neurites, hyphae and pollen tubes. Despite its relevance, chemotropism remains poorly understood and there is no generalized mechanism of either signaling or cellular effectors. We present evidence that two CHX H+/K+ antiporters are necessary for the chemotropic response of pollen tubes towards ovules in flowering plants. Pollen tubes of mutants for these proteins grow normally but are unable to perceive either negative and positive chemotropic stimuli. We determined that this defect is associated in the dynamic regimens of growth and ion dynamics, namely of oscillations of cytosolic pH and extracellular fluxes of H+, with the mutant showing steady oscillations and the wildtype irregular cycles. The phenotype can be rescued by genetics and pharmacology aimed at restoring capacity of H+ extrusion by H+-ATPases, suggesting that pH/H+ fluxes are necessary for sensitization of the intracellular mechanisms that lead to the change of growth axis. We used FHN modeling of plasma membrane potential to explore its role as integrator of these pH changes. Results are suggestive that the existence of standing domains of membrane depolarization could underlie some of these responses, acting upstream of any receptor binding mechanism.

Improved Nd distribution in Czochralski grown YAG crystals by implementation of the accelerated crucible rotation technique

Nd:YAG is a well-known laser material typically grown from the melt using the Czochralski (CZ) method, and like many other doped materials grown from the melt, it suffers from dopant segregation, giving an average Nd concentration in the crystal (Nd%) far less than that in the melt, with Nd variation along the growth axis. Here, the Nd segregation issue is addressed by the successful implementation of the Accelerated Crucible Rotation Technique (ACRT) with CZ. Compared to conventional CZ, ACRT provided improved Nd uniformity, higher Nd incorporation, and control of Nd% along the growth axis, even achieving higher Nd% in the crystal than the initial Nd from the overall melt. ACRT also affects the solid/liquid interface shape and thus the radial segregation. It is thus shown that ACRT and the mixing it provides is promising for achieving unconventional dopant profiles in CZ crystals.

Crystal phase evolution in kinked GaN nanowires

Seed-catalysed growth has been proved to be an ideal method to selectively tune the crystal structure of III–V nanowires along its growth axis. However, few results on relevant nitride NWs have been reported. In this study, we demonstrate the growth of epitaxial kinked wurtzite (WZ)/zinc-blende (ZB) heterostructure GaN NW arrays under the oxygen rich condition using hydride vapour–liquid–solid vapour phase epitaxy (VLS-HVPE). The typical GaN crystal includes WZ and ZB phases throughout the whole NW structure. A detailed structural analysis indicates that a stacking faults free zone was occasionally observed near the NW tips and in the relatively long kinked 〈11-23〉 directions segments (>200 nm). Furthermore, some NWs (<5%) develop phase boundaries, resulting in kinking and crystal phase evolution. A layer-by-layer growth mode was proposed to explain the crystal phase evolution along the phase boundaries. This study provides new insights into the controlled growth of wurtzite (WZ)/zinc-blende (ZB) heterostructure GaN NW.

Expression of the ghrelin/growth hormone secretagogue receptor axis and its functional role in promoting tumor growth in primary central nervous system lymphomas

Ghrelin and its receptor, growth hormone secretagogue receptor (GHS-R), have been found in a variety of malignant tumor tissues, suggesting a biological function of the ghrelin/GHS-R axis in tumor growth and progression. Among central nervous system tumors, primary central nervous system lymphomas (PCNSLs) are relatively rare and characterized by a rapid progression and poor prognosis. In order to clarify ghrelin expression and its functional role in promoting tumor growth and progression in PCNSLs, we undertook an immunohistochemical investigation for ghrelin and GHS-R expression in 43 patients and tested the effect of ghrelin inhibition on lymphoma cells. Furthermore, we investigated the expression of CD105, a marker for tumor angiogenesis, to explore its association with the ghrelin/GHS-R axis. The Kaplan-Meier method and Cox's proportional hazards regression model were used to determine the association of ghrelin/GHS-R expression with overall survival rate. The immunohistochemical study showed moderate/strong immunostaining of cells for ghrelin and GHS-R in 40 patients (93.0%) and 39 patients (90.7%), respectively. A ghrelin inhibitor did not affect tumor cell proliferation in vitro. Expression levels of ghrelin and GHS-R were divided into high and low groups by the rate of moderate-strong staining cells to tumor cells. The survival rate was significantly lower in patients with high GHS-R expression (P = 0.0368 by log-rank test; P = 0.0219 by Wilcoxon test). In addition, multivariate analysis of overall survival using Cox's proportional hazards regression model indicated that GHS-R was a significant independent prognostic factor (P = 0.0426). CD105 expression on tumor vessels was positive in 33 patients (33/37, 89.2%). There was a positive correlation between the moderate-strong staining rate of ghrelin and CD105-positive vessel count. These results indicated that the ghrelin/GHS-R axis plays a potential role in promoting tumor growth and progression through neoangiogenesis, rather than the proliferation of tumor cells.

Lateral straggling of implanted aluminum in 4H-SiC

The implantation of aluminum into 4H-SiC is studied using secondary ion mass spectrometry. In particular, two-dimensional concentration profiles are obtained, which allow the investigation of lateral straggling and its dependence on the crystallographic orientation. A high dose, medium energy aluminum implantation is studied in great detail. It shows an asymmetric distribution due to the 4°-off axis growth of the epitaxial layer. The lateral straggling is found to be in the range of several micrometers for a concentration of 1×1015 cm−3, which is contrary to the expectation given by most simulation studies. Implantations performed at different orientations support the idea that lateral straggling highly depends on the particular channeling opening.