MOLECULAR-GEOMETRY AND CHAIN ENTANGLEMENT - PARAMETERS FOR THE TUBE MODEL

The tube diameter in the reptation model is the distance between a given chain segment and its nearest segment in adjacent chains. This dimension is thus related to the cross-sectional area of polymer chains and the nearest approach among chains, without effects of thermal fluctuation and steric repulsion. Prior calculated tube diameters are much larger, about 5 times, than the actual chain cross-sectional areas. This is ascribed to the local freedom required for mutual rearrangement among neighboring chain segments. This tube diameter concept seems to us to infer a relationship to the corresponding entanglement spacing. Indeed, we report here that the critical molecular weight, M(c), for the onset of entanglements is found to be M(c) = 28 A/([R2]0/M), where A is the chain cross-sectional area and [R2]0 the mean-square end-to-end distance of a freely jointed chain of molecular weight M. The new, computed relationship between the critical number of backbone atoms for entanglement and the chain cross-sectional area of polymers, N(c) = A0,44, is concordant with the cross-sectional area of polymer chains being the parameter controlling the critical entanglement number of backbone atoms of flexible polymers.

靶向斑马鱼VEGF的shRNA表达载体的构建及其对斑马鱼胚胎血管发育的影响

血管内皮生长因子(vascular endothelial growth factor, VEGF)是一种多功能的细胞因子，其主要作用是促进血管内皮细胞增殖和增加血管通透性，是肿瘤及正常组织血管生成的中心调控因素，以VEGF为靶点的肿瘤血管靶向性治疗成为近几年肿瘤治疗的新途径。RNAi是近年来新发展的一项反向遗传学技术，是一种研究基因功能的有力工具。斑马鱼作为一种重要的模式生物，被广泛用于胚胎的分子发育机制、疾病模型的构建以及药物筛选等研究中。然而在斑马鱼中运用RNAi技术进行基因功能研究是一个相对较新的领域，研究资料较少，并且目前进行的斑马鱼RNAi实验中，siRNA大都是通过化学方法或体外转录合成的。体外合成的siRNA在进入体内后会被降解而无法达到持久阻抑基因表达的目的。因此本研究旨在探讨VEGF特异性siRNA表达载体对斑马鱼VEGF基因的沉默作用，通过分析表型及相关细胞因子的变化，阐明VEGF对斑马鱼胚胎血管生成的影响及作用机制。 研究通过计算机辅助设计软件，针对斑马鱼VEGF mRNA不同位点设计合成了4段含siRNA特异序列的DNA单链，经退火，克隆入pSilencer 4.1-CMV neo载体CMV启动子下游，构建了重组质粒pS1-VEGF、pS2-VEGF、pS3-VEGF及pS4-VEGF。 通过显微注射的方法将载体导入1-2细胞期斑马鱼体内，于胚胎发育的48 h采用RT-PCR的方法检测VEGF基因的表达量，研究不同干扰序列对VEGF基因表达的干涉作用。结果显示，针对不同位点的表达载体对VEGF基因表达的抑制效率有显著差异。它们对VEGF mRNA的抑制率分别为80.5%，42.8%，12.5%，40.7%。通过筛选我们得到了一条具有高效抑制作用的载体pS1-VEGF，该载体的相应序列靶向斑马鱼两个主要异构体VEGF165和VEGF121的共有外显子序列。 形态学检测结果显示，注射了pS1-VEGF的胚胎出现了心包膜水肿、血流速度减慢、循环红细胞堆积等症状。定量碱性磷酸酶染色显示，注射pS1-VEGF能够抑制斑马鱼胚胎新生血管的形成，当注射剂量为0.4 ng时，血管生成的抑制率为31.8%。NBT/BCIP血管染色显示，注射该载体后72 h，50%的斑马鱼肠下静脉、节间血管以及其它血管的发育受到不同程度的抑制。随着注射剂量的加大，血管发育受抑制的情况也随之加重，当注射剂量为1 ng时，只有心脏、头部及卵黄有血液循环。对干扰效果的特异性进行了研究，结果表明pS1-VEGF对斑马鱼内源基因胸苷酸合成酶（thymidylate synthase, TS）基因的表达没有明显的抑制作用。针对TS基因的shRNA表达载体及与斑马鱼没有同源性的对照载体对VEGF基因表达也没有明显的抑制作用。浓度梯度实验表明在0-1.2 ng的范围内干扰效果具有剂量依赖性。 以胚胎整体原位杂交的方法检测质粒对VEGF基因受体NRP1基因表达的影响，发现VEGF特异性shRNA表达载体能够引起NRP1基因表达的降低，说明斑马鱼中VEGF所介导的血管生成作用至少在部分上是依赖于NRP通路所调节的。 本研究工作为进一步研究斑马鱼基因功能、VEGF调控网络提供了一个快速、有效的手段，为阐明斑马鱼的血管生成机制提供了新的资料，为采用RNAi技术，以VEGF为靶点，以斑马鱼为模型对肿瘤进行基因治疗研究奠定了基础。

油气输导体系研究及应用─以准噶尔盆地东部白家海凸起侏罗系为例

Baijiahai uplift is an important hydrocarbon accumulation belt in eastern Jungger Basin, on which Cainan oilfield and lithologic hydrocarbon reservoir named Cai 43 have been discovered and both of them share the same target formation of Jurassic. However, in the subsequent exploration at this region, several wells that designed for lithologic traps of Jurassic were eventually failed, and that indicates the controlling factors of lithologic reservoir distribution are far more complicated than our previous expectation. This dissertation set the strata of the Jurassic in well Cai 43 region as the target, and based on the integrated analysis of structure evolution、fault sealing ability、simulations of sedimentary microfacies and reservoir beds、distribution analysis of high porosity-high permeability carrier beds、drive forces of hydrocarbons、preferential conduit system and conduit model as well as critical values of the reservoir physical properties for hydrocarbon charging, a special method that different from the conventional way to predict favorable lithologic traps was established. And with this method the controlling factors of the hydrocarbon reservoirs formation are figured out, and further more, the favorable exploration targets are point out. At Baijiahai uplift, fault plays as a crucial factor in the process of the hydrocarbon reservoir formation. In this study, it is found out that the availability of a fault that work as the seal for oil and gas are different. The critical value of the lateral mudstone smear factor (Kssf), which is used to measure the lateral sealing ability of fault, for oil is 3.9 while that for gas is 2.1; and the critical value of vertical sealing factor (F), which similarly a measurement for the vertical sealing ability of fault, for oil is 7.3 while that for gas is 5.1. Dongdaohaizi fault belt that possessed well lateral sealing ability since later Cretaceous have bad vertical sealing ability in later Cretaceous, however, it turns to be well now. Based on the comparison of the physical properties that respectively obtained from electronic log calculating、conventional laboratory rock analysis and the additive-pressure bearing laboratory rock analysis, we established the functions through which the porosity and permeability obtained though conventional method can be converted to the values of the subsurface conditions. With this method, the porosity and permeability of the Jurassic strata at the time of previous Tertiary and that in nowadays are reconstructed respectively, and then the characteristics of the distribution of high porosity-high permeability carrier beds in the evolution processes are determined. With the result of these works, it is found that both well Cai 43 region and Cainan oilfield are located on the preferential conduit direction of hydrocarbon migration. This conclusion is consistent with the result of the fluid potential analysis, in which fluid potential of nowadays and that of later Cretaceous are considered. At the same times, experiment of hydrocarbon injection into the addictive-pressure bearing rock is designed and conducted, from which it is found that, for mid-permeability cores of Jurassic, 0.03MPa is the threshold values for the hydrocarbon charging. And here, the conception of lateral pressure gradient is proposed to describe the lateral driving force for hydrocarbon migration. With this conception, it is found that hydrocarbons largely distributed in the areas where lateral pressure gradient is greater than 0. 03MPa/100m. Analysis of critical physical properties indicated that the value of the critical porosity and critical permeability varied with burial depth, and it is the throat radius of a certain reservoir bed that works as a key factor in controlling hydrocarbon content. Three parameters are proposed to describe the critical physical properties in this dissertation, which composite of effective oil-bearing porosity、effective oil-bearing permeability and preferential flow coefficient. And found that critical physical properties, at least to some extent, control the hydrocarbon distribution of Jurassic in Baijiahai uplift. Synthesize the content discussed above, this dissertation analyzed the key factors i.e., critical physical properties、driving force、conduit system and fluid potential, which controlled the formation of the lithologic reservoir in Baijiahai uplift. In all of which conduit system and fluid potential determined the direction of hydrocarbon migration, and substantially they are critical physical properties of reservoir bed and the lateral pressure gradient that controlled the eventually hydrocarbon distribution. At the same times, sand bodies in the major target formation that are recognized by reservoir bed simulation are appraised, then predict favorite direction of the next step exploration of lithologic reservoir.

降雨条件下碎石土滑坡稳定性研究

Debris Landslide is one of the types of landslides with the widest distribution, largest quantity, and the closest relationship with engineering construction. It is also one of the most important types of landslides that can cause disaster. This kind of landslide often occurs in the loose slopes which are made up of loose congeries formed by earth filling, residual soil, slope wash, dilapidation, landslide or full weathered material of hard rock. Rainfall is always the chief inducing factor of debris Landslide. Therefore, to research stability of debris Landslide during rainfall not only has important theoretical significance for understanding developing law and deformation and failure mechanism of debris landslide, but also has important practical significance for investigating, appraising, forecasting, preventing and controlling debris landslides. This thesis systematically summarized the relationships between rainfall and landslide, the method to survey water table in the landslides, the deformation and failure mechanism of debris landslide, and the progress in the stability analysis of landslides based on the analyses of data collected widely at home and abroad. The problems in the study of the stability of debris landslide during rainfall was reviewed and discussed. Due to the complicated geological conditions and the random rainfall conditions, the research on the landslides' stability must be based on engineering geological qualitative analysis. Through the collection of the data about the Panxi region and the Three Gorges Reservoir region, the author systematically summarized the engineering geological conditions, hydro-geological condition, distribution characteristics of stress field in the slope, physical and mechanical properties and hydro-mechanical properties of debris. In the viewpoint of dynamics of soil water and hydromechanics, physical process of rainfall to supply groundwater of debris landslides can be divided into two phases, i.e. non-saturated steady infiltrating phase and saturated unsteady supplying phase. The former can be described by mathematical model of surface water infiltration while the latter can be described by equivalent continuous medium model of groundwater seepage. With regard to specific hydrological geology system, we can obtain the dynamic variation law of water content, water table, landslide stability of rock and soil mass, along with quantity and duration of rainfall after the boundary condition on hydrological geology has been ascertained. This is a new way to study the response law of groundwater in the landslides during rainfall. After wet face of rock and soil mass connects with ground water table, the raising of water table will occur due to the supply of rainfall. Then interaction between ground water and rock and soil mass will occur, such as the action of physics, water, chemistry and mechanics, which caused the decrease of shearing strength of sliding zone. According to the action of groundwater on rock and soil mass, a concise mechanical model of debris landslide’s deformation was established during rainfall. The static equilibrium condition of landslide mass system was achieved according to the concise mechanical model, and then the typical deformation and failure process and failure mode of debris landslide during rainfall were discussed. In this thesis, the former limiting equilibrium slice method was modified and improved based on shearing strength theory of , a stability analysis program of debris landslide was established and developed taking account of the saturated-unsaturated seepage, by introducing the shearing strength theory of unsaturated soil mass made by (1978). The program has reasonable data storage and simple interface and is easy to operate, and can be perfectly used to carry out sensitivity analysis of influencing factors of landslides' stability, integrated with the program of Office Excel. The design of drainage engineering are always bases on empirical methods and is short of effective quantitative analysis and appraise, therefore, the conception of critical water table of debris landslide was put forward. For debris landslides with different kinds of slide face in the engineering practice, a program to search the critical water table of debris landslide was developed based on native groundwater table. And groundwater table in the slope should be declined below the critical water table in the drainage works, so the program can be directly used to guide drainage works in the debris landslide. Taking the slope deformation body in the back of former factory building of Muli Shawan hydroelectric power station as an example, a systematic and detailed research on debris landslides' stability during rainfall was researched systematically, the relationship among quantity of rainfall, water table and stability of slope was established, the debris landslides' stability in process of rainfall from dynamic viewpoint was analyzed and researched.

大型反倾岩体变形破坏机制及稳定性分析———以金沙江宽谷坝址龙蟠边坡为例

A large number of catastrophic accidents were aroused by the instability and destruction of anti-dip rock masses in the worldwide engineering projects, such as hydropower station, mine, railways and so on. Problems in relation to deformation and failure about anti-dip rock slopes are significant for engineering geology research. This dissertation takes the Longpan slope in the Jinsha River as a case to study the deformation mechanism of large-scale anti-dip rock masses and the slope stability analysis method. The primary conclusions are as follows. The Dale Reach of Jinsha River, from Longpan to the debouchment of Chongjiang tributary, is located in the southeastern margin of the Qinghai-Tibet Plateau. Longpan slope is the right embankment of Dale dam, it is only 26 km to the Shigu and 18 km to Tiger Leaping Gorge. The areal geology tectonic structures here area are complicated and blurry. Base on the information of geophysical exploration (CSAMT and seismology) and engineering geological investigation, the perdue tectonic pattern of Dale Reach is put forward for the first time in this paper. Due to the reverse slip of Longpan fault and normal left-rotation of Baihanchang fault, the old faulted valley came into being. The thick riverbed sediments have layered characters of different components and corresponding causes, which attribute to the sedimentary environments according with the new tectonic movements such as periodic mountain uplifting in middle Pleistocene. Longpan slope consists of anti-dip alternate sandstone and slate stratums, and the deformable volume is 6.5×107m3 approximately. It was taken for an ancient landslide or toppling failure in the past so that Dale dam became a vexed question. Through the latest field surveying, displacement monitoring and rock masses deforming characters analyses, the geological mechanism is actually a deep-seated gravitational bending deformation. And then the discrete element method is used to simulate the deforming evolution process, the conclusion accords very well with the geo-mechanical patterns analyses. In addition strength reduction method based on DEM is introduced to evaluate the factor of safety of anti-dip rock slope, and in accordance with the expansion way of the shear yielding zones, the progressive shear failure mechanism of large-scale anti-dip rock masses is proposed for the first time. As an embankment or a close reservoir bank to the lower dam, the stability of Longpan slope especially whether or not resulting in sliding with high velocity and activating water waves is a key question for engineering design. In fact it is difficult to decide the unified slip surface of anti-dip rock slope for traditional methods. The author takes the shear yielding zones acquired form the discrete element strength reduction calculation as the potential sliding surface and then evaluates the change of excess pore pressure and factor of stability of the slope generated by rapid drawdown of ponded water. At the same time the dynamic response of the slope under seismic loading is simulated through DEM numerical modeling, the following results are obtained. Firstly the effective effect of seismic inertia force is resulting in accumulation of shear stresses. Secondly the discontinuous structures are crucial to wave transmission. Thirdly the ultimate dynamic response of slope system takes place at the initial period of seismic loading. Lastly but essentially the effect of earthquake load to bringing on deformation and failure of rock slope is the coupling effect of shear stresses and excess pore water pressure accumulation. In view of limitations in searching the critical slip surface of rock slope of the existing domestic and international software for limit equilibrium slope stability analyses, this article proposes a new method named GA-Sarma Algorithm for rock slope stability analyses. Just as its name implies, GA-Sarma Algorithm bases on Genetic Algorithm and Sarma method. GA-Sarma Algorithm assumes the morphology of slip surface to be a broken line with traceability to extend along the discontinuous surface structures, and the slice boundaries is consistent with rock mass discontinuities such as rock layers, faults, cracks, and so on. GA-Sarma Algorithm is revolutionary method that is suitable for global optimization of the critical slip surface for rock slopes. The topics and contents including in this dissertation are closely related to the difficulties in practice, the main conclusions have been authorized by the engineering design institute. The research work is very meaningful and useful for the engineering construction of Longpan hydropower station.

North Wales Clinical Librarian project. Final project report

Urquhart, C., Durbin, J. & Turner, J. (2005). North Wales Clinical Librarian project. Final project report. Aberystwyth: Department of Information Studies. Summary report, plus individual site summary reports also available from http://users.aber.ac.uk/cju/ Sponsorship: NHS Trusts in North Wales

Granularity and disaggregation in compositional modelling with applications to ecological systems

J. Keppens and Q. Shen. Granularity and disaggregation in compositional modelling with applications to ecological systems. Applied Intelligence, 25(3):269-292, 2006.

A importância da educação pela arte no desenvolvimento de competências em alunos com necessidades educativas especificas

Dissertação apresentada à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências da Educação: Educação Especial, área de especialização em Domínio Cognitivo e Motor

Mapping the gene for autosomal dominant restless legs syndrome in an Irish family

Restless Legs Syndrome (RLS) is a common neurological disorder affecting nearly 15% of the general population. Ironically, RLS can be described as the most common condition one has never heard of. It is usually characterised by uncomfortable, unpleasant sensations in the lower limbs inducing an uncontrollable desire to move the legs. RLS exhibits a circadian pattern with symptoms present predominantly in the evening or at night, thus leading to sleep disruption and daytime somnolence. RLS is generally classified into primary (idiopathic) and secondary (symptomatic) forms. Primary RLS includes sporadic and familial cases of which the age of onset is usually less than 45 years and progresses slowly with a female to male ratio of 2:1. Secondary forms often occur as a complication of another health condition, such as iron deficiency or thyroid dysfunction. The age of onset is usually over 45 years, with an equal male to female ratio and more rapid progression. Ekbom described the familial component of the disorder in 1945 and since then many studies have been published on the familial forms of the disorder. Molecular genetic studies have so far identified ten loci (5q, 12q, 14p, 9p, 20p, 16p, 19p, 4q, 17p). No specific gene within these loci has been identified thus far. Association mapping has highlighted a further five areas of interest. RLS6 has been found to be associated with SNPs in the BTBD9 gene. Four other variants were found within intronic and intergenic regions of MEIS1, MAP2K5/LBXCOR1, PTPRD and NOS1. The pathophysiology of RLS is complex and remains to be fully elucidated. Conditions associated with secondary RLS, such as pregnancy or end-stage renal disease, are characterised by iron deficiency, which suggests that disturbed iron homeostasis plays a role. Dopaminergic dysfunction in subcortical systems also appears to play a central role. An ongoing study within the Department of Pathology (University College Cork) is investigating the genetic characteristics of RLS in Irish families. A three generation RLS pedigree RLS3002 consisting of 11 affected and 7 unaffected living family members was recruited. The family had been examined for four of the known loci (5q, 12q, 14p and 9p) (Abdulrahim 2008). The aim of this study was to continue examining this Irish RLS pedigree for possible linkage to the previously described loci and associated regions. Using informative microsatellite markers linkage was excluded to the loci on 5q, 12q, 14p, 9p, 20p, 16p, 19p, 4q, 17p and also within the regions reported to be associated with RLS. This suggested the presence of a new unidentified locus. A genome-wide scan was performed using two microsatellite marker screening sets (Research Genetics Inc. Mapping set and the Applied Biosystems Linkage mapping set version 2.5). Linkage analysis was conducted under an autosomal dominant model with a penetrance of 95% and an allele frequency of 0.01. A maximum LOD score of 3.59 at θ=0.00 for marker D19S878 indicated significant linkage on chromosome 19p. Haplotype analysis defined a genetic region of 6.57 cM on chromosome 19p13.3, corresponding to 2.5 Mb. There are approximately 100 genes annotated within the critical region. Sequencing of two candidate genes, KLF16 and GAMT, selected on the assumed pathophysiology of RLS, did not identify any sequence variant. This study provides evidence of a novel RLS locus in an Irish pedigree, thus supporting the picture of RLS as a genetically heterogeneous trait.

Four nations feminism: Una Troy and Menna Gallie

The emergence of four nations framework in literary and historical scholarship has helped us to arrive at a fuller understanding of the complex and overlapping histories of the islands of Britain and Ireland, while recent research into Wales and Ireland in particular has helped to make the map of our relations more fully comprehensible. But what is the relevance and meaning of the four nations context for womenâ s writing in Ireland and Wales? What part does gender play in the interconnected histories of Wales and Ireland, and how are questions of sexual and artistic identity addressed within texts that imagine British-Irish history in gendered terms? This lecture identifies finds evidence of a feminist reimagining of archipelagic relationships by two writers: Munster novelist and playwright Una Troy, and Welsh writer Menna Gallie, born into a mining community on the western edge of the South Wales coalfields. Both Troy and Gallie wrote novels that deploy plots of female friendship to interrogate the relationship between gender and national affiliation in a four nations context.

Chicana poetics: genre and style in Gloria Anzaldúa and Lorna Dee Cervantes

This thesis conducts a formal study of the poetry of Gloria Anzaldúa and Lorna Dee Cervantes, placing their work in dialogue with genre and style. These two Chicana poets are exemplary of politicised experimentation with poetics, underpinned by a keen awareness of the rich history of form, genre and style. In the work of each poet, two poetic modes are examined: one traditional, and one experimental. Anzaldúa’s uses of the dramatic monologue as a border genre, and her construction of [auto]poetics, stemming from her multi-genre, autobiographical approach to writing, are considered. Cervantes’s complex approach to the construction of docupoetics that achieves a depth of field in terms of merging a multidimensional approach to aesthetics with highly politicised transnational content, as well as her engagement with the longstanding poetic of elegy via various formal points of entry, is investigated. These poetic modes are primarily explored via close readings, supported by a multidisciplinary framework that includes Anzaldúa’s feminist theories of identity and writing, abjection theory, postcolonialism, and transnationalism. Overall, these four key areas demonstrate the ways in which aesthetics is a crucial consideration in the exploration of the broader issues of content and context in Chicana poetry.

Monstrative acts and becoming-monster: on identity, bodies, and the feminine other

Using two examples of literary monsters, the Creature in Mary Shelley’s Frankenstein (1818), and Grendel’s Mother in Beowulf, this thesis demonstrates the bearing fictional identities have on “real” bodies, through an examination of two further literary texts, David Henry Hwang’s play, M. Butterfly (1986) and J. M. Coetzee’s novel, Disgrace (1999). Western definitions of Being have historically divided body and mind, favouring the mind as formative of subjective experience and denigrating the body as secondary and impure. This thesis demonstrates that this mind/body binary is symptomatic of the masculine ontological imperative to disown the body and its effects on Being, simultaneously ridding itself of the feminine it believes is its irrational opposite. Using recent feminist reviews of the canon, which emphasise the body’s importance to ontology and demonstrate the conceptual association between the feminine and the corporeal, this thesis links performative identity practices to theories of monstrosity, explaining how fictional qualities adhere to monstrous bodies by proposing a new theoretical category, the “monstrative.” The monstrative is a performative force that makes the Other into a living sign of Otherness; however, unlike earlier theories of Othering, the monstrative accounts for the Other’s being other to herself. This thesis also attempts to read the misrepresented body of the Other as a possible site for more empowered identity performances, where the monstrous “I” is interpreted as a potentially positive model for identity practice, through the conceptualisation of identity as a process of Becoming rather than Being. The transferal from a noun to a verb not only emphasises the performativity of identity, but also suggests fluidity and multiplicity in identity practice, which always already indicates a monstrosity at work. Thus, while monstrative acts constitute bodies as monstrous, Becoming-monster is an empathetic response to the Other’s monstrosity.

Due to her tender age: Black girls and childhood on trial in South Carolina, 1885-1920

Drawing on local criminal court records in western and central South Carolina, this dissertation follows the legal experiences of black girls in South Carolina courts between 1885 and 1920, a time span that includes the aftermath of Reconstruction and the foundational years of Jim Crow. While scholars continue to debate the degree to which black children were included in evolving conversations about childhood and child protection, this dissertation argues that black girls were critical to turn-of-the century debates about all children's roles in society. Far from invisible in the courts and jails of their time, black girls found themselves in the crosshairs of varying forms of power --including intraracial community surveillance, burgeoning local government, Progressive reform initiatives and military policy -- particularly when it came to matters of sexuality and reproduction. Their presence in South Carolina courts established boundaries between early childhood, adolescence and womanhood and pushed legal stakeholders to consider the legal implication of age, race, and gender in criminal proceedings. Age had a complicated effect on black girls' legal encounters; very young black girls were often able to claim youth and escape harsher punishments, while courts often used judicial discretion to levy heavier sentences to adolescents and violent girl offenders. While courts helped to separate early childhood from the middle years, they also provided a space for African-American children and family to engage a legal system that was moving rapidly toward disenfranchising blacks.

The Innate Immune System in Acute and Chronic Wounds.

Significance: This review article provides an overview of the critical roles of the innate immune system to wound healing. It explores aspects of dysregulation of individual innate immune elements known to compromise wound repair and promote nonhealing wounds. Understanding the key mechanisms whereby wound healing fails will provide seed concepts for the development of new therapeutic approaches. Recent Advances: Our understanding of the complex interactions of the innate immune system in wound healing has significantly improved, particularly in our understanding of the role of antimicrobials and peptides and the nature of the switch from inflammatory to reparative processes. This takes place against an emerging understanding of the relationship between human cells and commensal bacteria in the skin. Critical Issues: It is well established and accepted that early local inflammatory mediators in the wound bed function as an immunological vehicle to facilitate immune cell infiltration and microbial clearance upon injury to the skin barrier. Both impaired and excessive innate immune responses can promote nonhealing wounds. It appears that the switch from the inflammatory to the proliferative phase is tightly regulated and mediated, at least in part, by a change in macrophages. Defining the factors that initiate the switch in such macrophage phenotypes and functions is the subject of multiple investigations. Future Directions: The review highlights processes that may be useful targets for further investigation, particularly the switch from M1 to M2 macrophages that appears to be critical as dysregulation of this switch occurs during defective wound healing.