The present disclosure provides peptides, or variants or analogs thereof, with between 8 and 30 amino acids, having growth factor receptor-binding capability, wherein the RMSD value of the structure coordinates of said peptide, variant or analog thereof with respect to PEPREF is 2.45 Å (Angstroms) or less.

Tissue regeneration forms an important part of the healing process subsequent to disease, trauma, or surgery. In situations where disease or trauma produces a tissue defect, for example a bone, cartilage, skin, vascular tissue, or eye retina defect, tissue regeneration is a central goal of recovery. It is not, however, a goal that is always or easily achieved and much research has been devoted to newer and more effective ways to promote tissue repair and regeneration. Conventional technics to achieve tissue regeneration involve the activation of tissue-specific stem cells present in adult tissues with repair and/or regenerative capabilities called mesenchymal stem cell(s) or MSC(s) using recombinant proteins called growth factors (GFs). MSCs or MSC-like cells may be found in the bone marrow, but also in tissues such as fat, umbilical cord blood, amniotic fluid, placenta, dental pulp, tendons, synovial membrane and skeletal muscle. Natural regulation of the MSCs is effected through the participation of a number of growth factors (GFs), including vascular endothelial growth factors (VEGF), which trigger angiogenesis crucial for the repair of most tissues, bone morphogenetic proteins (BMP), which induce the formation of new bone and regulate capillary stem cell activation, transforming growth factors (TGF), which induce cartilage formation, and platelet-derived growth factor-BB (PDGF-BB), which is involved in the formation of granulation tissues and the recruitment of stem cells. Naturally occurring growth factors are found within the tissues themselves and are only present in small amounts. Thus, to provide industrially useful and reproducible amounts of human growth factors, traditional technics involve the production of GFs by genetic recombination. These recombinant molecules are typically grafted onto the surface of a biocompatible material and placed, where needed, inside or on the body of a patient.
Bone
It is conventionally known that mature osteoblasts are the cells responsible for bone formation and are derived from osteoblast precursors. Differentiation of human bone marrow mesenchymal stem cells and osteoblast precursors is one of the important processes for bone regeneration. Osteoblasts differentiate from mesenchymal stem cells. Mature osteoblasts differentiate from osteoblast precursors and into osteocytes which are non-dividing cells. Upon cell activation osteoblasts begin to secrete some extracellular matrix around themselves. Calcification, i.e., deposition of insoluble calcium salts in the bone matrix, begins a short time after the matrix has been secreted. Upon termination of bone matrix synthesis, osteoblasts either undergo cell death by apoptosis or differentiate into osteocytes or bone lining cells. Mesenchymal stem cells are found in large numbers in the periosteum, the fibrous-like layer on the outside surface of bones, and in the bone marrow. During cellular differentiation of osteoblasts, the developing progenitor cells express the regulatory transcription factor Cbfa1/Runx2. A second important transcription factor required for osteoblastic differentiation is osterix. Osteoprogenitors differentiate under the influence of growth factors. Important growth factors in skeletal differentiation include bone morphogenetic proteins (BMPs), transforming growth factor beta (TGF-β) and fibroblast growth factors (FGFs). Differentiation of osteoblasts is also characterized by the expression of alkaline phosphatase as an early marker of pre-osteoblasts. As a result, acting on the differentiation cycle of mammal bone marrow mesenchymal stem cells and osteoblast precursors may have applications in bone tissue regeneration.
Osteoporosis
Osteoporosis is a progressive bone disease that is characterized by a decrease in bone mass and density which can lead to an increased risk of fracture. In osteoporosis, the bone mineral density (BMD) is reduced, bone microarchitecture deteriorates, and the amount and variety of proteins in bone are altered. Osteoporosis is defined by the World Health Organization as a bone mineral density of 2.5 standard deviations or more below the mean peak bone mass (average of young, healthy adults) as measured by dual-energy X-ray absorptiometry; the term "established osteoporosis" includes the presence of a fragility fracture. The treatment of osteoporotic fractures is often hindered by reduced bone healing and higher rates of complications. Studies in osteoporotic animal models revealed delayed callus formation and enchondral ossification, resulting in impaired biomechanical properties of the bone. The cellular sources of fracture healing are mesenchymal stem cells (MSCs). MSCs migrate to the fracture site, where they proliferate and differentiate into osteoblasts upon stimulation with osteoinductive cytokines. Molecular biological alterations of MSCs, such as decreased proliferative capacity, production of collagen I deficient matrix, preferableness of adipogenic differentiation, and impaired osteogenic differentiation have been described in osteoporotic patients. With regards to the osteoinduction of MSCs, key agents are BMPs. Of these, BMP-2 is one of the most potent osteoinductive cytokines which physiologically contributes to the early phase of fracture healing. Beyond that, BMP-2 is already clinically approved for the treatment of distinct fracture entities. The predominant role of BMP-2 in osteoinduction and bone formation led to a scientific quest regarding its involvement in the pathophysiology of osteoporosis. Osteoporotic animal models revealed inconsistent data with regard to BMP-2 expression levels. BMP-2 was found to be overexpressed in the callus of mandibles and down-regulated in MSCs derived from tibial and femoral bone. In humans, genetic polymorphisms in BMP-2 have been identified as risk factors for the development of familial osteoporosis and osteoporotic fractures. All these findings directly link the BMP pathways to osteoporosis. Other studies investigated the therapeutic potential of BMP-2 in osteoporotic animal models. The systemic administration of rhBMP-2 increased the volume of trabecular bone and stimulated bone formation in osteoporotic mice. The local application of adenoviral BMP-2 at the site of injury enhanced callus formation and improved mechanical properties of the healing bone in osteoporotic sheep. Stimulating the differentiation of MSCs and/or inducing growth factor activity, in particular of BMPs, may thus lead to the development of new osteoporosis treatments.
Cartilage
Although native chondrocytes offer little assistance to injured articular cartilage, these cells are responsible for the synthesis and turnover of the cartilage extracellular matrix (ECM), which provides an environment of nutrition diffusion for chondrocytes and provides the joint surface with biomechanical competence. Chondrogenic cells arise from pluripotential adult mesenchymal stem cells (MSCs) through a series of differentiation pathways. Subsequently, it was shown that a number of cytokines and transcription factors are involved in chondrocyte maturation and cartilage formation. Chondrogenic differentiation of MSCs is induced by various intrinsic and extrinsic factors. Growth factors play the most important role in this process. They represent a group of biologically active polypeptides produced by the body, which can stimulate cell proliferation, differentiation and maturation. In the hyaline cartilage, growth factors regulate homeostasis and integrity, as well as development. Important growth factors intervening in cartilage regeneration include TGF-β1, TGF-β3, BMP-2, BMP-4, BMP-7 and GDF-5. As a result, acting on the differentiation cycle of mammal mesenchymal stem cells and chondroblast precursors may have applications in cartilage tissue regeneration.
Muscles
Skeletal muscle is a highly complex and heterogeneous tissue serving a multitude of functions in the organism. The process of generating muscle—myogenesis—can be divided into several distinct phases. During embryonic myogenesis, mesoderm-derived structures generate the first muscle fibers of the body proper, and in subsequent waves additional fibers are generated along these template fibers. In the perinatal phase, muscle resident myogenic progenitors initially proliferate extensively but, later on, decrease as the number of myonuclei reaches a steady state and myofibrillar protein synthesis peaks. Once the muscle has matured, these progenitors will enter quiescence and henceforth reside within it as satellite cells. Adult skeletal muscle, like all renewing organs, relies on a mechanism that compensates for the turnover of terminally differentiated cells to maintain tissue homeostasis. This type of myogenesis depends on the activation of satellite cells that have the potential to differentiate into new fibers. The most comprehensively studied form of myogenesis takes place when mature muscle is damaged and large cohorts of satellite cells expand mitotically and differentiate to repair the tissue and reestablish homeostasis. Many similarities, such as common transcription factors and signaling molecules, between embryonic myogenesis and regeneration in the mature skeletal musculature have been discovered. It is now generally accepted that satellite cells are closely related to progenitors of somitic origin. The activation of the network of transcription factors that controls skeletal muscle development depends on paracrine factors that are released by adjacent tissues, such as the neural tube, notochord, surface ectoderm and lateral mesoderm. Several secreted factors have been identified that determine the spatial and temporal onset of myogenesis. However, no consensus has been reached as to whether these molecules instruct naive cells (instructive induction), amplify a pool of committed progenitors and/or enable a default differentiation pathway (permissive induction) or primarily prevent programmed cell death of muscle progenitor cells. Sonic hedgehog (SHH) and WNT signaling have been reported to have pivotal roles in the induction of myogenesis. Likewise, other signalling molecules, such as Noggin and bone morphogenetic proteins (BMPs)—which inactivate and activate receptors of the transforming growth factor-β (TGFβ) superfamily, respectively—are known to play an important part in orchestrating the activation of myogenesis. Muscle tissue degenerative diseases or disorders include, but are not limited to, myopathies, muscular atrophy, disuse atrophy, denervation atrophy, muscular dystrophies such as the Duchenne muscular dystrophy (DMD), and the Becker muscular dystrophy (BMD), fibrosis, fibrositis, muscle weakness, fatigue, cramps, fibromyalgia, or chronic muscle pain syndrome.
Vascular
The vasculature in the human body forms through two distinct processes: vasculogenesis and angiogenesis. Vasculogenesis is defined as the process of de novo blood vessel formation occurring when endothelial precursor cells (angioblasts) migrate and differentiate into endothelial cells which form the new vessel. These vascular trees are then extended through angiogenesis which is defined as the new vessel formation secondary to proliferation of endothelial cells from pre-existing vessels. Vasculogenesis as well as angiogenesis occur during the embryologic development of the circulatory system but also in the adult organism from circulating endothelial progenitor cells (derivatives of stem cells) able to contribute, albeit to varying degrees, to neovascularization. An example of where these processes can occur in adults is the revascularization following trauma, e.g., after cardiac ischemia. It is known that the ablation of the endothelial progenitor cells (EPCs) in the bone marrow leads to a significant decrease in the vasculature development which would place endothelial progenitor cells as a novel therapeutic target. The differentiation of the EPCs is a consequence of the interplay amongst different signaling molecules such as growth factors. These include FGF, VEGF, PDGF and others. Vascular endothelial growth factor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate. VEGF is a sub-family of growth factors, to be specific, the platelet-derived growth factor family of cystine-knot growth factors. VEGF causes an important signaling cascade in endothelial cells. Binding to VEGF receptor-2 (VEGFR-2) starts a tyrosine kinase signaling cascade that stimulates the production of factors that variously stimulate vessel permeability, proliferation/survival, migration and finally differentiation into mature blood vessels. Recent reports have also indicated that different somatic cells (other than the EPCs) could be reprogrammed towards distinct endothelial cell lineages. This somatic reprogramming as well as the stimulation of EPCs differentiation, both represent promising therapeutic targets in regenerative vascular medicine.
Wound Healing
Wound healing is a complex and dynamic process of replacing devitalized and missing cellular structures and tissue layers. Upon injury to the skin, a set of complex biochemical events takes place in a closely orchestrated cascade to repair the damage and restore the protective barrier which in the normal skin is formed by the epidermis (outermost layer) and the dermis (inner or deeper layer) which exist in a steady-state equilibrium. The human adult wound healing process can be divided into 4 distinct phases: hemostasis, inflammatory, fibroblastic, and maturation (or remodeling). These phases are initiated and regulated by various secreted factors such as growth factors. In the first phase, the damaged blood vessels are sealed via different substances secreted by the platelets such as the platelet-derived growth factor (PDGF). The second phase corresponds to an inflammatory response which causes the blood vessels to become leaky thus releasing plasma and PMN's into the surrounding tissue. The neutrophils phagocytize debris and microorganisms and provide the first line of defence against infection. The cells macrophages are able to phagocytize bacteria and provide a second line of defence. They also secrete a variety of chemotactic and growth factors such as fibroblast growth factor (FGF), epidermal growth factor (EGF), transforming growth factor beta (TGF β and interleukin-1 (IL-1) which appears to direct the next stages of wound healing. The third phase involves the replacement of dermal and subdermal tissues. The fibroblasts secrete the collagen framework onto which further dermal regeneration occurs. The pericytes which regenerate the outer layers of capillaries and the endothelial cells which produce the lining are involved in the angiogenesis. The keratinocytes are responsible for the epithelialization. In the final stage of epithelializtion, contracture occurs as the keratinocytes differentiate to form the protective outer layer or stratum corneum. The last and 4th phase of wound healing involves remodeling the dermal tissues to produce greater tensile strength. The principle cells involved in this process are the fibroblasts. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. Recent research has also shown that adult stem cells could be involved in wound healing. In particular hematopoietic progenitor cells (that give rise to mature cells in the blood) may have the ability to de-differentiate back into hematopoietic stem cells and/or trans-differentiate into non-lineage cells, such as fibroblasts. It is thought that the extent of the stem cell involvement in skin wound healing is complex as the epidermis and dermis could be reconstituted by mitotically active stem cells that reside at the apex of rete ridges (basal stem cells or BSC), the bulge of hair follicles (hair follicular stem cell or HFSC), and the papillary dermis (dermal stem cells). Moreover, the bone marrow may also contain stem cells that could play a major role in cutaneous wound healing. Therefore, activating adult stem cells as well as the different cells and growth factors intervening during the four phases of the skin wound healing process, most certainly represents a promising therapeutic target.
Tissue Closure
Wound healing not only applies to skin tissue repair but also to the closure of all tissue layers damaged e.g. in an injury or during surgery. For instance, during bone repair surgery, the different layers of tissues incised in order for the surgeon to reach the damaged bone part and repair it would all need to be closed for the overall healing process to occur. The mediation of this complex, "multi-layered" healing process, involves the participation of many different factors such as growth factors.
Neurons
For a long time, the human nervous system has been considered fixed and incapable or regeneration since neurons do not divide within the central nervous system (CNS). Recently in has been discovered that neural cells can be regenerated from neural stem cells (NSCs). These are self-renewing, multipotent adult stem cells that generate the main phenotype of the nervous system. They undergo asymmetric cell division into two daughter cells, one non-specialized and one specialized. NSCs primarily differentiate into neurons, astrocytes, and oligodendrocytes. NSCs are generated throughout an adult's life via the process of neurogenesis. NSCs can be differentiated to replace lost or injured neurons or in many cases even glial cells. NSCs are stimulated to begin differentiation via exogenous cues from their microenvironment, or the neural stem cell niche. This niche defines a zone in which stem cells are retained after embryonic development for the production of new cells of the nervous system. This continual supply of new neurons and glia then provides the postnatal and adult brain with an added capacity for cellular plasticity. Critical to the maintenance of the stem cell niche are microenvironmental cues and cell-cell interactions that act to balance stem cell quiescence with proliferation and to direct neurogenesis versus gliogenesis lineage decisions. Several proteins like different growth factors are involved in the mechanisms of the neural stem cell niche as well as in the maintenance and growth of the newly formed neurons. These include the BMPs, FGFs, PDGF, VEGF, TGF β, BDNF and others. Nerve growth factor (NGF) is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons (nerve cells). It also functions as a signaling molecule. While "nerve growth factor" refers to a single factor, "nerve growth factors" refers to a family of factors also known as neurotrophins. Other members of the neurotrophin family that are well recognized include Brain-Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT-3), and Neurotrophin 4/5 (NT-4/5). NGF is critical for the survival and maintenance of sympathetic and sensory neurons. Without it, these neurons undergo apoptosis. Nerve growth factor causes axonal growth. Studies have shown that it causes also axonal branching and elongation. Several brain diseases are considered to be caused by disorders in the neural stem cell niche and especially in the precise signaling of this microenvironment. Therefore restoring correct growth factor signaling is a promising target for the treatment of brain diseases.
Eye Retina
The vertebrate retina is a light-sensitive layer of tissue, lining the inner surface of the eye. Light striking the retina initiates a cascade of chemical and electrical events that ultimately trigger nerve impulses. These are sent to various visual centers of the brain through the fibers of the optic nerve. In vertebrate embryonic development, the retina and the optic nerve originate as outgrowths of the developing brain, so the retina is considered part of the central nervous system (CNS) and is actually brain tissue. Retinal development involves a complex progression of tissue induction, proliferation of retinal progenitor cell (RPC) populations and terminal differentiation of these cells into specific functional types. Growing evidence indicates that several extrinsic cues play a critical role in the retinal cell development. One such extrinsic molecule type, bone morphogenetic protein (BMP), is a member of the transforming growth factor (TGF)-β family of signaling molecules, which are known to regulate a variety of cell functions in the developing nervous system, including neural induction, cell fate determination, apoptosis, and proliferation. BMP-2, -4, and -7 and their receptors (BMPRs) are expressed in the eye during embryogenesis and are essential for multiple aspects of retinal development. There are many inherited and acquired diseases or disorders that may affect the retina like for example the macular degeneration. It is a degenerative disease that usually affects older adults and results in a loss of vision in the center of the visual field (the macula) because of damage to the retina. Age-related macular degeneration is the leading cause of irreversible blindness in North America. Regenerating the retina via the growth factor signaling responsible for its development is thus a significant potential therapeutic target.
Kidneys
The kidney is a complex tissue consisting of several different cell types including glomerular podocytes, endothelial cells, mesangial cells, interstitial cells, tubular epithelial cells, and connecting duct cells. These cell types interact to establish a precise cellular environment that functions as an efficient tissue. Kidney diseases are currently a global public health problem, with an incidence that has reached epidemic proportions and continues to climb worldwide. Kidney failure can be associated with chronic kidney disease (CKD), which is a progressive loss in renal function over a period of months or years. Renal fibrosis, the common pathological feature of CKDs, is characterized by excessive accumulation of ECM (extracellular matrix). TGF-β (transforming growth factor-β) and BMP-7 (bone morphogenetic protein-7), two key members in the TGF-β superfamily, play important but diverse roles in CKDs (chronic kidney diseases). Both TGF-β and BMP-7 share similar downstream Smad signalling pathways, but counter-regulate each other to maintain the balance of their biological activities. During renal injury in CKDs, this balance is significantly altered because TGF-β signalling is up-regulated by inducing TGF-β1 and activating Smad3, whereas BMP-7 and its downstream Smad1/5/8 are down-regulated. In the context of renal fibrosis, Smad3 is pathogenic, whereas Smad2 and Smad7 are renoprotective. However, this counter-balancing mechanism is also altered because TGF-β1 induces Smurf2, an ubiquitin E3-ligase, to target Smad7 as well as Smad2 for degradation. Thus overexpression of renal Smad7 restores the balance of TGF-β/Smad signaling and has therapeutic effect on CKDs. It may this be that restoring the BMP-7 signaling is a potential therapeutic target in renal regenerative therapies.
Ligaments and Tendons
Tendons and ligaments (T/L) are dense connective tissues of mesodermal origin. They connect and transmit force from muscle to bone and bone to bone, respectively. Both tissues are able to store elastic energy and withstand high tensile forces, on which locomotion is entirely dependent. T/L are predominantly composed of collagen type I fibrils organized in a highly hierarchical manner that is unique for the T/L. Other collagens (types XI, XII, XIV, and XV) and various proteoglycans (decorin, cartilage oligomeric matrix protein (COMP), byglican, lumican, fibromodulin, tenascin-C, etc.) are building the remaining T/L substance. The cellular content of T/L is dominated by tendon-specific fibroblasts named tenocytes. During embryonic development, the tendon-specific cells descend from a sub-set of mesenchymal progenitors condensed in the syndetome, a dorsolateral domain of the sclerotome. Moreover, Mesenchymal stem cells (MSCs), multipotent adult cells that give rise to tissues of mesodermal origin, have been shown to generate in vitro T/L progenitor cells. Several tendon injuries result from gradual wear and tear to the tendon from overuse or aging. Tendon healing is a complex and highly-regulated process that is initiated, sustained and eventually terminated by a large number and variety of molecules. Growth factors represent one of the most important molecule families involved in regeneration. The activity of five growth factors has been best characterized during this process: insulin-like growth factor-I (IGF-I), transforming growth factor beta (TGFbeta), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF). Stimulating the differentiation of MSCs and/or inducing growth factor activity thus represent two potentially significant therapeutic targets in T/L regeneration and healing.
Fertility and Reproduction
Reproduction (or procreation) is the biological process by which new offspring individual organisms are produced from their parents. Sexual reproduction is a biological process by which organisms create descendants that have a combination of genetic material contributed from two (usually) different members of the species. Fertility is the natural capability to produce offspring. The development and physiological functions of basic structures in the mammalian reproductive system are influenced by the tissue-specific expression of members of different growth factors families like the BMP family. The establishment of the germ line is a fundamental aspect of reproduction. Germ cell determination is induced in epiblast cells by the extraembryonic ectoderm, and is not acquired through the inheritance of preformed germ plasma. There is some strong evidence that BMP-4 and -8b play a central role in determining primordial germ cell (PGC) formation in the embryo. The genes encoding BMP-4 and -8b have overlapping expression in the extraembryonic ectoderm before gastrulation, i.e., before PGCs are seen. Thus, PGC formation requires BMP-4 expression. There is also evidence from knockout mammals that BMP-8b is required for PGC formation. Furthermore, there is increasing evidence that locally produced BMPs play a major role in the differentiation of the pituitary gonadotrope. Restoring the BMPs signaling would thus be an important factor in infertility therapies.
Hair
Tissue homeostasis and regeneration are regulated through balancing quiescence and activation of quiescent epithelial stem cells (SCs). Hair follicles (HFs) follow this process. Throughout adult life, they undergo dynamic, synchronized cycles of degeneration (catagen), quiescence (telogen), and regeneration (anagen). During telogen, which can last for months, HFSCs are quiescent and reside within a specialized microenvironment called the bulge. Within this niche, HFSCs surround the hair shaft produced in the previous cycle. Throughout telogen, the base of the bulge, called the secondary hair germ (HG), directly abuts the underlying mesenchymal dermal papillae (DP), a key signaling center for HFSCs. The telogen/anagen transition relies upon DP-HFSC crosstalk to generate the necessary threshold of activating factors. Upon activation, HFSCs in the HG are the first to proliferate and initiate HF regeneration, whereas HFSCs within the bulge become active several days later. As the new HF emerges, the DP stimulus is pushed increasingly further from niche SCs, which return to quiescence. In contrast, throughout anagen, relatively undifferentiated bulge cell progeny along the outer root sheath (ORS) accelerate proliferation as they approach the DP. This fuels a steady production of transiently amplifying matrix cells, which undergo a few divisions while in contact with DP and then terminally differentiate to form the hair and inner root sheath (IRS). At the anagen/catagen transition, matrix cells apoptosis and the DP retracts upward along with the dying/differentiating epithelial strand. As the HF reenters telogen, growth factors from the inner layer of non-SC niche cells and from surrounding dermal tissue impose a threshold, which must be overcome to initiate the next cycle. When cells in the telogen phase are not able to reenter into the anagen phase, hair stop their growth, and conditions such as hair loss emerge. As a result, acting on the differentiation cycle of mammal hair follicle mesenchymal stem cells and precursor cells may have applications in hair follicle tissue regeneration thus preventing hair-loss and activating hair-growth, preventing/treating alopecia areata, alopecia totalis, alopecia universalis, androgenic alopecia (male pattern baldness), telogen effluvium, anagen effluvium or chemotherapy-induced alopecia, but is not limited.
Skin
The skin constantly renews itself throughout adult life. Stem cells (SCs) residing in the epidermis ensure the maintenance of adult skin homeostasis, but they also participate in the repair of the epidermis after injuries. The skin protects the body from dehydration, injury and infection. The skin consists of an underlying dermis, separated by a basement membrane from the multilayered overlaying epidermis. The dermis is of mesodermal embryonic origin and contains as adult stem cells fibroblastic mesenchymal stem-cell-like cells. These cells have a multi-lineage differentiation potential, being also able to form adipose tissue or bones. The stratified epidermis is of ectodermal origin and composed of keratinocytes that differentiate to a water-impermeable stratum corneum. The terminally differentiated cells in the epidermis are shed from the skin, necessitating a continuous delivery of newly differentiating cells. The epidermis is completely renewed about every four weeks. Given that the differentiated cells cannot divide anymore, their replacement depends on epidermal stem cells. Skin stem cells are of special interest because they are easily accessible. In recent years, several products said to have a link with skin stem cells have found their way to the cosmetic products market such as AMATOKIN®, a face care product line commercialised by Voss Laboratories and said to stimulate stem cells in the skin, or Dior's CAPTURE® R60/80 XP product line used as anti-wrinkles whose mechanism is said to be based on the protection of the life force of stem cells. As a result, there is thus some potential in acting on the differentiation cycle of mammal skin mesenchymal stem cells and precursor cells with potential applications in skin tissue regeneration thus preventing wrinkles formation and generally improving skin appearance.
Blood
Blood is a bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those cells. When it reaches the lungs, gas exchange occurs wherein carbon dioxide is diffused out of the blood into the alveoli and oxygen is diffused into the blood. This oxygenated blood is pumped to the left hand side of the heart in the pulmonary vein and enters the left atrium. From here it passes through the bicuspid valve, through the ventricle and taken all around the body by the aorta. Blood contains antibodies, nutrients, oxygen and much more to help the body work. In vertebrates, it is composed of blood cells suspended in blood plasma. Plasma, which constitutes 55% of blood fluid, is mostly water (92% by volume), and contains dissipated proteins, glucose, mineral ions, hormones, carbon dioxide (plasma being the main medium for excretory product transportation), and blood cells themselves. Albumin is the main protein in plasma, and it functions to regulate the colloidal osmotic pressure of blood. Hematopoietic stem cells (HSCs) are the blood cells that give rise to all the other blood cells and are derived from the mesoderm. They are located in the red bone marrow, which is contained in the core of most bones. The HSCs give rise to the myeloid lineage (monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes/platelets, dendritic cells), and to the lymphoid lineages (T-cells, B-cells, NK-cells). The most abundant cells in the vertebrate blood are red blood cells (also called RBSs or erythrocytes). These contain hemoglobin, an iron-containing protein, which facilitates oxygen transport by reversibly binding to this respiratory gas and greatly increasing its solubility in blood. Blood cell degeneration-related diseases, conditions or disorders include, but are not limited to, Anemia, Iron-deficiency anemia, Anemia of chronic disease, Pernicious anemia, Aplastic anemia, Autoimmune hemolytic anemia, Thalassemia, Sickle cell anemia, Polycythemia vera, Vitamin deficiency anemia, Hemolytic anemia, Thrombocytopenia, Idiopathic thrombocytopenic purpura, Heparin-induced thrombocytopenia, Thrombotic thrombocytopenic purpura, Essential thrombocytosis (primary thrombocythemia), Thrombosis, Hemophilia, von Willebrand disease, Hypercoaguable state (hypercoagulable state), Deep venous thrombosis, Disseminated intravascular coagulation (DIC), Thrombocytopenia, Immune Thrombocytopenia (ITP), Drug-induced thrombocytopenia (DITP), Gestational thrombocytopenia, Thrombotic microangiopathies (TMA), Drug-induced thrombotic microangiopathies, Complement-mediated thrombotic microangiopathies, Mixed cryoglobulinemia, Eosinophilia, Eosinopenia, Idiopathic hypereosinophilic syndrome, Antiphospholipid syndrome (Hughes syndrome), Glanzmann's thrombasthenia, Wiskott-Aldrich syndrome (WAS), Leishmania infection, Toxoplasmosis, Hereditary hypogammaglobulinemia, Nonfamilial hypogammaglobulinemia, Leukopenia, Agranulocytosis, Basopenia, Bernard-Soulier syndrome (BSS), Malaria, Sepsis, or Hemolytic uremic syndrome (HUS).
Adipose Tissue
Adipose tissue is loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular endothelial cells and a variety of immune cells (i.e. adipose tissue macrophages (ATMs)). Adipose tissue is derived from preadipocytes. Its main role is to store energy in the form of lipids, although it also cushions and insulates the body. Pre-adipocytes are thought to be undifferentiated fibroblasts that can be stimulated to form adipocytes. The pre-adipocytes originate from mesenchymal stem cells. Areolar connective tissue is composed of adipocytes. The term "lipoblast" is used to describe the precursor of the adult cell. Adipose tissue degeneration-related diseases, conditions or disorders include, but are not limited to, Obesity, Dercum's disease (DD), Multiple symmetric lipomatosis (MSL), Familial multiple lipomatosis (FML), Lipodystrophy, Lipedema, or Atherosclerosis.
Lung
The lung is the essential respiration organ in many air-breathing animals. In mammals the two lungs are located near the backbone on either side of the heart. Their principal function is to transport oxygen from the atmosphere into the bloodstream, and to release carbon dioxide from the bloodstream into the atmosphere. A large surface area is needed for this exchange of gases, which is accomplished by the mosaic of specialized cells that form millions of tiny, exceptionally thin-walled air sacs called alveoli. Lung cells include, but are not limited to, type I pneumocytes, type II pneumocytes, clara cells and goblet cells. Lung tissue degeneration-related diseases, conditions or disorders include, but are not limited to, Asthma, Chronic obstructive pulmonary disease (COPD), Chronic bronchitis, Emphysema, Cystic fibrosis, Pulmonary edema, Acute respiratory distress syndrome (ARDS), Pneumoconiosis, Interstitial lung disease (ILD), Sarcoidosis, Idiopathic pulmonary fibrosis, Pulmonary embolism (PE), Pulmonary hypertension, Pleural effusion, Pneumothorax, Mesothelioma, Granulomatosis with polyangiitis (GPA), Goodpasture syndrome (GPS), Pulmonary hyperplasia, Infant respiratory distress syndrome (IRDS), Chronic obstructive pulmonary disease (COPD), Silicosis, Sleep Apnea, Severe Acute Respiratory Syndrome (SARS), Pulmonary fibrosis, Primary ciliary dyskinesia (PCD), Pneumoconiosis (Black Lung Disease), Hypersensitivity Pneumonitis, Cryptogenic Organizing Pneumonia (Bronchiolitis Obliterans Organizing Pneumonia (BOOP)), Byssinosis, Bronchopulmonary Dysplasia, Bronchiolitis, Bronchiectasis, Asbestosis, Pertussis, Middle Eastern Respiratory Syndrome (MERS), Pneumonia, Tuberculosis, Bronchitis, Histoplasmosis, Coccidioidomycosis (Cocci), or Acute bronchitis.
The present invention thus provides compounds, compositions, microenvironments, functionalised bioactive carriers, medical devices, kits, methods and processes for the design, preparation, manufacture and/or formulation of such compounds, compositions, functionalised bioactive carriers, medical devices and kits, and methods and uses thereof for regenerating or recoding mammalian tissues.

Compounds for inducing tissue formation and uses thereof


The invention provides a method of dipping a number of animals of a species with a pesticide using a formulation of the pesticide which is subject to stripping of the pesticide during dipping of successive animals or groups of animals, the method including:. establishing a predetermined level of a dipping liquid containing a first concentration of the pesticide (C.sub.IC) in a dipping vessel the concentration providing safe and effective pesticidal treatment; PA1 dipping the animals in the dipping liquid; and PA1 maintaining the predetermined level of the dipping liquid in the dipping vessel by addition thereto of a replenishment composition containing a second concentration of the pesticide. the second concentration of the pesticide (C.sub.CR) being greater than the first concentration of the pesticide, to thereby maintain a safe and pesticidally effective concentration of the pesticide.

The process for controlling pests, particularly ectoparasites in sheep and cattle by dipping has been in use for many years. Dipping is an inexpensive method for the control of a wide range of pests, including ectoparasites of the classes Insecta and Arachnida, and particularly including Lucilia cuprina and Lucilia sericata responsible for blowfly strike of sheep; Bovicola ovis (Sheep body (biting) louse) infestation of sheep; Psorergates ovis (itchmite) infestation of sheep; Psoroptes ovis (sheep scab mite) infestation of sheep; Melophagus ovinus (Sheep ked) infestation of sheep; Damalinia caprae (goat body (biting) louse) infestation of goats; Boophilus microplus (Cattle tick), Haemaphysalis spp. (Bush ticks), Rhipicephalus evertsi and Aponomna spp (red legged ticks), Rhipicephalus appendiculatus (brown ear tick) Hyalomma spp (Bont-legged tick) and Ambylomma spp. (Bont tick) infestation of bovid animals; Damalinia bovis (biting louse), Haematopinus eurysternus (short-nosed sucking louse), Haematopinus tuberculatus (buffalo louse), Haematopinus quadripertusus (tail switch louse), Linognathus vituli (long-nosed sucking louse) and Solenopotes capillatus (little blue sucking louse) infestations of cattle; Chorioptes bovis (Scrotal mange mite) infestation of cattle and sheep; Haematobia irritans exigua (Buffalo fly, Horn fly) annoyance of bovids; Hypoderma bovis (Warble fly) infestation of bovids; Glossina sp. (Tsetse fly) carrying sleeping sickness, a disease of economic importance principally in cattle; Chrysomya spp. (screw worm flies) of many livestock species; Musca spp. and Stomoxys calcitrans (Stable fly) which cause annoyance of mainly housed or intensively managed livestock.
Two types of dipping methods are commonly used, namely plunge dipping and shower dipping (which is also referred to as spray dipping). In plunge dipping the animals are fully immersed in dipping liquid contained in the dip or sump (vessel holding liquid). In shower or spray dipping a pump draws liquid from a sump (vessel holding liquid) and delivers the liquid via pipes to nozzles which spray the animals. Excess liquid returns to the sump via floor drains.
In the plunge dipping method, animals leaving the dip retain some of the dipping liquid in or on their exterior. This liquid may be carried away from the dip, causing a loss of dipping liquid from the dip. This loss of liquid is generally proportional to the number of animals which have passed through the dip.
In the shower dipping method, batches of animals (in the case of sheep, typically 25-70 animals/batch) are herded into a dipping station and are sprayed with the dipping liquid for a time period specified to adequately wet the animals. The liquid level in the sump of the shower dipping station initially drops rapidly as liquid is directed to the shower nozzles, however drains are generally provided to return liquid from the floor of the dipping station to allow its recycling. Some of the dipping liquid is retained in or on the surface of the animals and as a result the total dipping liquid is continually reduced. When the showering operation is completed, the animals leave the dipping station and the dipping liquid returns via the floor drains, resulting in a rapid rise in the liquid level in the sump. For smaller sumps, where the volume of dipping liquid in the return lines is a significant fraction of the total sump volume, the difference between sump level during and after dipping is proportionally greater. As referred to above, however there is also a net loss of dipping liquid from the sump between beginning and end of each batch treatment, and this net loss is directly proportional to the number of animals which have passed through the station.
The quantity of dipping liquid which is lost during plunge and spray dipping must be replaced when significant numbers of animals are to be treated. Replacement methods can be characterised either as intermittent or continuous. Intermittent replacement methods are characterised by replacement of dipping liquid in the sump only at discrete time points (between these discrete time points no replacement of dipping liquid occurs). In practice, intermittent replacement methods can involve:
periodic topping up of liquid in the sump (for both plunge and shower dipping stations). This is undertaken when some fixed portion, preferably no greater than 25%, of the sump volume has been expended, or PA1 batch-by-batch topping up of liquid in the sump (for both plunge and shower dipping stations). This is undertaken after each batch of animals has left the dipping station. PA1 establishing a predetermined level of a dipping liquid containing a first concentration of the pesticide (C.sub.IC) in a vessel said concentration providing safe and effective pesticidal treatment; PA1 dipping the animals in the dipping liquid; and PA1 maintaining the predetermined level of the dipping liquid in the vessel by addition thereto of a replenishment composition containing a second concentration of the pesticide PA1 comparing the graph determined in step (i) with the array of calculated stripping curves to determine the stripping factor corresponding to the closest fitting calculated stripping curve.
Continuous replacement methods are those wherein replacement liquid is available for progressive addition to the sump at all or most times throughout the dipping process. Replacement is usually achieved by the transfer of dipping liquid from a holding tank or vessel to the sump. It is important to note that in continuous replacement methods, the rate of addition of dipping liquid from the holding tank to the sump need not be steady, but may be adjusted in response to rate of loss of dipping liquid from the sump.
Hereinafter, the practice or method of periodic topping up or replacement of dipping liquid in the sumps of plunge or shower dipping stations will be denoted as periodic replenishment. Similarly, batch-by-batch topping up or replacement will be denoted batch replenishment and continuous topping up or replacement will be denoted continuous replenishment.
In replenishment methods, the quantity of dipping liquid in the sump of the dipping station is regulated either by:
a) maintaining its height at some predetermined level, or PA0 b) maintaining its height within a range which is fixed by predetermined lower and upper levels. PA0 (a) the nature of the active ingredient; PA0 (b) the nature of the formulation comprising the active ingredient, and in particular the nature of the solvent in the said formulation, if the active ingredient is maintained in the dipwash as an emulsion; PA0 (c) the dipping method (plunge or shower dip); and PA0 (d) the sump volume of the dipping station, or some other factor(s) highly correlated with sump volume. These related factors presumably could include features of dip operation that influence degree of exposure of the dipping liquid (active ingredient) to the stripping effect of the animal surfaces (e.g., length of the bath, swim distance and/or time in plunge dips, showering time/sump turnover in shower dips). PA0 (i) dipping a number of animals in a dipping liquid of initial concentration C.sub.IC contained in the vessel and maintaining the level of liquid in the vessel during dipping by replenishment of the liquid removed with a dipping liquid of the first concentration equal to C.sub.IC and preparing a graph of concentration of pesticide against numbers of animals. PA0 (ii) generating an array of calculated stripping curves showing the change in concentration of pesticide during dipping for a range of SF values using the formula ##EQU1## wherein V.sub.s is the volume of dipping liquid
For periodic replenishment plunge dips, the level of dipping liquid in the sump of the dipping station gradually declines from its maximum to its minimum predetermined level (eg. 75% of maximum). For periodic replenishment of shower dips, the level of dipping liquid in the sump of the dipping station when measured at immediately before the start of each batch gradually declines from its maximum to its minimum predetermined level (eg. 75% of maximum). For batch replenishment plunge dips, the level of dipping liquid in the sump of the dipping station gradually declines as animals of the batch pass through the dipping station. For batch replenished shower dips, the level of dipping liquid in the sump of the dipping station when measured at the conclusion of each batch is somewhat less than the level of dipping liquid in the sump when measured immediately before the start of each spray batch. For continuously replenished plunge dips, the level of dipping liquid in the sump remains steady at a single predetermined level (minor variations of less than 10% may occur in practice). For continuous replenishment shower dips, the level of dipping liquid in the sump immediately before the start of spraying of a given batch is the same as the level in the sump immediately before the start of spraying of the next batch (again minor variations of less than 10% may occur in practice).
A significant problem in the dipping process is stripping. Stripping is a process whereby animals preferentially remove the active (pesticidal) ingredient in the dipping liquid relative to the volume of dipping fluid removed. Stripping may lead to a number of undesirable consequences.
As a result of stripping the concentration of active ingredient in the sump decreases as increasing numbers of animals pass through the sump.
The latter portion of animals passing through the dipping station commonly obtain an undesirably low dose of active ingredient, leading to insufficient protection against pest species. The retention of pest activity on even a few dipped animals can lead to the rapid reinfestation of the entire group of animals increasing the risk to the health of the entire animal population. Additionally, exposure of pests to sublethal doses of pesticide can foster development of pesticide resistance.
The reduced dose received by latter animals can be offset by increasing the concentration of active ingredient in the initial dip, however this has the undesirable consequence that the first animals through the dipping station may obtain an undesirably high dose, leading to problems of pesticide contamination of animal products such as wool and meat. In wool processing, the accumulation of pesticide in lanolin may lead to effluent disposal problems following scouring of the fleece. Toxic effects for animals exposed to high pesticide doses are also possible.
As a consequence of removal of dipping liquid by animals passing through the dipping station and preferential removal of active ingredient in the stripping process, the problem of applying a uniform dose to all animals passing through the dipping station is complex.
British Patent 2,186,474 discloses a process in which a special dosing device dispenses concentrated active ingredient in proportion to the number of animals passing through the dipping sump (countering the effect of stripping) and the fluid level in the sump of the dipping station is also maintained by addition of diluent which is substantially water. An important component of the method of Stratford et al is the use of a sheep counting device to enable the correct dose of concentrated active ingredient to be applied to the sump. The method of Stratford et al is theoretically capable of providing a uniform dose of pesticide to all animals passing through the dipping station however the method has not been accepted by farmers. This is presumably because of the cost, complexity and inconvenience of installing, maintaining and calibrating the device for dispensing active ingredient in response to animal number. The requirement for calibration of this device is particularly inconvenient since the same active ingredient may strip at different rates in different use contexts.
Another approach to overcoming the problem of stripping of active ingredient in a dipping operation is to change the formulation of active ingredient. It has been noted that microencapsulation of the active ingredient overcomes the stripping problem (Ciba Geigy patent AU-B-80034/87) and it has also been found that changing the solvent carrier in a formulation of active ingredient can reduce the propensity of the pesticide on to undergo stripping. Reformulation to avoid stripping has the disadvantage of either high formulation cost (associated with microencapsulation) or insufficient reduction of stripping factor (associated with solvent variations). The pesticidal efficacy of microencapsulated formulations may also be reduced, particularly when rapid initial insect knock-down is desirable or when rapid diffusion of active ingredient through the wool grease is required.


A wireless PDA device with proximity detection includes a trigger for implementing a reminder alert to a user of a wireless PDA device based on the proximity of another wireless PDA device. The proximity detection may be accomplished by actual knowledge of proximity (e.g., using appropriate GPS detection and reporting to a centralized location), or more preferably inferred using the short range capability of wireless networks such as a piconet network by comparing the members of a current piconet network (presumed to be within the range of the relevant wireless PDA device). In a disclosed embodiment, an intelligent reminder table is implemented for use by an appropriate reminder application running on a wireless PDA device. The reminder table includes a proximity alert election on an entry-by-entry basis, and automatic reminder canceling based on proximity detection of another wireless PDA device relevant to the reminder. Example proximity alerts include reminding the user to wish a person happy birthday the next time they see them (i.e., the next time that the other person is proximate to the relevant PDA user). The intelligent reminder table also provides for the automatic cancellation of a reminder when the reminder relates to a meeting with the other PDA user detected as being proximate to the relevant PDA user within a given time frame of a reminder date/time.

1. Field of the Invention
The present invention relates to personal digital assistants (PDAs). More particularly, it relates to intelligent automation of a reminder and/or calendar system for a wireless PDA device.
2. Background of Related Art
Personal digital assistants (PDAs) and other hand-held portable computing devices are very popular consumer devices, particularly among the business sector. A PDA is a small, hand-held computer used to write notes, record names, addresses and phone numbers, to develop an appointment calendar, to read and write E-mail, and otherwise keep your life in order. PDA functionality is also incorporated into other electronic devices, e.g., cellular telephones.
Currently, PDA devices provide conventional reminder and calendar systems. These reminder systems allow a user to insert 'entries' into the PDA device asking for a reminder at a particular date and/or time. Alternatively, application programs such as Schedule Plus™ commercially available from Microsoft™ allow management of calendar functions on a personal computer (PC), and synchronization of the PC information with calendar information maintained on the PDA device.
To-do type reminders require frequent observation of the PDA device, and often a reminder involving another person the next time you see that person is seen too late, or after that person was seen. Moreover, reminders to attend a scheduled meeting are often provided even after a PDA user enters the meeting. If an audible alert is provided, the reminder can be disruptive to a meeting which starts earlier than scheduled. Moreover, cancellation of the reminder must be performed even after the meeting has occurred. This leads to excessive PDA operation, redundant reminders or reminders for events which have already taken place, and even to disruptions in meetings due to the PDA reminder alert itself.
There is a need for an intelligent and automatic reminder system for a PDA type device which reduces PDA operation time, reduces reminder redundancies, which eliminates reminders for events which have already taken place, and generally improves the accuracy of PDA reminders.

Intelligent reminders for wireless PDA devices


A personal computer is used to assist in the selection of television programs to be recorded at future times and to control a video tape recorder to implement the selected recordings. An application program allows the computer to receive data representing a schedule of future programs. The operator can perform data base operations on the data to obtain listings of programs of particular interest. A program to be recorded is selected by moving a cursor into position with the display of the program listing on the computer. An output device generates infrared signals to control the video tape recorder and a cable box to tune and record a selected program.

My U.S. Pat. No. 4,908,713 discloses a system for providing a schedule of future video programming available to a video recorder to a database memory located at the recorder so that the operator may display selected sections of the future schedule as an aid in choosing programs for recording. The schedule may be provided to the memory and updated either by broadcasting schedule information or by delivering disposable memories to the system on a subscription basis. Other of my applications disclose such systems in which the video recorder is programmed for unattended recording of a future program by simply pointing a cursor at the listing of that program on the schedule display. Since the system already stores the data required to record the program, it is unnecessary for the operator to re-enter the same data. My application Ser. No. 802,249 further discloses such a system in which the local memory stores the identification of programs that have been recorded and allows their display in order to select previously recorded programs for viewing.
These systems greatly simplify the problems of selecting programs for recording, actually performing the recording process, and viewing recorded programs. They suffer from the disadvantage of adding hardware and software to existing video cassette recorders or cable boxes which do not contain a schedule memory and a database program for selecting particular entries on the memory for display.

Method and apparatus for receiving customized television programming information by transmitting geographic location to a service provider through a wide-area network


An industrial robot may include a main body section, a first arm, a second arm, a third arm, a first speed reducer which connects the main body section and the first arm, a second speed reducer which connects the first arm and the second arm, and a connecting mechanism which connects the input shaft of the first speed reducer and the input shaft of the second speed reducer, and a second drive motor which drives the third arm. The speed reduction ratio of the first and second speed reducer are set such that the movement loci of a third articulation section which connects the second and third arm are rectilinear. The connecting mechanism connects the input shafts at a predetermined speed ratio. The second drive motor is mounted on the second arm closer to the tip than where a third articulation section is located.

Conventionally, an industrial robot for carrying a work-piece such as a semiconductor wafer has been known which is structured of a base, a link mechanism, an arm part and a hand part (see, for example, Patent Literature 1). In the industrial robot described in Patent Literature 1, the link mechanism is provided with a base side link part which is turnably attached to the base and an arm side link part which is turnably attached to the base side link part.
The base side link part is turnably held by a link mechanism motor which is incorporated into the base. Further, the base side link part is incorporated with a base side pulley which is fixed to the base, an arm part side pulley which is fixed to the arm side link part, and a belt which is stretched over the base side pulley and the arm part side pulley. The base side pulley and the arm part side pulley of the industrial robot are formed so that the ratio of their diameters is set to be 2:1 and, when the link mechanism motor is rotated, a tip end side of the arm side link part performs a linear operation.
Further, in the industrial robot, the arm part is turnably attached to a tip end side of the arm side link part. The arm part is connected with an arm part motor which is incorporated into the arm side link part. The arm part motor is incorporated into the arm side link part with an upper and lower direction as a direction of its turning shaft.
[PTL 1] Japanese Patent Laid-Open No. 2007-152490
In the industrial robot described in Patent Literature 1, the ratio of the diameter of the base side pulley to the diameter of the arm part side pulley is set to be 2:1. Further, loads of the arm side link part, the arm part and the hand part are applied to the belt which is stretched over the base side pulley and the arm part side pulley. Therefore, the sizes of the base side pulley, the arm part side pulley and the belt which are disposed in the inside of the base side link part tend to be increased. Accordingly, in the industrial robot, the size of the base side link part tends to be increased and, as a result, the industrial robot tends to be enlarged.
Further, in the industrial robot, the arm part motor is incorporated into the arm side link part with the upper and lower direction as a direction of its turning shaft and thus the thickness of the arm side link part is increased. Therefore, in the industrial robot, the height of the hand part tends to be increased and the minimum height (pass line) that the robot is accessible may be increased.

Industrial robot with protruding second drive motor


According to one embodiment of the present invention, a method for rendering a digital image having surface reflectance properties is disclosed. The method comprises creating a parametric texture map that comprises parameters for an equation that defines a surface structure in a manner in which the appearance of the surface structure includes surface reflectance properties. The method further comprises rendering a digital image using the parametric texture map.

Computer graphics systems are commonly employed for rendering graphical images. Conventional computer graphics systems commonly include a display device having a two-dimensional (2D) array of light emitting areas. The light emitting areas are usually referred to as "pixels," which is an abbreviation for picture elements. Such a graphics system typically employs hardware, software, or both to generate a 2D array of values that determines the colors or shades of grey that are to be emitted from the corresponding pixels of the display.
Computer graphics systems are commonly employed for the display of three-dimensional (3D) objects. Typically, such a system generates on a 2D display what appears to a viewer to be a 3D object by generating 2D views of the 3D object that is modeled in the computer memory. The 2D view of a 3D object that is generated at a particular time usually depends at least on a spatial relationship between the 3D object and a viewer of the 3D object at the particular time. This spatial relationship may be referred to as the view or eye point direction. For example, a car is a 3D object having a front and a back. However, whether one can see the taillights will depend on the position from which one is viewing the car. A view direction that is directly in front of the car will not show the taillights (but may instead show the headlights), while a view direction that is directly behind the car will show the taillights.
The process by which a computer graphics system generates the values for a 2D view of a 3D object is commonly referred to as image rendering or scan conversion. The graphics system usually renders a 3D object by subdividing the 3D object into a set of polygons and individually rendering each of the polygons. The values for a polygon that are rendered for a particular view direction usually depend on the surface features of the polygon and the effects of the lighting on the polygon. The surface features often include details such as surface colors and surface structures. The effects of lighting usually depend on a spatial relationship between the polygon and one or more light sources. This spatial relationship may be referred to as the light source direction. For example, if there is only one light source, the side of the object closest to the light source will be illuminated while the side of the object furthest from the light source might be in shadow.
Typically, the evaluation of the effects of lighting on an individual pixel in a polygon for a particular view direction involves a number of 3D vector calculations. One of ordinary skill in the art will recognize that the standard Blinn/Phong lighting equation is commonly used in computer graphics for performing lighting calculations for graphical images. Lighting calculations based on the Blinn/Phong equation generally includes floating-point, square-root and divide operations when used with normalized vectors. Such calculations are usually time-consuming and expensive whether performed in hardware or software.
One conventional method for reducing such computational overhead is to evaluate the effects of lighting at just a few areas of a polygon, such as the vertices, and then to interpolate the results across the entire polygon. Examples include methods that are commonly referred to as flat shading and Gouraud shading. Such methods usually reduce the number of calculations that are performed during scan conversion and thereby increase rendering speed. Unfortunately, such methods also usually fail to render shading features that are smaller than the areas of individual polygons. If the polygons are relatively large, the view will be noticeably distorted.
One conventional method for rendering features that are smaller than the area of a polygon is to employ what is referred to as a texture map. In general, a texture refers to a graphics data structure that models the surface appearance of an object. A texture may represent the visual experience of many materials and substances (e.g., terrain, plants, minerals, fur, and skin). Textures may be created digitally by sampling a physical surface utilizing photographic techniques. Alternatively, textures may be created manually utilizing a suitable graphics design application. Texture mapping involves mapping the surface appearance to a graphical surface modeled by a 3D structure. A typical texture map is a table that contains a pattern of color values for a particular surface feature. For example, a wood grain surface feature may be rendered using a surface model and a texture map that holds a color pattern for wood grain.
Texture mapping may be utilized for any number of applications. For example, texture mapping may be utilized by an architectural software application to generate a realistic depiction of a building based upon blueprint designs. For instance, a stucco texture may be wrapped onto a building frame by the architectural software application. Texture mapping may be additionally used to create special effects for movies, video game animation, website wallpapers, and/or the like. Texture mapping is desirable for these applications because it facilitates the representation of an object with an appreciable amount of realism and detail. Moreover, texture mapping may impart 3D qualities to the computer-generated image.
Texture mapping algorithms involve wrapping a texture over the surface of a model. Specifically, a 3D model or data structure of an object is created. For example, FIG. 1A depicts exemplary object 101 in R3 (i.e., 3D real space). The surface of object 101 may be represented as a set of polygons (typically triangles) in 3D space. The polygons are represented by their various vertices. The vertices are defined by coordinates in R3. For example, vertex 102 is defined by (x1, Y1, z1) and vertex 103 is defined by (x2, Y2, Z2)
As described above, most computer displays are only capable of displaying a 2D view of such 3D object 101. Accordingly, a mapping function is utilized to map the coordinates in R3 to coordinates in R2 (i.e., 2D real space). Typically, the mapping occurs by defining a view angle. FIG. 1B depicts such a mapping from object 101 of FIG. 1A to object 104. Vertex 102 is mapped to vertex 105 where vertex 105 is defined by two coordinates (X3, y3). Likewise, vertex 103 is mapped to vertex 106 where vertex 106 is defined by two coordinates (x4, y4). The mapping function allows the data to be represented in a form that may be displayed on a 2D display, such as a computer display.
Concurrently with the mapping, a texture is applied within the confines of the polygons of object 104 to provide a realistic appearance. For example, texture 201 of FIG. 2 may be applied to the polygons of object 104 to create a stone-like appearance. Texture 201 is typically implemented as a matrix of red-green-blue (RGB) values. The RGB values are mapped utilizing a suitable mapping function to the interior of the polygons of object 104. The final graphical image appears to have texture 201 "wrapped" around object 104.
However, this approach is limited as the final graphical image, to an extent, appears flat. Specifically, the graphical image does not appreciably vary in response to a change in illumination direction. Since it does not appreciably change under these conditions, localized shading or occlusions are not evident. Moreover, interreflections due to surface irregularities are not perceived.
Bump mapping is one texture mapping technique that addresses these limitations. Bump mapping involves creating a bump map of displacement values. The displacement values are utilized to perturb the surface normal vector. The perturbed surface normal vector is utilized to render shading in accordance with the Blinn/Phong lighting equation.
Materials, such as those that may comprise the surface of an object, include reflectance properties that define how a source light applied to the material is reflected. Different materials, such as a metal material, wood material, or cloth material, may each have different reflectance properties. As those of ordinary skill in the art will appreciate, the reflectance properties of a surface can be characterized by a Bidirectional Reflectance Distribution Function ("BRDF"), which generally characterizes the color of a surface as a function of incident light and exitant view directions.
In general, BRDF is a function that defines the way a material behaves based on different light directions and different view directions. For example, for an object of a given material (e.g., wood, cloth, metal, etc.), a viewer's perception of the object from a given direction will typically change if the direction at which light is directed toward the surface of such object changes. That is, the material of an object reflects light differently depending on the direction at which the light is directed toward the object, and a viewer typically perceives the object differently depending on the view direction and the direction at which light is directed toward the object. As an example, suppose a viewer is viewing an automobile. The viewer's perception of the metallic surface of the automobile (e.g., the specific color, etc.) generally depends, at least in part, on the direction at which the viewer is viewing the automobile and the direction at which light is directed toward the automobile. For instance, from a given viewing direction, a viewer may have one perception of the automobile's metallic surface with light applied thereto from a first direction (e.g., from a common direction at which the viewer is viewing the automobile), and the viewer may have a different perception of the automobile's metallic surface with light applied thereto from a second direction (e.g., at an angle skewed from the viewer's viewing direction). More specifically, from the viewer's perspective, the light is reflected differently by the automobile's metallic surface when the light is directed toward such surface from different directions. Thus, BRDF provides a further graphical imaging function that may be utilized in generating quality/realistic graphical images.
Accordingly, to render realistic graphical images, it is often desirable to utilize a BRDF. Various techniques have been developed in the prior art for utilizing a BRDF in rendering computer generated graphical images. In general, representations of reflectance functions may be categorized as either 1) parameterized models for specific kinds of BRDFs or 2) general approximation techniques.
The most familiar specialized parametric representation is likely the Phong model, which was one of the first reflectance models developed. See B. -T. Phong. "Illumination for Computer Generated Pictures," Comm. ACM, 18(6):311–317, June 1975. Ward has presented a more sophisticated model based on anisotropic Gaussian lobes fitted to various BRDFs. See G. Ward. "Measuring and Modeling Anisotropic Reflection," in Proc. SIGGRAPH, pages 265–272, July 1992. Also, He et al. have derived a physical-based model that is based on Kirchhoff diffraction, which also takes wavelength into account. See X. He, K. Torrance, F. Sillion, and D. Greenberg. "A Comprehensive Physical Model for Light Reflection," in Proc. SIGGRAPH, pages 175–186, July 1991. As a further example, of a specialized parametric representation, Poulin and Fournier have proposed a model based on self-shadowing of microcylinders. See P. Poulin and A. Fournier. "A Model for Anisotropic Reflection," in Proc. SIGGRAPH, pages 273–282, August 1990.
In addition to the techniques categorized as specialized parametric representation, there are many known BRDF approximation techniques. For example, Schröder and Sweldens have represented BRDFs using spherical wavelets. See P. Schröder and W. Sweldens. "Spherical Wavelets: Efficiently Representing Functions on the Sphere," in Proc. SIGGRAPH pages 161–172, August 1995. Koenderink et al. have expressed BRDFs in terms of an orthonormal basis using Zemike polynomials. See J. Koenderink, A. van Doom, and M. Stavridi. "Bidirectional Reflection Distribution Function Expressed in Terms of Surface Scattering Modes," in European Conference on Computer Vision, pages 28–39, 1996. Lafortune et al. have used an approximation based on the summation of generalized Phong cosine lobes. See E. Lafortune, S. -C. Foo, K. Torrance, and D. Greenberg. "Non-linear Approximation of Reflectance Functions." in Proc. SIGGRAPH, pages 117–126, August 1997. Additionally, Cabral et al. teach the use of spherical harmonics to represent BRDFs. See B. Cabral, N. Max, and R. Springmeyer. "Bidirectional Reflection Functions from Surface Bump Maps," in Proc. SIGGRAPH, pages 273–281, July 1987. As a further example of a BRDF approximation technique, Fournier used a sum of separable functions for representing reflectance models. See A. Fournier. "Separating Reflection Functions for Linear Radiosity," in Eurographics Rendering Workshop, pages 383–392, June 1995.
Existing techniques for rendering of BRDFs have typically been computationally inefficient, thereby resulting in relatively slow rendering of graphical images having reflectance properties. Although, Heidrich and Seidel have proposed a single pass rendering algorithm using texture mapping. See W. Heidrich and H. -P. Seidel. "Efficient Rendering of Anisotropic Surfaces Using Computer Graphics Hardware," in Image and Multi-dimensional DSP Wordshop (IMDSP), 1998. Additionally, Kautz and McCool have taught an interactive rendering technique with arbitrary BRDFs. See J. Kautz and D. McCool. "Interactive Rendering with Arbitrary BRDFs using Separable Approximations," in Eurographics Rendering Workshop, 1999, the disclosure of which is hereby incorporated herein by reference. As used herein, "interactive rendering" and "real-time rendering" are synonymous, and both terms refer to a performance metric in terms of frames per second. Interactive rendering implies that the user can interact with the rendering. The opposite (i.e., non-real-time or non-interactive rendering) would be software rendering wherein performance is measured in terms of seconds per frame. With non-interactive rendering, frames are rendered ahead of time in a static order, and the frames are then played back in sequence without the ability to alter the order.

System and method for rendering digital images having surface reflectance properties

Hewlett-Packard Development Company, L.P.


Task management supported by analytics has enhanced effectiveness through automated population splitting for generating models that predict task associated outcomes. Subpopulations are automatically analyzed for adequate sample size and selectively recombined based on characteristics of the subpopulations, such as to combine homogeneous subpopulations or to optimize a subpopulation characteristic. As an example, outbound calling campaign models are generated for time periods by splitting a sample population into time period subpopulations and combining subpopulation time periods having inadequate sample size so that combined subpopulations have a minimized total time period or greater similarity relative to other subpopulations.

1. Field of the Invention
The present invention relates in general to the field of task management support through analytics, and more particularly to a system and method for automated population splitting to assist task management through analytics.
2. Description of the Related Art
Analytics are often used to aid management of a variety of tasks. Generally, analytics use historical information to generate models that predict future outcomes. For example, linear and logistic regression analytical techniques apply selected independent variables to generate models that predict dependent variable outcomes based on the historical relationship of the independent and dependent variables. Such models are commonly used to predict outcomes for the extension of credit, such as mortgages, credit cards and auto loans. One common measure of an individual's creditworthiness is a credit score that compares the individual's financial characteristics with the characteristics of a modeled population. Generally, the more that the population and individual characteristics share in common with each other, the greater the predictive quality of a score for the individual that is generated from a model of the population. In order to obtain credit scores with adequate predictive quality, financial institutions tend to attempt to generate models from large populations. The predictive quality of models is usually estimated by a variety of techniques that consider population size and other factors.
The availability of powerful computers to process large sets of data has expanded the use of analytics for task management not only in the types of tasks that are managed, but also the frequency with which analytics are performed to obtain models that are current and accurate. One example is the use of analytics to predict whether a desired person will answer a telephone call to a telephone number, as described in U.S. Pat. No. 5,802,161 System and Method for Optimized Scheduling. Basically, a model predicts the likelihood that a right person will answer a telephone call during defined periods of a day and the predicted likelihoods are optimized so that the number of right person contacts is increased compared with random call placement. In some instances, models are applied based on hourly calling periods defined through a day. Optimized dependent variables include the maximum number of right party contacts, the maximum amount of revenue generated by the calls, the maximum number of cured accounts, the minimum number of canceled accounts, etc. . . . As contacts are made and accounts are handled, updated results allow additional modeling so that future contact attempts benefit from the application of the existing results.
One technique that helps to develop more accurate statistical predictive models through linear regression, logistic regression and other modeling techniques is to split the modeling population into relatively homogeneous subpopulations. Developing separate models for each of these subpopulations helps to maximize both the total amount of predictive power of the overall scoring system and the goodness of fit and validation of the subpopulation models. As a simple example, a subpopulation that has high-value mortgages often has a higher correlation for a selected dependent variable, such as likelihood of repaying credit or likelihood of answering a call at a defined time, with a given set of independent variables than does a population that includes individuals with sub-prime mortgages. During preparation of custom models, the number of subpopulations considered is typically limited due to the labor costs associated with developing and validating each model. For example, where a large number of variables are available, a skilled statistician might select certain variables to consider as subpopulations in a recursive manner, such as with the Classification and Regression Tree (CART) method. A binary tree of subpopulations is defined recursively with each node split into two sub-nodes and the splitting variable selected to establish subpopulations that are as homogeneous as possible in terms of the behavior of the regression response variable. Such selection of splitting variables and validation of models based on subpopulations is a labor-intensive, manual process typically performed by a skilled statistician that generally cannot be reliably automated. As an example, a natural hierarchy sometimes exists for the order in which splitting variables are used that is not amenable to automation. For instance, splitting populations based on types of loans before the amount of each loan naturally provides more homogeneous populations since different types of loans have different typical balance levels. As another example, splits into more than two nodes are sometimes desired or required.

This patent is subject to a terminal disclaimer.

System and method for automated population splitting to assist task management through analytics


The invention is a refastenable mechanical fastening system, made of free formed prongs joined to a substrate. The prongs taper and are nonperpendicularly oriented relative to the plane of the substrate. The prongs may also have an azimuthal angle relative to the machine direction of the substrate. Each prong has an engaging means projecting laterally from the periphery of the prong. The free formed prongs are manufactured by the process of extruding liquid material through the meshes of a deposting member onto a moving substrate to form the base of the prong, stretching the liquid material in a direction parallel to the plane of the substrate, severing the stretched material to form the distal end and engaging means of the prong. The advantageous usage of the fastening system in an article of manufacture, such as a disposable absorbent article specifically a diaper, is also disclosed.

Refastenable mechanical fastening systems are well known in the art. Typically, such fastening systems involve two major components, a prong which is joined to a substrate and engages with a complementary second component, the receiving surface. A projection of the prong of the fastening system penetrates the receiving surface and either engages or intercepts strands or fibers of the receiving surface. The resulting mechanical interference and physical obstruction prevent removal of the fastening system from the receiving surface until the separation forces exceed either the peel or shear strength of the fastening system.
Presently, refastenable mechanical fastening systems are made by at least two general methods. One method requires a plurality of filaments, each of which may be formed into two prongs. Examples of fastening systems produced by this method are shown in U.S. Pat. No. 2,717,437, issued Sep. 13, 1955 to de Mesteral and U.S. Pat. No. 3,943,981, issued Mar. 16, 1976 to De Brabandar which teach a raised pile of loops. Related teachings are shown in U.S. Pat. No. 4,216,257, issued Aug. 5, 1980 to Schams et al., U.S. Pat. No. 4,454,183, issued Jun. 12, 1984 to Wollman and U.S. Pat. No. 4,463,486, issued Aug. 7, 1984 to Matsuda. These references teach heating the ends of polymeric monofilaments. Other related teachings of fastening systems produced by the first method are disclosed in U.S. Pat. No. 4,307,493, issued Dec. 29, 1981 to Ochiai and U.S. Pat. No. 4,330,907, issued May 25, 1982 to Ochiai.
The second general method commonly utilized to manufacture mechanical fastening systems is to mold or extrude the systems as illustrated in U.S. Pat. No. 3,147,528, issued Sep. 8, 1964 to Erb and U.S. Pat. No. 3,594,863, issued Jul. 27, 1971 to Erb. Continuous injection molding is taught in U.S. Pat. No. 3,594,865, issued Jul. 27, 1971 to Erb.
Various prong structures are illustrated in the prior art. For example, the references discussed above teach fastening systems having stems of generally constant cross section. U.S. Pat. No. 3,708,833, issued Jan. 9, 1973 to Ribich et al. discloses a prong which is somewhat tapered from the proximal end to the distal end and perpendicularly projects from the substrate.
European Patent Application No. 0,276,970, published Aug. 3, 1988, by the Procter & Gamble Company in the name of Scripps discloses a fastening device having a constant cross section stem oriented at an angle between about 30.degree. and about 90.degree. relative to the base.
The fastening systems of the prior art are relatively expensive to produce, and the processes of the prior art are relatively slow. Additionally, the fastening systems of the prior art are irritating and abrasive to human skin and are, therefore, not well suited for applications which cause them to be in close proximity to human skin. There is, therefore, a need for a fast and inexpensive method of producing mechanical fastening systems. There is also a need for mechanical fastening systems which are non-irritating and non-abrasive to human skin.
Some of these needs have been addressed in U.S. patent application Ser. No. 07/668,817 filed Mar. 7, 1991 in the name of Dennis A. Thomas, entitled "Refastenable Mechanical Fastening Means and Process of Manufacture Therefor", which discloses a method of manufacturing a refastenable mechanical fastening system rapidly and inexpensively by a method similar to gravure printing.
However, the present invention discloses a faster and less expensive method of producing a mechanical fastening system than the prior art. The method of the present invention also produces a fastening system having an array of prongs that is more dense, and therefore is less abrasive and less irritating, than the fastening systems of the prior art.

Screen printing method for manufacturing a refastenable mechanical fastening system and fastening system produced therefrom


A fishing reel winding device is provided including a housing and a fishing reel clamp for fixing a fishing reel with respect to the housing. A fishing line spool assembly is rotatably mounted to the housing for feeding line to the fishing reel upon the rotation of the handle. A pair of friction arms are included for providing a force which abates rotation of the fishing line spool assembly.

1. Field of the Invention
The present invention relates to fishing reels and more particularly pertains to a new battery operated fishing reel line winder for feeding line between a fishing reel and spool.
2. Description of the Prior Art
The use of fishing reels is known in the prior art. More specifically, fishing reels heretofore devised and utilized are known to consist basically of familiar, expected and obvious structural configurations, notwithstanding the myriad of designs encompassed by the crowded prior art which have been developed for the fulfillment of countless objectives and requirements.
Known prior art fishing reels include U.S. Pat. No. 5,029,409; U.S. Pat. No. 3,951,354; U.S. Pat. No. Des. 251,656; U.S. Pat. No. 5,209,423; U.S. Pat. No. 4,934,627; and U.S. Pat. No. 4,545,548.
In these respects, the battery operated fishing reel line winder according to the present invention substantially departs from the conventional concepts and designs of the prior art, and in so doing provides an apparatus primarily developed for the purpose of feeding line between a fishing reel and spool.

Battery operated fishing reel line winder


A client-server based electronic medical record replaces paper records in outpatient clinics. The Internet provides physicians with the ability to use a Java-based client program to generate legible, complete notes for patient encounters that comply with HCFA guidelines. A pen-like input device for entering data into an electronic medical record is provided with one end which serves as a stylus or pointing device for being placed in contact with a touch screen and another end which has a microphone element for receiving speech signals. A microphone activation button or lever is provided to enable and disable speech recognition.

In order to improve healthcare for both the service provider and the recipient, it is imperative that the paper record method currently practiced be rendered obsolete by providing an electronic medical record that can be easily built and updated. In addition, with the internet playing a vastly increasing role in all of our lives, it is also imperative to utilize efficiencies that the internet provides in the healthcare environment, particularly at the point of care.
Radio took 38 years to reach 50 million listeners. Television required approximately 11 years to reach 60 million viewers. The Internet has garnered 50 million users in 5 years. Today, we are constantly reminded of the power and scale of the Internet. Without question, it is the greatest telecommunications revolution since the advent of the telephone. Its presence has created the networked economy, or the "digital economy".
The power of this newfound connectivity can precipitate productivity and efficiency gains of exponential proportions. With an unprecedented adoption curve, and generations of technical advances occurring at a breath-taking pace, the Internet has evolved from an academic medium for sharing rich research to a commercial delivery network of content, services, and workflow control.
Healthcare has endured inefficiencies, disparate legacy systems, and disjointed workflow with high latencies for many years. These difficulties are coupled with the fact that the healthcare experience has begun to deteriorate not only for the patient, but for the physician and support staff, as well.
With only an average of seven minutes of "face-to-face time" per visit, both the physician and the patient are left unfulfilled. The physician feels his/her number one priority, the quality of care, is forsaken, and the patient feels as though there is not enough time to be treated. The Internet and the digital economy can foster much needed change.

Input devices for entering data into an electronic medical record (EMR)

GE Medical Systems Information Technologies


Generally, the present disclosure is directed to systems that may be used to facilitate the retrieval and/or replacement of production and/or processing equipment that may be used for subsea oil and gas operations. In one illustrative embodiment, a method is disclosed that includes, among other things, removing at least a portion of trapped production fluid (101a, 101b) from subsea equipment (100) while the subsea equipment (100) is connected to a subsea equipment installation (185) in a subsea environment (180), and storing at least the removed portion of the trapped production fluid (101a, 101b) in a subsea containment structure (120, 120a, 120b, 132) that is positioned in the subsea environment (180). Additionally, the disclosed method also includes disconnecting the subsea equipment (100) from the subsea equipment installation (185) and retrieving the subsea equipment (100) from the subsea environment (180).

1. Field of the Invention
Generally, the present invention relates to equipment that is used for subsea oil and gas operations, and more particularly to methods that may be used to facilitate the retrieval and replacement of subsea oil and gas production and/or processing equipment.
2. Description of the Related Art
One of the most challenging activities associated with offshore oil and gas operations is the retrieval and/or replacement of equipment that may be positioned on or near the sea floor, such as subsea production and processing equipment and the like. As may be appreciated, subsea production and processing equipment, hereafter generally and collectively referred to as subsea equipment, may occasionally require routine maintenance or repair due to regular wear and tear, or due to the damage and/or failure of the subsea equipment that may be associated with unanticipated operational upsets or shutdowns, and the like. In such cases, operations must be performed to retrieve the subsea equipment from its location at the sea floor for repair, and to replace the subsea equipment so that production and/or processing operations may continue with substantially limited interruption.
In many applications, various cost and logistical design considerations may lead to configuring at least some subsea equipment components as part of one or more subsea production or processing equipment skid packages, generally referred to herein as subsea equipment packages or subsea equipment skid packages. For example, various mechanical equipment components, such as vessels, pumps, separators, compressors, and the like, may be combined in a common skid package with various interconnecting piping and flow control components, such as pipe, fittings, flanges, valves and the like. However, while skid packaging of subsea equipment generally provides many fabrication and handling benefits, it may present at least some challenges during hydrocarbon removal, depressurization, and retrieval of the equipment to the surface, as will be described below.
Depending on the size and complexity of a given subsea equipment skid package, the various equipment and piping components making up the skid package may contain many hundreds of gallons of hydrocarbons, or even more, during normal operation. In general, this volume of hydrocarbons in the subsea equipment skid package must be properly handled and/or contained during the equipment retrieval process so as to avoid an undesirable release of hydrocarbons to the surrounding subsea environment.
In many applications, subsea systems often operate in water depths of 5000 feet or greater, and under internal pressures in excess of 10,000 psi or more. It should be appreciated that while it may be technically feasible to shut in subsea equipment and retrieve it from those depths to the surface while maintaining the equipment under such high pressure, it can be difficult to safely handle and move the equipment package on and around an offshore platform or intervention vessel, as may be the case, while it is under such high pressure. Moreover, and depending on local regulatory requirements, it may not be permissible to move or transport such equipment and/or equipment skid packages while under internal pressure.
Yet another concern with subsea equipment is that problems can sometimes arise when flow through the equipment is stopped, for one reason or another, while the equipment is present in the subsea environment. For example, in some cases, flow through a given piece of subsea equipment may be intentionally stopped so that the equipment can be shut in and isolated for retrieval to the surface. In other cases, flow may inadvertently cease during inadvertent system shutdowns that occur as a result of operational upsets and/or equipment failures. Regardless of the reasons, when flow through the subsea equipment is stopped, hydrates and/or other undesirable hydrocarbon precipitates, such as asphaltenes, resins, paraffins, and the like, can sometimes form inside of the equipment. In such cases, the presence of any unwanted precipitates or hydrates can potentially foul the equipment and prevent a system restart after an inadvertent shut down, or they can complicate maintenance and/or repair efforts after the equipment has been retrieved to the surface. These issues must therefore generally be addressed during such times as when flow through the equipment ceases, such as by removal and/or neutralization of the constituents that may cause such problems.
In other cases, potentially damaging constituents, such as carbon dioxide (CO2) or hydrogen sulfide (H2S) and the like, may be present in solution in the liquid hydrocarbons that may be trapped inside of the equipment during shutdown. For example, hydrogen sulfide can potentially form sulfuric acid (H2SO4) in the presence of water, which may attack the materials of the some subsea equipment, particularly when flow through the equipment is stopped and the sulfuric acid may remain in contact with the wetted parts of the equipment for an extended period of time. Furthermore, it is well known that carbon dioxide may also be present in the trapped hydrocarbons, and can sometimes come out of solution and combine with any produced water that may be present in the equipment so as to form carbonic acid (H2CO3), which can also be damaging the materials that make up the wetted parts of the equipment during prolonged exposure. As with the above-described problems associated with hydrates and hydrocarbon precipitates, remedial measures are sometimes required to address such issues that are related to the various constituents that can cause material damage to wetted components when flow through the equipment is stopped.
Accordingly, there is a need to develop systems and equipment configurations that may be used to overcome, or at least mitigate, one or more of the above-described problems that may be associated with the retrieval and/or replacement of subsea oil and gas equipment.

Methods for retrieval and replacement of subsea production and processing equipment


A drive circuit and method of controlling a quantum well modulator are disclosed. The drive circuit can be disposed in an optical transceiver having a quantum well modulator configured to retro-modulate an incoming optical signal. The drive circuit can include separate modulating and bias voltage sources. A level of the modulating voltage and the bias voltage can be determined based on an ambient temperature of the optical transceiver and can be adjusted to compensate for variations in the optical performance of the quantum well modulator. The quantum well modulator can be controlled in intervals. The modulating voltage can be applied to the quantum well modulator during a first interval. A current associated with the modulating voltage can be returned to the modulation voltage source during a second interval. A timing of the first and second intervals can be based on electrical properties of the quantum well modulator.

The present invention relates to optical communications and, more specifically, to a retro-modulating optical transceiver.
In combat identification systems, an optical transceiver can employ modulators and/or reflectors to respond to an interrogating beam of light. The modulators control the incoming beam and the reflectors direct it back toward the source. Modulating retro-reflectors, in general, are becoming smaller, lighter, and faster. Also, modulating retro-reflectors are becoming increasingly portable and their use on the battlefield and in combat training is growing.