In genetics and developmental biology, somatic cell nuclear transfer (SCNT) is a laboratory strategy for creating a viable embryo from a body cell and an egg cell. The technique consists of taking an enucleated oocyte (egg cell) and implanting a donor nucleus from a somatic (body) cell. It is used in both therapeutic and reproductive cloning. Dolly the Sheep became famous for being the first successful case of the reproductive cloning of a mammal. "Therapeutic cloning" refers to the potential use of SCNT in regenerative medicine; this approach has been championed as an answer to the many issues concerning embryonic stem cells (ESC) and the destruction of viable embryos for medical use, though questions remain on how homologous the two cell types truly are.
The process of somatic cell nuclear transplant involves two different cells. The first being a female gamete, known as the ovum (egg/oocyte). In human SCNT experiments, these eggs are obtained through consenting donors, many times utilizing ovarian stimulation. The second being a somatic cell, referring to the cells of the human body. Skin cells, fat cells, and liver cells are only a few examples. The nucleus of the donor egg cell is removed and discarded, leaving it 'deprogrammed.' The nucleus of the somatic cell is also removed but is kept, the enucleated somatic cell is discarded. What is left is a lone somatic nucleus and an enucleated egg cell. These are then fused by inserting the somatic nucleus into the 'empty' ovum. After being inserted into the egg, the somatic cell nucleus is reprogrammed by its host egg cell. The ovum, now containing the somatic cell's nucleus, is stimulated with a shock and will begin to divide. The egg is now viable and capable of producing an adult organism containing all the necessary genetic information from just one parent. Development will ensue normally and after many mitotic divisions, this single cell forms a blastocyst (an early stage embryo with about 100 cells) with an identical genome to the original organism (i.e. a clone). Stem cells can then be obtained by the destruction of this clone embryo for use in therapeutic cloning or in the case of reproductive cloning the clone embryo is implanted into a host mother for further development and brought to term.
Somatic cell nuclear transplantation has become a focus of study in stem cell research. The aim of carrying out this procedure is to obtain pluripotent cells from a cloned embryo. These cells genetically matched the donor organism from which they came.This gives them the ability to create patient specific pluripotent cells, which could then be used in therapies or disease research.
Embryonic stem cells are undifferentiated cells of an embryo. These cells are deemed to have a pluripotent potential because they have the ability to give rise to all of the tissues found in an adult organism. This ability allows stem cells to create any cell type, which could then be transplanted to replace damaged or destroyed cells. Controversy surrounds human ESC work due to the destruction of viable human embryos. Leading scientists to seek an alternative method of obtaining stem cells, SCNT is one such method.
A potential use of stem cells genetically matched to a patient would be to create cell lines that have genes linked to a patient's particular disease. By doing so, an in vitro model could be created, would be useful for studying that particular disease, potentially discovering its pathophysiology, and discovering therapies. For example, if a person with Parkinson's disease donated his or her somatic cells, the stem cells resulting from SCNT would have genes that contribute to Parkinson's disease. The disease specific stem cell lines could then be studied in order to better understand the condition.
Another application of SCNT stem cell research is using the patient specific stem cell lines to generate tissues or even organs for transplant into the specific patient. The resulting cells would be genetically identical to the somatic cell donor, thus avoiding any complications from immune system rejection.
Only a handful of the labs in the world are currently using SCNT techniques in human stem cell research. In the United States, scientists at the Harvard Stem Cell Institute, the University of California San Francisco, the Oregon Health & Science University,Stemagen (La Jolla, CA) and possibly Advanced Cell Technology are currently researching a technique to use somatic cell nuclear transfer to produce embryonic stem cells. In the United Kingdom, the Human Fertilisation and Embryology Authority has granted permission to research groups at the Roslin Institute and the Newcastle Centre for Life. SCNT may also be occurring in China.
In 2005, a South Korean research team led by Professor Hwang Woo-suk, published claims to have derived stem cell lines via SCNT, but supported those claims with fabricated data. Recent evidence has proved that he in fact created a stem cell line from a parthenote.
Though there has been numerous successes with cloning animals, questions remain concerning the mechanisms of reprogramming in the ovum. Despite many attempts, success in creating human nuclear transfer embryonic stem cells has been limited. There lies a problem in the human cell's ability to form a blastocyst; the cells fail to progress past the eight cell stage of development. This is thought to be a result from the somatic cell nucleus being unable to turn on embryonic genes crucial for proper development. These earlier experiments used procedures developed in non-primate animals with little success. A research group from the Oregon Health & Science University demonstrated SCNT procedures developed for primates successfully reprogrammed skin cells into stem cells. The key to their success was utilizing oocytes in metaphase II (MII) of the cell cycle. Egg cells in MII contain special factors in the cytoplasm that have a special ability in reprogramming implanted somatic cell nuclei into cells with pluripotent states. When the ovum's nucleus is removed, the cell loses its genetic information. This has been blamed for why enucleated eggs are hampered in their reprogramming ability. It is theorized the critical embryonic genes are physically linked to oocyte chromosomes, enucleation negatively affects these factors. Another possibility is removing the egg nucleus or inserting the somatic nucleus causes damage to the cytoplast, affecting reprogramming ability. Taking this into account the research group applied their new technique in an attempt to produce human SCNT stem cells. In May 2013, the Oregon group reported the successful derivation of human embryonic stem cell lines derived through SCNT, using fetal and infant donor cells. Using MII oocytes from volunteers and their improved SCNT procedure, human clone embryos were successfully produced. These embryos were of poor quality, lacking a substantial inner cell mass and poorly constructed trophectoderm. The imperfect embryos prevented the acquisition of human ESC. The addition of caffeine during the removal of the ovum's nucleus and injection of the somatic nucleus improved blastocyst formation and ESC isolation. The ESC obtain were found to be capable of producing teratomas, expressed pluripotent transcription factors, and expressed a normal 46XX karyotype, indicating these SCNT were in fact ESC-like. This was the first instance of successfully using SCNT to reprogram human somatic cells. This study used fetal and infantile somatic cells to produce their ESC.
Late April 2014, the New York Stem Cell Foundation was successful in creating SCNT stem cells derived from adult somatic cells. One of these lines of stem cells was derived from the donor cells of a type 1 diabetic. The group was then able to successfully culture these stem cells and induce differentiation. When injected into mice, cells of all three of the germ layers successfully formed. The most significant of these cells, were those who expressed insulin and were capable of secreting the hormone. These insulin producing cells could be used for replacement therapy in diabetics, demonstrating real SCNT stem cell therapeutic potential.
The impetus for SCNT-based stem cell research has been decreased by the development and improvement of alternative methods of generating stem cells. Methods to reprogram normal body cells into pluripotent stem cells were developed in humans in 2007. The following year, this method achieved a key goal of SCNT-based stem cell research: the derivation of pluripotent stem cell lines that have all genes linked to various diseases. Some scientists working on SCNT-based stem cell research have recently moved to the new methods of induced pluripotent stem cells. Though recent studies have put in question how similar iPS cells are to embryonic stem cells. Epigenetic memory in iPS affects the cell lineage it can differentiate into. For instance, an iPS cell derived from a blood cell will be more efficient at differentiating into blood cells, while it will be less efficient at creating a neuron. This raises the question of how well iPS cells can mimic the gold standard ESC in experiments, as stem cells are defined as having the ability to differentiate into any cell type. SCNT stem cells do not pose such a problem and continue to remain relevant in stem cell studies.
This technique is currently the basis for cloning animals (such as the famous Dolly the sheep), and has been theoretically proposed as a possible way to clone humans. Using SCNT in reproductive cloning has proven difficult with limited success. High fetal and neonatal death make the process very inefficient. Resulting cloned offspring are also plagued with development and imprinting disorders in non-human species. For these reasons, along with moral and ethical objections, reproductive cloning in humans is proscribed. Most researchers believe that in the foreseeable future it will not be possible to use the current cloning technique to produce a human clone that will develop to term. It remains a possibility, though critical adjustments will be required to overcome current limitations during early embryonic development in human SCNT.
There is also the potential for treating diseases associated with mutations in mitochondrial DNA. Recent studies show SCNT of the nucleus of a body cell afflicted with one of these diseases into a healthy oocyte prevents the inheritance of the mitochondrial disease. This treatment does not involve cloning but would produce a child with three genetic parents. A father providing a sperm cell, one mother providing the egg nucleus and another mother providing the enucleated egg cell.
Interspecies nuclear transfer (iSCNT) is a means of somatic cell nuclear transfer used to facilitate the rescue of endangered species, or even to restore species after their extinction. The technique is similar to SCNT cloning which typically is between domestic animals and rodents, or where there is a ready supply of oocytes and surrogate animals. However, the cloning of highly endangered or extinct species requires the use of an alternative method of cloning. Interspecies nuclear transfer utilizes a host and a donor of two different organisms that are closely related species and within the same genus. In 2000, Robert Lanza was able to produce a cloned fetus of a gaur, Bos gaurus, combining it successfully with a domestic cow, Bos taurus.
Interspecies nuclear transfer provides evidence of the universality of the triggering mechanism of the cell nucleus reprogramming. For example, Gupta et al., explored the possibility of producing transgenic cloned embryos by interspecies somatic cell nuclear transfer (iSCNT) of cattle, mice, and chicken donor cells into enucleated pig oocytes. Moreover, NCSU23 medium, which was designed for in vitro culture of pig embryos, was able to support the in vitro development of cattle, mice, and chicken iSCNT embryos up to the blastocyst stage. Furthermore, ovine oocyte cytoplast may be used for remodeling and reprogramming of human somatic cells back to the embryonic stage.
SCNT can be inefficient. Stresses placed on both the egg cell and the introduced nucleus in early research were enormous, resulting in a low percentage of successfully reprogrammed cells. For example, in 1996 Dolly the sheep was born after 277 eggs were used for SCNT, which created 29 viable embryos. Only three of these embryos survived until birth, and only one survived to adulthood. As the procedure was not automated, but had to be performed manually under a microscope, SCNT was very resource intensive. The biochemistry involved in reprogramming the differentiated somatic cell nucleus and activating the recipient egg was also far from understood. However, by 2014, researchers were reporting success rates of 70-80% with cloning pigs and in 2016 a Korean company, Sooam Biotech, was reported to be producing 500 cloned embryos a day.
In SCNT, not all of the donor cell's genetic information is transferred, as the donor cell's mitochondria that contain their own mitochondrial DNA are left behind. The resulting hybrid cells retain those mitochondrial structures which originally belonged to the egg. As a consequence, clones such as Dolly that are born from SCNT are not perfect copies of the donor of the nucleus. This fact may also hamper the potential benefits of SCNT derived tissues/organs for therapy, as there may be an immunoresponse to the non-self mtDNA after transplant.
Proposals to use nucleus transfer techniques in human stem cell research raise a set of concerns beyond the moral status of any created embryo. These have led to some individuals and organizations who are not opposed to human embryonic stem cell research to be concerned about, or opposed to, SCNT research.
One concern is that blastula creation in SCNT-based human stem cell research will lead to the reproductive cloning of humans. Both processes use the same first step: the creation of a nuclear transferred embryo, most likely via SCNT. Those who hold this concern often advocate for strong regulation of SCNT to preclude implantation of any derived products for the intention of human reproduction, or its prohibition.
A second important concern is the appropriate source of the eggs that are needed. SCNT requires human eggs, which can only be obtained from women. The most common source of these eggs today are eggs that are produced and in excess of the clinical need during IVF treatment. This is a minimally invasive procedure, but it does carry some health risks, such as ovarian hyperstimulation syndrome.
Potentially millions of patients could benefit from stem cell therapy, and each patient would require a large number of donated eggs in order to successfully create a single custom therapeutic stem cell line. Such large numbers of donated eggs would exceed the number of eggs currently left over and available from couples trying to have children through assisted reproductive technology. Therefore, healthy young women would need to be induced to sell eggs to be used in the creation of custom stem cell lines that could then be purchased by the medical industry and sold to patients. It is so far unclear where all these eggs would come from.
Stem cell experts consider it unlikely that such large numbers of human egg donations would occur in a developed country because of the unknown long-term public health effects of treating large numbers of healthy young women with heavy doses of hormones in order to induce hyperovulation (ovulating several eggs at once). Although such treatments have been performed for several decades now, the long-term effects have not been studied or declared safe to use on a large scale on otherwise healthy women. Longer-term treatments with much lower doses of hormones are known to increase the rate of cancer decades later. Whether hormone treatments to induce hyperovulation could have similar effects is unknown. There are also ethical questions surrounding paying for eggs. In general, marketing body parts is considered unethical and is banned in most countries. Human eggs have been a notable exception to this rule for some time.
To address the problem of creating a human egg market, some stem cell researchers are investigating the possibility of creating artificial eggs. If successful, human egg donations would not be needed to create custom stem cell lines. However, this technology may be a long way off.
SCNT involving human cells is currently legal for research purposes in the United Kingdom, having been incorporated into the Human Fertilisation and Embryology Act 1990 in 2001. Permission must be obtained from the Human Fertilisation and Embryology Authority in order to perform or attempt SCNT.
In the United States, the practice remains legal, as it has not been addressed by federal law. However, in 2002, a moratorium on United States federal funding for SCNT prohibits funding the practice for the purposes of research. Thus, though legal, SCNT cannot be federally funded. American scholars have recently argued that because the product of SCNT is a clone embryo, rather than a human embryo, these policies are morally wrong and should be revised.
In 2003, the United Nations adopted a proposal submitted by Costa Rica, calling on member states to "prohibit all forms of human cloning in as much as they are incompatible with human dignity and the protection of human life." This phrase may include SCNT, depending on interpretation.
The Council of Europe's Convention on Human Rights and Biomedicine and its Additional Protocol to the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine, on the Prohibition of Cloning Human Being appear to ban SCNT of human beings. Of the Council's 45 member states, the Convention has been signed by 31 and ratified by 18. The Additional Protocol has been signed by 29 member nations and ratified by 14.
A somatic (Greek: /soma = body) or vegetal cell is any biological cell forming the body of an organism; that is, in a multicellular organism, any cell other than a gamete, germ cell, gametocyte or undifferentiated stem cell.
In contrast, gametes are cells that fuse during sexual reproduction, germ cells are cells that give rise to gametes, and stem cells are cells that can divide through mitosis and differentiate into diverse specialized cell types. For example, in mammals, somatic cells make up all the internal organs, skin, bones, blood and connective tissue, while mammalian germ cells give rise to spermatozoa and ova which fuse during fertilization to produce a cell called a zygote, which divides and differentiates into the cells of an embryo. There are approximately 220 types of somatic cells in the human body.
Theoretically, these cells are not germ cells (the source of gametes), they never transmit to their descendants the mutations they have undergone. However, in sponges, non-differentiated somatic cells form the germ line and, in Cnidaria, differentiated somatic cells are the source of the germline.
The word "somatic" is derived from the Greek word sma, meaning "body".
As multicellularity evolved many times, sterile somatic cells did too. The evolution of an immortal germline producing specialized somatic cells involved the emergence of mortality, and can be viewed in its simplest version in volvocine algae. Those species with a separation between sterile somatic cells and a germ line are called Weismannists. However, Weismannist development is relatively rare (e.g., vertebrates, arthropods, Volvox), as great part of species have the capacity for somatic embryogenesis (e.g., land plants, most algae, many invertebrates).
Like all cells, somatic cells contain DNA arranged in chromosomes. If a somatic cell contains chromosomes arranged in pairs, it is called diploid and the organism is called a diploid organism. (The gametes of diploid organisms contain only single unpaired chromosomes and are called haploid.) Each pair of chromosomes comprises one chromosome inherited from the father and one inherited from the mother. For example, in humans, somatic cells contain 46 chromosomes organized into 23 pairs. By contrast, gametes of diploid organisms contain only half as many chromosomes. In humans, this is 23 unpaired chromosomes. When two gametes (i.e. a spermatozoon and an ovum) meet during conception, they fuse together, creating a zygote. Due to the fusion of the two gametes, a human zygote contains 46 chromosomes (i.e. 23 pairs).
However, a large number of species have the chromosomes in their somatic cells arranged in fours ("tetraploid") or even sixes ("hexaploid"). Thus, they can have diploid or even triploid germline cells. An example of this is the modern cultivated species of wheat, Triticum aestivum L., a hexaploid species whose somatic cells contain six copies of every chromatid.
In recent years, the technique of cloning whole organisms has been developed in mammals, allowing almost identical genetic clones of an animal to be produced. One method of doing this is called "somatic cell nuclear transfer" and involves removing the nucleus from a somatic cell, usually a skin cell. This nucleus contains all of the genetic information needed to produce the organism it was removed from. This nucleus is then injected into an ovum of the same species which has had its own genetic material removed. The ovum now no longer needs to be fertilized, because it contains the correct amount of genetic material (a diploid number of chromosomes). In theory, the ovum can be implanted into the uterus of a same-species animal and allowed to develop. The resulting animal will be a nearly genetically identical clone to the animal from which the nucleus was taken. The only difference is caused by any mitochondrial DNA that is retained in the ovum, which is different from the cell that donated the nucleus. In practice, this technique has so far been problematic, although there have been a few high-profile successes, such as Dolly the Sheep and, more recently, Snuppy, the first cloned dog. Somatic cells have also been collected in the practice of cryoconservation of animal genetic resources as a means of conserving animal genetic material, including to clone livestock.
Development of biotechnology has allowed for the genetic manipulation of somatic cells. This biotechnology deals with some ethical controversy in human genetic engineering.
Embryonic and Somatic Stem Cells, Whats the Difference?
1) Proliferation; The stem cells are capable to renew even after long periods of inactivity and capable of self-renewal during cell division. 2) Unspecialized; They are unspecialized which later give arise to specialized cells. 3) Differentiation; They are able to differentiate them under special conditions and functions.
1) Embryonic stem cells. Those stem cells are derived from developing embryo. These cells are mostly use for in-vitro fertilization. 2) Somatic stem cells. Commonly known as adult stem cell. They are defined according to their location within the body.
Embryonic stem cells Somatic Pluripotent. Non pluripotent. Can easily grow in culture Not that easy. A large number of cells are required for stem cell replacement therapies.
The somatic stem cells can be further classified into mesenchymal stem cells and hematopoietic stem cells. The somatic stem cells are found in specific region of organ known as stem cell niche. The organs from where stem cell niche are found are in brain, skeletal muscle, gut, liver, pancreas, bone marrow, ovarian epithelium teeth, and testis.
The Somatic stem cells have been demonstrated as; Hematopoietic stem cells; Give rise to all kinds of blood cells. Mesenchymal stem cells; Give rise to all kinds of bone cells. Neural stem cells; Give rise to all kinds of neuronal and non neuronal cells in brain. Epithelial stem cells; Give rise to different kinds of cells of digestive tract. Skin stem cells; give rise to all the epidermis and ketatinocytes of skin.
Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues. More accurately known as somatic stem cells (from Greek , meaning of the body), because they are usually more plentiful in juvenile (child) than in adult animal and human bodies.
Scientific interest in adult stem cells is centered on their ability to divide or self-renew indefinitely, and generate all the cell types of the organ from which they originate, potentially regenerating the entire organ from a few cells. Unlike embryonic stem cells, the use of human adult stem cells in research and therapy is not considered to be controversial, as they are derived from adult tissue samples rather than human embryos designated for scientific research. They have mainly been studied in humans and model organisms such as mice and rats.
To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter cells, both endowed with stem cell properties, whereas asymmetric division produces only one stem cell and a progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before finally differentiating into a mature cell. It is believed that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.
Adult stem cells express transporters of the ATP-binding cassette family that actively pump a diversity of organic molecules out of the cell. Many pharmaceuticals are exported by these transporters conferring multidrug resistance onto the cell. This complicates the design of drugs, for instance neural stem cell targeted therapies for the treatment of clinical depression.
Adult stem cell research has been focused on uncovering the general molecular mechanisms that control their self-renewal and differentiation.
Discoveries in recent years have suggested that adult stem cells might have the ability to differentiate into cell types from different germ layers. For instance, neural stem cells from the brain, which are derived from ectoderm, can differentiate into ectoderm, mesoderm, and endoderm. Stem cells from the bone marrow, which is derived from mesoderm, can differentiate into liver, lung, GI tract and skin, which are derived from endoderm and mesoderm. This phenomenon is referred to as stem cell transdifferentiation or plasticity. It can be induced by modifying the growth medium when stem cells are cultured in vitro or transplanting them to an organ of the body different from the one they were originally isolated from. There is yet no consensus among biologists on the prevalence and physiological and therapeutic relevance of stem cell plasticity. More recent findings suggest that pluripotent stem cells may reside in blood and adult tissues in a dormant state. These cells are referred to as "Blastomere Like Stem Cells" (Am Surg. 2007 Nov;73:1106-10) and "very small embryonic like" - "VSEL" stem cells, and display pluripotency in vitro. As BLSC's and VSEL cells are present in virtually all adult tissues, including lung, brain, kidneys, muscles, and pancreas Co-purification of BLSC's and VSEL cells with other populations of adult stem cells may explain the apparent pluripotency of adult stem cell populations. However, recent studies have shown that both human and murine VSEL cells lack stem cell characteristics and are not pluripotent.
Hematopoietic stem cells are found in the bone marrow and umbilical cord blood and give rise to all the blood cell types.
Mammary stem cells provide the source of cells for growth of the mammary gland during puberty and gestation and play an important role in carcinogenesis of the breast. Mammary stem cells have been isolated from human and mouse tissue as well as from cell lines derived from the mammary gland. Single such cells can give rise to both the luminal and myoepithelial cell types of the gland, and have been shown to have the ability to regenerate the entire organ in mice.
Intestinal stem cells divide continuously throughout life and use a complex genetic program to produce the cells lining the surface of the small and large intestines. Intestinal stem cells reside near the base of the stem cell niche, called the crypts of Lieberkuhn. Intestinal stem cells are probably the source of most cancers of the small intestine and colon.
Mesenchymal stem cells (MSCs) are of stromal origin and may differentiate into a variety of tissues. MSCs have been isolated from placenta, adipose tissue, lung, bone marrow and blood, Wharton's jelly from the umbilical cord, and teeth (perivascular niche of dental pulp and periodontal ligament). MSCs are attractive for clinical therapy due to their ability to differentiate, provide trophic support, and modulate innate immune response. These cells have the ability to differentiate into various cell types such as osteoblasts, chondroblasts, adypocytes, neuroectodermal cells, and hepatocytes. Bioactive mediators that favor local cell growth are also secreted by MSCs. Anti-inflammatory effects on the local microenvironment, which promote tissue healing, are also observed. The inflammatory response can be modulated by adipose-derived regenerative cells (ADRC) including mesenchymal stem cells and regulatory T-lymphocytes. The mesenchymal stem cells thus alter the outcome of the immune response by changing the cytokine secretion of dendritic and T-cell subsets. This results in a shift from a pro-inflammatory environment to an anti-inflammatory or tolerant cell environment.
Endothelial stem cells are one of the three types of multipotent stem cells found in the bone marrow. They are a rare and controversial group with the ability to differentiate into endothelial cells, the cells that line blood vessels.
The existence of stem cells in the adult brain has been postulated following the discovery that the process of neurogenesis, the birth of new neurons, continues into adulthood in rats. The presence of stem cells in the mature primate brain was first reported in 1967. It has since been shown that new neurons are generated in adult mice, songbirds and primates, including humans. Normally, adult neurogenesis is restricted to two areas of the brain the subventricular zone, which lines the lateral ventricles, and the dentate gyrus of the hippocampal formation. Although the generation of new neurons in the hippocampus is well established, the presence of true self-renewing stem cells there has been debated. Under certain circumstances, such as following tissue damage in ischemia, neurogenesis can be induced in other brain regions, including the neocortex.
Neural stem cells are commonly cultured in vitro as so called neurospheres floating heterogeneous aggregates of cells, containing a large proportion of stem cells. They can be propagated for extended periods of time and differentiated into both neuronal and glia cells, and therefore behave as stem cells. However, some recent studies suggest that this behaviour is induced by the culture conditions in progenitor cells, the progeny of stem cell division that normally undergo a strictly limited number of replication cycles in vivo. Furthermore, neurosphere-derived cells do not behave as stem cells when transplanted back into the brain.
Neural stem cells share many properties with haematopoietic stem cells (HSCs). Remarkably, when injected into the blood, neurosphere-derived cells differentiate into various cell types of the immune system.
Olfactory adult stem cells have been successfully harvested from the human olfactory mucosa cells, which are found in the lining of the nose and are involved in the sense of smell. If they are given the right chemical environment these cells have the same ability as embryonic stem cells to develop into many different cell types. Olfactory stem cells hold the potential for therapeutic applications and, in contrast to neural stem cells, can be harvested with ease without harm to the patient. This means they can be easily obtained from all individuals, including older patients who might be most in need of stem cell therapies.
Hair follicles contain two types of stem cells, one of which appears to represent a remnant of the stem cells of the embryonic neural crest. Similar cells have been found in the gastrointestinal tract, sciatic nerve, cardiac outflow tract and spinal and sympathetic ganglia. These cells can generate neurons, Schwann cells, myofibroblast, chondrocytes and melanocytes.
Multipotent stem cells have also been derived from germ cells found in human testicles.
The therapeutic potential of adult stem cells is the focus of much scientific research, due to their ability to be harvested from the patient. In common with embryonic stem cells, adult stem cells have the ability to differentiate into more than one cell type, but unlike the former they are often restricted to certain types or "lineages". The ability of a differentiated stem cell of one lineage to produce cells of a different lineage is called transdifferentiation. Some types of adult stem cells are more capable of transdifferentiation than others, but for many there is no evidence that such a transformation is possible. Consequently, adult stem therapies require a stem cell source of the specific lineage needed, and harvesting and/or culturing them up to the numbers required is a challenge. Additionally, cues from the immediate environment (including how stiff or porous the surrounding structure/extracellular matrix is) can alter or enhance the fate and differentiation of the stem cells.
Pluripotent stem cells, i.e. cells that can give rise to any fetal or adult cell type, can be found in a number of tissues, including umbilical cord blood. Using genetic reprogramming, pluripotent stem cells equivalent to embryonic stem cells have been derived from human adult skin tissue. Other adult stem cells are multipotent, meaning they are restricted in the types of cell they can become, and are generally referred to by their tissue origin (such as mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, etc.). A great deal of adult stem cell research has focused on investigating their capacity to divide or self-renew indefinitely, and their potential for differentiation. In mice, pluripotent stem cells can be directly generated from adult fibroblast cultures.
Adult stem cell treatments have been used for many years to successfully treat leukemia and related bone/blood cancers utilizing bone marrow transplants. The use of adult stem cells in research and therapy is not considered as controversial as the use of embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo.
Early regenerative applications of adult stem cells has focused on intravenous delivery of blood progenitors known as Hematopetic Stem Cells (HSC's). CD34+ hematopoietic Stem Cells have been clinically applied to treat various diseases including spinal cord injury, liver cirrhosis  and Peripheral Vascular disease. Research has shown that CD34+ hematopoietic Stem Cells are relatively more numerous in men than in women of reproductive age group among spinal cord Injury victims. Other early commercial applications have focused on Mesenchymal Stem Cells (MSCs). For both cell lines, direct injection or placement of cells into a site in need of repair may be the preferred method of treatment, as vascular delivery suffers from a "pulmonary first pass effect" where intravenous injected cells are sequestered in the lungs. Clinical case reports in orthopedic applications have been published. Wakitani has published a small case series of nine defects in five knees involving surgical transplantation of mesenchymal stem cells with coverage of the treated chondral defects. Centeno et al. have reported high field MRI evidence of increased cartilage and meniscus volume in individual human clinical subjects as well as a large n=227 safety study. Many other stem cell based treatments are operating outside the US, with much controversy being reported regarding these treatments as some feel more regulation is needed as clinics tend to exaggerate claims of success and minimize or omit risks.
Somatic stem cells in the human endometrium.
The existence of human endometrial somatic stem cells was proposed in the mid-20th century for the first time. This hypothesis became stronger and was revised by two authors between 1978 and 1989. Nevertheless, it was not until 2004 that scientific evidence was first published. As we describe here, the great regenerative capability of the human endometrium has been finally questioned in the last 8 years, and this period can be considered the most productive in endometrial stem cell biology given the new scientific information recapitulated to date. We provide a detailed summary based on the actual scientific knowledge obtained about (1) the existence of somatic stem cells in murine (detected with label-retaining cell methods) and human (cells isolated by different methods) endometria, (2) the involvement of bone marrow as a putative extrauterine source of endometrial somatic stem cells, (3) the implication and biological pathways of these cells in several pathologies like endometriosis and endometrial cancer, and (4) the future of endometrial somatic stem cells in regenerative medicine to provide new strategies in autologous transplant and bioengineering.
An adult stem cell is thought to be an undifferentiated cell, found among differentiated cells in a tissue or organ. The adult stem cell can renew itself and can differentiate to yield some or all of the major specialized cell types of the tissue or organ. The primary roles of adult stem cells in a living organism are to maintain and repair the tissue in which they are found. Scientists also use the term somatic stem cell instead of adult stem cell, where somatic refers to cells of the body (not the germ cells, sperm or eggs). Unlike embryonic stem cells, which are defined by their origin (cells from the preimplantation-stage embryo), the origin of adult stem cells in some mature tissues is still under investigation.
Research on adult stem cells has generated a great deal of excitement. Scientists have found adult stem cells in many more tissues than they once thought possible. This finding has led researchers and clinicians to ask whether adult stem cells could be used for transplants. In fact, adult hematopoietic, or blood-forming, stem cells from bone marrow have been used in transplants for more than 40 years. Scientists now have evidence that stem cells exist in the brain and the heart, two locations where adult stem cells were not at firstexpected to reside. If the differentiation of adult stem cells can be controlled in the laboratory, these cells may become the basis of transplantation-based therapies.
The history of research on adult stem cells began more than 60 years ago. In the 1950s, researchers discovered that the bone marrow contains at least two kinds of stem cells. One population, called hematopoietic stem cells, forms all the types of blood cells in the body. A second population, called bone marrow stromal stem cells (also called mesenchymal stem cells, or skeletal stem cells by some), were discovered a few years later. These non-hematopoietic stem cells make up a small proportion of the stromal cell population in the bone marrow and can generate bone, cartilage, and fat cells that support the formation of blood and fibrous connective tissue.
In the 1960s, scientists who were studying rats discovered two regions of the brain that contained dividing cells that ultimately become nerve cells. Despite these reports, most scientists believed that the adult brain could not generate new nerve cells. It was not until the 1990s that scientists agreed that the adult brain does contain stem cells that are able to generate the brain's three major cell typesastrocytes and oligodendrocytes, which are non-neuronal cells, and neurons, or nerve cells.
Adult stem cells have been identified in many organs and tissues, including brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin, teeth, heart, gut, liver, ovarian epithelium, and testis. They are thought to reside in a specific area of each tissue (called a "stem cell niche"). In many tissues, current evidence suggests that some types of stem cells are pericytes, cells that compose the outermost layer of small blood vessels. Stem cells may remain quiescent (non-dividing) for long periods of time until they are activated by a normal need for more cells to maintain tissues, or by disease or tissue injury.
Typically, there is a very small number of stem cells in each tissue and, once removed from the body, their capacity to divide is limited, making generation of large quantities of stem cells difficult. Scientists in many laboratories are trying to find better ways to grow large quantities of adult stem cells in cell culture and to manipulate them to generate specific cell types so they can be used to treat injury or disease. Some examples of potential treatments include regenerating bone using cells derived from bone marrow stroma, developing insulin-producing cells for type1 diabetes, and repairing damaged heart muscle following a heart attack with cardiac muscle cells.
Scientists often use one or more of the following methods to identify adult stem cells: (1) label the cells in a living tissue with molecular markers and then determine the specialized cell types they generate; (2) remove the cells from a living animal, label them in cell culture, and transplant them back into another animal to determine whether the cells replace (or "repopulate") their tissue of origin.
Importantly, scientists must demonstrate that a single adult stem cell can generate a line of genetically identical cells that then gives rise to all the appropriate differentiated cell types of the tissue. To confirm experimentally that a putative adult stem cell is indeed a stem cell, scientists tend to show either that the cell can give rise to these genetically identical cells in culture, and/or that a purified population of these candidate stem cells can repopulate or reform the tissue after transplant into an animal.
As indicated above, scientists have reported that adult stem cells occur in many tissues and that they enter normal differentiation pathways to form the specialized cell types of the tissue in which they reside.
Normal differentiation pathways of adult stem cells. In a living animal, adult stem cells are available to divide for a long period, when needed, and can give rise to mature cell types that have characteristic shapes and specialized structures and functions of a particular tissue. The following are examples of differentiation pathways of adult stem cells (Figure 2) that have been demonstrated in vitro or in vivo.
Transdifferentiation. A number of experiments have reported that certain adult stem cell types can differentiate into cell types seen in organs or tissues other than those expected from the cells' predicted lineage (i.e., brain stem cells that differentiate into blood cells or blood-forming cells that differentiate into cardiac muscle cells, and so forth). This reported phenomenon is called transdifferentiation.
Although isolated instances of transdifferentiation have been observed in some vertebrate species, whether this phenomenon actually occurs in humans is under debate by the scientific community. Instead of transdifferentiation, the observed instances may involve fusion of a donor cell with a recipient cell. Another possibility is that transplanted stem cells are secreting factors that encourage the recipient's own stem cells to begin the repair process. Even when transdifferentiation has been detected, only a very small percentage of cells undergo the process.
In a variation of transdifferentiation experiments, scientists have recently demonstrated that certain adult cell types can be "reprogrammed" into other cell types in vivo using a well-controlled process of genetic modification (see Section VI for a discussion of the principles of reprogramming). This strategy may offer a way to reprogram available cells into other cell types that have been lost or damaged due to disease. For example, one recent experiment shows how pancreatic beta cells, the insulin-producing cells that are lost or damaged in diabetes, could possibly be created by reprogramming other pancreatic cells. By "re-starting" expression of three critical beta cell genes in differentiated adult pancreatic exocrine cells, researchers were able to create beta cell-like cells that can secrete insulin. The reprogrammed cells were similar to beta cells in appearance, size, and shape; expressed genes characteristic of beta cells; and were able to partially restore blood sugar regulation in mice whose own beta cells had been chemically destroyed. While not transdifferentiation by definition, this method for reprogramming adult cells may be used as a model for directly reprogramming other adult cell types.
In addition to reprogramming cells to become a specific cell type, it is now possible to reprogram adult somatic cells to become like embryonic stem cells (induced pluripotent stem cells, iPSCs) through the introduction of embryonic genes. Thus, a source of cells can be generated that are specific to the donor, thereby increasing the chance of compatibility if such cells were to be used for tissue regeneration. However, like embryonic stem cells, determination of the methods by which iPSCs can be completely and reproducibly committed to appropriate cell lineages is still under investigation.
(A) Nuclear DNA genotyping from four human NT-ESC lines (hESO-NT1, hESO-NT2, hESO-NT3, and hESO-NT4) determined by microsatellite parentage analysis. A total of 24 microsatellite markers were used for each analysis. The representative markers for D2S1333 and D4S413 loci demonstrate that the nuclear DNA in these cell lines was exclusively derived from the somatic HDF-f cell line. No contribution of oocyte nuclear DNA was detected. (B) mtDNA genotyping by Sanger sequencing demonstrated that all NT-ESC lines contain oocyte mtDNA. (C) Cytogenetic G-banding analysis confirmed that all NT-ESCs exhibited a normal 46XX karyotype (hESO-NT1 result is representative). (D) Human NT-ESCs expressed standard pluripotency markers detected by immunocytochemistry for antibodies against OCT4, NANOG, SOX2, SSEA-4, TRA-160, and TRA-181. Original magnification, 200; Ph, phase contrast. Note that the upper-left image for hESO-NT1 is the same shown in Figure 2F. The upper-right image for hESO-7 is the same shown in Figure S5 (upper-right). (E) Histological analysis of teratoma tumors produced after injection of human NT-ESCs into SCID mice. An arrow and arrowhead in the top panel indicate intestinal-type epithelium with goblet cells (endoderm) and cartilage (mesodermal), respectively. An arrow and arrowhead in the lower panel depict neuroecto-dermal (ectoderm) and muscle (mesoderm) tissues, respectively. Original magnification, 200. See also Figures S4 and S5 and Tables S4 and S5.
Induced pluripotent stem cells (iPSCs) are somatic cells that have been reprogrammed to a pluripotent state via introduction of defined transcription factors. iPSCs are a valuable resource for regenerative medicine, but whether iPSCs are identical to embryonic stem cells (ESCs) remains unclear. In this study, we performed comparative proteomic analyses of human somatic cells [human newborn foreskin fibroblasts (hFFs)], human iPSCs (hiPSCs) derived from hFFs, and H9 human ESCs (hESCs). We reprogrammed hFFs to a pluripotent state using 4 core transcription factors: Oct4 (O), Sox2 (S), Klf4 (K), and c-Myc (M). The proteome of hiPSCs induced by 4 core transcription factors was relatively similar to that of hESCs. However, several proteins, including dUTPase, GAPDH, and FUSE binding protein 3, were differentially expressed between hESCs and hiPSCs, implying that hiPSCs are not identical to hESCs at the proteomic level. The proteomes of iPSCs induced by introducing 3, 5, or 6 transcription factors were also analyzed. Our proteomic profiles provide valuable insight into the factors that contribute to the similarities and differences between hESCs and hiPSCs and the mechanisms of reprogramming.
A somatic (Greek: /soma = body) or vegetative cell is any biological cell forming the body of an organism; that is, in a multicellular organism, any cell other than a gamete, germ cell, gametocyte or undifferentiated stem cell.
In recent years, the technique of cloning whole organisms has been developed in mammals, allowing almost identical genetic clones of an animal to be produced. One method of doing this is called "somatic cell nuclear transfer" and involves removing the nucleus from a somatic cell, usually a skin cell. This nucleus contains all of the genetic information needed to produce the organism it was removed from. This nucleus is then injected into an ovum of the same species which has had its own genetic material removed. The ovum now no longer needs to be fertilized, because it contains the correct amount of genetic material (a diploid number of chromosomes). In theory, the ovum can be implanted into the uterus of a same-species animal and allowed to develop. The resulting animal will be a nearly genetically identical clone to the animal from which the nucleus was taken. The only difference is caused by any mitochondrial DNA that is retained in the ovum, which is different from the cell that donated the nucleus. In practice, this technique has so far been problematic, although there have been a few high profile successes, such as Dolly the Sheep and, more recently, Snuppy, the first cloned dog.
Development of Biotechnology has allowed for the genetic manipulation of somatic cells.This biotechnology deals with some ethical controversy in Human genetic engineering.


Are you interested in the value of flood-irrigated habitats to wetland-dependent birds, wet meadow conservation, or sustaining ranching for future generations? If so, check out this webinar entitled, "Meeting the Needs of Spring-migrating Waterfowl in the Intermountain West on Working Ranches", presented on December 16, 2014 by the IWJV Team of Josh Vest, Dave Smith, and Jeremy Maestas.
It provides a detailed look at the value of flood-irrigated wet meadow habitats to birds in a key landscape of the Intermountain West, an approach for balancing competing water resource demands, and the critical role that ranchers play in managing wetland habitats. This webinar is part of the Natural Resources Conservation Service's Working Agricultural Lands conservation webinar series.
The Blanca Wildlife Habitat Area is a complex of wetlands managed by the Bureau of Land Management (BLM) in the San Luis Valley of south-central Colorado. The San Luis Valley has been identified as a primary Key Site for shorebird conservation, particularly for passage birds such as Wilson's Phalaropes, American Avocets, and Baird's Sandpipers.


text:
Ricardo Gutiérrez Abascal (1883–1963), also known by his pseudonym Juan de la Encina, was a Spanish art critic.

Life
He was born in Bilbao, and educated in Germany.  In 1931 he was named director of the Madrid Museum of Modern Art but exiled to Mexico in 1939.  He authored The Masters of Modern Art (Los Maestros del Arte Moderno), Julio Antonio (1920), Victorio Macho (1926), and Altarpiece of Modern Painting (Retablo de la Pintura Moderna) (1953).  He was also known by the pseudonym Juan de la Encina.  He died in Mexico.

See also
 Victorio Macho
 Pilar de Zubiaurre

References

1883 births
1963 deaths
People from Bilbao
20th-century Spanish writers
20th-century Spanish male writers
Spanish anti-fascists
Spanish people of the Spanish Civil War (Republican faction)
Exiles of the Spanish Civil War in Mexico
Spanish expatriates in Germany

redpajama_set_name: RedPajamaWikipedia


To determine the rise of maximum temperature of a transformer, its load test is of utmost importance. Using suitable load impedance, small transformers can be put on full load. The full-load test of large transformers is not possible because considerable wastage of energy occurs and it is difficult to get a suitable load for absorbing full-load power. Sumpner's test is used to put large transformer on full load. This test can also be used to determine the efficiency of a transformer. Figure 1.45 shows the schematic diagram of Sumpner's test. This test is also known as back to back test or load test.
This test requires two identical transformers. The two primaries are connected in parallel and are energized at rated voltage and rated frequency. The wattmeter W1 records the reading of core loss of both the transformers. Next the two secondaries are connected in series in such a way that their polarities are in phase opposition and the reading of the voltmeter V2 becomes zero. With the help of voltage regulator fed from source, a voltage is injected to the secondary of the transformers, which is adjusted until the rated secondary current flows. The voltmeter reads a voltage, which is the leakage impedance drop of the two transformers. The reading of W1 remains unaltered. The wattmeter W2reads the total copper (Cu) loss of the two transformers. Although the transformers are not supplying any load current, this test measures the full iron loss as well as copper loss of the transformers. The net input during this test is W1 + W2. To measure the temperature rise, the two transformers are kept under rated loss conditions for several hours.


text:
.class synthetic Lorg/apache/http/conn/ssl/SSLSocketFactory$1;
.super Ljava/lang/Object;
.source "SSLSocketFactory.java"

# annotations
.annotation system Ldalvik/annotation/EnclosingClass;
    value = Lorg/apache/http/conn/ssl/SSLSocketFactory;
.end annotation

.annotation system Ldalvik/annotation/InnerClass;
    accessFlags = 0x1008
    name = null
.end annotation

redpajama_set_name: RedPajamaGithub


text:
Olivia Jade Has 'No Plans' to Return to USC Amid College Admissions Scandal
By Stephen Andrew - August 8, 2019 05:51 pm EDT
Lori Loughlin's daughter Olivia Jade reportedly has "no plans" to return to the University of Southern California, amid her parents' college admissions scandal. Loughlin and her husband Mossimo Giannulli were hit with bribery-related charges earlier this year in connection to an investigation that saw multiple high-profile institutions be impacted by false SAT test scores and admissions scams. Loughlin and Giannulli pleaded not guilty, and were subsequently charged with money laundering as well. The family has had a tough time, and now a source says that Olivia Jade is trying to look toward her future.
"Olivia has no plans to return to USC. She never wanted to attend USC to begin with, and now she is sure that USC isn't the place for her," the source told ET. "Right now her goal is to rebuild her brand and her business."
The source adds that Olivia Jade has sought her father's advice on how to save her brand "because he understands business." The source then continued, "He has been encouraging Olivia to create a new brand, either makeup or beauty related."
Regarding Olivia Jade's relationship with her mother, the source says she still has some "resentment" towards Loughlin.
"Therapy has helped to bring the family together during some really rough times. Olivia and her mother have been communicating and things have improved. Lori has apologized many times to her girls and has told them that she only wants the best for them," the source went on to say. "Olivia has forgiven her but she still carries some resentment because she realizes that this scandal has marked her and will never entirely go away."
"The girls are definitely scared for their mother and father. Until the court date has passed, they are just trying to get through the summer," the source also said.
While Olivia Jade may not go back to USC, ET reports that Bella might, as she is still a member of the school's chapter of the Kappa Kappa Gamma sorority.
In legal documents explaining the college admissions scam investigation and arrests, a press release from the U.S. Attorney's Office in Massachusetts read, "Dozens of individuals involved in a nationwide conspiracy that facilitated cheating on college entrance exams and the admission of students to elite universities as purported athletic recruits were arrested by federal agents in multiple states and charged in documents unsealed on March 12, 2019, in federal court in Boston."
Additionally, the legal documents accuse Loughlin and Giannulli of agreeing "to pay bribes totaling $500,000 in exchange for having their two daughters designated as recruits to the USC crew team — despite the fact that they did not participate in crew — thereby facilitating their admission to USC."
The couple's case will reportedly go to trial sometime in 2020.
WATI! Hit play and listen to GroupChat's NEW episode 19! We're talking MAJOR Oscar snubs, 'The Bachelor's epic Champagne Gate, what's going on with a specific 'DWTS' pro's marriage, and Kim Kardashian is catching some heat for what she says she DIDN'T do at a basketball game. Tap play and tune in!
Tristan Thompson Ejected for Slapping Grizzlies Player's Rear End During Friday Night's Game
'Little People, Big World' Star Amy and Matt Roloff Share Heartwarming Photos With Son Jacob on His Birthday
Meghan Markle and Prince Harry Reach Deal With Queen Elizabeth, Officially 'Step Back From Royal Duties'

redpajama_set_name: RedPajamaCommonCrawl


Newly opened residential and dementia care home, Chamberlain Court in Royal Tunbridge Wells, is holding an open day on Saturday 7th October 10:30am – 3pm.
The open day is aimed at anyone with questions or concerns about power of attorney, funding long-term care, and for those who are interested to know the available care options in Royal Tunbridge Wells.
Join us for a tour of Chamberlain Court and find out why we are a care home with a difference.


Learn more about current and upcoming initiatives within ICE.
ICE: Innovation = Creativity + Entrepreneurship ... How do ideas become reality (I2R)? How do opportunities emerge and implement? Whether startups and side hustles or corporate and social innovation we need a deeper, richer understanding of both micro and macro processes: What is the 'entrepreneurial mindset'? How does it emerge? How do we nurture it? Assess it? What is the 'entrepreneurial ecosystem'? (a/k/a 'innovation system') How do we nurture it? We are equally interested in deep, bleeding-edge research AND meaningful practice. Join us?
ICE is passionate about innovation and entrepreneurship: How to understand it, how to foster it and how to trigger it While we are intrigued by the deeper research questions, we are especially driven by work that brings together rigorous analysis and relevant application. Our audience will include scholars, educators, practitioners, and policy- makers. We envision a robust, productve conversation among these groups to advance our expertise by turning ideas into a reality.


"Taco bell beans are full of beef fat :( I was annoyed to discover"
"i agree, i love taco bell so its my weakness.... I've stopped using microwaves so eating warm food at the office is out of the question"
"i joined a couple days ago, its nice meeting other vegetarians who understand this life style"
"hey, i'm Paula - live in Atlanta... looking to meet 'like minded' people :-)"
"microwaves are very bad for you and your food... it poisons the food and radiation has an exposure area of 15 feet...."
Is cooking food in cooker, as well reduces food nutrition? ?


text:
Q: error: Unexpected error: Illegal name .$HelloControllerDefinition I have followed the Getting Started. First start of Application was Ok. Then I added a Controller as described (HelloController.java in src/main/java/helloworld. When I restart the server, I get the following error:
c:\dev\micronaut\helloworld>gradlew run

Task :compileJava FAILED
  Note: Creating bean classes for 1 type elements
  error: Unexpected error: Illegal name .$HelloControllerDefinition
  1 error

I am under Windows 10 with jdk 1.8_171

A: As Graeme Rocher mentioned, the class is missing it's package. If you add the line I've added below, it should work.
package helloworld;

import io.micronaut.http.annotation.*;

@Controller("/hello")
public class HelloController {
    @Get
    public String index() {
        return "Hello World";
    }
}

redpajama_set_name: RedPajamaStackExchange


We don't need velvet ropes and champagne service to provide a VIP experience here at Richmond International Raceway during our NASCAR weekends. Elevate your trip to America's Premier Short Track with the All-Inclusive Weekend Package, which is on sale now for just $320 per person.
Access to the Pit Stop Club on September 6, which includes indoor hospitality with all-you-can-eat food & unlimited sodas, water, beer and wine. As well as access to celebrity appearances, including Richard Childress!
So be part of the "in crowd" and take advantage of the limited availability, All-Inclusive Weekend Package for just $320. CLICK HERE or call 866-455-7223 to book your ticket to NASCAR paradise today!


text:
"Yes, I know this, because we are brothers and sisters who grew up together, so it's impossible not to like each other? So, we know each other best and accept everything about each other best, and we like it the most. No reservations?"
"Hmm, that's it, so—"
Therefore, it is only natural to let this love between sisters and brothers become a love between lovers?She raised her head expectantly, her pupils becoming wet.
"--Well, so, just stop here, isn't it great?"
However, Yubihama Kazuya did not say what she wanted to hear after all.
Just like a long and beautiful dream, until the end, it is developing in the direction that one wants, but at the last moment, the dream wakes up, and the reality is not as satisfactory as one thought.
"Why, do we stop here? If we stop here, is there any difference between us and other brothers and sisters?"
——We are obviously closer and better than the other siblings, and we don't want to be separated, don't we?
"I know, we and other siblings are always better."
"Yes, so Xiaohe thought about why we would be better without us. I have already thought about it. The reason why we are better is because--"
"——I actually seriously considered my sister's thoughts, and I also seriously considered my own feelings." However, it seemed that I did not want her to say that word resolutely. Broke her.
"Time to think is not enough? Actually, you can think harder, right?"
"Yes, it may not be enough," Kazuki smiled lightly, "In fact, I was not sure until the moment just now, but when I saw Senior Kitahara, I really realized that I might lose When I feel like I feel, I feel that my thoughts have been determined."
What is meant by "When I saw Senior Kitahara, my thoughts were already determined"?This is unfair?Obviously, you haven't finished thinking, have you?Obviously, you can think about it more?
"I like Senior Xiao Muyan, I don't want Senior Beiyuan to take away Senior Xiao Muyan, so—"
"--But Xiaohe, this is unfair, quite unfair!"
"Why is it called unfair?"
"Yeah, it's very unfair. You saw Senior Kitahara, that's why you are sure of your own mind, right? You saw Senior Kitahara, so you think you like Senior Omusao more without considering your feelings for me? But, Isn't this just because Kitahara-senior threatened your connection with Xiaomushu-sen? You only decided your own thoughts because the relationship was threatened. If you think you want to lose Xiaomushu Xuecai, you choose Xiaomushuxue. In terms of food, isn't that unfair to me?"
"Because, you didn't give me this chance to prove it!" She sobbed lowly, "I am different from Senior Xiao Muzhen. From beginning to end, you didn't give me any chance to connect with other boys, did you? All the people who like me have been driven away by you in advance, haven't they? So, from the beginning, I couldn't give you the feeling of'I'm about to lose Yuihama Yui', right?"
The air almost seemed not to continue to flow.
right?There is no way to refute this, she believes it.
After a long time--perhaps just a while later, she heard Heya's helpless voice: "I don't know how to refute it. Maybe, if there is such a possibility, Yui sister, you are right."
That's right, there is no way to refute it. In the quarrel between her and Yubihama Kazuya for so many years, one time finally ended with her victory.
"But, right now, I can still choose Senior Xiao Muzhen-even if I know that your sister is right, even if I know I did it because of the impulse of seeing Senior Kitahara."
Yuihama Yui and Kazuya Yuihama have been arguing and arguing. She has always been the one who speaks with emotion, and Kazaya has always been the one who convinces herself with reason and reason.
It's really unfair!When you won before, you said that you were a reasonable person, but this time, it was obvious that I was more reasonable than you, but you didn't listen to my reason!
What the hell is going on?
"By the way, I can do it too? For small businesses, Hayato, if I am ambiguous with them, if I do something irritating and pitiful--" she murmured.
"——Sister, you can't do it, right?"
She was stunned.
Then, she nodded weakly.
Yes, Yuihama Yui can't do it. If it does, it won't be Yuihama Yui.
"If I can make myself able to do this kind of thing, I will do it, really." She said heavily.
"But, that's probably not my favorite Yui sister, right?"
Do you like it at this time?At this time, saying "My favorite Yui sister?", really, too cunning, right?
"Xiaohe, don't you think you are really cunning?"
Yes, it's too cunning. I clearly rejected me and obviously didn't choose me, but I kept saying, like, like, like the most. Are you not, are you using your feelings to make me succumb?Isn't it that you make me even more unable to give up on you?
"Because, I can't help it," she watched her brother stand up again in silence and put on his coat, "because Yui sister is still my favorite Yui sister, I don't want Yui sister to become That way, so I can't lie to such Yui sister, can I?"
"I like my sister the most, but I can't respond to you only because of your heart." Kazuya said softly, and then walked out.
She stared at the back of Heya leaving, this time, she didn't stop him.
If I like my sister the most, why can't I respond!
She rushed out of the store, looking at the direction Yubihama Kazuya ran.
"Xiaohe, you are a liar, you are a big liar!"
——You clearly said that you won't lie to me. Only a liar will reject me when he likes me the most, right?
---------------------------------PS---------------- ----------------
In the case of codewords, the two chapters are actually in the same chapter, but I think if one chapter directly issues a card to Tuanzi, it will make everyone feel unbearable, so, the two chapters are more relaxed, right...
Chapter Fifty: Misunderstanding
Fengcheng University's entrance exam was on February 11, so, at least before that, Xiaomu Xuexue didn't have much room to relax. After that time, she locked herself in the room tightly and made a pair. The appearance of the test-takers preparing for the sprint, I don't know how many things I have reviewed-but a little bit of pressure and a goal, forcing myself to act, is better than doing nothing.
But it all ended on February 11.On the day of the exam, she didn't notify anyone. Even though she knew that her mother had prepared a congratulatory dinner at home, she still turned off her mobile phone and went to karaoke to sing by herself until her voice was hoarse-when she came home, she blushed The ears are red, and the exhausted look makes people wonder if something accident happened.
——If you are more rebellious, you actually want to drink a little alcohol secretly. That day, listening to your parents' remarks, "Even after the exam, there must be a student's self-esteem and a girl's self-love. Don't indulge yourself too much." Such preaching, she narrowed her eyes and thought.
But everything is over. She tried her best to finish the exam. Then, she can hide quietly where no one else knows, do nothing, think nothing, and slowly lick her wounds. Right?
When deciding to hold a birthday party, I thought it was a matter of course. The exam is over and I don't have too much pressure. Invite some people, or friends, or just people you know to celebrate and celebrate yourself. The end of high school life that has not been easy for these three years, right?
But now, this has become a burden!I wanted to cancel the birthday party, but in the end I gave up because I thought it was troublesome to call everyone to explain.
Anyway, she can always cope with the past, Xiao Muzhen Xuecai is already very good at doing these things.
Even if peace comes, she can pretend that nothing happened-probably, and then deal with it.
On the day of my birthday, it started to snow.
When she looked out of the frozen window, she suddenly had a strange idea-the tram was out of service and everyone was unable to come due to various accidents. That would be the best result!
Downstairs, it should be his younger brother who is busy helping him prepare for the birthday party-he clearly told him that there is nothing necessary.But probably because the exam is over, the child wants to find something to do, right?
"Actually, my mother originally proposed to go out together, but sister, you always wanted to have a birthday party, so you cancelled it in the end!" At the beginning, she vaguely remembered Xiaohong's words.


Swansea City winger Daniel James has joined Shrewsbury Town on a season-long loan.
The 19-year-old will team up with the League One side in time for their pre-season tour to Portugal from Sunday.
James, who signed for the Swans in August 2014 from Hull City's academy, had an impressive campaign for the club's under-23s last season as they claimed the PL2 (Division 2) league and cup double .
With nine goals from 31 appearances, the Wales Under-21 international was also called into the senior national side by Chris Coleman in June 2017 where he was an unused substitute against Serbia in their recent World Cup qualifier.
Included in the loan deal is an option for James to be recalled in January if requested.
Swansea City wish Daniel good luck at Shrewsbury for the forthcoming campaign.


Muse pulled her coat around her a little tighter. It was chilly, but she had to at least see if she could hear it tonight. It had been completely accidental the night her wanderings had brought her here. Now she'd been coming back every night for a week, hoping to hear more. The first few days had been quiet, but her perseverance had paid off - the music had played every night after that. Each night it was a little different, but there was a constant undercurrent of frustration with the world.
She took up her customary position near the window of 122 Break Street. After about an hour of waiting, it started again. Perhaps it was because she'd grown comfortable in the shadows, perhaps curiosity finally overcame her, but she slowly tried to peek through the window to see if maybe she could see a display of the title or some hint to the artist.
What she saw made her jaw drop. A tall man in a black suit stood by the window, a violin to his shoulder, and played. As she watched, she realized that he was making it up as he went along. A new element of the music, one so subtle she'd never noticed it, suddenly became clear - intermingled with the frustration was a strange sort of melancholy loneliness.
Realizing she was staring, perfectly visible, she ducked back under the window. Who was he?
The music stopped. The door opened and she took off running. He caught her, grunting as she elbowed him in the side, twice, but his grip on her shoulder didn't let up.
His expression hadn't changed much during the brief conversation, but now the piercing glare he gave her perfectly expressed how offended he was.
She shrugged, "But you didn't." Now she was confused. He wasn't offended anymore, but he was still looking at her with a strange gaze, like he was peering through her almost. She shivered.
"I shall interpret that as a 'no,'" he sighed, "but hospitality demands I offer, as it is all I have at the moment." He brought a cup of the hot liquid to her, which she sipped at carefully.


text:
The Jewish Week 07/21/2006
Perhaps the key question of the 21st century concerns the dwindling margin for error we have in responding to the growing threats around us. When a single individual or group can combine a malignant ideology with deadly technology to destroy numerous lives in an instant, and not even the strongest nation on earth can stop them, people naturally become squeamish. No wonder auto racing has never been so popular. Each waking moment we all feel like we are behind a NASCAR wheel, continuously straddling the precipice separating life from death, constantly forced to make instant choices between too-hasty action and fatal inaction. Our response time has become razor thin.
In the face of extreme danger, intolerance infects us. Although I have issues with the Patriot Act, Guantanamo and the House's xenophobic plan for immigration reform I can understand the fear that gave rise to them. We are petrified that some kind of mythical midnight is about to strike, and that fear is forcing us to act even at the cost of some of our basic human rights. If we need to err, let us err on the side of survival. There is no time to seek compromise. All that matters is to act.
The dread of passivity crosses party lines. In his recent documentary, "An Inconvenient Truth," Al Gore employs a popular experiment to drive home his point that the human race is falling asleep at the environmental wheel. In this experiment, a frog placed into boiling water immediately jumps out, whereas a frog placed into cold water will not even flinch if the water is slowly heated to the boiling point. It will train itself to tolerate the discomfort of each incremental shift in temperature and eventually, this weakness will lead to the frog's demise.
Bad news for the frog; worse news for us. In fact, I've read claims that, given their druthers, frogs would rather not be boiled alive. Humans are another story entirely. Gore's point is that we have tolerated a rate of global warming that has increased exponentially over recent years. Last year was the hottest on record, and scientists now expect the world's temperature to rise 2 to 4 degrees by 2100, much more at the polar icecaps. Oceans will soon rise precipitously, which will dramatically change the map of the world, and the administration has been fiddling while Nome burns. Gore sees literally no margin for error at this point. All that matters is that we act.
President Bush would say the same thing about Iran and North Korea.
Frogs are nearing the boiling point almost everywhere we look. As if to underscore the point, according to this month's Science magazine, up to 122 amphibian species have become extinct since 1980. And nearly a third of the more than 5,000 species that remain are also considered threatened. In an atmosphere of pending environmental catastrophe, frogs have become the proverbial canary in the mineshaft.
Greenland is melting and North Korea is launching its calling cards into the Sea of Japan. Iran is nearly nuclear and is already test firing its missiles — at Israel, by way of Lebanon. Until now the world has been extremely tolerant of these provocations. In Israel, rockets on Sderot were tolerated, until they began raining down on Ashkelon, Nahariya, Safed, Haifa and Tiberias.
The biblical plague of frogs, as we recall, was only the second of the 10 inflicted upon the Egyptians and a seemingly innocuous one at that. Exodus (8:2) tells us that the second plague began with only one frog. But when that frog was not properly dispensed with soon enough swarms of frogs were everywhere. Long before "An Inconvenient Truth," the frog was symbolic of the horrible consequences of inaction.
It's rather fitting that the first surface-to-surface missile purchased for the North Korean arsenal was the FROG 5, delivered from the Soviet Union in 1969 and 1970. Then came the Scud, a plague inflicted upon Israel by Iraq during the Gulf War. Now we've gone beyond FROGS, Scuds, Katyushas and Kassams. If only the world had been able to stop things when we were just dealing with FROGS, we wouldn't have gotten the Iranian Fajr-3s that are now being used against Haifa.
This proxy war featuring Hamas and Hezbollah is a test run for the real thing, when the ante could be raised considerably with the development of Iranian nuclear capacity. That's why it is now time for Israel and the world to jump from the quickly warming water, before it comes to its nuclear boil. Just as Israel crippled the Iraqi threat at Osiris in 1981, so does it now have the chance to win another war that the world needs so desperately to win.
There are many legends about the plague of frogs, some touting the heroism of the frogs themselves. In fact, unlike Gore's clueless amphibian, the frogs of the second plague took great pains to appear everywhere. They even jumped headfirst into blazing ovens and enmesh themselves in rising dough in order to ambush unwitting Egyptians cutting open their loaves of bread. These frogs were models for the proactive ethos this new century demands. But the frog also remains a reminder of the plague of passivity.
I've developed a bi-partisan bias toward preemptive action, whether the enemy is Iran's Mahmoud Ahmadinejad or Gore's greenhouse gasses. The calendar is also helping to remind Jews as to the need to be proactive in the face of danger.
The three weeks leading up to Tisha B'Av began this year, as if on cue, with the first strike on Haifa. Over the centuries, at times when the world seemed much larger and history moved more slowly, these three weeks have reminded Jews that the dreams of generations can go up in flames overnight. Now, in this hyped up, multi-tasking, 24/7, instant messaging, NASCAR era, "overnight" has just gotten a lot closer.
Labels: Ethics: Being a Mensch, Israel, Jewish Week "On One Foot" articles


text:
Andre Ward Stops Sergey Kovalev By 8th Round TKO
Kovalev did his best to hold on but was hit low for the third time without losing a point. Ward wasn't talking that way Saturday night.
Ward completed the turnaround with a big right hand that wobbled Kovalev in the eighth, then swarmed all over him, landing shots to the body when Kovalev sat on the ring rope, forcing referee Tony Weeks to signal an end to the bout. The first appeared to land directly on Kovalev's waistband, while the subsequent two strayed a shade lower-prompting the challenger to lurch forward and referee Tony Weeks to intervene at 2:29.
"I knew this time it was going to be different", Ward said.
"He's really lucky, 'Son of Judges, ' " Kovalev said of Ward, twisting Ward's "Son of God" nickname.
Both fighters swing and miss.
Last November's title fight between Andre Ward and Sergey Kovalev was one of the most controversial in boxing a year ago.
Regardless of the Kovalev camp trying to stir a controversy over the borderline shots, Ward was the deserved victor.
"I couldn't believe it, I could win", he said. "Great fighters have to raise their game to the next level, and that's what I had to do tonight". It doesn't mean you stop a fight every time somebody gets hurt.
'I don't have anything on the books right now for a cruiserweight fight, a heavyweight fight. In the second round Kovalev used an effective jab.
As the fight progressed, body shots (and a couple of low/borderline blows) from Ward started taking a toll on the Russian. Kovalev (30-2-1, 26 KOs) was badly hurt, and Ward went to him and began firing away. "I wasn't hurt and I could continue". The blow left Kovalev bent over in agony which resulted in Weeks calling a halt to the fight.
What Kovalev didn't address was his mounting fatigue and the punch that started it all-a clean, crisp shot to the jaw that put him in trouble in the first place.
According to CompuBox punch statistics, Ward landed only 80 of 238 punches (34 percent); Kovalev landed 95 of 407 (23 percent). "I thought I was doing very good".
"Is it possible for me to get on the Pound for Pound list now (at number one)?"
There were two questionable blows around the belt line that Kovalev felt were below the belt and he protested.
Ward, who won an Olympic gold in 2004 and hasn't lost a fight since he was 12, took a few rounds to find his mark but once he did the two engaged in close rounds that were hard to score. And now he's lost two fights consecutively, and has been stopped inside the distance for the first time in his career. Neither made any effort to touch gloves when given their final instructions, and once the bell rang, they both went after each other.
Even the one judge who had Kovalev ahead by three points entering Round 8 would have likely had Sergey ahead by a mere point heading into Round 9, assuming Ward would have been granted a 10-8 round.
Yet, while Kovalev added, "I want to get another fight", the rivalry seems to be over with no rematch clause in effect and Ward saying afterward he might want to move to cruiserweight.
And Ward emphasized that he was dealing with as much remorse as Kovalev was.
'I don't think Kovalev complained about it, he was in a submissive position.
In his post-fight interview, Kovalev questioned the intervention of Weeks and suggested that he had received an illegal punch.
On the undercard, two-time Olympic gold medalist Guillermo Rigondeaux defeated Moises Flores with a controversial fight-ending punch at the close of the first round to retain his WBA junior featherweight title.
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American student death prompts call for North Korea to release detainees
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Will Grier gets green light to play in 2017 for West Virginia
WVU fans have more than enough reason to be excited about Grier, seeing what he did with Florida's offense. He transferred to WVU after the season, then sat out the 2016 season under NCAA transfer rules.
Snap rival Instagram Stories' growth weighs on shares
Snap shares declined about 3 percent after the new Instagram Stories daily active user numbers were announced . This feature is part of Instagram version 10.26 which is now out for both iOS and Android .
Portuguese revenue authority investigating alleged tax fraud by Cristiano Ronaldo
In December, leaked documents suggested that Ronaldo had avoided tax on income allegedly held in offshore accounts. Cristiano Ronaldo has denied ever hiding any income from the taxman or committing any tax fraud in Spain .
Trump calls Warmbier's death a 'total disgrace'
Yun learned about Warmbier's condition in a meeting a week before the release from the North Korean ambassador at the U.N.in NY . Instead, he spent 17 months there in detention where his family believes he was tortured into a vegetative state.
With No. 1 draft pick, Sixers now say they 'control our circumstances'
But Al Jefferson and Avery Bradley were both solid picks late in the first round, and Jaylen Brown seems like a fine player. The 76ers were in position to make the deal because of the assets they acquired under former general manager Sam Hinkie.
Chinese tour agency axes visits to North Korea for U.S. citizens
Warmbier was sentenced to 15 years of hard labor, but was released and medically evacuated 17 months later. The University of Virginia student's parents said the 22 year old "has completed his journey home".
Tropical storm warning issued for Louisiana's Gulf Coast
Oil traders from Texas to Louisiana braced on Tuesday for supply disruptions as a potential tropical storm developing in the U.S. A tropical storm warning is in effect for Trinidad, Tobago, Grenada, part of Venezuela's east coast and Isla de Margarita.
Rafael Nadal wins historic 10th French Open title
Wawrinka began to strike some winners off his backhand, but could not find the necessary breakthrough while leading 15-30 at 1-3. Nine-time champion Rafael Nadal has won the second set of the French Open final 6-3 and leads third-seeded Stan Wawrinka 2-0.
Real Madrid reject Ronaldo exit talk
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Ronaldo summoned to answer judge's questions on tax fraud
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text:
using System;
using System.Collections.Generic;
using System.Xml.Serialization;
using System.Text;

namespace Amazon.EC2.Model
{
    /// <summary>
    /// Disassociates the specified elastic IP address
    /// from the instance to which it is assigned.
    /// </summary>
    /// <remarks>
    /// This is an idempotent operation. If you call it more
    /// than once, Amazon EC2 does not return an error.
    /// </remarks>
    [XmlRootAttribute(IsNullable = false)]
    public class DisassociateAddressRequest : EC2Request
    {
        private string publicIpField;
        private string associationIdField;

        /// <summary>
        /// IP address that you are disassociating from the instance.
        /// </summary>
        [XmlElementAttribute(ElementName = "PublicIp")]
        public string PublicIp
        {
            get { return this.publicIpField; }
            set { this.publicIpField = value; }
        }

        /// <summary>
        /// Sets the IP address that you are disassociating from the instance.
        /// </summary>
        /// <param name="publicIp">IP address that you are disassociating from
        /// the instance.</param>
        /// <returns>this instance</returns>
        [Obsolete("The With methods are obsolete and will be removed in version 2 of the AWS SDK for .NET. See http://aws.amazon.com/sdkfornet/#version2 for more information.")]
        public DisassociateAddressRequest WithPublicIp(string publicIp)
        {
            this.publicIpField = publicIp;
            return this;
        }

        /// <summary>
        /// Checks if PublicIp property is set
        /// </summary>
        /// <returns>true if PublicIp property is set</returns>
        public bool IsSetPublicIp()
        {
            return this.publicIpField != null;
        }

        /// <summary>
        /// Association ID corresponding to the VPC elastic IP address
        /// you want to disassociate.
        ///
        /// Condition: Required for VPC elastic IP addresses
        /// </summary>
        [XmlElementAttribute(ElementName = "AssociationId")]
        public string AssociationId
        {
            get { return this.associationIdField; }
            set { this.associationIdField = value; }
        }

        /// <summary>
        /// Sets the Association ID corresponding to the VPC elastic IP address
        /// you want to disassociate.
        /// </summary>
        /// <param name="associationId">Association ID corresponding to the VPC elastic IP address
        /// you want to disassociate.
        ///
        /// Condition: Required for VPC elastic IP addresses</param>
        /// <returns>this instance</returns>
        [Obsolete("The With methods are obsolete and will be removed in version 2 of the AWS SDK for .NET. See http://aws.amazon.com/sdkfornet/#version2 for more information.")]
        public DisassociateAddressRequest WithAssociationId(string associationId)
        {
            this.associationIdField = associationId;
            return this;
        }

        /// <summary>
        /// Checks if AssociationId property is set
        /// </summary>
        /// <returns>true if AssociationId property is set</returns>
        public bool IsSetAssociationId()
        {
            return this.associationIdField != null;
        }

    }
}


text:
British artists end the Olympic grand finale
26Feb 2012 26 Feb 2012
Music mash up closes out 2012 Olympics in London
LONDON – Britain may not dominate the podium at the 2012 Olympics, but it will rule the closing ceremony — an all-British spectacular celebrating the country's music "from Elgar to Adele."
Organizers announced Thursday that the ceremony theme will be "A Symphony of British Music," and will include established and up-and-coming artists performing a jukebox-full of iconic British songs.
"It is, in a sense, the soundtrack of our lives," said film and theater director Stephen Daldry, executive producer of the Olympic and Paralympic opening and closing ceremonies.
The ceremony's artistic director, Kim Gavin, said the Aug. 12 show would be an "elegant mashup of British music" packed with recognizable songs arranged in a symphonic structure.
The London Symphony Orchestra will provide musical backing for the celebration of a century of British popular music that stretches back to the late Edward Elgar, composer of the "Pomp and Circumstance Marches" and other staples of the classical repertoire.
Music director David Arnold said all the music, and all the performers, would be British.
"We go from — without saying we've booked anyone — Elgar to Adele," Arnold said.
The creative team is keeping the names of the musicians involved under wraps, although The Rolling Stones, Paul McCartney and the Spice Girls have all been suggested as possible performers.
Olympic officials did not say whether Adele, Britain's hottest musical export of the moment, had been asked to take part. The singer-songwriter's album "21" has spent a year on the charts, winning six Grammys earlier this month, including album of the year. Adele also won two trophies Tuesday at the Brit music awards.
Gavin, who has overseen tours for the band Take That and directed London's 2007 Princess Diana memorial concert, said the London Olympics closing ceremony would be "the biggest after-show party — the show being the sport."
His creative team is experienced at delivering spectacular shows. Arnold's credits include the James Bond films "Casino Royale" and "Quantum of Solace" and the TV series "Sherlock," while designer Es Devlin has created sets for tours by Kanye West, Jay Z and Lady Gaga and lighting designer Patrick Woodroofe has worked with Elton John and the Rolling Stones.
Devlin said the show, which will include 3,500 volunteer performers and hundreds of local schoolchildren, would be a visual extravaganza drawing on icons of British art and design.
The ceremony also will include a Carnival-style segment from the host of the 2016 games, Rio de Janeiro.
Branding of the event suggests London is aiming for a plucky, irreverent tone that makes a contrast to Beijing's 2008 Olympic closer, which was heavy on precision displays of fireworks, acrobatics and dancing.
The "Symphony of British Music" logo adopts a cut-and-paste type font and Union Jack backdrop that evokes the punk era.
While the July 27 Olympic opening ceremony, directed by "Slumdog Millionaire" director Danny Boyle, promises references to Shakespeare's "The Tempest," east London's industrial past, London buses and Britain's health service, the closer's aims sound more straightforward.
Gavin promised a "very colorful visual spectacular, one that will make you feel great walking home."
Some of the difference between the two ceremonies is the result of logistics. While Boyle can spend days preparing the Olympic Stadium for his opener, Gavin said he has 17 hours between the end of sporting events and the start of the final ceremony.
World Sports News
Tags: 2012 Olympics, Lond, London, U.S. Sports News, World sports news
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text:
est un film américain réalisé par Herbert Brenon et sorti en 1921.

Synopsis
En état d'ébriété, Laurence, le fils cadet des Mannerby, falsifie un chèque de 50 £ pour payer une dette à Carser, un joueur. Jacqueline Boggs, une jeune Américaine en visite chez les Mannerby, tombe amoureuse de Donald, qui l'épouse dans le but de résoudre les difficultés financières de la famille ; mais son sens de l'honneur l'empêche d'utiliser son argent. Donald rembourse cependant partiellement Carser, en vertu d'un accord selon lequel Laurence ne quittera pas la juridiction des tribunaux britanniques.

Fiche technique
 Réalisation : Herbert Brenon
 Scénario : Clara Beranger, Herbert Brenon d'après la pièce The Wonderfull Thing de Lillian Trimble Bradley et Forrest Halsey
 Production : Norma Talmadge Film Corporation
 Photographie : J. Roy Hunt
 Distributeur : Associated First National Pictures
 Durée : 70 minutes (7 bobines)
 Date de sortie :  (USA)

Distribution
 Norma Talmadge : Jacqueline Laurentine Boggs
 Harrison Ford : Donald Mannerby
 Julia Hoyt : Catherine Mannerby
 Howard Truesdale : James Sheridan Boggs
 Robert Agnew : Laurence Mannerby
 Ethel Fleming : Dulcie Mannerby Fosdick
 Mabel Bert : Lady Sophia Alexandria Mannerby
 Fanny Burke : Angelica Mannerby
 Walter McEwen : 'Smooth Bill' Carser
 Charles Craig : General Lancaster

Notes et références

Voir aussi

Liens externes

Film américain sorti en 1921
Film dramatique américain
Film américain en noir et blanc
Film muet américain
Adaptation d'une pièce de théâtre américaine au cinéma