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We characterize the atomic processes that underlie forming, reset, and set in HfO2-based resistive random access memory (RRAM) cells through molecular dynamics (MD) simulations, using an extended charge equilibration method to describe external electric fields. By tracking the migration of oxygen ions and the change in coordination of Hf atoms in the dielectric, we characterize the formation and dissolution of conductive filaments (CFs) during the operation of the device with atomic detail. Simulations of the forming process show that the CFs form through an oxygen exchange mechanism, induced by a cascade of oxygen displacements from the oxide to the active electrode, as opposed to aggregation of pre-existing oxygen vacancies. However, the filament breakup is dominated by lateral, rather than vertical (along the filament), motion of vacancies. In addition, depending on the temperature of the system, the reset can be achieved through a redox effect (bipolar switch), where oxygen diffusion is governed by the applied bias, or by a thermochemical process (unipolar switch), where the diffusion is driven by temperature. Unlike forming and similar to reset, the set process involves lateral oxygen atoms as well. This is driven by field localization associated with conductive paths.

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Nanocarrier systems are currently being developed for peptide, protein and gene delivery to protect them in the blood circulation and in the gastrointestinal tract. Polylactic acid (PLA) and poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with a new antimicrobial GIBIM-P5S9K peptide were obtained by the double emulsion solvent extraction/evaporation method. PLA- and PLGA-NPs were spherical with sizes between 300 and 400 nm for PLA and 200 and 300 nm for PLGA and <0.3 polydispersity index as determined by dynamic light scattering and scanning electron microscopy), having the zeta potential of >20 mV. The peptide-loading efficiency of PLA-NP and PLGA-NPs was 75% and 55%, respectively. PLA- and PLGA-NPs released around 50% of this peptide over 8 h. In 10% human sera the size of peptide loaded PLA- and PLGA-NPs increased between 25.2% and 39.3%, the PDI changed from 3.2 to 5.1 and the surface charge from -7.15 to 14.6 mV. Both peptide loaded PLA- and PLGA-NPs at 0.5 µM peptide concentration inhibited the growth of Escherichia coli O157:H7 (E. coli O157:H7), methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas. aeruginosa (P. aeruginosa). In contrast, free peptide inhibited at 10 µM but did not inhibit at 0.5 and 1 µM. These PLA- and PLGA-NPs presented <10% hemolysis indicating that they are hemocompatible and promising for delivery and protection system of GIBIM-P5S9K peptide.

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A woman aged 38 was referred to this center for surrogacy treatment, after subtotal ablation of her uterus due to a severe postpartum hemorrhage. Her hormonal profiles and ovarian structure were normal. The husband proved fertile and semen analysis was normal. The carrier, a woman 39 years old, fertile with two children of her own, and a long bonding friendship with the patient. After hormonal stimulation with gonadotropins and GnRH antagonist, six mature oocytes were obtained. These originated four embryos after in vitro fertilization, three of which were transferred to the carrier, achieving a singleton pregnancy which led to the birth of a normal child, now more than a year old. A lawsuit was filed after birth requesting the baby be registered with the biological parents name. The judge granted the request based on evidence and testimonies provided, international jurisprudence history and specification in Article 19 of the Argentine Constitution: "No inhabitant of the Nation shall be obliged to do what the law does not demand .nor be deprived of what it does not prohibit". This is an almost ideal example of the proceedings in a case of subrogation. However, we must always bear in mind the fact that in our country there is as yet no regulatory framework for these treatments, therefore there is a high probability of conflict.

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Una mujer de 38 años de edad fue derivada a nuestro centro para un tratamiento de maternidad subrogada, por haber sufrido la ablación subtotal de su útero a causa de una hemorragia puerperal grave. Su perfil hormonal y estructura ovárica eran normales. El esposo tenía fertilidad probada y un espermograma normal. La subrogante era una mujer de 39 años, fértil, con dos hijos propios y con un largo vínculo de amistad con la paciente. Luego de una estimulación con gonadotropinas y antagonista de Gn-RH se obtuvieron 6 ovocitos maduros por punción folicular, que originaron 4 embriones por fertilización in vitro. Tres de ellos evolucionaron y fueron transferidos a la subrogante, lográndose un embarazo único que concluyó con el nacimiento de una niña normal que ya tiene dos años cumplidos. Se inició una acción solicitando la inscripción de la beba ya nacida a nombre de los padres procreacionales. El juez finalmente la otorgó basándose en las pruebas y testimonios aportados, los antecedentes en la jurisprudencia internacional, y el hecho de que según el artículo 19 de la Constitución Nacional: "Ningún habitante de la Nación será obligado a hacer lo que no manda la ley, ni privado de lo que ella no prohíbe". Este es un ejemplo casi ideal de cómo se puede desarrollar un caso de subrogación. Sin embargo, hay que tener en cuenta que en nuestro país no existe aún un marco regulatorio para estos tratamientos, por lo que no queda exenta la posibilidad de conflicto.

A woman aged 38 was referred to this center for surrogacy treatment, after subtotal ablation of her uterus due to a severe postpartum hemorrhage. Her hormonal profiles and ovarian structure were normal. The husband proved fertile and semen analysis was normal. The carrier, a woman 39 years old, fertile with two children of her own, and a long bonding friendship with the patient. After hormonal stimulation with gonadotropins and GnRH antagonist, six mature oocytes were obtained. These originated four embryos after in vitro fertilization, three of which were transferred to the carrier, achieving a singleton pregnancy which led to the birth of a normal child, now more than a year old. A lawsuit was filed after birth requesting the baby be registered with the biological parents name. The judge granted the request based on evidence and testimonies provided, international jurisprudence history and specification in Article 19 of the Argentine Constitution: "No inhabitant of the Nation shall be obliged to do what the law does not demand .nor be deprived of what it does not prohibit". This is an almost ideal example of the proceedings in a case of subrogation .However, we must always bear in mind the fact that in our country there is as yet no regulatory framework for these treatments, therefore there is a high probability of conflict.

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Una mujer de 38 años de edad fue derivada a nuestro centro para un tratamiento de maternidad subrogada, por haber sufrido la ablación subtotal de su útero a causa de una hemorragia puerperal grave. Su perfil hormonal y estructura ovárica eran normales. El esposo tenía fertilidad probada y un espermograma normal. La subrogante era una mujer de 39 años, fértil, con dos hijos propios y con un largo vínculo de amistad con la paciente. Luego de una estimulación con gonadotropinas y antagonista de Gn-RH se obtuvieron 6 ovocitos maduros por punción folicular, que originaron 4 embriones por fertilización in vitro. Tres de ellos evolucionaron y fueron transferidos a la subrogante, lográndose un embarazo único que concluyó con el nacimiento de una niña normal que ya tiene dos años cumplidos. Se inició una acción solicitando la inscripción de la beba ya nacida a nombre de los padres procreacionales. El juez finalmente la otorgó basándose en las pruebas y testimonios aportados, los antecedentes en la jurisprudencia internacional, y el hecho de que según el artículo 19 de la Constitución Nacional: "Ningún habitante de la Nación será obligado a hacer lo que no manda la ley, ni privado de lo que ella no prohíbe". Este es un ejemplo casi ideal de cómo se puede desarrollar un caso de subrogación. Sin embargo, hay que tener en cuenta que en nuestro país no existe aún un marco regulatorio para estos tratamientos, por lo que no queda exenta la posibilidad de conflicto.(AU)

A woman aged 38 was referred to this center for surrogacy treatment, after subtotal ablation of her uterus due to a severe postpartum hemorrhage. Her hormonal profiles and ovarian structure were normal. The husband proved fertile and semen analysis was normal. The carrier, a woman 39 years old, fertile with two children of her own, and a long bonding friendship with the patient. After hormonal stimulation with gonadotropins and GnRH antagonist, six mature oocytes were obtained. These originated four embryos after in vitro fertilization, three of which were transferred to the carrier, achieving a singleton pregnancy which led to the birth of a normal child, now more than a year old. A lawsuit was filed after birth requesting the baby be registered with the biological parents name. The judge granted the request based on evidence and testimonies provided, international jurisprudence history and specification in Article 19 of the Argentine Constitution: "No inhabitant of the Nation shall be obliged to do what the law does not demand .nor be deprived of what it does not prohibit". This is an almost ideal example of the proceedings in a case of subrogation .However, we must always bear in mind the fact that in our country there is as yet no regulatory framework for these treatments, therefore there is a high probability of conflict.(AU)

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A woman aged 38 was referred to this center for surrogacy treatment, after subtotal ablation of her uterus due to a severe postpartum hemorrhage. Her hormonal profiles and ovarian structure were normal. The husband proved fertile and semen analysis was normal. The carrier, a woman 39 years old, fertile with two children of her own, and a long bonding friendship with the patient. After hormonal stimulation with gonadotropins and GnRH antagonist, six mature oocytes were obtained. These originated four embryos after in vitro fertilization, three of which were transferred to the carrier, achieving a singleton pregnancy which led to the birth of a normal child, now more than a year old. A lawsuit was filed after birth requesting the baby be registered with the biological parents name. The judge granted the request based on evidence and testimonies provided, international jurisprudence history and specification in Article 19 of the Argentine Constitution: "No inhabitant of the Nation shall be obliged to do what the law does not demand .nor be deprived of what it does not prohibit". This is an almost ideal example of the proceedings in a case of subrogation. However, we must always bear in mind the fact that in our country there is as yet no regulatory framework for these treatments, therefore there is a high probability of conflict.

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A 45-year-old woman received embryos from IVF by intracytoplasmic sperm injection (ICSI) with her own oocytes that were cryopreserved (slow freezing in a low-sodium medium) 11 years and 7 and a half months before, when she was 33 years old. From seven metaphase-II oocytes thawed, five survived, four were fertilized after ICSI and two cleaving embryos were transferred on day 3. A diamniotic dichorionic term pregnancy was achieved, ending with the delivery of two healthy girls. As far as is known, this case represents, to date, the longest storage period of cryopreserved human oocytes resulting in a live birth.

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Ad-ISF35 is an adenovirus (Ad) vector that encodes a mouse-human chimeric CD154. Ad-ISF35 induces activation of chronic lymphocytic leukemia (CLL) cells converting them into CLL cells capable of promoting immune recognition and anti-leukemia T-cell activation. Clinical trials in humans treated with Ad-ISF35-transduced leukemia cells or intranodal injection of Ad-ISF35 have shown objective clinical responses. To better understand the biology of Ad-ISF35 and to contribute to its clinical development, we preformed studies to evaluate biodistribution, persistence and toxicity of repeat dose intratumoral administration of Ad-ISF35 in a mouse model. Ad-ISF35 intratumoral administration induced tumor regression in more than 80% of mice bearing A20 tumors. There were no abnormalities in the serum chemistry. Mice receiving Ad-ISF35 presented severe extramedullary hematopoiesis and follicular hyperplasia in the spleen and extramedullary hematopoiesis with lymphoid hyperplasia in lymph nodes. After Ad-ISF35 injection, the vector was found primarily in the injected tumors with a biodistribution pattern that showed a rapid clearance with no evidence of Ad-ISF35 accumulation or persistence in the injected tumor or peripheral organs. Furthermore, pre-existing antibodies against Ad-5 did not abrogate Ad-ISF35 anti-tumor activity. In conclusion, intratumoral administration of Ad-ISF35 induced tumor regression in A20 tumor bearing mice without toxicities and with no evidence of vector accumulation or persistence.

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The prevalence of human papillomavirus (HPV) infections in 2109 females inhabiting five cities of Colombia was determined. Of the 49.2% with an HPV infection, 59.8% were infected with more than one viral type. Species 7 (of the the genus Alphapapillomavirus) was associated with multiple infections. Analysis of the socio-demographic data revealed a statistically significant protective effect associated with the status of civil union (civil recognition of cohabitation without marriage), and indigenous ethnicity proved to be a risk factor for HPV infection. This is the first study comparing HPV infection among women from geographical regions of Colombia with different socio-cultural structures.

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The erythrocyte-binding antigen 140 (EBA140) sequence was chemically synthesized in 61 20-mer sequential peptides covering the entire 3D7 protein strain, each of which was tested in erythrocyte-binding assays. Peptides 26135, 26144, 26147, 26160, 26170 and 26177 presented high erythrocyte-binding activity, with affinity constants ranging from 350 to 750 nM. Critical erythrocyte-binding residues were determined by competition-binding assays with glycine analogous peptides. Cross-linking assays with SDS-PAGE from high erythrocyte membrane protein binding peptides showed that all these peptides bound specifically to 25, 52 and 75 kDa erythrocyte membrane proteins. The nature of these receptor sites was studied in peptide-binding assays using enzyme-treated erythrocytes, showing that these protein receptors are susceptible to structural changes provoked by enzyme treatment (neuraminidase, trypsin or chymotrypsin). Inhibition invasion assays in 'in vitro' cultures showed that all specific high binding sequences were able to inhibit invasion by 11-69% at 200 microM concentration.

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Plasmodium falciparum sporozoite surface protein 2 (Pf SSP2), also called thrombospondin related anonymous protein (TRAP), is involved in the process of sporozoite invasion of hepatocytes. Pf SSP2/TRAP possesses two different adhesion domains sharing sequences and structural homology with von Willebrand factor A-domains and human repeat I thrombospondin (TSP). Pf SSP2/TRAP has also been implicated in sporozoite mobility and in mosquito salivary gland invasion processes. We tested 15-mer long synthetic peptides having five overlapping residues covering the complete protein Pf SSP2 sequence in binding assays to Hep G2 cells. In these 57 peptides, 21 high-activity binding peptides (HABPs) were identified; five were in the adhesion domains already described and 16 were in two regions toward the protein's carboxy and middle terminal part. Six HABPs showed conserved amino acid sequences: 3243 (21FLVNGRDVQNNIVDE35), 3279 (201FLVGCHPSDGKCNLY215), 3287 (241TASCGVWDEWSPCSV255), 3289 (251SPCSVTCGKGTRSRK265), 3327 (441ERKQSDPQSQDNNGNY455) and 3329 (451DNNGNRHVPNSEDREY465). The HABPs show saturable binding and dissociation constants between 140 and 900 nm with 40 000-855 000 binding sites per cell. The 3279 (201FLVGCHPSDGKCNLY215), 3323 (421NDKSDRYIPYSPLSP435) and 3331 (461SEDRETRPHGRNNENY475) HABPs have B epitopes in their sequences; these have previously been recognized by antibodies partially inhibiting hepatocyte invasion and development of the hepatic state. The 3287 (241TASCGVWDEWSPCSV255) and 3289 (251SPCSVTCGKGTRSRK265) HABPs share common sequences with the Pf SSP2/TRAP region II plus, which is present in a great number of adhesion proteins. Based on this information, six new peptides covering the high binding regions identified previously were synthesized and, using a competition assay, the amino acid involved in the binding were determined.

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Hepatocyte invasion by malaria parasites is mediated by specific molecular interactions. Several lines of evidence suggest the importance of the surface plasmodial circumsporozoite (CS) protein in the sporozoite invasion of hepatocytes. Identification of the sequences involved in binding to hepatocytes is an important step towards understanding the structural basis for the sporozoite-hepatocyte interaction. In this study, binding assays between Plasmodium falciparum CS peptides and HepG2 cells were performed. Fifteen overlapping residue 20 mer long peptides, spanning the entire CS sequence, were tested in HepG2 cell binding assays. Five High Binding Activity Peptides (HBAPs) to HepG2 cells were identified: 4593, (NANPNANPNANP); 4383, (NSRSLGENDDGNNEDNEKLR); 4388, (GNGQGHNMPNDPNRNVDENA); 4389, (HNMPNDPNRNVDENANANSA) and 4390, (DPNRNVDENANANSAVKNNN). The HBAP HepG2 interaction is independent of charge and amino-acid composition, but sequence dependent. Four HBAPs (4383, 4388, 4389 and 4390) are bound with similar affinity to a 50 kDa molecule. These HBAPs define three Hepatocyte Binding Sequences (HBSs): HBS-1, located between residues 68 and 87 (HBAP 4383); HBS-11, the repeat NANP region (HBAP 4593), for which anti repeat antibodies are able to specifically inhibit sporozoite invasion of hepatocytes have been reported; and HBS-111, between residues 286 and 315 (HBAPs 4388, 4388 and 4390), respectively. Interestingly, HBS 111 carries two earlier-reported B-epitopes (underlined) in peptides 4388, 4389 and 4390 (GNGQGHNMPNDPNRNVD ENANANSAVKNN) in its sequence. The HBSs reported here show lesser interspecie-variability than the entire protein in species invading the same kind of hepatic cells. This data supports these HBSs' important role in CS-protein function; they could be used as ligand by the sporozoite to invade hepatic cells.

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