Nature © Macmillan Publishers Ltd 1997the same direction. A zero value of H j indicates ferromagnetically coupled films. H j is known 7,14 to oscillate as a function of t because of the RKKY interaction. We can clearly distinguish two situations. In Fig. 4b (Cu spacer grown at room temperature) only a few oscillations take place, the oscillation with the short wavelength l being marginal. This is in contrast to the theoretical expectations 7 , which require l to dominate over Λ for geometrically perfect samples. On the other hand, when the Cu spacer is grown at low temperatures, more oscillations appear (Fig. 4c), and l dominates over Λ. We note that cooling a room-temperature-deposited wedge structure does not change the results given in Fig. 4b. Thus, lowtemperature deposition is essential to minimize thickness fluctuations. We also note that, in for example Fe/Cr multilayers, just the opposite occurs: the shortest-wavelength oscillation is favoured by high-temperature growth 15 .The smallest oscillations detected in this experiment correspond to an energy change of ϳ10 −8 eV per atom. This value represents a challenge both to first-principles calculations and to spectroscopies aimed at unveiling the electronic structure of solids. Moreover, although exceedingly small, this energy scale participates in deter-mining a macroscopic observable (in this case the threshold magnetic field H s ) and thus might play an important role in the design of metallic nanostructures for device application. Ⅺ

Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient1, especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders2. Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9)3,4 technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals). As a proof of concept of its therapeutic potential, we demonstrate the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa. The HITI method presented here establishes new avenues for basic research and targeted gene therapies.

SUMMARY Aging is the major risk factor for many human diseases. In vitro studies have demonstrated that cellular reprogramming to pluripotency reverses cellular age, but alteration of the aging process through reprogramming has not been directly demonstrated in vivo. Here, we report that partial reprogramming by short-term cyclic expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) ameliorates cellular and physiological hallmarks of aging and prolongs lifespan in a mouse model of premature aging. Similarly, expression of OSKM in vivo improves recovery from metabolic disease and muscle injury in older wild-type mice. The amelioration of age-associated phenotypes by epigenetic remodeling during cellular reprogramming highlights the role of epigenetic dysregulation as a driver of mammalian aging. Establishing in vivo platforms to modulate age-associated epigenetic marks may provide further insights into the biology of aging.

Background Lipoinjection is a promising treatment but has some problems, such as unpredictability and a low rate of graft survival due to partial necrosis. Methods To overcome the problems with lipoinjection, the authors developed a novel strategy known as cellassisted lipotransfer (CAL). In CAL, autologous adiposederived stem (stromal) cells (ASCs) are used in combination with lipoinjection. A stromal vascular fraction (SVF) containing ASCs is freshly isolated from half of the aspirated fat and recombined with the other half. This process converts relatively ASC-poor aspirated fat to ASC-rich fat. This report presents the findings for 40 patients who underwent CAL for cosmetic breast augmentation.Results Final breast volume showed augmentation by 100 to 200 ml after a mean fat amount of 270 ml was injected. Postoperative atrophy of injected fat was minimal and did not change substantially after 2 months. Cyst formation or microcalcification was detected in four patients. Almost all the patients were satisfied with the soft and naturalappearing augmentation. Conclusions The preliminary results suggest that CAL is effective and safe for soft tissue augmentation and superior to conventional lipoinjection. Additional study is necessary to evaluate the efficacy of this technique further.

Our results suggest that CAL is both effective and safe and potentially superior to conventional lipoinjection for facial recontouring. The authors have indicated no significant interest with commercial supporters.

Breast enhancement with artificial implants is one of the most frequently performed cosmetic surgeries but is associated with various complications, such as capsular contracture, that lead to implant removal or replacement at a relatively high rate. For replacement, we used transplantation of progenitor-supplemented adipose tissue (cell-assisted lipotransfer; CAL) in 15 patients. The stromal vascular fraction containing adipose tissue progenitor cells obtained from liposuction aspirates was used to enrich for progenitor cells in the graft. Overall, clinical results were very satisfactory, and no major abnormalities were seen on magnetic resonance imaging or mammogram after 12 months. Postoperative atrophy of injected fat was minimal and did not change substantially after 2 months. Surviving fat volume at 12 months was 155 +/- 50 mL (Right; mean +/- SD) and 143 +/- 80 mL (Left) following lipoinjection from an initial mean of 264 mL. These preliminary results suggest that CAL is a suitable methodology for the replacement of breast implants.

Excessive centrifugation can destroy adipocytes and adipose-derived stem cells, but appropriate centrifugation concentrates them, resulting in enhanced graft take. The authors tentatively recommend 1200 g as an optimized centrifugal force for obtaining good short- and long-term results in adipose transplantation.

Large cutaneous ulcers are, in severe cases, life threatening. As the global population ages, non-healing ulcers are becoming increasingly common. Treatment currently requires the transplantation of pre-existing epithelial components, such as skin grafts, or therapy using cultured cells. Here we develop alternative supplies of epidermal coverage for the treatment of these kinds of wounds. We generated expandable epithelial tissues using in vivo reprogramming of wound-resident mesenchymal cells. Transduction of four transcription factors that specify the skin-cell lineage enabled efficient and rapid de novo epithelialization from the surface of cutaneous ulcers in mice. Our findings may provide a new therapeutic avenue for treating skin wounds and could be extended to other disease situations in which tissue homeostasis and repair are impaired.