Showing papers by "Ludwig Maximilian University of Munich published in 2008"

Simultaneous inference in general parametric models.

Abstract: Simultaneous inference is a common problem in many areas of application. If multiple null hypotheses are tested simultaneously, the probability of rejecting erroneously at least one of them increases beyond the pre-specified significance level. Simultaneous inference procedures have to be used which adjust for multiplicity and thus control the overall type I error rate. In this paper we describe simultaneous inference procedures in general parametric models, where the experimental questions are specified through a linear combination of elemental model parameters. The framework described here is quite general and extends the canonical theory of multiple comparison procedures in ANOVA models to linear regression problems, generalized linear models, linear mixed effects models, the Cox model, robust linear models, etc. Several examples using a variety of different statistical models illustrate the breadth

A Rapid Bootstrap Algorithm for the RAxML Web Servers

Abstract: Despite recent advances achieved by application of high-performance computing methods and novel algorithmic techniques to maximum likelihood (ML)-based inference programs, the major computational bottleneck still consists in the computation of bootstrap support values. Conducting a probably insufficient number of 100 bootstrap (BS) analyses with current ML programs on large datasets—either with respect to the number of taxa or base pairs—can easily require a month of run time. Therefore, we have developed, implemented, and thoroughly tested rapid bootstrap heuristics in RAxML (Randomized Axelerated Maximum Likelihood) that are more than an order of magnitude faster than current algorithms. These new heuristics can contribute to resolving the computational bottleneck and improve current methodology in phylogenetic analyses. Computational experiments to assess the performance and relative accuracy of these heuristics were conducted on 22 diverse DNA and AA (amino acid), single gene as well as multigene, real-world alignments containing 125 up to 7764 sequences. The standard BS (SBS) and rapid BS (RBS) values drawn on the best-scoring ML tree are highly correlated and show almost identical average support values. The weighted RF (Robinson-Foulds) distance between SBS- and RBS-based consensus trees was smaller than 6% in all cases (average 4%). More importantly, RBS inferences are between 8 and 20 times faster (average 14.73) than SBS analyses with RAxML and between 18 and 495 times faster than BS analyses with competing programs, such as PHYML or GARLI. Moreover, this performance improvement increases with alignment size. Finally, we have set up two freely accessible Web servers for this significantly improved version of RAxML that provide access to the 200-CPU cluster of the Vital-IT unit at the Swiss Institute of Bioinformatics and the 128-CPU cluster of the CIPRES project at the San Diego Supercomputer Center. These Web servers offer the possibility to conduct large-scale phylogenetic inferences to a large part of the community that does not have access to, or the expertise to use, high-performance computing resources. (Maximum likelihood; phylogenetic inference; rapid bootstrap; RAxML; support values.)

Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization

Abstract: Inhalation of silica crystals causes inflammation in the alveolar space. Prolonged exposure to silica can lead to the development of silicosis, an irreversible, fibrotic pulmonary disease. The mechanisms by which silica and other crystals activate immune cells are not well understood. Here we demonstrate that silica and aluminum salt crystals activated inflammasomes formed by the cytoplasmic receptor NALP3. NALP3 activation required phagocytosis of crystals, and this uptake subsequently led to lysosomal damage and rupture. 'Sterile' lysosomal damage (without crystals) also induced NALP3 activation, and inhibition of either phagosomal acidification or cathepsin B activity impaired NALP3 activation. Our results indicate that the NALP3 inflammasome senses lysosomal damage as an endogenous 'danger' signal.

Superconductivity at 38 K in the iron arsenide (Ba1-xKx)Fe2As2.

Abstract: The ternary iron arsenide ${\mathrm{BaFe}}_{2}{\mathrm{As}}_{2}$ becomes superconducting by hole doping, which was achieved by partial substitution of the barium site with potassium. We have discovered bulk superconductivity at ${T}_{c}=38\text{ }\text{ }\mathrm{K}$ in $({\mathrm{Ba}}_{1\ensuremath{-}x}{\mathrm{K}}_{x}){\mathrm{Fe}}_{2}{\mathrm{As}}_{2}$ with $x\ensuremath{\approx}0.4$. The parent compound ${\mathrm{BaFe}}_{2}{\mathrm{As}}_{2}$ crystallizes in the tetragonal ${\mathrm{ThCr}}_{2}{\mathrm{Si}}_{2}$-type structure, which consists of $(\mathrm{FeAs}{)}^{\ensuremath{\delta}\ensuremath{-}}$ iron arsenide layers separated by ${\mathrm{Ba}}^{2+}$ ions. ${\mathrm{BaFe}}_{2}{\mathrm{As}}_{2}$ is a poor metal and exhibits a spin density wave anomaly at 140 K. By substituting ${\mathrm{Ba}}^{2+}$ for ${\mathrm{K}}^{+}$ ions we have introduced holes in the $(\mathrm{FeAs}{)}^{\ensuremath{-}}$ layers, which suppress the anomaly and induce superconductivity. The ${T}_{c}$ of 38 K in $({\mathrm{Ba}}_{0.6}{\mathrm{K}}_{0.4}){\mathrm{Fe}}_{2}{\mathrm{As}}_{2}$ is the highest in hole doped iron arsenide superconductors so far. Therefore, we were able to expand this class of superconductors by oxygen-free compounds with the ${\mathrm{ThCr}}_{2}{\mathrm{Si}}_{2}$-type structure.

Conditional variable importance for random forests

Abstract: Random forests are becoming increasingly popular in many scientific fields because they can cope with "small n large p" problems, complex interactions and even highly correlated predictor variables. Their variable importance measures have recently been suggested as screening tools for, e.g., gene expression studies. However, these variable importance measures show a bias towards correlated predictor variables. We identify two mechanisms responsible for this finding: (i) A preference for the selection of correlated predictors in the tree building process and (ii) an additional advantage for correlated predictor variables induced by the unconditional permutation scheme that is employed in the computation of the variable importance measure. Based on these considerations we develop a new, conditional permutation scheme for the computation of the variable importance measure. The resulting conditional variable importance reflects the true impact of each predictor variable more reliably than the original marginal approach.

The LHCb detector at the LHC

Abstract: The LHCb experiment is dedicated to precision measurements of CP violation and rare decays of B hadrons at the Large Hadron Collider (LHC) at CERN (Geneva). The initial configuration and expected performance of the detector and associated systems, as established by test beam measurements and simulation studies, is described.

Large recurrent microdeletions associated with schizophrenia

Abstract: Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia.

Arbuscular mycorrhiza: the mother of plant root endosymbioses.

Abstract: Arbuscular mycorrhiza (AM), a symbiosis between plants and members of an ancient phylum of fungi, the Glomeromycota, improves the supply of water and nutrients, such as phosphate and nitrogen, to the host plant. In return, up to 20% of plant-fixed carbon is transferred to the fungus. Nutrient transport occurs through symbiotic structures inside plant root cells known as arbuscules. AM development is accompanied by an exchange of signalling molecules between the symbionts. A novel class of plant hormones known as strigolactones are exuded by the plant roots. On the one hand, strigolactones stimulate fungal metabolism and branching. On the other hand, they also trigger seed germination of parasitic plants. Fungi release signalling molecules, in the form of 'Myc factors' that trigger symbiotic root responses. Plant genes required for AM development have been characterized. During evolution, the genetic programme for AM has been recruited for other plant root symbioses: functional adaptation of a plant receptor kinase that is essential for AM symbiosis paved the way for nitrogen-fixing bacteria to form intracellular symbioses with plant cells.

Single-cycle nonlinear optics.

Abstract: Nonlinear optics plays a central role in the advancement of optical science and laser-based technologies. We report on the confinement of the nonlinear interaction of light with matter to a single wave cycle and demonstrate its utility for time-resolved and strong-field science. The electric field of 3.3-femtosecond, 0.72-micron laser pulses with a controlled and measured waveform ionizes atoms near the crests of the central wave cycle, with ionization being virtually switched off outside this interval. Isolated sub-100-attosecond pulses of extreme ultraviolet light (photon energy {approx} 80 electron volts), containing {approx} 0.5 nanojoule of energy, emerge from the interaction with a conversion efficiency of {approx} 10{sup -6}. These tools enable the study of the precision control of electron motion with light fields and electron-electron interactions with a resolution approaching the atomic unit of time ({approx} 24 attoseconds).

A Kernel Method for the Two-Sample Problem

Abstract: We propose a framework for analyzing and comparing distributions, allowing us to design statistical tests to determine if two samples are drawn from different distributions. Our test statistic is the largest difference in expectations over functions in the unit ball of a reproducing kernel Hilbert space (RKHS). We present two tests based on large deviation bounds for the test statistic, while a third is based on the asymptotic distribution of this statistic. The test statistic can be computed in quadratic time, although efficient linear time approximations are available. Several classical metrics on distributions are recovered when the function space used to compute the difference in expectations is allowed to be more general (eg. a Banach space). We apply our two-sample tests to a variety of problems, including attribute matching for databases using the Hungarian marriage method, where they perform strongly. Excellent performance is also obtained when comparing distributions over graphs, for which these are the first such tests.

Strong dispersive coupling of a high-finesse cavity to a micromechanical membrane.

Abstract: In recent years micromechanical devices have been developed that can strongly couple to light, by integrating them within optical cavities. A main goal has been to cool the devices optomechanically, freezing out all thermal vibrations, so that the object's motion eventually becomes limited by quantum mechanical fluctuations. This would make it possible to study a new range of quantum behaviour of mechanical objects. Thompson et al. report an improved design of such a system, involving a movable membrane sandwiched between two rigid high-quality mirrors. In previous designs one of the mirrors had to double-up as a microresonator. The new device achieves substantial cooling, from room temperature to 6.8 mK. It should eventually be possible to reach the quantum-limited ground state with this system. A report on an improved design of an optomechanical system in which a movable membrane is placed between two rigid high-quality mirrors, as opposed to previous designs where one of the mirrors has a double function as the microresonator; it's claimed that it is feasible to reach the quantum-limited ground state with this new design. Macroscopic mechanical objects and electromagnetic degrees of freedom can couple to each other through radiation pressure. Optomechanical systems in which this coupling is sufficiently strong are predicted to show quantum effects and are a topic of considerable interest. Devices in this regime would offer new types of control over the quantum state of both light and matter1,2,3,4, and would provide a new arena in which to explore the boundary between quantum and classical physics5,6,7. Experiments so far have achieved sufficient optomechanical coupling to laser-cool mechanical devices8,9,10,11,12, but have not yet reached the quantum regime. The outstanding technical challenge in this field is integrating sensitive micromechanical elements (which must be small, light and flexible) into high-finesse cavities (which are typically rigid and massive) without compromising the mechanical or optical properties of either. A second, and more fundamental, challenge is to read out the mechanical element’s energy eigenstate. Displacement measurements (no matter how sensitive) cannot determine an oscillator’s energy eigenstate13, and measurements coupling to quantities other than displacement14,15,16 have been difficult to realize in practice. Here we present an optomechanical system that has the potential to resolve both of these challenges. We demonstrate a cavity which is detuned by the motion of a 50-nm-thick dielectric membrane placed between two macroscopic, rigid, high-finesse mirrors. This approach segregates optical and mechanical functionality to physically distinct structures and avoids compromising either. It also allows for direct measurement of the square of the membrane’s displacement, and thus in principle the membrane’s energy eigenstate. We estimate that it should be practical to use this scheme to observe quantum jumps of a mechanical system, an important goal in the field of quantum measurement.

Coding for Errors and Erasures in Random Network Coding

Abstract: The problem of error-control in random linear network coding is considered. A ldquononcoherentrdquo or ldquochannel obliviousrdquo model is assumed where neither transmitter nor receiver is assumed to have knowledge of the channel transfer characteristic. Motivated by the property that linear network coding is vector-space preserving, information transmission is modeled as the injection into the network of a basis for a vector space V and the collection by the receiver of a basis for a vector space U. A metric on the projective geometry associated with the packet space is introduced, and it is shown that a minimum-distance decoder for this metric achieves correct decoding if the dimension of the space V capU is sufficiently large. If the dimension of each codeword is restricted to a fixed integer, the code forms a subset of a finite-field Grassmannian, or, equivalently, a subset of the vertices of the corresponding Grassmann graph. Sphere-packing and sphere-covering bounds as well as a generalization of the singleton bound are provided for such codes. Finally, a Reed-Solomon-like code construction, related to Gabidulin's construction of maximum rank-distance codes, is described and a Sudan-style ldquolist-1rdquo minimum-distance decoding algorithm is provided.

Identification of loci associated with schizophrenia by genome-wide association and follow-up

Abstract: We carried out a genome-wide association study of schizophrenia (479 cases, 2,937 controls) and tested loci with P < 10(-5) in up to 16,726 additional subjects. Of 12 loci followed up, 3 had strong independent support (P < 5 x 10(-4)), and the overall pattern of replication was unlikely to occur by chance (P = 9 x 10(-8)). Meta-analysis provided strongest evidence for association around ZNF804A (P = 1.61 x 10(-7)) and this strengthened when the affected phenotype included bipolar disorder (P = 9.96 x 10(-9)).

Tumor Regression in Cancer Patients by Very Low Doses of a T Cell–Engaging Antibody

Abstract: Previous attempts have shown the potential of T cells in immunotherapy of cancer. Here, we report on the clinical activity of a bispecific antibody construct called blinatumomab, which has the potential to engage all cytotoxic T cells in patients for lysis of cancer cells. Doses as low as 0.005 milligrams per square meter per day in non-Hodgkin's lymphoma patients led to an elimination of target cells in blood. Partial and complete tumor regressions were first observed at a dose level of 0.015 milligrams, and all seven patients treated at a dose level of 0.06 milligrams experienced a tumor regression. Blinatumomab also led to clearance of tumor cells from bone marrow and liver. T cell-engaging antibodies appear to have therapeutic potential for the treatment of malignant diseases.

Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60)

Abstract: Summary Background Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is used to treat patients with non-Hodgkin lymphoma. Interval decrease from 3 weeks of treatment (CHOP-21) to 2 weeks (CHOP-14), and addition of rituximab to CHOP-21 (R-CHOP-21) has been shown to improve outcome in elderly patients with diffuse large B-cell lymphoma (DLBCL). This randomised trial assessed whether six or eight cycles of R-CHOP-14 can improve outcome of these patients compared with six or eight cycles of CHOP-14. Methods 1222 elderly patients (aged 61–80 years) were randomly assigned to six or eight cycles of CHOP-14 with or without rituximab. Radiotherapy was planned to sites of initial bulky disease with or without extranodal involvement. The primary endpoint was event-free survival; secondary endpoints were response, progression during treatment, progression-free survival, overall survival, and frequency of toxic effects. Analyses were done by intention to treat. The trial is registered on National Cancer Institute website, number NCT00052936 and as EU-20243. Findings 3-year event-free survival was 47·2% after six cycles of CHOP-14 (95% CI 41·2–53·3), 53·0% (47·0–59·1) after eight cycles of CHOP-14, 66·5% (60·9–72·0) after six cycles of R-CHOP-14, and 63·1% (57·4–68·8) after eight cycles of R-CHOP-14. Compared with six cycles of CHOP-14, the improvement in 3-year event-free survival was 5·8% (−2·8–14·4) for eight cycles of CHOP-14, 19·3% (11·1–27·5) for six cycles of R-CHOP-14, and 15·9% (7·6–24·2) for eight cycles of R-CHOP-14. 3-year overall survival was 67·7% (62·0–73·5) for six cycles of CHOP-14, 66·0% (60·1–71·9) for eight cycles of CHOP-14, 78·1% (73·2–83·0) for six cycles of R-CHOP-14, and 72·5% (67·1–77·9) for eight cycles of R-CHOP-14. Compared with treatment with six cycles of CHOP-14, overall survival improved by −1·7% (−10·0–6·6) after eight cycles of CHOP-14, 10·4% (2·8–18·0) after six cycles of R-CHOP-14, and 4·8% (−3·1–12·7) after eight cycles of R-CHOP-14. In a multivariate analysis that used six cycles of CHOP-14 without rituximab as the reference, and adjusting for known prognostic factors, all three intensified regimens improved 3-year event-free survival (eight cycles of CHOP-14: RR [relative risk] 0·76 [0·60–0·95], p=0·0172; six cycles of R-CHOP-14: RR 0·51 [0·40–0·65], p Interpretation Six cycles of R-CHOP-14 significantly improved event-free, progression-free, and overall survival over six cycles of CHOP-14 treatment. Response-adapted addition of chemotherapy beyond six cycles, though widely practiced, is not justified. Of the four regimens assessed in this study, six cycles of R-CHOP-14 is the preferred treatment for elderly patients, with which other approaches should be compared.

Complementary Feeding: A Commentary by the ESPGHAN Committee on Nutrition

Abstract: This position paper on complementary feeding summarizes evidence for health effects of complementary foods. It focuses on healthy infants in Europe. After reviewing current knowledge and practices, we have formulated these conclusions: Exclusive or full breast-feeding for about 6 months is a desirable goal. Complementary feeding (ie, solid foods and liquids other than breast milk or infant formula and follow-on formula) should not be introduced before 17 weeks and not later than 26 weeks. There is no convincing scientific evidence that avoidance or delayed introduction of potentially allergenic foods, such as fish and eggs, reduces allergies, either in infants considered at increased risk for the development of allergy or in those not considered to be at increased risk. During the complementary feeding period, >90% of the iron requirements of a breast-fed infant must be met by complementary foods, which should provide sufficient bioavailable iron. Cow's milk is a poor source of iron and should not be used as the main drink before 12 months, although small volumes may be added to complementary foods. It is prudent to avoid both early ( or=7 months) introduction of gluten, and to introduce gluten gradually while the infant is still breast-fed, inasmuch as this may reduce the risk of celiac disease, type 1 diabetes mellitus, and wheat allergy. Infants and young children receiving a vegetarian diet should receive a sufficient amount ( approximately 500 mL) of breast milk or formula and dairy products. Infants and young children should not be fed a vegan diet.

Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease.

Abstract: The neurodegeneration observed in Alzheimer's disease has been associated with synaptic dismantling and progressive decrease in neuronal activity. We tested this hypothesis in vivo by using two-photon Ca2+ imaging in a mouse model of Alzheimer's disease. Although a decrease in neuronal activity was seen in 29% of layer 2/3 cortical neurons, 21% of neurons displayed an unexpected increase in the frequency of spontaneous Ca2+ transients. These "hyperactive" neurons were found exclusively near the plaques of amyloid beta-depositing mice. The hyperactivity appeared to be due to a relative decrease in synaptic inhibition. Thus, we suggest that a redistribution of synaptic drive between silent and hyperactive neurons, rather than an overall decrease in synaptic activity, provides a mechanism for the disturbed cortical function in Alzheimer's disease.

Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis

Abstract: 34 and the only effective treatment is liver transplantation. During the 56th Meeting of the American Association for the Study of Liver Diseases, the International Ascites Club held a Focused Study Group (FSG) on HRS for the purpose of reporting the results of an international workshop and to reach a consensus on a new definition, criteria for diagnosis and recommendations on HRS treatment. A similar workshop was held in Chicago in 1994 in which standardised nomenclature and diagnostic criteria for refractory ascites and HRS were established. 5 The introduction of innovative treatments and improvements in our understanding of the pathogenesis of HRS during the previous decade led to an increasing need to undertake a new consensus meeting. This paper reports the scientific rationale behind the new definitions and recommendations.

Spin-density-wave anomaly at 140 K in the ternary iron arsenide BaFe 2 As 2

Abstract: The ternary iron arsenide ${\text{BaFe}}_{2}{\text{As}}_{2}$, with the tetragonal ${\text{ThCr}}_{2}{\text{Si}}_{2}$-type structure, exhibits a spin-density-wave (SDW) anomaly at 140 K, very similar to LaFeAsO, which is the parent compound of the iron arsenide superconductors. ${\text{BaFe}}_{2}{\text{As}}_{2}$ is a poor Pauli-paramagnetic metal and undergoes a structural and magnetic phase transition at 140 K, accompanied by strong anomalies in the specific heat, electrical resistance, and magnetic susceptibility. In the course of this transition, the space-group symmetry changes from tetragonal $(I4/mmm)$ to orthorhombic $(Fmmm)$. $^{57}\text{F}\text{e}$ M\"ossbauer spectroscopy experiments show a single signal at room temperature and full hyperfine field splitting below the phase-transition temperature (5.2 T at 77 K). Our results suggest that ${\text{BaFe}}_{2}{\text{As}}_{2}$ can serve as a parent compound for oxygen-free iron arsenide superconductors.

Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine.

Abstract: Objective:To develop consensus statements for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients.Participants:A multidisciplinary, multispecialty task force of experts in critical care medicine was convened from the membership of the Society of Critical Car

A rational approach to perioperative fluid management.

Abstract: Replacement of assumed preoperative deficits, in addition to generous substitution of an unsubstantiated increased insensible perspiration and third space loss, plays an important role in current perioperative fluid regimens. The consequence is a positive fluid balance and weight gain of up to 10 kg, which may be related to severe complications. Because the intravascular blood volume remains unchanged and insensible perspiration is negligible, the fluid must accumulate inside the body. This concept brings into question common liberal infusion regimens. Blood volume after fasting is normal, and a fluid-consuming third space has never been reliably shown. Crystalloids physiologically load the interstitial space, whereas colloidal volume loading deteriorates a vital part of the vascular barrier. The endothelial glycocalyx plays a key role and is destroyed not only by ischemia and surgery, but also by acute hypervolemia. Therefore, undifferentiated fluid handling may increase the shift toward the interstitial space. Using the right kind of fluid in appropriate amounts at the right time might improve patient outcome.

Adipokines and insulin resistance.

Abstract: Obesity is associated with an array of health problems in adult and pediatric populations. Understanding the pathogenesis of obesity and its metabolic sequelae has advanced rapidly over the past decades. Adipose tissue represents an active endocrine organ that, in addition to regulating fat mass and nutrient homeostasis, releases a large number of bioactive mediators (adipokines) that signal to organs of metabolic importance including brain, liver, skeletal muscle, and the immune system— thereby modulating hemostasis, blood pressure, lipid and glucose metabolism, inflammation, and atherosclerosis. In the present review, we summarize current data on the effect of the adipose tissue-derived hormones adiponectin, chemerin, leptin, omentin, resistin, retinol binding protein 4, tumor necrosis factor-α and interleukin-6, vaspin, and visfatin on insulin resistance.

Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain.

Abstract: Reactive gliosis is the universal reaction to brain injury, but the precise origin and subsequent fate of the glial cells reacting to injury are unknown. Astrocytes react to injury by hypertrophy and up-regulation of the glial-fibrillary acidic protein (GFAP). Whereas mature astrocytes do not normally divide, a subpopulation of the reactive GFAP+ cells does so, prompting the question of whether the proliferating GFAP+ cells arise from endogenous glial progenitors or from mature astrocytes that start to proliferate in response to brain injury. Here we show by genetic fate mapping and cell type-specific viral targeting that quiescent astrocytes start to proliferate after stab wound injury and contribute to the reactive gliosis and proliferating GFAP+ cells. These proliferating astrocytes remain within their lineage in vivo, while a more favorable environment in vitro revealed their multipotency and capacity for self-renewal. Conversely, progenitors present in the adult mouse cerebral cortex labeled by NG2 or the receptor for the platelet-derived growth factor (PDGFRα) did not form neurospheres after (or before) brain injury. Taken together, the first fate-mapping analysis of astrocytes in the adult mouse cerebral cortex shows that some astrocytes acquire stem cell properties after injury and hence may provide a promising cell type to initiate repair after brain injury.