QuickDrop: Efficient Federated Unlearning by Integrated Dataset Distillation

Federated Unlearning (FU) aims to delete specific training data from an ML model trained using Federated Learning (FL). We introduce QuickDrop, an efficient and original FU method that utilizes dataset distillation (DD) to accelerate unlearning and drastically reduces computational overhead compared to existing approaches. In QuickDrop, each client uses DD to generate a compact dataset representative of the original training dataset, called a distilled dataset, and uses this compact dataset during unlearning. To unlearn specific knowledge from the global model, QuickDrop has clients execute Stochastic Gradient Ascent with samples from the distilled datasets, thus significantly reducing computational overhead compared to conventional FU methods. We further increase the efficiency of QuickDrop by ingeniously integrating DD into the FL training process. By reusing the gradient updates produced during FL training for DD, the overhead of creating distilled datasets becomes close to negligible. Evaluations on three standard datasets show that, with comparable accuracy guarantees, QuickDrop reduces the duration of unlearning by 463.8x compared to model retraining from scratch and 65.1x compared to existing FU approaches. We also demonstrate the scalability of QuickDrop with 100 clients and show its effectiveness while handling multiple unlearning operations

Therapeutic effects of combined meloxicam and glucosamine sulfate treatment on patients with osteoarthritis, and its effect on serum CTX-Ⅰ, CTX-Ⅱ, COMP and MMP-3

Purpose: To study the therapeutic influence of meloxicam-glucosamine sulfate combination in patients with osteoarthritis and their effect on serum CTX-I, CTX-II, COMP and MMP-3. Methods: A total of 88 patients with osteoarthritis were assigned to control (n = 44) and treatment groups (n = 44), using the random number table method. Control group was given 7.5 mg of meloxicam, while treatment group received 0.5 g of glucosamine sulfate capsule in addition to meloxicam. Both groups were treated continuously for 8 weeks. Serum levels of C-terminal telopeptide of type I collagen (CTX-I), C-terminal telopeptide of type II collagen (CTX-II), cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase-3 (MMP-3) were compared for the two groups after treatment. Results: Lysholm score significantly increased in the two groups after treatment. Serum CTX-I, CTX-II, COMP and MMP-3 in the two groups were significantly lower than before treatment, but the reductions were more pronounced in the treatment group (p < 0.05). During treatment, mild vomiting and pruritus of the skin appeared in both groups, but these were relieved after symptomatic treatment without any serious adverse reactions. Conclusion: Treatment with a combination of meloxicam and glucosamine sulfate produces significant beneficial effects in patients with osteoarthritis by reduction of clinical symptoms, pain relief and reduction of serum CTX-I, CTX-II, MMP-3 and COMP

GSK-3 signaling in developing cortical neurons is essential for radial migration and dendritic orientation

GSK-3 is an essential mediator of several signaling pathways that regulate cortical development. We therefore created conditional mouse mutants lacking both GSK-3α and GSK-3β in newly born cortical excitatory neurons. Gsk3-deleted neurons expressing upper layer markers exhibited striking migration failure in all areas of the cortex. Radial migration in hippocampus was similarly affected. In contrast, tangential migration was not grossly impaired after Gsk3 deletion in interneuron precursors. Gsk3-deleted neurons extended axons and developed dendritic arbors. However, the apical dendrite was frequently branched while basal dendrites exhibited abnormal orientation. GSK-3 regulation of migration in neurons was independent of Wnt/β-catenin signaling. Importantly, phosphorylation of the migration mediator, DCX, at ser327, and phosphorylation of the semaphorin signaling mediator, CRMP-2, at Thr514 were markedly decreased. Our data demonstrate that GSK-3 signaling is essential for radial migration and dendritic orientation and suggest that GSK-3 mediates these effects by phosphorylating key microtubule regulatory proteins.DOI: http://dx.doi.org/10.7554/eLife.02663.001eLife digestIn the brain, one of the most striking features of the cerebral cortex is that its neurons are organized into different layers that are specifically connected to one another and to other regions of the brain. How newly generated neurons find their appropriate layer during the development of the brain is an important question; and, in humans, when this process goes awry, it can often result in seizures and mental retardation.An enzyme called GSK-3 regulates several major signaling pathways important to brain development. The GSK-3 enzyme switches other proteins on or off by adding phosphate groups to them.Morgan-Smith et al. set out to better understand the role of GSK-3 in brain development by deleting the genes for this enzyme specifically in the cerebral cortex of mice. Mice have two genes that encode slightly different forms of the GSK-3 enzyme. Deleting both of these in different groups of neurons during brain development revealed that a major group of neurons need GSK-3 in order to migrate to the correct layer. Specifically, the movement of neurons from where they arise in the central region of the brain to the outermost layer (a process called radial migration) was disrupted when the GSK-3 genes were deleted.Morgan-Smith et al. further found that cortical neurons without GSK-3 were unable to develop the shape needed to undertake radial migration because they failed to switch from having many branches to having just two main branches. Additional experiments revealed that these abnormalities did not depend on certain signaling pathways, such as the Wnt-signaling pathway or the PI3K signaling pathway that can control GSK-3 activity.Instead, Morgan-Smith et al. found that two proteins that are normally targeted by the GSK-3 enzyme have fewer phosphate groups than normal in the cortical neurons that did not contain the enzyme: both of these proteins regulate the shape of neurons by interacting with the molecular ‘scaffolding’ within the cell. The GSK-3 enzyme was already known to modify the activities of many other proteins that affect the migration of cells. Thus, the findings of Morgan-Smith et al. suggest that this enzyme may coordinate many of the mechanisms thought to underlie this process during brain development.DOI: http://dx.doi.org/10.7554/eLife.02663.00

Layer specific and general requirements for ERK/MAPK signaling in the developing neocortex

Aberrant signaling through the Raf/MEK/ERK (ERK/MAPK) pathway causes pathology in a family of neurodevelopmental disorders known as 'RASopathies' and is implicated in autism pathogenesis. Here, we have determined the functions of ERK/MAPK signaling in developing neocortical excitatory neurons. Our data reveal a critical requirement for ERK/MAPK signaling in the morphological development and survival of large Ctip2+ neurons in layer 5. Loss of Map2k1/2 (Mek1/2) led to deficits in corticospinal tract formation and subsequent corticospinal neuron apoptosis. ERK/MAPK hyperactivation also led to reduced corticospinal axon elongation, but was associated with enhanced arborization. ERK/MAPK signaling was dispensable for axonal outgrowth of layer 2/3 callosal neurons. However, Map2k1/2 deletion led to reduced expression of Arc and enhanced intrinsic excitability in both layers 2/3 and 5, in addition to imbalanced synaptic excitation and inhibition. These data demonstrate selective requirements for ERK/MAPK signaling in layer 5 circuit development and general effects on cortical pyramidal neuron excitability

Probiotic Lactobacillus rhamnosus GG Induces Alterations in Ileal Microbiota With Associated CD3-CD19-T-bet+IFNγ+/- Cell Subset Homeostasis in Pigs Challenged With Salmonella enterica Serovar 4,[5],12:i:-

Salmonella enterica serovar 4,[5],12:i:- (S. 4,[5],12:i:-) is an emerging foodborne pathogen causing salmonellosis in humans and animals. Probiotic Lactobacillus rhamnosus GG (LGG) is an effective strategy for controlling enteric infections through maintaining gut microbiota homeostasis and regulating the intestinal innate immune response. Here, LGG was orally administrated to newly weaned piglets for 1 week before S. 4,[5],12:i:- challenge. S. 4,[5],12:i:- challenge led to disturbed gut microbiota, characterized by increased levels of Psychrobacter, Chryseobacterium indoltheticum, and uncultured Corynebacteriaceae populations, as well as an aberrant correlation network in Prevotellaceae NK3B31 group-centric species. The beneficial effect of LGG correlated with attenuating the expansion of Prevotellaceae NK3B31 group. Fusobacterium only found in the pigs treated with LGG was positively correlated with Lactobacillus animalis and Propionibacterium. Administration of LGG induced the expansion of CD3-CD19-T-bet+IFNγ+ and CD3-CD19-T-bet+IFNγ- cell subsets in the peripheral blood at 24 h after a challenge of S. 4,[5],12:i:-. S. 4,[5],12:i:- infection increased the population of intraepithelial CD3-CD19-T-bet+IFNγ+ and CD3-CD19-T-bet+IFNγ- cells in the ileum; however, this increase was attenuated via LGG administration. Correlation analysis revealed that LGG enriched Flavobacterium frigidarium and Facklamia populations, which were negatively correlated with intraepithelial CD3-CD19-T-bet+IFNγ+ and CD3-CD19-T-bet+IFNγ- cells in the ileum. The present data suggest that probiotic LGG alters gut microbiota with associated CD3-CD19-T-bet+IFNγ+/- cell subset homeostasis in pigs challenged with S. enterica 4,[5],12:i:-. LGG may be used in potential gut microbiota-targeted therapy regimens to regulate the specific immune cell function and, consequently, control enteric infections

MEK Is a Key Regulator of Gliogenesis in the Developing Brain

We have defined functions of MEK in regulating gliogenesis in developing cerebral cortex using loss and gain of function mouse genetics. Radial progenitors deficient in both Mek1 and Mek2 fail to transition to the gliogenic mode in late embryogenesis, and astrocyte and oligodendroglial precursors fail to appear. In exploring mechanisms, we found that the key cytokine regulated gliogenic pathway is attenuated. Further, the Ets transcription family member Etv5/Erm is strongly regulated by MEK and Erm overexpression can rescue the gliogenic potential of Mek deleted progenitors. Remarkably, Mek1/2 deleted mice surviving postnatally exhibit cortices almost devoid of astrocytes and oligodendroglia and exhibit neurodegeneration. Conversely, expression of constitutively active MEK1 leads to a major increase in numbers of astrocytes in the adult brain. We conclude that MEK is essential for acquisition of gliogenic competence by radial progenitors, and that levels of MEK activity regulate gliogenesis in the developing cortex

GSK-3 is a master regulator of neural progenitor homeostasis

The development of the brain requires the exquisite coordination of progenitor proliferation and differentiation to achieve complex circuit assembly. It has been suggested that glycogen synthase kinase 3 (GSK-3) acts as an integrating molecule for multiple proliferation and differentiation signals because of its essential role in the RTK, Wnt and Shh signaling pathways. We created conditional mutations that deleted both the α and β forms of GSK-3 in mouse neural progenitors. GSK-3 deletion resulted in massive hyperproliferation of neural progenitors along the entire neuraxis. Generation of both intermediate neural progenitors and postmitotic neurons was markedly suppressed. These effects were associated with the dysregulation of β-catenin, Sonic Hedgehog, Notch and fibroblast growth factor signaling. Our results indicate that GSK-3 signaling is an essential mediator of homeostatic controls that regulate neural progenitors during mammalian brain development

Erratum: A multi-objective optimization-based layer-by-layer blade-coating approach for organic solar cells: Rational control of vertical stratification for high performance (Energy and Environmental Science (2019) 12 (3118-3132) DOI: 10.1039/C9EE02295C)

The Acknowledgements section should have included the following sentence: "This work was performed in part on the SAXS/ WAXS beamline at the Australian Synchrotron, part of ANSTO". The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers

A multi-objective optimization-based layer-by-layer blade-coating approach for organic solar cells:Rational control of vertical stratification for high performance

A major breakthrough in organic solar cells (OSCs) in the last thirty years was the development of the bulk heterojunction (BHJ) solution processing strategy, which effectively provided a nanoscale phase-separated morphology, aiding in the separation of Coulombically bound excitons and facilitating charge transport and extraction. Compared with the application of the layer-by-layer (LbL) approach proposed in the same period, the BHJ spin-coating technology shows overwhelming advantages for evaluating the performance of photovoltaic materials and achieving more-efficient photoelectric conversion. Thus, in this study, we have further compared the BHJ and LbL processing strategies via the doctor-blade coating technology because it is a roll-to-roll compatible high-throughput thin film fabrication route. We systematically evaluated multiple target parameters, including morphological characteristics, optical simulation, physical kinetics, device efficiency, and blend stability issues. It is worth emphasizing that our findings disprove the old stereotypes such as the BHJ processing method is superior to the LbL technology for the preparation of high-performance OSCs and the LbL approach requires an orthogonal solvent and donor/acceptor materials with special solubility. Our studies demonstrate that the LbL blade-coating approach is a promising strategy to effectively reduce the efficiency-stability gap of OSCs and even a superior alternative to the BHJ method in commercial applications