Approximating a Target Surface with 1-DOF Rigid Origami

We develop some design examples for approximating a target surface at the final rigidly folded state of a developable quadrilateral creased paper, which is folded with a 1-DOF rigid folding motion from the planar state. The final rigidly folded state is reached due to the clashing of panels. Now we can approximate some specific types of non-developable surfaces, but we do not yet fully understand how to approximate an arbitrary surface with a developable creased paper that has limited DOFs. Our designs might have applications in areas related to the formation of a shell structure from a planar region

On rigid origami III: local rigidity analysis.

In this article, rigid origami is examined from the perspective of rigidity theory. First- and second-order rigidity are defined from local differential analysis of the consistency constraint; while the static rigidity and prestress stability are defined after finding the form of internal force and load. We will show the hierarchical relation among these local rigidities with examples representing different levels. The development of theory here follows the same path as the conventional rigidity theory for bar-joint frameworks, but starts with different high-order rotational constraints. We also bring new interpretation to the internal force and geometric error of constraints associated with energy. Examining the different aspects of the rigidity of origami might give a novel perspective for the development of new folding patterns, or for the design of origami structures where some rigidity is required

On rigid origami III: local rigidity analysis.

In this article, rigid origami is examined from the perspective of rigidity theory. First- and second-order rigidity are defined from local differential analysis of the consistency constraint; while the static rigidity and prestress stability are defined after finding the form of internal force and load. We will show the hierarchical relation among these local rigidities with examples representing different levels. The development of theory here follows the same path as the conventional rigidity theory for bar-joint frameworks, but starts with different high-order rotational constraints. We also bring new interpretation to the internal force and geometric error of constraints associated with energy. Examining the different aspects of the rigidity of origami might give a novel perspective for the development of new folding patterns, or for the design of origami structures where some rigidity is required

New Rigid-foldable Developable Quadrilateral Creased Papers

This article extends the range of 1-DOF rigid-foldable developable quadrilateral creased papers. In a previous article, we put forward a sufficient and necessary condition for a quadrilateral creased paper to be rigid-foldable, and introduce a special sufficient condition that is convenient for practical use, generating quadrilateral creased paper by stitching basic units. In this article we develop new flat-foldable units and show how these can be used to construct a series of more complex rigid-foldable developable quadrilateral creased papers

A simple, combinatorial algorithm for solving SDD systems in nearly-linear time

Original manuscript January 28, 2013In this paper, we present a simple combinatorial algorithm that solves symmetric diagonally dominant (SDD) linear systems in nearly-linear time. It uses little of the machinery that previously appeared to be necessary for a such an algorithm. It does not require recursive preconditioning, spectral sparsification, or even the Chebyshev Method or Conjugate Gradient. After constructing a "nice" spanning tree of a graph associated with the linear system, the entire algorithm consists of the repeated application of a simple update rule, which it implements using a lightweight data structure. The algorithm is numerically stable and can be implemented without the increased bit-precision required by previous solvers. As such, the algorithm has the fastest known running time under the standard unit-cost RAM model. We hope the simplicity of the algorithm and the insights yielded by its analysis will be useful in both theory and practice.National Science Foundation (U.S.) (Award 0843915)National Science Foundation (U.S.) (Award 1111109)Alfred P. Sloan Foundation (Research Fellowship)National Science Foundation (U.S.). Graduate Research Fellowship Program (Grant 1122374

Mitochondrial Functions Are Compromised in CD4 T Cells From ART-Controlled PLHIV

The hallmark of HIV/AIDS is a gradual depletion of CD4 T cells. Despite effective control by antiretroviral therapy (ART), a significant subgroup of people living with HIV (PLHIV) fails to achieve complete immune reconstitution, deemed as immune non-responders (INRs). The mechanisms underlying incomplete CD4 T cell recovery in PLHIV remain unclear. In this study, CD4 T cells from PLHIV were phenotyped and functionally characterized, focusing on their mitochondrial functions. The results show that while total CD4 T cells are diminished, cycling cells are expanded in PLHIV, especially in INRs. HIV-INR CD4 T cells are more activated, displaying exhausted and senescent phenotypes with compromised mitochondrial functions. Transcriptional profiling and flow cytometry analysis showed remarkable repression of mitochondrial transcription factor A (mtTFA) in CD4 T cells from PLHIV, leading to abnormal mitochondrial and T cell homeostasis. These results demonstrate a sequential cellular paradigm of T cell over-activation, proliferation, exhaustion, senescence, apoptosis, and depletion, which correlates with compromised mitochondrial functions. Therefore, reconstituting the mtTFA pathway may provide an adjunctive immunological approach to revitalizing CD4 T cells in ART-treated PLHIV, especially in INRs

A Matter of Life or Death: Productively Infected and Bystander CD4 T Cells in Early HIV Infection

CD4 T cell death or survival following initial HIV infection is crucial for the development of viral reservoirs and latent infection, making its evaluation critical in devising strategies for HIV cure. Here we infected primary CD4 T cells with a wild-type HIV-1 and investigated the death and survival mechanisms in productively infected and bystander cells during early HIV infection. We found that HIV-infected cells exhibited increased programmed cell death, such as apoptosis, pyroptosis, and ferroptosis, than uninfected cells. However, productively infected (p24+) cells and bystander (p24-) cells displayed different patterns of cell death due to differential expression of pro-/anti-apoptotic proteins and signaling molecules. Cell death was triggered by an aberrant DNA damage response (DDR), as evidenced by increases in γH2AX levels, which inversely correlated with telomere length and telomerase levels during HIV infection. Mechanistically, HIV-infected cells exhibited a gradual shortening of telomeres following infection. Notably, p24+ cells had longer telomeres compared to p24- cells, and telomere length positively correlated with the telomerase, pAKT, and pATM expressions in HIV-infected CD4 T cells. Importantly, blockade of viral entry attenuated the HIV-induced inhibition of telomerase, pAKT, and pATM as well as the associated telomere erosion and cell death. Moreover, ATM inhibition promoted survival of HIV-infected CD4 T cells, especially p24+ cells, and rescued telomerase and AKT activities by inhibiting cell activation, HIV infection, and DDR. These results indicate that productively infected and bystander CD4 T cells employ different mechanisms for their survival and death, suggesting a possible pro-survival, pro-reservoir mechanism during early HIV infection

Long Non-Coding RNA GAS5 Regulates T Cell Functions via miR21-Mediated Signaling in People Living With HIV

T cells are critical for the control of viral infections and T cell responses are regulated by a dynamic network of non-coding RNAs, including microRNAs (miR) and long non-coding RNAs (lncRNA). Here we show that an activation-induced decline of lncRNA growth arrest-specific transcript 5 (GAS5) activates DNA damage response (DDR), and regulates cellular functions and apoptosis in CD4 T cells derived from people living with HIV (PLHIV) via upregulation of miR-21. Notably, GAS5-miR21-mediated DDR and T cell dysfunction are observed in PLHIV on antiretroviral therapy (ART), who often exhibit immune activation due to low-grade inflammation despite robust virologic control. We found that GAS5 negatively regulates miR-21 expression, which in turn controls critical signaling pathways involved in DNA damage and cellular response. The sustained stimulation of T cells decreased GAS5, increased miR-21 and, as a result, caused dysfunction and apoptosis in CD4 T cells. Importantly, this inflammation-driven T cell over-activation and aberrant apoptosis in ART-controlled PLHIV and healthy subjects (HS) could be reversed by antagonizing the GAS5-miR-21 axis. Also, mutation of the miR-21 binding site on exon 4 of GAS5 gene to generate a GAS5 mutant abolished its ability to regulate miR-21 expression as well as T cell activation and apoptosis markers compared to the wild-type GAS5 transcript. Our data suggest that GAS5 regulates TCR-mediated activation and apoptosis in CD4 T cells during HIV infection through miR-21-mediated signaling. However, GAS5 effects on T cell exhaustion during HIV infection may be mediated by a mechanism beyond the GAS5-miR-21-mediated signaling. These results indicate that targeting the GAS5-miR-21 axis may improve activity and longevity of CD4 T cells in ART-treated PLHIV. This approach may also be useful for targeting other infectious or inflammatory diseases associated with T cell over-activation, exhaustion, and premature immune aging