Patch It If You Can: Increasing the Efficiency of Patch Generation Using Context

Although program repair is a tremendous aspect of a software system, it can be extremely challenging. An Automated Program Repair (APR) technique has been proposed to solve this problem. Among them, template-based APR shows good performance. One of the key properties of the template-based APR technique for practical use is its efficiency. However, because the existing techniques mainly focus on performance improvement, they do not sufficiently consider the efficiency. In this study, we propose EffiGenC, which efficiently explores the patch ingredient search space to improve the overall efficiency of the template-based APR. EffiGenC defines the context using the concept of extended reaching definition from compiler theory. EffiGenC constructs the search space by collecting the ingredient required for patching in the context. We evaluated EffiGenC on the Defects4j benchmark. EffiGenC decreases the number of candidate patches from 27% to 86% compared to existing techniques. EffiGenC also correctly/plausibly fixes 47/72 bugs. For Future work, we will solve the search space problem that exists in multiline bugs using context

Elimination of Non-targeted Photoacoustic Signals for Combined Photoacoustic and Ultrasound Imaging

As a molecular imaging modality, photoacoustic imaging has been in the spotlight because it can provide an optical contrast image of physiological information and a relatively deep imaging depth. However, its sensitivity is limited despite the use of exogenous contrast agents due to the background photoacoustic signals generated from non-targeted absorbers such as blood and boundaries between different biological tissues. Additionally, clutter artifacts generated in both in-plane and out-of-plane imaging region degrade the sensitivity of photoacoustic imaging. We propose a method to eliminate the non-targeted photoacoustic signals. For this study, we used a dual-modal ultrasound-photoacoustic contrast agent that is capable of generating both backscattered ultrasound and photoacoustic signal in response to transmitted ultrasound and irradiated light, respectively. The ultrasound images of the contrast agents are used to construct a masking image that contains the location information about the target site and is applied to the photoacoustic image acquired after contrast agent injection. In-vitro and in-vivo experimental results demonstrated that the masking image constructed using the ultrasound images makes it possible to completely remove non-targeted photoacoustic signals. The proposed method can be used to enhance clear visualization of the target area in photoacoustic images. IEEE1

Synthesis of Magnetic Ferrite Nanoparticles with High Hyperthermia Performance via a Controlled Co-Precipitation Method

Magnetic nanoparticles (MNPs) that exhibit high specific loss power (SLP) at lower metal content are highly desirable for hyperthermia applications. The conventional co-precipitation process has been widely employed for the synthesis of magnetic nanoparticles. However, their hyperthermia performance is often insufficient, which is considered as the main challenge to the development of practicable cancer treatments. In particular, ferrite MNPs have unique properties, such as a strong magnetocrystalline anisotropy, high coercivity, and moderate saturation magnetization, however their hyperthermia performance needs to be further improved. In this study, cobalt ferrite (CoFe2O4) and zinc cobalt ferrite nanoparticles (ZnCoFe2O4) were prepared to achieve high SLP values by modifying the conventional co-precipitation method. Our modified method, which allows for precursor material compositions (molar ratio of Fe+3:Fe+2:Co+2/Zn+2 of 3:2:1), is a simple, environmentally friendly, and low temperature process carried out in air at a maximum temperature of 60 °C, without the need for oxidizing or coating agents. The particles produced were characterized using multiple techniques, such as X-ray diffraction (XRD), dynamic light scattering (DLS), transmission electron microscopy (TEM), ultraviolet-visible spectroscopy (UV–Vis spectroscopy), and a vibrating sample magnetometer (VSM). SLP values of the prepared nanoparticles were carefully evaluated as a function of time, magnetic field strength (30, 40, and 50 kA m−1), and the viscosity of the medium (water and glycerol), and compared to commercial magnetic nanoparticle materials under the same conditions. The cytotoxicity of the prepared nanoparticles by in vitro culture with NIH-3T3 fibroblasts exhibited good cytocompatibility up to 0.5 mg/mL. The safety limit of magnetic field parameters for SLP was tested. It did not exceed the 5 × 109 Am−1 s−1 threshold. A saturation temperature of 45 °C could be achieved. These nanoparticles, with minimal metal content, can ideally be used for in vivo hyperthermia applications, such as cancer treatments

The Heating Efficiency and Imaging Performance of Magnesium Iron Oxide@tetramethyl Ammonium Hydroxide Nanoparticles for Biomedical Applications

Multifunctional magnetic nanomaterials displaying high specific loss power (SLP) and high imaging sensitivity with good spatial resolution are highly desired in image-guided cancer therapy. Currently, commercial nanoparticles do not sufficiently provide such multifunctionality. For example, Resovist® has good image resolution but with a low SLP, whereas BNF® has a high SLP value with very low image resolution. In this study, hydrophilic magnesium iron oxide@tetramethyl ammonium hydroxide nanoparticles were prepared in two steps. First, hydrophobic magnesium iron oxide nanoparticles were fabricated using a thermal decomposition technique, followed by coating with tetramethyl ammonium hydroxide. The synthesized nanoparticles were characterized using XRD, DLS, TEM, zeta potential, UV-Vis spectroscopy, and VSM. The hyperthermia and imaging properties of the prepared nanoparticles were investigated and compared to the commercial nanoparticles. One-dimensional magnetic particle imaging indicated the good imaging resolution of our nanoparticles. Under the application of a magnetic field of frequency 614.4 kHz and strength 9.5 kA/m, nanoparticles generated heat with an SLP of 216.18 W/g, which is much higher than that of BNF (14 W/g). Thus, the prepared nanoparticles show promise as a novel dual-functional magnetic nanomaterial, enabling both high performance for hyperthermia and imaging functionality for diagnostic and therapeutic processes

Exosome-based photoacoustic imaging guided photodynamic and immunotherapy for the treatment of pancreatic cancer

Exosomes, which are released from all cells and take part in cell-to-cell communication, have been utilized as drug delivery vehicles in many recent studies. Immunotherapy is an emerging technology which uses patients' innate immune systems. In immunotherapy, immune cells are stimulated through antibodies, the other immune cells and genetic modifications for the purposes of, for instance, cancer therapy. In this study, tumor-derived re-assembled exosome (R-Exo) was simultaneously utilized as both a drug delivery carrier and an immunostimulatory agent. A chlorin e6 photosensitizer was loaded into tumor-derived exosomes during exosomal re-assembly. After this modification, R-Exo retains its original average size and has the same membrane proteins, which allows for targeting of tumor cells. Chlorin e6-loaded R-Exo (Ce6-R-Exo) can be visualized by photoacoustic imaging and can efficiently generate reactive oxygen species inside tumor cells under laser irradiation. In addition, Ce6-R-Exo increased the release of cytokines from immune cells, which indicates that these modified exosomes can be used as an immunotherapeutic agent. In conclusion, we developed a novel strategy that enables photoacoustic imaging-guided photodynamic and immune-combination therapy for the treatment of cancer with tumor-derived Ce6-R-Exo. © 2020 Elsevier B.V.FALS

CRISRP/Cas9-mediated knockout of Mct8 reveals a functional involvement of Mct8 in testis and sperm development in a rat

Thyroid hormone (TH) has long been believed to play a minor role in male reproduction. However, evidences from experimental model of thyrotoxicosis or hypothyroidism suggests its role in spermatogenesis. Cellular action of TH requires membrane transport via specific transporters such as monocarboxylate transporter 8 (MCT8). SLC16A2 (encodes for MCT8) inactivating mutation in humans can lead to Allan-Herndon Dudley-syndrome, a X-linked psychomotor and growth retardation. These patients present cryptorchidism which suggests a role of MCT8 during spermatogenesis. In this study, we found that Mct8 is highly expressed during early postnatal development and decreases its expression in the adulthood of testis of wild-type male rats. Histological analysis revealed that spermatogonia largely lacks MCT8 expression while spermatocytes and maturing spermatids highly express MCT8. To further understand the role of Mct8 during spermatogenesis, we generated Slc16a2 (encodes MCT8) knockout rats using CRISPR/Cas9. Serum THs (T3 and T4) level were significantly altered in Slc16a2 knockout rats when compared to wild-type littermates during early to late postnatal development. Unlike Slc16a2 knockout mice, Slc16a2 knockout rats showed growth delay during early to late postnatal development. In adult Slc16a2 knockout rats, we observed reduced sperm motility and viability. Collectively, our data unveil a functional involvement of MCT8 in spermatogenesis, underscoring the importance of TH signaling and action during spermatogenesis.Y

Nanocomposites of Molybdenum Disulfide/Methoxy Polyethylene Glycol-<i>co</i>-Polypyrrole for Amplified Photoacoustic Signal

Photoacoustic activity is the generation of an ultrasonic signal via thermal expansion or bubble formation, stimulated by laser irradiation. Photoacoustic nanoplatforms have recently gained focus for application in bioelectric interfaces. Various photoacoustic material types have been evaluated, including gold nanoparticles, semiconductive π-conjugating polymers (SP), etc. In this study, surfactant-free methoxy-polyethylene glycol-<i>co</i>-polypyrrole copolymer (mPEG-<i>co</i>-PPyr) nanoparticles (NPs) and mPEG-<i>co</i>-PPyr NP/molybdenum disulfide (mPEG-<i>co</i>-PPyr/MoS₂) nanocomposites (NCs) were prepared and their photoacoustic activity was demonstrated. The mPEG-<i>co</i>-PPyr NPs and mPEG-<i>co</i>-PPyr/MoS₂ NCs both showed photoacoustic signal activity. The mPEG-<i>co</i>-PPyr/MoS₂ NCs presented a higher photoacoustic signal amplitude at 700 nm than the mPEG-<i>co</i>-PPyr NPs. The enhanced photoacoustic activity of the mPEG-<i>co</i>-PPyr/MoS₂ NCs might be attributed to heterogeneous interfacial contact between mPEG-<i>co</i>-PPyr and the MoS₂ nanosheets due to complex formation. Laser ablation of MoS₂ might elevate the local temperature and facilitate the thermal conductive transfer in the mPEG-<i>co</i>-PPyr/MoS₂ NCs, amplifying PA signal. Our study, for the first time, demonstrates enhanced PA activity in SP/transition metal disulfide (TMD) composites as photoacoustic nanoplatforms

Improved chondrogenic performance with protective tracheal design of Chitosan membrane surrounding 3D-printed trachea

In recent tracheal tissue engineering, limitations in cartilage reconstruction, caused by immature delivery of chondrocyte-laden components, have been reported beyond the complete epithelialization and integration of the tracheal substitutes with the host tissue. In an attempt to overcome such limitations, this article introduces a protective design of tissue-engineered trachea (TraCHIM) composed of a chitosan-based nanofiber membrane (CHIM) and a 3D-printed biotracheal construct. The CHIM was created from chitosan and polycaprolactone (PCL) using an electrospinning process. Upon addition of chitosan to PCL, the diameter of electrospun fibers became thinner, allowing them to be stacked more closely, thereby improving its mechanical properties. Chitosan also enhances the hydrophilicity of the membranes, preventing them from slipping and delaminating over the cell-laden bioink of the biotracheal graft, as well as protecting the construct. Two weeks after implantation in Sprague-Dawley male rats, the group with the TraCHIM exhibited a higher number of chondrocytes, with enhanced chondrogenic performance, than the control group without the membrane. This study successfully demonstrates enhanced chondrogenic performance of TraCHIM in vivo. The protective design of TraCHIM opens a new avenue in engineered tissue research, which requires faster tissue formation from 3D biodegradable materials, to achieve complete replacement of diseased tissue.11Nsciescopu