Miracle-dz/UniFAR-FTUs huggingface dataset:
Protecting Million-User iOS Apps with Obfuscation: Motivations, Pitfalls, and Experience

In recent years, mobile apps have become the infrastructure of many popular Internet services. It is now fairly common that a mobile app serves a large number of users across the globe. Different from web-based services whose important program logic is mostly placed on remote servers, many mobile apps require complicated client-side code to perform tasks that are critical to the businesses. The code of mobile apps can be easily accessed by any party after the software is installed on a rooted or jailbroken device. By examining the code, skilled reverse engineers can learn various knowledge about the design and implementation of an app. Real-world cases have shown that the disclosed critical information allows malicious parties to abuse or exploit the app-provided services for unrightful profits, leading to significant financial losses for app vendors. One of the most viable mitigations against malicious reverse engineering is to obfuscate the software before release. Despite that security by obscurity is typically considered to be an unsound protection methodology, software obfuscation can indeed increase the cost of reverse engineering, thus delivering practical merits for protecting mobile apps. In this paper, we share our experience of applying obfuscation to multiple commercial iOS apps, each of which has millions of users. We discuss the necessity of adopting obfuscation for protecting modern mobile business, the challenges of software obfuscation on the iOS platform, and our efforts in overcoming these obstacles. Our report can benefit many stakeholders in the iOS ecosystem, including developers, security service providers, and Apple as the administrator of the ecosystem.
Long-term safety of tiotropium/olodaterol Respimat® in patients with moderate-to-very severe COPD and renal impairment in the TONADO® studies

Introduction The safety, lung function efficacy, and symptomatic benefits of combined tiotropium and olodaterol in patients with COPD were established in the 1-year TONADO® studies (NCT01431274; NCT01431287). As tiotropium is predominantly excreted by the kidneys, the long-term safety profile of tiotropium/olodaterol was investigated in patients with renal impairment in a prespecified safety analysis of the TONADO studies. Methods These were 2 replicate, randomized, double-blind, parallel-group, 52-week Phase III studies that assessed tiotropium/olodaterol compared with tiotropium or olodaterol alone (all via Respimat®) in patients with moderate-to-very severe COPD. In this analysis, renal impairment was defined as mild (creatinine clearance [CLcr] 60–89 mL/min), moderate (CLcr 30–59 mL/min) or severe (CLcr 15–29 mL/min). Adverse events (AEs) were pooled from both studies. Results Of 3,041 patients included in this analysis, 1,333 (43.8%) had mild, 404 (13.3%) had moderate, and 5 (0.2%) had severe renal impairment; these were distributed equally between treatment groups. Almost one-quarter of all treated patients (23.4%) had a history of cardiac disorder, 45.6% had hypertension, and 13.3% had glucose metabolism disorders, including diabetes. AEs with olodaterol, tiotropium, and tiotropium/olodaterol occurred in 75.1%, 70.8%, and 72.0% of patients with no renal impairment, 75.7%, 74.0%, and 73.3% with mild renal impairment, and 84.3%, 79.5%, and 79.7% with moderate renal impairment, respectively. There was no notable effect of renal impairment on the proportion of patients with an AE, and no differences were observed between tiotropium/olodaterol versus the monocomponents. There was no difference in the incidence of major adverse cardiac events, renal and urinary tract AEs, or potential anticholinergic effects with increasing severity of renal impairment. Conclusion Over half the patients enrolled in the TONADO studies had renal impairment, and there was a high level of pre-existing cardiovascular comorbidity. The safety and tolerability of tiotropium/olodaterol is comparable to the monocomponents, irrespective of the level of renal impairment.
Intel MPX Explained

Memory-safety violations are the primary cause of security and reliability issues in software systems written in unsafe languages. Given the limited adoption of decades-long research in software-based memory safety approaches, as an alternative, Intel released Memory Protection Extensions (MPX)---a hardware-assisted technique to achieve memory safety. In this work, we perform an exhaustive study of Intel MPX architecture along three dimensions: (a) performance overheads, (b) security guarantees, and (c) usability issues. We present the first detailed root cause analysis of problems in the Intel MPX architecture through a cross-layer dissection of the entire system stack, involving the hardware, operating system, compilers, and applications. To put our findings into perspective, we also present an in-depth comparison of Intel MPX with three prominent types of software-based memory safety approaches. Lastly, based on our investigation, we propose directions for potential changes to the Intel MPX architecture to aid the design space exploration of future hardware extensions for memory safety.
VEGF and PDGF modulates the glial response to a cortical stab injury

Traumatic injury to the brain initiates an increase in astrocyte and microglial infiltration as part of an inflammatory response to injury. Increased astrogliosis around the injury impedes regeneration of axons through the injury, while activated microglia release inflammatory mediators. The persistent inflammatory response can lead to local progressive cell death. Modulating the astrocyte and microglial response to traumatic injury therefore has potential therapeutic benefit in brain repair. We examine the modulatory effect of a single bolus of vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) in combination on astrocytes and microglia to acute cerebral injury. A combination of VEGF and PDGF (20 pg) was injected into the striatum of adult male Sprague-Dawley rats. The effects of treatment were assessed by quantitative immunofluorescence microscopy analyzing astrocytes and microglia across the stab injury over time. Treatment delayed the onset of astrogliosis in the centre and edge of the stab injury up to day 5; however, increased astrogliosis at areas remote to the stab injury up to day 5 was observed. A persistent astrocytic response was observed in the centre and edge of the stab injury up to day 60. Treatment altered microglia cell morphology and numbers across the stab injury, with a decrease in ramified microglia, but an increase in activated and phagocytic microglia up to day 5 after stab injury. The increased microglial response from 10 until day 60 was comprised of the ramified morphology. Thus, VEGF and PDGF applied at the same time as a stab injury to the brain initially delayed the inflammatory response up to day 5 but evoked a persistent astrogliosis and microglial response up to 60 days.
An Experience Report on Defect Modelling in Practice: Pitfalls and Challenges

Over the past decade with the rise of the Mining Software Repositories (MSR) field, the modelling of defects for large and long-lived systems has become one of the most common applications of MSR. The findings and approaches of such studies have attracted the attention of many of our industrial collaborators (and other practitioners worldwide). At the core of many of these studies is the development and use of analytical models for defects. In this paper, we discuss common pitfalls and challenges that we observed as practitioners attempt to develop such models or reason about the findings of such studies. The key goal of this paper is to document such pitfalls and challenges so practitioners can avoid them in future efforts. We also hope that other academics will be mindful of such pitfalls and challenges in their own work and industrial engagements.
Synthesis and study of structural and magnetic properties of superparamagnetic Fe3O4@SiO2 core/shell nanocomposite for biomedical applications

Objective(s): This paper describes coating of magnetite nanoparticles (MNPs) with amorphous silica shells. Materials and Methods: First, magnetite (Fe3O4) NPs were synthesized by co-precipitation method and then treated with stabilizer molecule of trisodium citrate to enhance their dispersibility. Afterwards, coating with silica was carried out via a sol-gel approach in which the electrostatically stabilized MNPs were used as seeds. The samples were characterized by means of X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy and vibrating sample magnetometer (VSM). Results: The results of XRD analysis implied that the prepared nanocomposite consists of two compounds of crystalline magnetite and amorphous silica that formation of their core/shell structure with the shell thickness of about 5 nm was confirmed by TEM images. The magnetic studies also indicated that produced Fe3O4@SiO2 core/shell nanocomposite exhibits superparamagnetic properties at room temperature. Conclusion: These core/shell structure due to having superparamagnetic property of Fe3O4 and unique properties of SiO2, offers a high potential for many biomedical applications.
The tumour suppressor OPCML promotes AXL inactivation by the phosphatase PTPRG in ovarian cancer

In ovarian cancer, the prometastatic RTK AXL promotes motility, invasion and poor prognosis. Here, we show that reduced survival caused by AXL overexpression can be mitigated by the expression of the GPI‐anchored tumour suppressor OPCML. Further, we demonstrate that AXL directly interacts with OPCML, preferentially so when AXL is activated by its ligand Gas6. As a consequence, AXL accumulates in cholesterol‐rich lipid domains, where OPCML resides. Here, phospho‐AXL is brought in proximity to the lipid domain‐restricted phosphatase PTPRG, which de‐phosphorylates the RTK/ligand complex. This prevents AXL‐mediated transactivation of other RTKs (cMET and EGFR), thereby inhibiting sustained phospho‐ERK signalling, induction of the EMT transcription factor Slug, cell migration and invasion. From a translational perspective, we show that OPCML enhances the effect of the phase II AXL inhibitor R428 in vitro and in vivo. We therefore identify a novel mechanism by which two spatially restricted tumour suppressors, OPCML and PTPRG, coordinate to repress AXL‐dependent oncogenic signalling.
Side-chain conformations in 4-α-helical bundles

The distribution of the χ1, χ2 dihedral angles in a dataset In the present study, the role of the geometric constraints consisting of 12 unrelated 4-α-helical bundle proteins was posed by a specific topology to the side-chain dihedral angles determined and qualitatively compared with that observed was investigated. As a model for protein topology, the 4-αin globular proteins. The analysis suggests that the helical bundle motif was used. This simple, recurrent tertiary 4-α-helical bundle motif could occasionally impose steric motif consists of four α-helices packed against each other in constraints on side chains: (i) the side-chain conformations an antiparallel manner at an angle of about 20° (Figure 1a) are limited to only a subset of the conformations observed (Weber and Salemme, 1980; Cohen and Parry, 1986). The αin globular proteins and for some amino acids they are helices are usually connected together with loop regions; sterically more constrained than those in helical regions alternatively, the bundle is formed as an assembly of helices of globular proteins; (ii) aspartic acid and asparagine belonging to different polypeptide chains, as is the case with occasionally adopt rotamers that have not been previously the ColE1 Rop protein (Banner et al., 1987; Presnell and reported for globular or helical proteins; (iii) some rotamers Cohen, 1989; Harris et al., 1994). The amino acid sequences of tyrosine and isoleucine are predominantly or exclusively of the helices follow a specific pattern of hydrophilic and associated with hydrophobic core positions (a, d); (iv) hydrophobic residues of the type (a,b,c,d,e,f,g)n (Crick, 1953). mutations in the hydrophobic core occur preferentially This pattern is repeated every seven residues (heptads). Posibetween residue types which among other physicochemical tions a and d form the core of the bundle and are generally properties also share a predominant rotamer. occupied by hydrophobic amino acids (Figure 1b).
PHYLOGENETIC ANALYSIS AMONG FOUR SECTIONS OF THE GENUS DENDROBIUM SW. (ORCHIDACEAE) BASED ON LOW COPY NUCLEAR GENE (XDH) SEQUENCES IN PENINSULAR MALAYSIA

The present study focused on the molecular phylogeny of the four sections (Aporum, Crumenata, Strongyle, and Bolbidium) of the genus Dendrobium SW. (Orchidaceae) based upon low copy nuclear gene, Xanthine Dehydrogenase (Xdh) sequences using maximum parsimony (MP), maximum likelihood (ML) and Bayesian (BI) methods. Single and low copy nuclear genes have been increasingly used in phylogenetic reconstruction because they contain large amounts of genetic information and are biparentally inherited. Classifications based on morphological characters have not been able to clearly divide these four sections and neither do they support their monophyletic origins. Therefore, detailed analysis using molecular data is required to ascertain their status. This study includes 20 species of genus Dendrobium and 2 species from genus Bulbophyllum (section Sestochilus) as outgroup taxa. According to the results, the aligned sequences consisted of 733 nucleotide characters of which 131characters were parsimony informative. The analysis revealed that the nuclear genes can be reliable marker for the phylogenetic study of genus Dendrobium. The results suggested that the four sections are probably best considered as one section instead of four and based on the International Code of Botanical Nomenclature (ICBN) rules can be named as section Aporum for this new classification.
Optimal configuration of remanufacturing supply network with return quality decision

This research studies the configuration problem of a remanufacturing production network together with the decision for return quality thresholds, in which, the manufacturer has multiple remanufacturing facilities to satisfy different market demands. Quality of returns is stochastic, while demand for remanufactured products is either stochastic or deterministic. The problem we considered is to determine facilities to operate, minimum quality to accept into each operating facility, return quantity and demand allocation simultaneously so that the system’s profit is maximised. The problem is formulated as a mixed integer non-linear programming model. Through the use of a numerical example, the impact of quantity of returns, total spending, quality uncertainty, demand uncertainty and transportation cost on the remanufacturing system is analysed.
Molecular and cellular aspects and regulation of intestinal lactase-phlorizin hydrolase

Carbohydrates are hydrolyzed in the intestinal lumen by specific enzymes to monosaccharides before transport across the brush border membrane of epithelial cells into the cell interior. The enzymes implicated in the digestion of carbohydrates in the intestinal lumen are membrane-bound g1ycoproteins that are expressed at the apical domain of the enterocytes. Absent or reduced activity of one of these enzymes is the cause of disaccharide intolerance and malabsorption, the symptoms of which are abdominal pain, cramps or distention, flatulence, nausea and osmotic diarrhea. Lactose intolerance is the most common intestinal disorder that is associated with an absence or drastically reduced levels of an intestinal enzyme, in this case lactase-phlorizin hydrolase (LPH). The pattern of reduction of activity has been termed late onset of lactase deficiency or adult type hypolactasia. It was thought that the regulation of LPH was posttranslational and was associated with altered structural features of the enzyme. Recent studies, however, suggest that the major mechanism of regulation of LPH is transcriptional. Other forms of lactose intolerance include the rare congenital lactase deficiency and secondary forms, such as those caused by mucosal injury, due to infectious gastroenteritis, celiac disease, parasitic infection, drug-induced enteritis and Crohn 's disease . This review will shed light on important strucural and biosynthetic aspects of LPH, the role played by particular regions of the LPH protein in its transport, polarized sorting, and function, as well as on the gene expession and regulation of the activity of the enzyme.
Technostress Creators and Burnout: A Job Demands-Resources Perspective

Although prior research has examined the influence of technostress creators on various job outcomes, insights into the influence of individual technostress creators and their impacts on job outcomes are rather limited. In this research, by providing a technological component to the existing Job Demand-Resource framework, we investigate the relationship between individual technostress creators and burnout in an Indian context. We also examine the interaction among technostress creators to identify the mediating impact of techno-invasion and techno-insecurity. Analyzing a total of 163 responses, collected through an online survey we found encouraging pieces of evidence for our hypotheses. Specifically, our findings revealed that among the five technostress creators, only techno-invasion and techno-insecurity are positively related to burnout in an employee. The contributions of the study to theory and practice are also discussed.
Ocean-estuary coupling in the Oregon upwelling region: abundance and transport of juvenile fish and of crab megalopae

Numerous species of fish and invertebrates move between the continental shelf and estuaries during their early life-history. The physical mechanisms that regulate such movement and the extent of coupling between the near-shore ocean and estuaries are poorly understood. It is unclear how, or whether, similar physical mechanisms regulate transport to the outer coast and between the outer coast and estuarine areas. We used high frequency light trap collections at 2 sites, outer coastal and estuarine, to compare the timing and magnitude of the relative abundance of juvenile fish and crab megalopae. The time series of juvenile fish and crab megalopae were statisti- cally compared with physical variables indicative of wind and tidal conditions to identify potential transport mechanisms. Species examined included juvenile Engraulis mordax (northern anchovy), Sardinops sagax (Pacific sardine), Sebastes melanops and S. caurinus (black and copper rockfish), and megalopae of Cancer magister (Dungeness crab), C. oregonensis and C. productus combined (pygmy and red rock crabs), and Pagurus spp. (hermit crabs). The abundances of juvenile E. mordax and S. sagax and C. magister megalopae in the estuary were significantly cross-correlated with abundances at the outer coast (at 0 to -4 d lags). These data support the idea that estuarine ingress may be a 2-stage process with initial arrival in the near-shore as the first stage and subsequent entrance into nearby estuaries as the second stage. Significant cross correlations between species abundance and physical variables indicative of wind-driven transport, both upwelling and down- welling-related, and tidal transport, specifically the spring-neap tidal cycle, were found at both the outer coast and estuarine site. These data indicate that both wind-driven and tidal transport may contribute to the cross-shelf transport and estuarine ingress of organisms.
A modular dCas9-SunTag DNMT3A epigenome editing system overcomes pervasive off-target activity of direct fusion dCas9-DNMT3A constructs

DNA methylation is a covalent modification of the genome that plays important roles in genome regulation and vertebrate development. Although detection of this modification in the genome has been possible for several decades, the ability to deliberately and specifically manipulate local DNA methylation states in the genome has been extremely limited. Consequently, this has impeded the direct determination of the consequence of DNA methylation on transcriptional regulation and transcription factor binding in the native chromatin context. Thus, highly specific targeted epigenome editing tools are needed to address this outstanding question. Recent adaptations of genome editing technologies, such as the fusion of the DNMT3A methyltransferase catalytic domain to catalytically inactive Cas9 (dC9-D3A), have aimed to provide new tools for altering DNA methylation at desired loci. Here, we performed a deeper analysis of the performance of these tools, revealing consistent off-target binding events and DNA methylation deposition in the genome, limiting the capacity of these tools to unambiguously assess the functional consequences of DNA methylation. To address this, we developed a modular dCas9-SunTag (dC9Sun-D3A) system that can recruit multiple DNMT3A catalytic domains to a target site for editing DNA-methylation. dC9Sun-D3A is tunable, specific and exhibits much higher induction of DNA methylation at target sites than the dC9-D3A direct fusion protein. Importantly, genome-wide characterization of dC9Sun-D3A binding sites and DNA methylation revealed minimal off-target protein binding and induction of DNA methylation with dC9Sun-D3A, compared to pervasive off-target binding and methylation by the dC9-D3A direct fusion construct. Furthermore, we used dC9Sun-D3A to test the impact of DNA methylation upon the DNA binding of CTCF and NRF1 upon targeted methylation of their core binding sites, demonstrating the binding sensitivity of these proteins to DNA methylation in situ. Overall, this modular dC9Sun-D3A system enables precise DNA methylation deposition with the lowest amount of off-target DNA methylation reported to date, allowing accurate functional determination of the role of DNA methylation at single loci.
Computational and experimental platform for understanding and optimizing water flux and salt rejection in nanoporous membranes.

Affordable clean water is both a global and a national security issue as lack of it can cause death, disease, and international tension. Furthermore, efficient water filtration reduces the demand for energy, another national issue. The best current solution to clean water lies in reverse osmosis (RO) membranes that remove salts from water with applied pressure, but widely used polymeric membrane technology is energy intensive and produces water depleted in useful electrolytes. Furthermore incremental improvements, based on engineering solutions rather than new materials, have yielded only modest gains in performance over the last 25 years. We have pursued a creative and innovative new approach to membrane design and development for cheap desalination membranes by approaching the problem at the molecular level of pore design. Our inspiration comes from natural biological channels, which permit faster water transport than current reverse osmosis membranes and selectively pass healthy ions. Aiming for an order-of-magnitude improvement over mature polymer technology carries significant inherent risks. The success of our fundamental research effort lies in our exploiting, extending, and integrating recent advances by our team in theory, modeling, nano-fabrication and platform development. A combined theoretical and experimental platform has been developed to understand the interplay between water flux and ion rejection in precisely-defined nano-channels. Our innovative functionalization of solid state nanoporous membranes with organic protein-mimetic polymers achieves 3-fold improvement in water flux over commercial RO membranes and has yielded a pending patent and industrial interest. Our success has generated useful contributions to energy storage, nanoscience, and membrane technology research and development important for national health and prosperity.