Raster-scan optoacoustic mesoscopy (RSOM) offers high-resolution non-invasive insights into skin pathophysiology, which holds promise for disease diagnosis and monitoring in dermatology and other fields. However, RSOM is quite vulnerable to vertical motion of the skin, which can depend on the part of the body being imaged. Motion correction algorithms have already been proposed, but they are not fully automated, they depend on anatomical segmentation pre-processing steps that might not be performed successfully, and they are not site- specific. Here, we determined for the first time the magnitude of the micrometric vertical skin displacements at different sites on the body that affect RSOM. The quantifi- cation of motion allowed us to develop a site-specific correction algorithm. The algorithm is fully automated and does not need prior anatomical information. We found that the magnitude of the vertical motion depends strongly on the site of imaging and is caused by breathing, heart beating, and arterial pulsation. The developed algorithm resulted in more than 2-fold improvement in the signal-to-noise ratio of the reconstructed images at every site tested. Proposing an effective automated motion correction algorithm paves the way for realizing the full clinical potential of RSOM.

Unlike traditional static type checking, the type system in the Dart programming language is unsound by design, even for fully annotated programs. The rationale has been that this allows compile-time detection of likely errors and enables code completion in integrated development environments, without being restrictive on programmers. Despite unsoundness, judicious use of type annotations can ensure useful properties of the runtime behavior of Dart programs. We present a formal model of a core of Dart with a focus on its type system, which allows us to elucidate the causes of unsoundness. Our main contribution is a characterization of message-safe programs and a theorem stating that such programs will never encounter ‘message-not-understood’ errors at runtime. Message safety is less restrictive than traditional type soundness, and we argue that it forms a natural intermediate point between dynamically typed and statically typed Dart programs.

Optoacoustic (photoacoustic) dermoscopy offers two principal advantages over conventional optical imaging applied in dermatology. First, it yields high-resolution cross-sectional images of the skin at depths not accessible to other non-invasive optical imaging methods. Second, by resolving absorption spectra at multiple wavelengths, it enables label-free 3D visualization of morphological and functional features. However, the relation of pulse energy to generated bandwidth and imaging depth remains poorly defined. In this paper, we apply computer models to investigate the optoacoustic frequency response generated by simulated skin. We relate our simulation results to experimental measurements of the detection bandwidth as a function of optical excitation energy in phantoms and human skin. Using raster-scan optoacoustic mesoscopy, we further compare the performance of two broadband ultrasonic detectors (a bandwidth of 20-180 and 10-90MHz) in acquiring optoacoustic readouts. Based on the findings of this paper, we propose energy ranges required for skin imaging with considerations of laser safety standards.

Post-transcriptional regulation of gene expression plays a crucial role in many bacterial pathways. In particular, the translation of mRNA can be regulated by trans-acting, small, non-coding RNAs (sRNAs) or mRNA-binding proteins, each of which has been successfully treated theoretically using two-component models. An important system that includes a combination of these modes of post-transcriptional regulation is the Colicin E2 system. DNA damage, by triggering the SOS response, leads to the heterogeneous expression of the Colicin E2 operon including the cea gene encoding the toxin colicin E2, and the cel gene that codes for the induction of cell lysis and release of colicin. Although previous studies have uncovered the system's basic regulatory interactions, its dynamical behavior is still unknown. Here, we develop a simple, yet comprehensive, mathematical model of the colicin E2 regulatory network, and study its dynamics. Its post-transcriptional regulation can be reduced to three hierarchically ordered components: the mRNA including the cel gene, the mRNA-binding protein CsrA, and an effective sRNA that regulates CsrA. We demonstrate that the stationary state of this system exhibits a pronounced threshold in the abundance of free mRNA. As post-transcriptional regulation is known to be noisy, we performed a detailed stochastic analysis, and found fluctuations to be largest at production rates close to the threshold. The magnitude of fluctuations can be tuned by the rate of production of the sRNA. To study the dynamics in response to an SOS signal, we incorporated the LexA-RecA SOS response network into our model. We found that CsrA regulation filtered out short-lived activation peaks and caused a delay in lysis gene expression for prolonged SOS signals, which is also seen in experiments. Moreover, we showed that a stochastic SOS signal creates a broad lysis time distribution. Our model thus theoretically describes Colicin E2 expression dynamics in detail and reveals the importance of the specific regulatory components for the timing of toxin release.

Unlike traditional static type checking, the type system in the Dart programming language is unsound by design, even for fully annotated programs. The rationale has been that this allows compile-time detection of likely errors and enables code completion in integrated development environments, without being restrictive on programmers. Despite unsoundness, judicious use of type annotations can ensure useful properties of the runtime behavior of Dart programs. We present a formal model of a core of Dart with a focus on its type system, which allows us to elucidate the causes of unsoundness. Our main contribution is a characterization of message-safe programs and a theorem stating that such programs will never encounter 'message not understood' errors at runtime. Message safety is less restrictive than traditional type soundness, and we argue that it forms a natural intermediate point between dynamically typed and statically typed Dart programs.

Raster-scan optoacoustic mesoscopy (RSOM) comes with high potential for in vivo diagnostic imaging in dermatology, since it allows for high resolution imaging of the natural chromophores melanin, and hemoglobin at depths of several millimeters. We have applied ultra-wideband RSOM, in the 10-160 MHz frequency band, to image healthy human skin at distinct locations. We analyzed the anatomical information contained at different frequency ranges of the optoacoustic (photoacoustic) signals in relation to resolving features of different skin layers in vivo. We further compared results obtained from glabrous and hairy skin and identify that frequencies above 60 MHz are necessary for revealing the epidermal thickness, a prerequisite for determining the invasion depth of melanoma in future studies. By imaging a benign nevus we show that the applied RSOM system provides strong contrast of melanin-rich structures. We further identify the spectral bands responsible for imaging the fine structures in the stratum corneum, assessing dermal papillae, and resolving microvascular structures in the horizontal plexus.

Optoacoustic (photoacoustic) imaging uniquely visualizes optical contrast in high resolution and comes with very attractive characteristics for clinical imaging applications. In this paper, we showcase the performance of a scanner based on a 24 MHz center-frequency 128 element array, developed for applications in dermatology. We perform system characterization to examine the imaging performance achieved. We then showcase its imaging ability on healthy tissue and cancer. Finally, we image burns and human lesions in vivo and gain insights on the benefits and challenges of this approach as it is considered for diagnostic and treatment follow-up applications in dermatology and beyond.

Web application programmers must be aware of a wide range of potential security risks. Although the most common pitfalls are well described and categorized in the literature, it remains a challenging task to ensure that all guidelines are followed. For this reason, it is desirable to construct automated tools that can assist the programmers in the application development process by detecting weaknesses. Many vulnerabilities are related to Web application code that stores references to application state in the generated HTML documents to work around the statelessness of the HTTP protocol. In this article, we show that such client-state manipulation vulnerabilities are amenable to tool-supported detection. We present a static analysis for the widely used frameworks Java Servlets, JSP, and Struts. Given a Web application archive as input, the analysis identifies occurrences of client state and infers the information flow between the client state and the shared application state on the server. This makes it possible to check how client-state manipulation performed by malicious users may affect the shared application state and cause leakage or modifications of sensitive information. The warnings produced by the tool help the application programmer identify vulnerabilities before deployment. The inferred information can also be applied to configure a security filter that automatically guards against attacks at runtime. Experiments on a collection of open-source Web applications indicate that the static analysis is able to effectively help the programmer prevent client-state manipulation vulnerabilities. The analysis detects a total of 4,802 client-state parameters in ten applications, whereof 4,437 are classified as safe and 241 reveal exploitable vulnerabilities.

Web application programmers must be aware of a wide range of potential security risks. Although the most common pitfalls are well described and categorized in the literature, it remains a challenging task to ensure that all guidelines are followed. For this reason, it is desirable to construct automated tools that can assist the programmers in the application development process by detecting weaknesses. Many vulnerabilities are related to web application code that stores references to application state in the generated HTML documents to work around the statelessness of the HTTP protocol. In this paper, we show that such client-state manipulation vulnerabilities are amenable to tool supported detection. We present a static analysis for the widely used frameworks Java Servlets, JSP, and Struts. Given a web application archive as input, the analysis identifies occurrences of client state and infers the information flow between the client state and the shared application state on the server. This makes it possible to check how client-state manipulation performed by malicious users may affect the shared application state and cause leakage or modifications of sensitive information. The warnings produced by the tool help the application programmer identify vulnerabilities. Moreover, the inferred information can be applied to configure a security filter that automatically guards against attacks. Experiments on a collection of open source web applications indicate that the static analysis is able to effectively help the programmer prevent client-state manipulation vulnerabilities.