Austin Speech Labs

Overexpression of anti-apoptotic proteins such as BCL-xL is a hallmark of various cancers and a major driver of resistance to conventional chemotherapies. While small-molecule BCL-xL inhibitors have shown promising outcomes, their clinical use is hindered by dose-limiting toxicities, especially thrombocytopenia. Proteolysis-targeting chimeras (PROTACs) offer a promising alternative by promoting selective degradation of target proteins via the ubiquitin-proteasome system, thereby reducing off-target effects associated with small molecule inhibitors. However, rational design and optimization of PROTACs remain challenging due to the need to balance simultaneous interactions with both an E3 ubiquitin ligase and the target protein. Here we employ native mass spectrometry (MS) as a rapid, label-free platform to screen and characterize the formation and stability of ternary complexes between BCL-xL, VHL E3 ligase complex (VCB), and various targeting PROTACs. Native MS enables direct detection of binary BCL-xL●PROTAC and ternary BCL-xL●PROTAC●VCB complexes and provides semi-quantitative insights into PROTAC affinity and cooperativity with both binding partners. Furthermore, we explore the dissociation pathways of these complexes in the gas phase using collision-induced dissociation (CID) and ultraviolet photodissociation (UVPD), revealing distinct fragmentation and subunit release patterns that reflect the structural organization and gas-phase stability of the complexes. Variable-temperature ESI-MS (vT-ESI) further allows assessment of thermal stabilities of the complexes in solution. Together, our study demonstrates the power of native MS to both screen and mechanistically characterize PROTAC-induced ternary complex formation.

Abstract Natural gas hydrate is ice‐like mixture of gas (mostly methane) and water that is widely found in sediments along the world's continental margins and within and beneath permafrost and glaciers in a near‐surface depth interval where the pressure is sufficiently high and temperature sufficiently low for gas hydrate to be stable. We categorize the myriad of geological gas hydrate deposits into five characteristic types. We then review the multiple quantitative models that have proposed to describe the genesis of these deposits and describe how each may have formed. We emphasize the importance of coupling multiphase flow (free gas and liquid water) and multicomponent reactive transport with geological history to describe the dynamical processes of gas hydrate formation and evolution in geological systems. A better insight into the kinetics of methane formation from microbial biogenesis and the processes of multiphase flow at the pore scale will advance our knowledge of how these systems form. By understanding the generation and evolution of gas hydrate through time, we will better decipher the role of gas hydrate in the carbon cycle, its potential to contribute to climate change and geohazards, and how to design optimal strategies for gas production from hydrate reservoirs.

Background: Research suggests that Acute Post-Stroke Aphasia (APSA) improves with Intensive Speech Therapy (IST). However there is scarce research comparing IST for APSA vs Chronic Post-stroke Aphasia (CPSA), and the relation to Time Post Stroke (TPS). We hypothesized that IST creates improvement for both APSA and CPSA patients irrespective of TPS. Methods: We examined 26 participants chosen from the existing database of Austin Speech Labs, age range 23-79 yrs (mean 53 yrs). Clients that attended all eight weeks of therapy consistently were chosen. All clients received group and individual therapy using different computer applications every time they attended a session. The hours spent in therapy varied due to the individualized nature of the therapy program, but averaged 442 hours (range 80 -2,279 hours). Clients maintained their hours per week for at least eight weeks, which was defined as the IST “Boot Camp(BC)” interval. We classified clients into two groups, CPSA (n=12) and APSA (n=14) depending on TPS. CPSA clients had come to ASL at least one year post-stroke onset while APSA clients had come less than one year post-stroke. Two tests , Western Aphasia Battery (WAB) or Examining for Aphasia- Fourth Edition (EFA-4) were administered at enrollment and at discharge or every six months to avoid memorization. ASL Language Evaluation to test automatic speech, auditory comprehension, naming, reading, writing, and expressive language was done after every BC session. Results: APSA and CPSA clients differed on several levels. TPS was 1 to19.5 yrs, age was 23 - 75 yrs in CPSA compared to 0.08 - 0.75 yrs TPS, 30 - 79 yrs age in APSA. CPSA had four females(F) and nine males(M) while APSA had two F and 12 M. Using an independent samples test we found no significant differences in final scores between between APSA and CPSA participants across aphasia types. Secondly, using a bivariate correlation test, we found no correlation between TPS and post test scores across all categories. Lastly, age had no effect on treatment response; elderly and young clients improved equally with IST. Conclusion: IST can help CPSA clients as much as those with APSA. Research is continuing to determine the minimal and optimal length and duration of IST to produce and maintain improved language function.

As the production, storage, and exchange of information become more extensive and important in the functioning of societies, the problem of protecting the information from unintended and undesired usage becomes more complex. In modern societies, protection of information involves many interdependent technological and policy issues related to information confidentiality, integrity, anonymity, authenticity, utility, and so on. Information hiding techniques are receiving much attention today. Digital audio, video, and images are increasingly furnished with distinguishing but imperceptible marks, which may contain a hidden copyright notice or serial number or even help to prevent unauthorized copying directly. Digital watermarking and steganography may protect information, conceal secrets, or are used as core primitives in digital rights' management schemes. Alongside the aforementioned types of digital media steganography, currently, the target of increased interest is network steganography—a part of information hiding focused on modern networks. It is a method of hiding secret data in users' normal data transmissions. Steganographic techniques arise and evolve with the development of network protocols and mechanisms and are expected to be used in secret communication or information sharing. Presently, it becomes a hot topic owing to the proliferation of information networks and multimedia services in networks and social networks. The purpose of establishing applications of information hiding may be varied—possible uses can fall into the category of legal actions or illicit activity. Frequently, the illegal aspect is accentuated—starting from criminal communication, through information leakage from protected systems and cyber weapon exchange, up to industrial espionage. Recently discovered malware such as Duqu and Alureon point to the alleged utilization of information hiding techniques in botnets for covert communication in the command-and-conquer channels, which proves that information hiding poses important challenges to investigators. On the other side of the spectrum lie legitimate uses, which include circumvention of web censorship and surveillance, computer forensics (tracing and identification), and copyright protection (e.g. watermarking images). Papers must be written in English and describe original research not published or currently under review by other journals or conferences. All relevant papers submitted will go through an external review process. Concerning the preparation of the manuscript, please refer to the “Instructions for Authors” page at the journal website, http://onlinelibrary.wiley.com/journal/10.1002/%28ISSN%291939-0122/homepage/ForAuthors.html Furthermore, the manuscript must be submitted through the online submission system: http://mc.manuscriptcentral.com/scn by selecting the corresponding track. When submitting papers, the authors should identify “Manuscript Type” as “Special Issue,” enter “Running Head” as “SCN-SI-066” and “Special Issue Title” as “Trends in modern information hiding: techniques, applications and detection.” Contributing authors might also be asked to review some of the papers submitted to this special issue. All papers will be rigorously reviewed on the basis of their quality: originality, high scientific quality, good organization and clear writing, sufficient support for assertions and conclusion, appropriate title, abstract that include important points of the paper, satisfactory English, pertinent references, and clear tables and figures. Manuscript submission: 1 March 2014 Acceptance/rejection notification: before 1 July 2014 Expected publication: 2015