The Roles of Trust in Government and Sense of Community in the COVID-19 Contact Tracing Privacy Calculus: Mixed Method Study Using a 2-Wave Survey and In-Depth Interviews.

BACKGROUND: Contact tracing technology has been adopted in many countries to aid in identifying, evaluating, and handling individuals who have had contact with those infected with COVID-19. Singapore was among the countries that actively implemented the government-led contact tracing program known as TraceTogether. Despite the benefits the contact tracing program could provide to individuals and the community, privacy issues were a significant barrier to individuals' acceptance of the program. OBJECTIVE: Building on the privacy calculus model, this study investigates how the perceptions of the 2 key groups (ie, government and community members) involved in the digital contact tracing factor into individuals' privacy calculus of digital contact tracing. METHODS: Using a mixed method approach, we conducted (1) a 2-wave survey (n=674) and (2) in-depth interviews (n=12) with TraceTogether users in Singapore. Using structural equation modeling, this study investigated how trust in the government and the sense of community exhibited by individuals during the early stage of implementation (time 1) predicted privacy concerns, perceived benefits, and future use intentions, measured after the program was fully implemented (time 2). Expanding on the survey results, this study conducted one-on-one interviews to gain in-depth insights into the privacy considerations involved in digital contact tracing. RESULTS: The results from the survey showed that trust in the government increased perceived benefits while decreasing privacy concerns regarding the use of TraceTogether. Furthermore, individuals who felt a connection to community members by participating in the program (ie, the sense of community) were more inclined to believe in its benefits. The sense of community also played a moderating role in the influence of government trust on perceived benefits. Follow-up in-depth interviews highlighted that having a sense of control over information and transparency in the government's data management were crucial factors in privacy considerations. The interviews also highlighted surveillance as the most prevalent aspect of privacy concerns regarding TraceTogether use. In addition, our findings revealed that trust in the government, particularly the perceived transparency of government actions, was most strongly associated with concerns regarding the secondary use of data. CONCLUSIONS: Using a mixed method approach involving a 2-wave survey and in-depth interview data, we expanded our understanding of privacy decisions and the privacy calculus in the context of digital contact tracing. The opposite influences of privacy concerns and perceived benefit on use intention suggest that the privacy calculus in TraceTogether might be viewed as a rational process of weighing between privacy risks and use benefits to make an uptake decision. However, our study demonstrated that existing perceptions toward the provider and the government in the contact tracing context, as well as the perception of the community triggered by TraceTogether use, may bias user appraisals of privacy risks and the benefits of contact tracing.

Rapid and sensitive detection of gram-negative bacteria using surface-immobilized polymyxin B.

Although detection of gram-negative bacteria (GNB) in body fluids is important for clinical purpose, traditional gram staining and other recently developed methods have inherent limitations in terms of accuracy, sensitivity, and convenience. To overcome the weakness, this study proposed a method detecting GNB based on specific binding of polymyxin B (PMB) to lipopolysaccharides (LPS) of GNB. Fluorescent microscopy demonstrated that surface immobilized PMB using a silane coupling agent was possible to detect fluorescent signal produced by a single Escherichia coli (a model GNB) cell. Furthermore, the signal was selective enough to differentiate between GNB and gram-positive bacteria. The proposed method could detect three cells per ml within one hour, indicating the method was very sensitive and the sensing was rapid. These results suggest that highly multifold PMB binding on each GNB cell occurred, as millions of LPS are present on cell wall of a GNB cell. Importantly, the principle used in this study was realized in a microfluidic chip for a sample containing E. coli cells suspended in porcine plasma, demonstrating its potential application to practical uses. In conclusion, the proposed method was accurate, sensitive, and convenient for detecting GNB, and could be applied clinically.

Factors affecting the safe sexual behaviors of Korean young adults by gender: a structural equation model.

PURPOSE: The aim of this study was to determine the factors that influence safe sexual behaviors of Korean young adults and identify differences by gender. METHODS: This study aimed to determine which factors affected safe sexual behaviors based on the Theory of Planned Behavior. Data from 437 Korean young adults (in their 20s and 30s) were collected via online survey between January 3 and January 28, 2022. The questionnaire included items on sexual body image, sexual role perception, sexual attitudes, sexual socialization, sexual communication, and safe sexual behaviors. Structural equation modeling was performed. RESULTS: According to the overall model fit of the hypothetical model, the final model was acceptable and explained 49% of safe sexual behaviors. Sexual attitudes (ß=-.70, p<.001) and sexual communication (ß=.53, p<.001) directly affected safe sexual behaviors, and sexual role perception (ß=.42, p<.001) indirectly affected safe sexual behaviors in a combined model. There were gender differences in the path from sexual attitudes (ß=-.94, p<.001) and sexual communication (ß=.66, p<.001) to safe sexual behaviors and from sexual body image (ß=.27, p<.001) to sexual communication. CONCLUSION: Sexual attitudes and sexual communication were predictors of safe sexual behaviors, which differed by gender. Strategies that consider sexual attitudes, sexual communication, sexual role perception, and differences between men and women should be developed to improve the safe sexual behaviors of young adults.

SGRN: A Cas12a-driven Synthetic Gene Regulatory Network System.

Gene regulatory networks, which control gene expression patterns in development and in response to stimuli, use regulatory logic modules to coordinate inputs and outputs. One example of a regulatory logic module is the gene regulatory cascade (GRC), where a series of transcription factor genes turn on in order. Synthetic biologists have derived artificial systems that encode regulatory rules, including GRCs. Furthermore, the development of single-cell approaches has enabled the discovery of gene regulatory modules in a variety of experimental settings. However, the tools available for validating these observations remain limited. Based on a synthetic GRC using DNA cutting-defective Cas9 (dCas9), we designed and implemented an alternative synthetic GRC utilizing DNA cutting-defective Cas12a (dCas12a). Comparing the ability of these two systems to express a fluorescent reporter, the dCas9 system was initially more active, while the dCas12a system was more streamlined. Investigating the influence of individual components of the systems identified nuclear localization as a major driver of differences in activity. Improving nuclear localization for the dCas12a system resulted in 1.5-fold more reporter-positive cells and a 15-fold increase in reporter intensity relative to the dCas9 system. We call this optimized system the "Synthetic Gene Regulatory Network" (SGRN, pronounced "sojourn").

Different contribution of exoelectrogens in methanogenesis via direct interspecies electron transfer (DIET) by the different substrate in continuous anaerobic bioreactor.

Direct interspecies electron transfer (DIET) is a syntrophic mechanism for electron transfer between exo- and endoelectrogens. Previous studies have demonstrated that methanogenesis performance was significantly improved via the DIET mechanism through conductive materials (CMs) under batch conditions with a single substrate, while that under continuous condition is still under investigation. To investigate how the DIET via CM on methanogenesis performance was changed in response to the different substrates (acetate versus glucose)-fed in continuous anaerobic bioreactors, continuous bioreactors were operated by cross-feeding with acetate and glucose. Acetate-fed conditions showed 0.40 day shorten lagtime, 1.88- and 1.22-folds higher methane production rate, and ultimate methane production than glucose-fed conditions, respectively. Burkholderiaceae- and Anaerolineaceae-related exo-electrogenic populations were enriched with low abundance of Geobacter species in batch reactors. Furthermore, influent substrates affected the distribution of the enriched populations. Taken together, the results suggested that different syntrophic associations contributed methane production by DIET in continuous bioreactors.

Can the Internet of Things Persuade Me? An Investigation Into Power Dynamics in Human-Internet of Things Interaction.

The advent of artificial intelligence (AI) and the Internet of Things (IoT) has revolutionized user experience with objects. Things can perform social roles and convey persuasive messages to users, posing an important research question for communication and human-computer interaction researchers: What are the factors and underlying mechanisms that shape persuasive effects of IoT? Bridging the reactance theory and the computers are social actors paradigm, this study focuses on how power dynamics are shaped in human-IoT interactions and its implications on persuasion. Specifically, the study examines the effects of the social role assigned to the IoT mobile app agent and the scope of IoT controlled by the app on users' perceived power and subsequent persuasive outcomes. The results reveal that when the mobile IoT app is for controlling a smart home, the servant (vs. companion) agent elicits greater perceived power over IoT for users, leading to less threat-to-freedom and better persuasive outcomes, including attitude, intention, and actual behavior. However, such a difference is not observed when the mobile app is for controlling a single smart device (i.e., smart fridge). The study findings offer valuable implications for communication practitioners interested in using IoT as a persuasive tool.

A comparative assessment of action plans on antimicrobial resistance from OECD and G20 countries using natural language processing.

Following the launch of the Global Action Plan on antimicrobial resistance (AMR-GAP) in 2015, most OECD and G20 countries developed their own national action plans (AMR-NAPs). This is the first paper that deploys natural language processing (NLP) techniques to systematically measure and compare the extent to which AMR-NAPs from 21 OECD and G20 countries align with the AMR-GAP in terms of the strategic objectives and interventions. We quantify the extent of alignment based on two NLP metrics: term-frequency (TF) and term-frequency-inverse document frequency (TF-IDF). Quantifying TF allows us to compare the relative prominence of strategic objectives and interventions, whereas quantifying TF-IDF enables us to identify interventions that occur more frequently in each AMR-NAP. Similar to the AMR-GAP, in our sample, terms associated with optimizing antimicrobial use in human and animal health have the highest frequency (TF = 0. 287), whereas terms linked to raising AMR awareness and education have the lowest frequency (TF = 0.066). Substantial cross-country variation exists in the distribution of interventions that are distinctly frequent in each AMR-NAP. We also report new evidence on the selected policy design and monitoring and evaluation features of these documents. Our results suggest a high degree of congruence between the AMR-GAP and AMR-NAPs, with notable diversity in the spate of interventions that OECD and G20 countries discuss in their action plans.

Evaluation of Swab-Seq as a scalable, sensitive assay for community surveillance of SARS-CoV-2 infection.

The ongoing SARS-CoV-2 pandemic and subsequent demand for viral testing has led to issues in scaling diagnostic lab efforts and in securing basic supplies for collection and processing of samples. This has motivated efforts by the scientific community to establish improved protocols that are more scalable, less resource intensive, and less expensive. One such developmental effort has resulted in an assay called "Swab-Seq", so named because it was originally developed to work with dry nasal swab samples. The existing gold standard test consists of RNA extracted from a nasopharyngeal (NP) swab that is subjected to quantitative reverse transcription polymerase chain reaction (qRT-PCR). Swab-Seq adapts this method to a next-generation sequencing readout. By pairing this modification with extraction-free sampling techniques, Swab-Seq achieves high scalability, low cost per sample, and a reasonable turnaround time. We evaluated the effectiveness of this assay in a community surveillance setting by testing samples collected from both symptomatic and asymptomatic individuals using the traditional NP swab. In addition, we evaluated extraction-free sampling techniques (both saliva and saline mouth gargle samples). We found the assay to be as clinically sensitive as the qRT-PCR assay, adaptable to multiple sample types, and able to easily accommodate hundreds of samples at a time. We thus provide independent validation of Swab-Seq and extend its utility regarding sample type and sample stability. Assays of this type greatly expand the possibility of routine, noninvasive, repeated testing of asymptomatic individuals suitable for current and potential future needs.

The Influence of Normative Perceptions on the Uptake of the COVID-19 TraceTogether Digital Contact Tracing System: Cross-sectional Study.

BACKGROUND: In 2020, the Singapore government rolled out the TraceTogether program, a digital system to facilitate contact tracing efforts in response to the COVID-19 pandemic. This system is available as a smartphone app and Bluetooth-enabled token to help identify close contacts. As of February 1, 2021, more than 80% of the population has either downloaded the mobile app or received the token in Singapore. Despite the high adoption rate of the TraceTogether mobile app and token (ie, device), it is crucial to understand the role of social and normative perceptions in uptake and usage by the public, given the collective efforts for contact tracing. OBJECTIVE: This study aimed to examine normative influences (descriptive and injunctive norms) on TraceTogether device use for contact tracing purposes, informed by the theory of normative social behavior, a theoretical framework to explain how perceived social norms are related to behaviors. METHODS: From January to February 2021, cross-sectional data were collected by a local research company through emailing their panel members who were (1) Singapore citizens or permanent residents aged 21 years or above; (2) able to read English; and (3) internet users with access to a personal email account. The study sample (n=1137) was restricted to those who had either downloaded the TraceTogether mobile app or received the token. RESULTS: Multivariate (linear and ordinal logistic) regression analyses were carried out to assess the relationships of the behavioral outcome variables (TraceTogether device usage and intention of TraceTogether device usage) with potential correlates, including perceived social norms, perceived community, and interpersonal communication. Multivariate regression analyses indicated that descriptive norms (unstandardized regression coefficient ß=0.31, SE=0.05; P<.001) and injunctive norms (unstandardized regression coefficient ß=0.16, SE=0.04; P<.001) were significantly positively associated with the intention to use the TraceTogether device. It was also found that descriptive norms were a significant correlate of TraceTogether device use frequency (adjusted odds ratio [aOR] 2.08, 95% CI 1.66-2.61; P<.001). Though not significantly related to TraceTogether device use frequency, injunctive norms moderated the relationship between descriptive norms and the outcome variable (aOR 1.12, 95% CI 1.03-1.21; P=.005). CONCLUSIONS: This study provides useful implications for the design of effective intervention strategies to promote the uptake and usage of digital methods for contact tracing in a multiethnic Asian population. Our findings highlight that influence from social networks plays an important role in developing normative perceptions in relation to TraceTogether device use for contact tracing. To promote the uptake of the TraceTogether device and other preventive behaviors for COVID-19, it would be useful to devise norm-based interventions that address these normative perceptions by presenting high prevalence and approval of important social referents, such as family and close friends.

Web-based behavioral intervention to reduce exposure to phthalate metabolites, bisphenol A, triclosan, and parabens in mothers with young children: A randomized controlled trial.

In this study, a web-based behavioral intervention was designed, which aimed to reduce exposure to phthalate metabolites, bisphenol A, triclosan, and parabens in mothers with young children. A randomized controlled design with two groups was used to verify the effects of the intervention pre- and post-test. In total, 51 mothers participated in the study, categorizing 26 and 25 in the intervention and control groups, respectively. The web-based behavioral intervention focused on changes in diet, personal care products, and health behavior and reinforced behavior through encouragement. This program included an educational video, a game for locating endocrine disruptors at home, a method for locating facilities potentially emitting endocrine disruptors, resources, and a questions and answers mode. Data were collected from May 18 to June 30, 2020. Participants allocated to the intervention group were provided access to the behavioral intervention website via a computer or smartphone. Participants allocated to the control group were sent written information about endocrine disruptors via mail. For both the intervention and control groups, questionnaire results and maternal urine samples were assessed at baseline, during the intervention, and after one month. After the intervention, the urinary concentrations of mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), bisphenol A (BPA), methylparaben (MP), ethylparaben (EP), and propylparaben (PP) were found to be significantly decreased in the intervention group. Compared with the control group, the intervention group showed significantly decreased urinary geometric mean values of MEHP, MEOHP, BPA, MP, and PP after one month compared with those during the intervention (3.8%, 16.3%, 28.4%, 9.2%, and 24.4%, respectively). Hence, the web-based behavioral intervention was effective at reducing the exposure to endocrine disruptors in mothers with young children.

Effect of microbial community structure in inoculum on the stimulation of direct interspecies electron transfer for methanogenesis.

To investigate how the seed microbial community structure affects the improvement of methanogenesis efficiency through direct interspecies electron transfer (DIET), a biomethane potential (BMP) test was conducted using sludge collected from a total of six anaerobic digesters. DIET-stimulating microbial populations were investigated by 16S rRNA gene sequence analysis. Correlations between microbial community composition and methane production performance by DIET were analyzed. The methane production rate increased under all conditions when granular activated carbon (GAC) was injected regardless of the inoculum type. However, redundancy analysis indicated a significant correlation between the inoculum microbial community and lag time. In a network analysis, Methanolinea species distributed in the inocula formed a single modularity with lag time, suggesting that the methanogens in the inocula might reduce the lag time of methanogenesis through DIET. Overall, this study revealed that the inoculum microbial community composition is an important factor affecting methane production efficiency by DIET.

Recent advances in methanogenesis through direct interspecies electron transfer via conductive materials: A molecular microbiological perspective.

Conductive materials can serve as biocatalysts during direct interspecies electron transfer for methanogenesis in anaerobic reactors. However, the mechanism promoting direct interspecies electron transfer in anaerobic reactors, particularly under environments in which diverse substrates and microorganisms coexist, remains to be elucidated from a scientific or an engineering point of view. Currently, many molecular microbiological approaches are employed to understand the fundamentals of this phenomenon. Here, the direct interspecies electron transfer mechanisms and relevant microorganisms identified to date using molecular microbiological methods were critically reviewed. Moreover, molecular microbiological methods for direct interspecies electron transfer used in previous studies and important findings thus revealed were analyzed. This review will help us better understand the phenomena of direct interspecies electron transfer using conductive materials and offer a framework for future molecular microbiological studies.

When Facebook Becomes a Part of the Self: How Do Motives for Using Facebook Influence Privacy Management?

This study examines how three different motivations for using an SNS (i.e., self-expression, belonging, and memory archiving) influence multi-facets of privacy boundary management on the platform mediated by self-extension to it. In recognition of the fact that information management on SNSs often goes beyond the "disclosure-withdrawal" dichotomy, the study investigates the relationships between the three SNS motives and privacy boundary management strategies (i.e., collective boundary and boundary turbulence management). An online survey with Facebook users (N = 305) finds that the three Facebook motivations are positively correlated to users' self-extension to Facebook. The motivations for using Facebook are positively associated with the management of different layers of privacy boundaries (i.e., basic, sensitive, and highly sensitive), when Facebook self-extension is mediated. In addition, the three motives have indirect associations with potential boundary turbulence management mediated by Facebook self-extension. Extending the classic idea that privacy is deeply rooted in the self, the study demonstrates that perceiving an SNS as part of the self-system constitutes a significant underlying psychological factor that explains the linkage between motives for using SNSs and privacy management.

Effect of broad-spectrum biofilm inhibitor raffinose, a plant galactoside, on the inhibition of co-culture biofilm on the microfiltration membrane.

A membrane bioreactor (MBR) integrates process such as membrane filtration and biological treatment of activated sludge. However, organic, inorganic and biological matters cause membrane fouling, which seriously affects membrane performance. The goal of this study was to evaluate the biofouling inhibition capacity of raffinose during the MBR process. The results showed that 0-1,000 µM raffinose significantly reduced the formation of the P. aeruginosa and S. aureus co-culture biofilm by about 25-52 % in a concentration-dependent manner. In addition, the effect of raffinose on the microfiltration membrane biofilm was tested in a flow reactor and lab-scale MBR unit. The results showed that the co-culture biofilm and transmembrane pressure were decreased by raffinose treatment compared to those by furanone C-30 treatment. These results clearly demonstrated that raffinose, broad-spectrum biofilm inhibitor, inhibits biofilm formation in mixed cultures and could be used to mitigate biofouling in MBR processes.

Can Liking, Commenting, and Sharing Enhance Persuasion? The Interaction Effect between Modality Interactivity and Agency Affordances on Smokers' Quitting Intentions.

This article examines whether the persuasive potential of modality interactivity on anti-smoking websites can be harnessed by adding agency affordances, such as the like, comment, and share features. Using a 2 × 2 factorial experiment with a current smoker sample (N = 154), we investigated the interaction effects between modality interactivity (low vs. high) and agency affordances (absence vs. presence) on persuasion outcomes. The results showed that the effects of modality interactivity on telepresence, systematic processing, and change in quitting intentions varied depending on the existence of agency affordances on the website. Agency affordances on the anti-smoking website led to a greater sense of agency and systematic processing on the website content. Only in the presence of agency affordances did modality interactivity enhance the feeling of telepresence, which led to greater quitting intentions than in the control condition. Without agency affordances, modality interactivity diminished systematic processing, leading to lower quitting intentions.

Effect of inoculum concentration on methanogenesis by direct interspecies electron transfer: Performance and microbial community composition.

To understand the effect of inoculum concentration on direct interspecies electron transfer (DIET) for methanogenesis, batch-type anaerobic bioreactors with different inoculum concentrations were operated with and without supplemented granular activated carbon (GAC). With decrease in inoculum concentration, GAC-supplemented bioreactors showed faster methane production rates and reduced lag times. Geobacter species were specifically enriched on the GAC surfaces under lower inoculum concentration conditions. Together, the relative abundance of aceticlastic methanogens (competitors of Geobacter species for acetate) gradually decreased when the inoculum concentration increased. These results suggested that the specific enrichment of Geobacter species by outcompeting with aceticlastic methanogens through low inoculum concentrations on GAC surfaces accelerated methanogenesis by DIET via GAC in anaerobic bioreactors. Taken together, the results of this study suggested that inoculum concentration is an important factor in stimulating DIET for methane production.

Small-Molecule-Targeting Hairpin Loop of hTERT Promoter G-Quadruplex Induces Cancer Cell Death.

Increased telomerase activity is associated with malignancy and poor prognosis in human cancer, but the development of targeted agents has not yet provided clinical benefit. Here we report that, instead of targeting the telomerase enzyme directly, small molecules that bind to the G-hairpin of the hTERT G-quadruplex-forming sequence kill selectively malignant cells without altering the function of normal cells. RG260 targets the hTERT G-quadruplex stem-loop folding but not tetrad DNAs, leading to downregulation of hTERT expression. To improve physicochemical and pharmacokinetic properties, we derived a small-molecule analog, RG1603, from the parent compound. RG1603 induces mitochondrial defects including PGC1α and NRF2 inhibition and increases oxidative stress, followed by DNA damage and apoptosis. RG1603 injected as a single agent has tolerable toxicity while achieving strong anticancer efficacy in a tumor xenograft mouse model. These results demonstrate a unique approach to inhibiting the hTERT that functions by impairing mitochondrial activity, inducing cell death.

Antibacterial application of covalently immobilized photosensitizers on a surface.

Singlet oxygen produced by irradiating photosensitizers (PSs) can be used to kill pathogens during water treatment. Chemical immobilization of the PSs on surfaces can maintain their disinfection function long-term. In this study, two model PSs (rose bengal (RB) and hematoporphyrin (HP)) were immobilized on a glass surface using a silane coupling agent with an epoxide group, and their antibacterial properties were analyzed. Fourier transform infrared spectroscopy demonstrated that a covalent bond formed between the epoxide group and hydroxyl group in the PSs. A large proportion of the immobilized PSs (approximately 50%) was active in singlet oxygen production, which was evidenced by a comparative analysis with free PSs. RB was more effective at producing singlet oxygen than HP. The immobilized PSs were durable in terms of repeated use. On the other hand, singlet oxygen produced by the PSs was effective at killing bacteria, mostly for Gram-positive bacteria (> 90% death for 2 h of irradiation), by damaging the cell membrane. The preferable antibacterial property against Gram-positive bacteria compared with that against Gram-negative bacteria suggested efficient penetrability of singlet oxygen across the cell membrane, which led to cell death. Taken together, it was concluded that immobilization of PSs on surfaces using the silane coupling agent proposed in this study was effective at killing Gram-positive bacteria by forming singlet oxygen.

Direct interspecies electron transfer via conductive materials: A perspective for anaerobic digestion applications.

Anaerobic digestion (AD) is a microbial process that produces renewable energy in the form of methane by treating organic waste and high-strength wastewater. Recent studies have demonstrated that conductive materials can promote direct interspecies electron transfer (DIET) between exoelectrogenic bacteria and methanogenic archaea. DIET via conductive materials is more effective for methane production than interspecies electron transfer using electron carriers such as hydrogen, a principal route of methane production in conventional AD. This critical review presents the current understanding of DIET via conductive materials for methane production, summarizes the relevant studies published to date, and analyzes these studies with regard to conductive materials, substrates, inocula, performance, and microorganisms. Based on this analysis, possible future directions are suggested for practical DIET applications via conductive materials in AD.

A Pharmacological Chaperone Molecule Induces Cancer Cell Death by Restoring Tertiary DNA Structures in Mutant hTERT Promoters.

Activation of human telomerase reverse transcriptase (hTERT) is necessary for limitless replication in tumorigenesis. Whereas hTERT is transcriptionally silenced in normal cells, most tumor cells reactivate hTERT expression by alleviating transcriptional repression through diverse genetic and epigenetic mechanisms. Transcription-activating hTERT promoter mutations have been found to occur at high frequencies in multiple cancer types. These mutations have been shown to form new transcription factor binding sites that drive hTERT expression, but this model cannot fully account for differences in wild-type (WT) and mutant promoter activation and has not yet enabled a selective therapeutic strategy. Here, we demonstrate a novel mechanism by which promoter mutations activate hTERT transcription, which also sheds light on a unique therapeutic opportunity. Promoter mutations occur in a core promoter region that forms tertiary structures consisting of a pair of G-quadruplexes involved in transcriptional silencing. We show that promoter mutations exert a detrimental effect on the folding of one of these G-quadruplexes, resulting in a nonfunctional silencer element that alleviates transcriptional repression. We have also identified a small drug-like pharmacological chaperone (pharmacoperone) molecule, GTC365, that acts at an early step in the G-quadruplex folding pathway to redirect mutant promoter G-quadruplex misfolding, partially reinstate the correct folding pathway, and reduce hTERT activity through transcriptional repression. This transcription-mediated repression produces cancer cell death through multiple routes including both induction of apoptosis through inhibition of hTERT's role in regulating apoptosis-related proteins and induction of senescence by decreasing telomerase activity and telomere length. We demonstrate the selective therapeutic potential of this strategy in melanoma cells that overexpress hTERT.