Miracle-dz/UniFAR-FTUs huggingface dataset:
Redefining Pleiotropic Drug Resistance in a Pathogenic Yeast: Pdr1 Functions as a Sensor of Cellular Stresses in Candida glabrata

Candida glabrata is a prominent opportunistic fungal pathogen of humans. The increasing incidence of C. glabrata infections is attributed to both innate and acquired resistance to antifungals. Previous studies suggest the transcription factor Pdr1 and several target genes encoding ABC transporters are critical elements of pleiotropic defense against azoles and other antifungals. This study utilizes Hermes transposon insertion profiling to investigate Pdr1-independent and Pdr1-dependent mechanisms that alter susceptibility to the frontline antifungal fluconazole. Several new genes were found to alter fluconazole susceptibility independent of Pdr1 (CYB5, SSK1, SSK2, HOG1, TRP1). A bZIP transcription repressor of mitochondrial function (CIN5) positively regulated Pdr1 while hundreds of genes encoding mitochondrial proteins were confirmed as negative regulators of Pdr1. The antibiotic oligomycin activated Pdr1 and antagonized fluconazole efficacy likely by interfering with mitochondrial processes in C. glabrata. Unexpectedly, disruption of many 60S ribosomal proteins also activated Pdr1, thus mimicking the effects of the mRNA translation inhibitors. Cycloheximide failed to fully activate Pdr1 in a cycloheximide-resistant Rpl28-Q38E mutant. Similarly, fluconazole failed to fully activate Pdr1 in a strain expressing a low-affinity variant of Erg11. Fluconazole activated Pdr1 with very slow kinetics that correlated with the delayed onset of cellular stress. These findings are inconsistent with the idea that Pdr1 directly senses xenobiotics and support an alternative hypothesis where Pdr1 senses cellular stresses that arise only after engagement of xenobiotics with their targets. Importance Candida glabrata is an opportunistic pathogenic yeast that causes discomfort and death. Its incidence has been increasing because of natural defenses to our common antifungal medications. This study explores the entire genome for impacts on resistance to fluconazole. We find several new and unexpected genes can impact susceptibility to fluconazole. Several antibiotics can also alter the efficacy of fluconazole. Most importantly, we find that Pdr1 – a key determinant of fluconazole resistance – is not regulated directly through binding of fluconazole and instead is regulated indirectly by sensing the cellular stresses caused by fluconazole blockage of sterol biosynthesis. This new understanding of drug resistance mechanisms could improve the outcomes of current antifungals and accelerate the development of novel therapeutics.
Renal Neoplasia Occurring in Patients With PTEN Hamartoma Tumor Syndrome

The aim of this study was to assess the histopathologic spectrum of renal tumors in patients with PTEN hamartoma tumor syndrome (PHTS), with a specific focus on potential features predictive of the underlying syndrome. A multi-institutional study was conducted to obtain clinical and pathologic data on renal tumors arising in patients with PHTS, either diagnosed by germline mutational analysis or clinical criteria for Cowden syndrome. Histologic sections of the renal tumors were re-reviewed for classification. Twelve renal epithelial tumors from 9 patients were identified (4 males and 5 females, with a mean age of 41.8 y), 7 of whom carried germline PTEN mutations. All 12 renal epithelial tumors were renal cell carcinomas (RCCs): 5 were chromophobe RCCs, 4 papillary RCCs, and 3 RCC not otherwise specified. Pathologic stage distribution was: 7 (59%) pT1a, 2 (17%) pT1b, 1 (8%) pT2a, 1 (8%) pT2b, and 1 (8%) pT3a. World Health Organization/International Society of Urological Pathology (WHO/ISUP) histologic grade was applicable in 7 (54%) nonchromophobe tumors: 4 (57%) G2, 2 (29%) G3, and 1 (14%) G4. An unexpected histologic finding was the presence of 2 patients with incidental microscopic collections of intrarenal adipocytes that had no features of angiomyolipoma (and were negative with 2 sensitive PEComa markers: cathepsin-K and GPNMB); both were classified as lipoma/“lipomatous hamartomas. ” The average follow-up interval was 67.8 months (13 to 172 mo): 5 patients had no evidence of disease, 2 were lost to follow-up, 1 died of other (non-PHTS) causes (ie, prostate cancer), and 1 was alive with metastatic RCC to the lung (RCC not otherwise specified with rhabdoid differentiation). All tumors showed loss of nuclear PTEN staining by immunohistochemistry. Fumarate hydratase was retained and 2SC was negative in all papillary RCCs. CK7 was moderate-strong/diffuse positive in 4 of 5 chromophobe RCCs and in 3 of 4 papillary RCCs. Renal epithelial tumors associated with PHTS represent a heterogeneous group of RCCs, but classic chromophobe and papillary RCC are most common. The majority have a favorable clinical behavior as would be predicted by subtype. In contrast to other hereditary renal neoplasia syndromes, morphologic features of the RCCs do not allow identification of PHTS-associated neoplasia with any degree of specificity in the absence of clinical setting and/or prior history, but the presence of microscopic “lipomas” within the kidney may provide a clue in rare cases. Therefore, clinical suspicion and genetic counseling with germline testing remain necessary for identifying PHTS-associated RCC.
Information Theory and Linearization Patterns of English Phrasal Prepositional Verbs

• This makes sense if we make the reasonable assumption that communication operates within a noisy channel. If a single linguistic item carrying a massive amount of information is somehow lost, then the message becomes very difficult to comprehend. If all items are weighted relatively equally, however, then it is possible to piece the message back together even if there are errors in transmission or reception.
Profiling of the Klebsiella pneumoniae Phosphoproteome under Iron-Limited and Iron-Replete Conditions

Klebsiella pneumoniae was compared across iron-limited and iron-replete conditions to assess changes within the phosphoproteome using quantitative mass spectrometry. These comparative proteomic data provide insights into cellular responses to nutrient limitation and how nutrient requirements may be exploited to provide potential antimicrobial targets. ABSTRACT Klebsiella pneumoniae was compared across iron-limited and iron-replete conditions to assess changes within the phosphoproteome using quantitative mass spectrometry. These comparative proteomic data provide insights into cellular responses to nutrient limitation and how nutrient requirements may be exploited to provide potential antimicrobial targets.
Lifetime Traumatic Brain Injury and Risk of Post-Concussive Symptoms in the Millennium Cohort Study

Traumatic brain injury (TBI) is prevalent among active duty military service members, with studies reporting up to 23% experiencing at least one TBI, with 10–60% of service members reporting at least one subsequent repeat TBI. A TBI has been associated with an increased risk of cumulative effects and long-term neurobehavioral symptoms, impacting operational readiness in the short-term and overall health in the long term. The association between multiple TBI and post-concussive symptoms (PCS), however, defined as symptoms that follow a concussion or TBI, in the military has not been adequately examined. Previous studies in military populations are limited by methodological issues including small sample sizes, the use of non-probability sampling, or failure to include the total number of TBI. To overcome these limitations, we examined the association between the total lifetime number of TBI and total number of PCS among U.S. active duty military service members who participated in the Millennium Cohort Study. A secondary data analysis was conducted using the Millennium Cohort Study's 2014 survey (n = 28,263) responses on self-reported TBI and PCS (e.g., fatigue, restlessness, sleep disturbances, poor concentration, or memory loss). Zero-inflated negative binomial models calculated prevalence ratios (PRs) and 95% confidence intervals (CIs) for the unadjusted and adjusted associations between lifetime TBIs and PCS. A third of military participants reported experiencing one or more TBIs during their lifetime with 72% reporting at least one PCS. As the mean number of PCS increased, mean lifetime TBIs increased. The mean number of PCS by those with four or more TBI (4.63) was more than twice that of those with no lifetime TBI (2.28). One, two, three, and four or more TBI had 1.10 (95% CI: 1.06–1.15), 1.19 (95% CI: 1.14–1.25), 1.23 (95% CI: 1.17–1.30), and 1.30 times (95% CI: 1.24–1.37) higher prevalence of PCS, respectively. The prevalence of PCS was 2.4 (95% CI: 2.32–2.48) times higher in those with post-traumatic stress disorder than their counterparts. Active duty military service members with a history of TBI are more likely to have PCS than those with no history of TBI. These results suggest an elevated prevalence of PCS as the number of TBI increased. This highlights the need for robust, longitudinal studies that can establish a temporal relationship between repetitive TBI and incidence of PCS. These findings have practical relevance for designing both workplace safety prevention measures and treatment options regarding the effect on and from TBI among military personnel.
Measuring the 3D shape of high temperature objects using blue sinusoidal structured light

The visible light radiated by some high temperature objects (less than 1200 °C) almost lies in the red and infrared waves. It will interfere with structured light projected on a forging surface if phase measurement profilometry (PMP) is used to measure the shapes of objects. In order to obtain a clear deformed pattern image, a 3D measurement method based on blue sinusoidal structured light is proposed in this present work. Moreover, a method for filtering deformed pattern images is presented for correction of the unwrapping phase. Blue sinusoidal phase-shifting fringe pattern images are projected on the surface by a digital light processing (DLP) projector, and then the deformed patterns are captured by a 3-CCD camera. The deformed pattern images are separated into R, G and B color components by the software. The B color images filtered by a low-pass filter are used to calculate the fringe order. Consequently, the 3D shape of a high temperature object is obtained by the unwrapping phase and the calibration parameter matrixes of the DLP projector and 3-CCD camera. The experimental results show that the unwrapping phase is completely corrected with the filtering method by removing the high frequency noise from the first harmonic of the B color images. The measurement system can complete the measurement in a few seconds with a relative error of less than 1 : 1000.
Recent updates in the use of pharmacological therapies for downstaging in patients with hepatocellular carcinoma

ABSTRACT Introduction Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, but only 20–30% of patients benefit from potentially curative treatments such as liver resection or transplantation. This article reviews conventional treatments and recent progress in pharmacotherapy for advanced HCC, with a focus on downstaging unresectable tumors to resectable status. Areas covered In this article, conventional treatments and recent progress in pharmacotherapy for advanced HCC, aiming at downstaging from unresectable to resectable status, are reviewed. Future prospectives of combination therapies using immune checkpoint inhibitors were also introduced by reviewing recent clinical trials, paying attention to the objective response rate as its potential of downstaging treatments. Expert opinion The newly developed pharmacological therapies showed higher responses. Although various tumor statuses in advanced HCC hamper detailed analysis of successful conversion rate, the novel combined immunotherapies are expected to provide more opportunities for subsequent curative surgery for initially unresectable advanced HCC. The conversion treatment strategies for unresectable HCC should be separately discussed for ‘technically resectable but oncologically unfavorable’ HCC and metastatic or invasive HCC beyond curative surgical treatments. The optimal downstaging treatment strategy for advanced HCC is awaited. Elucidation of preoperatively available factors that predict successful downstaging will allow the tailoring of promising initial treatments leading to conversion surgery.
A pump-probe experiment in cw-mode on ionization of Rydberg atoms

Rydberg atoms are in the focus of intense research due to the peculiar properties which make them interesting candidates for quantum optics and quantum information applications. In this work we study the ionization of Rydberg atoms due to their interaction with a trapping laser field, and a reaction microscope is used to measure photoelectron angular and energy distributions. Reaction microscopes are excellent tools when brandished against atomic photoionization processes involving pulsed lasers; the timing tied to each pulse is crucial in solving the subsequent equations of motion for the atomic fragments in the spectrometer field. However, when used in pump-probe schemes, which rely on continuous wave probe lasers, vital information linked to the time of flight is lost. This study reports on a method in which the standard ReMi technique is extended in time through coincidence measurements. This is then applied to the photoionization of $^6$Li atoms initially prepared in optically pumped $2^{2}S_{1/2}$ and $2^{2}P_{3/2}$ states. Multi-photon excitation from a tunable femtosecond laser is exploited to produce Rydberg atoms inside an infrared optical dipole trap; the structure and dynamics of the subsequent cascade back towards ground is evaluated.
Large electro-opto-mechanical coupling in VO2 neuristors

Biological neurons are electro-mechanical systems, where the generation and propagation of an action potential is coupled to generation and transmission of an acoustic wave. Neuristors, such as VO2, characterized by insulator-metal transition (IMT) and negative differential resistance, can be engineered as self-oscillators, which are good approximations of biological neurons in the domain of electrical signals. In this study, we show that these self-oscillators are coupled electro-opto-mechanical systems, with better energy conversion coefficients than the conventional electromechanical or electrooptical materials. This is due to the significant contrast in the material's resistance, optical refractive index and density across the induced temperature range in a Joule heating driven IMT. We carried out laser interferometry to measure the opto-mechanical response while simultaneously driving the devices electrically into self-oscillations of different kinds. We analyzed films of various thicknesses, engineered device geometry and performed analytical modelling to decouple the effects of refractive index change vis-a-vis mechanical strain in the interferometry signal. We show that the effective piezoelectric coefficient (d13*) for our neuristor devices is 660 pm/V, making them viable alternatives to Pb-based piezoelectrics for MEMS applications. Furthermore, we show that the effective electro-optic coefficient (r13*) is ~22 nm/V, which is much larger than that in thin-film and bulk Pockels materials.
Prefix-free Graphs and Suffix Array Construction in Sublinear Space

A recent paradigm shift in bioinformatics from a single reference genome to a pangenome brought with it several graph structures. These graph structures must implement operations, such as efficient construction from multiple genomes and read mapping. Read mapping is a well-studied problem in sequential data, and, together with data structures such as suffix array and Burrows-Wheeler transform, allows for efficient computation. Attempts to achieve comparatively high performance on graphs bring many complications since the common data structures on strings are not easily obtainable for graphs. In this work, we introduce prefix-free graphs, a novel pangenomic data structure; we show how to construct them and how to use them to obtain well-known data structures from stringology in sublinear space, allowing for many efficient operations on pangenomes.
DR-HAI: Argumentation-based Dialectical Reconciliation in Human-AI Interactions

We present DR-HAI -- a novel argumentation-based framework designed to extend model reconciliation approaches, commonly used in human-aware planning, for enhanced human-AI interaction. By adopting an argumentation-based dialogue paradigm, DR-HAI enables interactive reconciliation to address knowledge discrepancies between an explainer and an explainee. We formally describe the operational semantics of DR-HAI, provide theoretical guarantees, and empirically evaluate its efficacy. Our findings suggest that DR-HAI offers a promising direction for fostering effective human-AI interactions.
Multi-Scale Cross Contrastive Learning for Semi-Supervised Medical Image Segmentation

Semi-supervised learning has demonstrated great potential in medical image segmentation by utilizing knowledge from unlabeled data. However, most existing approaches do not explicitly capture high-level semantic relations between distant regions, which limits their performance. In this paper, we focus on representation learning for semi-supervised learning, by developing a novel Multi-Scale Cross Supervised Contrastive Learning (MCSC) framework, to segment structures in medical images. We jointly train CNN and Transformer models, regularising their features to be semantically consistent across different scales. Our approach contrasts multi-scale features based on ground-truth and cross-predicted labels, in order to extract robust feature representations that reflect intra- and inter-slice relationships across the whole dataset. To tackle class imbalance, we take into account the prevalence of each class to guide contrastive learning and ensure that features adequately capture infrequent classes. Extensive experiments on two multi-structure medical segmentation datasets demonstrate the effectiveness of MCSC. It not only outperforms state-of-the-art semi-supervised methods by more than 3.0% in Dice, but also greatly reduces the performance gap with fully supervised methods.
Cross-Lingual Cross-Age Group Adaptation for Low-Resource Elderly Speech Emotion Recognition

Speech emotion recognition plays a crucial role in human-computer interactions. However, most speech emotion recognition research is biased toward English-speaking adults, which hinders its applicability to other demographic groups in different languages and age groups. In this work, we analyze the transferability of emotion recognition across three different languages--English, Mandarin Chinese, and Cantonese; and 2 different age groups--adults and the elderly. To conduct the experiment, we develop an English-Mandarin speech emotion benchmark for adults and the elderly, BiMotion, and a Cantonese speech emotion dataset, YueMotion. This study concludes that different language and age groups require specific speech features, thus making cross-lingual inference an unsuitable method. However, cross-group data augmentation is still beneficial to regularize the model, with linguistic distance being a significant influence on cross-lingual transferability. We release publicly release our code at https://github.com/HLTCHKUST/elderly_ser.
Temporal Analysis of Misinformation on Parler

Social media platforms have facilitated the rapid spread of dis- and mis-information. Parler, a US-based fringe social media platform that positions itself as a champion of free-speech, has had substantial information integrity issues. In this study, we seek to characterize temporal misinformation trends on Parler. Comparing a dataset of 189 million posts and comments from Parler against 1591 rated claims (false, barely true, half true, mostly true, pants on fire, true) from Politifact, we identified 231,881 accuracy-labeled posts on Parler. We used BERT-Topic to thematically analyze the Poltifact claims, and then compared trends in these categories to real world events to contextualize their distribution. We identified three distinct categories of misinformation circulating on Parler: COVID-19, the 2020 presidential election, and the Black Lives Matter movement. Our results are significant, with a surprising 69.2% of posts in our dataset found to be 'false' and 7.6% 'barely true'. We also found that when Parler posts ('parleys') containing misinformation were posted increased around major events (e.g., George Floyd's murder).
Exploration of strongly correlated states in SmB6 through a comparison of its two-coil pick-up response to that of Bi2Se3

Earlier studies on the Kondo insulator SmB6 reveal the presence of a bulk Kondo insulating gap between 30 - 50 K, and the emergence of a conducting surface state only below 4 K. Here, we compare the two-coil mutual inductance pick-up response of SmB6 single crystal with that of a conventional topological insulator (TI), Bi2Se3 single crystal. From these studies we identify three distinct temperature regimes for SmB6, viz., (i) T>= T*(~ 66 K), (ii) (40 K~) T_g<= T<T*, and (iii) T<T_g. At T* in SmB6, we observe a peak in the temperature-dependent AC pickup signal which corresponds to the peak in the broad hump feature in the bulk DC susceptibility measurements and features in the resistivity measurements. A dip in the pickup signal at T_g in SmB6 correlates with the evidence for the opening of a bulk Kondo gap in transport measurements. Our study of the pickup signal in SmB6 suggests the presence of a thin (submicron order thickness) high conducting surface layer from a temperature just below T_g. In this T regime in SmB6, the pickup signal shows a distinct square root frequency (f) dependence compared to the linear f dependence found in Bi2Se3. Across all the different T regimes, distinct AC frequency dependence and scaling properties are observed. Our results suggest that above T*, weak exchange interactions cause electrons to scatter from random ion sites. Electronic correlations gradually strengthen with the onset of Kondo like hybridization, setting in from below T*, and at T_g, a strongly correlated Kondo gap opens up in the bulk of the material. The appearance of the thin high conducting surface layer is nearly coincident with the onset of bulk Kondo insulating state below T_g in SmB6.
Enhancing Traffic Flow Efficiency through an Innovative Decentralized Traffic Control Based on Traffic Bottlenecks

To address the challenge of conflicting traffic flows that complete on opposing cycle times in a specific phase of the traffic light, we proposed a novel decentralized traffic light control methodology based on the identification of the congestion's bottleneck and its influence. By computing the cost of each congested tree, this methodology, called the Tree Method, prioritizes bottlenecks based on global influence, i.e., their impact on the entire road network. To test this methodology, we used SUMO (Simulation of Urban Mobility) as a traffic simulator to run various simulations with both realistic and abstract Origin-Destination (OD) matrices under different traffic loads. By prioritizing traffic flows based on their global cost, rather than merely local ones, the Tree Method accurately identified the root cause of traffic-tree congestion and its effect along the traffic upstream. It exhibited major improvements in both the throughput and the average travel time measurements. Further in-depth analyses of individual simulation runs and time-based performance demonstrated that the Tree Method is superior compared to other methods, not only in terms of average performance but also for the majority of drivers and throughout most of the time. Another significant advantage of this method is its simplicity of analysis, facilitating real-time adjustments in each cycle and aligning with the inherent feedback dynamics of traffic flows. This feature makes the Tree Method highly suitable for integration into actual traffic control systems.