Miracle-dz/UniFAR-FTUs huggingface dataset:
Energy Efficient Single-Ended 6-T SRAM for Multimedia Applications

Image processing and other multimedia applications require large embedded storage. In some of the earlier works approximate memory has been shown as a potential energy-efficient solution for such error-tolerant applications. In this brief, we propose a single ended 6-T (SE6T) static random access memory (SRAM) cell which has about 50% less dynamic power compared to conventional 6-T SRAM cell with the same bit error rate (BER). Since image processing applications are tolerant to errors, ultra low voltage power-efficient embedded memories with BER can be used for storage. We show that 1 KB (<inline-formula> <tex-math notation="LaTeX">$256 \times 32$ </tex-math></inline-formula>) SE6T memory consumes <inline-formula> <tex-math notation="LaTeX">$ {0.45\times }$ </tex-math></inline-formula> dynamic power, <inline-formula> <tex-math notation="LaTeX">$ {0.83\times }$ </tex-math></inline-formula> leakage power and takes <inline-formula> <tex-math notation="LaTeX">$ {0.60\times }$ </tex-math></inline-formula> area as compared to conventional 6T SRAM memory for similar peak signal to noise ratio (PSNR). We have also proposed heterogeneous SE6T 1K SRAM memory and show that for a given power budget, PSNR enhances by at least by 14 dB compared to when homogeneous (identically sized bit-cells) SE6T SRAM memory are used. When compared with heterogeneous 6T SRAM memory, the heterogeneous SE6T SRAM memory consumes <inline-formula> <tex-math notation="LaTeX">$ {0.44\times }$ </tex-math></inline-formula> dynamic power, <inline-formula> <tex-math notation="LaTeX">$ {0.86\times }$ </tex-math></inline-formula> leakage power and takes <inline-formula> <tex-math notation="LaTeX">$ {0.6\times }$ </tex-math></inline-formula> area for almost similar PSNR. For a given PSNR, the SE6T memory is <italic>cumulatively</italic> better in terms of design complexity, area and power when compared with other hybrid and heterogeneous approximate memories.
Suicide and Cardiovascular Death Among Patients With Multiple Primary Cancers in the United States

Background Previous studies have demonstrated that patients with a cancer diagnosis have an elevated risk of suicide and cardiovascular death. However, the effects of the diagnosis of multiple primary cancers (MPCs) on the risk of suicide and cardiovascular death remain unclear. This study aimed to identify the risk of suicide and cardiovascular death among patients with MPCs in the United States. Methods Patients with a single or MPC(s) between 1975 and 2016 were selected from the Surveillance, Epidemiology, and End Results database in a retrospective cohort study. Mortality rates and standardized mortality ratios (SMRs) of suicides and cardiovascular diseases among patients with MPCs were estimated. Results Of the 645,818 patients diagnosed with MPCs included in this analysis, 760 and 36,209 deaths from suicides and cardiovascular diseases were observed, respectively. The suicide and cardiovascular-disease mortality rates were 1.89- (95% CI, 1.76–2.02) and 1.65-times (95% CI, 1.63–1.67), respectively, that of the general population. The cumulative mortality rate from both suicides and cardiovascular diseases among patients with MPCs were significantly higher than those of patients with a single primary cancer (Both p < 0.001). In patients with MPCs diagnosed asynchronously, the cumulative incidence rates of suicides and cardiovascular deaths were higher than those diagnosed synchronously. Among all MPCs, cancers of the pancreas and esophagus had the highest SMRs of suicide (5.98 and 5.67, respectively), while acute myeloid leukemia and brain cancer had the highest SMRs of cardiovascular diseases (3.87 and 3.62, respectively). The SMR of suicide was highest within 1 year after diagnosis, while that of cardiovascular diseases was highest 5 years after diagnosis. Conclusions This study showed that the mortality rates from suicides and cardiovascular diseases among patients with MPCs were higher than those with a single primary cancer. Therefore, our results underscore the need for psychological assessment and targeted preventive interventions for suicides and cardiovascular diseases among patients with MPCs.
The low-dimensional structures formed by tricategories

Abstract We form tricategories and the homomorphisms between them into a bicategory, whose 2-cells are certain degenerate tritransformations. We then enrich this bicategory into an example of a three-dimensional structure called a locally cubical bicategory, this being a bicategory enriched in the monoidal 2-category of pseudo double categories. Finally, we show that every sufficiently well-behaved locally cubical bicategory gives rise to a tricategory, and thereby deduce the existence of a tricategory of tricategories.
Mathematical definition of general systems based on semiotics and set theory (part of statics)

We clarified the connection between measurements and partitions, and discussed the meaning of semiotics for measurements based on functions. The terms of property and relation quantity were defined by our understanding of partitions and functions. Farther more, we discussed correspondences established between two quantities, and the theorems of complete set based on it. Finally, we presented the structure which can afford the obligation of general system, and also the definitions of subsystem and isomorphism.
Large errors increase the generalization of locomotor adaptation depending on the error direction

Generalization in motor adaptation involves the transfer of movements beyond the adaptation context. We investigated the effect of size (large vs. small) and direction (unidirectional vs. bidirectional) of performance errors during adaptation on the generalization of walking patterns from a split-belt treadmill (training context) to overground (testing context). We hypothesized that unusual errors (i.e., large unidirectional or bidirectional errors) would serve as contextual cues limiting generalization. The size of unidirectional errors was modulated either implicitly (i.e., gradual vs. semi-abrupt split-belt perturbations) or explicitly (i.e., through instructed visual feedback). Bidirectional errors were induced by a sudden removal of the split-perturbation after a long adaptation period, resulting in errors in the opposite direction to those at the start of the adaptation period. Our findings did not support our hypothesis. We found that bidirectional, but not large, performance errors limited generalization across contexts, which could be mediated by two distinct mechanisms. On the one hand, bidirectional errors upon removal of the split-perturbation are also experienced when transitioning to overground walking. Thus, bidirectional errors may facilitate switching between distinct walking patterns, thereby limiting generalization. On the other hand, large unidirectional errors induce more motor adaptation, which might lead to more generalization.
Hydrophobic mismatch drives self-organization of designer proteins into synthetic membranes

The extent to which membrane biophysical properties, such as hydrophobic thickness, can drive membrane protein organization remains unknown. Inspired by this question, we used de novo protein design, molecular dynamic simulations, and cell-free systems to elucidate how membrane-protein hydrophobic mismatch affects protein integration and organization in synthetic lipid membranes. We found that membranes must deform to accommodate membrane-protein hydrophobic mismatch, which reduces the expression and co-translational insertion of membrane proteins into synthetic membranes. We used this principle to sort proteins both between and within membranes, thereby achieving one-pot assembly of vesicles with distinct functions and controlled split-protein assembly, respectively. Our results shed light on protein organization in biological membranes and provide a framework to self-organizing membrane-based materials with new functions.
PPP2R1A Regulates Migration Persistence through the WAVE Shell Complex

The RAC1-WAVE-Arp2/3 signaling pathway generates branched actin networks that power lamellipodium protrusion of migrating cells. Feedback is thought to control protrusion lifetime and migration persistence, but its molecular circuitry remains elusive. Using proteomics, we identified PPP2R1A among proteins differentially associated with the WAVE complex subunit ABI1 when RAC1 was activated and downstream generation of branched actin was blocked. PPP2R1A was found to associate at the lamellipodial edge with a novel form of WAVE complex, the WAVE Shell Complex (WSC), that contains NHSL1 instead of the Arp2/3 activating subunit WAVE as in the canonical WAVE Regulatory Complex (WRC). PPP2R1A was required for persistence in random and directed migration assays and for RAC1-dependent actin polymerization in cell extracts. PPP2R1A requirement was abolished by NHSL1 depletion. PPP2R1A mutations found in tumors impaired WSC binding and migration regulation, suggesting that this novel function of PPP2R1A is critical for its tumor suppressor activity.
Genomic Insights of Bruneian Malays

The Malays and their many sub-ethnic groups collectively make up one of the largest population groups in Southeast Asia. However, their genomes, especially those from Brunei, remain very much underrepresented and understudied. Here, we analysed the publicly available WGS and genotyping data of two and 39 Bruneian Malay individuals, respectively. NGS reads from the two individuals were first mapped against the GRCh38 human reference genome and their variants called. Of the total ∼5.28 million short nucleotide variants and indels identified, ∼217K of them were found to be novel; with some predicted to be deleterious and associated with risk factors of common non-communicable diseases in Brunei. Unmapped reads were next mapped against the recently reported novel Chinese and Japanese genomic contigs and de novo assembled. ∼227 Kbp genomic sequences missing in GRCh38 and a partial open reading frame encoding a potential novel small zinc finger protein were successfully discovered. Interestingly, although the Malays in Brunei, Singapore and Malaysia share >83% common variants, principal component and admixture analysis comparing the genetic structure of the local Malays against other Asian population groups suggested that they are genetically closer to some Filipino ethnic groups than the Malays in Malaysia and Singapore. Taken together, our work provides the first comprehensive insight into the genomes of the Bruneian Malay population.
Imaging Clostridioides difficile Spore Germination and Germination Proteins

Germination by C. difficile spores is the first step in the establishment of potentially life-threatening C. difficile infection (CDI). A deeper understanding of the mechanism by which spores germinate may provide insight for how to either prevent spore germination into a disease-causing vegetative form or trigger germination prematurely when the spore is either in the outside environment or in a host environment that does not support the establishment of colonization/disease. ABSTRACT Clostridioides difficile spores are the infective form for this endospore-forming organism. The vegetative cells are intolerant to oxygen and poor competitors with a healthy gut microbiota. Therefore, in order for C. difficile to establish infection, the spores have to germinate in an environment that supports vegetative growth. To initiate germination, C. difficile uses Csp-type germinant receptors that consist of the CspC and CspA pseudoproteases as the bile acid and cogerminant receptors, respectively. CspB is a subtilisin-like protease that cleaves the inhibitory propeptide from the pro-SleC cortex lytic enzyme, thereby activating it and initiating cortex degradation. Though several locations have been proposed for where these proteins reside within the spore (i.e., spore coat, outer spore membrane, cortex, and inner spore membrane), these have been based, mostly, on hypotheses or prior data in Clostridium perfringens. In this study, we visualized the germination and outgrowth process using transmission electron microscopy (TEM) and scanning electron microscopy (SEM) and used immunogold labeling to visualize key germination regulators. These analyses localize these key regulators to the spore cortex region for the first time. IMPORTANCE Germination by C. difficile spores is the first step in the establishment of potentially life-threatening C. difficile infection (CDI). A deeper understanding of the mechanism by which spores germinate may provide insight for how to either prevent spore germination into a disease-causing vegetative form or trigger germination prematurely when the spore is either in the outside environment or in a host environment that does not support the establishment of colonization/disease.
Term-seq reveals an abundance of conditional, Rho-dependent termination in Mycobacterium tuberculosis .

Accurately controlled termination of transcription is critical for gene expression and adaptation to changing environments. The aim of this study was to define transcription termination sites in Mycobacterium tuberculosis at nucleotide resolution. To this end, we applied Term-seq to cultures of M. tuberculosis and established that by far the most abundant mechanism of transcription termination is Rho-dependent. Moreover, we find that conditional or premature termination of transcription regulates a large proportion of genes and that this is often associated with translated upstream open reading frames (uORFs). Finally, our results show that overlapping ORFs are abundant in many cases in the absence of a recognisable Shine-Dalgarno sequence, indicating tightly coordinated/coupled translation. Our results provide a detailed image and comprehensive catalogue of novel M. tuberculosis cis -regulatory elements, where Rho-dependent conditional termination of transcription and translational coupling together play major roles in gene expression control.
Genetic architecture of trophic adaptations in cichlid fishes

Since Darwin, biologists have sought to understand the evolution and origins of phenotypic adaptations. The skull is particularly diverse due to intense natural selection such as feeding biomechanics. We investigate the genetic and molecular origins of trophic adaptation using Lake Malawi cichlids, which have undergone an exemplary evolutionary radiation. We analyze morphological differences in the lateral and ventral head among an insectivore that eats by suction feeding, an obligate biting herbivore, and their F2 hybrids. We identify variation in a series of morphologies including mandible width, mandible length, and buccal length that directly affect feeding kinematics and function. Using quantitative trait loci (QTL) mapping, we find that many genes of small effects influence these craniofacial adaptations. Intervals for some traits are enriched in genes related to potassium transport and sensory systems, the latter suggesting correlation between feeding structures and sensory adaptations for foraging. Craniofacial phenotypes largely map to distinct genetic intervals, and morphologies in the head do not correlate. Together, these suggest that craniofacial traits are mostly inherited as separate modules, which confers a high potential for the evolution of morphological diversity. Though these traits are not restricted by genetic pleiotropy, functional demands of feeding and sensory structures likely introduce constraints on variation. In all, we provide insights into the quantitative genetic basis of trophic adaptation, identify mechanisms that influence the direction of morphological evolution, and provide molecular inroads to craniofacial variation.
Computational multiphase characterization of perfusion trends inside biomimetic reduced-order dense tumors

Dense fibrous extracellular constitution of solid tumors exerts high resistance to diffusive transport into it; additionally, the scarcity of blood and lymphatic flows hinders convection. The complexity of fluidic transport mechanisms in such tumor environments still presents open questions with translational end goals. For example, clinical diagnosis and targeted drug delivery platforms for such dense tumors can ideally benefit from a quantitative framework on plasma uptake into the tumor. In this study, we present a computational model for physical parameters that may influence blood percolation and penetration into a simple biomimetic solid tumor geometry. The model implements 3-phase viscous laminar transient simulation to mimic the transport physics inside a tumor-adhering blood vessel and measures the constituent volume fractions of the three considered phases, viz. plasma, RBCs (Red Blood Cells, also known as “erythrocytes”), and WBCs (White Blood Cells, also known as “leukocytes”) at three different flow times, while simultaneously recording the plasma pressure and velocity at the entry point to the tumor’s extracellular space. Subsequently, to quantify plasma perfusion within the tumor zone, we have proposed a reduced-order 2D transport model for the tumor entry zone and its extracellular space for three different fenestra diameters: 0.1, 0.3, and 0.5 μm; the simulations were 2-phase viscous laminar transient. The findings support the hypothesis that plasma percolation into the tumor is proportional to the leakiness modulated by the fenestra openings, quantifiable through the opening sizes.
Plant Signals Anticipate the Induction of the Type III Secretion System in Pseudomonas syringae pv. actinidiae, Facilitating Efficient Temperature-Dependent Effector Translocation

Plant diseases—their occurrence and severity—result from the impact of three factors: the host, the pathogen, and the environmental conditions, interconnected in the disease triangle. Time was further included as a fourth factor accounting for plant disease, leading to a more realistic three-dimensional disease pyramid to represent the evolution of disease over time. ABSTRACT Disease resistance in plants depends on a molecular dialogue with microbes that involves many known chemical effectors, but the time course of the interaction and the influence of the environment are largely unknown. The outcome of host-pathogen interactions is thought to reflect the offensive and defensive capabilities of both players. When plants interact with Pseudomonas syringae, several well-characterized virulence factors contribute to early bacterial pathogenicity, including the type III secretion system (T3SS), which must be activated by signals from the plant and environment to allow the secretion of virulence effectors. The manner in which these signals regulate T3SS activity is still unclear. Here, we strengthen the paradigm of the plant-pathogen molecular dialogue by addressing overlooked details concerning the timing of interactions, specifically the role of plant signals and temperature on the regulation of bacterial virulence during the first few hours of the interaction. Whole-genome expression profiling after 1 h revealed that the perception of plant signals from kiwifruit or tomato extracts anticipated T3SS expression in P. syringae pv. actinidiae compared to apoplast-like conditions, facilitating more efficient effector transport in planta, as revealed by the induction of a temperature-dependent hypersensitive response in the nonhost plant Arabidopsis thaliana Columbia-0 (Col-0). Our results show that in the arms race between plants and bacteria, the temperature-dependent timing of bacterial virulence versus the induction of plant defenses is probably one of the fundamental parameters governing the outcome of the interaction. IMPORTANCE Plant diseases—their occurrence and severity—result from the impact of three factors: the host, the pathogen, and the environmental conditions, interconnected in the disease triangle. Time was further included as a fourth factor accounting for plant disease, leading to a more realistic three-dimensional disease pyramid to represent the evolution of disease over time. However, this representation still considers time only as a parameter determining when and to what extent a disease will occur, at a scale from days to months. Here, we show that time is a factor regulating the arms race between plants and pathogens, at a scale from minutes to hours, and strictly depends on environmental factors. Thus, besides the arms possessed by pathogens and plants per se, the opportunity and the timing of arms mobilization make the difference in determining the outcome of an interaction and thus the occurrence of plant disease.
Tracking hematopoietic stem cell evolution in a Wiskott–Aldrich clinical trial

Hematopoietic Stem Cells (HSC) are the cells that give rise to 7 all other blood cells and, as such, they are crucial in the healthy 8 development of individuals. Wiskott-Aldrich Syndrome (WAS) is a 9 severe disorder aﬀecting the regulation of hematopoietic cells and is 10 caused by mutations in the WASP gene. We consider data from a 11 revolutionary gene therapy clinical trial, where HSC harvested from 12 3 WAS patients’ bone marrow have been edited and corrected using 13 viral vectors. Upon re-infusion into the patient, the HSC multiply 14 and diﬀerentiate into other cell types. The aim is to unravel the cell 15 multiplication and cell diﬀerentiation process, which has until now 16 remained elusive. 17 This paper models the replenishment of blood lineages resulting 18 from corrected HSC via a multivariate, density-dependent Markov 19 process and develops an inferential procedure to estimate the dy- 20 namic parameters given a set of temporally sparsely observed tra- 21 jectories. Starting from the master equation, we derive a system of 22 non-linear diﬀerential equations for the evolution of the ﬁrst- and 23 second-order moments over time. We use these moment equations in 24 a generalized method-of-moments framework to perform inference. 25 The performance of our proposal has been evaluated by consider- 26 ing diﬀerent sampling scenarios and measurement errors of various 27 strengths using a simulation study. We also compared it to another 28 state-of-the-art approach and found that our method is statistically 29 more eﬃcient. By applying our method to the WAS gene therapy 30 data we found strong evidence for a myeloid-based developmental
MEBOCOST: Metabolite-mediated Cell Communication Modeling by Single Cell

We developed MEBOCOST, a computational algorithm for quantitatively inferring metabolite-mediated intercellular communications using single cell RNA-seq data. The algorithm identifies cell-cell communications in which metabolites, such as lipids, are secreted by sender cells and traveled to interact with sensor proteins of receiver cells. The sensor proteins on receiver cell might be cell surface receptors, transporters across the cell membrane, or nuclear receptors. MEBOCOST relies on a comprehensive database of metabolite-sensor partners, which we manually curated from the literatures and other public sources. MEBOCOST defines sender and receiver cells for an extracellular metabolite based on the expression levels of the enzymes and sensors, respectively, thus identifies metabolite-sensor communications between the cells. Applying MEBOCOST to mouse brown adipose tissue (BAT) successfully recaptured known metabolite-mediated cell communications and further identified new communications. Additionally, MEBOCOST identified a set of BAT intercellular metabolite-sensor communications that was regulated by cold exposure of the mice. MEBOCOST will be useful to numerous researchers to investigate metabolite-mediated cell-cell communications in many biological and disease models. The MEBOCOST software is freely available at https://github.com/zhengrongbin/MEBOCOST.