Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling the impact of single-cell stochasticity and size control on the population growth rate in asymmetrically dividing cells

Microbial populations show striking diversity in cell growth morphology and lifecycle [1]; however, our understanding of how these factors influence the growth rate of cell populations remains limited. We use theory and simulations to predict the impact of asymmetric cell division, cell size regulation and single-cell stochasticity on the population growth rate. Our model predicts that coarse-grained noise in the single-cell growth rate λ decreases the population growth rate, as previously seen for symmetrically dividing cells [2]. However, for a given noise in λ we find that dividing asymmetrically can enhance the population growth rate for cells with strong size control (between a “sizer” and an “adder”). To reconcile this finding with the abundance of symmetrically dividing organisms in nature, we propose that additional constraints on cell growth and division must be present which are not included in our model, and we explore the effects of selected extensions thereof. Further, we find that within our model, epigenetically inherited generation times may arise due to size control in asymmetrically dividing cells, providing a possible explanation for recent experimental observations in budding yeast [3]. Taken together, our findings provide insight into the complex effects generated by non-canonical growth morphologies.
The role of aquaporin-4 in optic nerve head astrocytes in experimental glaucoma

Purpose To study aquaporin channel expression in astrocytes of the mouse optic nerve (ON) and the response to IOP elevation in mice lacking aquaporin 4 (AQP4 null). Methods C57BL/6 (B6) and AQP4 null mice were exposed to bead-induced IOP elevation for 3 days (3D-IOP), 1 and 6 weeks. Mouse ocular tissue sections were immunolabeled against aquaporins 1(AQP1), 4(AQP4), and 9(AQP9). Ocular tissue was imaged to identify normal AQP distribution, ON changes, and axon loss after IOP elevation. Ultrastructure examination, cell proliferation, gene expression & transport block was also analyzed. Results B6 mice presented abundant AQP4 in Müller cells, astrocytes of retina and myelinated ON (MON), but minimal expression in prelaminar and unmyelinated ON (UON). MON of AQP4 nulls had smaller ON area, smaller axon diameter, higher axon density, and larger proportionate axon area than B6 (all p≤0.05). Bead-injection led to comparable 3D-IOP elevation (p=0.42) and axonal transport blockade in both strains. In B6, AQP4 distribution was unchanged after 3D-IOP. At baseline, AQP1 and AQP9 were present in retina, but not in UON and this was unaffected after IOP elevation in both strains. In 3D-IOP mice, ON astrocytes and microglia proliferated, more in B6 than AQP4 null. After 6 week IOP elevation, axon loss occurred equally in the two mouse types (24.6%, AQP4 null vs. 23.3%, B6). Conclusion Lack of AQP4 was neither protective nor detrimental to the effects of IOP elevation. The minimal presence of AQP4 in UON may be a vital aspect of the regionally specific phenotype of astrocytes in the mouse optic nerve head.
Differences in evolutionary accessibility determine which equally effective regulatory motif evolves to generate pulses

Transcriptional regulatory networks (TRNs) are enriched for certain “motifs”. Motif usage is commonly interpreted in adaptationist terms, i.e. that the optimal motif evolves. But certain motifs can also evolve more easily than others. Here, we computationally evolved TRNs to produce a pulse of an effector protein. Two well-known motifs, type 1 incoherent feed-forward loops (I1FFLs) and negative feedback loops (NFBLs), evolved as the primary solutions. Which motif evolves more often depends on selection conditions, but under all conditions, either motif achieves similar performance. I1FFLs generally evolve more often than NFBLs, unless we select for a tall pulse. I1FFLs are more evolutionarily accessible early on, before the effector protein evolves high expression; when NFBLs subsequently evolve, they tend to do so from a conjugated I1FFL-NFBL genotype. In the empirical S. cerevisiae TRN, output genes of NFBLs had higher expression levels than those of I1FFLs. These results suggest that evolutionary accessibility, and not relative functionality, shapes which motifs evolve in TRNs, and does so as a function of the expression levels of particular genes.
High-temperature structural evolution of hexagonal multiferroic YMnO3 and YbMnO3

Neutron powder diffraction studies on the structural evolution of hexagonal multiferroic YMnO3 and YbMnO3 from 1000 K to 1400 K, and from 1000 K to 1350 K, respectively, are presented. The temperature evolution of diffraction patterns suggests that YMnO3 undergoes a phase transition to a non-polar structure above 1200 K, while YbMnO3 remains ferroelectric up to 1350 K. Detailed structural parameters were obtained as a function of temperature from Rietveld refinements. Based on this result, the distinct differences in temperature behaviour between YMnO3 and YbMnO3, and the origin of the ferroelectricity in these hexagonal multiferroics are discussed.
Chemical exhaustion of RPA in cancer treatment

Replication protein A (RPA) plays essential roles in DNA replication, repair, recombination and the DNA-damage response (DDR). We have developed second generation RPA inhibitors (RPAi’s) that block the RPA-DNA interaction. These DNA-binding inhibitors (DBi’s) can elicit a state of cellular RPA exhaustion resulting in single agent in vitro anticancer activity across a broad spectrum of cancers and in vivo activity in two non-small cell lung cancer models. The cellular response to RPAi treatment suggests a threshold exists before RPA inhibition induces cell death. Chemical RPA exhaustion potentiates the anticancer activity of other DDR inhibitors as well as traditional DNA damaging cancer therapeutics. Consistent with the chemical RPA exhaustion model, we demonstrate that the effects of RPAi on replication fork dynamics and DNA damage signaling are similar to other known DDR inhibitors. In accordance with the RPA threshold model, retrospective analysis of lung cancer patient data demonstrates high RPA expression as a negative prognostic biomarker for overall survival in smoking-related lung cancers. Similarly, relative expression of RPA is a predictive marker for response to chemotherapy. These observations are consistent with the increase in RPA expression serving as an adaptive mechanism that allows tolerance of the genotoxic stress resulting from carcinogen exposure. These data demonstrate a unique mechanism of action of RPAi’s eliciting a state of RPA exhaustion that impacts the DDR and may provide an effective therapeutic option for difficult to treat lung cancers. Graphical Abstract
Biofouling of metal surfaces : study of adsorbed biomolecules and prevention strategy based on renewable copolymer layer

Biofouling refers to the accumulation of organisms and their products onto surfaces immersed in a biological aqueous environment. It includes molecular-, micro- and macro-fouling. Molecular fouling is the initial step of biofouling, in which a conditioning film is formed by adsorption of organic biomolecules. Furthermore, surface-associated aggregates of microorganisms with their extracellular polymeric substances (EPS) are called biofilm, known to provoke the biocorrosion of metals. Chlorination is still the most common treatment to control biofouling of cooling condensers fed with fresh- or seawater in power plants, provoking harmful effects to the aquatic environment. An environmental-friendly way to replace chlorination is thus highly desired. The aim of this thesis is to design a renewable poly(ethylene oxide) (PEO)-based coating on metals (Ti, stainless steel and Al brass) used in cooling condensers, with a view to reduce biofouling. Adsorption of a PEO-poly(propylene oxide)-PEO copolymer was performed on native and hydrophobized metal surfaces. Three proteins (albumin, fibrinogen, cytochrome C) and Pseudomonas 2021, a marine bacterium, were used as model molecular- and micro-fouling agents, respectively. The results show that the adsorbed triblock copolymer prevents protein adsorption and significantly reduces bacterial adhesion on hydrophobized metal substrates, but not on native ones. The copolymer conformation plays a key role in biofouling reduction; it is believed to form a brush structure on hydrophobized substrates. In addition, proteins were highlighted as an important constituent of EPS and their conditioning films, as analyzed by X-ray photoelectron spectroscopy. This confirms the relevance of preventing protein adsorption to reduce biofouling.
Profiling of Extracellular Small RNAs Highlights a Strong Bias towards Non-Vesicular Secretion

Extracellular environment consists of a plethora of different molecules, including extracellular miRNA that can be secreted in association with extracellular vesicles (EVs) or soluble protein complexes (non-EVs). Yet, it is generally accepted that most of the biological activity is attributed to EV-associated miRNAs. The capability of EVs to transport cargoes has attracted much interest towards developing EVs as therapeutic short RNA carriers by using endogenous loading strategies for miRNA enrichment. Here, by overexpressing miRNA and shRNA sequences of interest in source cells and using size exclusion liquid chromatography (SEC) to separate the cellular secretome into EV and non-EV fractions, we saw that strikingly, <2% of all secreted overexpressed miRNA were found in association with EVs. To see whether the prominent non-EV miRNA secretion also holds true at the basal expression level of native miRNA transcripts, both fractions were further analysed by small RNA sequencing. This revealed a global correlation of EV and non-EV miRNA abundance to that of their parent cells and showed an enrichment only for miRNAs with a relatively low cellular expression level. Further quantification showed that similarly to the transient overexpression context, an outstanding 96.2-99.9% of total secreted miRNA at its basal level was secreted to the non-EV fraction. Yet, even though EVs contain only a fraction of secreted miRNAs, these molecules were found stable at 37°C in serum-containing environment, indicating that if sufficient miRNA loading to EVs is achieved, EVs can remain miRNA delivery-competent for a prolonged period of time. This study suggests that the passive endogenous EV loading strategy can be a relatively wasteful way of loading miRNA to EVs and active miRNA loading approaches are needed for developing advanced EV miRNA therapies in the future.
Empty Sella Syndrome as a Window Into the Neuroprotective Effects of Prolactin

BACKGROUND To correlate structural integrity of visual pathway white matter tracts with prolactin levels in a patient who demonstrates downward herniation of the optic chiasm secondary to medical treatment of a prolactinoma. METHODS A 36-year-old woman with a prolactinoma presented with progressive bilateral visual field defects nine years after initial diagnosis and medical treatment. She was diagnosed with empty-sella syndrome and instructed to stop cabergoline. Hormone testing was conducted in tandem with routine clinical evaluations over one year and the patient was followed with diffusion magnetic resonance imaging (dMRI), optical coherence tomography (OCT), and automated perimetry at three time points. Five healthy controls underwent a complementary battery of clinical and neuroimaging tests at a single time point. RESULTS Shortly after discontinuing cabergoline, diffusion metrics in the optic tracts were within the range of values observed in healthy controls. However, following a brief period where the patient resumed cabergoline (of her own volition), there was a decrease in serum prolactin with a corresponding decrease in visual ability and increase in radial diffusivity (p<0.001). Those measures again returned to their baseline ranges after discontinuing cabergoline a second time. CONCLUSIONS These results demonstrate the sensitivity of dMRI to detect rapid and functionally significant microstructural changes in white matter tracts secondary to alterations in serum prolactin levels. The inverse relations between prolactin and measures of diffusion and visual function provide support for a neuroprotective role of prolactin in the injured nervous system.
The Circadian Clock in the Retinal Pigment Epithelium Controls the Diurnal Rhythm of Phagocytic Activity

The diurnal peak of phagocytosis by the retinal pigment epithelium (RPE) of photoreceptor outer segments (POS) is under circadian control, and it is believed that this process involves interactions from both the retina and RPE. Previous studies have demonstrated that a functional circadian clock exists within multiple retinal cell types and RPE cells. Thereby, the aim of the current study was to determine whether the circadian clock in the retina and or RPE controls the diurnal phagocytic peak of photoreceptor outer segments and whether selective disruption of the circadian clock in the RPE would affect RPE cells function and the viability during aging. To that aim, we first generated and validated an RPE tissue-specific KO of the essential clock gene, Bmal1, and then we determined the daily rhythm in phagocytic activity by the RPE in mice lacking a functional circadian clock in the retina or RPE. Then using electroretinography, spectral domain-optical coherence tomography, and optomotor response measurements of visual function we determined the effect of Bmal1 removal in young (6-month old) and old (18-month old) mice. RPE morphology and lipofuscin accumulation was also determined in young and old mice. Our data show that the circadian clock in the RPE controls the daily diurnal phagocytic peak of POS. Surprisingly, the lack of a functional RPE circadian clock or the diurnal phagocytic peak does not result in any detectable age-related degenerative phenotype in the retina or RPE. Thus, our results demonstrate that the loss of the circadian clock in the RPE or the lack of the daily peak in phagocytosis of POS does not result in deterioration of photoreceptors or the RPE during aging.
The generation of cortical novelty responses through inhibitory plasticity

Animals depend on fast and reliable detection of novel stimuli in their environment. Indeed, neurons in multiple sensory areas respond more strongly to novel in comparison to familiar stimuli. Yet, it remains unclear which circuit, cellular and synaptic mechanisms underlie those responses. Here, we show that inhibitory synaptic plasticity readily generates novelty responses in a recurrent spiking network model. Inhibitory plasticity increases the inhibition onto excitatory neurons tuned to familiar stimuli, while inhibition for novel stimuli remains low, leading to a network novelty response. Generated novelty responses do not depend on the exact temporal structure but rather on the distribution of presented stimuli. By including tuning of inhibitory neurons, the network further captures stimulus-specific adaptation. Finally, we suggest that disinhibition can control the amplification of novelty responses. Therefore, inhibitory plasticity provides a flexible, biologically-plausible mechanism to detect the novelty of bottom-up stimuli, enabling us to make numerous experimentally testable predictions.
EFFECT OF LAND TENURE ON ADOPTION OF CLIMATE CHANGE ADAPTATION. EVIDENCE FROM MALAWI

The definitive aim of this study was to bring to fore the evidence of the importance of tenure considerations in the designing, development, and implementation of climate change programs. This was done by analyzing how land tenure affects the use of adaptation strategies in Malawi. Using secondary data from the Integrated Household Survey (IHS4), a multinomial logit model was fitted to analyze determinants of adoption of climate change adaptation strategies. Land tenure has shown to significantly affect the adoption of the technologies in question. Insecure arrangements such as borrowing and renting land tend to discourage adoption. The proliferation of borrowed or rented in Malawi’s agricultural sector necessitates intervention to encourage adaptation on those farms to avoid land degradation.
In silico validation and fabrication of matrix diffusion based polymeric transdermal films for repurposing gabapentin hydrochloride in oncogenic neuropathic pain

Background Gabapentin (GBP) is an FDA approved drug for the treatment of partial and secondary generalized seizures, apart from also being used for diabetic neuropathy. GBP displays highly intricate mechanism of action and its inhibitory response in elevated antagonism of NMDA (N-methyl-D-aspartate receptor) receptor and has potential in controlling neuropathic pain of cancer origin. Objective Therefore, in the present study, we have selected BCATc (Pyridoxal 5’-phosphate dependent branched-chain aminotransferase cytosolic) enzyme that is highly expressed in neuropathic stress conditions and have analysed the GBP as its competitive inhibitor by modeling, docking and checking its pharmacokinetic suitability through ADMET. Though in this study the results exhibited higher efficacy of GBP in controlling neuropathic pain, the drug shows certain potential therapeutic limitations like shorter half-life, repetitive dosing, high inter subjective variability. Methods Therefore, a suitable and equally efficacious drug delivery method was also designed and developed by loading GBP transdermal patches (GBP-TDP) by solvent evaporation method using PVP and HPMC in ratio of 2:1 as a polymer base for reservoir type of TDP. Also, PEG 400 was used as a plasticizer and PVA (4%) was taken for backing membrane preparation and then the optimized GBP-TDP was subjected for physical characterization, optimization and ex vivo release kinetics. Results and conclusion The results showed desired specifications with uneven and flaky surface appearance giving avenue for controlled release of the drugs with 75.58% of drug release in 12 hrs. , further suggesting that GBP-TDP can be used as an effective tool against diabetic neuropathy pain.
PVC-Based Cobalt and Manganese Phthalocyanine Coated Graphite Electrodes for Determination of Thiocyanate

ABSTRACT Thiocyanate selective electrodes were prepared by incorporating cobalt and manganese phthalocyanines into plasticized ploy(vinyl chloride) membranes which were directly coated on the surface of graphite electrodes. A calibration plot with Nernstian slope for thiocyanate was observed over a linear range of five decades of concentration (1x10−6-1x10− M). The electrode has a fast response time, very low detection limit (5x10−7 M thiocyanate), is easy to prepare, and could be used for over a month. The proposed sensor revealed good selectivity for thiocyanate over several anions and could be used over a wide pH range. Applications of the electrode to the potentiometric titration of silver ion with thiocyanate and determination of thiocyanate in urine samples are reported.
Minds Make Societies: How Cognition Explains the World Humans Create

A watershed book that masterfully integrates insights from evolutionary biology, genetics, psychology, economics, and more to explore the development and workings of human societies "There is no good reason why human societies should not be described and explained with the same precision and success as the rest of nature. " Thus argues evolutionary psychologist Pascal Boyer in this uniquely innovative book. Integrating recent insights from evolutionary biology, genetics, psychology, economics, and other fields, Boyer offers precise models of why humans engage in social behaviors such as forming families, tribes, and nations, or creating gender roles. In fascinating, thought-provoking passages, he explores questions such as, Why is there conflict between groups? Why do people believe low-value information such as rumors? Why are there religions? What is social justice? What explains morality? Boyer provides a new picture of cultural transmission that draws on the pragmatics of human communication, the constructive nature of memory in human brains, and human motivation for group formation and cooperation.
Silicon Composite Electrode with High Capacity and Long Cycle Life

A nanosilicon-based composite electrode that can achieve more than 700 cycles at a high capacity of 960 mAh/g of electrode was prepared using aqueous processing in an acidic medium. The buffering of the aqueous solution is mandatory to promote covalent bonding between Si particles and the carboxymethyl cellulose (CMC) binder. The latter is claimed to allow the formation of mechanically stronger contacts within the composite electrode in addition to the CMC bridging of the Si and carbon black particles.
Quantitative X-ray diffraction analysis using clay mineral standards extracted from the samples to be analysed

Abstract In the quantitative X-ray diffraction analysis of a series of samples, the problems arising from the variable compositions and degrees of crystallinity of clay minerals were overcome to a great extent by the use of standards extracted from the samples. Procedures are given for separation of the montmorillonite standard by differential settling of Na-montmorillonite solvated in an ethanol solution and for isolation of the kaolinite, mica, and chlorite standards by density separation of their Na-forms in thallous formate. Calibration curves were prepared from the X-ray diffractograms obtained for series of known mixtures of Ca-forms of the standards and the internal standard boehmite using both powder and smear-oriented mounting techniques.
Surface Soil Aggregation, Trace, and Heavy Metal Enrichment Under Long-Term Application of Farm Yard Manure and Mineral Fertilizers

Abstract The DNPK trial was started at Samaru in 1950 to assess the nutrient imbalances resulting from the increasing use of mineral fertilizers on some poorly buffered soils, improve and optimize productivity of these soils under intensive agricultural land use. Aggregation, trace, and heavy metals enrichment were studied in some selected plots under this trial, with a view to identify treatment(s) that best improve soil quality over a long-term period. Soils under treatments involving sole cowdung (D), cowdung + phosphorus (DP) fertilizer, and cowdung + nitrogen, phosphorus, and potassium (DNPK) fertilizers recorded higher mean weight diameter, lower soil bulk density, and higher percentage of aggregates greater than 1-mm diameter. Hence, these three treatments are better aggregated to withstand wind erosion. However, the DNPK treatment was the only one, which consistently, recorded lower trace and heavy metals content.
PEMBUATAN KARBON AKTIF DARI TANAH GAMBUT

Indonesia is one of the country that proposed as a country tag has the world's largest peat, while the carbon content in peat is quite high, namely ± 60%. To increase the economical value of peat in a mann~r ti'. at is p1"ocessed into. actilrated carbon. This research aims to make activated carbon from tJa.e peat soil and nutrient concentrations studied the influence of activators and activation times for the quality activated carbon produced Raw materials used to make activated carbon is peat derived from central Kalimantan. H2S04 solution is used as the activator. While Iod solution, a solution of potassium iodide and thiosulphate solution 0.1 N is used as active carbon absorbent testing agent. Set of variables: 550 OC temperoTitff ew/mniralifm, c:ur/mniralifiii li"il'ie of 2 hoiti'S; pml, eva} 40 mesh parlide size, we:ighl of}OO grams of active carbon, the comparison of the char activator 1: 10 and the drying temperature is 120 Oc. Carried out activator concentration are 5%, 10%, 15%, 20% and 25% and time of immersion / activation are 1, 1.5, 2, 2.5, 3 (h). Research results are measured from the active carbon absorbent rate of Iodine solution. Best results absorbed rate measured as 21.88% were obtained in 20% H2S04 concentration and activation time of2.5 hours.