Miracle-dz/UniFAR-FTUs huggingface dataset:
Pronounced capping effect of olaminosomes as nanostructured platforms in ocular candidiasis management

Abstract The aim of this study was to formulate and boost ocular targeting of Fenticonazole Nitrate (FTN)-loaded olaminosomes in order to improve drug corneal permeation and candidiasis treatment. Olaminosomes were formulated by ethanol injection technique applying a central composite design. The independent variables were: span 80 amount (mg) (A), oleylamine concentration (mg%) (B) and oleic acid: drug ratio (C). The dependent responses were: percent entrapment efficiency (EE %), particle size (PS), poly-dispersity index (PDI), zeta potential (ZP) and in vitro drug release after 10 hours (Q10h). Numerical optimization by Design-Expert® software was adopted to select the optimum formula. This formula was chosen based on highest EE %, ZP (as absolute value) and Q10h and lowest PS and PDI. The optimum formula was subjected to further in vitro characterization via Differential scanning calorimetry, Transmission electron microscopy, Fourier transform infrared spectroscopy, pH determination, effect of storage, influence of terminal sterilization, detection of Minimal Inhibitory Concentration and ex vivo corneal penetration analysis. Safety and antifungal activity of the optimum formula were tested through various in vivo studies like ocular irritancy, corneal tolerance, corneal uptake and susceptibility test. The optimum formula with the maximum desirability value (0.972) revealed EE% (84.24%), PS (117.55 nm), ZP (−74.85 mV) and Q10h (91.26%) respectively. The optimum formula demonstrated ocular tolerance with enhanced corneal penetration behavior (428.66 µg/cm2) and boosted antifungal activity (56.13%) compared to FTN suspension (174.66 µg/cm2 and 30.83%). The previous results ensured the ability of olaminosomes to enhance the corneal penetration and antifungal efficacy of Fenticonazole Nitrate.
Metal‐poor stars don’t blush: Broadband colors of confirmed cool subdwarfs in the SDSS.

The colors of low‐mass, metal‐poor stars are determined using an unprecedented sample of 3,000 spectroscopically confirmed cool and ultra‐cool subdwarfs of spectral subtype M0–M8, a sample which increases the census of spectroscopically confirmed M subdwarfs by almost an order of magnitude. Color‐color diagrams in the Sloan Digital Sky Survey ugriz system and the Two Micron All Sky Survey JHK system indicates that M subdwarfs do not “blush” as much as their Solar‐metallicity analogs (the M dwarf), as they are significantly bluer in r‐i, i‐z, and J‐K. Further, it appears that these color terms are a function of metallicity, the more metal‐poor the star, the bluer. In (g‐r)/(r‐i) color‐color‐space, the M dwarfs/subdwarfs extend on a grid which separates the stars along spectral subclass (i.e. metallicity) and spectral subtype. This not only makes it straightforward to identify M subdwarfs in deep photometric surveys, but suggests that faint, low‐mass subdwarfs could be classified, and their metallicities es.
A Phase III Study of Pafolacianine Injection (OTL38) for Intraoperative Imaging of Folate Receptor–Positive Ovarian Cancer (Study 006)

PURPOSE The adjunctive use of intraoperative molecular imaging (IMI) is gaining acceptance as a potential means to improve outcomes for surgical resection of targetable tumors. This confirmatory study examined the use of pafolacianine for real-time detection of folate receptor–positive ovarian cancer. METHODS This phase III, open-label, 11-center study included subjects with known or suspected ovarian cancer, scheduled to undergo cytoreductive surgery. The objectives were to confirm safety and efficacy of pafolacianine (0.025 mg/kg IV), given ≥ 1 hour before intraoperative near-infrared imaging to detect macroscopic lesions not detected by palpation and normal white light. RESULTS From March 2018 through April 2020, 150 patients received a single infusion of pafolacianine (safety analysis set); 109 patients with folate receptor–positive ovarian cancer comprised the full analysis set for efficacy. In 33.0% of patients (95% CI, 24.3 to 42.7; P < .001), pafolacianine with near-infrared imaging identified additional cancer on tissue not planned for resection and not detected by white light assessment and palpation, exceeding the prespecified threshold of 10%. Among patients who underwent interval debulking surgery, the rate was 39.7% (95% CI, 27.0 to 53.4; P < .001). The sensitivity to detect ovarian cancer was 83%, and the patient false-positive rate was 24.8%. Investigators reported achieving complete R0 resection in 62.4% (68 of 109) of patients. Drug-related adverse events were reported by 30% of patients (45 of 150) and most commonly included nausea, vomiting, and abdominal pain. No drug-related serious adverse events or deaths were reported. CONCLUSION This phase III study of pafolacianine met its primary efficacy end point, identifying additional cancers not otherwise identified or planned for resection. Pafolacianine may offer an important real-time adjunct to current surgical approaches for ovarian cancer.
Modelling economic high-frequency time series

In this paper we introduce the STAR-STGARCH model that can characterizenonlinear behaviour both in the conditional mean and the conditionalvariance. A modelling cycle for this family of models, consisting ofspecification, estimation, and evaluation stages is constructed.Misspecification tests for the estimated model are obtained using standardasymptotic distribution theory. We illustrate the actual modelling byapplying the STAR-STGARCH model family to two series of dailyobservations, the Swedish OMX index and the exchange rate JPY-USD.
Heart rate variability changes in patients with obstructive sleep apnea: A systematic review and meta‐analysis

Obstructive sleep apnea is a common sleep breathing disorder related to autonomic nervous function disturbances. Heart rate variability is an important non‐invasive indicator of autonomic nervous system function. The PubMed, Embase, Medline and Web of Science databases were systematically searched for English literature comparing patients with obstructive sleep apnea with controls up to May 2021. Heart rate variability outcomes, including integrated indices (parasympathetic function and total variability), time domain indices (the standard deviation of NN intervals and the root mean square of the successive differences between normal heartbeats) and frequency domain indices (high‐frequency, low‐frequency, very‐low‐frequency and the ratio of low‐frequency to high‐frequency) were derived from the studies. Twenty‐two studies that included 2565 patients with obstructive sleep apnea and 1089 healthy controls were included. Compared with controls, patients with obstructive sleep apnea exhibited significantly reduced parasympathetic function. For the obstructive sleep apnea severity subgroup meta‐analysis, patients with severe obstructive sleep apnea had significantly lower parasympathetic function, high‐frequency, root mean square of the successive differences between normal heartbeats and standard deviation of NN intervals, and higher low‐frequency and ratios of low‐frequency to high‐frequency. However, only the ratio of low‐frequency to high‐frequency was significantly higher in patients with moderate obstructive sleep apnea than in controls. Finally, for the collection time analysis, patients with obstructive sleep apnea had significantly higher low‐frequency and ratio of low‐frequency to high‐frequency at night, significantly lower parasympathetic function, high‐frequency, root mean square of the successive differences between normal heartbeats and standard deviation of NN intervals, and a higher ratio of low‐frequency to high‐frequency during the day than controls. Autonomic function impairment was more serious in patients with severe obstructive sleep apnea. During sleep, low‐frequency can well reflect the impairment of autonomic function in obstructive sleep apnea, and the ratio of low‐frequency to high‐frequency may play an important role in obstructive sleep apnea diagnosis.
Connexins orchestrate progression of breast cancer metastasis to the brain by promoting FAK activation

Brain metastasis is a complication of increasing incidence in patients with breast cancer at advanced disease stage. It is a severe condition characterized by a rapid decline in quality of life and poor prognosis. There is a critical clinical need to develop effective therapies to prevent and treat brain metastases. Here, we describe a unique and robust spontaneous preclinical model of breast cancer metastasis to the brain (4T1-BM2) in mice that has been instrumental in uncovering molecular mechanisms guiding metastatic dissemination and colonization of the brain. Key experimental findings were validated in the additional murine D2A1-BM2 model and in human MDA231-BrM2 model. Gene expression analyses and functional studies, coupled with clinical transcriptomic and histopathological investigations, identified connexins (Cxs) and focal adhesion kinase (FAK) as master molecules orchestrating breast cancer colonization of the brain. Cx31 promoted homotypic tumor cell adhesion, heterotypic tumor-astrocyte interaction, and FAK phosphorylation. FAK signaling prompted NF-κB activation inducing Lamc2 expression and laminin 332 (laminin 5) deposition, α6 integrin–mediated adhesion, and sustained survival and growth within brain parenchyma. In the MDA231-BrM2 model, the human homologous molecules CX43, LAMA4, and α3 integrin were involved. Systemic treatment with FAK inhibitors reduced brain metastasis progression. In conclusion, we report a spontaneous model of breast cancer metastasis to the brain and identified Cx-mediated FAK–NF-κB signaling as a mechanism promoting cell-autonomous and microenvironmentally controlled cell survival for brain colonization. Considering the limited therapeutic options for brain metastatic disease in cancer patients, we propose FAK as a therapeutic candidate to further pursue in the clinic. Description FAK inhibition impedes brain metastasis by suppressing connexin-FAK–induced NF-κB signaling, laminin deposition, and integrin-dependent survival. Breast-brain ConneXion Development of brain metastases in patients with breast cancer markedly worsens disease prognosis. Preventing or slowing the development of brain metastasis could ameliorate disease outcome. Here, Lorusso et al. used in vitro and in vivo models to show that connexins (Cxs) and focal adhesion kinase (FAK) likely play a major role in cancer brain invasion. Cx-mediated FAK activation promoted cell adhesion, tumor-astrocyte interaction, and tumor survival within the brain parenchyma. In vivo, in a spontaneous model of breast cancer–induced brain metastases, FAK inhibitors reduced brain metastasis progression, suggesting that targeting the Cx-FAK signaling might help prevention and treatment of breast cancer–associated brain metastasis.
Hyperoside-loaded TPGs/mPEG-PDLLA self-assembled polymeric micelles: preparation, characterization and in vitro/in vivo evaluation

Abstract Hyperoside (Hyp) self-assembled polymeric micelles (Hyp-PMs) were purposely developed to enhance aqueous solubility, in vivo availability and anti-oxidative effect of Hyp. In preparing Hyp-PMs, we employed the thin film dispersion method with the micelles consisting of TPGs and mPEG2000-PDLLA3000. The particle size, polydispersity index and zeta potential of Hyp-PMs were 67.42 ± 1.44 nm, 0.229 ± 0.015 and −18.67 ± 0.576 mV, respectively, coupled with high encapsulation efficiency （EE）of 90.63 ± 1.45% and drug loading (DL) of 6.97 ± 1.56%. Furthermore, the value of critical micelle concentration (CMC) was quite low, which indicated good stability and improved self-assembly ability of Hyp-PMs. Also, trend of in vitro Hyp release from Hyp-PMs demonstrated enhanced solubility of Hyp. Similarly, in comparison with free Hyp, oral bioavailability of Hyp-PMs was improved (about 8 folds) whilst half-life of Hyp-PMs was extended (about 3 folds). In vitro anti-oxidative effect showed obvious strong scavenging DPPH capability of Hyp-PMs, which may be attributed to its smaller size and better solubility. Altogether, Hyp-PMs may serve as a possible strategy to potentially enhance aqueous solubility, bioavailability and anti-oxidative effect of Hyp, which may play a key role in Hyp application in the pharmaceutical industries. Graphical Abstract
Immediate and sustained effects of verbal labels for newly-learned categories

Labels for the categories have been found to facilitate learning by boosting accuracy. According to the label-feedback hypothesis, this facilitation is due to a mechanism selectively sensitising perceptual dimensions. To further investigate the label-facilitation phenomenon, one group of participants in our study learned both named and hard-to-name artificial categories, in a novel, within-subjects design. Another group of participants was administered a—highly similar—paired-associate task purportedly not involving sensitization of dimensions. Results showed that labels boosted accuracy during learning, but only when learning to categorise—not when learning to associate. The label-feedback hypothesis posits that labels exert an influence also after new categories have been learned. To test for sustained effects of labels, we administered a post-learning visual discrimination task while monitoring participants’ eye movements and analysing dwell time on the trained shapes. There was some indication of sustained effects of labels for newly-learned categories, but there was no effect following learning to associate. Our results suggest that labels for newly learned categories have immediate effects during learning and that the effects of labels may also be sustained during post-learning processing.
An affine version of a theorem of Nagata

Let R be an affine k-domain over the field k. The paper's main result is that, if R admits a non-trivial embedding in a polynomial ring K[s] for some field K containing k, then R can be embedded in a polynomial ring F[t] which extends R algebraically. This theorem can be applied to subrings of a ring which admits a non-zero locally nilpotent derivation. In this way, we obtain a concise new proof of the cancellation theorem for rings of transcendence degree one for fields of characteristic zero.
Detection of interstellar CCD

The first detection of interstellar CCD has been obtained in the N = 3-2, J = 7/2-5/2 line at 216.3732 GHz towards the Kleinman-Low nebula. An abundance ratio CCD/CCH of 0.045 is found, indicating in this molecule a deuterium enhancement similar to that found for HNC, but an order of magnitude higher than for HCN. Negative results towards DR 21(OH), NGC 2264, L 134N, TM Cl, Rho OphB2, and IRC 10216 rule out a stronger D enhancement for CCD than for other deuterated molecules in these sources. Predictions of currently developed ion-molecule reaction schemes are consistent with the CCD line detected and the negative results.
Tunable band gap in Bi(Fe1−xMnx)O3 films

In order to investigate band gap tunability in polar oxides, we measured the optical properties of a series of Bi(Fe1−xMnx)O3 thin films. The absorption response of the mixed metal solid solutions is approximately a linear combination of the characteristics of the two end members, a result that demonstrates straightforward band gap tunability in this system.
Dominant effects of the histone mutant H3-L61R on Spt16-gene interactions in budding yeast

ABSTRACT Recent studies have unveiled an association between an L61R substitution within the human histone H3.3 protein and the presentation of neurodevelopmental disorders in two patients. In both cases, the mutation responsible for this substitution is encoded by one allele of the H3F3A gene and, if this mutation is indeed responsible for the disease phenotypes, it must act in a dominant fashion since the genomes of these patients also harbour three other alleles encoding wild-type histone H3.3. In our previous work in yeast, we have shown that most amino acid substitutions at H3-L61 cause an accumulation of the Spt16 component of the yFACT histone chaperone complex at the 3’ end of transcribed genes, a defect we have attributed to impaired yFACT dissociation from chromatin following transcription. In those studies, however, the H3-L61R mutant had not been tested since it does not sustain viability when expressed as the sole source of histone H3 in cells. In the present work, we show that H3-L61R impairs proper Spt16 dissociation from genes when co-expressed with wild-type histone H3 in haploid cells as well as in diploid cells that express the mutant protein from one of four histone H3-encoding alleles. These results, combined with other studies linking loss of function mutations in human Spt16 and neurodevelopmental disorders, provide a possible molecular mechanism underlying the neurodevelopmental disorders seen in patients expressing the histone H3.3 L61R mutant.
Socioeconomic resilience to climatic extremes in a freshwater fishery

Heterogeneity is a central feature of ecosystem resilience, but how this translates to socioeconomic resilience depends on people’s ability to track shifting resources in space and time. Here, we quantify how climatic extremes have influenced how people (fishers) track economically valuable ecosystem services (fishing opportunities) across a range of spatial scales in rivers of the northern Rocky Mountains, USA, over the past three decades. Fishers opportunistically shifted from drought-sensitive to drought-resistant rivers during periods of low streamflows and warm temperatures. This adaptive behavior stabilized fishing pressure and expenditures by a factor of 2.6 at the scale of the regional fishery (i.e., portfolio effect). However, future warming is predicted to homogenize habitat options that enable adaptive behavior by fishers, putting ~30% of current spending at risk across the region. Maintaining a diverse portfolio of fishing opportunities that enable people to exploit shifting resources provides an important resilience mechanism for mitigating the socioeconomic impacts of climate change on fisheries.
Evidence that cervical cancer cells cultured as tumorspheres maintain high CD73 expression and increase their protumor characteristics through TGF‐β production

Recently, a link between the biological activity of CD73 and tumorigenicity in solid tumors has been proposed. We previously reported that the generation of adenosine (Ado) by the activity of CD73 in cervical cancer (CC) cells induces transforming growth factor‐beta 1 (TGF‐β1) production to maintain CD73 expression. In the present study, we analyzed the participation of TGF‐β1 in CD73 expression and the development of protumoral characteristics in CaSki CC cells cultured as tumorspheres (CaSki‐T) and in monolayers (CaSki‐M). Compared with those in CaSki‐M cells, CD73 expression and Ado generation ability were significantly increased in CaSki‐T cells. CaSki‐T cells exhibited enrichment in the CSC‐like phenotype due to increases in the expression levels of stem cell markers (CD49f, CK17, and P63; OCT4 and SOX2), greater sphere formation efficiency (SFE), and an increase in the percentage of side population (SP) cells. Interestingly, compared with CaSki‐M cells, CaSki‐T cells produced a greater amount of TGF‐β1 and presented a marked protumor phenotype characterized by a significant decrease in the expression of major histocompatibility complex class‐I (MHC‐I) molecules, an increase in the expression of multidrug resistance protein‐I (MRP‐I) and vimentin, and an increase in the protein expression levels of Snail‐1 and Twist, which was strongly reversed with TGF‐β1 inhibition. These results suggest that the presence of TGF‐β1−CD73–Ado feedback loop can promote protumoral characteristics in the CC tumor microenvironment.
The Classical Groups

In this renowned volume, Hermann Weyl discusses the symmetric, full linear, orthogonal, and symplectic groups and determines their different invariants and representations. Using basic concepts from algebra, he examines the various properties of the groups. Analysis and topology are used wherever appropriate. The book also covers topics such as matrix algebras, semigroups, commutators, and spinors, which are of great importance in understanding the group-theoretic structure of quantum mechanics. Hermann Weyl was among the greatest mathematicians of the twentieth century. He made fundamental contributions to most branches of mathematics, but he is best remembered as one of the major developers of group theory, a powerful formal method for analyzing abstract and physical systems in which symmetry is present. In The Classical Groups, his most important book, Weyl provided a detailed introduction to the development of group theory, and he did it in a way that motivated and entertained his readers. Departing from most theoretical mathematics books of the time, he introduced historical events and people as well as theorems and proofs. One learned not only about the theory of invariants but also when and where they were originated, and by whom. He once said of his writing, "My work always tried to unite the truth with the beautiful, but when I had to choose one or the other, I usually chose the beautiful. " Weyl believed in the overall unity of mathematics and that it should be integrated into other fields. He had serious interest in modern physics, especially quantum mechanics, a field to which The Classical Groups has proved important, as it has to quantum chemistry and other fields. Among the five books Weyl published with Princeton, Algebraic Theory of Numbers inaugurated the Annals of Mathematics Studies book series, a crucial and enduring foundation of Princeton's mathematics list and the most distinguished book series in mathematics.
Smaller Circuits for Arbitrary n-qubit Diagonal Computations

A unitary operator U=\sum u_{j,k} |k><j| is called diagonal when u_{j,k}=0 unless j=k. The definition extends to quantum computations, where j and k vary over the 2^n binary expressions for integers 0,1 . , 2^n-1, given n qubits. Such operators do not affect outcomes of the projective measurement {<j| ; 0<= j<= 2^n-1} but rather create arbitrary relative phases among the computational basis states {|j>; 0<= j<= 2^n-1}. These relative phases are often required in applications. Constructing quantum circuits for diagonal computations using standard techniques requires either O(n^2 2^n) controlled-not gates and one-qubit Bloch sphere rotations or else O (n 2^n) such gates and a work qubit. This work provides a recursive, constructive procedure which inputs the matrix coefficients of U and outputs such a diagram containing 2^{n+1}-3 alternating controlled-not gates and one-qubit z-axis Bloch sphere rotations. Up to a factor of two, these circuits are the smallest possible. Moreover, should the computation U be a tensor of diagonal one-qubit computations of the form R_z(\alpha)=e^{-i \alpha/2}|0><0|+ e^{i \alpha/2} |1><1|, then a cancellation of controlled-not gates reduces our circuit to that of an n-qubit tensor.
Transient Radio Neutron Stars

Here I will review the high time resolution radio sky, focusing on millisecond scales. This is primarily occupied by neutron stars, the well-known radio pulsars and the recently identified group of transient sources known as Rotating RAdio Transients (RRATs). The RRATs appear to be abundant in the Galaxy, which at first glance may be difficult to reconcile with the observed supernova rate. However, as I will discuss, it seems that the RRATs can be explained as pulsars which are either extreme nullers, highly variable or weak/distant. I will re-cap some recent results including a re-analysis of the Parkes Multi-beam Pulsar Survey, which has identified several new sources, as well as the unusual timing behaviour of RRAT J1819-1458. This leads to an examination of where RRATs fit within the evolution of neutron stars post-supernova.