gebhart/patrepeval huggingface dataset:
The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy (2011)

The evolution of drug-resistant pathogens is a major challenge for 21st century medicine. Drug use practices vigorously advocated as resistance management tools by professional bodies, public health agencies, and medical schools represent some of humankind's largest attempts to manage evolution. It is our contention that these practices have poor theoretical and empirical justification for a broad spectrum of diseases. For instance, rapid elimination of pathogens can reduce the probability that de novo resistance mutations occur. This idea often motivates the medical orthodoxy that patients should complete drug courses even when they no longer feel sick. Yet "radical pathogen cure" maximizes the evolutionary advantage of any resistant pathogens that are present. It could promote the very evolution it is intended to retard. The guiding principle should be to impose no more selection than is absolutely necessary. We illustrate these arguments in the context of malaria; they likely apply to a wide range of infections as well as cancer and public health insecticides. Intuition is unreliable even in simple evolutionary contexts; in a social milieu where in-host competition can radically alter the fitness costs and benefits of resistance, expert opinion will be insufficient. An evidence-based approach to resistance management is required.
CDYL1 fosters double-strand break-induced transcription silencing and promotes homology-directed repair (2017)

Cells have evolved DNA damage response (DDR) to repair DNA lesions and thus preserving genomic stability and impeding carcinogenesis. DNA damage induction is accompanied by transient transcription repression. Here, we describe a previously unrecognized role of chromodomain Y-like (CDYL1) protein in fortifying double-strand break (DSB)-induced transcription repression and repair. We showed that CDYL1 is rapidly recruited to damaged euchromatic regions in a poly (ADP-ribose) polymerase 1 (PARP1)-dependent, but ataxia telangiectasia mutated (ATM)-independent, manner. While the C-terminal region, containing the enoyl-CoA hydratase like (ECH) domain, of CDYL1 binds to poly (ADP-ribose) (PAR) moieties and mediates CDYL1 accumulation at DNA damage sites, the chromodomain and histone H3 trimethylated on lysine 9 (H3K9me3) mark are dispensable for its recruitment. Furthermore, CDYL1 promotes the recruitment of enhancer of zeste homolog 2 (EZH2), stimulates local increase of the repressive methyl mark H3K27me3, and promotes transcription silencing at DSB sites. In addition, following DNA damage induction, CDYL1 depletion causes persistent G2/M arrest and alters H2AX and replication protein A (RPA2) phosphorylation. Remarkably, the 'traffic-light reporter' system revealed that CDYL1 mainly promotes homology-directed repair (HDR) of DSBs in vivo. Consequently, CDYL1-knockout cells display synthetic lethality with the chemotherapeutic agent, cisplatin. Altogether, our findings identify CDYL1 as a new component of the DDR and suggest that the HDR-defective 'BRCAness' phenotype of CDYL1-deficient cells could be exploited for eradicating cancer cells harboring CDYL1 mutations.
Zeolitic imidazolate framework 8 (ZIF‐8) reinforced macroporous resin D101 for selective solid‐phase extraction of 1‐naphthol and 2‐naphthol from phenol compounds (2017)

Macroporous resin has been attracting intensive attention due to its critical role in separation and purification of natural products. Herein, a zeolitic imidazolate framework 8 reinforced macroporous resin D101 was prepared via a room temperature growth method and used for dispersive SPE of 1-naphthol and 2-naphthol. The parameters affecting the adsorption and desorption efficiency such as the sample pH, adsorbent amount, extraction time, desorption solvent, and desorption time were investigated. The as-prepared adsorbent showed selectivity for 1-naphthol and 2-naphthol compared to other phenols. Under the optimum dispersive SPE conditions, the detection of 1-naphthol and 2-naphthol coupled with a CZE method was conducted and the LODs for 1-naphthol and 2-naphthol were 1.37 and 1.43 ng/mL, respectively. Moreover, the results of urine sample analysis showed the spiked recoveries to be in the range of 96.2-106.9%. This study indicated that D101@ZIF-8 (where ZIF is zeolitic imidazolate framework) is a promising selective adsorbent for the analysis of 1-naphthol and 2-naphthol in urine samples.
Toll-Like Receptor 4 Expression on Lymphoma Cells Is Critical for Therapeutic Activity of Intratumoral Therapy With Synthetic TLR4 Agonist Glucopyranosyl Lipid A (2020)

Intratumoral (IT) injections of Glucopyranosyl lipid A (G100), a synthetic toll-like receptor 4 (TLR4) agonist formulated in a stable emulsion, resulted in T-cell inflammation of the tumor microenvironment (TME) and complete cure of 60% of mice with large established A20 lymphomas. Strong abscopal effects on un-injected lesions were observed in a bilateral tumor model and surviving mice resisted a secondary tumor challenge. Depletion of CD8 T-cells, but not CD4 or NK cells, abrogated the anti-tumor effect. Unexpectedly, TLR4 knock-out rendered A20 tumors completely non-responsive to G100. <i>In vitro</i> studies showed that GLA has direct effect on A20 cells, but not on A20 cells deficient for TLR4. As shown by genotyping and phenotyping analysis, G100 strongly activated antigen presentation functions in A20 cells <i>in vitro</i> and <i>in vivo</i> and induced their apoptosis in a dose dependent manner. Similarly, the TLR4 positive human mantle cell lymphoma line Mino showed <i>in vitro</i> activation with G100 that was blocked with an anti-TLR4 antibody. In the A20 model, direct activation of B-lymphoma cells with G100 is sufficient to induce protective CD8 T-cell responses and TLR4 expressing human B-cell lymphomas may be amenable to this therapy as well.
A study on interference detection scheme using AIC for UWB MB-OFDM systems (2011)

Ultra-Wide Band (UWB) spectrum causes interference to primary wireless communication systems whose spectra overlap the UWB band because UWB systems make use of huge bandwidth compared with the primary systems. Therefore, we have to implement Detect-And-Avoid (DAA) techniques to detect the primary system and control the signal transmitted from the UWB devices. Although there is the energy detection scheme for detecting the primary signal based on a threshold, it is difficult to find an appropriate threshold. In this paper, we investigate a novel detection scheme for UWB Multi-Band OFDM system. The proposed method detects the presence of the primary system using estimates of the primary signal and the noise variance based on the maximum likelihood criterion. Moreover, we introduce Akaike Information Criterion (AIC) in order to select the most suitable primary signal model out of some possible models. As a result, the proposed method dynamically find the threshold to detect the presence of the primary signal in sharp contrast to the conventional energy detection method which uses a static threshold. By the computer simulations, we show that the proposed method outperforms the conventional method with respect to missed-detection and false-detection probabilities.
Image Preprocessing for Stereoscopic Visual Odometry at Night (2018)

Cameras are a primary sensor for many robotics perception tasks. However, cameras' performance degrades in low-light conditions. In this paper, we propose a simple preprocessing pipeline to enhance captured images in low-light conditions. This pipeline is developed with visual odometry application in outdoor environments in mind. The pipeline is evaluated on a manually collected dataset and compared to the base case with no preprocessing applied.
Intraoperative Monitoring for Hearing Preservation and Restoration in Acoustic Neuroma Surgery (2000)

The present article reports on our experience with hearing preservation during 158 acoustic neuroma (AN) operations via the retrosigmoid-transmeatal (RS-TM) approach with the aid of intraoperative auditory monitoring. Several auditory monitoring methods are described. Of these, the bipolar cochlear nerve action potential (CNAP) was found to be the most helpful in preserving hearing. Of 106 patients with useful hearing preoperatively, more than 50% had useful hearing after surgery. Electrical auditory brainstem responses were useful in the placement of an auditory brain stem implant (ABI) in 4 patients with neurofibromatosis type 2 (NF2). All 4 reported speech perception benefit and use their ABIs regularly in their lives. It is our firm belief that intraoperative auditory monitoring has a pivotal role in the preservation and restoration of hearing in AN surgery.
TGF‐β‐induced fibrotic stress increases G‐quadruplex formation in human fibroblasts (2019)

Scar formation after wound healing is a major medical problem. A better understanding of the dynamic nuclear architecture of the genome during wound healing could provide insights into the underlying pathophysiology and enable novel therapeutic strategies. Here, we demonstrate that TGF-β-induced fibrotic stress increases formation of the dynamic secondary DNA structures called G-quadruplexes in skin fibroblasts, which is coincident with increased expression of collagen 1. This G-quadruplex formation is attenuated by a small molecule inhibitor of intracellular Ca<sup>2+</sup> influx and an anti-fibrotic compound. In addition, we identify G-quadruplex-forming sequences in the promoter region of COL1A1, which encodes collagen 1, and confirm their ability to form G-quadruplex structures under physiologically relevant conditions. Our findings reveal a link between G-quadruplexes and scar formation that may lead to novel therapeutic interventions.
Epigenetics in T‐cell acute lymphoblastic leukemia (2014)

Normal T-cell development is a strictly regulated process in which hematopoietic progenitor cells migrate from the bone marrow to the thymus and differentiate from early T-cell progenitors toward mature and functional T cells. During this maturation process, cooperation between a variety of oncogenes and tumor suppressors can drive immature thymocytes into uncontrolled clonal expansion and cause T-cell acute lymphoblastic leukemia (T-ALL). Despite improved insights in T-ALL disease biology and comprehensive characterization of its genetic landscape, clinical care remained largely similar over the past decades and still consists of high-dose multi-agent chemotherapy potentially followed by hematopoietic stem cell transplantation. Even with such aggressive treatment regimens, which are often associated with considerable side effects, clinical outcome is still extremely poor in a significant subset of T-ALL patients as a result of therapy resistance or hematological relapses. Recent genetic studies have identified recurrent somatic alterations in genes involved in DNA methylation and post-translational histone modifications in T-ALL, suggesting that epigenetic homeostasis is critically required in restraining tumor development in the T-cell lineage. In this review, we provide an overview of the epigenetic regulators that could be implicated in T-ALL disease biology and speculate how the epigenetic landscape of T-ALL could trigger the development of epigenetic-based therapies to further improve the treatment of human T-ALL.
Differential LiveMycobacterium tuberculosis-,M. bovisBCG-, Recombinant ESAT6-, and Culture Filtrate Protein 10-Induced Immunity in Tuberculosis (2009)

The high prevalence of Mycobacterium tuberculosis makes it imperative that immune responses to evaluate could be predictive of infection. We investigated live Mycobacterium- and recombinant antigen-induced cytokine and chemokine responses in patients with active tuberculosis (TB) compared with those of healthy controls from an area where TB is endemic (ECs). M. tuberculosis-, M. bovis BCG-, ESAT6-, and culture filtrate protein 10 (CFP10)-induced responses were determined in peripheral blood mononuclear cells from patients with pulmonary TB (n = 38) and ECs (n = 39). The levels of the cytokines gamma interferon (IFN-gamma) and interleukin-10 (IL-10) and the chemokines CCL2, CCL3, and CXCL9 were measured. The levels of M. tuberculosis- and BCG-induced IFN-gamma secretion were significantly reduced (P = 0.002 and P < 0.01, respectively), while the amount of IL-10 induced by both virulent (P < 0.01) and avirulent (P = 0.002) mycobacteria was increased in patients with TB. The ESAT6-induced IFN-gamma responses were increased in the patients with TB (P = 0.013) compared with those in the EC group. When tuberculin skin test (TST)-negative (TST(-); induration, <10 mm) and TST-positive (TST(+)) donors were studied separately, both TST(-) and TST(+) individuals showed increased IFN-gamma responses to M. tuberculosis compared with the responses of the patients with TB (P = 0.037 and P = 0.006, respectively). However, only TST(+) ECs showed reduced IFN-gamma responses to ESAT6 (P = 0.008) compared with the responses of the patients with TB. The levels of M. tuberculosis-induced CCL2 (P = 0.006) and CXCL9 (P = 0.017) were greater in the patients with TB. The levels of CCL3 secretion in response to Mycobacterium and antigen stimulation were comparable between the two groups. While the levels of ESAT6-induced chemokines did not differ between the patients with TB and the ECs, the levels of CFP10-induced CCL2 (P = 0.01) and CXCL9 (P = 0.001) were increased in the patients. These data indicate differential host IFN-gamma, CXCL9, and CCL2 responses to live mycobacteria and mycobacterial antigens and have implications for the identification of potential biomarkers of infection which could be used for the diagnosis of TB.
HYBRIDIZATION STUDIES WITH SPECIES OF CYNODON FROM EAST AFRICA AND MALAGASY (1969)

A collection of 198 accessions of Cynodon from East Africa and Malagasy was grown in uniform nurseries at Stillwater, Okla., and classified morphologically, studied cytologically, and tested for crossability in hybridization studies. The following taxa were recognized: C. arcuatus, C. plectostachyus, C. aethiopicus, C. nlemfuensis var. nlemfuensis, C. nlemfuensis var. robustas, C. dactylon var. aridus, C. dactylon var. coursii , and C. dactylon var. dactylon . The magnitude of barriers to gene flow was estimated by ease of hybridization and by sterility of the hybrids obtained. C. arcuatus and C. plectostachyus are well isolated from all other species in the genus. The others are sufficiently related that they may be intercrossed. The barriers to gene flow vary demonstrably in strength between different combinations of taxa. The magnitude of a barrier required to establish species limits is, perhaps, more a matter of subjective opinion than a scientific conclusion. It was concluded that no completely satisfactory classification of the genus is possible. The system adopted was a compromise between classical morphological concepts of species, the biological concept of species, and pragmatic utility.
Brain Death and the Persistent Vegetative State: Similarities and Contrasts (1989)

Brain death and the persistent vegetative state (PVS) share the following features: 1.) There is death of neurons in the brain; 2.) Both require an etiology which is capable of causing neuronal death. 3.) The potential for cognition is totally and permanently lost; 4.) Intensive medical support is usually withdrawn. In contrast, the diagnosis of brain death depends on death of the brainstem, while PVS implies permanent and total loss of forebrain function. While brainstem death can be diagnosed clinically, accurate prognosis in PVS requires additional investigation. Thus far, the EEG is the most specific test of neuronal function in the cerebral cortex. Brain death is equivalent to death, while PVS is not; management of the latter is more complex because of medical, social, ethical and legal factors.
Minimally Invasive Unicondylar Arthroplasty in the Post-Meniscectomy Knee: Repicci Knee (2002)

Loss of the meniscus decreases contact area, resulting in increased stress on the articular cartilage of the knee. Osteoarthritis frequently develops and sclerotic bone is exposed on the articular surfaces of the joint. In the medial compartment, this process is characterized by loss of articular cartilage and anterior cruciate ligament and medial cruciate ligament laxity in the extension gap, with no corresponding laxity in the flexion gap. This focal articular and ligamentous imbalance may persist for a decade or more. Minimally invasive unicondylar arthroplasty is a low-morbidity procedure that resurfaces the medial compartment and rebalances ligaments while preserving bone for future arthroplasty procedures.
Neuroadaptive Model Following Controller Design for Non-Affine and Non-Square Aircraft Systems (2009)

Aircrafts with high performance requirements or structural damage, often operate in conditions characterized by rapidly changing nonlinear aerodynamic phenomena. A neural network based model-following adaptive control design is proposed in this paper for stable control of aircrafts in such scenarios. These systems have control dependent nonlinearities making their mathematical characterization non-affine in control and they are usually nonsquare too. The uncertainties that occur during the flight are estimated online with weight update adaptation laws derived by using the Lyapunov theory to ensure boundedness of the estimation errors and the weights. The nonsquare system model is re-structured by using slack variables to facilitate the design of control using the dynamic inversion technique. Typically, when large changes appear in the aerodynamic derivatives, fast adaptation is required to ensure the system stability. But the drawback with using high adaptive gains is that they could result in high frequency oscillations in the control signal that excite the unmodeled dynamics of the plant. A novel observer structure is employed in this paper that enables fast adaptation without inducing any high frequency oscillations. The proposed method is applied to the short period dynamics of a fighter aircraft and is compared with the recently popular L1 adaptive control technique. Simulation results demonstrate the potential of the proposed method.
Beneficial Effect of a Small Pharmacologic Chaperone on the Established Alzheimer’s Disease Phenotype (2022)

Taken together, our findings demonstrate that pharmacologic stabilization of the retromer recognition core is beneficial also after the AD-like pathologic phenotype is established.
Role of π-Bonding for Trigonal Level Splittings in Chromium(III) Complexes. 4. Doublet States and Zeeman Level Splittings in [Cr(bpy)3]3+ (1996)

A detailed analysis of Zeeman splittings of highly resolved spin-forbidden transitions in [Cr(bpy)3](PF6)3 is presented. Assignments of vibronic bands are made based on low-temperature absorption, emission, and infrared spectra. The pattern of doublet states, obtained for H = 0 and H = 5 T, is consistent with angular overlap model (AOM) calculations, which allow one to consider σ- and π-interactions between the metal-d and relevant ligand orbitals and the particular angular geometry of the chromophore simultaneously. The observed level splittings are found to result from the combined effect of trigonal distortion and contributions of the symmetry adapted dπ-orbitals involved due to coupling with corresponding counterparts from the bidentate ligand (phase coupling). The larger splitting of the lowest excited state 2Eg(Oh) in the analogous ClO4- salt is due to the more distorted geometry of the [CrN6] moiety. Related properties of the bipyridine ligand, which turn out to show donor behavior in the present compounds, and the acetylacetonate ligand are discussed, and AOM parameters for the metal−ligand π-interaction are correlated with results of MO calculations.
Field emission studies of novel ZnO nanostructures in high and low field regions (2006)

A study of the field emission characteristics of novel structures of ZnO, namely marigolds, multipods and microbelts, has been carried out in both the close proximity configuration and the conventional field emission microscope. The use of a conventional field emission microscope overcomes the drawback of arc formation at high field values. The nonlinearity in the Fowler–Nordheim (F–N) plot, a characteristic feature of semiconductors has been observed and explained on the basis of electron emission from both the conduction and the valence bands. The current stability exhibited by these structures is also promising for future device applications.
Transfer of nanomembranes from solution to a solid frame via reflow of low surface tension liquids (2012)

Nanomembranes represent a novel building block for nanosystems, characterized by a thickness below 100 nm and a giant aspect ratios. A typical procedure for nanomembrane fabrication starts from an ultrathin layer deposited on some kind of a sacrificial substrate. The nanomembrane is released by etching away the substrate, leaving the nanomembrane to freely float in the solvent. This solvent may be water or some other liquid. Many different types of nanomembranes can be made by this procedure, but only a limited number can survive the capillary forces during the extraction from solvent. In this paper we propose a novel, generally applicable method for freeing nanomembranes from the solvent via direct in-situ substitution of the solvent in meniscus with a low surface tension liquid. The proposed method ensures high production yields, is not very dependent on experimental skills, and avoids introduction of contaminants into the nanomembrane structure.
Empirical Likelihood for Contextual Bandits (2020)

We apply empirical likelihood techniques to contextual bandit policy value estimation, confidence intervals, and learning. We propose a tighter estimator for off-policy evaluation with improved statistical performance over previous proposals. Coupled with this estimator is a confidence interval which also improves over previous proposals. We then harness these to improve learning from contextual bandit data. Each of these is empirically evaluated to show good performance against strong baselines in finite sample regimes.
Lactobacillus reuteri -produced cyclic dipeptides quench agr -mediated expression of toxic shock syndrome toxin-1 in staphylococci (2011)

The production of the staphylococcal exotoxin toxic shock syndrome toxin-1 (TSST-1) by Staphylococcus aureus has been associated with essentially all cases of menstruation-associated toxic shock syndrome (TSS). In this work, we show that the human vaginal isolate Lactobacillus reuteri RC-14 produces small signaling molecules that are able to interfere with the staphylococcal quorum-sensing system agr, a key regulator of virulence genes, and repress the expression of TSST-1 in S. aureus MN8, a prototype of menstrual TSS S. aureus strains. Quantitative real-time PCR data showed that transcription from the Ptst promoter, as well as the P2 and P3 promoters of the agr system from all four agr subgroups of S. aureus, was strongly inhibited in response to growth with L. reuteri RC-14 cultural supernatant. Alterations in the transcriptional levels of two other virulence-associated regulators sarA and saeRS were also observed, indicating a potential overall influence of L. reuteri RC-14 signals on the production of virulence factors in S. aureus. S. aureus promoter-lux reporter strains were used to screen biochemically fractionated L. reuteri RC-14 supernatant, and the cyclic dipeptides cyclo(L-Phe-L-Pro) and cyclo(L-Tyr-L-Pro) were identified as the signaling molecules. The results from this work contribute to a better understanding of interspecies cell-to-cell communication between Lactobacillus and Staphylococcus, and provide a unique mechanism by which endogenous or probiotic strains may attenuate virulence factor production by bacterial pathogens.