gebhart/patrepeval huggingface dataset:
Complete Genome Sequence of the Anaerobic, Protein-Degrading Hyperthermophilic Crenarchaeon Desulfurococcus kamchatkensis (2008)

Desulfurococcus kamchatkensis is an anaerobic organotrophic hyperthermophilic crenarchaeon isolated from a terrestrial hot spring. Its genome consists of a single circular chromosome of 1,365,223 bp with no extrachromosomal elements. A total of 1,474 protein-encoding genes were annotated, among which 205 are exclusive for D. kamchatkensis. The search for a replication origin site revealed a single region coinciding with a global extreme of the nucleotide composition disparity curve and containing a set of crenarchaeon-type origin recognition boxes. Unlike in most archaea, two genes encoding homologs of the eukaryotic initiator proteins Orc1 and Cdc6 are located distantly from this site. A number of mobile elements are present in the genome, including seven transposons representing IS607 and IS200/IS605 families and multiple copies of miniature inverted repeat transposable elements. Two large clusters of regularly interspaced repeats are present; none of the spacer sequences matches known archaeal extrachromosomal elements, except one spacer matches the sequence of a resident gene of D. kamchatkensis. Many of the predicted metabolic enzymes are associated with the fermentation of peptides and sugars, including more than 30 peptidases with diverse specificities, a number of polysaccharide degradation enzymes, and many transporters. Consistently, the genome encodes both enzymes of the modified Embden-Meyerhof pathway of glucose oxidation and a set of enzymes needed for gluconeogenesis. The genome structure and content reflect the organism's nutritionally diverse, competitive natural environment, which is periodically invaded by viruses and other mobile elements.
Inhibition of 3β-hydroxysteroid dehydrogenase by abiraterone: A rationale for increasing drug exposure in castration-resistant prostate cancer. (2012)

4645 Background: Treatment with abiraterone acetate (abi) increases the survival of men with castration-resistant prostate cancer (CRPC). Resistance to abi invariably occurs, probably due in part to up-regulation of steroidogenic enzymes and/or other mechanisms that sustain the synthesis of dihydrotestosterone (DHT), which raises the possibility of reversing resistance by concomitant inhibition of other required steroidogenic enzymes. The 1,000 mg daily abi dose was selected for the phase III trials despite the absence of dose-limiting toxicities at higher doses. Based on the 3β-hydroxyl, Δ 5 -structure, we hypothesized that abi also inhibits 3β-hydroxysteroid dehydrogenase/isomerase (3βHSD), which is absolutely required for the intratumoral synthesis of DHT in CRPC, regardless of origins or routes of synthesis. Methods: We tested if abi inhibits recombinant 3βHSD2 activity in vitro or endogenous 3βHSD activity in LNCaP and LAPC4 cells, including conversion of [ 3 H]-dehydroepiandrosterone (DHEA) to androstenedione (AD), androgen receptor (AR) nuclear translocation, expression of AR-responsive genes, and LAPC4 xenograft growth in orchiectomized mice supplemented with DHEA. Results: Abi has a mixed inhibition pattern of 3βHSD2 in vitro, blocks the conversion from DHEA to AD and DHT with an IC 50 of &lt; 1 µM in CRPC cell lines, inhibits AR nuclear translocation and expression of TMPRSS2, and decreases CRPC xenograft growth in DHEA-supplemented mice. Conclusions: Abi blocks 3βHSD enzymatic activity, synthesis of AD and DHT, inhibits the AR-response, and suppresses growth of CRPC cells at concentrations that are clinically achievable. Variable abi inhibition of 3βHSD might account in part for the heterogeneous clinical response to abi. More importantly, 3βHSD inhibition with abi might be clinically harnessed to reverse resistance to CYP17A1 inhibition at the standard dose by dose-escalation, or simply by administration with food to increase drug exposure.
Hardness and softness in theab initiostudy of polyatomic systems (1993)

A combination of the maximum hardness (MH) principle, and the local version of the hard and soft acids and bases (HSAB) principle is tested as a tool to describe the stability and reactivity of polyatomic systems. The local HSAB principle describes regional differences in reactivity whereas the MH principle selects the most stable configuration. This approach is tested using ab initio density functional theory techniques. Total-energy calculations fully confirm the validity of both principles.
Financial sustainability of a health micro-insurance scheme: a theoretical investigation (2023)

The article attempts to outline a business model of a for-profit insurance firm initiating a health micro-insurance (MHI) scheme and investigates whether it can sustain financially in that endeavour. We show that when a firm cannot observe and monitor the effort taken by beneficiaries in prevention, the presence of a nodal agency (any voluntary local organisation like NGO) is very crucial in maintaining the financial sustainability of the scheme. If the individual claims are independent and identically distributed, under certain conditions the level of expected claims is decreasing in NGO's effort level. The firm can set a lower risk-loading with the higher monitoring effort of the NGO.
Simplivariate Models: Ideas and First Examples (2008)

One of the new expanding areas in functional genomics is metabolomics: measuring the metabolome of an organism. Data being generated in metabolomics studies are very diverse in nature depending on the design underlying the experiment. Traditionally, variation in measurements is conceptually broken down in systematic variation and noise where the latter contains, e.g. technical variation. There is increasing evidence that this distinction does not hold (or is too simple) for metabolomics data. A more useful distinction is in terms of informative and non-informative variation where informative relates to the problem being studied. In most common methods for analyzing metabolomics (or any other high-dimensional x-omics) data this distinction is ignored thereby severely hampering the results of the analysis. This leads to poorly interpretable models and may even obscure the relevant biological information. We developed a framework from first data analysis principles by explicitly formulating the problem of analyzing metabolomics data in terms of informative and non-informative parts. This framework allows for flexible interactions with the biologists involved in formulating prior knowledge of underlying structures. The basic idea is that the informative parts of the complex metabolomics data are approximated by simple components with a biological meaning, e.g. in terms of metabolic pathways or their regulation. Hence, we termed the framework 'simplivariate models' which constitutes a new way of looking at metabolomics data. The framework is given in its full generality and exemplified with two methods, IDR analysis and plaid modeling, that fit into the framework. Using this strategy of 'divide and conquer', we show that meaningful simplivariate models can be obtained using a real-life microbial metabolomics data set. For instance, one of the simple components contained all the measured intermediates of the Krebs cycle of E. coli. Moreover, these simplivariate models were able to uncover regulatory mechanisms present in the phenylalanine biosynthesis route of E. coli.
Id1 and PD-1 Combined Blockade Impairs Tumor Growth and Survival of KRAS-mutant Lung Cancer by Stimulating PD-L1 Expression and Tumor Infiltrating CD8+ T Cells (2020)

The use of PD-1/PD-L1 checkpoint inhibitors in advanced NSCLC is associated with longer survival. However, many patients do not benefit from PD-1/PD-L1 blockade, largely because of immunosuppression. New immunotherapy-based combinations are under investigation in an attempt to improve outcomes. <i>Id1</i> (inhibitor of differentiation 1) is involved in immunosuppression. In this study, we explored the potential synergistic effect of the combination of <i>Id1</i> inhibition and pharmacological PD-L1 blockade in three different syngeneic murine <i>KRAS</i>-mutant lung adenocarcinoma models. TCGA analysis demonstrated a negative and statistically significant correlation between PD-L1 and <i>Id1</i> expression levels. This observation was confirmed in vitro in human and murine <i>KRAS</i>-driven lung cancer cell lines. In vivo experiments in <i>KRAS</i>-mutant syngeneic and metastatic murine lung adenocarcinoma models showed that the combined blockade targeting <i>Id1</i> and PD-1 was more effective than each treatment alone in terms of tumor growth impairment and overall survival improvement. Mechanistically, multiplex quantification of CD3<sup>+</sup>/CD4<sup>+</sup>/CD8<sup>+</sup> T cells and flow cytometry analysis showed that combined therapy favors tumor infiltration by CD8<sup>+</sup> T cells, whilst in vivo CD8<sup>+</sup> T cell depletion led to tumor growth restoration. Co-culture assays using CD8<sup>+</sup> cells and tumor cells showed that T cells present a higher antitumor effect when tumor cells lack <i>Id1</i> expression. These findings highlight that <i>Id1</i> blockade may contribute to a significant immune enhancement of antitumor efficacy of PD-1 inhibitors by increasing PD-L1 expression and harnessing tumor infiltration of CD8<sup>+</sup> T lymphocytes.
Ultra-Compact Mid-IR Modulators Based on Electrically Tunable Optical Antennas (2014)

We demonstrated electrical tuning of optical antennas over a broad wavelength range (~1100 nm, ~20% of the resonance frequency) and achieved optical modulators at the mid-infrared wavelength range with nanosecond response time.
Computational Analysis of Alternative Polyadenylation in Embryonic Stem Cells and Induced Pluripotent Cells (2012)

The 3’ untranslated region (3’UTR) of mRNA plays important roles in posttranscriptional control of gene expression. Over half of the human genes have multiple polyadenylation sites in 3’UTRs, leading to 3’UTR isoforms containing different cis elements. Alternative polyadenylation (APA) has been found to be dynamically regulated in different tissue types and under various cellular conditions. Embryonic stem (ES) cells have the ability to self-renew and differentiate into any cell type in the adult body. Posttranscriptional gene regulation through cis elements in 3’UTRs is increasingly found to be important for these functions. In addition, various methods have recently been developed to induce differentiated cells to ES-like cells, called induced pluripotent stem (iPS) cells. Here we show a computational method to examine regulation of 3’UTR by APA using DNA microarray data. We applied this method to ES cells and iPS cells derived from different cell types.
Syk activation of phosphatidylinositol 3-kinase/Akt prevents HtrA2-dependent loss of X-linked inhibitor of apoptosis protein (XIAP) to promote survival of Epstein-Barr virus+ (EBV+) B cell lymphomas. (2012)

View Large Image Figure ViewerDownload Hi-res image Download (PPT)VOLUME 286 (2011) PAGES 37368–37378 PAGE 37371: Due to an inadvertent error, the wrong image was presented for part of Fig. 1C. The correct image is shown below. The last sentence of the figure legend to Fig. 1 should read, “data are representative of n ≥ 2 independent experiments.” The conclusions of the paper remain unchanged. PAGE 37373: Due to an inadvertent error, the wrong image was presented for part of Fig. 3A. The correct image is shown below. The figure legend is correct as it appears. The conclusions of the paper remain unchanged.
High-dose therapy plus autologous hematopoietic stem cell transplantation for human immunodeficiency virus (HIV)-related lymphoma: results and impact on HIV disease. (2004)

HDC/AHSCT is feasible in AIDS-related lymphoma, in terms of harvesting, engraftment, adverse events and HIV control. It should be proposed to patients with poor-prognosis chemosensitive lymphoma.
Quantum Machine Learning with Quantum Image Representations (2022)

Image classification is an important task in many practical applications. Recently, there have been various works on classification problems using quantum neural network (QNN). Different data encoders have been investigated, but efficient quantum encoding schemes for high-dimensional data such as images are still an open question. In this study, we investigate popular representation formats of quantum images, namely FRQI and NEQR, as data encoders for quantum neural networks. It is found that the FRQI format not only provides the best classification accuracy compared to NEQR and other popular encoding methods but also is consistent across different circuit depths of QNN. It should be noted that FRQI is notorious for its probabilistic representation in quantum image processing. The finding of this study is interesting because FRQI can play an important role in the field of quantum machine learning.
Ex Vivo Expansion of SCID-Repopulating CD34+CD90+CD49f+Hematopoietic Stem & Progenitor Cells From Non-Enriched Human Umbilical Cord Blood with Novel Azole-Based Small Molecules (2018)

Umbilical cord blood (UCB) transplantations in adults are limited by low number of total nucleated cells (TNC) and hematopoietic stem & progenitor cells (HSPC) that delays neutrophil engraftment compared to bone marrow (BM) or peripheral blood grafts. To expand HSPCs from non-enriched mono-nucleated cells (MNC) or CD34+ purified UCB; we developed a proprietary library of 50 small molecules using structure-activity relationship studies of the parent p38 MAPK inhibitor, SB203580. Freshly-thawed UCB-MNC or purified CD34+ cells were cultured in expansion medium supplemented with each compound and a basal cytokine cocktail. The effects of the expansion protocol were measured based on phenotypic and functional assays. In expansion cultures initiated with MNCs lasting up to 11 days, one structural analogue, C7, resulted in a 1554.1 ± 27.8–fold increase of absolute CD45+CD34+CD38–CD45RA–progenitors which was at least 3.7–fold higher than control cultures (P < .01; n = 3). Functional colony forming unit assays showed a significant increase of granulocyte-macrophage colonies from C7 treated cells (P < .01; n = 6). A cytokine cocktail comprising of SCF, TPO, and FLT-3L was essential for expansion. The addition of C7 boosted primitive HSPC expansion (CD34+CD90+CD49f+) by 633.3 ± 8.5–fold over 10 days, which was at least 7.4–fold higher than control cultures (P < .001; n = 3). Transplantation of C7 expanded UCB grafts (n = 11) at dosage of 2.5x107 cells/kg to sub-lethally irradiated NOD SCID Gamma (NSG) mice resulted in 3.2– and 2.1–fold higher engraftment of human CD45+ cells in the peripheral blood (PB) by day 21 compared to non-expanded (P = .0030; n = 6) and cytokine expanded grafts (P = .0005; n = 12) respectively. Analysis of the NSG BM at week 2 showed significantly (P < .001, n = 14) higher proportion of human CD34+ and myeloid cells from C7 expanded graft compared to non-expanded graft that contained mostly CD3+ T–cells. Analysis of NSG BM at week 19 showed that C7 expanded grafts maintained human HSPC and multi-lineage engraftment accompanied by stable human CD45+ cells engraftment in secondary recipients. Comparison of C7 to molecules such as SR-1, UM171 and NAM showed that C7 produced optimal expansion (P < .01; n = 3) when cultures were initiated with MNC. Expansion of magnetic column purified CD34+ cells resulted in >280–fold expansion of absolute HSPC cells within 11 days, which resulted in significantly (P < .0001; n = 6) better multi-lineage engraftment in the NSG PB and BM compared to cytokine expanded graft. C7 is the first proprietary small molecule that could expand UCB HSPC without the need to perform prior CD34/CD133 based stem cell enrichment. With CD34 selection this molecule is also able to attain superior HSPC expansion. The C7 expanded grafts retain both phenotypic markers along with the ability to support early human cell engraftment in NSG PB and contribute to long-term BM hematopoiesis.
Protective effect of forphenicinol, a low molecular weight immunomodifier, against infection with Pseudomonas aeruginosa in mice and its mechanisms. (1987)

The oral administration of forphenicinol increased the survival rate of both normal and immunodepressed mice intraperitoneally or intratracheally infected with clinically isolated strains of Pseudomonas aeruginosa. The therapeutic effect of amikacin on intraperitoneal infection with P. aeruginosa was enhanced by combined use with forphenicinol. Forphenicinol did not enhance the bactericidal activity of polymorphonuclear cells (PMN) towards P. aeruginosa in vitro, but enhanced it in vivo. In vitro study indicated that the macrophages taken from mice treated with forphenicinol or the cultured supernatant of these macrophages enhanced the bactericidal activity of PMN. The protective effect of forphenicinol against P. aeruginosa infection was thus suggested to be due to macrophage activation followed by the enhancement of the bactericidal activity of PMN.
Variability of the modified Balance Error Scoring System at baseline using objective and subjective balance measures (2015)

The high variability and large number of errors in the SS raises concerns over the utility of the SS in identifying suspected concussion.
Modeling Alzheimer’s disease with iPSC-derived brain cells (2019)

Alzheimer's disease is a devastating neurodegenerative disorder with no cure. Countless promising therapeutics have shown efficacy in rodent Alzheimer's disease models yet failed to benefit human patients. While hope remains that earlier intervention with existing therapeutics will improve outcomes, it is becoming increasingly clear that new approaches to understand and combat the pathophysiology of Alzheimer's disease are needed. Human induced pluripotent stem cell (iPSC) technologies have changed the face of preclinical research and iPSC-derived cell types are being utilized to study an array of human conditions, including neurodegenerative disease. All major brain cell types can now be differentiated from iPSCs, while increasingly complex co-culture systems are being developed to facilitate neuroscience research. Many cellular functions perturbed in Alzheimer's disease can be recapitulated using iPSC-derived cells in vitro, and co-culture platforms are beginning to yield insights into the complex interactions that occur between brain cell types during neurodegeneration. Further, iPSC-based systems and genome editing tools will be critical in understanding the roles of the numerous new genes and mutations found to modify Alzheimer's disease risk in the past decade. While still in their relative infancy, these developing iPSC-based technologies hold considerable promise to push forward efforts to combat Alzheimer's disease and other neurodegenerative disorders.
Pulse asymmetries and write nonlinearities in the write equalization process for magnetic tape recording (1999)

In this paper, we compare experimental measurements of magnetic tape recording signals with the results of simulation. Specifically, nonlinearities associated with the write equalization process are examined. It is found that the depth dependent vector Preisach model (VPM) of the magnetic recording process is able to semi-quantitatively reproduce nonlinearities that are seen in the readback from real heads and media. The failure of standard linear superposition models even qualitatively to capture these effects is demonstrated. Furthermore, the VPM shows, through the recorded magnetisation distribution, that demagnetizing effects from the data transitions can distort the write equalization pulses, if the pulses follow the data transitions too closely. This leads to a directional asymmetry in the writing process, such that symmetrically placed write equalization pulses do not lead to the most symmetrical waveforms.
A peer-selection algorithm for information retrieval (2010)

A novel method for creating collection summaries is developed, and a fully decentralized peer-selection algorithm is described. This algorithm finds the most promising peers for answering a given query. Specifically, peers publish per-term synopses of their documents. The synopses of a peer for a given term are divided into score intervals and for each interval, a KMV (K Minimal Values) synopsis of its documents is created. The synopses are used to effectively rank peers by their relevance to a multi-term quer. The proposed approach is verified by experiments on a large real-world dataset. In particular, two collections were created from this dataset, each with a different number of peers. Compared to the state-of-the-art approaches, the proposed method is effective and efficient even when documents are randomly distributed among peers
Pressure-Transient Behavior of Horizontal Wells With and Without Gas Cap or Aquifer (1991)

Summary New analytic solutions are presented in real time and as Laplace transforms for horizontal wells in reservoirs bounded at the top and bottom by horizontal planes. Two types of boundary conditions are considered at these planes, and the Laplace-transform pressure solutions are used to include wellbore-storage and skin effects. Solutions are based on the uniform-flux, line-source solution, but differ from most existing solutions owing to the use of pressure averaging to approximate the infinite-conductivity wellbore condition and use of the correct equivalent wellbore radius for an anisotropic reservoir. New flow periods (regimes) are identified, and simple equations and existence criteria are presented for the various flow periods that can occur during a transient test.
Effects on the buoyant density of rabbit platelets of ADP and agents that increase the concentration of cyclic AMP (1985)

Rabbit platelets were aggregated by adenosine diphosphate (ADP), allowed to deaggregate and then separated into density subpopulations by centrifugation through discontinuous Stractan density gradients. Although ADP causes little or no release of the contents of the amine storage granules of rabbit platelets, ADP caused a decrease in platelet density as compared with control platelets subjected to the same procedures except for exposure to ADP. The density change persisted for at least four hours. The apparent size of platelets stimulated with ADP increased initially, but returned to control values during a one-hour period. A similar decrease in platelet density was observed with an albumin density gradient. Under conditions in which aggregation did not occur in response to ADP with ethylenediaminetetraacetic acid (EDTA) in the medium, little or no decrease in platelet density was observed. Agglutination with polylysine did not change platelet density. Thus, not only agents such as thrombin and plasmin that cause the release of the contents of the platelet granules decrease platelet density, but ADP also has this effect. Platelets would be exposed to all of these stimuli during thromboembolic processes, and their effect on platelets may account for the decrease in platelet density observed previously in experiments with rabbits with indwelling aortic catheters. Agents that increase the concentration of cyclic AMP (cAMP) in platelets (PGE1, adenosine, dibutyryl cAMP, forskolin, and papaverine) also decreased platelet density. This effect persisted when the platelets were washed and resuspended in fresh medium and was also demonstrable in plasma. Platelet size was gradually increased by prostaglandin E1 (PGE1) which maintains platelets in a disc shape and does not cause the release of granule contents, indicating that the decrease in platelet density caused by PGE1 may be attributable to platelet swelling.