gebhart/patrepeval huggingface dataset:
PTK6 regulates growth and survival of endocrine therapy-resistant ER+ breast cancer cells (2017)

The non-receptor tyrosine kinase, PTK6/BRK, is highly expressed in multiple tumor types, including prostate, ovarian, and breast cancers, and regulates oncogenic phenotypes such as proliferation, migration, and survival. PTK6 inhibition also overcomes targeted therapy resistance of HER2+ breast cancer. Although PTK6 is highly expressed in ER+ Luminal breast cancers, the role of PTK6 in this subtype has not been elucidated. In this study, we investigated the functions of PTK6 in ER+ Luminal breast cancer cells, including those that are relatively resistant to estrogen deprivation or targeted endocrine therapies used in the treatment of ER+ cancers. Enhanced expression of PTK6 in ER+ breast cancer cells enhances growth of ER+ breast cancer cells, including tamoxifen-treated cells. Downregulation of PTK6 in ER+ breast cancer cells, including those resistant to tamoxifen, fulvestrant, and estrogen deprivation, induces apoptosis, as evidenced by increased levels of cleaved PARP, and an increase in the AnnexinV+ population. PTK6 downregulation impairs growth of these cells in 3D Matrigel<sup>TM</sup> cultures, and virtually abrogates primary tumor growth of both tamoxifen-sensitive and resistant MCF-7 xenografts. Finally, we show that p38 MAPK activation is critical for PTK6 downregulation-induced apoptosis, a mechanism that we previously reported for survival of HER2+ breast cancer cells, highlighting conserved mechanisms of survival regulation by PTK6 across breast cancer subtypes. In conclusion, our studies elucidate critical functions of PTK6 in ER+ Luminal breast cancers and support PTK6 as an attractive therapeutic target for ER+ breast cancers.
SARS-CoV-2: Possible Factors Contributing to Serious Consequences ofCOVID-19? (2021)

Background and Objectives: The recently discovered coronavirus, SARS-CoV-2 has infected over 170 million people (as of 31th May 2021) since it was elucidated in December 2019. The number of SARS-CoV-2 cases and mortality rates vary from country to country, and unfortunately, the United Kingdom ranks in the top 5 countries with the most deaths as of 31th May 2021. Methods: A literature review was conducted during May 2021 to examine if factors such as gut microbiome, ethnic diversity, high cancer rates, obesity and alcohol consumption may have contributed to the higher number of cases and mortality due to SARS-CoV-2 in the UK. Results: The western diet is associated with a less diverse gut microbiome, as well as obesity, and contributes to the severity of SARS-CoV-2 infection. Moreover, people belonging to Black and South Asian ethnic groups in the UK have an increased risk of death due to SARS-CoV-2 infection. Given the high number of cancer patients in the UK, as well as excess consumption of alcohol, higher mortality rates were observed, most likely due to people possessing a less diverse gut microbiome and/or weakened immune system. Conclusion: Targeting the gut microbiome in developing potential therapeutics against SARS-COV-2 is of value, and further studies are needed to understand the specific role of the gut microbiome.
DECIBEL: Improving Audio Chord Estimation for Popular Music by Alignment and Integration of Crowd-Sourced Symbolic Representations (2020)

Automatic Chord Estimation (ACE) is a fundamental task in Music Information Retrieval (MIR) and has applications in both music performance and MIR research. The task consists of segmenting a music recording or score and assigning a chord label to each segment. Although it has been a task in the annual benchmarking evaluation MIREX for over 10 years, ACE is not yet a solved problem, since performance has stagnated and modern systems have started to tune themselves to subjective training data. We propose DECIBEL, a new ACE system that exploits widely available MIDI and tab representations to improve ACE from audio only. From an audio file and a set of MIDI and tab files corresponding to the same popular music song, DECIBEL first estimates chord sequences. For audio, state-of-the-art audio ACE methods are used. MIDI files are aligned to the audio, followed by a MIDI chord estimation step. Tab files are transformed into untimed chord sequences and then aligned to the audio. Next, DECIBEL uses data fusion to integrate all estimated chord sequences into one final output sequence. DECIBEL improves all tested state-of-the-art ACE methods by over 3 percent on average. This result shows that the integration of musical knowledge from heterogeneous symbolic music representations is a suitable strategy for addressing challenging MIR tasks such as ACE.
Cost effective method for DFIG fault ride-through during symmetrical voltage dip (2010)

This paper presents a cost-effective scheme to improve the fault ride through capability of wind turbines with doubly fed induction generators. As an alternative to using crowbar, the proposed scheme includes the stator side series-connected braking resistors, dc-link chopper and coordinated control strategy of the whole system. The proposed scheme enable the rotor converter always be connected to the system such that the DFIG will not lose controllability during fault and can almost immediately generate reactive power to support the grid after the beginning of the fault. The series-connected braking resistors can help the transient decay very fast and, at the same time, dissipate the energy of the wind turbine to reduce the rotor speed deviation during fault. Dynamic behavior of DFIG-based wind turbines during grid faults is discussed based on theoretical analysis and simulation results. It is shown that the proposed scheme can not only help the whole system ride through the fault but also reduce the stress on turbine mechanical systems.
Further Morphologic Studies on Collagen Injected into Canine Vocal Folds (1991)

We compared the morphologic fate of three types of soluble bovine collagen injected into vocal folds of dogs: 1) Zyderm collagen implant containing 35 mg/mL of collagen (ZCI I), 2) Zyderm collagen implant containing 65 mg/mL of collagen (ZCI II), and 3) GAX collagen containing 35 mg/mL of collagen minimally cross-linked with 0.0075% glutaraldehyde. Light and electron microscopy showed good host tolerance and a long-term persistence of the three types of collagen at the site of injection. The collagen implants were progressively colonized by fibroblasts and capillaries accompanied by host collagen deposition. No inflammatory process or foreign body reaction occurred, in contrast to the typical host reaction to injected Teflon. The colonization of GAX collagen was slower than for ZCI I and ZCI II. No other significant difference was evident among the three types of injectable collagen. All three appear to be very suitable materials for laryngeal implants; moreover, they seem to best meet accepted requirements for a good implant: they are easy to inject, they are well tolerated, and they persist for a long time. We prefer GAX collagen for clinical use because of its lower reactivity and higher stability, and because overinjection is not necessary (GAX shrinks less than ZCI I and ZCI II).
Universal modular fluidic and electronic interfacing platform for microfluidic devices (2017)

A universal modular fluidic and electronic interfacing platform for microfluid devices has been designed, built and tested. The platform supports interfacing chips with up to 8 fluidic and 72 electrical connections. The current module set consists of a high frequency oscillator module, a charge amplifier module, a resonator actuator module and a weather station module. These modules can be used to characterize e.g. pressure sensors, density sensors and Coriolis mass flow sensors. For latter device, the platform with these modules performs approximately 2.5 times better in lower noise than the conventional setup. Besides, chip packaging is two to three times less labor intensive.
Blood-brain barrier genomics and the use of endogenous transporters to cause drug penetration into the brain. (2003)

Blood-brain barrier (BBB) genomics enables the rapid discovery of novel transporters that are expressed at the brain capillary endothelium. The BBB transporters are potential conduits to the brain that therapeutic drugs may use to gain passage across the BBB. Due to the small volume of brain occupied by the endothelium (10(-3) parts of the brain), it is necessary to build a BBB genomics program that is separate from a whole-brain genomics analysis. It is estimated that approximately 15% of all genes selectively expressed at the BBB encode for transporter proteins, and that only approximately 50% of BBB transporters are currently known. The development of a BBB genomics program and the discovery of novel BBB transporters could lead to the invention of new approaches to solving the BBB drug delivery problem.
MicroRNA-21 Promotes Fibrosis of the Kidney by Silencing Metabolic Pathways (2012)

Scarring of the kidney is a major public health concern, directly promoting loss of kidney function. To understand the role of microRNA (miRNA) in the progression of kidney scarring in response to injury, we investigated changes in miRNA expression in two kidney fibrosis models and identified 24 commonly up-regulated miRNAs. Among them, miR-21 was highly elevated in both animal models and in human transplanted kidneys with nephropathy. Deletion of miR-21 in mice resulted in no overt abnormality. However, miR-21(-/-) mice suffered far less interstitial fibrosis in response to kidney injury, a phenotype duplicated in wild-type mice treated with anti-miR-21 oligonucleotides. Global derepression of miR-21 target mRNAs was readily detectable in miR-21(-/-) kidneys after injury. Analysis of gene expression profiles up-regulated in the absence of miR-21 identified groups of genes involved in metabolic pathways, including the lipid metabolism pathway regulated by peroxisome proliferator-activated receptor-α (Pparα), a direct miR-21 target. Overexpression of Pparα prevented ureteral obstruction-induced injury and fibrosis. Pparα deficiency abrogated the antifibrotic effect of anti-miR-21 oligonucleotides. miR-21 also regulated the redox metabolic pathway. The mitochondrial inhibitor of reactive oxygen species generation Mpv17l was repressed by miR-21, correlating closely with enhanced oxidative kidney damage. These studies demonstrate that miR-21 contributes to fibrogenesis and epithelial injury in the kidney in two mouse models and is a candidate target for antifibrotic therapies.
Persistent, reliable, decentralised file system-DFS (2002)

This paper describes the architecture of a global, distributed, reliable data store. The system is based on a decentralised peer to peer network and uses cryptographic checksums to ensure validity and security and erasure codes to distribute fragments across the network to a set of peers whose attributes match the parameters specified by the user’s preferences.
Increased Numbers of Monocyte-Derived Dendritic Cells during Successful Tumor Immunotherapy with Immune-Activating Agents (2013)

Local treatment with selected TLR ligands or bacteria such as bacillus Calmette-Guérin increases antitumor immune responses and delays tumor growth. It is thought that these treatments may act by activating tumor-associated dendritic cells (DCs), thereby supporting the induction of antitumor immune responses. However, common parameters of successful immune activation have not been identified. We used mouse models to compare treatments with different immune-activating agents for the ability to delay tumor growth, improve priming of tumor-specific T cells, and induce early cytokine production and DC activation. Treatment with polyinosinic-polycytidylic acid or a combination of monosodium urate crystals and Mycobacterium smegmatis was effective at delaying the growth of s.c. B16 melanomas, orthotopic 4T1 mammary carcinomas, and reducing 4T1 lung metastases. In contrast, LPS, monosodium urate crystals, or M. smegmatis alone had no activity. Effective treatments required both NK1.1(+) and CD8(+) cells, and resulted in increased T cell priming and the infiltration of NK cells and CD8(+) T cells in tumors. Unexpectedly, both effective and ineffective treatments increased DC numbers and the expression of costimulatory molecules in the tumor-draining lymph node. However, only effective treatments induced the rapid appearance of a population of monocyte-derived DCs in the draining lymph node, early release of IL-12p70 and IFN-γ, and low IL-10 in the serum. These results suggest that the activation of existing DC subsets is not sufficient for the induction of antitumor immune responses, whereas early induction of Th1 cytokines and monocyte-derived DCs are features of successful activation of antitumor immunity.
Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1 (2016)

<b>Purpose:</b> While immune checkpoint inhibitors are disrupting the management of patients with cancer, anecdotal occurrences of rapid progression (i.e., hyperprogressive disease or HPD) under these agents have been described, suggesting potentially deleterious effects of these drugs. The prevalence, the natural history, and the predictive factors of HPD in patients with cancer treated by anti-PD-1/PD-L1 remain unknown.<b>Experimental Design:</b> Medical records from all patients (<i>N</i> = 218) prospectively treated in Gustave Roussy by anti-PD-1/PD-L1 within phase I clinical trials were analyzed. The tumor growth rate (TGR) prior ("REFERENCE"; REF) and upon ("EXPERIMENTAL"; EXP) anti-PD-1/PD-L1 therapy was compared to identify patients with accelerated tumor growth. Associations between TGR, clinicopathologic characteristics, and overall survival (OS) were computed.<b>Results:</b> HPD was defined as a RECIST progression at the first evaluation and as a ≥2-fold increase of the TGR between the REF and the EXP periods. Of 131 evaluable patients, 12 patients (9%) were considered as having HPD. HPD was not associated with higher tumor burden at baseline, nor with any specific tumor type. At progression, patients with HPD had a lower rate of new lesions than patients with disease progression without HPD (<i>P</i> < 0.05). HPD is associated with a higher age (<i>P</i> < 0.05) and a worse outcome (overall survival). Interestingly, REF TGR (before treatment) was inversely correlated with response to anti-PD-1/PD-L1 (<i>P</i> < 0.05) therapy.<b>Conclusions:</b> A novel aggressive pattern of hyperprogression exists in a fraction of patients treated with anti-PD-1/PD-L1. This observation raises some concerns about treating elderly patients (>65 years old) with anti-PD-1/PD-L1 monotherapy and suggests further study of this phenomenon. <i>Clin Cancer Res; 23(8); 1920-8. ©2016 AACR</i><i>See related commentary by Sharon, p. 1879</i>.
A Distributed Slack Bus Model and Its Impact on Distribution System Application Techniques (2005)

Distribution system operating environments are changing rapidly. For example, with the steady and significant increase in dispersed generation expected, planning and operating application techniques must also change. The paper re-evaluates the single slack bus assumption typically employed in steady-state distribution power flow solvers. Specifically, a distributed slack bus model, based on the concept of generator domains, is discussed and integrated into a power flow solver. Improved representation and allocation of distribution system losses to multiple generators is expected to impact other application techniques, such as capacitor placement, service restoration, etc. In addition, economic impacts of dispersed generation are significant and simulation results are presented to highlight this impact.
Discordant Outcomes following Failure of Antiretroviral Therapy Are Associated with Substantial Differences in Human Immunodeficiency Virus-Specific Cellular Immunity (2003)

Many individuals chronically infected with human immunodeficiency virus type 1 (HIV-1) experience a recrudescence of plasma virus during continuous combination antiretroviral therapy (ART) due either to the emergence of drug-resistant viruses or to poor compliance. In most cases, virologic failure on ART is associated with a coincident decline in CD4(+) T lymphocyte levels. However, a proportion of discordant individuals retain a stable or even increasing CD4(+) T lymphocyte count despite virological failure. In order to address the nature of these different outcomes, we evaluated virologic and immunologic variables in a prospective, single-blinded, nonrandomized cohort of 53 subjects with chronic HIV-1 infection who had been treated with continuous ART and monitored intensively over a period of 19 months. In all individuals with detectable viremia on ART, multiple drug resistance mutations with similar impacts on viral growth kinetics were detected in the pol gene of circulating plasma virus. Further, C2V3 env gene analysis demonstrated sequences indicative of CCR5 coreceptor usage in the majority of those with detectable plasma viremia. In contrast to this homogeneous virologic pattern, comprehensive screening with a range of antigens derived from HIV-1 revealed substantial immunologic differences. Discordant subjects with stable CD4(+) T lymphocyte counts in the presence of recrudescent virus demonstrated potent virus-specific CD4(+) and CD8(+) T lymphocyte responses. In contrast, subjects with virologic failure associated with declining CD4(+) T lymphocyte counts had substantially weaker HIV-specific CD4(+) T lymphocyte responses and exhibited a trend towards weaker HIV-specific CD8(+) T lymphocyte responses. Importantly the CD4(+) response was sustained over periods as long as 11 months, confirming the stability of the phenomenon. These correlative data lead to the testable hypothesis that the consequences of viral recrudescence during continuous ART are modulated by the HIV-specific cellular immune response.
In-depth Analysis of IS6110 Genomic Variability in the Mycobacterium tuberculosis Complex (2022)

The insertion sequence (IS) <i>6110</i> is a repetitive mobile element specific for the <i>Mycobacterium tuberculosis</i> complex (MTBC) used for years to diagnose and genotype this pathogen. It contains the overlapping reading frames <i>orfA</i> and <i>orfB</i> that encode a transposase. Its genetic variability is difficult to study because multiple copies are present in the genome. IS<i>6110</i> is randomly located, nevertheless some preferential locations have been reported, which could be related to the behaviour of the strains. The aim of this work was to determine the intra- and inter-strain genetic conservation of this element in the MTBC. For this purpose, we analysed 158 sequences of IS<i>6110</i> copies from 55 strains. Eighty-four copies were from 17 strains for which we knew all the locations in their genome. In addition, we studied 74 IS<i>6110</i> copies in 38 different MTBC strains in which the location was characteristic of different families including Haarlem, LAM, S, and L6 strains. We observed mutation in 13.3% of the copies studied and we found 10 IS<i>6110</i> variants in 21 copies belonging to 16 strains. The high copy number strains showed 6.2% of their IS<i>6110</i> copies mutated, in contrast with the 31.1% in the low-copy-number strains. The apparently more ancient copy localised in the DR region was that with more variant copies, probably because this was the most studied location. Notably, all Haarlem and X family strains studied have an IS<i>6110</i> in <i>Rv0403c</i>, suggesting a common origin for both families. Nevertheless, we detected a variant specific for the X family that would have occurred in this location after the phylogenetic separation. This variant does not prevent transposition although it may occur at a lower frequency, as X strains remain with low copy number (LCN) of IS<i>6110</i>.
Expression of nisin genes in cheese—A quantitative real-time polymerase chain reaction approach (2010)

The role of bacteriocins in different environments has not been thoroughly explained, mainly because of the difficulties related to the detection of their production. Nisin, an antimicrobial peptide produced by Lactococcus lactis has a long history of safe use in food products and has been studied from many aspects of genetics, biosynthesis, immunity, regulation, and mode of action. Still, some aspects concerning the dynamics of nisin gene expression remain unknown, especially in complex media like cheese. The main objective of the present study was to quantify in a cheese-like medium the expression of nisin genes in L. lactis M78, a well-characterized nisin A producer isolated from raw milk. The expression of all 11 genes involved in nisin biosynthesis was evaluated during cheese production by real-time reverse transcription-PCR. Total RNA was extracted from cheeses using a direct extraction method without prior separation of microbial cells. The M78 strain grew well in experimental cheeses, producing detectable amounts of nisin after 4 h of fermentation. The presence of nisin as an activator modified both the expression of nisin genes and the accumulation of active nisin. Four groups could be distinguished based on gene expression as a function of time: nisA, nisFEG, nisRK and nisBTCIP. Based on nisin-producing strain growth, nisin activity, function of nisin genes, and their location, correlations were established that contribute to the explanation of regulation of nisin biosynthesis and immunity. This study is the first in which the evolution of bacteriocin gene transcripts has been quantified rigorously in a cheese-like medium.
A diversity antenna for very small 800-MHz band portable telephones (1994)

A diversity antenna comprising a short whip antenna top loaded with a small cylinder and a new built-in antenna has been developed for very small portable telephones in the 800-MHz band. Wire-grid analyses and whip antenna experiments yielded good radiation characteristic results when the equivalent electrical length of the whip antenna equalled a half wavelength. The built-in antenna features extreme compactness, its size being one-third that of a conventional planar inverted-F antenna. The characteristics were investigated experimentally, and an antenna of 3.5 cc volume with a gain of -1 dBd and a bandwidth of 30 MHz was designed at 879 MHz. Finally, the diversity characteristics were subjected to field measurements and a diversity correlation of 0.26 was obtained.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Design by contract: the lessons of Ariane (1997)

Design by contract is the principle that the interfaces between modules of a software system-especially a mission-critical one-should be governed by precise specifications. The contracts cover mutual obligations (pre-conditions), benefits (post-conditions), and consistency constraints (invariants). Together, these properties are known as assertions, and are directly supported in some design and programming languages. A recent $500 million software error provides a sobering reminder that this principle is not just a pleasant academic ideal. On June 4, 1996, the maiden flight of the European Ariane 5 launcher crashed, about 40 seconds after takeoff. The rocket was uninsured. The French space agency, CNES (Centre National d'Etudes Spatiales), and the European Space Agency (ESA) immediately appointed an international inquiry board. The board makes several recommendations with respect to software process improvement. There is a simple lesson to be learned from this event: reuse without a precise, rigorous specification mechanism is a risk of potentially disastrous proportions. It is regrettable that this lesson has not been heeded by such recent designs as IDL, Ada 95 or Java. None of these languages has built-in support for design by contract. Effective reuse requires design by contract. Without a precise specification attached to each reusable component, no-one can trust a supposedly reusable component. Without a specification, it is probably safer to redo than to reuse.