gebhart/patrepeval huggingface dataset:
Genome-wide RNAi analysis reveals that simultaneous inhibition of specific mevalonate pathway genes potentiates tumor cell death (2015)

The mevalonate (MVA) pathway is often dysregulated or overexpressed in many cancers suggesting tumor dependency on this classic metabolic pathway. Statins, which target the rate-limiting enzyme of this pathway, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), are promising agents currently being evaluated in clinical trials for anti-cancer efficacy. To uncover novel targets that potentiate statin-induced apoptosis when knocked down, we carried out a pooled genome-wide short hairpin RNA (shRNA) screen. Genes of the MVA pathway were amongst the top-scoring targets, including sterol regulatory element binding transcription factor 2 (SREBP2), 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1 (HMGCS1) and geranylgeranyl diphosphate synthase 1 (GGPS1). Each gene was independently validated and shown to significantly sensitize A549 cells to statin-induced apoptosis when knocked down. SREBP2 knockdown in lung and breast cancer cells completely abrogated the fluvastatin-induced upregulation of sterol-responsive genes HMGCR and HMGCS1. Knockdown of SREBP2 alone did not affect three-dimensional growth of lung and breast cancer cells, yet in combination with fluvastatin cell growth was disrupted. Taken together, these results show that directly targeting multiple levels of the MVA pathway, including blocking the sterol-feedback loop initiated by statin treatment, is an effective and targetable anti-tumor strategy.
Land-cover change in the Tatra Mountains, with a particular focus on vegetation (2020)

This paper evaluates land-cover change in the high mountain landscapes of parts of the Tatra Mountains (Western Carpathians, Europe). As well as carrying out a basic analysis of land-cover changes, we compared how these changes related to several abiotic variables and socio-economic influences. We used a geographic information system to analyse aerial images from surveys made in 1955, 1986 and 2010. The areas studied have undergone a number of changes, due most importantly to the establishment of a national park, long-term forestry management, natural disturbances, land abandonment, and the development of tourism. With regard to changes in vegetation cover, it is debatable whether these are related to climate change or to land-use change. Our study revealed two main changes: coniferous forest disturbance, and the expansion of shrubs (Pinus mugo) into the alpine zone. We also observed a slight upward shift of vegetation boundaries for coniferous forest, shrubs and alpine meadows over a period of more than 50 years (1956 to 2010). If we take into consideration (1) that forest ecosystems (and the tree line) have been changed significantly by human influence, and (2) that windstorms provoking outbreaks of spruce bark beetle are not a new phenomenon but more or less periodical in the Tatra Mountains, our results cannot provide clear evidence that climate change is partly responsible for the shift to higher elevations of the boundaries of mountain vegetation.
Algorithmic transformation techniques for efficient exploration of alternative application instances (2002)

Following the Y-chart paradigm for designing a system, an application and an architecture are modeled separately and mapped onto each other in an explicit design step. Next, a performance analysis for alternative application instances, architecture instances and mappings has to be done, thereby exploring the design space of the target system. Deriving alternative application instances is not trivially done. Nevertheless, many instances of a single application exist that are worth to be derived for exploration. In this paper, we present algorithmic transformation techniques for systematic and fast generation of alternative application instances that express task-level concurrency hidden in an application in some degree of explicitness. These techniques help a system designer to speedup significantly the design space exploration process.
Implementation of national whole-genome sequencing of Mycobacterium tuberculosis, National Public Health Laboratory, Singapore, 2019—2022 (2023)

The National Tuberculosis Programme (NTBP) monitors the occurrence and spread of tuberculosis (TB) and multidrug-resistant TB (MDR-TB) in Singapore. Since 2020, whole-genome sequencing (WGS) of <i>Mycobacterium tuberculosis</i> isolates has been performed at the National Public Health Laboratory (NPHL) for genomic surveillance, replacing spoligotyping and mycobacterial interspersed repetitive unit-variable number tandem repeats analysis (MIRU-VNTR). Four thousand three hundred and seven samples were sequenced from 2014 to January 2023, initially as research projects and later developed into a comprehensive public health surveillance programme. Currently, all newly diagnosed culture-positive cases of TB in Singapore are prospectively sent for WGS, which is used to perform lineage classification, predict drug resistance profiles and infer genetic relationships between TB isolates. This paper describes NPHL's operational and technical experiences with implementing the WGS service in an urban TB-endemic setting, focusing on cluster detection and genomic drug susceptibility testing (DST). Cluster detection: WGS has been used to guide contact tracing by detecting clusters and discovering unknown transmission networks. Examples have been clusters in a daycare centre, housing apartment blocks and a horse-racing betting centre. Genomic DST: genomic DST prediction (gDST) identifies mutations in core genes known to be associated with TB drug resistance catalogued in the TBProfiler drug resistance mutation database. Mutations are reported with confidence scores according to a standardized approach referencing NPHL's internal gDST confidence database, which is adapted from the World Health Organization (WHO) TB drug mutation catalogue. Phenotypic-genomic concordance was observed for the first-line drugs ranging from 2959/2998 (98.7 %) (ethambutol) to 2983/2996 (99.6 %) (rifampicin). Aspects of internal database management, reporting standards and caveats in results interpretation are discussed.
A dramatic concentration effect on the stereoselectivity of N-glycosylation for the synthesis of 2′-deoxy-β-ribonucleosides (2012)

A dramatic concentration effect on the stereoselectivity of N-glycosylation, which is attributable to a low-concentration-facilitated remote-participation, has been disclosed, leading to convenient synthesis of the 2'-deoxy-β-ribonucleosides of biological significance.
High Dose Chemotherapy and Transplantation of Hematopoietic Progenitors from Murine D3 Embryonic Stem Cells (2005)

Differentiating embryonic stem (ES) cells are an increasingly important source of hematopoietic progenitors, useful for both basic research and clinical applications. To date, characteristics of specific factors capable of influencing hematopoietic cell fate from ES cells remains elusive. We report that mMSC Feeder Layer and the combination of VEGF, SCF and TPO strongly promote hematopoietic differentiation. The results showed that the cells induced from ES-D3 expressed hematopoietic progenitor antigens (CD34 and CD117), myelocyte cell antigen (CD11b), erythrocyte cell antigen (Ter119), and transcription factors (Flk-1, GATA-2, SCL, beta-H1 and beta-major). Furthermore, those induced differentiated cells were injected into female C57BL/6 mice which were treated with high dose topotecan chemotherapy to restore part of their blood system function. We observed rapid white blood cell recovery, which suggested that the infusion of differentiated cells has a positive impact on hematopoiesis. The Sry gene in peripheral blood, bone marrow and spleen of transplanted female mice was confirmed by PCR analysis, which affirmed the existence of the chimera.
Development and validation of a cellular host response test as an early diagnostic for sepsis (2021)

Sepsis must be diagnosed quickly to avoid morbidity and mortality. However, the clinical manifestations of sepsis are highly variable and emergency department (ED) clinicians often must make rapid, impactful decisions before laboratory results are known. We previously developed a technique that allows the measurement of the biophysical properties of white blood cells as they are stretched through a microfluidic channel. In this study we describe and validate the resultant output as a model and score-the IntelliSep Index (ISI)-that aids in the diagnosis of sepsis in patients with suspected or confirmed infection from a single blood draw performed at the time of ED presentation. By applying this technique to a high acuity cohort with a 23.5% sepsis incidence (n = 307), we defined specific metrics-the aspect ratio and visco-elastic inertial response-that are more sensitive than cell size or cell count in predicting disease severity. The final model was trained and cross-validated on the high acuity cohort, and the performance and generalizability of the model was evaluated on a separate low acuity cohort with a 6.4% sepsis incidence (n = 94) and healthy donors (n = 72). For easier clinical interpretation, the ISI is divided into three interpretation bands of Green, Yellow, and Red that correspond to increasing disease severity. The ISI agreed with the diagnosis established by retrospective physician adjudication, and accurately identified subjects with severe illness as measured by SOFA, APACHE-II, hospital-free days, and intensive care unit admission. Measured using routinely collected blood samples, with a short run-time and no requirement for patient or laboratory information, the ISI is well suited to aid ED clinicians in rapidly diagnosing sepsis.
Maladies vectorielles à tiques et modifications de l'écosystème en Lorraine. (2002)

Le nombre de victimes de maladies vectorielles a tiques s'est particulierement accru en Lorraine depuis le milieu des annees 90. A elle seule, une meilleure connaissance de ces pathologies ne suffit pas a expliquer l'augmentation d'incidence. La proliferation des tiques represente un facteur preponderant dans l'emergence de ces pathologies, elle est la consequence d'une modification de l'ecosysteme. La prophylaxie reposant essentiellement sur l'information, elle suppose une bonne comprehension de la biologie et de l'habitat des tiques vectrices. Les particularites geographiques de la region pourraient representer un facteur d'emergence supplementaire.
Exact and explicit solution algorithm for linear programming problem with a second-order cone (2011)

This paper proposes a exact solution algorithm to explicitly obtain the exact optimal solution of a secondorder cone programming problem with box constraints of decision variables. The proposed solution algorithm is based on a parametric solution approach to determine the optimal strict region of parameters, and the main procedures are to perform deterministic equivalent transformations for the main problem and to solve the KKT condition of auxiliary problem without the loss of optimality.
Antigen receptors and somatic hypermutation in B-cell chronic lymphocytic leukemia with Richter's transformation. (2006)

The combined findings suggest a role for the Ig gene diversification apparatus during Richter's transformation and show that distinct RS-B-CLL may recognize recurrent antigenic epitopes.
Zinc and Liver Disease (2012)

Zinc is an essential trace element required for normal cell growth, development, and differentiation. It is involved in DNA synthesis, RNA transcription, and cell division and activation. It is a critical component in many zinc protein/enzymes, including critical zinc transcription factors. Zinc deficiency/altered metabolism is observed in many types of liver disease, including alcoholic liver disease (ALD) and viral liver disease. Some of the mechanisms for zinc deficiency/altered metabolism include decreased dietary intake, increased urinary excretion, activation of certain zinc transporters, and induction of hepatic metallothionein. Zinc deficiency may manifest itself in many ways in liver disease, including skin lesions, poor wound healing/liver regeneration, altered mental status, or altered immune function. Zinc supplementation has been documented to block/attenuate experimental ALD through multiple processes, including stabilization of gut-barrier function, decreasing endotoxemia, decreasing proinflammatory cytokine production, decreasing oxidative stress, and attenuating apoptotic hepatocyte death. Clinical trials in human liver disease are limited in size and quality, but it is clear that zinc supplementation reverses clinical signs of zinc deficiency in patients with liver disease. Some studies suggest improvement in liver function in both ALD and hepatitis C following zinc supplementation, and 1 study suggested improved fibrosis markers in hepatitis C patients. The dose of zinc used for treatment of liver disease is usually 50 mg of elemental zinc taken with a meal to decrease the potential side effect of nausea.
Tank bottom leak detection using AE: on the mechanism of the occurrence of AE bursts due to leakage (1998)

During leak and bubble tests on a test tank, AE bursts are frequently detected along with the pressure change due to the unsteady flow close to the hole. A model, based on a postulated unsteady state and concentrating on the relationship between the flow and the velocity gradient, is presented to explain the occurrence of AE burst, It is suggested that only the stream that is crossing the steep velocity gradient near the hole edge will produce strong AE bursts. An unsteady flow is considered favourable for such stream to occur, therefore producing more AE bursts.
Evidence for type 2 cytokine production and lymphocyte activation in the early phases of HIV-1 infection (1996)

The early phase of HIV infection is immunologically characterized by type 2 cytokine secretion and alterations in the expression of phenotypic markers, and closely resembles the more advanced phases of HIV infection. These immunologic alterations are temporally limited by the successive return to a more normal profile. Thus, HIV infection is an immunological complex dynamic process even in its earliest phases.
A Closed Concept for Synchronization and Cell Search in 3GPP LTE Systems (2009)

In this paper we investigate the time and frequency synchronization as well as the sector and cell search for the 3GPP long term evolution (LTE) downlink. The proposed algorithms rely on the synchronization and cell-specific reference signals and are hence compliant to most recent 3GPP specifications. Time and (fractional) frequency offset coarse synchronization are performed in the time domain with the cyclic prefix based autocorrelation, while the sector and cell as well as the integer frequency offset are estimated in the frequency domain by using the primary and secondary synchronization signals. To improve the cell detection reliability, the estimated cell is afterwards confirmed through the cell-specific reference signal. All algorithms are evaluated under multipath channel conditions and an initial carrier frequency mismatch. Compromising high performance with reasonable implementation complexity, we draw a practical solution for an LTE receiver.
A Fair Consensus Protocol for Transaction Ordering (2018)

We present Helix, a blockchain-based consensus protocol for fair ordering of transactions among nodes in a distributed network. Helix advances in rounds, where in each round, the primary node (elected among the network nodes) proposes a potential block (a successive set of transactions). In order to be included in the blockchain, a block must pass validation by an elected committee of nodes. Helix nodes are presumed to have two primary preferences. They prefer to be elected as committee members. Additionally, because each transaction is associated with one of the network nodes, they prefer to prioritize their own transactions over those of others. In light of these individual preferences, our definition of fairness incorporates three key elements. First, the process of electing nodes to committees is random and unpredictable. Second, a correlated sampling scheme is used in order to guarantee random selection and ordering of pending transactions in blocks. Third, transactions are encrypted in order to hide their associations with their respective nodes and prevent censorship. Through the corresponding threshold decryption process we obtain an unpredictable and non-manipulable randomness beacon, which serves both the election process and the correlated sampling scheme. We define a quantitative measure of fairness in the protocol, prove theoretically that fairness manipulation in Helix is significantly limited, and present experiments evaluating fairness in practice.
History of Spinal Fusion: Where we Came from and Where we are Going (2020)

Spinal fusion surgery is performed all over the world to help patients with cervical and thoracolumbar pathology. As outcomes continue to improve in patients with spine-related pathology, it is important to understand how we got to modern day spinal fusion surgery. Scientific innovations have ranged from the first spinal fusions performed with basic instrumentation in the late nineteenth century to contemporary tools such as pedicle screws, bone grafts, and interbody devices. This article tracks this technological growth so that surgeons may better serve their patients in treating spine-related pain and disability.
Electrochemical evidence of H• produced by ultrasound (2001)

Electrochemical evidence of H˙ produced by cavitation as the result of ultrasonic irradiation of an aqueous solution is presented.
Massively parallel digital transcriptional profiling of single cells (2016)

ABSTRACT Characterizing the transcriptome of individual cells is fundamental to understanding complex biological systems. We describe a droplet-based system that enables 3′ mRNA counting of up to tens of thousands of single cells per sample. Cell encapsulation in droplets takes place in ∼6 minutes, with ∼50% cell capture efficiency, up to 8 samples at a time. The speed and efficiency allow the processing of precious samples while minimizing stress to cells. To demonstrate the system′s technical performance and its applications, we collected transcriptome data from ∼¼ million single cells across 29 samples. First, we validate the sensitivity of the system and its ability to detect rare populations using cell lines and synthetic RNAs. Then, we profile 68k peripheral blood mononuclear cells (PBMCs) to demonstrate the system′s ability to characterize large immune populations. Finally, we use sequence variation in the transcriptome data to determine host and donor chimerism at single cell resolution in bone marrow mononuclear cells (BMMCs) of transplant patients. This analysis enables characterization of the complex interplay between donor and host cells and monitoring of treatment response. This high-throughput system is robust and enables characterization of diverse biological systems with single cell mRNA analysis.
Method to minimize the low-frequency neutral-point voltage oscillations with time-offset injection for neutral-point-clamped inverters (2013)

This paper proposes a method to reduce the low-frequency neutral-point voltage oscillations. The neutral-point voltage oscillations are considerably reduced by adding a time-offset to the three phase turn-on times. The proper time-offset is simply calculated considering the phase currents and dwell time of small and medium voltage vectors. The proposed method does not affect the outputs and there is no increase in the switching frequency. Further, it does not require additional hardware or complex calculations. Simulation and experimental results verify the validity and feasibility of the proposed strategy.
CECAL LIGATION AND PUNCTURE VERSUS COLON ASCENDENS STENT PERITONITIS: TWO DISTINCT ANIMAL MODELS FOR POLYMICROBIAL SEPSIS (2004)

Colon ascendens stent peritonitis (CASP) and cecal ligation and puncture (CLP), two animal models designed to closely mimic the clinical course of intra-abdominal sepsis, were compared. In the past, immunomodulatory therapies developed in animal studies failed to be successful in humans. As a consequence, the established animal sepsis models were criticized. It has been proposed that present models had to be reevaluated, and new, clinically more relevant models should be evolved. CLP procedure was performed puncturing once (CLP[1]) or twice (CLP[2]) the ligated cecum of C57BL/6 mice. In the CASP model, a stent with defined diameter was surgically inserted into the ascending colon. Survival, bacterial load, immunohistochemistry, and serum cytokine levels were analyzed in the groups. Survival after CASP procedure correlated strongly with the stent diameter, whereas the number of punctures in CLP did not significantly change survival rate. Bacterial loads of peritoneal lavage, liver, and lung, as well as serum cytokine levels (tumor necrosis factor, interleukin 1 beta, interleukin 10) steadily increased from 6 to 24 h after the CASP procedure. In contrast, continuously low amounts of bacteria and cytokines were found in CLP mice at any point of time. Twenty-four hours after CLP surgery, the ligated cecum was covered by adhesive small bowel loops, whereas in CASP mice, the intestinal leakage was then still present. The CASP model mimics closely the clinical course of diffuse peritonitis with early and steadily increasing systemic infection and inflammation (systemic inflammatory response syndrome). In contrast, CLP reveals a model of intra-abdominal abscess formation with sustained and minor signs of systemic inflammation.
Long-Term Performance of Hemofilters in Continuous Hemofiltration (1996)

We measured the filter performance of six polyamide hemofilters with a running time exceeding 72 h applied for continuous hemofiltration in intensive care patients. The sieving coefficients for urea and creatinine were close to unity and remained constant. The sieving coefficient of polyfructosan (mean molecular weight 3 kD) was around 0.75 and did not change with running time. The hydraulic permeability remained also unchanged. The relationships between blood pressure and blood flow and between blood flow and filtration rate remained linear, and the gradient did not change with time. We conclude that a daily routine change of polyamide hemofilters applied in continuous arteriovenous hemofiltration and presumably in continuous venovenous hemofiltration is not necessary within the first 72 h of treatment, unless a major decrease in the filtration rate occurs.
Guerra del Pacífico entre Perú, Bolivia y Chile. El viaje de Prado (Diciembre 1879) y la falsificación de misivas. (2012)

During the Pacific War between Bolivia, Chile and Peru (1879-1883), the journey of the Peruvian President Mariano Ignacio Prado en December of 1879 at this event had led to a series of false documents and false interpretations to try to justify the trip.