gebhart/patrepeval huggingface dataset:
Effects of afterload on regional left ventricular torsion (1996)

Maximal regional torsion of the left ventricle is afterload dependent. The afterload response of torsion appears related to the effects of afterload on end-systolic volume.
The Role of Adenosine A2AReceptor, CYP450s, and PPARs in the Regulation of Vascular Tone (2017)

Adenosine is an endogenous mediator involved in a myriad of physiologic functions, including vascular tone regulation. It is also implicated in some pathologic conditions. Four distinct receptor subtypes mediate the effects of adenosine, such as its role in the regulation of the vascular tone. Vascular tone regulation is a complex and continuous process which involves many mechanisms and mediators that are not fully disclosed. The vascular endothelium plays a pivotal role in regulating blood flow to and from all body organs. Also, the vascular endothelium is not merely a physical barrier; it is a complex tissue with numerous functions. Among adenosine receptors, A<sub>2A</sub> receptor subtype (A<sub>2A</sub>AR) stands out as the primary receptor responsible for the vasodilatory effects of adenosine. This review focuses on important effectors of the vascular endothelium, including adenosine, adenosine receptors, EETs (epoxyeicosatrienoic acids), HETEs (hydroxyeicosatetraenoic acids), PPARs (peroxisome proliferator-activated receptors), and K<sub>ATP</sub> channels. Given the impact of vascular tone regulation in cardiovascular physiology and pathophysiology, better understanding of the mechanisms affecting it could have a significant potential for developing therapeutic agents for cardiovascular diseases.
Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond (2016)

A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemistry programs. The data for all of these assays are presented and analyzed to show how outstanding leads for many indications can be selected. These results reveal the immense potential for translating the dispersed expertise in biological assays involving human pathogens into drug discovery starting points, by providing open access to new families of molecules, and emphasize how a small additional investment made to help acquire and distribute compounds, and sharing the data, can catalyze drug discovery for dozens of different indications. Another lesson is that when multiple screens from different groups are run on the same library, results can be integrated quickly to select the most valuable starting points for subsequent medicinal chemistry efforts.
Optimum Battery Size for Fuel Cell Hybrid Electric Vehicle— Part I (2006)

This study explores different hybridization levels of a midsized vehicle powered by a polymer electrolyte membrane fuel cell stack. The energy buffer considered is a lead-acid-type battery. The effects of the battery size on the overall energy losses for different drive cycles are determined when dynamic programming determines the optimal current drawn from the fuel cell system. The different hybridization levels are explored for two cases: (i) when the battery is only used to decouple the fuel cell system from the voltage and current demands from the traction motor to allow the fuel cell system to operate as close to optimally as possible and (ii) when regenerative braking is included in the vehicle with different efficiencies. The optimal power-split policies are analyzed to quantify all the energy losses and their paths in an effort to clarify the hybridization needs for a fuel cell vehicle. Results show that without any regenerative braking, hybridization will not decrease fuel consumption unless the vehicle is driving in a mild drive cycle (city drive with low speeds). However, when the efficiency of the regenerative braking increases, the fuel consumption (total energy losses) can be significantly lowered by choosing an optimal battery size.
Levels of Proinflammatory Cytokines, Oxidative Stress, and Tissue Damage Markers in Patients with Acute Heart Failure with and without Cardiorenal Syndrome Type 1 (2018)

Patients affected by CRS type 1 present increased levels of proinflammatory cytokines and oxidative stress markers, increased levels of tissue damage markers, and lower hemoglobin levels. All these factors may be implicated in the pathophysiology of CRS type 1 syndrome.
ChemInform Abstract: Synthesis of Glycosides of α‐D‐Mannopyranose 6‐(α‐D‐Glucopyranosyl Phosphate). (1986)

Abstract Die Kondensation des aus (Ia) dargestellten Benzoats (Ib) mit den Glykosylphosphaten (II) führt zu den Glykosiden (III), deren alkalische Deblockierung die gewünschten‐Phosphorsäurediester (IV) liefert.
ChemInform Abstract: INNERORBITALE PHOTOELEKTRONENSPEKTROSKOPIE AEHNLICHER PHOSPHORVERBINDUNGS‐PAARE (1972)

Abstract Der Einfluß von Diastereoisomerie und Substituenten auf die Bindungsenergien in den cyclischen Strukturen der diastereomeren Verbindungen (I) und (II) und der Phosphornitride (III) wird anhand der mittels innerorbitaler Photoelektronenspektroskopie ermittelten Daten diskutiert.
A 16-element phased-array receiver IC for 60-GHz communications in SiGe BiCMOS (2010)

A 0.12-μm SiGe phased-array Rx IC for beam-steered wireless communication in the 60-GHz band is described. It has 16 RF phase-shifting front-ends with 11° digital phase resolution and hybrid passive-active RF signal combining. It achieves 7.4-7.9 dB NF (not including 12-dB array gain) over the 4 IEEE channels. The IC has a double-conversion superheterodyne Rx core with a maximum of 72 dB of power gain in 1-dB steps, and the on-chip synthesizer achieves <; -90 dBc/Hz Rx phase noise at 1MHz offset. The IC draws 1.8 W at 2.7 V with a die area of 38 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . It has been packaged with 16 antennas in a 288-pin organic BGA and phased-array beamsteering has been demonstrated, along with 5+ Gb/s wireless links using 16-QAM OFDM.
A Dual Inhibitor of DYRK1A and GSK3β for β‐Cell Proliferation: Aminopyrazine Derivative GNF4877 (2020)

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.
WHO consultation on group B Streptococcus vaccine development: Report from a meeting held on 27–28 April 2016 (2016)

Globally, group B Streptococcus (GBS) remains a leading cause of sepsis and meningitis in infants in the first 90days of life. Intrapartum antibiotic prophylaxis (IAP) for women at increased risk of transmitting GBS to their newborns has been effective in reducing part, but not all, of the GBS disease burden in many high income countries (HICs). In low- and middle-income countries (LMICs), IAP use is low. Immunization of pregnant women with a GBS vaccine represents an alternative strategy to protecting newborns and young infants, through transplacental antibody transfer and potentially by reducing new vaginal colonization. This vaccination strategy was first suggested in the 1970s and several potential GBS vaccines have completed phase I/II clinical trials. During the 2015 WHO Product Development for Vaccines Advisory Committee meeting, GBS was identified as a high priority for the development of a vaccine for maternal immunization because of the major public health burden posed by GBS in LMICs, and the high technical feasibility for successful development. Following this meeting, the first WHO technical consultation on GBS vaccines was held on the 27th and 28th of April 2016, to consider development pathways for such vaccines, focused on their potential role in reducing newborn and young infant deaths and possibly stillbirths in LMICs. Discussion topics included: (1) pathophysiology of disease; (2) current gaps in the knowledge of global disease burden and serotype distribution; (3) vaccine candidates under development; (4) design considerations for phase III trials; and (5) pathways to licensure, policy recommendations and use. Efforts to address gaps identified in each of these areas are needed to establish the public health need for, the development and deployment of, efficacious GBS vaccines. In particular, more work is required to understand the global disease burden of GBS-associated stillbirths, and to develop quality-assured standardized antibody assays to identify correlates of protection.
Activation of GPR4 by Acidosis Increases Endothelial Cell Adhesion through the cAMP/Epac Pathway (2020)

Endothelium-leukocyte interaction is critical for inflammatory responses. Whereas the tissue microenvironments are often acidic at inflammatory sites, the mechanisms by which cells respond to acidosis are not well understood. Using molecular, cellular and biochemical approaches, we demonstrate that activation of GPR4, a proton-sensing G protein-coupled receptor, by isocapnic acidosis increases the adhesiveness of human umbilical vein endothelial cells (HUVECs) that express GPR4 endogenously. Acidosis in combination with GPR4 overexpression further augments HUVEC adhesion with U937 monocytes. In contrast, overexpression of a G protein signaling-defective DRY motif mutant (R115A) of GPR4 does not elicit any increase of HUVEC adhesion, indicating the requirement of G protein signaling. Downregulation of GPR4 expression by RNA interference reduces the acidosis-induced HUVEC adhesion. To delineate downstream pathways, we show that inhibition of adenylate cyclase by inhibitors, 2′,5′-dideoxyadenosine (DDA) or SQ 22536, attenuates acidosis/GPR4-induced HUVEC adhesion. Consistently, treatment with a cAMP analog or a Gi signaling inhibitor increases HUVEC adhesiveness, suggesting a role of the Gs/cAMP signaling in this process. We further show that the cAMP downstream effector Epac is important for acidosis/GPR4-induced cell adhesion. Moreover, activation of GPR4 by acidosis increases the expression of vascular adhesion molecules E-selectin, VCAM-1 and ICAM-1, which are functionally involved in acidosis/GPR4-mediated HUVEC adhesion. Similarly, hypercapnic acidosis can also activate GPR4 to stimulate HUVEC adhesion molecule expression and adhesiveness. These results suggest that acidosis/GPR4 signaling regulates endothelial cell adhesion mainly through the Gs/cAMP/Epac pathway and may play a role in the inflammatory response of vascular endothelial cells.
Design and Analysis of MIMO Spatial Multiplexing Systems With Quantized Feedback (2006)

This paper investigates the problem of transmit beamforming in multiple-antenna spatial multiplexing (SM) systems employing a finite-rate feedback channel. Assuming a fixed number of spatial channels and equal power allocation, we propose a new criterion for designing the codebook of beamforming matrices that is based on minimizing an approximation to the capacity loss resulting from the limited rate in the feedback channel. Using the criterion, we develop an iterative design algorithm that converges to a locally optimum codebook. Under the independent identically distributed channel and high signal-to-noise ratio (SNR) assumption, the effect on channel capacity of the finite-bit representation of the beamforming matrix is analyzed. Central to this analysis is the complex multivariate beta distribution and tractable approximations to the Voronoi regions associated with the code points. Furthermore, to compensate for the degradation due to the equal power allocation assumption, we propose a multimode SM transmission strategy wherein the number of data streams is determined based on the average SNR. This approach is shown to allow for effective utilization of the feedback bits resulting in a practical and efficient multiple-input multiple-output system design
Listeners lengthen phrase boundaries in self-paced music. (2016)

Previous work has shown that musicians tend to slow down as they approach phrase boundaries (<i>phrase-final lengthening</i>). In the present experiments, we used a paradigm from the action perception literature, the dwell time paradigm (Hard, Recchia, & Tversky, 2011), to investigate whether participants engage in phrase boundary lengthening when self-pacing through musical sequences. When participants used a key press to produce each successive chord of Bach chorales, they dwelled longer on boundary chords than nonboundary chords in both the original chorales and atonal manipulations of the chorales. When a novel musical sequence was composed that controlled for metrical and melodic contour cues to boundaries, the dwell time difference between boundaries and nonboundaries was greater in the tonal condition than in the atonal condition. Furthermore, similar results were found for a group of nonmusicians, suggesting that phrase-final lengthening in musical production is not dependent on musical training and can be evoked by harmonic cues.
Analysis of envelope signal injection for improvement of RF amplifier intermodulation distortion (2004)

Adaptive bias techniques based on envelope signal power detection have been proposed for linearity enhancement and DC current reduction in RF amplifiers. Experimental results show an improvement in amplifier linearity, although asymmetric intermodulation distortion (IMD) was observed. This paper studies the effects of the magnitude and phase of the envelope signal injection on amplifier linearity, and illustrates a technique in which the IMD can be optimally cancelled.
Machine learning with validation to detect diabetic microvascular complications using clinical and metabolomics data (2022)

ABSTRACT AIMS Using machine learning integrated with clinical and metabolomic data to identify biomarkers associated with diabetic kidney disease (DKD) and diabetic retinopathy (DR), and to improve the performance of DKD/DR detection models beyond traditional risk factors. METHODS We examined a population-based cross-sectional sample of 2,772 adults with type 1 or type 2 diabetes from Singapore Epidemiology of Eye Diseases study (SEED, 2004-2011). LASSO logistic regression (LASSO) and gradient boosting decision tree (GBDT) were used to select markers of prevalent DKD (defined as an eGFR &lt; 60ml/min/1.73m2) and prevalent DR (defined as an ETDRS severity level ≥ 20) from an expanded set of 19 established risk factors and 220 NMR-quantified circulating metabolites. Risk assessment models were developed based on the variable selection results and externally validated in UK Biobank (n=5,843, 2007-2010). Model performance (AUC with 95% CI, sensitivity, and specificity) of machine learning was compared to that of traditional logistic regression adjusted for age, gender, diabetes duration, HbA 1c %, systolic BP, and BMI. RESULTS SEED participants had a median age of 61.7 years, with 49.1% female, 20.2% having DKD, and 25.4% having DR. UK Biobank participants had a median age of 61.0 years, with 39.2% female, 6.4% having DKD, and 5.7% having DR. Both algorithms identified diabetes duration, insulin usage, age, and tyrosine as the most important factors of both DKD and DR. DKD was additionally associated with CVD, hypertension medication, and three metabolites (lactate, citrate, and cholesterol esters to total lipids ratio in intermediate-density-lipoprotein); While DR was additionally associated with HbA 1c , blood glucose, pulse pressure, and alanine. Machine-learned models for DKD and DR detection outperformed traditional logistic regression in both internal (AUC: 0.832-0.838 vs. 0.743 for DKD, and 0.779-0.790 vs. 0.764 for DR) and external validation (AUC: 0.737-0.790 vs. 0.692 for DKD, and 0.778 vs. 0.760 for DR). CONCLUSIONS Machine-learned biomarkers suggested insulin resistance to be a primary factor associated with diabetic microvascular complications. Integrating machine learning with biomedical big data enabled biomarker discovery from a wide range of correlated variables, which may facilitate our understanding of the disease mechanisms and improve disease screening.
Propagation Issues for Cognitive Radio (2009)

Cognitive radios are expected to work in bands below about 3.5 GHz and may be used for a variety of applications, e.g., broadband fixed wireless access, mobile and nomadic access, etc. Cognitive radio system designers must have access to a wide range of channel models covering a wide span of operating frequencies, carrier bandwidths, deployment conditions, and environments. This paper provides a comprehensive overview of the propagation channel models that will be used for the design of cognitive radio systems. We start with classical models for signal loss versus distance and discuss their dependence on the physical properties of the environment and operating frequency. Here we also introduce the concept of log-normal shadowing resulting from signal blockage by man-made and natural features. Next, we discuss the time-varying nature of the wireless channel, introduced as a result of the motion of objects in the channel. This is followed by a discussion on the dispersion of the signal caused by various effects of propagation, especially in the time and frequency domains. Angular dispersion, which is discussed next, is important because cognitive radios may be based on modems that exploit the spatial domain. Lastly, we summarize channel models that have been standardized for fixed and mobile systems.
Simultaneous All-optical Wavelength Switching using a Nonlinear Loop Mirror (1999)

High performance optical communication and signal processing systems have been demonstrated employing architectures based on wavelength division multiplexed (WDM) formats or optical time division (OTDM) formats.
Supplementary Figure 2 from Reactivation of Suppressed RhoB is a Critical Step for the Inhibition of Anaplastic Thyroid Cancer Growth (2023)

Supplementary Figure 2 from Reactivation of Suppressed RhoB is a Critical Step for the Inhibition of Anaplastic Thyroid Cancer Growth
The prognostic impact of serum albumin in double hit/double expressing aggressive B cell lymphomas: A pilot study evaluating SAAB scoring system. (2016)

e19044 Background: Double hit lymphomas (DHL) [rearrangements of MYC and BCL2/BCL6, and double expressing lymphomas (DEL) [expression of MYC and BCL6/BCL2 by immunohistochemistry] represent a subset of diffuse large B-cell lymphoma (DLBCL) with poor overall survival (OS). Several prognostic scores have been tested to clinically stratify these patients with the double hit score (DHS) being the most recently developed model (Petrich 2014). We explored the use of serum albumin (SA) as prognostic factor in DHL as previously shown in DLBCL (Dalia 2013). Methods: We included 100 patients from Moffitt Cancer Center database from January 2008 to December 2015 with DHL and performed a retrospective chart review. Recorded clinical data included SA, hemoglobin, age, International Prognostic Index (IPI), DHS, and lymphopenia. Pairwise Cox Comparison was used to develop a weighted scoring system. Kaplan-Meier method with Cox proportional hazard model was used to determine OS. Results: The median age was 63 (18-87), stage III/IV in 73.1%, bulky disease (>10cm) in 47.4%, B symptoms in 41.67%, CNS involvement in 14.1% , extranodal (EN) involvement in 34.7% of the patients. Patients with DHL and DEL were 60.2% and 39.8%, respectively. The median OS for the cohort was 15 months. Multivariate analysis identified Age > 60 (1 point), SA <3.7 (4 points), bulky disease (2 points) and Stage III/IV (1 point) as prognostically significant. LDH and EN dropped from the model. SAAB scoring consisted of 3 groups: Very good (0-2), Good (3-5), Poor (6-8). The 3-years OS was compared among scoring systems (Table 1). Conclusions: Compared to the R-IPI and DHS, the new SAAB score better discriminated prognostic groups in DHL/DEL. Confirmation in a larger and multicenter study is needed to validate these findings. SA might represent a surrogate of comorbid status and worse biology in patients with DHL/DEL. Score (N=100) 3 Year-OS P-value SAAB 0.005 Very good (SAAB = 0-2) 45% Good (SAAB 3-5) 30% Poor (SAAB = 6-8) NA* R-IPI 0.437 Very Good (R-IPI = 0) 100% Good (R-IPI = 1-2) 30% Poor (R-IPI = 3-5) 32% Double Hit Score (DHS) 0.281 Low (DHS = 0) 26% Intermediate (DHS = 1) 29% High (DHS = 2 or more) 27% *Highest survival was 18 months.
2-Substituted 4-(Trifluoromethyl)phenols by Directed ortho-Lithiation (2001)

A broad variety of 2-substituted 4-(trifluoromethyl)phenols can be prepared in a large scale by o-lithiation and reaction with electrophiles in good to excellent yields. The key for the selectivity is the superior ortho-directing effect of the THP-protected hydroxy group (OTHP) as compared to the CF3-group.
ChemInform Abstract: ADENOSINE DEAMINASE INHIBITORS. SYNTHESIS OF DEAZA ANALOGS OF ERYTHRO‐9‐(2‐HYDROXY‐3‐NONYL) ADENINE (1984)

Abstract Ausgehend von den Chlornitropyridinen (I) bzw. (VI) werden, wie im Formelschema skizziert, die Verbindungen (V), (IX) und (XIII) synthetisiert.