gebhart/patrepeval huggingface dataset:
Myocardial Protection in Heart Surgery (2011)

One of the unmet clinical needs in heart surgery is the prevention of myocardial stunning and necrosis that occurs as a result of ischemia-reperfusion. Myocardial stunning, a frequent consequence after heart surgery, is characterized by a requirement for postoperative inotropic support despite a technically satisfactory heart operation. In high-risk patients with marginal cardiac reserve, stunning is a major cause of prolonged critical care and may be associated with as much as a 5-fold increase in mortality. In contrast, the frequency of myocardial necrosis (myocardial infarction [MI]) after cardiac surgery is less appreciated and its consequences are much more subtle. The consequences may not be apparent for months to years. While we now have a much better understanding of the molecular mechanisms underlying myocardial stunning and MI, we still have no effective way to prevent these complications, nor a consistently effective means to engage the well-studied endogenous mechanisms of cardioprotection. The failure to develop clinically effective interventions is multifactorial and can be attributed to reliance on findings obtained from subcellular and cellular studies, to drawing conclusions from preclinical large animal studies that have been conducted in a disease-free state, and to accepting less than robust surrogate markers of injury in phase II clinical trials. These factors also explain the disappointing failure to identify effective adjuvant therapy in the setting of percutaneous coronary revascularization for acute MI (AMI) and reperfusion injury. These issues have contributed to the disappointing outcomes of large and costly phase III trials, resulting in a lack of enthusiasm on the part of the pharmaceutical industry to engage in further drug development for this indication. The purpose of this review is to (1) define the scope of the clinical problem; (2) summarize the outcomes of selected phases II and III clinical trials; and (3) identify the gap that needs to be closed in order to address the unmet clinical need.
Penicillin Enhances the Toll‐Like Receptor 2–Mediated Proinflammatory Activity ofStreptococcus pneumoniae (2003)

The Streptococcus pneumoniae cell-wall components peptidoglycan and lipoteichoic acid activate Toll-like receptor 2 (TLR2), which transduces an inflammatory response. After exposure to penicillin, type 2 S. pneumoniae strain D39, but not the isogenic autolysin-deficient mutant AL2, induced significantly enhanced interleukin-8 promoter activity in TLR2-transfected HeLa cells. Lag-phase D39 exhibited enhanced TLR2 activation after exposure to penicillin at levels below the minimum inhibitory concentration (MIC); in contrast, early log-phase S. pneumoniae were most active when exposed to the MIC. This enhancement was not ablated by heat treatment but was attenuated by autolysin inhibitors. The antimicrobial activity of moxifloxacin and erythromycin was not associated with TLR2 activation by S. pneumoniae. These data show that penicillin treatment of S. pneumoniae releases proinflammatory cell-wall components that activate TLR2 and that this activity is dependent on autolysin, the growth phase of the organism, and the antibiotic concentration.
Treatment of therapeutically resistant non-unions with bone grafts and pulsing electromagnetic fields. (1982)

This study reviews the cases of eighty-three adults with ununited fractures who were treated concomitantly with bone-grafting and pulsed electromagnetic fields. An average of 1.5 years had elapsed since fracture and the use of this combined approach. Nearly one-third of the patients had a history of infection, and an average of 2.4 prior operations had failed to produce bone union. Thirty-eight patients who were initially treated with grafts and pulsed electromagnetic fields for ununited fractures with wide gaps, synovial pseudarthrosis, and malalignment achieved a rate of successful healing of 87 per cent. Forty-five patients who had initially been treated unsuccessfully with pulsing electromagnetic fields alone had bone-grafting and were re-treated with pulsing electromagnetic fields. Ninety-three per cent of these fractures healed. The residual failure rate after two therapeutic attempts, one of which was operative, was 1.5 per cent. The median time to union for both groups of patients was four months.
Thyrotropin-releasing hormone binding to the mouse pituitary receptor does not involve ionic interactions. A model for neutral peptide binding to G protein-coupled receptors. (1992)

Thyrotropin-releasing hormone, TRH (< Glu-His-Proamide), and [N tau-Me-His]TRH (MeTRH) are present as neutral and positively charged forms at physiologic pH, and it was possible that they bind to the TRH receptor (TRH-R) as charged (protonated) species. Binding affinities of TRH and MeTRH to endogenous rat TRH-Rs and to transfected wild type mouse TRH-Rs decreased below pH 7.1. Half-maximal decreases in binding occurred at the approximate pK alpha values of these ligands. Asp to Ala mutations in extracellular loop 1, TM-4, and TM-5 did not decrease binding affinity, but an Asp to Ala mutation in TM-2 caused the affinity to decrease 8-fold. The pH dependences of binding of MeTRH, however, were similar in wild type and all mutant receptors and were consistent with the protonated form of MeTRH binding less well. Thus, the binding of TRH to its receptor does not involve ionic interactions and may be a prototype for binding of neutral peptide ligands to G protein-coupled receptors.
Thioesterase from Cereulide Biosynthesis Is Responsible for Oligomerization and Macrocyclization of a Linear Tetradepsipeptide (2020)

Cereulide is a toxic cyclic depsidodecapeptide produced in <i>Bacillus cereus</i> by two nonribosomal peptide synthetases, CesA and CesB. While highly similar in structure to valinomycin and with a homologous biosynthetic gene cluster, recent work suggests that cereulide is produced via a different mechanism that relies on a noncanonical coupling of two didepsipeptide-peptidyl carrier protein (PCP) bound intermediates. Ultimately this alternative mechanism generates a tetradepsipeptide-PCP bound intermediate that differs from the tetradepsipeptide-PCP intermediate predicted from canonical activity of CesA and CesB. To differentiate between the mechanisms, both tetradepsipeptides were prepared as <i>N</i>-acetyl cysteamine thioesters (SNAC), and the ability of the purified recombinant terminal CesB thioesterase (CesB TE) to oligomerize and macrocyclize each substrate was probed. Only the canonical substrate is converted to cereulide, ruling out the alternative mechanism. It was demonstrated that CesB TE can use related tetradepsipeptide substrates, such as the valinomycin tetradespipetide and a hybrid cereulide-valinomycin tetradepsipetide in conjunction with its native substrate to generate chimeric natural products. This work clarifies the biosynthetic origins of cereulide and provides a powerful biocatalyst to access analogues of these ionophoric natural products.
Therapeutic Plasma Levels of OKT3 Muromonab Are Effective as Second-Line and Subsequent Treatment in Recipients of Stem Cell Allografts with Steroid-Resistant Acute Graft-Versus-Host Disease. (2004)

Abstract Acute graft-versus-host disease (aGvHD) remains a major complication in recipients of hematopoietic cell allografts and is associated with poor outcome. Salvage treatment is difficult after failure of steroids. OKT3 muromonab is a monoclonal murine IgG2a antibody directed against the CD3 antigen on T-lymphocytes that has proven effective in transplant settings both of solid organs and bone marrow. Here we report on the results of OKT3 treatment in 43 patients who had received stem-cell or bone marrow allografts for hematologic malignancies and subsequently been diagnosed with steroid-resistant aGvHD. Overall, 48 treatment cycles of OKT3 (5 mg intravenous injection once daily) were administered for acute GvHD of grades II (n = 12), III (n = 27) and IV (n = 9). Mean duration of OKT3 therapy was 9 (range, 1 –16) days. Twenty cycles of OKT3 were administered as second line and 28 as third-plus line (third line, n = 14; fourth line, n = 14) treatment regimens. Side effects were mild to moderate, comprising fever, dyspnea, tachycardia, and vomiting. Thirty of 42 evaluable patients responded to therapy for an overall response rate of 69 %. Complete remissions were seen in 6 (11.9 %) and partial remissions in 24 patients (57.1 %). Response to treatment was 88.8 % for skin GvHD; 53.3 % for gut aGvHD; and 8.7 % for liver involvement. Recurrent or progressive acute GvHD was observed in 23 patients (54.8 %) after a median of 9 (range, 1 – 58) days. Pharmacokinetic studies of monoclonal antibody OKT3 were performed in 17 patients, 16 of whom achieved at least a partial remission. Treatment duration was &amp;gt; 5 days in 16 patients. Adequate plasma levels (&amp;gt; 1000 ng/ml) were observed in 13 patients after a median of 6 (1 – 11) days on treatment. OKT3 concentration became undetectable at a median of merely 4 (3 – 11) days after discontinuation of therapy. Survival at 100 days from transplantation was 58.1 % and at one year, 25.5 % with the most important causes of death being infectious complications (44.7%) and GvHD (33.2%). Patients treated with OKT3 earlier in the course of aGVHD showed a trend to better survival: 35% of patients with 2nd-line therapy were alive at one year from transplantation, compared to 17.4% with 3rd- plus line treatment (p=0.21). There was also a trend to a better one-year survival for patients with grade II (33% of patients alive) when compared to grade III/IV aGvHD (16% of patients alive; p=0.24). Thus, a significant proportion of patients with corticosteroid-resistant acute GvHD showed a response to salvage treatment with OKT3. More effective antimicrobial prophylaxis and treatment are mandatory to overcome considerable treatment-related mortality in those high-risk patients.
On max-min fair ow optimization in wireless mesh networks (2011)

The paper is devoted to modeling wireless mesh networks (WMN) through mixed-integer programming (MIP) formulations that allow to precisely characterize the link data rate capacity and transmission scheduling using the notion of time slots. Such MIP models are formulated for several cases of the modulation and coding schemes (MCS) assignment. We present a general way of solving the max-min fairness (MMF) trac objective for WMN using the formulated capacity models. Thus the paper combines WMN radio link modeling with a non-standard way of dealing with uncertain trac, a combination that has not, to our knowledge, been treated so far by exact optimization models. We discuss several ways, including a method based on the so called compatible or independent sets, of solving the arising MIP problems. We also present an extensive numerical study that illustrates the running time eciency of dierent solution approaches, and the inuence of the MCS selection options and the number of time slots on trac performance of a WMN. Exact joint optimization modeling of the WMN capacity and the MMF trac objectives forms the main contribution of the paper.
On Antenna Q-factor Characterization with Generative Adversarial Networks (2020)

This paper introduces a novel way to reproduce antennas with Q-factor within a pre-determined threshold using Generative Adversarial Networks (GAN), a class of artificial intelligence algorithm. Instead of optimizing the Q-factor using a conventional optimization techniques, a GAN is trained to learn the distribution on desirable parameter vectors of the antenna and its Q-factor as obtained from a full wave solver. The trained GAN is subsequently used to generate antenna parameters from the learned distribution with a predicted Q-factor. The predicted antenna parameters are imported to CST and simulated using the parameters generated by GAN and the Q-factors are analyzed. The results obtained provides an unique perspective to learning the correlation between antenna parameter distribution and its Q-factor. Simulation results are provided to explain this approach of reproducing antennas with a low Q-factor.
A curvature based descriptor invariant to pose and albedo derived from photometric data (2002)

Gaussian curvature is an invariant local descriptor of smooth surfaces. We present an object signature which is a condensed representation of the distribution of Gaussian curvature information at visible object points. An invariant related to Gaussian curvature at a point is derived from the covariance matrix of the photometric values in a neighborhood about that point. In addition, we introduce an albedo-normalization method that is capable of cancelling albedo on Lambertian surfaces. We use three illumination conditions, two of which are unknown. The three-tuple of intensity values at a point is related via a one-to-one mapping to the surface normal at that point. The determinant of the covariance matrix of the local three-tuples is invariant to albedo, rotation and translation. The collection of determinants over mutually illuminated object points is combined into a signature distribution which is albedo, rotation, translation, and scale invariant. An object recognition methodology using these signatures is proposed.
Etiology and Outcome of Diarrhea After Transplantation: A Prospective Study Marrow (1994)

Background/Aims: Acute diarrhea after marrow transplant is usually ascribed to acute graft-vs.-host disease (GVHD) or infection, with a reported 40%-50% incidence of infection. The aim of this study was to determine the incidence of acute diarrhea after transplantation, its causes, and its outcome. Methods: Two hundred ninety-six patients were followed up; patients with diarrhea were studied using standard evaluation of stool plus immunoelectron microscopy; assays for astrovirus, picobirnavirus, and Norwalk virus; and geneprobe methods for toxin-producing Escherichia co/i. In 38 patients with diarrhea, intestinal biopsy specimens and duodenal fluid were also analyzed. Results: One hundred fifty acute diarrhea1 episodes developed in 126 patients (an incidence of 43%). Intestinal infection was found in 20 of 150 episodes: viruses (astrovirus, adenovirus, cytomegalovirus, and rotavirus) in 12 patients, nosocomially acquired bacteria (Clostridium difM/e and Aeromonas) in 7 patients, and mixed infection in 1 patient. Acute GVHD was responsible for 72 of 150 episodes (48%). Clinical signs and symptoms of infection and GVHD were similar. In 58 of 150 episodes (39%), no clear etiology could be found for self-limited diarrhea. Conclusions: Intestinal infection accounted for 13% and acute GVHD for 48% of diarrhea1 episodes. The most common infecting organisms were astrovirus, C. difficile, and adenovirus. Most cases of diarrhea after marrow transplant are not caused by infection.
The CD40 TRAF family member interacting motif carries the information to rescue WEHI 231 cells from anti-IgM-induced growth arrest (1998)

Engagement of the antigen receptor on WEHI 231 murine B lymphoma cells leads to growth arrest and induction of apoptosis. Concomitant signaling through CD40 sustains proliferation and rescues the cells from apoptosis. At the molecular level, CD40 has been shown to activate nuclear factor κB (NF-κB) and stress-activated protein kinase (SAPK). The aim of our present study was to define the stretch of the CD40 cytoplasmic tail responsible for mediating these effects in WEHI 231 cells. Using recombinant retroviruses with the enhanced green fluorescent protein as selection marker we transduced WEHI 231 cells with chimeric molecules consisting of the extracellular and transmembrane region of human CD40 or rat CD4 and selected portions of the murine CD40 tail. Chimeric molecules with cytoplasmic fragments encompassing the “CD40 tumor necrosis factor-associated factor family member interacting motif” (TIM) were able to sustain growth and to uphold NF-κB activity as efficiently as the whole intracellular region of CD40. While the potential of the motif relative to the whole cytoplasmic tail was independent of the heterologous part of the chimeras it was strongly influenced by its distance to the membrane. Placing the 17-aminoacid stretch of the motif too close to the membrane, i. e. only two or four amino acids apart, destroyed its capacity to mitigate the anti-IgM effect. Activation of SAPK through the chimeric molecules always correlated with their ability to activate NF-κB activity and to rescue the cells from apoptosis induced by antigen receptor ligation. Our data indicate that CD40-TIM carries most if not all of the information needed to deliver the signals responsible for sustaining growth in anti-IgM-stimulated WEHI 231 cells.
Half-Life Extended Nanobody-Based CD38-Specific Bispecific Killercell Engagers Induce Killing of Multiple Myeloma Cells (2022)

CD38 is a target for immunotherapy of multiple myeloma. Llama-derived CD38-specific nanobodies allow easy reformatting into mono-, bi- and multispecific proteins. To evaluate the utility of nanobodies for constructing CD38-specific nanobody-based killer cell engagers (nano-BiKEs), we generated half-life extended nano-BiKEs (HLE-nano-BiKEs) by fusing a CD38-specific nanobody to a CD16-specific nanobody for binding to the Fc-receptor on NK cells and further to an albumin-specific nanobody to extend the half-life <i>in vivo</i>. HLE-nano-BiKEs targeting three different epitopes (E1, E2, E3) of CD38 were expressed in transiently transfected HEK-6E cells. We verified specific and simultaneous binding to CD38 on myeloma cells, CD16 on NK cells, and to albumin. We tested the capacity of these HLE-nano-BiKEs to mediate cytotoxicity against CD38-expressing multiple myeloma cell lines and primary myeloma cells from human bone marrow biopsies in bioluminescence and flowcytometry assays with NK92 cells as effector cells. The results revealed specific time- and dose-dependent cytolysis of CD38+ myeloma cell lines and effective depletion of CD38-expressing multiple myeloma cells from primary human bone marrow samples. Our results demonstrate the efficacy of CD38-specific HLE-nano-BiKEs <i>in vitro</i> and <i>ex vivo</i>, warranting further preclinical evaluation <i>in vivo</i> of their therapeutic potential for the treatment of multiple myeloma.
Transient Solute Distributions from the Basic Equation of the Ultra-centrifuge (1953)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTransient Solute Distributions from the Basic Equation of the Ultra-centrifugeDavid F. Waugh and David A. YphantisCite this: J. Phys. Chem. 1953, 57, 3, 312–318Publication Date (Print):March 1, 1953Publication History Published online1 May 2002Published inissue 1 March 1953https://pubs.acs.org/doi/10.1021/j150504a012https://doi.org/10.1021/j150504a012research-articleACS PublicationsRequest reuse permissionsArticle Views33Altmetric-Citations22LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
High levels of dietary homocysteine (Hcy) accelerate impulse propagation across the murine atrioventricular node (AVN) (2008)

Patients with elevated levels of Hcy have been reported to be at greater risk of developing cardiac arrhythmias and sudden cardiac death (SCD). However, the mechanism that initiates Hcy‐induced arrhythmias is unknown. Since intracellular Ca 2+ is important in the modulation of AVN conduction and Hcy regulates Ca 2+ transients, we hypothesize that Hcy increases impulse conduction across the AVN facilitating conduction of atrial tachyarrhythmias to the ventricles. Using intracardiac electrophysiologic techniques, we report that in diet induced hyperhomocysteinemic (HHcy) C57BL/6 mice, high levels of Hcy elicited significantly shorter PR intervals (P=.0056) than in mice on a regular diet. The AH interval of intracardiac electrograms in HHcy mice revealed an accelerated conduction (32.4±6.0msec) compared to controls (44.0±7.3msec, P=.0069). However, HV conduction remained unchanged. Ventricular programmed stimulation demonstrated a trend to induced non‐sustained ventricular tachycardia (VT) in HHcy mice. Our preliminary results demonstrate for the first time that high levels of dietary Hcy increase impulse propagation from atria to ventricles suggesting a potential mechanism for conduction of supraventricular arrhythmias in HHcy mice.
Filtering ADCs for wireless receivers: A survey (2017)

Analog to digital converters (ADC) are used in wireless receivers to process signals in the presence of blockers. These blockers, usually much larger than the signal itself, necessitate the use of a filter upfront to reduce the dynamic range requirement of the ADC. A filtering ADC can be created by placing both the filter and the ADC in a global feedback loop, with improvement in noise and power efficiency. This paper reviews and analyzes two design methodologies for analog filtering ADCs, where the filter response is defined by analog circuits. Then, a digital filtering ADC architecture is discussed that takes advantage of the programmability of digital circuits.
A Systematic Review of Tools to Measure Respiratory Rate in Order to Identify Childhood Pneumonia (2018)

Pneumonia is the leading infectious cause of death in children worldwide, with most deaths occurring in developing countries. Measuring respiratory rate is critical to the World Health Organization's guidelines for diagnosing childhood pneumonia in low-resource settings, yet it is difficult to accurately measure. We conducted a systematic review to landscape existing respiratory rate measurement technologies. We searched PubMed, Embase, and Compendex for studies published through September 2017 assessing the accuracy of respiratory rate measurement technologies in children. We identified 16 studies: 2 describing manual devices and 14 describing automated devices. Although both studies describing manual devices took place in low-resource settings, all studies describing automated devices were conducted in well-resourced settings. Direct comparison between studies was complicated by small sample size, absence of a consistent reference standard, and variations in comparison methodology. There is an urgent need for affordable and appropriate innovations that can reliably measure a child's respiratory rate in low-resource settings. Accelerating development or scale-up of these technologies could have the potential to advance childhood pneumonia diagnosis worldwide.