gebhart/patrepeval huggingface dataset:
Secretory quality control constrains functional selection-associated protein structure innovation (2022)

Biophysical models suggest a dominant role of structural over functional constraints in shaping protein evolution. Selection on structural constraints is linked closely to expression levels of proteins, which together with structure-associated activities determine in vivo functions of proteins. Here we show that despite the up to two orders of magnitude differences in levels of C-reactive protein (CRP) in distinct species, the in vivo functions of CRP are paradoxically conserved. Such a pronounced level-function mismatch cannot be explained by activities associated with the conserved native structure, but is coupled to hidden activities associated with the unfolded, activated conformation. This is not the result of selection on structural constraints like foldability and stability, but is achieved by folding determinants-mediated functional selection that keeps a confined carrier structure to pass the stringent eukaryotic quality control on secretion. Further analysis suggests a folding threshold model which may partly explain the mismatch between the vast sequence space and the limited structure space of proteins.
High Dose Inhalation with Gaseous Nitric Oxide in COVID-19 Treatment (2022)

A method of treatment of a new coronavirus infection COVID-19 in patients undergoing high flow oxygenation is proposed and technically implemented; the method is based on high-dose inhalation of gaseous nitric oxide (NO) with the patient's spontaneous breathing. The results of the treatment of this disease demonstrating the high efficiency of the new method are presented. A possible mechanism of the blocking effect of high doses of inhaled nitric oxide on the replication of the SARS-CoV-2 virus is discussed; it is based on the formation of dinitrosyl iron complexes in the respiratory tract and lungs of COVID-19 patients with thiol-containing ligands acting as donors of NO and nitrosonium NO<sup>+</sup> cations in a living organism that have a cytotoxic effect on the SARS CoV-2 virus.
A Reverse Jensen Inequality Result with Application to Mutual Information Estimation (2021)

The Jensen inequality is a widely used tool in a multitude of fields, such as for example information theory and machine learning. It can be also used to derive other standard inequalities such as the inequality of arithmetic and geometric means or the Hölder inequality. In a probabilistic setting, the Jensen inequality describes the relationship between a convex function and the expected value. In this work, we want to look at the probabilistic setting from the reverse direction of the inequality. We show that under minimal constraints and with a proper scaling, the Jensen inequality can be reversed. We believe that the resulting tool can be helpful for many applications and provide a variational estimation of mutual information, where the reverse inequality leads to a new estimator with superior training behavior compared to current estimators.
Der EP3-Antagonist L798,106 reduziert Proliferation und Migration von SK-BR-3 Mammakarzinom-Zellen (2019)

Eine Überexpression von Cyclooxygenase-2 sowie erhöhte Spiegel von Prostaglandin E2 (PGE2) spielen eine wichtige Rolle in der Entstehung verschiedener Karzinome, wie auch der des Mammakarzinoms. Kürzlich konnten wir zeigen, dass eine erhöhte Expression des PGE2-Rezeptors EP3 einen positiven prognostischen Faktor bezüglich des progressionsfreien Überlebens und des Gesamtüberlebens beim Mammakarzinom darstellt. Die vorliegende Arbeit analysiert nun die Expression des EP3-Rezeptors auf Mammakarzinom-Zelllinien sowie funktionelle Aspekte und zugrundeliegende Signalwege unter EP3-Stimulation oder EP3-Antagonisierung.
Femtosecond Excitation of Nonthermal Carrier Populations in GaAs Quantum Wells (1986)

We report the first direct observation of nonthermal photoexcited carrier distributions in GaAs quantum-well structures. We present experimental studies which show that these distributions thermalize within 200 fs. In addition we are able to show that near the band edge the effect of long-range Coulomb screening on the bleaching of the two-dimensional-exciton resonances is much weaker than that of the Pauli exclusion principle.
Data from Bacterial Prostatitis Enhances 2-Amino-1-Methyl-6-Phenylimidazo[4,5-<i>b</i>]Pyridine (PhIP)–Induced Cancer at Multiple Sites (2023)

&lt;div&gt;Abstract&lt;p&gt;Dietary carcinogens, such as 2-amino-1-methyl-6-phenylimidazo[4,5-&lt;i&gt;b&lt;/i&gt;]pyridine (PhIP), and chronic inflammation have each been implicated as etiologic agents in prostate cancer. We hypothesized that bacterial prostatitis would accelerate PhIP-induced preinvasive lesions in the rat prostate. Male Fischer 344 rats were assigned into 4 groups: Control (untreated), PhIP (200 ppm in the diet for 20 weeks), &lt;i&gt;Escherichia coli&lt;/i&gt; (&lt;i&gt;E. coli&lt;/i&gt;, prostatic inoculation in week 10), or PhIP + &lt;i&gt;E. coli&lt;/i&gt;. Study animals were monitored for a total of 52 weeks and were euthanized as necessary based on strict criteria for health status and tumor burden. Animals treated with &lt;i&gt;E. coli&lt;/i&gt; initially developed acute and chronic inflammation in all lobes of the prostate, whereas inflammation was observed predominantly in the ventral lobe at time of death. PhIP + &lt;i&gt;E. coli–&lt;/i&gt;treated animals exhibited a marked decrease in survival compared with PhIP-alone–treated animals as a result of an increase in the number of invasive cancers that developed at multiple sites, including the skin, small intestine, and Zymbal's gland. Despite their earlier mortality, PhIP + &lt;i&gt;E. coli&lt;/i&gt;–treated animals developed an increased average number of precancerous lesions within the prostate compared with PhIP-treated animals, with a significantly increased Ki-67 index. Multiplexed serum cytokine analysis indicated an increase in the level of circulating IL6 and IL12 in PhIP + &lt;i&gt;E. coli&lt;/i&gt;–treated animals. Elevated serum IL6 levels correlated with the development of precancerous lesions within the prostate. These results suggest that bacterial infections and dietary carcinogens, two conceivably preventable cancer risk factors, may synergistically promote tumorigenesis. &lt;i&gt;Cancer Prev Res; 8(8); 683–92. ©2015 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Projections onto the Hemisphere (2008)

In this paper we present a simple method for handling projections on the hemisphere. The proposed method defines a coordinate system on the hemisphere surface that eectively converts the hemisphere to an in- finite plane tangent to the top of the hemisphere, which is called the gradient space. Using this coordinate system, projections onto the hemisphere are replaced by simple perspective projections onto the gradient space. This ap- proach totally eliminates the non-linearities caused by the spherical surface and permits exact hemisphere pro- jection computations using only a single projection op- eration. We present dierent sampling techniques on the gradient space and provide qualitative comparisons.
Extracting deep neural network bottleneck features using low-rank matrix factorization (2014)

In this paper, we investigate the use of deep neural networks (DNNs) to generate a stacked bottleneck (SBN) feature representation for low-resource speech recognition. We examine different SBN extraction architectures, and incorporate low-rank matrix factorization in the final weight layer. Experiments on several low-resource languages demonstrate the effectiveness of the SBN configurations when compared to state-of-the-art hybrid DNN approaches.
Pathologic complete response (pCR) to neoadjuvant chemoradiation (CRT) of uT2uN0 rectal cancer (RC) treated by local excision (LE): Results of the ACOSOG Z6041 trial. (2010)

3510 Background: LE alone is an effective treatment for selected T1 RCs, however, for T2 RCs it results in unacceptable local recurrence and survival. The Z6041 phase II trial investigates the efficacy of CRT and LE for treating T2N0 RC. Methods: Patients (pts) with ultrasound-staged T2N0 RC and ECOG PS ≤ 2 were treated with capecitabine (825 mg/m2 days 1-14 and 22-35) and oxaliplatin (50 mg/m2 weeks 1, 2, 4 and 5) during radiation (RT) (total dose 54 Gy) followed by LE. Due to toxicity, the dose of RT was reduced to 50.4 Gy and capecitabine to 725 mg/m2 (5 days/week/5 weeks). Pts were evaluated for clinical and pathologic response. pCR was defined as ypT0N0. The association between pCR rate and pre-treatment pt and tumor characteristics were assessed by logistic regression. The agreement between clinical and pathologic assessment of response was evaluated by sensitivity and specificity. Results: Of the 90 pts accrued (66% male; age [mean ± SD], 63 ± 11; 83% ECOG PS 0, and 89% white), 6 pts did not receive treatment per protocol, 1 did not have surgery due to toxicity, 2 pts are unevaluable (data pending). For the 81 pts with available data, 57 treated with the original and 27 with the revised regimen, the average tumor diameter was 2.9 ± 0.8 cm and distance from anal verge, 5.0 ± 2.0 cm. Chemotherapy and RT were completed per protocol in 81% and 89% of pts, respectively. A total of 36 pts achieved pCR (44%; 95% CI, 33%, 55%), 26 (46%) in the original and 10 (40%) in the revised regimen. Overall, 52 (64%) tumors were downstaged (ypT0-1), and 5 pts (6%) had ypT3 tumors. Five LE specimens contained lymph nodes; only one with a T3 tumor had a positive node. Resection margins were negative in 98% of pts. No pre-treatment tumor characteristic or treatment variable was associated with pCR. A complete clinical response was concordant with pCR in 31 of 36 pts (sensitivity 86%, specificity 70%). Conclusions: The pCR rate with capecitabine and oxaliplatin-based CRT for early stage RC is higher than for stage II-III tumors, and is one of the highest reported in a cooperative group setting. Resection margins were negative in all but 1 pt. The ability of surgeons to predict a pCR was higher than previously reported. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis Roche, sanofi-aventis
Reverse Transcription-Loop-mediated Isothermal Amplification (RT-LAMP) Assay for Zika Virus and Housekeeping Genes in Urine, Serum, and Mosquito Samples (2018)

Reverse Transcription-loop-mediated Isothermal Amplification Rt-lamp Assay For Zika Virus And Housekeeping Genes In Urine Serum And Mosquito Samples - Video. JoVE publishes peer-reviewed scientific video protocols to accelerate biological, medical, chemical and physical research. Watch our scientific video articles. JoVE is the world-leading producer and provider of science videos with the mission to improve scientific research, scientific journals, and education. Millions of scientists, educators and students at thousands of universities, colleges, hospitals and biopharmaceutical companies worldwide use JoVE for their research, teaching and learning.
8×8 array of cascadable differential pairs of optical thyristors for parallel optical interconnects (1995)

We report on the fabrication of the first monolithic array of 8/spl times/8 differential pairs of optical thyristors. The 64 thyristor pairs have a common anode and a common cathode, such that the complete array has only 2 electrical contact pads for the electrical power supply. Each differential pair of the array is an optoelectronic switch which can emit and receive dual-rail code binary optical data perpendicular to the chip surface. The required optical input energy for switching is only 50 fJ, and the bit rate is at present 25 Mbit/sec.
A Novel Lossless Snubber for Boost Converters (2006)

Advanced transportation technologies, such as hybrid-electric vehicles, battery-electric vehicles, and fuel cell vehicles, rely on high-power DC/DC converters to interconnect and manage their power systems. Boost converters are especially useful in stepping-up the voltage from a battery or fuel cell to match the electric motor voltage range. However, conventional high-power boost converters are very large and heavy, partly due to the large inductors used in the design. These heavy components negatively affect the fuel economy of the vehicles, add cost to the vehicle, and may add difficulty for packaging. The solution is to implement a method which reduces the switching losses in the converter so that the switching frequency can be increased and hence the size of the inductors, and overall converter, can be reduced. This paper proposes a new lossless snubber circuit that greatly reduces the switching losses of the IGBT in the converter. The circuit uses no additional magnetic components, has a simple control strategy, is relatively low-cost, and is shown to provide a boost in efficiency even while greatly reducing the size of the converter. Thermal considerations are taken into account to provide practical simulation results
High Molecular Weight Protein Phosphatase Type 1 Dephosphorylates the Retinoblastoma Protein (1997)

pRb controls cell proliferation by restricting inappropriate entry of cells into the cell division cycle. As dephosphorylation of pRb during mitotic exit activates its growth suppressive function, identification of the protein phosphatase that dephosphorylates pRb, and characterization of the mechanism of its regulation, are essential to elucidating the mechanisms of cell growth control. By fractionating mitotic CV-1P cell extracts, we identify the protein phosphatase which dephosphorylates pRb as a type 1 serine/threonine phosphoprotein phosphatase (PP1). Molecular sizing analyses indicate that the catalytic enzyme (PP1c) is present in a high molecular weight complex, with a predicted molecular mass of 166 kDa. PP1-interacting proteins in the mitotic cell extracts are identified. Two PP1-interacting proteins (41 and 110 kDa) are shown to form distinct complexes with PP1c from fractions of separated mitotic cell extracts containing phosphorylase phosphatase activity. However, only the 110-kDa PP1-interacting protein is present in fractions containing pRb-directed phosphatase activity, identifying this protein as a putative activator of PP1 function toward pRb during mitosis.
IL-3 Induces Basophil Expansion In Vivo by Directing Granulocyte-Monocyte Progenitors to Differentiate into Basophil Lineage-Restricted Progenitors in the Bone Marrow and by Increasing the Number of Basophil/Mast Cell Progenitors in the Spleen (2009)

Recent work has established important roles for basophils in regulating immune responses. To exert their biological functions, basophils need to be expanded to critical numbers. However, the mechanisms underlying basophil expansion remain unclear. In this study, we established that IL-3 played an important role in the rapid and specific expansion of basophils. We found that the IL-3 complex (IL-3 plus anti-IL-3 Ab) greatly facilitated the differentiation of GMPs into basophil lineage-restricted progenitors (BaPs) but not into eosinophil lineage-restricted progenitors or mast cells in the bone marrow. We also found that the IL-3 complex treatment resulted in approximately 4-fold increase in the number of basophil/mast cell progenitors (BMCPs) in the spleen. IL-3-driven basophil expansion depended on STAT5 signaling. We showed that GMPs but not common myeloid progenitors expressed low levels of IL-3 receptor. IL-3 receptor expression was dramatically up-regulated in BaPs but not eosinophil lineage-restricted progenitors. Approximately 38% of BMCPs expressed the IL-3R alpha-chain. The up-regulated IL-3 receptor expression was not affected by IL-3 or STAT5. Our findings demonstrate that IL-3 induced specific expansion of basophils by directing GMPs to differentiate into BaPs in the bone marrow and by increasing the number of BMCPs in the spleen.
Synthesis of Chiral α-Aminoalkylpyrimidines Using an Enantioselective Three-Component Reaction (2004)

A range of chiral α-aminoalkylpyrimidines has been prepared in a modular fashion in 5 steps with up to 98% ee. The key step is a CuBr-catalyzed enantioselective asymmetric three-component synthesis of propargylic amines.
Thermomechanical properties of small-carbohydrate–water glasses and ‘rubbers’. Kinetically metastable systems at sub-zero temperatures (1988)

Aqueous solutions of 24 small carbohydrates have been analysed by low-temperature differential scanning calorimetry (d.s.c.). The method, based on analogue derivative thermograms, measured two thermomechanical properties characteristic of each non-crystallizing solute: T′g, the sub-zero glass transition temperature of a maximally freeze-concentrated solution and W′g, the amount of unfrozen water (UFW) kinetically immobilized in the glass at T′g. For 84 low-molecular-weight polyhydroxy compounds (PHCs) analysed to date, T′g ranged from –85 °C for ethylene glycol to –13.5 °C for maltoheptaose, and increased monotonically with increasing Mw. T′g plotted vs.M–1w showed a linear correlation characteristic of an homologous family of glass-forming linear oligomers. W′g ranged from 1.9 g UFW g–1 for ethylene glycol to 0.2–0.3 g UFW g–1 for several sugars and polyols, including maltoheptaose, and decreased with increasing T′g, showing fair linear correlations for several series of homologous solutes. We describe here the use of T′g and W′g, as invariant physico-chemical properties of glass-forming solutions at sub-zero temperatures, to interpret thermomechanical behaviour of small-carbohydrate–water systems in non-equilibrium glassy and ‘rubbery’ states, define structure–activity relationships and explain and often predict functional behaviour of such PHCs in various applications.
Bayesian Joint Topic Modelling for Weakly Supervised Object Localisation (2017)

We address the problem of localisation of objects as bounding boxes in images with weak labels. This weakly supervised object localisation problem has been tackled in the past using discriminative models where each object class is localised independently from other classes. We propose a novel framework based on Bayesian joint topic modelling. Our framework has three distinctive advantages over previous works: (1) All object classes and image backgrounds are modelled jointly together in a single generative model so that "explaining away" inference can resolve ambiguity and lead to better learning and localisation. (2) The Bayesian formulation of the model enables easy integration of prior knowledge about object appearance to compensate for limited supervision. (3) Our model can be learned with a mixture of weakly labelled and unlabelled data, allowing the large volume of unlabelled images on the Internet to be exploited for learning. Extensive experiments on the challenging VOC dataset demonstrate that our approach outperforms the state-of-the-art competitors.
About global null controllability of a quasi-static thermoelastic contact system (2005)

We study the null controllability properties of a system that models
the temperature evolution of a one-dimensional thermoelastic rod that may come
into contact with a rigid obstacle. Basically the system dynamics is described by
a one-dimensional nonlocal heat equation with a nonlinear and nonlocal boundary
condition of Newmann type at the free end of the rod. We study the control problem
and treat the case when the control is distributed over the whole space domain.
 
In [8], we proved that if the initial condition is smooth and the system has a
strong solution, then there is a control that brings the system to zero. The proof was
based on changing the control variable and using Aubin's Compactness Lemma. In
this paper, we focus on the null controllability of the weak solutions. We establish
the existence of a control that steers the system to zero. Our approach consists of
approximating the initial condition by the smooth functions and then proving that
the obtained sequence of strong solutions converges to a weak solution of the desired
type. The uniqueness of a weak solution is established only under special assumptions
on the parameters of the system.
End-systolic measures of regional ventricular performance. (1986)

Dimension change measures of regional ventricular function, such as absolute or percent wall thickening (delta T or % delta T) or segmental shortening (delta L or % delta L), are highly load dependent. In 16 anesthetized mongrel dogs we assessed use of the end-systolic pressure-thickness and end-systolic pressure-length relationships (ESPTR, ESPLR) as more load-independent measures of regional function. We found that the ESPTR and ESPLR could be measured without detectable baroreceptor-mediated reflex changes in cardiac contractile state. Systemic administration of dobutamine shifted the ESPTR to the right and the ESPLR to the left of control, mainly due to a change in the slope (Ees) of the relationships. Both delta T, % delta T and delta L, % delta L failed to detect the positive inotropic effect of dobutamine because of an associated reduction in preload. With systemic administration of propranolol, ESPTR, ESPLR, delta T, % delta T, and delta L, % delta L detected the negative inotropic effect. Thus systemic propranolol shifted the ESPTR to the left and the ESPLR to the right of control, mainly due to a change in Ees. Regional administration of dobutamine shifted the ESPTR and the ESPLR in the direction of positive contractility in the region receiving the drug, whereas simple dimension change measures of regional function failed to detect the inotropic effect because preload fell and the timing of regional end-systole was altered. With regional propranolol both the ESPTR, ESPLR and simple dimension change measures detected the negative inotropic effect. Thus the ESPTR, ESPLR is a reliable measure of regional ventricular function and may be better than simple dimension change measures of regional function, particularly when loading conditions or the timing of regional systole is altered by an intervention.
Crystal structure of 3-benzoylmorphin-6-one-17-carboxamide ethanol solvate (1:0.333), C24H20N2O5 · 0.333C2H5OH (2005)

Article Crystal structure of 3-benzoylmorphin-6-one-17-carboxamide ethanol solvate (1:0.333), C24H20N2O5 · 0.333 C2H5OH was published on April 1, 2005 in the journal Zeitschrift für Kristallographie - New Crystal Structures (volume 220, issue 1-4).
Stem cell therapy for ischemic heart diseases (2017)

Recently, stem cell-derived exosomes emerge as a critical player in paracrine mechanism of stem cell-based therapy. It is promising to exploit exosomes-based cell-free therapy for ischemic heart diseases in the future.