gebhart/patrepeval huggingface dataset:
The ability of lens alpha crystallin to protect against heat-induced aggregation is age-dependent (1992)

Alpha crystallin was prepared from newborn and aged bovine lenses. SDS-PAGE and tryptic peptide mapping demonstrated that both preparations contained only the alpha-A and alpha-B chains, with no significant contamination of other crystallins. Compared with alpha crystallin from the aged lens, alpha crystallin from the newborn lens was much more effective in the inhibition of beta L crystallin denaturation and precipitation induced in vitro by heat. Together, these results demonstrate that during the aging process, the alpha crystallins lose their ability to protect against protein denaturation, consistent with the hypothesis that the alpha crystallins play an important role in the maintenance of protein native structure in the intact lens.
Anomaly detection algorithm based on life pattern extraction from accumulated pyroelectric sensor data (2008)

This paper describes an algorithm of behavior labeling and anomaly detection for elder people living alone. In order to grasp the personpsilas life pattern, we set some pyroelectric sensors in the house and measure the personpsilas movement data all the time. From those sequential data, we extract two kinds of information, time and duration, and calculate two-dimensional probabilistic density function of them. Using this function, we try to classify behavior labels and detect anomaly. Here, we assume two kinds of anomaly, ldquothe rare behaviorsrdquo and ldquothe changes of life patternrdquo. The algorithm is confirmed to work on real behavior data through the experiment on about 400 days data.
A Multi-TW Few-cycle Optical Parametric Chirped Pulse Amplifier (2009)

We report on the generation of 8 fs, 125 mJ pulses in a noncollinear optical parametric chirped pulse amplifier with a temporal contrast reaching 10 orders of magnitude at 5 ps before the main pulse. © 2009 Optical Society of America.
Evaluation of the Ultrasensitive Roche Amplicor HIV-1 Monitor Assay for Quantitation of Human Immunodeficiency Virus Type 1 RNA (1999)

The ultrasensitive Amplicor HIV-1 Monitor test (Roche Diagnostic Systems) was evaluated for precision, linearity, and sensitivity and was compared to the standard Amplicor assay. The ultrasensitive assay reliably quantified samples in the range from 50 to 50,000 human immunodeficiency virus type 1 RNA copies/ml with acceptable correlation with the standard Amplicor test.
A novel mechanism of inhibition of high-voltage activated calcium channels by α-conotoxins contributes to relief of nerve injury-induced neuropathic pain (2010)

α-Conotoxins that are thought to act as antagonists of nicotinic acetylcholine receptors (nAChRs) containing α3-subunits are efficacious in several preclinical models of chronic pain. Potent interactions of Vc1.1 with other targets have suggested that the pain-relieving actions of α-conotoxins might be mediated by either α9α10 nAChRs or a novel GABA(B) receptor-mediated inhibition of N-type calcium channels. Here we establish that three α-conotoxins, Vc1.1, AuIB and MII have distinct selectivity profiles for these three potential targets. Their potencies after intramuscular administration were then determined for reversal of allodynia produced by partial nerve ligation in rats. Vc1.1, which potently inhibits α9α10 nAChRs and GABA(B)/Ca(2+) channels but weakly blocks α3β2 and α3β4 nAChRs, produced potent, long-lasting reversal of allodynia that were prevented by pre-treatment with the GABA(B) receptor antagonist, SCH50911. α-Conotoxin AuIB, a weak α3β4 nAChR antagonist, inhibited GABA(B)/Ca(2+) channels but did not act on α9α10 nAChRs. AuIB also produced reversal of allodynia. These findings suggest that GABA(B) receptor-dependent inhibition of N-type Ca(2+) channels can mediate the sustained anti-allodynic actions of some α-conotoxins. However, MII, a potent α3β2 nAChR antagonist but inactive on α9α10 and α3β4 nAChRs and GABA(B)/Ca(2+) channels, was demonstrated to have short-acting anti-allodynic action. This suggests that α3β2 nAChRs may also contribute to reversal of allodynia. Together, these findings suggest that inhibition of α9α10 nAChR is neither necessary nor sufficient for relief of allodynia and establish that α-conotoxins selective for GABA(B) receptor-dependent inhibition of N-type Ca(2+) channels relieve allodynia, and could therefore be developed to manage chronic pain.
What and where: a bayesian inference theory of visual attention (2010)

In the theoretical framework described in this thesis, attention is part of the inference process that solves the visual recognition problem of what is where. The theory proposes a computational role for attention and leads to a model that predicts some of its main properties at the level of psychophysics and physiology. In our approach, the main goal of the visual system is to infer the identity and the position of objects in visual scenes: spatial attention emerges as a strategy to reduce the uncertainty in shape information while feature-based attention reduces the uncertainty in spatial information. Featural and spatial attention represent two distinct modes of a computational process solving the problem of recognizing and localizing objects, especially in difficult recognition tasks such as in cluttered natural scenes. We describe a specific computational model and relate it to the known functional anatomy of attention. We show that several well-known attentional phenomena—including bottom-up pop-out effects, multiplicative modulation of neuronal tuning curves and shift in contrast responses—emerge naturally as predictions of the model. We also show that the bayesian model predicts well human eye fixations (considered as a proxy for shifts of attention) in natural scenes. Finally, we demonstrate that the same model, used to modulate information in an existing feedforward model of the ventral stream, improves its object recognition performance in clutter. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253-1690.)
Causality considerations in distributed, persistent operating systems (1994)

In this paper we describe a new persistent distributed operating system. The Grasshopper system is designed to allow flexibility in the way in which persistence is provided. A key element of this flexibility is concerned with issues of global consistency. The Grasshopper kernels cooperate with user level entities in order to maintain and find globally consistent states using vector time. Further flexibility is provided by allowing the kernels to implement either eager or lazy consistency policies. 1
Vascular safety issues in CML patients treated with BCR/ABL1 kinase inhibitors (2014)

Vascular safety is an emerging issue in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs). Whereas imatinib exhibits a well-documented and favorable long-term safety profile without obvious accumulation of vascular events, several types of vascular adverse events (VAEs) have been described in patients receiving second- or third-generation BCR/ABL1 TKIs. Such VAEs include pulmonary hypertension in patients treated with dasatinib, peripheral arterial occlusive disease and other arterial disorders in patients receiving nilotinib, and venous and arterial vascular occlusive events during ponatinib. Although each TKI interacts with a unique profile of molecular targets and has been associated with a unique pattern of adverse events, the mechanisms of drug-induced vasculopathy are not well understood. Here, recent data and concepts around VAEs in TKI-treated patients with CML are discussed, with special reference to potential mechanisms, event management, and strategies aimed at avoiding occurrence of such events in long-term treated patients.
Femtosecond laser hyperdoping and micro/nanotexturing of silicon for photovoltaics (2012)

We have developed a technique, optical hyperdoping, for doping semiconductors to unusually high levels and endowing them with remarkable optoelectronic properties. By irradiating silicon (Si) with a train of femtosecond laser pulses in the presence of heavy chalcogen (sulfur, selenium, and tellurium) compounds, a 100-300 nm thin layer of Si is doped to nonequilibrium levels (~1 at. %). Hyperdoped silicon exhibits near-unity photon absorptance from the ultraviolet (&lambda; &lt; 0.25 &#956;m) to the mid-infrared (&lambda; &gt; 2.5 &mu;m), even though crystalline silicon is normally transparent to wavelengths &lambda; &gt; 1.1 &mu;m due to its band gap at 1.1 eV. Concurrent to doping, we are also able to use fs-laser irradiation to create light-trapping surface textures on the micro- and nanometer scales. Together, optical hyperdoping and surface texturing represent a route towards high-performance thin film photovoltaic devices.
Pseudophase-Change Effects in Turbulent Channel Flow under Transcritical Temperature Conditions (2017)

We have performed direct numerical simulations (DNS) of compressible turbulent channel flow at supercritical pressure with top and bottom isothermal walls kept respectively at a supercritical (Ttop &gt; Tpb) and subcritical temperature (Tbot &lt; Tpb), where Tpb is the pseudoboiling temperature. The DNS are conducted using a high-order discretization of the fully compressible Navier-Stokes equations in conservative form closed with the Peng-Robinsion (PR) state equation. Bulk density is adjusted to obtain a bulk pressure of approximately pb = 1.1pcr where pcr is the critical pressure of the working fluid. Top-to-bottom temperature differences investigated are DT = 5 K, 10 K, and 20 K, where Ttop/bot = Tpb +- DT / 2; buoyancy effects are neglected. Varying DT modifies the average location of pseudophase change from ypb/h = -0.23 (DT = 5 K) to 0.89 (DT = 20 K), where h is the channel half-height and y = 0 the centerline position. Real-fluid effects cause visible deviations from classical scaling laws in the mean velocity profile. Enstrophy generation due stretching and tilting decreases with DT. The proximity to the pseudotransitioning layer inhibits the intensity of the velocity fluctuations, while enhancing the density and temperature fluctuations. Conditional probability analysis reveals that the sheet of fluid undergoing pseudophase change is characterized by a dramatic reduction in the kurtosis of density fluctuations and becomes thinner as DT is increased. Instantaneous visualizations show dense fluid ejections from the pseudoliquid viscous sublayer, some reaching the channel core, causing positive values of density skewness in the respective buffer-layer region (vice versa for the top wall).
Fast Computation of Combustion Phasing and its Influence on Classifying Random or Deterministic Patterns (2015)

The classification between a sequence of highly variable combustion events that have an underlying deterministic pattern and a sequence of combustion events with similar level of variability but random characteristics is important for control of combustion phasing. In the case of high cyclic variation (CV) with underlying deterministic patterns, it is possible to apply closed loop combustion control on a cyclic-basis with a fixed mean value, such as injection timing in homogeneous charge compression ignition (HCCI) or spark timing in spark ignition (SI) applications, to contract the CV. In the case of a random distribution, the high CV can be avoided by shifting operating conditions away from the unstable region via advancing or retarding the injection timing or the spark timing in the mean-sense. Therefore, the focus of this paper is on the various methods of computing CA50 for analysing and classifying cycle-to-cycle variability. The assumptions made to establish fast and possibly on-line methods can alter the distribution of the calculated parameters from cycle-to-cycle, possibly leading to incorrect pattern interpretation and improper control action. Finally, we apply a statistical technique named “permutation entropy” for the first time on classifying combustion patterns in HCCI and SI engine for varying operating condition. Then the various fast methods for computing CA50 feed the two statistical methods, permutation and the Shannon entropy, and their differences and similarities are highlighted.
Mechanistic insight into RET kinase inhibitors targeting the DFG-out conformation in RET-rearranged cancer (2017)

Oncogenic fusion events have been identified in a broad range of tumors. Among them, RET rearrangements represent distinct and potentially druggable targets that are recurrently found in lung adenocarcinomas. Here, we provide further evidence that current anti-RET drugs may not be potent enough to induce durable responses in such tumors. We report that potent inhibitors such as AD80 or ponatinib that stably bind in the DFG-out conformation of RET may overcome these limitations and selectively kill RET-rearranged tumors. Using chemical genomics in conjunction with phosphoproteomic analyses in RET-rearranged cells we identify the CCDC6-RETI788N mutation and drug-induced MAPK pathway reactivation as possible mechanisms, by which tumors may escape the activity of RET inhibitors. Our data provide mechanistic insight into the druggability of RET kinase fusions that may be of help for the development of effective therapies targeting such tumors.
High-speed label-free photoacoustic histopathology (2020)

In tumor resection surgery, the entire tumor must be removed to prevent local recurrence of cancer. To achieve effective and successful tumor resection surgery, an intraoperative examination is performed for quick decision-making during the surgical process. Examination of frozen sections is a common method, but it has limitations that it requires time-consuming tissue processing procedures which leads to interpretation errors. Photoacoustic microscopy (PAM) with ultraviolet (UV) laser is a promising intraoperative surgical margin assessment method that provides depth-resolved and label-free imaging of cell nuclei without sectioning and staining. Despite these advantages, conventional PAM still has limited imaging speed that does not allow real-time imaging, because it achieves the volumetric images by raster scanning using 2-axis step motors. To overcome the limitation, we developed a high-speed reflection-mode OR-PAM based on a UV scanner. Using the scanner module, it took 180 seconds to acquire one volumetric data over 1 &times; 1 mm<sup>2</sup>. In an <i>in-vitro</i> test, the measured lateral and axial resolution were 1.2 &mu;m and 65.1 &mu;m, respectively. We performed ex-vivo experiments on paraffin sections of tissues after deparaffinization that had been excised from a kidney, liver, colon-cancer and a liver-cancer patient. We could find structures in tumorous tissues distinguishable from normal tissues in 4 &times; 8 mm<sup>2</sup> which is clinically meaningful FOV. We could also identify single nucleus in UV-PAM images, and match it with the corresponding nucleus in microscopic images.
Dynamic Security Optimization for N-1 Secure Operation of Power Systems with 100% Non-Synchronous Generation: First experiences from Hawai'i Island (2021)

This paper presents some of our first experiences and findings in the ARPA-E project ReNew100, which is to develop an operator support system to enable stable operation of power system with 100% non-synchronous (NS) generation. The key to 100% NS system, as found in many recent studies, is to establish the grid frequency reference using grid-forming (GFM) inverters. In this paper, we demonstrate in Electro-Magnetic-Transient (EMT) simulations, based on Hawai'i big island system with 100% NS capacity, that a system can be operated stably with the help of GFM inverters and appropriate controller parameters for the inverters. The dynamic security optimization (DSO) is introduced for optimizing the inverter control parameters to improve stability of the system towards N-1 contingencies. DSO is verified for five critical N-1 contingencies of big island system identified by Hawaiian Electric. The simulation results show significant stability improvement from DSO. The results in this paper share some insight, and provide a promising solution for operating grid in general with high penetration or 100% of NS generation.
ChemInform Abstract: Recent Applications of DAST and Ruppert′s Reagent to the Fluorination and Trifluoromethylation of Carbohydrate Compounds (1999)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Mast cells mediate substance P-induced bladder inflammation through an NK1receptor-independent mechanism (2002)

The role of neurokinin-1 receptors (NK1R) in the interaction between mast cells and substance P (SP) in bladder inflammation was determined. Mast cell-deficient Kit(W)/Kit(W-v), congenic normal (+/+), and Kit(W)/Kit(W-v) mice that were reconstituted with bone marrow cells isolated from NK1R(-/-) mice were challenged by instillation of SP, antigen, or saline into the urinary bladder. Twenty-four hours after challenge, the bladders were prepared for morphological assessment and gene expression. SP-induced bladder inflammation was mast cell dependent and did not require NK1R expression on the mast cell. Cluster analysis identified functionally significant genes that were dependent on the presence of mast cells for their upregulation regardless of stimulus. Those include serine protein inhibitor 2.2, maspin, mitogen- and stress-activated protein kinase 2, and macrophage colony-stimulating factor 1. Our findings demonstrate that while mast cells are essential for both antigen- and SP-induced bladder inflammation, there are common genes and unique genes expressed in each type of inflammatory reaction. When combined with unique animal models, gene array analysis provides a useful approach for identifying and characterizing pathways involved in bladder inflammation.
Data from Genetic Alterations in the PI3K/AKT Pathway and Baseline AKT Activity Define AKT Inhibitor Sensitivity in Breast Cancer Patient-derived Xenografts (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;AZD5363/capivasertib is a pan-AKT catalytic inhibitor with promising activity in combination with paclitaxel in triple-negative metastatic breast cancer harboring PI3K/AKT-pathway alterations and in estrogen receptor–positive breast cancer in combination with fulvestrant. Here, we aimed to identify response biomarkers and uncover mechanisms of resistance to AZD5363 and its combination with paclitaxel.&lt;/p&gt;Experimental Design:&lt;p&gt;Genetic and proteomic markers were analyzed in 28 HER2-negative patient-derived xenografts (PDXs) and in patient samples, and correlated to AZD5363 sensitivity as single agent and in combination with paclitaxel.&lt;/p&gt;Results:&lt;p&gt;Four PDX were derived from patients receiving AZD5363 in the clinic which exhibited concordant treatment response. Mutations in &lt;i&gt;PIK3CA&lt;/i&gt;/&lt;i&gt;AKT1&lt;/i&gt; and absence of mTOR complex 1 (mTORC1)-activating alterations, for example, in &lt;i&gt;MTOR&lt;/i&gt; or &lt;i&gt;TSC1&lt;/i&gt;, were associated with sensitivity to AZD5363 monotherapy. Interestingly, excluding &lt;i&gt;PTEN&lt;/i&gt; from the composite biomarker increased its accuracy from 64% to 89%. Moreover, resistant PDXs exhibited low baseline pAKT S473 and residual pS6 S235 upon treatment, suggesting that parallel pathways bypass AKT/S6K1 signaling in these models. We identified two mechanisms of acquired resistance to AZD5363: cyclin D1 overexpression and loss of &lt;i&gt;AKT1&lt;/i&gt; p.E17K.&lt;/p&gt;Conclusions:&lt;p&gt;This study provides insight into putative predictive biomarkers of response and acquired resistance to AZD5363 in HER2-negative metastatic breast cancer.&lt;/p&gt;&lt;/div&gt;
Competition between distinct ApoE alleles and mCRP for the endothelial receptor CD31 differentially regulates neurovascular inflammation and Alzheimer’s disease pathology (2021)

Abstract BACKGROUND C-reactive protein (CRP) in peripheral inflammation is associated with increased Alzheimer’s disease (AD) risk in Apolipoprotein E4 (ApoE4), but not ApoE3 or E2, humans. It remains unknown whether peripheral monomeric CRP (mCRP) induces AD pathogenesis through some receptor of blood-facing endothelia in the brain in an ApoE genotype dependent fashion. METHODS We used human samples, ApoE knock-in and deficient mouse models, and primary brain endothelia. Different ApoE mice were intraperitoneally (i.p.) injected with mCRP. The characterizations by immunostaining, proximity ligation assay (PLA) and siRNA were conducted to identify the receptor for mCRP. Brain microvessel and endothelia were isolated for RNA sequencing to explore the molecular pathway. RESULTS We demonstrate that CD31 (PECAM-1), a blood-facing endothelial receptor in brain, is a competitive target of both mCRP and ApoE protein. ApoE2 competes more strongly with mCRP for CD31 than ApoE4 does, and expressing ApoE4 or knocking out ApoE gene results in higher levels of mCRP-CD31 binding, leading to a decrease of CD31 expression but an increase in CD31 phosphorylation, along with greater cerebrovascular damage and AD pathology. This competitive binding mediates differential endothelial molecular responses depending on ApoE genotype, increasing cerebrovascular inflammation and mitochondria impairment in ApoE4 mice, while inducing vasculogenesis and protective changes in the presence of ApoE2. CONCLUSIONS Our study reveals a novel and dynamic endothelial ApoE-mCRP-CD31 pathway for AD pathogenesis during chronic inflammation and provides some insight into the opposing ApoE4-neurodegenerative and ApoE2-neuroprotective effects in AD. Clinical Perspective WHAT IS NEW? CD31 is a competitive target of both mCRP and ApoE in brain endothelia in an ApoE-allele dependent pattern mCRP increases CD31 phosphorylation in the brain endothelia and damages cerebrovasculature in ApoE4 carriers and AD brains mCRP expression results in neuroprotective or neurodegenerative pathway activation in an ApoE-dependent manner WHAT ARE THE CLINICAL IMPLICATIONS? Although ApoE4 is a major genetic risk factor of AD, some ApoE4 carriers do not develop AD by the age of 90. Elderly people often experience peripheral inflammatory attacks and develop chronic low-grade inflammation, which results in the formation and release of mCRP. Because CRP is routine clinical laboratory test, clinicians can use blood CRP level to predict AD risk in ApoE4 carriers. Evidence of Apoe4 genotype and chronic low-grade inflammation stages marked by elevated CRP levels should be targeted in personalized treatment and clinical trials for AD.