gebhart/patrepeval huggingface dataset:
The Carboxyl-terminal Tyrosine Residue of Protein-tyrosine Phosphatase α Mediates Association with Focal Adhesion Plaques (2000)

The receptor protein-tyrosine phosphatase alpha (PTPalpha) is involved in the activation of c-Src kinase as well as in down-regulation of the insulin signal. To investigate the role of PTPalpha in activation of the Src kinase in more detail we tried to overexpress this phosphatase in NIH3T3 fibroblasts. Although PTPalpha has been overexpressed in rat embryonic fibroblasts and in embryonic carcinoma cells and should increase mitogenic responses we were not able to achieve a detectable overexpression. In contrast, expression of partially (C442S) or completely inactive (C442S,C732S) PTPalpha or of phosphatase active PTPalpha containing mutation Y781F or Y798F was possible. The level of expression, however, was reduced to background after several passages of lines expressing PTPalphaC442S,C732S and PTPalphaY781F. When employed in a focus formation assay, only infection with virus encoding PTPalphaY798F induced Src-dependent formation of foci. In immunofluorescence studies, PTPalphaC442S and PTPalphaY781F but not PTPalphaY798F colocalized with proteins found in focal adhesion plaques. Treatment of PTPalphaC442S-overexpressing cells with vanadate abolished this colocalization and led to proteolytic processing of the phosphatase. We conclude that tyrosine 798 in PTPalpha is important for localization at focal adhesion plaques. Inhibition of phosphatases by vanadate treatment releases PTPalpha from focal adhesions.
Analytical modeling for what-if analysis in complex cloud computing applications (2013)

Modern cloud applications are complex distributed systems with tens or hundreds of interacting software components. An important management task in cloud computing platforms is to predict the impact of a certain workload or reconfiguration change on the performance of the application. Such predictions require the design of "what-if" models of the application that take as input hypothetical changes in the application's workload or environment and estimate its impact on performance. We present a workload-based what-if analysis system that uses commonly available monitoring information in large scale systems to enable the administrators to ask a variety of workload-based "what-if" queries about the system. We use a network of queues to analytically model the behavior of large distributed cloud applications. Our system automatically generates node-level queueing models and then uses model composition to build system-wide models. We employ a simple what-if query language and an intelligent query execution algorithm that employs on-the-fly model construction and a change propagation algorithm to efficiently answer queries on large scale systems. We have built a prototype and have used traces from two large production cloud bapplications from a financial institution as well as real-world synthetic applications to evaluate its what-if modeling framework. Our experimental evaluation validates the accuracy of our node-level resource usage, latency and workload models and then shows how our system enables what-if analysis in four different cloud applications.
Similarities between Immunoglobulins and Transplantation Antigens in Amino‐Acid Sequence and Disulfide‐Bond Distribution (1979)

Papain‐solubilized HLA‐A, HLA‐B and HLA‐C antigens (referred to as HLA antigens) were cleaved by limited proteolysis to yield two large fragments. The NH 2 ‐terminal 20000‐ M r fragment contains one immunoglobulin‐like disulfide bridge which encompasses some 55–60 amino acid residues. The other fragment, with a molecular weight of about 12000, is devoid of carbohydrate but contains an immunoglobulin‐like disulfide bond. Fragments of similar sizes were also obtained when the isolated HLA antigen heavy chain was subjected to acid cleavage in 70% formic acid. The combined amino acid content of the isolated 22000‐ M r and 11000‐ M r acid cleavage fragments was very similar, if not identical, to that of the intact 33000‐ M r HLA antigen heavy chain. These data suggested that the acid preferentially cleaved a single aspartyl‐prolyl bond in the heavy chain, as supported by the fact that the 11000‐ M r fragment had proline as its NH 2 ‐terminal residue. Each one of the two acid cleavage fragments contained an immunoglobulin‐like disulfide bridge. While the 41 NH 2 ‐terminal residues of the intact HLA antigen heavy chain did not display any homology with immunoglobulin sequences, the 31 NH 2 ‐terminal residues of the 11000‐ M r acid cleavage fragment displayed as much homology with β 2 ‐microglobulin and the constant immunoglobulin homology regions as they did among themselves. This information strongly suggests that immunoglobulins, β 2 ‐microglobulin and the HLA antigen heavy chains have had a related evolution. Moreover, the HLA antigen heavy chain has most probably arisen by a gene duplication event involving the same ancestral gene which gave rise to the immunoglobulin chains.
Structural, Biochemical, and Phylogenetic Analyses Suggest That Indole-3-Acetic Acid Methyltransferase Is an Evolutionarily Ancient Member of the SABATH Family (2007)

The plant SABATH protein family encompasses a group of related small-molecule methyltransferases (MTs) that catalyze the S-adenosyl-L-methionine-dependent methylation of natural chemicals encompassing widely divergent structures. Indole-3-acetic acid (IAA) methyltransferase (IAMT) is a member of the SABATH family that modulates IAA homeostasis in plant tissues through methylation of IAA's free carboxyl group. The crystal structure of Arabidopsis (Arabidopsis thaliana) IAMT (AtIAMT1) was determined and refined to 2.75 A resolution. The overall tertiary and quaternary structures closely resemble the two-domain bilobed monomer and the dimeric arrangement, respectively, previously observed for the related salicylic acid carboxyl methyltransferase from Clarkia breweri (CbSAMT). To further our understanding of the biological function and evolution of SABATHs, especially of IAMT, we analyzed the SABATH gene family in the rice (Oryza sativa) genome. Forty-one OsSABATH genes were identified. Expression analysis showed that more than one-half of the OsSABATH genes were transcribed in one or multiple organs. The OsSABATH gene most similar to AtIAMT1 is OsSABATH4. Escherichia coli-expressed OsSABATH4 protein displayed the highest level of catalytic activity toward IAA and was therefore named OsIAMT1. OsIAMT1 exhibited kinetic properties similar to AtIAMT1 and poplar IAMT (PtIAMT1). Structural modeling of OsIAMT1 and PtIAMT1 using the experimentally determined structure of AtIAMT1 reported here as a template revealed conserved structural features of IAMTs within the active-site cavity that are divergent from functionally distinct members of the SABATH family, such as CbSAMT. Phylogenetic analysis revealed that IAMTs from Arabidopsis, rice, and poplar (Populus spp.) form a monophyletic group. Thus, structural, biochemical, and phylogenetic evidence supports the hypothesis that IAMT is an evolutionarily ancient member of the SABATH family likely to play a critical role in IAA homeostasis across a wide range of plants.
Supp Figure 3 from Involvement of Epigenetics and EMT-Related miRNA in Arsenic-Induced Neoplastic Transformation and Their Potential Clinical Use (2023)

&lt;p&gt;Supp Figure 3. Association of miRNA expression with water arsenic concentration and creatinine adjusted urine arsenic concentration (Mann-Whitney U test).&lt;/p&gt;
Enabling Sustainable Clouds: The Case for Virtualizing the Energy System (2021)

Cloud platforms' growing energy demand and carbon emissions are raising concern about their environmental sustainability. The current approach to enabling sustainable clouds focuses on improving energy-efficiency and purchasing carbon offsets. These approaches have limits: many cloud data centers already operate near peak efficiency, and carbon offsets cannot scale to near zero carbon where there is little carbon left to offset. Instead, enabling sustainable clouds will require applications to adapt to when and where unreliable low-carbon energy is available. Applications cannot do this today because their energy use and carbon emissions are not visible to them, as the energy system provides the rigid abstraction of a continuous, reliable energy supply. This vision paper instead advocates for a ``carbon first'' approach to cloud design that elevates carbon-efficiency to a first-class metric. To do so, we argue that cloud platforms should virtualize the energy system by exposing visibility into, and software-defined control of, it to applications, enabling them to define their own abstractions for managing energy and carbon emissions based on their own requirements.
Absolute Security in High-Frequency Wireless Links (2022)

Security against eavesdropping is one of the key concerns in the design of any communication system. Many common considerations of the security of a wireless communication channel rely on comparing the signal level measured by Bob (the intended receiver) to that accessible to Eve (an eavesdropper). Frameworks such as Wyner's wiretap model ensure the security of a link, in an average sense, when Bob's signal-to-noise ratio exceeds Eve's. Unfortunately, because these guarantees rely on statistical assumptions about noise, Eve can still occasionally succeed in decoding information. The goal of achieving exactly zero probability of intercept over an engineered region of the broadcast sector, which we term absolute security, remains elusive. Here, we describe the first architecture for a wireless link which provides absolute security. Our approach relies on the inherent properties of broadband and high-gain antennas, and is therefore ideally suited for implementation in millimeter-wave and terahertz wireless systems, where such antennas will generally be employed. We exploit spatial minima of the antenna pattern at different frequencies, the union of which defines a wide region where Eve is guaranteed to fail regardless of her computational capabilities, and regardless of the noise in the channels. Unlike conventional zero-forcing beam forming methods, we show that, for realistic assumptions about the antenna configuration and power budget, this absolute security guarantee can be achieved over most possible eavesdropper locations. Since we use relatively simple frequency-multiplexed coding, together with the underlying physics of a diffracting aperture, this idea is broadly applicable in many contexts.
Female Rats Do Not Exhibit Free Fatty Acid–Induced Insulin Resistance (2002)

It is well described that excessive lipid metabolism can cause insulin resistance in both animals and humans, and this has been implicated as a causative factor in the development of insulin resistance and type 2 diabetes in humans. Recently, we have shown that intravenous lipid emulsion (liposyn) infusion during a 120-min euglycemic-hyperinsulinemic clamp led to significant reductions in insulin action and fatty acid translocase (FAT/CD36) skeletal muscle protein expression. After reviewing the literature, it became evident that essentially all past studies, including our own, were conducted in male animals. Therefore, to determine whether there were sex determinants of fat-induced insulin resistance, we assessed the impact of free fatty acid (FFA) elevation on insulin action in female rats. Here, we report that a fourfold elevation in plasma FFA concentration induced a 40% reduction in the insulin-stimulated glucose disposal rate, a 30% decline in insulin-stimulated skeletal muscle insulin substrate receptor-1 (IRS-1) phosphorylation, a 48% decrease in IRS-1-associated phosphatidylinositol (PI) 3-kinase activity, and a 50% reduction in muscle FAT/CD36 protein expression in male rats. In striking contrast, we found no effect of FFA elevation to cause insulin resistance, changes in IRS-1/PI 3-kinase, or FAT/CD36 protein levels in female animals. Our findings indicate that female animals are protected from lipid-induced reductions in insulin action.
The reliability of parafoveal cone density measurements (2014)

With the AOSLOs used here, reliable cone density measurements can be obtained between observers and between instruments. Additional work is needed to determine how these results vary with differences in image quality.
Preserving operational information in spectrum access system with dishonest users (2017)

Privacy has been regarded as one of the most critical issues in light of promoting the development of centralized spectrum management, hence attracting wide attention. However, researchers in the current literature are usually protecting users' privacy based on the assumption that all users are honest, which is reasonable but not practical. In this paper, we investigate the privacy issue among different tiers of users in the centralized spectrum access system (SAS), mainly focusing on honest Priority Access Licenses (PALs) and dishonest General Authorized Accesses (GAAs). To that end, we propose an authentication scheme to prevent GAAs from using other users' information by the aid of a public key cryptosystem. Moreover, we propose a “punishment and forgiveness” scheme, which draws support from GAAs' reputation stores (RSs) and reputation histories (RHs), to encourage GAAs to engage in positive and true activities. Besides, we propose a privacy preservation scheme cooperating with the “punishment and forgiveness” scheme (PS-PFS) in order to effectively mitigate the impact of dishonest users while fully preserving all users' privacy as well as successfully realizing spectrum sharing.
A randomized phase II study of a novel antigen-presenting cell-targeted hCG-β vaccine (the CDX-1307 regimen) in muscle-invasive bladder cancer. (2010)

TPS228 Background: hCG-β is frequently expressed and correlates with poor prognosis in a number of common epithelial cancers (Iles 2007). Patients (pts) with invasive bladder cancer and elevated hCG-β levels are much more likely to develop metastasis and die earlier (Iles 1996). We have developed a dendritic cell-targeted vaccine, CDX-1307, by genetically coupling hCG-β to a human monoclonal antibody targeting mannose receptors. CDX-1307 efficiently stimulates both MHC-I and II hCG-β-specific T-cell responses in vitro (Ramakrishna 2004/2007). CDX-1307 has completed a phase I study to define an immunogenic regimen and safety profile for phase II studies. The study design included administration in combination with GM-CSF (GM), the TLR3 agonist Poly-ICLC (PIC), and/or the TLR7/8 agonist resiquimod (R), in pts with advanced cancers known to frequently express hCG-β (Morse, iSBTc 2009). Treatment was well tolerated with no DLT. Significant hCG-β–specific cellular and humoral immune responses were detected in pts receiving the combination with all 3 adjuvants. Indications of clinical benefit (disease stabilization and/or reduction in tumor markers) were seen in a subset of patients. These data support further evaluation in newly diagnosed, resectable, hCG-β+ bladder cancer pts, who may have greatest potential for response to immunologic intervention. Methods: A phase II, multicenter trial randomizes (1:1) 60 chemo-naive pts with newly diagnosed, nonmetastatic, resectable, muscle invasive, hCG-β+ bladder cancer to (a) neoadjuvant gemcitabine/cisplatin chemotherapy (GC) or (b) CDX-1307 (2.5 mg) with GM, PIC and R (the CDX-1307 regimen), both with neoadjuvant GC and in the adjuvant setting to prolong immunity. The primary efficacy objective is to estimate the 2-year PFS (95% confidence interval extending ≤18.5% about the point estimate). Besides safety and immune response (during neoadjuvant GC and adjuvantly), additional antitumoral effect will be assessed including radiographic and pathologic tumor response to neoadjuvant vaccination, immune response at the tumor site and persistence of hCG-b expression. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celldex Therapeutics Celldex Therapeutics Celldex Therapeutics
Hydrolytic Condensation of Tin(IV) Alkoxide Compounds to Form Particles with Well‐Defined Morphology (1991)

The sol‐gel‐type condensation of tin(IV) ethoxide [Sn(OEt) 4 ] n (where OEt is ethoxide) under basic conditions produced spherical, submicrometer‐sized tin(IV) oxide (cassiterite) particles. Transmission electron microscopy and powder X‐ray diffraction data indicated that the grain size was approximately 20 to 30 Å (2 to 3 nm). The mixed‐metal alkoxide compound [ZnSn(OEt) 6 ] was hydrolyzed under analogous conditions to give either spherical or octahedral submicrometer‐sized crystalline particles of ZnSn(OH) 6 depending on the solvents used. These data demonstrated that the stoichiometry of the mixed‐metal alkoxide precursor was retained during condensation. Thermal treatment of ZnSn(OH) 6 resulted in crystallization of ZnSnO 3 at approximately 676°C. At neutral pH, hydrolysis of [ZnSn(OEt) 6 ] resulted in formation of a high surface area (261 m 2 /g) amorphous powder.
The dance of the nanobubbles: detecting acoustic backscatter from sub-micron bubbles using ultra-high frequency acoustic microscopy (2020)

Nanobubbles have gained attention for their use as highly stable ultrasound (US) contrast agents, but assessment of individual nanobubble size remains a challenge. Current sizing techniques require either extensive sample preparation or depend on assumed values of nanobubble density that are not well characterized. An US based approach would be desirable; however, probing individual nanobubbles using US transducers at clinical frequencies is not feasible due to the comparatively long acoustic wavelengths employed. Here we present a technique which can be used to estimate nano- or microbubble size by virtue of the amount of motion detected in an M-Mode image acquired using an acoustic microscope equipped with a 200 MHz transducer. A sample of a bubble-containing solution is incorporated into a phantom composed of molten agarose. The solidified agarose gel contains pores with well-defined sizes dictated by the agarose concentration. Bubbles in the gel matrix that are smaller in diameter than the gel pore size are capable of undergoing stochastic motion which manifests as intensity fluctuations in M-Mode images. Conversely, bubbles which are larger than the agarose pores become trapped and produce static M-Mode intensity patterns. In this study, agarose gels with concentrations ranging from 0.25% to 1.25% (mean pore sizes ranging from 2.68 μm to 0.34 μm) were loaded with either nanobubbles (mean diameter 0.326 μm) or microbubbles (mean diameter 2.71 μm) and imaged at 200 MHz. In the nanobubble loaded gels, M-Mode fluctuations were clearly visible up to a gel concentration of 1% (pore size of 0.39 μm). In contrast, the microbubble loaded gels exhibited minimal M-Mode fluctuation even at agarose concentrations of 0.25% (2.68 μm pore size). Autocorrelation curves generated from the M-Mode data demonstrated a clear trend of curve flattening (loss of motion) when the pore size was comparable to mean bubble diameter, indicating that individual bubbles trapped in the agarose pores are the main source of acoustic backscatter. In the future, decay parameters extracted from the autocorrelation curves could potentially be used as indicators of mean bubble diameter for bubble populations of unknown size.
Simple methods of measuring the net photorefractive phase shift and coupling constant (1993)

We report measurements of the photorefractive phase shift and coupling constant of several photorefractive materials. We solve the problem of beam coupling and diffraction in a material with a dynamically written grating for arbitrary input beams. These solutions are used to determine the beam coupling as a function of the photorefractive phase ø and coupling constant g when one beam is either sinusoidally phase modulated or ramped in phase. Experimental results are obtained for LiNbO(3), BaTiO(3), and for paraelectric potassium lithium tantalate niobate as a function of applied electric field.
Microglial pannexin-1 channel activation is a spinal determinant of joint pain (2018)

Chronic joint pain such as mechanical allodynia is the most debilitating symptom of arthritis, yet effective therapies are lacking. We identify the pannexin-1 (Panx1) channel as a therapeutic target for alleviating mechanical allodynia, a cardinal sign of arthritis. In rats, joint pain caused by intra-articular injection of monosodium iodoacetate (MIA) was associated with spinal adenosine 5'-triphosphate (ATP) release and a microglia-specific up-regulation of P2X7 receptors (P2X7Rs). Blockade of P2X7R or ablation of spinal microglia prevented and reversed mechanical allodynia. P2X7Rs drive Panx1 channel activation, and in rats with mechanical allodynia, Panx1 function was increased in spinal microglia. Specifically, microglial Panx1-mediated release of the proinflammatory cytokine interleukin-1β (IL-1β) induced mechanical allodynia in the MIA-injected hindlimb. Intrathecal administration of the Panx1-blocking peptide <sup>10</sup>panx suppressed the aberrant discharge of spinal laminae I-II neurons evoked by innocuous mechanical hindpaw stimulation in arthritic rats. Furthermore, mice with a microglia-specific genetic deletion of Panx1 were protected from developing mechanical allodynia. Treatment with probenecid, a clinically used broad-spectrum Panx1 blocker, resulted in a striking attenuation of MIA-induced mechanical allodynia and normalized responses in the dynamic weight-bearing test, without affecting acute nociception. Probenecid reversal of mechanical allodynia was also observed in rats 13 weeks after anterior cruciate ligament transection, a model of posttraumatic osteoarthritis. Thus, Panx1-targeted therapy is a new mechanistic approach for alleviating joint pain.
The Discovery/Development Transition (2018)

This chapter focuses on the conviction that minimizing the time to the first dose in man (FIM) is an important competitive advantage during drug development. The time from the first synthesis (FS) of a compound in discovery to the FIM can be minimized during the discovery/development transition. The strategies that one company (Bristol-Myers Squibb, BMS) used to effect this time in the mid-1990s, as well as the rationale for doing so, are detailed. Their application today in BMS, small biotech, and contract manufacturing and research organizations (CMOs, CROs) suggests that they are still relevant 20 years later and will likely remain relevant for the foreseeable future. The chapter briefly discusses some examples to highlight the importance of CROs in today's pharmaceutical research and development ecosystem. One of the fundamental changes in the industry has been the growth of the small biotechnology sector.
Assessment of Fluid Status in Peritoneal Dialysis (2012)

Fluid management is recognized as a basic component of management of patients on dialysis. Fluid overload is an important adverse factor in patient outcomes, and the negative effects of fluid depletion, including on residual renal function, are also increasingly being recognized. The complexities of fluid distribution in renal failure need to be understood to inform assessment of hydration. Clinical assessment of hydration is insensitive to abnormalities in hydration. BIA is the most promising technique for objective assessment of fluid status, but it is essential that the underlying principles and limitations are understood, and that results from BIA are utilized in conjunction with clinical assessment rather than in isolation.