gebhart/patrepeval huggingface dataset:
Role of phosphatidylinositol 3,4,5-trisphosphate in regulating the activity and localization of 3-phosphoinositide-dependent protein kinase-1 (1999)

3-Phosphoinositide-dependent protein kinase-1 (PDK1) interacts stereoselectively with the d-enantiomer of PtdIns(3,4,5)P3 (KD 1.6 nM) and PtdIns(3,4)P2 (KD 5.2 nM), but binds with lower affinity to PtdIns3P or PtdIns(4,5)P2. The binding of PtdIns(3,4,5)P3 to PDK1 was greatly decreased by making specific mutations in the pleckstrin homology (PH) domain of PDK1 or by deleting it. The same mutations also greatly decreased the rate at which PDK1 activated protein kinase Balpha (PKBalpha) in vitro in the presence of lipid vesicles containing PtdIns(3,4,5)P3, but did not affect the rate at which PDK1 activated a PKBalpha mutant lacking the PH domain in the absence of PtdIns(3,4,5)P3. When overexpressed in 293 or PAE cells, PDK1 was located at the plasma membrane and in the cytosol, but was excluded from the nucleus. Mutations that disrupted the interaction of PtdIns(3,4,5)P3 or PtdIns(4,5)P2 with PDK1 abolished the association of PDK1 with the plasma membrane. Growth-factor stimulation promoted the translocation of transfected PKBalpha to the plasma membrane, but had no effect on the subcellular distribution of PDK1 as judged by immunoelectron microscopy of fixed cells. This conclusion was also supported by confocal microscopy of green fluorescent protein-PDK1 in live cells. These results, together with previous observations, indicate that PtdIns(3,4,5)P3 plays several roles in the PDK1-induced activation of PKBalpha. First, it binds to the PH domain of PKB, altering its conformation so that it can be activated by PDK1. Secondly, interaction with PtdIns(3,4,5)P3 recruits PKB to the plasma membrane with which PDK1 is localized constitutively by virtue of its much stronger interaction with PtdIns(3,4,5)P3 or PtdIns(4,5)P2. Thirdly, the interaction of PDK1 with PtdIns(3,4,5)P3 facilitates the rate at which it can activate PKB.
A Stille cyclisation approach to (−)-periplanone-B: studies in alkene-selective ring-closing metathesis and an improved chromium(II)-mediated synthesis of (E )-alkenylstannanes from aldehydes (1999)

A synthesis of the dienone 7 via an efficient intramolecular Stille cross-coupling reaction, an improved chromium(II)-mediated synthesis of (E)-alkenylstannanes from aldehydes using Bu3SnCHI2 in DMF, and a synthesis of the substituted (–)-dienone 25 via ring-closing alkene metathesis to give dihydropyran 22 are described. The synthesis of (–)-dienone 25 constitutes a formal synthesis of (–)-periplanone-B.
Pathogenic APP mutations near the gamma-secretase cleavage site differentially affect Abeta secretion and APP C-terminal fragment stability (2001)

Release of amyloid beta (Abeta) from the amyloid precursor protein (APP) requires cleavages by beta- and gamma-secretases and plays a crucial role in Alzheimer's disease (AD) pathogenesis. Missense mutations in the APP gene causing familial AD are clustered around the beta-, alpha- and particular gamma-secretase cleavage sites. We systematically compare in primary neurons the effect on APP processing of a series of clinical APP mutations (two of which not characterized before) located in close proximity to the gamma-secretase cleavage site. We confirm and extend previous observations showing that all these mutations (T714I, V715M, V715A, I716V, V717I and V717L) affect gamma-secretase cleavage causing an increased relative ratio of Abeta42 to Abeta40. Taking advantage of these extended series of APP mutations we were able to demonstrate an inverse correlation between these ratios and the age at onset of the disease in the different families. In addition, a subset of mutations caused the accumulation of APP C-terminal fragments indicating that these mutations also influence the stability of APP C-terminal fragments. However, it is unlikely that these fragments contribute significantly to the disease process.
RTSNet: Deep Learning Aided Kalman Smoothing (2022)

The smoothing task is the core of many signal processing applications. It deals with the recovery of a sequence of hidden state variables from a sequence of noisy observations in a one-shot manner. In this work we propose RTSNet, a highly efficient model-based and data-driven smoothing algorithm. RTSNet integrates dedicated trainable models into the flow of the classical Rauch-Tung-Striebel (RTS) smoother, and is able to outperform it when operating under model mismatch and non-linearities while retaining its efficiency and interpretability. Our numerical study demonstrates that although RTSNet is based on more compact neural networks, which leads to faster training and inference times, it outperforms the state-of-the-art, data-driven smoother in a non-linear use case.
Design of PEO‐based ruthenium carbene for aqueous metathesis polymerization. Synthesis by the “macromonomer method” and application in the miniemulsion metathesis polymerization of norbornene (2006)

Abstract Novel water‐soluble ruthenium carbene complexes with finely tuned structure and properties in solution are reported. These ruthenium‐based initiators were found to exhibit great catalytic activity in aqueous miniemulsion ring‐opening metathesis polymerization of norbornene. Stable particles of polynorbornene could be generated in the 200–250 nm size range stabilized with a nonionic surfactant (polystyrene‐ b ‐poly(ethylene oxide)). © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 2784–2793, 2006
A 54% Power-Saving Static Fully-Interruptible Single-Phase-Clocked Shared-Keeper Flip-Flop in 14nm CMOS (2019)

A low clock power, static, fully-interruptible, single-phase-clocked, shared-keeper flip-flop without local clock inverters and no write-back failure reduces the clock transistor count to 6 instead of 12 in conventional transmission-gate flip-flop, achieving 54 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">%</sup> reduction in total cell level power and 100mV improved V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">MIN.</sub> An experimental microcontroller with shared-keeper sequentials, fabricated in 14nm CMOS, shows 6.5% lower measured chip level power at iso-frequency compared to the previously published single-phase-clocked AOI sequentials at 0.75V, 25°C.
Vinylation and polymerization with trivinylaluminum. I. Vinylation of organic halides as a model for termination in cationic polymerization leading to vinyl end groups (1978)

Abstract An improved synthesis of trivinylaluminum (V 3 Al) is described. The proton magnetic resonance (PMR) spectrum of V 3 Al was recorded and analyzed. A new vinylation method involving the use of V 3 Al as the vinylating agent has been developed, and the vinylation of organic halides by V 3 Al was studied at −30, −50 and −70°C. Primary alkyl chlorides, such as methyl and methylene chloride, do not react with V 3 Al and were used as solvents. Secondary chlorides such as 2‐chloropropane also do not react. t ‐Butyl chloride gives rise to t ‐butylethylene (70–98%), depending on reaction conditions, and the allylic chlorides, 3‐chloro‐1‐butene, and 3‐chloro‐3‐methyl‐1‐butene, yield the expected vinylated products and their isomers (∼90%). Allyl and benzyl chloride do not react under the conditions tried. The reaction between V 3 Al and the ditertiary dichloride 2,6‐dichloro‐2,6‐dimethylheptane yields several isomeric C 13 H 24 and C 11 H 20 hydrocarbons; however, surprisingly, C 9 H 16 does not form. The C 13 hydrocarbons arise by divinylation at the termini of the dichloride, while the C 11 hydrocarbons are formed by vinylation at one and proton elimination at the other terminus of the dichloride. The presence of unsaturated C 13 H 24 and C 11 H 20 isomers is most likely due to proton induced isomerization. These results are explained by a proximity effect involving vinylation at one end of the dichloride by V 3 Al followed by rapid reaction of the second chlorine (mostly) by V 2 AlCl generated in situ during the first vinylation in the proximity of the chloride. At the other chlorine terminus V 2 AlCl causes either a second vinylation (leading to C 13 hydrocarbons) or a proton elimination (leading to C 11 hydrocarbons). The absence of C 9 H 16 among the reaction products indicates that V 3 Al exclusively effects vinylation. The RCl + V 3 Al ← RV + V 2 AlCl reaction may be regarded as a model for initiation followed by immediate termination in cationic olefin polymerization, a process leading to vinyl‐ended polymers.
Gangliosides induce autophagic cell death in astrocytes (2010)

Gangliosides released under pathological conditions may induce autophagic cell death of astrocytes, identifying a neuropathological role for gangliosides.
PPDL - Privacy Preserving Deep Learning Using Homomorphic Encryption (2022)

Deep Learning Models such as Convolution Neural Networks (CNNs) have shown great potential in various applications. However, these techniques will face regulatory compliance challenges related to privacy of user data, especially when they are deployed as a service on a cloud platform. Such concerns can be mitigated by using privacy preserving machine learning techniques. The purpose of our work is to explore a class of privacy preserving machine learning technique called Fully Homomorphic Encryption in enabling CNN inference on encrypted real-world dataset. Fully homomorphic encryption face the limitation of computational depth. They are also resource intensive operations. We run our experiments on MNIST dataset to understand the challenges and identify the optimization techniques. We used these insights to achieve the end goal of enabling encrypted inference for binary classification on melanoma dataset using Cheon-Kim-Kim-Song (CKKS) encryption scheme available in the open-source HElib library.
Piezoelectric buckling-based NEMS relays for millivolt mechanical logic (2014)

We report on the design, fabrication, characterization, and scaling analysis of buckling-based NEMS relays that use, for the first time, piezoelectric actuation. The generated stress from anchored piezoelectric films is employed to buckle a clamped-clamped beam to connect the source and drain, while the residual stress is used to control the actuation voltage. This demonstration is the first of its kind to exploit residual stress to deliver a highly scalable switching mechanism that exhibits low actuation voltage (~1.8 V), and uniquely achieves an equivalent electric body bias via mechanical methods. Analytical and FEA simulation show a linear dependence of the switching voltage on the residual stress, while the voltage vs. stress tuning slope is reduced linearly with scaling the piezoelectric film thickness (-16.6 mV/MPa for 10 nm thick AlN film). A scaling analysis shows that millivolt switching is possible for aggressively miniaturized relays.
Contribution of pilus type 2b to invasive disease caused by a Streptococcus agalactiae ST-17 strain (2017)

The data suggest an important role of pilus 2b in mediating GBS infection and host cell interaction of strains belonging to the hypervirulent GBS ST-17 lineage.
30 years of American Society for Neural Therapy and Repair (ASNTR): A personal perspective at the intersection of science, politics, and culture (2023)

The American Society for Neural Therapy and Repair (ASNTR) started 30 years ago in 1993 as the American Society for Neural Transplantation (ASNT), with an emphasis on neural transplantation. Through the years, the Society has been shaped as much by our expanding knowledge of neurodegenerative disorders and how to treat them as it has by politics and culture. What once felt like a leash on neuroscience research, has turned into an advantage as neural transplantation evolved into Neural Therapy and Repair. As a Co-Founder this brief commentary provides a personalized account of our research during the Society's years.
Dicer Is Required for Maintaining Adult Pancreas (2009)

Dicer1, an essential component of RNA interference and the microRNA pathway, has many important roles in the morphogenesis of developing tissues. Dicer1 null mice have been reported to die at E7.5; therefore it is impossible to study its function in adult tissues. We previously reported that Dicer1-hypomorphic mice, whose Dicer1 expression was reduced to 20% in all tissues, were unexpectedly viable. Here we analyzed these mice to ascertain whether the down-regulation of Dicer1 expression has any influence on adult tissues. Interestingly, all tissues of adult (8-10 week old) Dicer1-hypomorphic mice were histologically normal except for the pancreas, whose development was normal at the fetal and neonatal stages; however, morphologic abnormalities in Dicer1-hypomorphic mice were detected after 4 weeks of age. This suggested that Dicer1 is important for maintaining the adult pancreas.
Towards adaptive test of multi-core RF SoCs (2013)

This paper discusses how adaptive test techniques can be applied to multi-core RF SoCs, together with design implementation and test challenges. Various techniques specific to RF circuits covering calibration trims, power management modules, co-existence issues, concurrent testing, and test measurements are explained. Results on different designs are presented. Together, they highlight the need and scope of adaptive test for RF circuits, and share a new dimension in the test of multi-core circuits, under different constraints of design, test and test equipment.
Advanced TCAD simulation of local mismatch in 14nm CMOS technology FinFETs (2015)

Local statistical variability (mismatch) is very important in advanced CMOS technologies critically affecting, among others, SRAM supply and holding voltages, performance and yield. TCAD simulation of statistical variability is essential for identification of variability sources and their control in the technology development and optimization. It also plays an important role in the development of accurate statistical compact models for SRAM design, statistical standard cell characterization and statistical circuit simulation and verification. In this paper we compare the TCAD simulation results of statistical variability in 14nm CMOS FinFET technology with Silicon measurements in order to understand the relative role of key statistical variability sources, to assist the technology optimization and to generate target characteristics for statistical compact model extraction.
Bioactive PCL microspheres with enhanced biocompatibility and collagen production for functional hyaluronic acid dermal fillers (2022)

Polymeric microspheres containing magnesium hydroxide (MH) and a bioactive agent (BA), such as apocynin (APO) and astaxanthin (ATX), have been prepared as functional dermal fillers with enhanced physicochemical and biological performance. In this study, polycaprolactone (PCL)-based microspheres were produced with a uniform size of about 30-40 μm by utilizing a membrane emulsification device. MH from the PCL/MH microspheres effectively neutralized acidic products from PCL degradation. For <i>in vitro</i> cell experiments, when acidic degradation products (6-hydroxycaproic acid, HCA) were treated with MH, the acidic pH was neutralized to induce wound healing and suppress inflammation. The microspheres comprised of BA had a sustained release of the BA, without an initial burst release. Remarkably, the ATX added into the microspheres was maintained for 16 weeks and displayed positive attributes, such as tissue regeneration and collagen production improvement, as noted by <i>in vivo</i> testing. Overall, these results suggest that the bioactive PCL microspheres containing ATX have excellent potential as a functional dermal filler for skin aesthetics and facial plastic surgery.
Accurate monitoring of an interferometric fiber-optic sensor with a multimode semiconductor laser (1999)

A technique for monitoring interferometric sensors by correlation of the optical signal from the sensor with the signal from a phase-modulated reference interferometer is described. The technique is applied to temperature measurement with a fiber Fabry-Perot sensing head. We extend the 7 degrees C unambiguous measurement range obtained with a 1.3-mum laser diode as the light source to 43 degrees C by adding a second laser diode emitting at 1.55mum . Experimentally, a rms phase-measurement error of +/-0.28rad , corresponding to a temperature error of +/-0.32 degrees C , was achieved with a low-quality multimode Fabry-Perot laser. The phase error was improved to +/-0.14rad , corresponding to a temperature error of +/-0.16 degrees C , by use of a distributed-feedback laser diode.
Rotationally symmetric wavefront coding for extended depth of focus with annular phase mask (2015)

Wavefront coding (WFC) with a cubic phase mask (CPM) for extended depth of focus (EDOF) has been studied since 1995. However, the asymmetric surface shape of a CPM has several disadvantages, such as necessity of a square aperture, directional artifacts in images, rotational adjustment during assembly, defocus-dependent lateral image displacement, and difficulty in fabrication. To overcome these disadvantages, we propose an annular phase mask (APM) with a rotationally symmetric form. An APM adds the phase of the parabolic profile in plural annuluses and phase steps between annuluses to the penetrating light. We confirmed an EDOF effect comparable to that of a CPM in our APM design by simulation. The depth of focus of a WFC system with the APM was estimated to be about 6.8 times larger than that of a conventional system. The effect observed in the experiments using a fabricated APM is consistent with the simulation result.
Degradation analysis of tribologically loaded carbon nanotubes and carbon onions (2023)

Abstract Coating laser-patterned stainless-steel surfaces with carbon nanotubes (CNT) or carbon onions (CO) forms a tribological system that provides effective solid lubrication. Lubricant retention represents the fundamental mechanism of this system, as storing the particles inside the pattern prevents lubricant depletion in the contact area. In previous works, we used direct laser interference patterning to create line patterns with three different structural depths on AISI 304 stainless-steel platelets. Electrophoretic deposition subsequently coated the patterned surfaces with either CNTs or COs. Ball-on-disc friction tests were conducted to study the effect of structural depth on the solid lubricity of as-described surfaces. The results demonstrated that the shallower the textures, the lower the coefficient of friction, regardless of the applied particle type. This follow-up study examines the carbon nanoparticles’ structural degradation after friction testing on substrates patterned with different structural depths (0.24, 0.36, and 0.77 µm). Raman characterization shows severe degradation of both particle types and is used to classify their degradation state within Ferrari’s three-stage amorphization model. It was further shown that improving CNT lubricity translates into increasing particle defectivity. This is confirmed by electron microscopy, which shows decreasing crystalline domains. Compared to CNTs, CO-derived tribofilms show even more substantial structural degradation.
Effect of Combination Endocrine Therapy (LHRH Agonist and Flutamide) on Normal Prostate and Prostatic Adenocarcinoma (1991)

The histopathology of 23 radical prostatectomies from patients with prostatic adenocarcinoma pretreated for 3-6 months with combination therapy including a luteinizing hormone-releasing hormone agonist and the antiandrogen drug flutamide was reviewed and compared with the pretreatment biopsies or transurethral resection material. After combination therapy, benign prostatic glands showed marked atrophy with prominent basal-cell layers, basal-cell hyperplasia, and epithelial-cell vacuolization. Immature squamous-cell metaplasia was present in seven cases. Residual carcinoma, on the other hand, was found in 19 of the 23 cases, and in 8 of these, tumor cells were either vacuolated or had scanty cytoplasm. Residual tumor was present as only one focus in 13 cases, and in 3 of these it was composed of single cells with a "hemangiopericytoma-like" pattern. An immunohistochemical study for prostatic acid phosphatase and prostatic-specific antigen could be carried out on paraffin blocks from 19 biopsies and 18 prostatectomies. After combination therapy, a reduction in staining (intensity and number of positive cells) was observed for the two markers in both normal prostate and carcinoma but with more pronounced effects on the latter. The present data show that temporary combination therapy before radical prostatectomy causes marked and very characteristic changes in normal prostatic tissue as well as in the prostatic tumor. These histologic patterns enter the differential diagnosis of a variety of atrophic, metaplastic, and proliferative lesions of the prostate gland. The pathologist must be aware of these histologic changes when looking at biopsy or resection material of treated patients.
Accurate Sequence Alignment using Distributed Filtering on GPU Clusters (2011)

Abstract—Advent of next generation gene sequencing machines has led to computationally intensive alignment problems that can take many hours on a modern computer. Considering the fast increasing rate of introduction of new short sequences that are sequenced, the large number of existing sequences and inaccuracies in the sequencing machines, short sequence alignment has become a major challenge in High Performance Computing. In practice gaps as well as mismatches are found in genomic sequences, resulting in an edit distance problem. In this paper we describe the design of a distributed filter, based on shifted masks, to quickly reduce the number of potential matches in the presence of gaps and mismatches. Furthermore, we present a hybrid dynamic programming method, optimized for GPGPU targets, to process the filter outputs and find the accurate number of insertions, deletions and mismatches. Finally we present results from experiments performed on an NCSA cluster of 128 GPU units using the Hadoop framework. I.
Abstract 2808: Characterization of KRAS rearrangements in metastatic prostate cancer (2011)

Abstract In this study, we employed a novel integrative genomic-based approach to explore driving gene fusions contributing to the progression of advanced prostate cancer. This method, called amplification breakpoint ranking and assembly (ABRA), leverages the in vivo amplification and breakpoint analysis in cancer cells to assemble novel gene fusions and predict their tumorigenicity. Using ABRA, we nominated KRAS as a gene fusion with the ubiquitin-conjugating enzyme UBE2L3 in the DU145 cell line- which was originally derived from a metastatic prostate cancer to the brain. Interestingly, analysis of tissues revealed that 2 out of 62 metastatic prostate cancers harbored aberrations at the KRAS locus. In DU145 cells, UBE2L3-KRAS produces a chimerical protein which is readily ubiquitinated and relative instable, whereas specific knock-down of the fusion attenuates cell invasion and xenograft growth. Further, ectopic expression of the UBE2L3-KRAS fusion protein in NIH 3T3 fibroblasts and RWPE prostate epithelial cells exhibits substantial transforming activity in vitro and in vivo. In NIH 3T3 cells, UBE2L3-KRAS attenuates the MEK/ERK pathway, which is commonly engaged by oncogenic mutant KRAS. Instead, it enriches Ras proteins in late endosome, and diverts signaling to the AKT and p38 MAPK pathways. While a number of oncogenic activating point mutations of KRAS have been identified, this is the first description of a mutant chimeric version of KRAS that is oncogenic and thus may represent a new class of cancer-related alteration. This study also suggests that this aberration may drive metastatic progression in a subset of prostate cancers, which may be targeted by anti-KRAS therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2808. doi:10.1158/1538-7445.AM2011-2808