gebhart/patrepeval huggingface dataset:
Probing Selectivity and Creating Structural Diversity Through Hybrid Polyketide Synthases (2020)

Engineering polyketide synthases (PKS) to produce new metabolites requires an understanding of catalytic points of failure during substrate processing. Growing evidence indicates the thioesterase (TE) domain as a significant bottleneck within engineered PKS systems. We created a series of hybrid PKS modules bearing exchanged TE domains from heterologous pathways and challenged them with both native and non-native polyketide substrates. Reactions pairing wildtype PKS modules with non-native substrates primarily resulted in poor conversions to anticipated macrolactones. Likewise, product formation with native substrates and hybrid PKS modules bearing non-cognate TE domains was severely reduced. In contrast, non-native substrates were converted by most hybrid modules containing a substrate compatible TE, directly implicating this domain as the major catalytic gatekeeper and highlighting its value as a target for protein engineering to improve analog production in PKS pathways.
The effect of nitrogen partitioning on the magnetic properties of FeAlN films (1996)

The amount of /spl gamma/'-Fe/sub 4/N phase in FeAlN films has been manipulated by varying the substrate temperature during RF diode sputter deposition. It was found that increasing substrate temperature leads to greater amounts of /spl gamma/'-Fe/sub 4/N precipitation under constant nitrogen flow. It is shown that this precipitation correlates with low coercivities at elevated temperatures and leads to a more negative saturation magnetostriction constant in the films. On the other hand, the magnetostriction constant increases with increasing nitrogen flow at the same substrate deposition temperature. This increase is attributed to the increasing amount of nitrogen in the /spl alpha/-Fe phase. It is shown that the amount of nitrogen in the /spl alpha/-Fe phase is controlling the magnetostriction constant of the film, rather than the /spl gamma/'-Fe/sub 4/N phase.
Integration of physical, breakpoint and genetic maps of chromosome 22. Localization of 587 yeast artificial chromosomes with 238 mapped markers (1995)

Detailed physical maps of the human genome are important resources for the identification and isolation of disease genes and for studying the structure and function of the genome. We used data from STS content mapping of YACs and natural and induced chromosomal breakpoints to anchor contigs of overlapping yeast artificial chromosome (YAC) clones spanning extensive regions of human chromosome 22. The STSs were assigned to specific regions (bins) on the chromosome using cell lines from a somatic hybrid mapping panel defining a maximum of 25 intervals. YAC libraries were screened by PCR amplification of hierarchical pools of yeast DNA with 238 markers, and a total of 587 YAC clones were identified. These YACs were assembled into contigs based upon their shared STS content using a simulated annealing algorithm. Fifteen contigs, containing between 2 and 74 STSs were assembled, and ordered along the chromosome based upon the cytogenetic breakpoint, meiotic and PFG maps. Additional singleton YACs were assigned to unique chromosomal bins. These ordered YAC contigs will be useful for identifying disease genes and chromosomal breakpoints by positional cloning and will provide the foundation for higher resolution physical maps for large scale sequencing of the chromosome.
Supercritically-Dried Porous Silicon Powders with Surface Areas Exceeding 1000 m2/g (2015)

International audience
Automatic classification of atherosclerotic plaques imaged with intravascular OCT(Conference Presentation) (2016)

A novel computational method for plaque tissue characterization based on Intravascular Optical Coherence Tomography (IV-OCT) is presented. IV-OCT is becoming a powerful tool for the clinical evaluation of atherosclerotic plaques; however, it requires a trained expert for visual assessment and interpretation of the imaged plaques. Moreover, due to the inherit effect of speckle and the scattering attenuation of the optical scheme the direct interpretation of OCT images is limited. To overcome these difficulties, we propose to automatically identify the A-line profiles of the most significant plaque types (normal, fibrotic, or lipid-rich) and their respective abundance by using a probabilistic framework and blind alternated least squares to achieve the optimal decomposition. In this context, we present preliminary results of this novel probabilistic classification tool for intravascular OCT that relies on two steps. First, the B-scan is pre-processed to remove catheter artifacts, segment the lumen, select the region of interest (ROI), flatten the tissue surface, and reduce the speckle effect by a spatial entropy filter. Next, the resulting image is decomposed and its A-lines are classified by an automated strategy based on alternating-least-squares optimization. Our early results are encouraging and suggest that the proposed methodology can identify normal tissue, fibrotic and lipid-rich plaques from IV-OCT images.
Enhancement of nonlinear self-action in CS/sub 2/ for nanosecond optical limiting (2001)

Summary form only given. We have shown that the nonlinear refraction in CS/sub 2/ for nanosecond pulses is due to a combination of the molecular reorientation (Kerr) effect and electrostriction. The latter works best for tightly focused beams and longer pulses. Modeling indicates that without the electrostrictive effect, the CS/sub 2/ would not be able to protect the PbPc cell from optical damage. We have also studied other mechanisms that might further improve the CS/sub 2/ limiting, including solutions of two-photon absorbers in the CS/sub 2/ and the suspension of carbon black particles in the CS/sub 2/. Carbon black suspensions (CBS) are known to produce strong limiting due to their nonlinear scattering properties. We show how the addition of CBS to the CS/sub 2/ enhances the limiting effect at low to moderate energies with a small penalty in linear transmittance.
Drug Nanocrystals (2020)

Drug nanocrystals are particulate-level approach to improve the solubility properties and drug release behavior especially for poorly soluble drug materials. Applications can be found from immediate release systems to controlled release formulations, and though the oral route is most interesting, also formulations, for example, for ocular, parenteral, topical, and pulmonary drug delivery have been studied. Because the number of poorly soluble new pharmaceutical entities is all the time increasing and due to the relative simplicity, high drug loading capacity, and cost efficiency of the nanocrystallization methods, the utilization of these techniques in drug delivery has been intensively studied during the last three decades. Besides the scientific research and increased number of publications, this has also been seen in the numerous nanocrystal-based therapeutical products already seen on the market. In this chapter, drug nanocrystals, and their characteristic properties, production, and analytics are thoroughly reviewed, and nanocrystal-based formulations and drug delivery routes are evaluated followed by some future perspectives.
Gabapentin therapy for amyotrophic lateral sclerosis: lack of improvement in neuronal integrity shown by MR spectroscopy. (2003)

No improvement in neuronal integrity was detected in motor and nonmotor cerebral regions after GBP treatment. This result agrees with that of prior investigations showing the equivocal clinical effectiveness of GBP for ALS and supports the validity of the NAA/Cr ratio as a surrogate of therapeutic effectiveness.
Robust Wireless Power Receiver for Multi-Tone Waveforms (2019)

This paper presents a multi-tone wireless power receiver (WPRx) that can operate efficiently across various waveforms with a different number of tones. Conventional wireless power receivers have a significant efficiency dependence on the power levels and loading conditions. In this work, the conventional WPRx is also verified experimentally to be highly dependent on the input waveforms and their number of tones. Thus, a multi-tone WPRx is proposed using a configurable dc-to-dc voltage boost converter to track the optimal efficiency using external reference voltage. The proposed multi-tone WPRx is prototyped and characterized across different waveforms within a 10-MHz bandwidth at 2.4-GHz with a wide range of input power levels. The measured results show a significant suppression (of four times) in the efficiency variations across the different number of tones relative to conventional WPRx. For instance, at -10-dBm input power level, the standard deviation in the efficiency of the proposed WPRx, across different waveforms, is less than 1/4 that of the conventional WPRx while maintaining a very close average efficiency across these waveforms. While the conventional WPRx can be optimized only for a single type of waveforms, the proposed multi-tone WPRx can maintain a stable efficiency across different waveforms with minimum variations.
Large‐volume leukapheresis for collection of mononuclear cells for hematopoietic rescue in Hodgkin's disease (1995)

LVL provides a useful method of collecting MNCs for hematopoietic rescue in patients with Hodgkin's disease. The patient's baseline MNC count provides a useful estimate of the volume required for LVL.
A Convenient Dehydration Procedure for the Synthesis of Enantiomerically Pure Cyanohydrins (2000)

Starting from protected α-hydroxy amides, cyanohydrins (α-hydroxy nitriles) are obtained through dehydration by cyanuric chloride/DMF in excellent yield. The advantages of the procedure are the extremely mild reaction conditions that prevent racemization.
BTN3A is a prognosis marker and a promising target for Vγ9Vδ2 T cells based-immunotherapy in pancreatic ductal adenocarcinoma (PDAC) (2017)

Vγ9Vδ2 T cells are anti-tumor immune effectors of growing interest in cancer including Pancreatic Ductal Adenocarcinoma (PDAC), an especially aggressive cancer characterized by a hypoxic and nutrient-starved immunosuppressive microenvironment. Since Butyrophilin 3 A (BTN3A) isoforms are critical activating molecules of Vγ9Vδ2 T cells, we set out to study BTN3A expression under both basal and stress conditions in PDAC primary tumors, and in novel patient-derived xenograft and PDAC-derived cell lines. BTN3A2 was shown to be the most abundant isoform in PDAC and was stress-regulated. Vγ9Vδ2 T cells cytolytic functions against PDAC required BTN3A and this activity was strongly enhanced by the agonist anti-BTN3A 20.1 mAb even under conditions of hypoxia. In PDAC primary tumors, we established that BTN3A expression and high plasma levels of soluble BTN3A were strongly associated with a decreased survival. These findings may have important implications in the design of new immunotherapeutic strategies that target BTN3A for treating PDAC.
Sol–Gel Route to Zirconia–Pt-Nanoelectrode Arrays 8 nm in Radius: Their Geometrical Impact in Mass Transport (2012)

The fabrication of advanced nanoelectrode arrays and their electrochemical characterization are presented. These nanoelectrode arrays are constituted of nanoperforations of 8 nm in radius leading to platinum and protected by an inorganic matrix made of crystalline zirconia. These nanoelectrodes arrays provide a ceramic support with a high thermal and chemical stability. These devices present a well characterized structure with a control of size, shape, and spacing of the nanoelectrodes, allowing studying in depth both the mass transport and the charge transfer properties in the nanometer range. The radial diffusion occurs when the experimental scan rate is superior to a theoretical scan rate estimated from the model proposed by Amatore and colleagues. The coupling between electrochemical analysis and nanoscale structural characterizations successfully demonstrates that the theory defined for microelectrode arrays can be directly transposed for well-defined metal-ceramic nanocomposite nanoelectrodes.
In Situ Mass Spectral and Infrared Studies of the Gas‐Phase Evolution and Decomposition Pathways of Cu II  ( hfac ) 2 : Application in the Development of Plasma‐Assisted Chemical Vapor Deposition of Copper (1995)

Results are presented from in situ, real‐time, mass spectral, and infrared studies of the gas‐phase evolution and decomposition pathways of the copper(II) β‐diketonate precursor bis(1,1,1,5,5,5‐hexafluoroacetylacetonato)copper(II),, during plasma‐assisted CVD (PACVD) of copper. Quadrupole mass spectrometry (QMS) investigations focused on determining the ionization efficiency curves and appearance potentials of under real CVD processing conditions. The resulting curves and associated potentials were then employed to identify the most likely precursor decomposition pathways and examine relevant implications for thermal and plasma‐assisted CVD of copper from . The QMS studies were complemented with real‐time Fourier‐transform infrared (FTIR) spectroscopy of the CVD processing environment to establish a basic understanding of plasma effects on copper precursor evolution and decomposition, and to determine optimum plasma CVD processing windows. Real‐time FTIR absorption spectra of the gas‐phase species in the CVD reactor were collected and analyzed for various plasma power densities. Key changes in precursor stretching and bending infrared (IR) bands were subsequently identified through a systematic comparison of the spectra of hydrogen plasma‐exposed , collected as a function of varying plasma power density, and the fingerprint spectra of non‐plasma‐exposed H(hfac) and . The resulting FTIR findings were used to develop optimum plasma processing conditions for providing the high concentration of reactive hydrogen species needed for the clean and efficient reduction of the precursor, without inducing undesirable gas‐phase reactions. The results demonstrated that FTIR does provide a reliable in situ, accurate, and nonintrusive technique for monitoring the gas‐phase evolution of metallorganics and associated reactants in the CVD reactor and allowing critical adjustments for optimal copper film quality.
Evolving computer intrusion scripts for vulnerability assessment and log analysis (2005)

Evolutionary computation is used to construct undetectable computer attack scripts. Using a simulated operating system, we show that scripts can be evolved to cover their tracks and become difficult to detect from log file analysis.
The cellular matrix: a feature of tensile bearing dense soft connective tissues. (2002)

The term connective tissue encompasses a diverse group of tissues that reside in different environments and must support a spectrum of mechanical functions. Although the extracellular matrix of these tissues is well described, the cellular architecture of these tissues and its relationship to tissue function has only recently become the focus of study. It now appears that tensile-bearing dense connective tissues may be a specific class of connective tissues that display a common cellular organization characterized by fusiform cells with cytoplasmic projections and gap junctions. These cells with their cellular projections are organised into a complex 3-dimensional network leading to a physically, chemically and electrically connected cellular matrix. The cellular matrix may play essential roles in extracellular matrix formation, maintenance and remodelling, mechanotransduction and during injury and healing. Thus, it is likely that it is the interaction of both the extracellular matrix and cellular matrix that provides the basis for tissue function. Restoration of both these matrices, as well as their interaction must be the goal of strategies to repair these connective tissues damaged by either injury or disease.
Use of burn wound biopsies in the diagnosis and treatment of burn wound infection (1993)

Improvements in both general care and wound care have favorably influenced the outcome of burn patients. Principal among these improvements have been the use of effective topical antimicrobial chemotherapy and the early postburn removal of ischemic nonviable burned tissue by excision, which have reduced the incidence of invasive burn wound infection as a cause of death [6]. Even so, current burn wound care is imperfect and certain patients, usually those with extensive burns that involve more than 50 % of the total body surface (particularly children and the elderly), escape from microbial control and develop invasive burn wound infection [10].
Bispezifische Antikörper: Hoffnungsträger in der Krebsimmuntherapie (2021)

Abstract Nearly seventy years have passed since the first attempts to fuse the antibodies, „ magic bullets “ with exquisite target specificity, into multispecific agents that can connect a targeted cell with an effector immune cell. Such efforts have triggered a plethora of engineering advancements to optimize the antigen engagement. Even the most conserved domains of the antibody molecule have been modified to achieve two unique chains pairing, or with an introduction of novel antigen binding sites.
Feasibility of Interference Alignment for Full-Duplex MIMO Cellular Networks (2015)

본 논문은 전 이중 다중 안테나 셀룰라 네트워크에서 간섭 정렬 타당성을 다루고 있다. 간섭 정렬을 위한 필요충분조건 정립과, 달성 가능 합 자유도를 대칭 네트워크에 내에서 설명했다. 실험결과 기존 반 이중 통신의 합 자유도 보다 향상 되는 것을 확인 할 수 있다. The feasibility condition of interference alignment (IA) for full-duplex (FD) multiple-input multipleoutput (MIMO) cellular networks is considered. The necessary and sufficient condition on the IA feasibility is established, characterizing the achievable sum degrees of freedom (DoF). The results demonstrate that FD operation with appropriate IA is able to improve the sum DoF on the conventional half-duplex operation.
Dysregulation of splicing proteins in head and neck squamous cell carcinoma (2016)

Signaling plays an important role in regulating all cellular pathways. Altered signaling is one of the hallmarks of cancers. Phosphoproteomics enables interrogation of kinase mediated signaling pathways in biological systems. In cancers, this approach can be utilized to identify aberrantly activated pathways that potentially drive proliferation and tumorigenesis. To identify signaling alterations in head and neck squamous cell carcinoma (HNSCC), we carried out proteomic and phosphoproteomic analysis of HNSCC cell lines using a combination of tandem mass tag (TMT) labeling approach and titanium dioxide-based enrichment. We identified 4,920 phosphosites corresponding to 2,212 proteins in six HNSCC cell lines compared to a normal oral cell line. Our data indicated significant enrichment of proteins associated with splicing. We observed hyperphosphorylation of SRSF protein kinase 2 (SRPK2) and its downstream substrates in HNSCC cell lines. SRPK2 is a splicing kinase, known to phosphorylate serine/arginine (SR) rich domain proteins and regulate splicing process in eukaryotes. Although genome-wide studies have reported the contribution of alternative splicing events of several genes in the progression of cancer, the involvement of splicing kinases in HNSCC is not known. In this study, we studied the role of SRPK2 in HNSCC. Inhibition of SRPK2 resulted in significant decrease in colony forming and invasive ability in a panel of HNSCC cell lines. Our results indicate that phosphorylation of SRPK2 plays a crucial role in the regulation of splicing process in HNSCC and that splicing kinases can be developed as a new class of therapeutic target in HNSCC.
Distribution of ApoBII, MCT118 (D1S80), YNZ22 (D17S30), and COL2A1 Amp-FLPs (amplified fragment length polymorphisms) in Caucasoid population of Slovakia. (1994)

Amp-FLPs are simple and rapid tools for genetic characterization of both individuals and populations. This paper presents allele frequencies of four Amp-FLPs (ApoBII, MCT118, YNZ22, and COL2A1) based on the analysis of more than 100 unrelated Caucasoid Slovaks. The proportion of heterozygotes observed and expected, and the probability that two individuals taken at random from the population would be identical in a given polymorphism (PI), was determined for each Amp-FLP.
Selective expansion of regulatory T cells by kidney-tethered IL2 mutein (2021)

Abstract Regulatory T cells (Treg) play a critical role in maintaining graft tolerance following organ transplantation, and increased numbers of Tregs in solid-tissue grafts such as the kidney are associated with improved graft survival and function. Therapeutic approaches that increase Tregs offer a promising alternative to current standard-of-care treatment consisting of broad-acting immunosuppressants and their attendant side effects. While efforts to expand Tregs ex vivo for infusion into patients have shown promise, they present manufacturing and administration challenges. Low dose (LD) interleukin 2 (IL-2) drives Treg proliferation and function via the heterotrimeric IL-2 receptor expressed on Tregs and has been shown to expand Tregs in vivo, including in the context of transplantation. However, IL-2 can also activate other immune cells including conventional T cells and Natural Killer (NK) cells, which express IL-2Rb/CD122 and IL-2g/CD132, and this could accelerate rejection. We have enhanced IL-2 selectivity for Treg by introducing mutations that increase affinity for CD25 and decrease affinity for CD122/CD132, resulting in Treg specific expansion. Here, we demonstrate that this IL-2 Mutein (IL-2M) can be “tethered” to the kidney via a bifunctional antibody targeting a tubule-specific protein. This kidney-tethered IL-2M maintains Treg selectivity and localizes to the kidney with extended tissue PK. Moreover, in a CD34-NSG mouse model, animals dosed with kidney-tethered IL-2M exhibited prolonged kidney Treg expansion compared to a systemic, non-tethered IL-2M. This approach has the potential to substantially improve kidney graft acceptance while reducing adverse effects and improving patient quality of life.
Long-term efficacy and safety of eladocagene exuparvovec in patients with AADC deficiency (2021)

Aromatic L-amino acid decarboxylase deficiency results in decreased neurotransmitter levels and severe motor dysfunction. Twenty-six patients without head control received bilateral intraputaminal infusions of a recombinant adeno-associated virus type 2 vector containing the human aromatic L-amino acid decarboxylase gene (eladocagene exuparvovec) and have completed 1-year evaluations. Rapid improvements in motor and cognitive function occurred within 12 months after gene therapy and were sustained during follow-up for >5 years. An increase in dopamine production was demonstrated by positron emission tomography and neurotransmitter analysis. Patient symptoms (mood, sweating, temperature, and oculogyric crises), patient growth, and patient caretaker quality of life improved. Although improvements were observed in all treated participants, younger age was associated with greater improvement. There were no treatment-associated brain injuries, and most adverse events were related to underlying disease. Post-surgery complications such as cerebrospinal fluid leakage were managed with standard of care. Most patients experienced mild to moderate dyskinesia that resolved in a few months. These observations suggest that eladocagene exuparvovec treatment for aromatic L-amino acid decarboxylase deficiency provides durable and meaningful benefits with a favorable safety profile.