gebhart/patrepeval huggingface dataset:
Phytohormone derivatives targeted to several cancer hallmarks (2015)

As purines play vital roles in many biological processes the effects of modifying substituents on the purine ring on diverse biological activities warrant close examination, to elucidate the structure-activity relations of their interactions with proteins involved in tumour growth, cancer cell survival, angiogenesis and metastasis. Purines are highly amenable to the chemical manipulations required, and we have exploited this feature to prepare massive libraries of purine derivatives with wide arrays of types and combinations of functional groups at all seven reactive centres on the exterior of the purine heterocycle. The success of olomoucine, roscovitine (licensed to Cyclacel Pharmaceuticals; it is currently in phase IIb clinical trials – see www.ClinicalTrials.gov) and related drugs based on the purine scaffold has prompted and directed parallel advances in the preparation of related heterocyclic systems. We are currently trying to develop (sub)nanomolar inhibitors and rigorously characterise their effects on hallmark features of tumorous cells and systems/cells representing other diseases. In the design and optimization of kinase inhibitors, a key challenge is to elucidate the highly complex interactions involved in targeted processes to ensure that candidate agents have the desired selectivity. This will require comprehensive screening of the activities of a wide range of inhibitors against kinomes of selected cells, detailed in vitro analyses and, the synergistic application of advanced HTP technologies, using both traditional and novel strategies.
Gene trap expression and mutational analysis for genes involved in the development of the mammalian nervous system (1998)

We have used a large-scale gene trap approach for the isolation and mutation of genes that might play roles in the developing nervous system. After in vitro integration of two different gene trap vectors (pGT1.8geo: Skarnes et al. [1995] Proc. Natl. Acad. Sci. USA 92:6592-6596; IRES beta geo: Chowdhury et al. [1997] Nucleic Acids Res. 25:1531-1536) in mouse embryonic stem (ES) cell lines, we created 64 transgenic mouse lines. The expression analysis of the reporter gene during embryogenesis of heterozygous embryos revealed 47 lines with a variety of patterns. Around one-third (36%) of these gene trap lines showed spatiotemporal expression that was either restricted predominantly in the developing nervous system (11 lines; 17%) or widespread but with very high levels of expression in the nervous tissue (12 lines; 19%). In most cases, a correlation was found between the in vitro and the in vivo patterns of the reporter gene expression. Thus far, preliminary mutant analysis of 16 gene trap lines with potentially interesting expression patterns in the developing nervous system showed that mice homozygous for eight (50%) insertions were lethal, whereas the homozygous mice from five gene trap lines (31%) showed a lower than expected Mendelian ratio of live homozygous animals. Analysis of beta-galactosidase reporter gene expression during embryogenesis has shown that four transgenic lines are useful lacZ in situ markers for specific regions of the developing nervous system. Here, we discuss some in vivo and in vitro selection criteria that may increase the number of the trapped genes potentially involved in the control of neural development and some future strategies to improve further the efficiency of the gene trap approach.
Free-electron interactions with photonic GKP states: universal control and quantum error correction (2023)

We show that the coherent interaction between free electrons and photons can be used for universal control of continuous-variable photonic quantum states in the form of Gottesman-Kitaev-Preskill (GKP) qubits. Specifically, we find that electron energy combs enable non-destructive measurements of the photonic state and can induce arbitrary gates. Moreover, a single electron interacting with multiple photonic modes can create highly entangled states such as Greenberger-Horne-Zeilinger states and cluster states of GKPs.
30-GHz-band over 5-W power performance of short-channel AlGaN/GaN heterojunction FETs (2005)

This paper describes the small-signal characterization through delay-time analysis and high-power operation of the Ka-band of AlGaN/GaN heterojunction field-effect transistors (FETs). An FET with a gatewidth of 100 /spl mu/m and a gate length of 0.09 /spl mu/m has exhibited a current gain cutoff frequency (f/sub T/) of 81 GHz, a maximum frequency of oscillation (fmax) of 187 GHz, and a maximum stable gain of 10.5 dB at 30 GHz (8.3 dB at 60 GHz). Delay-time analysis has demonstrated channel electron velocities of 1.50/spl times/10/sup 7/ to 1.75/spl times/10/sup 7/ cm/s in a gate-length range of 0.09-0.25 /spl mu/m. State-of-the-art performance-saturated power of 5.8 W with a linear gain of 9.2 dB and a power-added efficiency of 43.2%-has been achieved at 30 GHz using a single chip having a gatewidth of 1.0 mm and a gate length of 0.25 /spl mu/m.
Design, Fabrication, and Characterization of a Compact Hierarchical Manifold Microchannel Heat Sink Array for Two-Phase Cooling (2019)

High-heat-flux removal is critical for the next-generation electronic devices to reliably operate within their temperature limits. A large portion of the thermal resistance in a traditional chip package is caused by thermal resistances at interfaces between the device, heat spreaders, and the heat sink; embedding the heat sink directly into the heat-generating device can eliminate these interface resistances and drastically reduce the overall thermal resistance. Microfluidic cooling within the embedded heat sink improves the heat dissipation, with two-phase operation offering the potential for dissipation of very high heat fluxes while maintaining moderate chip temperatures. To enable multichip stacking and other heterogeneous packaging approaches, it is important to densely integrate all fluid flow paths into the device; volumetric heat dissipation emerges as a performance metric in this new heat sinking paradigm. In this paper, a compact hierarchical manifold microchannel design is presented that utilizes an integrated multilevel manifold distributor to feed coolant to an array of microchannel heat sinks. The flow features in the manifold layers and microchannels are fabricated in silicon wafers using deep reactive-ion etching. The heat source is simulated via Joule heating using thin-film platinum heaters. The on-chip spatial temperature measurements are made using four-wire resistance temperature detectors. The individual manifold layers and the microchannel-bearing wafers are diced and bonded into a sealed stack via thermocompression bonding using gold layers at the mating surfaces. Thermal and hydrodynamic testing is performed by pumping the dielectric fluid HFE-7100 through the device at a known flow rate, temperature, and pressure at different levels of chip heat input. A volumetric heat density of up to 2870 W/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> is dissipated at a chip temperature less than 112 °C and microchannel pressure drop less than 27 kPa. The overall pressure drop is governed by flowing through the manifold, rather than the microchannels, in this compact heat sink that occupies envelope of 5 mm × 5 mm × 2.3 mm including all the functional flow features.
The Evolving Role of Prostate-Specific Membrane Antigen–Based Diagnostics and Therapeutics in Prostate Cancer (2019)

Prostate-specific membrane antigen (PSMA)-based imaging seeks to fill some critical gaps in prostate cancer staging and response assessment, and may select patients for treatment with radiolabeled PSMA conjugates. In biochemical recurrence, at prostate-specific antigen (PSA) levels as low as 0.2 ng/dL, <sup>68</sup>Ga-PSMA imaging has demonstrated a 42% detection rate of occult metastatic disease, and detection has been greater than 95% when PSA levels are higher than 2 ng/dL. This may facilitate novel approaches, including salvage lymphadenectomy or metastasis-directed radiation therapy, in patients with oligometastatic disease. PSMA-based imaging has shown promise in evaluating treatment response in hormone-sensitive and castration-resistant disease; however, additional longitudinal assessment is needed given the heterogeneity in uptake changes after the initiation of androgen-deprivation therapy. Changes in uptake must be taken in context of RECIST measurements and other response parameters, given the potential for growth of PSMA-negative lesions and persistent uptake in treated bone lesions of uncertain significance. For selecting patients to receive PSMA-targeted radioconjugate therapy, standardized uptake value thresholds remain to be established. Nevertheless, preliminary data from <sup>177</sup>Lu-PSMA theranostic trials have yielded PSA responses in up to 57% of patients, as well as pain relief and improved quality of life. Thrombocytopenia was the most common grade 3 or greater toxicity; however, grade 1 xerostomia occurred frequently and was cited as the most common reason for treatment discontinuation.
Electrical detection of surface plasmon resonance phenomena by a photoelectronic device integrated with gold nanoparticle plasmon antenna (2013)

We have proposed a concept of a photoelectronic hybrid device utilizing gold nanoparticles (GNPs), which are supposed to function not only as the plasmon antenna but also as the sensing part. The photocurrent in the fabricated device, consisting of a transparent Nb-doped TiO2 channel and Au electrodes, was enhanced more than eight times at a specific wavelength with GNP arrays located between the electrodes, indicating that surface plasmon resonance was electrically detected with the hybrid device. This result will open new doors for ultra-small biosensor chips integrated with multi-functional solid-state devices.
3D Integration : a technological toolbox (2008)

Today 3D integration technology is investigated at every microelectronic device fabrication stage. Semiconductor layers, transistors, wafers and chips are stacked to create new functionalities, enhance device performance or develop innovative systems on a chip. 3D integration technology enables bringing them together on one chip. This can be done either as a sequence of bonding and processing stages or by the bonding of dies processed in parallel. Several different approaches have been developed in order to perform 3D integration. In order to enable the full range of 3D devices from heterogeneous systems packaging to high density via IC stacking, LETI has developed key integration stages and implemented them in 3D demonstrator devices. In this paper, the generic toolbox developed at LETI is described. Several key technologies developed for parallel medium and high density 3-D integration for circuit or chip stacking are reviewed. Direct oxide or copper bonding technology, micro insert technology, die-to-wafer self-assembly, wafer thinning process and copper TSV process are discussed. New developments in sequential 3D approach are also presented.
Dual Polarization L-Shaped Slot Array Antenna for 5G Metal-Rimmed Mobile Phone (2018)

In this paper, dual polarization phased array antenna for 5G metal-rimmed mobile phone is proposed. The proposed antenna consists of two $1 \times 8$ arrays where the upper eight elements and the lower eight elements have different linear polarization. To arrange many elements in the metal rim of the mobile phone, the L-shaped slot antenna is chosen which has less size than the conventional inclined slot antenna. The resonance frequency is 28GHz (5G mm-wave band) and the mutual coupling between the antenna elements is less than 19.7dB. The proposed phased array antenna shows wide beam steering range sufficient for 5G mobile communication.
ICA Based Disturbance Specific Control Charts (2007)

This paper demonstrates a general method for simplifying multivariate process monitoring so as to allow the use of traditional SPC tools while facilitating process diagnosis. We pool data recycled from factorial design experiments to develop latent variable representations of complex processes which are directly identified with process steps or segments. Our method models disturbances in the process rather than the process itself. The methodology is illustrated on the problem of monitoring electrical test (E-Test) data from a semiconductor manufacturing process. Development and production data from a working semiconductor plant are used to estimate a factor model that is used to develop univariate control charts for particular types of process disturbances. Detection and false alarm rates for data with known disturbances are given. The charts correctly detect and classify all the disturbance cases with a very low false alarm rate.
Multiple Pathways for Vacuolar Sorting of Yeast Proteinase A (1996)

The sorting of the yeast proteases proteinase A and carboxypeptidase Y to the vacuole is a saturable, receptor-mediated process. Information sufficient for vacuolar sorting of the normally secreted protein invertase has in fusion constructs previously been found to reside in the propeptide of proteinase A. We found that sorting of such a hybrid protein is dependent on the vacuolar protein-sorting receptor Vps10p. This was unexpected, as strains disrupted for VPS10 sort more than 85% of the proteinase A to the vacuole. Consistent with a role for Vps10p in sorting of proteinase A, we found that 1) overproduction of Vps10p suppressed the missorting phenotype associated with overproduction of proteinase A, 2) overproduction of proteinase A induced missorting of carboxypeptidase Y, 3) vacuolar sorting of proteinase A in a deltavps10 strain was readily saturated by modest overproduction of proteinase A, and 4) Vps10p and proteinase A interact directly and specifically as shown by chemical cross-linking. Interestingly, overexpression of two telomere-linked VPS10 homologues, VTH1 and VTH2 suppressed the missorting phenotypes of a deltavps10 strain. However, disruption of the VTH1 and VTH2 genes did not affect the sorting of proteinase A. We conclude that proteinase A utilizes at least two mechanisms for sorting, a Vps10p-dependent path and a Vth1p/Vth2p/Vps10p-independent path.
Loss of the intracellular enzyme QPCTL limits chemokine function and reshapes myeloid infiltration to augment tumor immunity (2022)

ABSTRACT Tumor-associated macrophages are composed of distinct populations arising from monocytes or tissue macrophages, with a poorly understood link to disease pathogenesis. Here, we demonstrate that mouse monocyte migration was supported by glutaminyl-peptide cyclotransferase-like (QPCTL), an enzyme that mediates N-terminal modification of several subtrates, including the monocyte-chemoattractants CCL2 and CCL7, protecting them from proteolytic inactivation. Knockout of Qpctl disrupted monocyte homeostasis, attenuated tumor growth and reshaped myeloid cell infiltration, with loss of monocyte-derived populations with immunosuppressive and pro-angiogenic profiles. Antibody blockade of the receptor CSF1R, which more broadly eliminates tissue macrophages, reversed tumor growth inhibition in Qpctl −/− mice, and prevented lymphocyte infiltration. Modulation of QPCTL synergized with anti-PD-L1 to expand CD8 + T cells and limit tumor growth. QPCTL inhibition constitutes an effective approach for myeloid cell-targeted cancer immunotherapy.
Relationship between esophageal muscle thickness and intraluminal pressure in patients with esophageal spasm (2002)

We previously showed, in normal subjects, a positive correlation between the esophageal contraction amplitude and peak muscle thickness. The goal of this study was to determine the relationship between esophageal muscle thickness and contraction amplitude in patients with high-amplitude peristaltic and simultaneous contractions. Eleven patients with high-amplitude peristaltic contractions, 8 with diffuse esophageal spasm (DES), 7 with nonspecific (NS) motor disorder of the esophagus, and 10 normal subjects were studied using simultaneous pressure and ultrasound imaging. Pressure was recorded by manometry and ultrasound imaging with a high-frequency ultrasound probe catheter. Recordings were performed in the lower esophageal sphincter (LES) and at 2, 4, 6, 8, and 10 cm above the LES during resting state and swallow-induced contractions. Baseline esophageal muscle was thicker in the distal, compared with the proximal esophagus both in normal subjects and patient groups. Patients with DES and nutcracker esophagus (NC) have a higher baseline muscle thickness compared with normal and NS patients. Correlation between the peak pressure and the peak muscle thickness was weaker in patients with NC and DES compared with normal subjects and patients with NS. Whereas normal subjects have good correlation between delta (difference between peak and baseline) muscle thickness and peak pressures, this relationship was absent in patients with NC and DES. Increase in contraction amplitude in patients with NC and DES was associated with an increase in baseline thickness of esophageal muscularis propria. Increase in baseline thickness was specific to patients with spastic motor disorders and was not seen in patients with NS.
Information foraging in debugging (2009)

Programmers spend a substantial fraction of their debugging time by navigating through source code, yet little is known about how programmers navigate. With the continuing growth in size and complexity of software, this fraction of time is likely to increase, which presents challenges to those seeking both to understand and address the needs of programmers during debugging. 
Therefore, we investigated the applicability a theory from another domain, namely information foraging theory, to the problem of programmers’ navigation during software maintenance. The goal was to determine the theory’s ability to provide a foundational understanding that could inform future tool builders aiming to support programmer navigation.
To perform this investigation, we first defined constructs and propositions for a new variant of information foraging theory for software maintenance. We then operationalized the constructs in different ways and built three executable models to allow for empirical investigation. We developed a simple information-scent-only model of navigation, a more advanced model of programmer navigation, named Programmer Flow by Information Scent (PFIS), which accounts for the topological structure of source code, and PFIS 2, a refinement of PFIS that maintains an up-to-date model of source code on the fly and models information scent even in the absence of explicit information about stated goals.
We then used the models in three empirical studies to evaluate the applicability of information foraging theory to this domain. First, we conducted a lab study of 12 IBM programmers working on a bug report and feature request. Second, we conducted an analysis of issues and revisions collected from Sourceforge.net. Finally, we collected programmer navigation behavior, revisions and issues from a field study of programmers working in various groups at IBM.
All three models predicted programmers’ navigation behavior, including where programmers allocated their time among patches, where programmers went, or where programmers made changes to fix defects. These results indicate that information foraging theory can predict and explain programmer navigation behavior, and imply that tools based on the principles of information foraging theory will be able to predict subsequent navigation behavior and potentially assist where programmers should go to make changes to fix bugs.
High-resolution two-dimensional angle measurement technique based on fringe analysis (2003)

A novel angle-measurement technique based on fringe analysis for phase-measuring profilometry is proposed. A two-dimensional (2-D) angle between two mirror surfaces is determined by least-squares fitting of a plane to the 2-D distribution of the phase difference introduced by the 2-D tilt angle. To evaluate the performance of the proposed technique, numerical simulations that use the Fourier-transform technique and the phase-shift technique for fringe analysis were performed, and the results are compared. A 2-D angle-measurement interferometer based on a Mirau interference microscope was developed that demonstrated the validity of the proposed principle. It is shown by simulation and experiment that the proposed 2-D angle-measurement technique can achieve both a wide measurement range and a high angular resolution simultaneously.
Spinal dura mater: biophysical characteristics relevant to medical device development (2018)

Understanding the relevant biophysical properties of the spinal dura mater is essential to the design of medical devices that will directly interact with this membrane or influence the contents of the intradural space. We searched the literature and reviewed the pertinent characteristics for the design, construction, testing, and imaging of novel devices intended to perforate, integrate, adhere or reside within or outside of the spinal dura mater. The spinal dura mater is a thin tubular membrane composed of collagen and elastin fibres that varies in circumference along its length. Its mechanical properties have been well-described, with the longitudinal tensile strength exceeding the transverse strength. Data on the bioelectric, biomagnetic, optical and thermal characteristics of the spinal dura are limited and sometimes taken to be similar to those of water. While various modalities are available to visualise the spinal dura, magnetic resonance remains the best modality to segment its structure. The reaction of the spinal dura to imposition of a foreign body or other manipulations of it may compromise its biomechanical and immune-protective benefits. Therefore, dural sealants and replacements are of particular clinical, research and commercial interest. In conclusion, existing devices that are in clinical use for spinal cord stimulation, intrathecal access or intradural implantation largely adhere to traditional designs and their attendant limitations. However, if future devices are built with an understanding of the dura's properties incorporated more fully into the designs, there is potential for improved performance.
Biomaterials for stem cell differentiation (2010)

Stem cell-based therapeutic treatments hold great promise in treating diseases by replacement of body parts and organs through the generation of new tissues. Directing the controlled differentiation of stem cells into a lineage-specific manner requires a controlled biophysical and biochemical microenvironment and signals. Biomaterials may act as artificial microenvironments and therefore, can deliver stem cell regulatory signals in a precise and near-physiological fashion. A variety of biomaterials are being developed that support cellular attachment, proliferation and most importantly lineage-specific differentiation. Development of new intelligent biomaterials in synergy with cell biology will advance stem cell-based clinical therapeutics. This review discusses the various biomaterials, in particular polymers, applied towards the goal of lineage-specific differentiation of stem cells.