gebhart/patrepeval huggingface dataset:
PLK1 stabilizes a MYC-dependent kinase network in aggressive B cell lymphomas (2018)

Concordant activation of MYC and BCL-2 oncoproteins in double-hit lymphoma (DHL) results in aggressive disease that is refractory to treatment. By integrating activity-based proteomic profiling and drug screens, polo-like kinase-1 (PLK1) was identified as an essential regulator of the MYC-dependent kinome in DHL. Notably, PLK1 was expressed at high levels in DHL, correlated with MYC expression, and connoted poor outcome. Further, PLK1 signaling augmented MYC protein stability, and in turn, MYC directly induced PLK1 transcription, establishing a feed-forward MYC-PLK1 circuit in DHL. Finally, inhibition of PLK1 triggered degradation of MYC and of the antiapoptotic protein MCL-1, and PLK1 inhibitors showed synergy with BCL-2 antagonists in blocking DHL cell growth, survival, and tumorigenicity, supporting clinical targeting of PLK1 in DHL.
The bandwidth deficit problem in loosely coupled WLAN-to-cellular vertical handover (2007)

Seamless WLAN-to-cellular handover is often difficult to achieve, since WLAN coverage can often be lost very quickly. Recent results have shown that successful handover may require that the WLAN link be allowed to rate-adjust itself to very low values (e.g., 1-2 Mbps) before the vertical handover is completed. When this occurs the call temporarily occupies a WLAN bandwidth far higher than the value for which it was originally provisioned. This effect is referred to as the vertical handover bandwidth deficit problem. In this paper we consider the effects of the bandwidth deficit problem on system performance, and how the problem can be mitigated. It is shown that this bandwidth demand can result in significant vertical handover dropping due to a lack of bandwidth on the WLAN access point. A static bandwidth reservation scheme motivated by the classical cellular guard channel approach is first considered and is found to result in an unacceptable increase in the WLAN new call blocking rate. A novel transient bandwidth reservation scheme accompanied by a momentary forced handover mechanism is proposed to overcome the shortcomings of the static approach in multiple AP WLANs. Our presented results show that almost two orders of magnitude reduction in the vertical handover dropping rate can be achieved while maintaining an acceptable new call blocking rate at the WLAN AP.
Exacerbated Type II Interferon Response Drives Hypervirulence and Toxic Shock by an Emergent Epidemic Strain of Streptococcus suis (2013)

Streptococcus suis, a major porcine pathogen, can be transmitted to humans and cause severe symptoms. A large human outbreak associated with an unusual streptococcal toxic shock-like syndrome (STSLS) was described in China. Albeit an early burst of proinflammatory cytokines following Chinese S. suis infection was suggested to be responsible for STSLS case severity, the mechanisms involved are still poorly understood. Using a mouse model, the host response to S. suis infection with a North American intermediately pathogenic strain, a European highly pathogenic strain, and the Chinese epidemic strain was investigated by a whole-genome microarray approach. Proinflammatory genes were expressed at higher levels in mice infected with the Chinese strain than those infected with the European strain. The Chinese strain induced a fast and strong gamma interferon (IFN-γ) response by natural killer (NK) cells. In fact, IFN-γ-knockout mice infected with the Chinese strain showed significantly better survival than wild-type mice. Conversely, infection with the less virulent North American strain resulted in an IFN-β-subjugated, low inflammatory response that might be beneficial for the host to clear the infection. Overall, our data suggest that a highly virulent epidemic strain has evolved to massively activate IFN-γ production, mainly by NK cells, leading to a rapid and lethal STSLS.
Joint Antenna Detection and Bayesian Channel Estimation for Non-Coherent User Terminals (2020)

In this paper, we propose a method of improving the channel estimates for non-coherent multi-antenna terminals, which are terminals that cannot control the relative phase between its antenna ports, with channels that can be considered constant over multiple time slots. The terminals have multiple antennas and are free to choose whichever antenna they want to use in each time slot. An unknown phase shift is introduced in each time slot as we cannot guarantee that the terminals are phase coherent across time slots. We compare three different clustering techniques that we use to detect the active antenna. We also compare a set of different statistical and heuristic estimators for the channels and the phase shifts. We evaluate the methods by using correlated Rayleigh fading and three different bounds on the uplink capacity. The accuracy of the capacity bounds are verified with bit-error-rate simulations. With our proposed methods we can have an SNR improvement of approximately 2 dB at 1 bit/s/Hz.
THYMIC RECOGNITION OF CLASS II MAJOR HISTOCOMPATIBILITY COMPLEX ALLOPEPTIDES INDUCES DONOR-SPECIFIC UNRESPONSIVENESS TO RENAL ALLOGRAFTS (1993)

Recent data show that intrathymic injection of allogeneic cells induces donor-specific unresponsiveness to allografts. There is also evidence to suggest that, in addition to recognizing intact MHC molecules, T cells can recognize processed MHC peptides, although the role of this indirect mode of allo-recognition in allograft rejection is unknown. We report that a single intrathymic injection of 100 micrograms of a mixture of eight 25-mer synthetic polymorphic class II MHC allopeptides, representing the full-length sequence of RT1.Bu beta and RT1.Du beta (WF) into incompatible (RT1l) LEW recipients, induced a state of long-term unresponsiveness to subsequent engraftment 2 days later of WF, but not third party (RT1n) BN renal allografts. Intrathymic injection of 100 micrograms of either RT1.Bu beta or RT1.Du beta peptide mixtures alone were insufficient to prolong renal allograft survival. Intravenous or intrasplenic injection of the allopeptide mixture did not affect renal allograft survival, establishing the role of thymic recognition of class II MHC allopeptides in inducing systemic unresponsiveness. The induction of intrathymic donor-specific unresponsiveness was abrogated if thymectomy was performed on the day of renal transplantation or 5 days later. PBLs from long-term surviving animals exhibited marked reduction of proliferation to WF, but not third party BN stimulator lymphocytes in the standard mixed lymphocyte response assay in vitro. These observations emphasize the role of recognition of processed MHC molecules in vascularized allograft rejection and confirm the role of the thymus in acquired systemic tolerance to alloantigens.
Micro-sonicator for spore lysis (2023)

A micro-sonicator for spore lysis. Using micromachining technology, the micro-sonicator uses ultrasonic excitation of spores to perform spore and cell lysis. The micro-sonicator comprises a container with a cavity therein for retaining the sample in an ultrasonic transmission medium, the cavity being closed by a silicon membrane to which an electrode and piezoelectric material are attached, with the electrode and piezoelectric material being electrically connected to an AC signal generator which causes the membrane to flex and vibrate at the frequency of the applied voltage.
Development, Optimization, and Integration of Inline Phase-Change Switches for Reconfigurable RF Systems (2018)

The goal of any switch is to enable reconfiguration, flexibility, or adaptability for the network in which it is being implemented. Electrical switches that operate at radio frequencies (RF) are designed to increase system functionality and flexibility, such as routing signals to different locations or changing the frequency response of a circuit. Unfortunately, current state-of-the-art (SOA) RF switches do not have the performance, size, or cost in order to enable the large scale flexibility seen in modern digital system-on-chips (SoCs) and FPGAs. Non-volatile chalcogenides present a unique opportunity to create analog SoCs, as low loss, low power consumption, small size, and low cost integration are all simultaneously achievable in this material system. This thesis details the first demonstration, performance, and integration of 4-terminal, indirectly heated phase-change switches for reconfigurable RF systems. The first demonstration of device functionality outperformed SOA FET-based RF switches in terms of frequency performance (1.1 THz Fco, or 145 fs Ron*Coff), and was improved by over an order of magnitude over the course of this research (12.5 THz Fco, or 12.7 fs Ron*Coff). The investigations into power handling have resulted in an extracted threshold field of 12.6 V/μm in 50:50 GeTe, an improvement in OFF-state power handling from 18 dBm to 29 dBm, and a switch with a simultaneous Ron, Coff, Fco, Vth, PRFmax,off, and reliability of 1.2 Ω, 12.3 fF, 10.6 THz, 6 V, 28 dBm, and &gt;500,000 cycles, respectively. A correlation between the DC Vth and the RF power handling was demonstrated, identifying the fundamental mechanism for power handling limitations. Three different reconfigurable RF system prototypes were fabricated using heterogeneous integration of these phase-change switches with a multifunction SiGe BiCMOS MMIC. Problems with the RF performance of the system highlighted the need for an improved integration of these phase-change switches. A back-end-of-line (BEOL), CMOS-compatible monolithic integration process was then experimentally demonstrated for the first time, detailing the benefits of future monolithically integrated phase-change switches on a variety of semiconductor technologies.
Role of Counterion Concentration in Determining Micelle Aggregation:  Evaluation of the Combination of Constraints from Small-Angle Neutron Scattering, Electron Paramagnetic Resonance, and Time-Resolved Fluorescence Quenching (2004)

Small-angle neutron scattering (SANS) has been used to study a series of aqueous solutions of (i) the anionic surfactant sodium dodecyl sulfate and the simple electrolyte sodium chloride and (ii) the cationic surfactants dodecyltrimethylammonium bromide and dodecyltrimethylammonium chloride, in the presence of sodium bromide and sodium chloride, respectively. For all three systems, the surfactant spans a wide concentration range, and by suitable choices of electrolyte concentration, it is possible to engineer these solutions to have the same concentration of counterions in the aqueous phase. According to a recent hypothesis by Bales et al. (J. Phys. Chem. B 2001, 105, 6798), such a series is expected to produce micelles having the same aggregation number (Nagg), a point verified by time-resolved fluorescence quenching (TRFQ) and electron paramagnetic resonance (EPR). The SANS results presented here are in good agreement with the TRFQ and EPR studies. We therefore show unequivocally that the sizes and shapes of these surfactant micelles depend only on the free counterion concentration, a conclusion supported by conventional theories of micellization. Subsequently, for the SDS data, a comparison is made between fitting the SANS data to a model in which the aggregation number and degree of hydration are constrained and fitting them to a model in which these features are fittable parameters. In essence, both approaches yield the same conclusion. Such an approach is not possible with the cationic surfactants, as the contrast between the hydrated shell and the core is minimal.
Heterochromatin-Associated Protein 1, HP1Hsα, in Breast Cancer Invasion and Metastasis (2005)

Heterochromatin has repressive effects on euchromatic gene expression. The mechanisms contributing to gene silencing are not known, however silencing has been shown to be modulated in part by heterochromatin-associated protein 1, HP1Hsα. We have identified a reduction in HP1Hsα expression in invasive/metastatic human breast cancer cell lines and in tumor cells from distant metastases. Furthermore, HP1Hsα transfected invasive/metastatic breast cancer cells show a reduction in the invasive phenotype indicating that HP1Hsα is involved in modulating specific biological activities in the metastatic cascade. Here, we discuss the role of heterochromatin and HP1Hsα expression in breast cancer invasion and metastasis with regard to gene silencing, chromatin packaging, and nuclear architecture. In addition, we introduce working models for mechanisms of HP1Hsα function that will be addressed with future studies.
Susceptibility of pretreated wood sections of Norway spruce (Picea abies) clones to enzymatic hydrolysis (2011)

The structure of softwoods, which confers resistance to degradation through hydrolysis and decay, currently limits their use for the production of biofuels. However, since wood is very heterogeneous, it is possible that differences in wood properties within and between trees could differentially affect its processability. In this research, heartwood (inner) and sapwood (outer) from Norway spruce ( Picea abies (L.) Karst.) clones were enzymatically hydrolyzed by Trichoderma viride cellulases after concentrated acid pretreatment. Wood sections with two particle sizes were compared based on their susceptibility to enzymatic hydrolysis, evaluated by assaying the formation of hydrolysis products and measured as reducing sugar yield (RSY). We also studied the relationship between RSY and the susceptibility to Heterobasidion parviporum wood decay and whether these traits are reflected in wood density and yield. Wood from the outer section produced more RSY with higher glucan but lower lignin content than wood from the inner section. Furthermore, susceptibility to enzymatic hydrolysis was positively correlated with H. parviporum wood decay, while both processes were negatively correlated with wood density. Our results revealed the importance of clonal trials for identifying suitable lignocellulosic biomass when considering wood properties and indicate that potential genotypes for the production of biofuels are not necessarily the most productive.
Trends In Microbial Synthesis of Natural Products and Biofuels (2009)

Ever since the era of recombinant DNA technology for natural product biosynthesis emerged (292), microorganisms are increasingly becoming common production platforms for many fine chemicals, including natural products and biofuels, that are currently being produced either through chemical methods or using plant and organ cell cultures. The rapid elucidation of biosynthetic pathways made possible through advanced genomic tools has made natural products again the molecules of choice for drug development. Indeed, half of the drugs currently in clinical use are natural products and it is expected that the market size of biotechnology-derived small molecules will exceed billion U.S.$100 in 2010 and billion U.S.$400 in 2030 (3, 293). There are still many challenges facing the use of microorganisms for high-value chemical synthesis. For example, further developments of recent advances are necessary to make a fermentation-based biobutanol industry that can compete effectively with petrochemically derived butanol. As such, we believe that biocatalyst factories such as E. coli and S. cerevisiae will not only continue to be highly attractive alternatives to traditional chemical manufacturing but the application of powerful systems biology approaches will facilitate their expanded role in industrial applications (294-296).
Utilization of Myosin and Actin Bundles for the Transport of Molecular Cargo (2010)

The utilization of motor proteins for the movement and assembly of synthetic components is currently a goal of nanoengineering research. Application of the myosin actin motor system for nanotechnological uses has been hampered due to the low flexural rigidity of individual F-actin filaments. Here it is demonstrated how actin bundling can be used to affect the translational behavior of myosin-propelled filaments, transport molecules across a motor-patterned surface, and that the movement of bundled actin can be regulated photonically. These data suggest that actin bundling may significantly improve the applicability of the myosin motor for future nanotechnological applications.
Human leukocyte cathepsin G. Subsite mapping with 4-nitroanilides, chemical modification, and effect of possible cofactors (1985)

The extended substrate binding site of cathepsin G from human leukocytes has been mapped by using a series of peptide 4-nitroanilide substrates. The enzyme has a significant preference for substrates with a P1 Phe over those with the other aromatic amino acids Tyr and Trp. The S2 subsite was mapped with the substrates Suc-Phe-AA-Phe-NA where AA was 13 of the 20 amino acid residues commonly found in proteins. The best residues were Pro and Met. The S3 subsite was mapped with the sequence Suc-AA-Pro-Phe-NA by using 14 different amino acid residues for AA. The two best residues were the isosteric Val and Thr. No significant improvement in reactivity was obtained by extending the substrate to include seven different P4 residues. The kinetic parameters for cathepsin G are significantly slower than those for many other serine proteases. Changes in the reaction conditions and addition of possible cofactors or ligands were in general found to have little effect on the enzymatic activity, while chemical modifications and proteolysis destroyed the activity of cathepsin G. Cathepsin G hydrolyzed peptides containing model desmosine residues and prefers the hydrophobic picolinoyllysine derivative over lysine by substantial margins at both the S4 and S2 subsites but will not tolerate it at S3. Substrates with sequences related to the cathepsin G cleavage site in angiotensin I and angiotensinogen, and the reactive site of alpha 1-antichymotrypsin, were hydrolyzed effectively by enzyme, but with unexceptional rates. Our results indicate that the natural substrate(s) and function(s) of cathepsin G still remain to be discovered.
Organic solvent-free production of colloidally stable spherical lignin nanoparticles at high mass concentrations (2022)

Organic solvent-free production of lignin nanoparticles opens a new and scalable route to lignin-based nanogels and other materials.
Bidirectional isolated non-resonant DAB DC-DC converter for ultra-wide input voltage range applications (2014)

This paper details efficiency optimized operation and design of a bi-directional and isolated five-level Dual Active Bridge (5LDAB) converter for an application that requires ultra-wide voltage and power ranges. The rated power of the considered converter is 7.5kW, the specified input voltage range is 150V ≤ V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">dc1</sub> ≤ 800V and the output voltage is constant, V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">dc2</sub> = 700V. In order to achieve high efficiency levels in a wide operating range, a modulation scheme is proposed to minimize the transformer rms current. Results of transformer rms currents and of efficiencies are presented for the 5LDAB and compared with the results obtained for an efficiency optimized conventional Dual Active Bridge (DAB) converter. Compared with the DAB topology, the 5LDAB converter can achieve an overall reduction of transformer rms currents and of conduction losses in the higher voltage regime of the operating range.
Optimization of triazole-based TGR5 agonists towards orally available agents (2012)

With the challenge of striking the balance of TGR5 potency and clearance, the screening strategy as well as medicinal chemistry strategy are discussed in this article.
1200V SiC JFET in Cascode Light Configuration: Comparison versus Si and SiC Based Switches (2011)

A 1200 V SiC JFET has been demonstrated to achieve ultra-low switching losses ten times lower than for industrial grade 1200V Si IGBT. The low switching losses are also shown to compete with the fastest 600V class MOSFET in the market, yielding 1.1% higher PFC stage efficiency for 340 kHz switching frequency, when same device on-resistances were measured. The proposed normally-on JFET also differentiates over the IGBT by its purely Ohmic output characteristics without any voltage threshold, and by a monolithically integrated body diode with practically zero reverse recovery. In this paper we outline as well how the other pre-requisites for a 1200 V SiC switch in applications such as photovoltaic systems and UPS can be fulfilled by the proposed JFET solution: long-term reliability, product cost optimization by low specific on-resistance combined with reasonable process window expectations. Finally, a normally-off like safe operation behavior is ensured by a dedicated driving scheme utilizing a low-voltage Si MOSFET as protection device at system start-up and for system failure conditions.
How I treat nodular lymphocyte-predominant Hodgkin lymphoma (2020)

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity with distinct pathologic and clinical characteristics. Unlike the malignant cells in classical Hodgkin lymphoma, the disease-defining lymphocyte-predominant cells in NLPHL are consistently positive for CD20, but do not express CD30. The clinical course of NLPHL is indolent in the majority of cases. Most patients present with early-stage disease at the initial diagnosis. First-line treatment of stage IA NLPHL usually consists of limited-field radiotherapy alone. Patients with early-stage NLPHL other than stage IA and intermediate-stage disease mostly receive combined-modality treatment, whereas individuals with advanced NLPHL are treated with chemotherapy alone. In relapsed NLPHL, conventional chemotherapy, anti-CD20 antibodies, and radiotherapy represent active treatment modalities. Only patients with poor-risk characteristics such as early disease recurrence are candidates for aggressive salvage treatment with high-dose chemotherapy and autologous stem cell transplantation. The overall and relative survival of patients with NLPHL is excellent as indicated by a low excess mortality compared with the general population. This article discusses treatment options for patients with NLPHL and factors that influence the choice of therapy on the basis of the available data and 2 clinical cases.