gebhart/patrepeval huggingface dataset:
Stabilizing Inactive Conformations of MALT1 as an Effective Approach to Inhibit Its Protease Activity (2020)

Abstract The paracaspase MALT1 (mucosa associated lymphoid tissue lymphoma translocated gene 1) plays an important role in various immune pathways and is proposed as a therapeutic target for autoimmune disorders as well as different types of cancer, such as diffuse large B‐cell lymphoma (DLBCL). Different mechanisms are explored to inhibit the protease activity of MALT1 and two unrelated chemical scaffolds are discovered. Biophysical and structural studies reveal that both scaffolds stabilize the protease in an inactive conformation. While one ligand binds to the allosteric site at the interface between the caspase and the Ig3 domain, the other ligand binds to the active site using a so far undescribed mechanism. Iterative structure‐based drug discovery on one scaffold results in the identification of a potent, selective, and orally bioavailable MALT1 inhibitor.
Broad epitope coverage of a human in vitro antibody library (2016)

Successful discovery of therapeutic antibodies hinges on the identification of appropriate affinity binders targeting a diversity of molecular epitopes presented by the antigen. Antibody campaigns that yield such broad "epitope coverage" increase the likelihood of identifying candidates with the desired biological functions. Accordingly, epitope binning assays are employed in the early discovery stages to partition antibodies into epitope families or "bins" and prioritize leads for further characterization and optimization. The collaborative program described here, which used hen egg white lysozyme (HEL) as a model antigen, combined 3 key capabilities: 1) access to a diverse panel of antibodies selected from a human in vitro antibody library; 2) application of state-of-the-art high-throughput epitope binning; and 3) analysis and interpretation of the epitope binning data with reference to an exhaustive set of published antibody:HEL co-crystal structures. Binning experiments on a large merged panel of antibodies containing clones from the library and the literature revealed that the inferred epitopes for the library clones overlapped with, and extended beyond, the known structural epitopes. Our analysis revealed that nearly the entire solvent-exposed surface of HEL is antigenic, as has been proposed for protein antigens in general. The data further demonstrated that synthetic antibody repertoires provide as wide epitope coverage as those obtained from animal immunizations. The work highlights molecular insights contributed by increasingly higher-throughput binning methods and their broad utility to guide the discovery of therapeutic antibodies representing a diverse set of functional epitopes.
Deep Q‑Learning Based Resource Management in IRS-Assisted VLC Systems (2022)

&lt;p&gt;Visible Light Communication (VLC) is a promising enabling technology for the next-generation wireless networks, as it complements radio-frequency (RF)-based communications by providing wider bandwidth, higher data rates, and immunity to interference from electromagnetic sources. However, due to its unique characteristics, VLC is highly sensitive to the line-of-sight (LoS) blockage. Recently, intelligent reflecting surface (IRS) has been proposed as an innovative solution that dynamically reconfigures the wireless environment. The present contribution proposes a two-stage resource management framework in an indoor VLC system: In the first stage, a maximum possible fairness (MPF) algorithm is presented in order to maximize the fairness amongst the users. In the second stage, deep Q-learning is exploited in order to maximize the overall spectral efficiency (SE). The corresponding numerical results have shown that the proposed DQL-MPF framework exhibits superior performance in terms of the overall SE, achieved at fast convergence rate. More specifically, when the noise power is high and the number of users is relatively large, the DQL-MPF algorithm achieves a more than tenfold overall SE compared to the Baseline scheme. Moreover, the synergy between the MPF and the DQL algorithms is investigated. To this end, we demonstrate that the MPF algorithm maximizes the fairness amongst the users while the DQL algorithm maximizes the overall SE and improves the robustness against the noise.&lt;/p&gt;
Novel Imaging Technologies in Laparoscopic Gynecologic Surgery: A Systematic Review (2017)

Novel imaging technologies continued to be introduced into the operative setting. In particular, novel image-enhanced laparoscopic techniques are being explored for use in gynecologic operations. This systematic review describes these technologies in four relevant areas of gynecologic surgery. The PubMed database was searched for human, English-language studies, and the reference lists of retrieved articles were reviewed. An analysis of pooled data from 34 studies that met inclusion criteria was performed. The results suggest that image-enhanced technology may be useful in several common gynecologic procedures. Auto- and drug-enhanced fluorescence laparoscopy allow for increased detection of nonpigmented endometriotic lesions. Using these technologies for peritoneal staging of ovarian malignancy is of uncertain benefit. Drug-enhanced fluorescence laparoscopy for sentinel lymph node (SLN) detection in patients with uterine or cervical malignancy is feasible, showing a high rate of SLN detection, but a low sensitivity of identifying metastases. Finally, their use in intra-operative visualization of the ureter is promising. The majority of available data was from feasibility studies with limited sample sizes. Nevertheless, the results described in this systematic review support the expectation that these upcoming image-enhanced laparoscopy techniques will play a more important role in the future care of gynecologic patients.
Proteoglycan-4 is an Essential Regulator of Synovial Macrophage Polarization and Inflammatory Macrophage Joint Infiltration (2021)

Abstract Background: Synovial macrophages (SMs) perform a multitude of functions that include clearance of cell debris and foreign bodies, tissue immune surveillance, and resolution of inflammation. At one end of the macrophage polarization spectrum is the inflammatory phenotype (M1), which secretes IL-1β, IL-6 and expresses iNOS. On the opposite end of the spectrum is the anti-inflammatory phenotype (M2) which is characterized by the secretion of IL-10 and TGF-β. PRG4 is an important regulator of synovial hyperplasia and fibrotic remodeling and the involvement of SM activation in PRG4’s homeostatic role is yet to be defined. Our objectives were to study PRG4’s importance to SM homeostasis, M1 and M2 polarization and joint infiltration of bone marrow-derived macrophages (BMDMs) and investigate the role of SMs in mediating synovial fibrosis in Prg4 gene-trap ( Prg4 GT/GT ) murine knee joints. Methods : SM phenotyping in Prg4 GT/GT and Prg4 +/+ joints was performed using flow cytometry and the balance between CD86+/CD206- (M1) and CD86-/CD206+ (M2) SMs was studied as animals aged. Expression of iNOS and IL-6 in CD86+ SMs, arginase-1 in CD206+ SMs and the impact of Prg4 recombination on SM polarization and BMDM infiltration following a TLR2 agonist challenge were determined. Inflammatory SMs were depleted using liposomal clodronate and synovial membrane thickness and expression of fibrotic markers: α-SMA, PLOD2 and collagen type I (COL-I) were assessed using immunohistochemistry. Results: Total macrophages in Prg4 GT/GT joints were higher than corresponding age-matched Prg4 +/+ joints ( p&lt;0.0001 ) and the percentages of CD86+/CD206- and CD86+/CD206+ SMs increased in Prg4 GT /GT joints as animals aged ( p&lt;0.0001 ), whereas the percentage of CD86-/CD206+ SMs decreased ( p&lt;0.001 ). CD86+ SMs expressed iNOS and IL-6 compared to CD86- SMs ( p&lt;0.0001 ) while CD206+ SMs also expressed arginase-1. Prg4 re-expression limited the accumulation of CD86+ SMs, increased CD86-/CD206+ SMs and attenuated BMDM recruitment ( p&lt;0.001 ). Liposomal clodronate reduced inflammatory SMs and in turn reduced synovial hyperplasia, α-SMA, PLOD2 and COL-I expression in the synovium ( p&lt;0.0001 ). Conclusions: SM accumulation in the joint and the balance between inflammatory and anti-inflammatory SM subsets are regulated by PRG4. In the absence of PRG4’s role, the synovium is populated with inflammatory macrophages that drive synovial fibrosis.
Clinical Applications of Procedural Changes by Experienced and Novice Pediatric Physical Therapists (1996)

Some scholars propose that physical therapists use formal decision analyses in making clinical decisions, but these processes are time consuming. Other researchers suggest physical therapists make rapid, on the spot, clinical decisions based on improvisation and intuition. This study explores how frequently pediatric physical therapists change their therapy procedures within a therapy session. Procedural changes are illustrated and described using qualitative research methods to portray the practice of three experienced and three novice pediatric physical therapists. These clinicians were videotaped during 48 hourly sessions with 18 children who were diagnosed with diplegic cerebral palsy. Then, videotapes were used to elicit retrospective think-aloud dialogues, which were transcribed, coded, and analyzed to assess how frequently therapists verbalized changing their therapy procedures. Treatment videotapes of five sessions were further analyzed to highlight and illustrate how one experienced clinician applied procedural changes with one child. Findings revealed that experienced clinicians verbalized changing their procedures approximately every 46 seconds compared with a mean of every 86 seconds by novices. Six treatment activities accounted for 72% of the treatment time and illustrate how one experienced clinician applied procedural changes within sessions of therapy over four months of weekly treatment with one child. Generally, the rapid procedural changes found in this study suggest formal decision analyses are not practical for within-session decision making in pediatric physical therapy. Rapid procedural changes by experienced therapists seemed to be in “harmony” with the children, based on their large repertoire of clinical experience. In contrast, novices verbalized “abrupt” procedural changes based on lists of treatments activities. These results provide valuable insights into clinical practice and decision making in pediatric physical therapy.
Deletion of the Mycobacterium tuberculosis pknH Gene Confers a Higher Bacillary Load during the Chronic Phase of Infection in BALB/c Mice (2005)

The role of the serine/threonine kinase PknH in the physiology and virulence of Mycobacterium tuberculosis was assessed by the construction of a pknH deletion mutant. Deletion of the pknH gene did not affect sensitivity to the antimycobacterial drug ethambutol, although it was previously thought to be involved in regulating expression of emb genes encoding arabinosyl transferases, the targets of ethambutol. Nevertheless, transcription analyses revealed that genes associated with mycobacterial cell wall component synthesis, such as emb and ini operons, are downstream substrates of the PknH signaling cascade. In vitro survival studies revealed that a mutant with a deletion of the pknH gene displayed increased resistance to acidified nitrite stress, suggesting that nitric oxide is one of the potential environmental triggers for PknH activation. The effect of pknH deletion on mycobacterial virulence was investigated in BALB/c mice. In this model, the DeltapknH mutant was found to survive and replicate to a higher bacillary load in mouse organs than its parental strain and the pknH-complemented strain. In contrast, another closely related kinase mutant, the DeltapknE mutant, obtained from the same parental strain, was not affected in its virulence phenotype. Infection of THP-1 cells or in vitro growth studies in 7H9 medium did not reveal a significant in vitro growth advantage phenotype for the DeltapknH mutant. In conclusion, we propose that the serine/threonine kinase PknH plays a role in regulating bacillary load in mouse organs to facilitate adaptation to the host environment, possibly by enabling a regulated chronic infection by M. tuberculosis.
Sensing Tablet Grasp + Micro-mobility for Active Reading (2015)

The orientation and repositioning of physical artefacts (such as paper documents) to afford shared viewing of content, or to steer the attention of others to specific details, is known as micro-mobility. But the role of grasp in micro-mobility has rarely been considered, much less sensed by devices. We therefore employ capacitive grip sensing and inertial motion to explore the design space of combined grasp + micro-mobility by considering three classes of technique in the context of active reading. Single user, single device techniques support grip-influenced behaviors such as bookmarking a page with a finger, but combine this with physical embodiment to allow flipping back to a previous location. Multiple user, single device techniques, such as passing a tablet to another user or working side-by-side on a single device, add fresh nuances of expression to co-located collaboration. And single user, multiple device techniques afford facile cross-referencing of content across devices. Founded on observations of grasp and micro-mobility, these techniques open up new possibilities for both individual and collaborative interaction with electronic documents.
Poly(vinyl chloride‐g‐butyl rubber) (1976)

Abstract The synthesis of poly(vinyl chloride‐ g ‐butyl rubber) and some of its physical properties are described. The key to the synthesis involves copolymerization initiation of an isobutylene–isoprene charge by a PVC/Et 2 AlCl initiator system with 1,2‐dichloroethane as solvent. The graft is a thermoplastic; cast films are flexible and optically clear. Proof of grafting is the crosslinking with S 2 Cl 2 of the pentane‐extracted product in THF solution. Crosslinking the butyl rubber moiety in the graft reduces overall stress properties.
Special Words on Special Sections (2002)

The <i>Journal of Micro/Nanopatterning, Materials, and Metrology</i> (JM3) publishes peer-reviewed papers on the core enabling technologies that address the patterning needs of the electronics industry.
Diaboloidal mirrors: algebraic solution and surface shape approximations (2021)

A new type of optical element that can focus a cylindrical wave to a point focus (or vice versa) is analytically described. Such waves are, for example, produced in a beamline where light is collimated in one direction and then doubly focused by a single optic. A classical example in X-ray optics is the collimated two-crystal monochromator, with toroidal mirror refocusing. The element here replaces the toroid, and in such a system provides completely aberration free, point-to-point imaging of rays from the on-axis source point. We present an analytic solution for the mirror shape in its laboratory coordinate system with zero slope at the centre, and approximate solutions, based on bending an oblique circular cone and a bent right circular cylinder, that may facilitate fabrication and metrology.
Multi-domain ASON/GMPLS network operation: current status and future evolution (2007)

This paper describes clarifications and comparisons of routing models for multi-domain optical networks as well as the current status and future perspective for ASON/GMPLS technologies. The three routing models, the per-domain routing, the ASON hierarchical routing, and the PCE-based routing, have been being standardized for the ASON/GMPLS multi-domain networks. In this paper, we compare these three routing models in terms of path computation capabilities, on-line multiple path planning capability and inter-domain confidentiality. According to our analyses, the PCE-based routing and the ASON hierarchical routing models have rich path computation capabilities enough for multi-domain ASON/GMPLS network operation, while the per-domain routing does not provide much capabilities. One of the significant issues left for the ASON hierarchical routing model is an appropriate abstraction mechanism which strongly affects the path computation capabilities and inter-domain confidentiality. In addition to the sufficient path computation capabilities, the PCE-based routing model offers the on-line bulk optimization for multiple requests. Therefore, we concluded that the PCE-based routing is the most suitable for multi-domain ASON/GMPLS networks.
ChemInform Abstract: Synthesis, Electrical Conductivity and Electron Paramagnetic Resonance Spectroscopy of Polymers Derived from NOPF6‐Doped XYZ‐Triheterocycles Based on Pyrrole, Furan and Thiophene. (1993)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Synthesis and GABA Receptor Potency of 3‐Thiomethyl‐4‐(hetero)aryl‐5‐amino‐1‐phenylpyrazoles. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
In Situ Optical Quantification of Extracellular Electron Transfer using Plasmonic Metal Oxide Nanocrystals (2020)

Abstract Extracellular electron transfer (EET) is a critical form of microbial metabolism that enables respiration on a variety of inorganic substrates, including metal oxides. However, quantifying current generated by electroactive bacteria has been predominately limited to biofilms formed on electrodes. To address this, we developed a platform for quantifying EET flux from cell suspensions using aqueous dispersions of infrared plasmonic tin-doped indium oxide nanocrystals. Tracking the change in optical extinction during electron transfer enabled quantification of current generated by planktonic Shewanella oneidensis cultures. Using this method, we differentiated between starved and actively respiring cells, between cells of varying genotype, and between cells engineered to differentially express a key EET gene using an inducible genetic circuit. Overall, our results validate the utility of colloidally stable plasmonic metal oxide nanocrystals as quantitative biosensors in native biological environments and contribute to a fundamental understanding of planktonic S. oneidensis electrophysiology using simple in situ spectroscopy.
Microchannel Anechoic Corner for Size-Selective Separation and Medium Exchange via Traveling Surface Acoustic Waves (2015)

We demonstrate a miniaturized acoustofluidic device composed of a pair of slanted interdigitated transducers (SIDTs) and a polydimethylsiloxane microchannel for achieving size-selective separation and exchange of medium around polystyrene particles in a continuous, label-free, and contactless fashion. The SIDTs, deposited parallel to each other, produce tunable traveling surface acoustic waves (TSAWs) at desired locations, which, in turn, yield an anechoic corner inside the microchannel that is used to selectively deflect particles of choice from their streamlines. The TSAWs with frequency fR originating from the right SIDT and propagating left toward the microchannel normal to the fluid flow direction, laterally deflect larger particles with diameter d1 from the hydrodynamically focused sample fluid that carries other particles as well with diameters d2 and d3, such that d1 > d2 > d3. The deflected particles (d1) are pushed into the top-left corner of the microchannel. Downstream, the TSAWs with frequency fL, such that fL > fR, disseminating from the left SIDT, deflect the medium-sized particles (d2) rightward, leaving behind the larger particles (d1) unaffected in the top-left anechoic corner and the smaller particles (d3) in the middle of the microchannel, thereby achieving particle separation. A particle not present in the anechoic corner could be deflected rightward to realize twice the medium exchange. In this work, the three-way separation of polystyrene particles with diameters of 3, 4.2, and 5 μm and 3, 5, and 7 μm is achieved using two separate devices. Moreover, these devices are used to demonstrate multimedium exchange around polystyrene particles ∼5 μm and 7 μm in diameter.
Interleukin‐2 receptor common γ‐chain signaling cytokines regulate activated T cell apoptosis in response to growth factor withdrawal: Selective induction of anti‐apoptotic (bcl‐2, bcl‐xL) but not pro‐apoptotic (bax, bcl‐xS) gene expression (1996)

Cytokine deprivation from activated T cells leads to apoptosis associated with down-regulation of the bcl-2 gene product. It is not clear, however, how cytokines other than interleukin-2 (IL-2) may affect this process and regulate the involvement of other apoptosis-modulating genes. We show that a group of cytokines including IL-2 (IL-2R gamma), prevent the apoptosis of IL-2-deprived activated T cells. This rescue involves the induction of the anti-apoptosis genes bcl-2 and bcl-xL), but causes little change in expression of bax and bcl-xS, which promote apoptosis. Furthermore, the prevention of apoptosis and induction of proliferation by the common gamma chain cytokines can be dissociated. Thus, when proliferation is blocked, the common gamma chain cytokines still induce up-regulation of bcl-2 relative to bax and retard apoptosis. These cytokines can thus regulate the persistence or removal of effector T cells by coordinating the balance between genes which promote and those which inhibit apoptosis, events which are probably mediated at least in part by signals through the common gamma chain. These data also implicate inappropriate T cell apoptosis resulting from a dysfunctional common gamma-chain as part of the pathophysiological defect in patients with X-linked severe-combined immunodeficiency (SCID).
Heavy Ion Bit Response and Analysis of 256 Megabit Non-Volatile Spin-Torque-Transfer Magnetoresistive Random Access Memory (STT-MRAM) (2018)

Heavy-ion testing was performed recently on 256 Mb STT-MRAMs as a function of fluence and LET for Ne, Ar, Kr, and Au heavy ions. Zero hard-errors were observed in STT-MRAM (Spin-Torque-Transfer Magneto-resistive Random Access Memory) bits in this first-known heavy-ion testing of STT-MRAMs that are based on second-generation MRAM technology. Results from this STT-MRAM heavy-ion testing are compared to heavy-ion test results from Honeywell toggle-bit MRAMs that are based on first-generation MRAM technology. Based on this testing, the changes in the Magnetic Tunnel Junction (MTJ) between first-generation and second-generation MRAM technology were not observed to degrade heavy-ion characteristics; and heavy-ion performance potentially may have been improved.
Predictors of Early Recurrence of Adenocarcinoma of the Head of the Pancreas after Curative Resection (2015)

Objective To determine the time to recurrence of pancreatic adenocarcinoma of the head of the pancreas after curative resection at one tertiary-care Health Care Campus and to determine the factors that predict early recurrence. Methods Retrospective data was gathered from 64 consecutive pancreatic adenocarcinoma patients undergoing curative Whipple procedures from 2007-2011. Patients were divided into early recurrence, within 185 days, and late or no recurrence. Results Disease-free survival after 6 months was 64%; at 8 months, it was 50%. Factors that contributed to early recurrence included increased age at surgery (P=0.03746), larger tumor size on pathology (P=0.0093), and resection margins less than 0.1mm (P=0.0471). Larger tumor size as measured by endoscopic ultrasound showed a trend for early recurrence (P=0.086821). Conclusions Aggressive screening and detection mechanisms for pancreatic carcinoma should be applied more frequently and with increased age to ensure identification of pancreatic carcinoma before large growth in tumor size.