gebhart/patrepeval huggingface dataset:
Secreted Proteases Control the Timing of Aggregative Community Formation in Vibrio cholerae (2021)

Bacteria orchestrate collective behaviors using the cell-cell communication process called quorum sensing (QS). QS relies on the synthesis, release, and group-wide detection of small molecules called autoinducers. In Vibrio cholerae, a multicellular community aggregation program occurs in liquid, during the stationary phase, and in the high-cell-density QS state. Here, we demonstrate that this aggregation program consists of two subprograms. In one subprogram, which we call void formation, structures form that contain few cells but provide a scaffold within which cells can embed. The other subprogram relies on flagellar machinery and enables cells to enter voids. A genetic screen for factors contributing to void formation, coupled with companion molecular analyses, showed that four extracellular proteases, Vca0812, Vca0813, HapA, and PrtV, control the onset timing of both void formation and aggregation; moreover, proteolytic activity is required. These proteases, or their downstream products, can be shared between void-producing and non-void-forming cells and can elicit aggregation in a normally nonaggregating V. cholerae strain. Employing multiple proteases to control void formation and aggregation timing could provide a redundant and irreversible path to commitment to this community lifestyle. <b>IMPORTANCE</b> Bacteria can work as collectives to form multicellular communities. Vibrio cholerae, the bacterium that causes the disease cholera in humans, forms aggregated communities in liquid. Aggregate formation relies on a chemical communication process called quorum sensing. Here, we show that, beyond overarching control by quorum sensing, there are two aggregation subprograms. One subprogram, which we call void formation, creates a scaffold within which cells can embed. The second subprogram, which allows bacteria to enter the scaffold, requires motility. We discovered that four extracellular proteases control the timing of both void formation and aggregation. We argue that, by using redundant proteases, V. cholerae ensures the reliable execution of this community formation process. These findings may provide insight into how V. cholerae persists in the marine environment or colonizes the human host, as both lifestyles are central to the spread of the disease cholera.
A Gapless, Unambiguous Genome Sequence of the Enterohemorrhagic Escherichia coli O157:H7 Strain EDL933 (2014)

Escherichia coli EDL933 is the prototypic strain for enterohemorrhagic E. coli serotype O157:H7, associated with deadly food-borne outbreaks. Because the publicly available sequence of the EDL933 genome has gaps and >6,000 ambiguous base calls, we here present an updated high-quality, unambiguous genome sequence with no assembly gaps.
Deep Learning Based Ultrasound Image Reconstruction Method: A Time Coherence Study (2019)

Recently, deep learning entered the ultrasound (US) image reconstruction community, demonstrating unprecedented performances on image reconstruction tasks. The use of deep neural networks to reconstruct, restore or enhance US images has been challenged on its capability to preserve time-coherence, mostly because of their inherent non-linear properties. Most novel image reconstruction methods are typically only evaluated on static images, lacking any demonstration of their potential applicability to other imaging modes, such as vector flow imaging (VFI) and shear-wave elastography, which heavily rely on the time-coherence of consecutive reconstructed images. In this work, we demonstrate that our previously proposed convolutional neural network (CNN)-based image restoration approach, trained exclusively to improve the quality of static images, does not harm the time-coherence of consecutive frames in the context of VFI. Using dynamical numerical phantoms inspired by the synthetic aperture vector flow imaging (SA-VFI) challenge, we quantitatively show that the use of such an image restoration technique does not damage vector flow estimations, computed with a state-of-the-art speckle tracking algorithm, on simple phantoms with constant echogenicity, and that it even has the potential to improve such estimations in more complex scenarios.
A subclass of archaeal U8-tRNA sulfurases requires a [4Fe–4S] cluster for catalysis (2022)

Sulfuration of uridine 8, in bacterial and archaeal tRNAs, is catalyzed by enzymes formerly known as ThiI, but renamed here TtuI. Two different classes of TtuI proteins, which possess a PP-loop-containing pyrophosphatase domain that includes a conserved cysteine important for catalysis, have been identified. The first class, as exemplified by the prototypic Escherichia coli enzyme, possesses an additional C-terminal rhodanese domain harboring a second cysteine, which serves to form a catalytic persulfide. Among the second class of TtuI proteins that do not possess the rhodanese domain, some archaeal proteins display a conserved CXXC + C motif. We report here spectroscopic and enzymatic studies showing that TtuI from Methanococcus maripaludis and Pyrococcus furiosus can assemble a [4Fe-4S] cluster that is essential for tRNA sulfuration activity. Moreover, structural modeling studies, together with previously reported mutagenesis experiments of M. maripaludis TtuI, indicate that the [4Fe-4S] cluster is coordinated by the three cysteines of the CXXC + C motif. Altogether, our results raise a novel mechanism for U8-tRNA sulfuration, in which the cluster is proposed to catalyze the transfer of sulfur atoms to the activated tRNA substrate.
Comparing multilayer perceptron to Deep Belief Network Tandem features for robust ASR (2011)

In this paper, we extend the work done on integrating multilayer perceptron (MLP) networks with HMM systems via the Tandem approach. In particular, we explore whether the use of Deep Belief Networks (DBN) adds any substantial gain over MLPs on the Aurora2 speech recognition task under mismatched noise conditions. Our findings suggest that DBNs outperform single layer MLPs under the clean condition, but the gains diminish as the noise level is increased. Furthermore, using MFCCs in conjunction with the posteriors from DBNs outperforms merely using single DBNs in low to moderate noise conditions. MFCCs, however, do not help for the high noise settings.
Vaccines against sexually transmitted diseases (2003)

Human sexually transmitted infections are prevalent throughout the world. Several have been associated with adverse pregnancy outcome and increased susceptibility to HIV infection, in addition to the discomfort of inflammation of the genital tract. Yet vaccines to protect against the infection at the genital mucosa are not available. Hepatitis B is an exception, but this virus becomes systemic and protection may be at the systemic level. Sexually transmitted diseases (STDs) have long been associated with reproductive failure in cattle. These infections cause considerable economic loss, which has been a stimulus to investigation. Consequently, vaccines and mechanisms of immune protection have been studied quite thoroughly. The results obtained with two commercially available vaccines will be used to illustrate principles of protective immunity against STDs. Both Campylobacter fetus subsp. venerealis and Tritrichomonas foetus are only transmitted sexually and both cause reproductive failure in cattle.
Continuous intrahepatic infusion of floxuridine and leucovorin through an implantable pump for the treatment of hepatic metastases from colorectal carcinoma (1990)

Based on laboratory studies showing enhanced cytotoxicity of floxuridine (FUDR) when used with high doses of leucovorin (LV), a pilot study of FUDR and LV through an implantable pump was initiated for the treatment of hepatic metastases from colorectal cancer. The highest dose of LV that could be administered, taking into account the constraints of the capacity of the pump and the solubility of LV, was 120 mg/m2/d. Due to the possibility of added toxicity, 25% of this dose was initially used. Twenty-four patients were treated at three dose levels. Eight patients were treated with the combination of LV (30 mg/m2/d) and FUDR (0.3 mg/kg/d) for a 14-day infusion through the pump, alternating with 2 weeks of saline. All eight patients had a greater than 50% decrease in measurable disease (PR) and a greater than 50% decrease in carcinoembryonic antigen (CEA) value; however, sclerosing cholangitis developed in two of these patients within 4 months. The next seven patients were treated with a lower dose of FUDR (0.2 mg/kg/d) and the same dose of LV, both for 14 days. Four of seven patients had a PR, and toxicity was decreased with no biliary sclerosis. A third regimen explored the combination of FUDR (0.3 mg/kg/d) and LV (30 mg/m2/d) for 7 days, alternating with 1 week of saline, to evaluate a shorter interval of treatment with the same overall dose intensity. Six of nine patients had a PR and all patients had a greater than 50% decrease in CEA value; sclerosing cholangitis developed in three of these patients. The overall response rate was 72%, with 18 of 25 patients alive after 1 year. The median survival time has not been determined, but it is greater than 27 months. FUDR with LV appeared to be effective in the treatment of hepatic metastases from colorectal carcinoma, but hepatic toxicity appeared to be greater than that previously reported with FUDR alone.
Noninvasive Diffuse Optical Measurement for Monitoring Hemodynamic Response of Radiation Treatment in Head and Neck Tumors (2008)

This study further explores the feasibility of diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS) to measure hemodynamic responses of head and neck tumors during the chemotherapy and radiation therapy.
Abstract 3737: Identifying novel therapeutic targets for cancer stem cell differentiation. (2013)

Abstract A growing body of evidence supports a role for cancer stem cells in the initiation and maintenance of a wide range of tumors. Cancer stem cells appear to be less sensitive to current treatments, necessitating the discovery of novel strategies for targeting this cell type. We hypothesize that driving cancer stem cells to differentiate will be an effective approach for inhibiting tumor growth and recurrence. Indeed, this strategy is used for the treatment of Acute Promyelocytic Leukemia, which presents with an accumulation of promyelocytes. Treatment with all-trans retinoic acid drives these cells to differentiate into neutrophils and leads to complete remission in over 90% of patients. The goal of our work is to identify druggable nodes to drive epithelial cancer stem cells to differentiate, leading to inhibition of tumor growth. We are currently focused on colorectal cancer, for which there is a high unmet medical need. Each year, more than 1.2 million new cases of colorectal adenocarcinoma are reported. It is estimated that 80% of colon tumors have mutations in the adenomatous polyposis coli (APC) gene, which results in constitutive activation of the Wnt pathway and nuclear accumulation of β-catenin. Wnt signaling activates the transcription of genes that drive cell proliferation. Recent studies have shown that β-catenin is necessary for the maintenance of colorectal adenocarcinomas with APC mutations. Indeed, β-catenin knockdown in colon cancer cells drives them to differentiate and decreases their proliferative capacity, reducing tumor size in vivo. We have developed a number of methods to monitor this process in vitro, and will present our efforts to screen for novel targets that can drive colon tumor stem cells to differentiate. Citation Format: Germán L. Vélez Reyes, Haidi Yang, Aaron Wilson, Martin Henault, Elizabeth Frias, Michael Schlabach, Margaret Mclaughlin, Nathan Ross, Gregory Hoffman, Amy Chen, Marc Hild, Aron Jaffe. Identifying novel therapeutic targets for cancer stem cell differentiation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3737. doi:10.1158/1538-7445.AM2013-3737
Design and Optimization of Sparse Planar Antenna Arrays for Wireless 3-D Local Positioning Systems (2017)

In this paper the design and measurement verification of optimized planar sparse arrays for use in wireless localization applications are presented. Existing literature on array optimization has mainly been concerned with arrays intended for imaging applications. As the array requirements for 3-D localization in multipath environments are essentially different, we made an analysis of the array parameters important for this specific application. The set of challenging practically relevant requirements for the optimization of the planar array layout was defined, including a restriction to a small number of antennas and minimal interelement distance bigger than $\lambda /2$ . An adapted multi-objective particle swarm optimization stochastic algorithm was employed to optimize array for the robust and precise direction of arrival of a single source inside a wide angular scan range up to ±60° in azimuth and elevation planes. Two optimized receive arrays consisting of eight patches were manufactured and measured to present the trade-off achieved under the desired requirements. The effects of optimized array parameters on the performance of 3-D positioning are validated by angle measurements in an anechoic chamber and different indoor scenarios.
Beyond the Shockley-Queisser limit : intermediate band and tandem solar cells leveraging silicon and CdTe technology (2016)

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2016.
Long-term multilineage engraftment of autologous genome-edited hematopoietic stem cells in nonhuman primates (2016)

Key Points This study is the first to show that genome-editing approaches can modify multilineage, long-term repopulating cells in a large animal model. We demonstrate that the persistence of genome-edited hematopoietic stem cells can be tracked in vivo in a mutation-specific manner.
Frequency Agile Slot Antenna Using Contactless Capacitive Loading (2022)

With the development of modern wireless systems, the spectral environment has become increasingly crowded. This has spawned a strong interest in frequency, bandwidth, and pattern reconfigurable antennas, which can adaptively tune their response to reduce interference. Most recent development in frequency reconfigurable antennas has focused on tuning by use of microelectromechanical systems, pin diodes, or varactors. However, these tuning techniques are ill-suited for high power applications due to breakdown, non-linear effects, and other performance issues. These problems can be solved by the use of mechanical tuning. In this paper, a piezoelectric linear actuator tuned slot antenna is presented. The design is based upon changing the capacitive loading of a slot antenna, and thereby increasing the electrical length, through physical displacement of a metal plate. The antenna was simulated, fabricated, and measured to tune a full octave from 2-4 GHz while maintaining a maximum return loss of greater than 9.0 dB. Simulations also show a 65.74% to 95.75% radiation efficiency across S-band. A broadside realized gain of greater than 1.73 dB was measured over the entire tuning range. Moreover, the tuning mechanism was proven robust above other methods by withstanding up to 100 W of power incident on the feed at 3 GHz.
A phase 2 study to assess the pharmacokinetics and pharmacodynamics of CPX-351 and its effects on cardiac repolarization in patients with acute leukemias (2019)

Clinicaltrials.gov identifier: NCT02238925.
P075 Epithelial Toll-like receptor 3-dependent synthesis of complement factor B and local complement activation in inflammatory bowel disease (2014)

presence of myofibroblasts in all layers of the intestinal wall. Ulcerative colitis (UC) is classically considered to be a purely mucosal disease although rarely transmural complications such as strictures and stenosis develop. Fibrogenesis in UC has not been studied systematically yet and may be a neglected phenomenon. We therefore investigated whether there is a different fibrotic load in acute vs longstanding UC and whether the degree of fibrosis in UC correlates with the severity of inflammation. Methods: Colectomy specimens from all UC patients operated at the AMC between 2007 2012 were reviewed. Specimens from patients with recent onset refractory therapy UC (diagnosis 10 years) were selected. Patients operated for colon cancer without UC served as controls. On HE 29% vs 33% vs 54%, p = 0.009). Between acute and late UC there was no difference in collagen deposition, however between UC together and controls there was more collagen I expression in the mucosa, MM and muscularis externa (50% vs 10%, p = 0.02; 28% vs 10%, p = 0.048; 71% vs 20%, p = 0.003). In both early and long UC duration, we did not find a correlation between inflammation or collagen deposition or MM thickness. There was a negative correlation between inflammation and aSMA positivity in the submucosa (R = 0.51, p = 0.003) and MM (R = 0.37, p = 0.04). Conclusions: In our series of colectomy specimens, there is more collagen deposition in UC than in controls. No association between disease duration and increased collagen deposition could be found. Expression of aSMA however is lower in UC and correlates with inflammation. Fibrosis in UC does not appear to increase significantly over time.
Differentiating bacterial spores from hoax materials by Raman spectroscopy (2004)

The bioterrorism of October 2001 caused by the distribution of anthrax through the U.S. postal system was compounded by the significant delay associated with positive identification of the <i>Bacillus anthracis</i> spores and the unknown extent of their distribution along the eastern seaboard. In the ensuing two years, literally thousands of hoaxes, letters containing harmless powders, have been mailed creating additional anxiety. Thus, there is a need for instruments and/or methods that can not only identify anthrax-causing spores to save lives, but also identify hoax materials to eliminate costly shutdowns. Here we present Raman spectra of <i>Bacillus cereus</i> spores, an anthrax surrogate, as well as of 30 common substances that might be used as hoax materials. We also examine the choice of laser excitation, 785 nm or 1064 nm, and its impact on the ability to measure visible particles in 5 minutes or less, and to provide a complete answer to the question of suspicious material identity.
Abstract 5002: Anti-tumor activity of a novel anti-human PD-1 antibody BGB-A317 in mouse models (2016)

Abstract Background: Programmed death receptor-1 (PD-1) is a co-inhibitory immune checkpoint molecule. The engagement of PD-1 by its ligands negatively regulates T cell function and induces immune tolerance in both normal and pathological conditions, especially in cancer. BGB-A317 is a novel humanized IgG4 anti-PD-1 antibody under clinical development. The anti-tumor activity of BGB-A317 was evaluated in mouse models and reported here. Material and methods: NOD/SCID mice transplanted with human peripheral blood monocyte (PBL-SCID models) were employed to examine the anti-tumor activity and pharmacokinetics of BGB-A317. In these models, human PBMCs (4-5×106) from healthy donors were co-injected with human tumor cells (A431, 2.5×106) or primary tumor tissue fragments derived from cancer patients (BCCO-028 and BCLU-054, 3×3×3 mm3) subcutaneously in the right flank of the mice. BCCO-028 is human colon cancer and BCLU-054 is human non-small cell lung cancer (NSCLC). The mice were then treated with BGB-A317 or PBS intra-peritoneally once a week from the day of tumor implantation. The tumor infiltrated lymphocytes and PD-L1 expression were examined by immunohistochemistry staining and flow cytometry. Results: In A431 model, 3 doses of BGB-A317, 1, 3, 10mg/kg, were examined. All three doses of BGB-A317 induced significant tumor growth inhibition (TGI) on day 29 (78%, 89%, and 89%, respectively) (p &amp;lt; 0.001 vs. vehicle treatment). Both AUC0-168h and Cmax of BGB-A317 after single dose (day 1, 1st dose) or at steady state (day 29, 5th dose) increased proportionally from 1 to 10 mg/kg. There was about 2-fold accumulation in drug levels (AUC0-168h and Cmax) at the steady state compared to those after single dose. Increased lymphocyte infiltration and PD-L1 expression were observed in BGB-A317 treated groups. In BCCO-028 model, BGB-A317 at 10 mg/kg QW induced significant tumor growth inhibition, with 83% TGI (p &amp;lt; 0.05 vs. vehicle treatment) on day 36. In BCLU-054 model, BGB-A317 at 10 mg/kg QW induced significant tumor growth inhibition, with 45% of TGI (p &amp;lt; 0.05 vs. vehicle treatment) on day 23. BGB-A317 treatment had no significant impact on animal body weight throughout all of the studies. Conclusions: BGB-A317 demonstrated significant anti-tumor activity in 3 human cancer xenograft PBL-SCID mouse models, including A431 human epidermoid carcinoma, BCCO-028 colon cancer, and BCLU-054 NSCLC models. Citation Format: Xiaomin Song, Zhiyu Tang, Tong Zhang, Mingming Guo, Wenfeng Gong, Yong Liu, Ningning Zhang, Yilu Zhang, Yanjuan Zhang, Jie Ma, Jing Song, Kang Li, Lai Wang. Anti-tumor activity of a novel anti-human PD-1 antibody BGB-A317 in mouse models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5002.
Terahertz Wireless Links Using Diffuse Scattering From Rough Surfaces (2019)

We describe measurements of the diffuse bistatic scattering of a modulated terahertz beam incident on five metallic rough surfaces, to investigate the implications of surface roughness for non-line-of-sight (NLOS) wireless data links at frequencies at and above 100 GHz. The measurements were performed using transmitter and receiver modules, operating at several frequencies from 100 to 400 GHz. We investigate the dependence of the scattering patterns on surface roughness parameters, including rms height and correlation length. The results are consistent with numerical models for scattering from a rough surface. They support the design of bistatic methods for future multiple antenna systems, remote sensing, imaging, and localization in the terahertz range. We demonstrate for the first time that data links which incorporate an NLOS reflection in a nonspecular direction can be established at frequencies above 100 GHz, with low bit error rates.