gebhart/patrepeval huggingface dataset:
AinS and a new family of autoinducer synthesis proteins (1995)

In Vibrio fischeri, the autoinducer N-3-oxohexanoyl-L-homoserine lactone (AI-1) governs the cell density-dependent induction of the luminescence operon via the LuxR transcriptional activator. The synthesis of AI-1 from bacterial metabolic intermediates is dependent on luxI. Recently, we found a second V. fischeri autoinducer molecule, N-octanoyl-L-homoserine lactone (AI-2), that in E. coli also activates the luminescence operon via LuxR. A locus independent of luxI was identified as being required for AI-2 synthesis. This 2.7-kb ain (autoinducer) locus was characterized by transposon insertion mutagenesis, deletion and complementation analysis, and DNA sequencing. A single 1,185-bp gene, ainS, was found to be the sole exogenous gene necessary for the synthesis of AI-2 in Escherichia coli. In addition, a V. fischeri ainS mutant produced AI-1 but not AI-2, confirming that in its native species ainS is specific for the synthesis of AI-2. ainS is predicted to encode a 45,580-Da protein which exhibits no similarity to LuxI or to any of the LuxI homologs responsible for the synthesis of N-acyl-L-homoserine lactones in a variety of other bacteria. The existence of two different and unrelated autoinducer synthesis genes suggests the occurrence of convergent evolution in the synthesis of homoserine lactone signaling molecules. The C-terminal half of AinS shows homology to a putative protein in Vibrio harveyi, LuxM, which is required for the synthesis of a V. harveyi bioluminescence autoinducer. Together, AinS and LuxM define a new family of autoinducer synthesis proteins. Furthermore, the predicted product of another gene, ainR, encoded immediately downstream of ainS, shows homology to LuxN, which is similarly encoded downstream of luxM in V. harveyi and proposed to have sensor/regulator functions in the bioluminescence response to the V. harveyi auto inducer. This similarity presents the possibility that AI-2, besides interacting with LuxR, also interacts with AinR under presently unknown conditions.
Deoxycholate is an important releaser of peptide YY and enteroglucagon from the human colon. (1993)

Peptide YY (PYY) and enteroglucagon are hormonal peptides found in endocrine cells of the distal intestinal mucosa. Although it is known that plasma concentrations of both peptides increase in response to feeding, the mechanism by which ingested food causes release of colonic hormones is not understood. The release of PYY and enteroglucagon was measured in response to intraluminal stimuli in 176 patients having investigative colonoscopy. Introduction of air, saline (isotonic and hypertonic), glucose (isotonic and hypertonic), oleic acid (without bile salts), and casein hydrolysate all failed to release PYY but glucose caused a small but significant increase in enteroglucagon concentrations. In contrast with the lack of effect of nutrients, infusion of deoxycholic acid produced a rapid and marked dose responsive increase in plasma PYY concentrations when introduced into the sigmoid colon. PYY release was statistically significant at doses between 3.3 mM to 30 mM; for example 10 mM deoxycholate caused a sixfold increase in plasma PYY concentrations. Infusion of 10 mM deoxycholate into the transverse colon or caecum produced an increase of PYY that was similar to the responses in the sigmoid colon. There was also a significant release of enteroglucagon in response to infusion of this bile salt into the sigmoid colon at doses between 3.3 mM and 30 mM. The enteroglucagon response to 10 mM deoxycholate was similar in all three colonic regions. When oleic acid was added to deoxycholate as an emulsion, the release of PYY and enteroglucagon was similar to that seen with the bile salt alone. These findings suggest that bile salts may play an important part in the control of colonic endocrine function and may explain the increased circulating concentrations of colonic regulatory peptides that are seen in malabsorption states and after small bowel resection in humans.
Structural Basis for Recognition of Urokinase-type Plasminogen Activator by Plasminogen Activator Inhibitor-1 (2011)

Plasminogen activator inhibitor-1 (PAI-1), together with its physiological target urokinase-type plasminogen activator (uPA), plays a pivotal role in fibrinolysis, cell migration, and tissue remodeling and is currently recognized as being among the most extensively validated biological prognostic factors in several cancer types. PAI-1 specifically and rapidly inhibits uPA and tissue-type PA (tPA). Despite extensive structural/functional studies on these two reactions, the underlying structural mechanism has remained unknown due to the technical difficulties of obtaining the relevant structures. Here, we report a strategy to generate a PAI-1·uPA(S195A) Michaelis complex and present its crystal structure at 2.3-Å resolution. In this structure, the PAI-1 reactive center loop serves as a bait to attract uPA onto the top of the PAI-1 molecule. The P4-P3' residues of the reactive center loop interact extensively with the uPA catalytic site, accounting for about two-thirds of the total contact area. Besides the active site, almost all uPA exosite loops, including the 37-, 60-, 97-, 147-, and 217-loops, are involved in the interaction with PAI-1. The uPA 37-loop makes an extensive interaction with PAI-1 β-sheet B, and the 147-loop directly contacts PAI-1 β-sheet C. Both loops are important for initial Michaelis complex formation. This study lays down a foundation for understanding the specificity of PAI-1 for uPA and tPA and provides a structural basis for further functional studies.
Identification and characterization of E. coli CRISPR‐cas promoters and their silencing by H‐NS (2010)

Inheritable bacterial defence systems against phage infection and foreign DNA, termed CRISPR (clustered regularly interspaced short palindromic repeats), consist of cas protein genes and repeat arrays interspaced with sequences originating from invaders. The Cas proteins together with processed small spacer-repeat transcripts (crRNAs) cause degradation of penetrated foreign DNA by unknown mechanisms. Here, we have characterized previously unidentified promoters of the Escherichia coli CRISPR arrays and cas protein genes. Transcription of precursor crRNA is directed by a promoter located within the CRISPR leader. A second promoter, directing cas gene transcription, is located upstream of the genes encoding proteins of the Cascade complex. Furthermore, we demonstrate that the DNA-binding protein H-NS is involved in silencing the CRISPR-cas promoters, resulting in cryptic Cas protein expression. Our results demonstrate an active involvement of H-NS in the induction of the CRISPR-cas system and suggest a potential link between two prokaryotic defence systems against foreign DNA.
Characterization of Kerogen and Source Rock Maturation Using Solid-State NMR Spectroscopy (2015)

Solid-state NMR methods common to the analysis of polymers and other rigid solids are utilized for the study of kerogen, bitumen, and the organic content in source rocks. The use of straightforward nondestructive techniques, primarily employing solid-state NMR, is shown to provide useful information about both individual samples and changes between samples that cover a range of thermal maturities of type II kerogen. In addition to aromatic fraction and chemical structure, one of the most striking changes to isolated kerogen with maturity is the distribution of pore sizes, studied with both 129Xe NMR and complementary nitrogen physisorption, that may help to understand the process of bitumen generation. Ultimately, direct in situ analysis of source rock samples that allow kerogen and bitumen to be distinguished is desirable, as it would eliminate the time and effort to isolate and prepare kerogen samples. By proper consideration and removal of the background, we find that a clear 13C NMR signal can be obtained from source rock with total organic carbon weight as low as 2%. Simple 1H NMR methods are shown to quickly provide a qualitative measurement of the bitumen in source rocks, while 13C cross-polarization is found to be an easy method to distinguish kerogen from bitumen.
The WD repeats of Tup1 interact with the homeo domain protein alpha 2. (1994)

Tup1 and Ssn6 transcriptionally repress a wide variety of genes in yeast but do not appear to bind DNA. We provide genetic and biochemical evidence that the DNA-binding protein alpha 2, a regulator of cell-type-specific genes, recruits the Tup1/Ssn6 repressor by directly interacting with Tup1. This interaction is mediated by a region of Tup1 containing seven copies of the WD repeat, a 40 amino acid motif of unknown function found in many other proteins. We have found that a single WD repeat will interact with alpha 2, indicating that the WD repeat is a protein-protein interaction domain. Furthermore, a fragment of Tup1 containing primarily WD repeats provides at least partial repression in the absence of Ssn6, suggesting that the repeats also mediate interaction between Tup1 and other components of the repression machinery.
Antibody responses in the lungs of mice following oral immunization with Salmonella typhimurium aroA and invasive Escherichia coli strains expressing the filamentous hemagglutinin of Bordetella pertussis (1991)

The filamentous hemagglutinin (FHA) of Bordetella pertussis was expressed in the attenuated aroA mutant of Salmonella typhimurium, SL3261, and in a strain of Escherichia coli harboring Shigella flexneri plasmid pWR110, which encodes bacterial invasiveness for epithelial cells. Expression of FHA in these strains did not interfere with their ability to invade Henle cells. Immunoglobulins A and G specific for FHA were detected in lung washes of mice following oral immunization with the live recombinant organisms; antibody levels were significantly higher than those in mice immunized with killed bacteria administered orally or intraperitoneally. Live oral vaccines carrying protective antigens of B. pertussis may be an important alternative to new-generation component vaccines against whooping cough.
Algorithms for Quantum Systems — Quantum Algorithms (2003)

This chapter contains sections titled: Introduction Fast Quantum Signal Transforms Quantum Error-correcting Codes Efficient decomposition of quantum operations into given one-parameter groups Simulation of Hamiltonians References
Microbial Synthesis of Semiconductor PbS Nanocrystallites (2002)

The use of microbes as producers of semiconductor nanocrystals is demonstrated. When torulopsis yeast is challenged with lead, it builds intracellular spherical crystallites of PbS, 2–5 nm in diameter (see Figure for an HR-TEM image) and pure by X-ray diffraction. The crystals, which can be isolated by freeze-thawing, show a sharp absorption maximum at 330 nm, corresponding to a bandgap of 3.75 eV.
Melanoma Treatment With Phenolic or Catecholic Compounds (1977)

<h3>To the Editor.—</h3> In a recentArchiveseditorial (113:421, 1977), Lerner and Nordlund suggested that selected cases of melanoma be treated with phenolic or catecholic compounds after resection of the primary tumor. The inference was that such a program would improve survival of patients with melanoma. I have also been interested in this same question, and I attempted to answer it with the use of the Fortner melanotic melanoma No. 1 hamster series. I selected for study four highly active depigmenting agents—one each from the hydroquinones, the mercaptoethylamines, the catechols, and the parasubstituted phenols. These compounds were injected intralesionally into small tumor papules five days a week for four weeks. No inhibition in tumor growth or in survival was obtained.<sup>1</sup>Frenk and Ott had a similar result in their experiments.<sup>2</sup>These data do not support the concept that depigmenting compounds may be useful in the treatment of malignant
Graft Fixation in Cruciate Ligament Reconstruction (2000)

Cruciate ligament reconstruction has progressed dramatically in the last 20 years. Anatomic placement of ligament substitutes has fostered rehabilitation efforts that stress immediate and full range of motion, immediate weightbearing, neuromuscular strength and coordination, and early return to athletic competition (3 months). This has placed extreme importance on secure graft fixation at the time of ligament reconstruction. Current ligament substitutes require a bony or soft tissue component to be fixed within a bone tunnel or on the periosteum at a distance from the normal ligament attachment site. Fixation devices have progressed from metal to biodegradable and from far to near-normal native ligament attachment sites. Ideally, the biomechanical properties of the entire graft construct would approach those of the native ligament and facilitate biologic incorporation of the graft. Fixation should be done at the normal anatomic attachment site of the native ligament (aperture fixation) and, over time, allow the biologic return of the histologic transition zone from ligament to fibrocartilage, to calcified fibrocartilage, to bone. The purpose of this article is to review current fixation devices and techniques in cruciate ligament surgery.
Targeting the Loss of the von Hippel-Lindau Tumor Suppressor Gene in Renal Cell Carcinoma Cells (2007)

Late-stage clear cell renal carcinoma poses a formidable clinical challenge due to the high mortality rate associated with this disease. Molecular and genetic studies have identified functional loss of the von Hippel-Lindau (VHL) gene as a frequent and crucial event in the development of the malignant phenotype of clear cell renal carcinomas. Loss of VHL function thus represents a pathognomonic molecular defect for therapeutic exploitation. The objective of this study was to evaluate the possibility of targeting VHL loss through pharmacologic means. Chromomycin A3 (ChA3) was identified through in silico analysis of existing publicly available drug profiles from the National Cancer Institute as an agent that seemed to selectively target VHL-deficient clear cell renal carcinoma cells. Genotype-selective toxicity was first determined through short-term viability assays and then confirmed with clonogenic studies. Coculture of fluorescently labeled VHL-deficient and VHL-positive cells showed discriminate killing of the VHL-deficient cells with ChA3. Mechanistically, overexpression of hypoxia-inducible factor (HIF)-2alpha in VHL-positive clear cell renal carcinoma cells phenocopied loss of VHL with respect to ChA3 toxicity, establishing ChA3 as a HIF-dependent cytotoxin. This study shows the feasibility of selectively targeting the loss of the VHL tumor suppressor gene in clear cell renal carcinoma for potential clinical benefit and may have greater ramifications in the development of new targeted therapies for the treatment of cancer and other genetic diseases.
In silico identified CCR4 antagonists target regulatory T cells and exert adjuvant activity in vaccination (2008)

Adjuvants are substances that enhance immune responses and thus improve the efficacy of vaccination. Few adjuvants are available for use in humans, and the one that is most commonly used (alum) often induces suboptimal immunity for protection against many pathogens. There is thus an obvious need to develop new and improved adjuvants. We have therefore taken an approach to adjuvant discovery that uses in silico modeling and structure-based drug-design. As proof-of-principle we chose to target the interaction of the chemokines CCL22 and CCL17 with their receptor CCR4. CCR4 was posited as an adjuvant target based on its expression on CD4(+)CD25(+) regulatory T cells (Tregs), which negatively regulate immune responses induced by dendritic cells (DC), whereas CCL17 and CCL22 are chemotactic agents produced by DC, which are crucial in promoting contact between DC and CCR4(+) T cells. Molecules identified by virtual screening and molecular docking as CCR4 antagonists were able to block CCL22- and CCL17-mediated recruitment of human Tregs and Th2 cells. Furthermore, CCR4 antagonists enhanced DC-mediated human CD4(+) T cell proliferation in an in vitro immune response model and amplified cellular and humoral immune responses in vivo in experimental models when injected in combination with either Modified Vaccinia Ankara expressing Ag85A from Mycobacterium tuberculosis (MVA85A) or recombinant hepatitis B virus surface antigen (rHBsAg) vaccines. The significant adjuvant activity observed provides good evidence supporting our hypothesis that CCR4 is a viable target for rational adjuvant design.
Impact Assessment of Climate and Land-Use Changes on Flooding Behavior in the Upper Ciliwung River, Jakarta, Indonesia (2016)

The hydrological conditions upstream of the Ciliwung watershed are changing due to climate and land-use changes. Any changes in this area may increase the flood frequencies which may have countless consequences downstream of the watershed where the Jakarta city is located. We simulated the effects of land-use and climate changes on flooding (e.g., peak flow and river discharge) in the upper Ciliwung River basin in Greater Jakarta, Indonesia. Hydrologic Modeling System (HEC-HMS), a rainfall-runoff simulation model, was used to simulate peak river discharge values for current and future conditions. The model was calibrated and validated based on the observed river discharge data from February 2007 and January 1996, respectively. The statistical analysis showed that the performance of the model is satisfactory, with Nash–Sutcliffe efficiency 0.64 and 0.58 for calibration and validation, respectively. The coefficients of determination values are 0.86 and 0.82, respectively. The effect of the projected land-use changes alone in 2030 increased the peak flow by approximately 20%. When considering the land-use changes in conjunction with the future climate scenario, the peak flow based on the precipitation corresponding to a 50-year return period in 2030 increased by 130%. Based on the results of this study, it is urgent that a flood management plan be implemented in the target area to reduce flooding in the near future.
Cognitive swarms for rapid detection of objects and associations in visual imagery (2005)

We have developed a new optimization-based framework for computer vision that combines ideas from particle swarm optimization (PSO) and statistical pattern recognition to rapidly and accurately detect and classify objects in visual imagery. Swarm intelligence is used to locate objects by optimizing the classification confidence level. We have used our cognitive swarm framework to rapidly detect people, ground vehicles, and boats, and to recognize behaviors based on object associations, such as people exiting and entering vehicles, for applications in security, surveillance, target recognition, and automotive active safety.
Broadband CDMA for personal communications systems (1991)

Multipath propagation in a broadband CDMA environment is described. A propagation model for broadband spread-spectrum signals is presented. Experimental results relating to the sharing of the band by fixed service microwave users and mobile personal communications network (PCN) users are discussed. Field tests indicate that PCN systems can provide high-quality communications when sharing the spectrum with fixed-service microwave systems in suburban and urban areas.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Parafascicular-Center Median Nuclei Stimulation for Intractable Pain and Dyskinesia (Painful-Dyskinesia) (1980)

Medial thalamus stimulation was used to treat chronic intractable pain associated with dyskinesia. Relief from both the pain and the motor disorder occurred concomitantly. However, maximum pain reduction was attained at a relatively faster rate than maximum reduction from the motor disability. It is postulated that pathologic changes in the center median nucleus secondary to lenticulo-striate-internal capsular lesions account, in part, for both the pain and the dyskinesia. Electrical stimulation of the center median(n) parafascicular nuclear complex presumably simultaneously activates both the neurohumeral and tertiary sensory pain inhibitory system for pain control, and the suprasegmental gamma system for motor control.
The problem is osteolysis. (1995)

Recent studies have generated considerable information that reveals substantial support for major change in the understanding of total hip arthroplasty and its current state. Although some of these observations appear unrelated at first glance, they can be drawn together to support the thesis that osteolysis is the dominant problem in total hip arthroplasty. These observations are as follows: (1) Five-year followup data are required for a minimum assessment of a new concept in total hip design and material because osteolysis is uncommon before that time. (2) Excellent fixation can be achieved on the femoral side with good cementing and good cementless techniques. Thus, femoral component loosening is less of an issue currently. (3) Many acetabular components become loose because of the ingress of particulate debris that leads to linear bone loss at the interface with the pelvis, a process that is biologically akin to the more florid forms of osteolysis. Thus, much acetabular component loosening represents a form of osteolysis. (4) Many cementless femoral reconstructions have developed a high incidence of femoral osteolysis. (5) Many cementless sockets have developed a high incidence of pelvic osteolysis. Taken in conjunction, these observations suggest that periprosthetic osteolysis is the leading problem in contemporary total hip replacement.
The role of the ocularist. (1990)

The ocularist plays a significant role in the rehabilitation of patients suffering the loss of an eye. As with any role, the function of the ocularist is a multidisciplinary one, involving a wide range of services in the overall management of the patient.
The Wnt secretion protein Evi/Gpr177 promotes glioma tumourigenesis (2011)

Malignant astrocytomas are highly aggressive brain tumours with poor prognosis. While a number of structural genomic changes and dysregulation of signalling pathways in gliomas have been described, the identification of biomarkers and druggable targets remains an important task for novel diagnostic and therapeutic approaches. Here, we show that the Wnt-specific secretory protein Evi (also known as GPR177/Wntless/Sprinter) is overexpressed in astrocytic gliomas. Evi/Wls is a core Wnt signalling component and a specific regulator of pan-Wnt protein secretion, affecting both canonical and non-canonical signalling. We demonstrate that its depletion in glioma and glioma-derived stem-like cells led to decreased cell proliferation and apoptosis. Furthermore, Evi/Wls silencing in glioma cells reduced cell migration and the capacity to form tumours in vivo. We further show that Evi/Wls overexpression is sufficient to promote downstream Wnt signalling. Taken together, our study identifies Evi/Wls as an essential regulator of glioma tumourigenesis, identifying a pathway-specific protein trafficking factor as an oncogene and offering novel therapeutic options to interfere with the aberrant regulation of growth factors at the site of production.