gebhart/patrepeval huggingface dataset:
BRED: A Simple and Powerful Tool for Constructing Mutant and Recombinant Bacteriophage Genomes (2008)

Advances in DNA sequencing technology have facilitated the determination of hundreds of complete genome sequences both for bacteria and their bacteriophages. Some of these bacteria have well-developed and facile genetic systems for constructing mutants to determine gene function, and recombineering is a particularly effective tool. However, generally applicable methods for constructing defined mutants of bacteriophages are poorly developed, in part because of the inability to use selectable markers such as drug resistance genes during viral lytic growth. Here we describe a method for simple and effective directed mutagenesis of bacteriophage genomes using Bacteriophage Recombineering of Electroporated DNA (BRED), in which a highly efficient recombineering system is utilized directly on electroporated phage DNA; no selection is required and mutants can be readily detected by PCR. We describe the use of BRED to construct unmarked gene deletions, in-frame internal deletions, base substitutions, precise gene replacements, and the addition of gene tags.
Novel microbubble preparation technologies (2008)

Gas microbubbles, stabilised by a surfactant or polymer coating, have become well established over the past 20–30 years as the most effective type of contrast agent available for ultrasound radiography. More recently, their potential for use in therapeutic applications including targeted drug delivery, gene therapy, thrombolysis and focused ultrasound surgery has also been investigated. Developments in both diagnostic and therapeutic applications have greatly increased the need for more advanced preparation technologies which provide a high degree of control over microbubble size, composition, stability and uniformity. Conventional processing techniques such as sonication and high shear emulsification offer high yield and low cost production but poor control over microbubble size and uniformity. This is being addressed by the development of new technologies, such as membrane emulsification, inkjet printing, electrohydrodynamic atomisation and microfluidic processing which offer significant improvements in terms of control over microbubble characteristics. The aim of this paper is to review the range of techniques available for microbubble preparation and how these have evolved to keep pace with advances in clinical practice.
Deletion of Braun lipoprotein gene (lpp) and curing of plasmid pPCP1 dramatically alter the virulence of Yersinia pestis CO92 in a mouse model of pneumonic plague (2009)

Deletion of the murein (Braun) lipoprotein gene, lpp, attenuates the Yersinia pestis CO92 strain in mouse models of bubonic and pneumonic plague. In this report, we characterized the virulence of strains from which the plasminogen activating protease (pla)-encoding pPCP1 plasmid was cured from either the wild-type (WT) or the Deltalpp mutant strain of Y. pestis CO92 in the mouse model of pneumonic infection. We noted a significantly increased survival rate in mice infected with the Y. pestis pPCP(-)/Deltalpp mutant strain up to a dose of 5000 LD(50). Additionally, mice challenged with the pPCP(-)/Deltalpp strain had substantially less tissue injury and a strong decrease in the levels of most cytokines and chemokines in tissue homogenates and sera when compared with the WT-infected group. Importantly, the Y. pestis pPCP(-)/Deltalpp mutant strain was detectable in high numbers in the livers and spleens of some of the infected mice. In the lungs of pPCP(-)/Deltalpp mutant-challenged animals, however, bacterial numbers dropped at 48 h after infection when compared with tissue homogenates from 1 h post-infection. Similarly, we noted that this mutant was unable to survive within murine macrophages in an in vitro assay, whereas survivability of the pPCP(-) mutant within the macrophage environment was similar to that of the WT. Taken together, our data indicated that a significant and possibly synergistic attenuation in bacterial virulence occurred in a mouse model of pneumonic plague when both the lpp gene and the virulence plasmid pPCP1 encoding the pla gene were deleted from Y. pestis.
Network 10 Considered Harmful (Some Practices Shouldn't be Codified) (1994)

This document restates the arguments for maintaining a unique address
space. Concerns for Internet architecture and operations, as well as
IETF procedure, are explored. This memo provides information for the
Internet community. This memo does not specify an Internet standard of
any kind.
Sortase‐catalysed anchoring of surface proteins to the cell wall of Staphylococcus aureus (2001)

Many surface proteins of Gram-positive bacteria are anchored to the cell wall envelope by a transpeptidation mechanism, requiring a C-terminal sorting signal with a conserved LPXTG motif. Sortase, a membrane protein of Staphylococcus aureus, cleaves polypeptides between the threonine and the glycine of the LPXTG motif and catalyses the formation of an amide bond between the carboxyl-group of threonine and the amino-group of peptidoglycan cross-bridges. S. aureus mutants lacking the srtA gene fail to anchor and display some surface proteins and are impaired in the ability to cause animal infections. Sortase acts on surface proteins that are initiated into the secretion (Sec) pathway and have their signal peptide removed by signal peptidase. The S. aureus genome encodes two sets of sortase and secretion genes. It is conceivable that S. aureus has evolved more than one pathway for the transport of 20 surface proteins to the cell wall envelope.
The Berlin Brain–Computer Interface: Non-Medical Uses of BCI Technology (2010)

Brain-computer interfacing (BCI) is a steadily growing area of research. While initially BCI research was focused on applications for paralyzed patients, increasingly more alternative applications in healthy human subjects are proposed and investigated. In particular, monitoring of mental states and decoding of covert user states have seen a strong rise of interest. Here, we present some examples of such novel applications which provide evidence for the promising potential of BCI technology for non-medical uses. Furthermore, we discuss distinct methodological improvements required to bring non-medical applications of BCI technology to a diversity of layperson target groups, e.g., ease of use, minimal training, general usability, short control latencies.
[Research Advances on Programmed Cell Death Receptor-1 Antibody in the Treatment of Lymphoma--Review]. (2019)

Abstract Tumor cells avoid immune surveillance by overexpressing ligands of checkpoint receptors on tumor cells or adjacent cells, resulting in inability or exhaustion of T cells. Numerous studies have shown that lymphoma cells highly expressed programmed cell death ligand-1 (PD-L1), suggesting that PD-1 may become an important target for lymphoma treatment. By targeting the PD-1 protein, the cellular activity of T cells will be significantly enhanced, and the tumor growth will be inhibited. Recently, antibodies against PD-1 have shown high efficacy and safety in the clinical studies of lymphoma, which are expected to become the targeted therapeutic drugs for lymphoma. In order to deeply understand the application of PD-1 antibody in treatment of lymphoma, this review briefly summaries the present state of lymphoma studies, the action mechanism and preparation method of PD-1 antibody in clinical treatment of lymphoma.
Polyetheylenimine-Polyplexes of Spiegelmer NOX-A50 Directed against Intracellular High Mobility Group Protein A1 (HMGA1) Reduce Tumor Growth in Vivo (2010)

High mobility group A1 (HMGA1) proteins belong to a group of architectural transcription factors that are overexpressed in a range of human malignancies, including pancreatic adenocarcinoma. They promote anchorage-independent growth and epithelial-mesenchymal transition and are therefore suggested as potential therapeutic targets. Employing in vitro selection techniques against a chosen fragment of HMGA1, we have generated biostable l-RNA oligonucleotides, so-called Spiegelmers, that specifically bind HMGA1b with low nanomolar affinity. We demonstrate that the best binding Spiegelmers, NOX-A50 and NOX-f33, compete HMGA1b from binding to its natural binding partner, AT-rich double-stranded DNA. We describe a formulation method based on polyplex formation with branched polyethylenimine for efficient delivery of polyethylene glycol-modified Spiegelmers and show improved tissue distribution and persistence in mice. In a xenograft mouse study using the pancreatic cancer cell line PSN-1, subcutaneous administration of 2 mg/kg per day NOX-A50 formulated in polyplexes showed an enhanced delivery of NOX-A50 to the tumor and a significant reduction of tumor volume. Our results demonstrate that intracellular targets can be successfully addressed with a Spiegelmer using polyethylenimine-based delivery and underline the importance of HMGA1 as a therapeutic target in pancreatic cancer.
Ten years' experience with enteral levodopa infusions for motor fluctuations in Parkinson's disease (1998)

We report our long-term experience using enteral levodopa infusions in 22 patients with Parkinson's disease and severe motor fluctuations. Amelioration of intractable dyskinesias was the most important factor that determined whether patients chose to continue using the infusion pump system. Mechanical and physical problems associated with enteral access were the most common reasons for which patients discontinued pump use. Nearly all patients continued to have dramatically increased on time for the duration of follow up, suggesting that technically less-cumbersome systems that provide continuous dopaminergic stimulation are worthwhile and should be developed.
A Primer on 11 U.S.C. § 328(a) and its use in Alternative Billing Methods in Bankruptcy (1999)

Compensation of attorneys and professionals in the bankruptcy field is one of the most written about areas in bankruptcy law. Professionals, both familiar and unfamiliar with the mandates of the Bankruptcy Code and Federal Rules of Bankruptcy Procedure, are having an increasingly difficult time obtaining approval for the envisioned compensation. Problems generally do not arise for debtors' attorneys in the run-of-the-mill Chapter 7 case or Chapter 13 case. Flat fees are charged in most of these cases, and applications to employ debtors' attorneys are not filed. Therefore, retention orders are not entered. However, outside the run-of-the-mill Chapter 7 or 13 case, in Chapter 11 cases, or when an attorney or professional is hired for a special purpose under section 327(e), problems regarding the particular compensation may arise.\nIn the past, most courts used a traditional fee arrangement based upon reasonable hours and a reasonable rate, commonly referred to as the "lodestar" approach, when approving fees. Because the lodestar method is not always the desired fee arrangement, professionals are increasingly attempting to use various fee arrangements, which in the past were not commonly used by bankruptcy professionals. However, in the bankruptcy arena, these nonlodestar fee arrangements are confusing, inconsistently applied, and potentially dangerous to professionals.\nSection 328(a) is a useful tool with alternative fee arrangements. Section 328 allows professionals to obtain court approval of the particular terms and conditions of employment at the beginning of a case. The preapproval of the terms and conditions under section 328 minimizes problems at the time the application for compensation is filed because bankruptcy courts must apply the terms of employment as approved, unless the terms prove to have been improvident in light of developments unanticipated at the time of entry of the retention order. This provides professionals a tremendous benefit: predictability of their compensation. However, professionals must properly seek and obtain a retention order under section 328(a) at the outset of their employment to enjoy the benefit of pre-approved terms and conditions.\nThe difficulty is that many lawyers and judges do not understand, or even realize, the impact of the useful tool provided in section 328(a). This generalization does not apply to all jurisdictions or bars; however, at the very least it appears that there is great confusion regarding the impact of section 328(a), particularly at the time of the application for compensation. This Article analyzes the history of section 328(a), its use and effect, and various alternative fee arrangements which have developed in bankruptcy practice.
Assessment of the Severity of Hypoglycemia and Glycemic Lability in Type 1 Diabetic Subjects Undergoing Islet Transplantation (2004)

Currently, the major indications for solitary islet transplantation are recurrent severe hypoglycemia and labile glucose control. Quantifying these problems remains subjective. We have developed a scoring system for both hypoglycemia and glycemic lability, established normative data, and used them in patients who have undergone islet transplantation. A composite hypoglycemic score (HYPO score) was devised based on the frequency, severity, and degree of unawareness of the hypoglycemia. In addition, using 4 weeks of glucose records, a lability index (LI) was calculated based on the change in glucose levels over time and compared with a clinical assessment of glycemic lability. A mean amplitude of glycemic excursions (MAGE) was also calculated based on 2 consecutive days of seven readings each day. These scores were determined in 100 randomly selected subjects with type 1 diabetes from our general clinic to serve as a control group and in patients before and after islet transplantation. The mean age of the control diabetic subjects was 38.4 +/- 1.3 years (+/-SE), with a duration of diabetes of 21.5 +/- 1.1 years. The median HYPO score in the control subjects was 143 (25th to 75th interquartile range: 46-423). The LI in the diabetic control subjects was 223 (25th to 75th interquartile range: 130-329 mmol/l(2)/h.week(-1)). The LI correlated much more closely than the MAGE with the clinical assessment of lability. A HYPO score of > or = 1,047 (90th percentile) or an LI > or = 433 mmol/l(2)/h.week(-1) (90th percentile) indicated serious problems with hypoglycemia or glycemic lability, respectively. The islet transplant patients (n = 51) were 42.1 +/- 1.4 years old, with a duration of diabetes of 25.7 +/- 1.4 years. Islet transplant patients had a mean HYPO score of 1,234 +/- 184 pretransplant, which was significantly higher than that of the control subjects (P < 0.001), which became negligible posttransplantation with the elimination of hypoglycemia. The median LI pretransplant was 497 mmol/l(2)/h.week(-1) (25th to 75th interquartile range: 330-692), significantly higher than that of control subjects (P < 0.001), and fell to 40 (25th to 75th interquartile range: 14-83) within a month after the final transplant. In those who had lost graft function, the LI rose again. The HYPO score and LI provide measures of the extent of problems with hypoglycemia and glycemic lability, respectively, complement the clinical assessment of the problems with glucose control before islet transplantation, and will allow comparison of selection of subjects for transplants between centers.
Identification and analysis of a novel human surface CD5- B lymphocyte subset producing natural antibodies (1992)

Abstract The production of “natural” autoantibodies or antibodies, i.e., Ig that bind a variety of self- and/or exogenous Ag and arise independently of known immunization, is though to be a feature of CD5+ B lymphocytes. To determine whether other lymphocyte subsets exist that might be committed to the production of natural antibodies, human peripheral blood B cells were sorted on the basis of surface CD5 expression and differential expression of surface CD45RA (CD5+CD45RAintermediate(int), CD5-CD45RAlow(lo), and CD5-CD45RAhigh(hi)), and analyzed for the type of Ig produced after EBV infection and culture. Like their CD5+ counterparts, most CD5-CD45RAlo B lymphocytes were precursors of cells producing IgM, a major proportion of which displayed the Ag-binding features of natural antibodies. In contrast, CD5-CD45RAhi B cells comprised a high frequency of IgG-producing cell precursors, possibly including memory B lymphocytes. Six of seven IgM mAb generated from sorted CD5-CD45RAlo B cells and three of four IgM mAb from sorted CD5+ B cells were polyreactive, binding with different affinities (Kd, 10(-5) to 10(-8) M) to two or more Ag; the remaining mAb from CD5-CD45RAlo and the mAb from CD5+ B cells each bound to a single Ag (Kd, 10(-7) to 10(-8) M), β-galactosidase and ssDNA, respectively. CD5-CD45RAlo B cells account for 4.1 +/- 1.2% (mean +/- SD in 11 healthy subjects; CD5+ B cells, 23.3 +/- 6.9%) of total B lymphocytes and display the features of quiescent cells. In a given individual, the number of CD5-CD45RAlo B cells remains constant over time. CD5-CD45RAlo and CD5+ B cells bear surface CD11b and CD14, at densities and/or frequencies apparently higher than those of CD5-CD45RAhi B lymphocytes. Despite their surface CD5- phenotype, CD45RAlo B cells express CD5+ mRNA at levels comparable with those of CD5+ B lymphocytes, whereas CD5-CD45RAhi B cells express only trace amounts of CD5 mRNA. The commitment to natural antibody production and the degree of CD5 mRNA expression suggest that the newly defined CD5-CD45RAlo B cell subset is related to CD5+ B lymphocytes, and may constitute the human homologue of the mouse Ly-1-"sister" B cell population.
Measurement of Central Venous Pressure from a Peripheral Intravenous Catheter in the Lower Extremity (2005)

Provided that the PVP increases to a sustained inspiratory breath and occlusion above the intravenous site, there is a clinically useful correlation between the PVP and the CVP.
Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene. (1999)

Activation of telomerase is one of the rate-limiting steps in human cell immortalization and carcinogenesis Human telomerase is composed of at least two protein subunits and an RNA component. Regulation of expression of the catalytic subunit, human telomerase reverse transcriptase (hTERT), is suggested as the major determinant of the enzymatic activity. We report here the cloning and characterization of the 5'-regulatory region of the hTERT gene. The highly GC-rich content of the 5' end of the hTERT cDNA spans to the 5'-flanking region and intron 1, making a CpG island. A 1.7-kb DNA fragment encompassing the hTERT gene promoter was placed upstream of the luciferase reporter gene and transiently transfected into human cell lines of fibroblastic and epithelial origins that differed in their expression of the endogenous hTERT gene. Endogenous hTERT-expressing cells, but not nonexpressing cells, showed high levels of luciferase activity, suggesting that the regulation of hTERT gene expression occurs mainly at the transcriptional level. Additional luciferase assays using a series of constructs containing unidirectionally deleted fragments revealed that a 59-bp region (-208 to -150) is required for the maximal promoter activity. The region contains a potential Myc oncoprotein binding site (E-box), and cotransfection of a c-myc expression plasmid markedly enhanced the promoter activity, suggesting a role of the Myc protein in telomerase activation. Identification of the regulatory regions of the hTERT promoter sequence will be essential in understanding the molecular mechanisms of positive and negative regulation of telomerase.
Cholestasis caused by lipid emulsions. (1982)

Liver function was observed in 35 patients receiving intravenous feeding for more than three weeks. A progressive cholestatic jaundice occurred in ten of 18 patients receiving a lipid emulsion in a dose of 3 grams per kilogram per day. Only one of 17 patients receiving a dose of 1 gram per kilogram per day showed evidence of cholestasis. Neither the type of amino acid preparation used nor the dosage appeared to be a factor. Similarly, the contribution to calories from dextrose did not influence the frequency of cholestasis. The cholestatic jaundice improved with the return to normal of liver function when the lipid emulsion dosage was reduced or intravenous feeding was discontinued.
Simulation of saturation and relaxation of intersubband absorption in doped quantum wells (1988)

We have simulated the saturation and relaxation of intersubband absorption in doped GaAs quantum wells, in which radiation excites electrons between the ground and higher subbands. Screened longitudinal optic (LO) phonon, hot LO phonon, acoustic phonon, intrasubband scattering, conduction-band nonparabolicity, and intervalley scattering were included in our simulation. We find that the change in absorption relaxes with a time constant of about 5 ps after pulsed excitation. Under continuous excitation the absorption saturates as a nearly homogeneously broadened system.
Slow Wave Sleep Deficiency Insomnia: A Problem in Thermo‐Downregulation at Sleep Onset (1987)

ABSTRACT The following review article attempts to develop the argument that a regulated, rapid drop in rectal, core‐body temperature following sleep onset is a necessary prerequisite to the presence of sustained slow wave sleep (NREM Stage 4). Based upon this premise, a theory1 is presented to suggest that the slow wave sleep deficiency so commonly associated with chronic, primary insomnia (Gaillard, 1976, 1978) is the result of a failure in the thermoregulatory system to show a regulated, rapid decrease in body temperature with sleep onset which persists for the first 1–2 hrs into the sleep period.
Identification of the sequence encoding N-acetylneuraminate-9-phosphate phosphatase (2005)

The synthesis of N-acetylneuraminate (Neu5Ac), the main form of sialic acid, proceeds in vertebrates through the condensation of N-acetylmannosamine 6-phosphate and phosphoenolpyruvate to Neu5Ac-9-phosphate, followed by the dephosphorylation of the latter by a specific phosphatase. The sequence encoding Neu5Ac-9-phosphate phosphatase (Neu5Ac-9-Pase; E.C. 3.1.3.29) has not been determined until now. In this work, we have purified Neu5Ac-9-Pase more than 1000-fold from rat liver. Its dependency on Mg2+ and the fact that it was inhibited by vanadate and Ca2+ suggested that it belonged to the haloacid dehalogenase family of phosphatases. Trypsin digestion and mass spectrometry analysis of a polypeptide of about 30 kDa that co-eluted with the activity in the last purification step indicated the presence of a protein designated "haloacid dehalogenase-like hydrolase domain containing 4." The human ortholog of this protein is encoded by a 2-exon gene present on chromosome 20p11. The human protein was overexpressed in Escherichia coli as a fusion protein with a polyHis tag and purified to homogeneity. The recombinant enzyme displayed a >230-fold higher catalytic efficiency on Neu5Ac-9-phosphate than on its second best substrate. Its properties were similar to those of the enzyme purified from rat liver. Neu5Ac inhibited the enzymatic activity by 50% at 15 mM, indicating that no significant inhibition is exerted at physiological concentrations of Neu5Ac. The identification of the gene encoding Neu5Ac-9-Pase will facilitate studies aimed at testing its potential implication in unexplained forms of glycosylation deficiency.