gebhart/patrepeval huggingface dataset:
Diagnostic value of urine sTREM-1 for sepsis and relevant acute kidney injuries: a prospective study (2011)

Abstract Introduction We explored the diagnostic value of a urine soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) for early sepsis identification, severity and prognosis assessment, and for secondary acute kidney injury (AKI). We compared this with white blood cell (WBC) counts, serum C-reactive protein (CRP), serum procalcitonin (PCT), urine output, creatinine clearance (CCr), serum creatinine (SCr), and blood urea nitrogen (BUN). Methods We enrolled 104 subjects admitted to the ICU: 16 cases with systemic inflammatory response syndrome (SIRS); 35 with sepsis and 53 with severe sepsis. Results for urine sTREM-1, WBC, serum CRP and serum PCT were recorded on days 1, 3, 5, 7, 10, and 14. For 17 sepsis cases diagnosed with secondary AKI, comparisons between their urine sTREM-1, urine output, CCr, SCr and BUN at diagnosis and 48 h before diagnosis were made. Results On the day of admission to the ICU, and compared with the SIRS group, the sepsis group exhibited higher levels of urine sTREM-1 and Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) scores ( P &lt; 0.05). Areas under the curve (AUC) shaped by the scores were 0.797 (95% CI 0.711 to 0.884) and 0.722 (95% CI 0.586 to 0.858), respectively. On days 1, 3, 5, 7, 10, and 14, urine sTREM-1, serum PCT and WBC levels registered higher in the severe sepsis group in contrast to the sepsis group ( P &lt; 0.05). Urine sTREM-1 and serum PCT levels continuously increased among non-survivors, while WBC and serum CRP levels in both groups declined. For 17 patients with AKI, urine sTREM-1, SCr and BUN levels at 48 h before AKI diagnosis were higher, and CCr level was lower than those for non-AKI subjects ( P &lt; 0.05). AUC for urine sTREM-1 was 0.922 (95% CI 0.850 to 0.995), the sensitivity was 0.941, and the specificity was 0.76 (based on a cut-off point of 69.04 pg/ml). Logistic regression analysis showed that urine sTREM-1 and severity were risk factors related to AKI occurrence. Conclusions Besides being non-invasive, urine sTREM-1 testing is more sensitive than testing WBC, serum CRP, and serum PCT for the early diagnosis of sepsis, as well as for dynamic assessments of severity and prognosis. It can also provide an early warning of possible secondary AKI in sepsis patients. Trial Registration ClinicalTrial.gov identifier NCT01333657
2-Phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives: synthesis and antidepressant activity (1990)

A series of 2-phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives was examined for the ability to inhibit both rat brain imipramine receptor binding and the synaptosomal uptake of norepinephrine (NE) and serotonin (5-HT). Neurotransmitter uptake inhibition was highest for a subset of 2-phenyl-2-(1-hydroxycyclohexyl)dimethylethylamines in which the aryl ring has a halogen or methoxy substituent at the 3- and/or 4-positions. Potential antidepressant activity in this subset was assayed in three rodent models--the antagonism of reserpine-induced hypothermia, the antagonism of histamine-induced ACTH release, and the ability to reduce noradrenergic responsiveness in the rat pineal gland. An acute effect seen in the rat pineal gland with several analogues, including 1-[1-(3,4-dichlorophenyl)-2-(dimethylamino)ethyl]cyclohexanol (23) and 1-[2-(dimethylamino)-1)-(4-methoxyphenyl)ethyl]cyclohexanol (4), was taken as a possible correlate of a rapid onset of antidepressant activity. Compound 4 (venlafaxine) is presently undergoing clinical evaluation.
Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy (2017)

Among infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug. (Funded by Biogen and Ionis Pharmaceuticals; ENDEAR ClinicalTrials.gov number, NCT02193074 .).
In Situ Biochemical Demonstration That P-Glycoprotein Is a Drug Efflux Pump with Broad Specificity (2000)

While P-glycoprotein (Pgp) is the most studied protein involved in resistance to anti-cancer drugs, its mechanism of action is still under debate. Studies of Pgp have used cell lines selected with chemotherapeutics which may have developed many mechanisms of resistance. To eliminate the confounding effects of drug selection on understanding the action of Pgp, we studied cells transiently transfected with a Pgp-green fluorescent protein (GFP) fusion protein. This method generated a mixed population of unselected cells with a wide range of Pgp-GFP expression levels and allowed simultaneous measurements of Pgp level and drug accumulation in living cells. The results showed that Pgp-GFP expression was inversely related to the accumulation of chemotherapeutic drugs. The reduction in drug concentration was reversed by agents that block multiple drug resistance (MDR) and by the UIC2 anti-Pgp antibody. Quantitative analysis revealed an inverse linear relationship between the fluorescence of Pgp-GFP and MDR dyes. This suggests that Pgp levels alone limit drug accumulation by active efflux; cooperativity between enzyme, substrate, or inhibitor molecules is not required. Additionally, Pgp-GFP expression did not change cellular pH. Our study demonstrates the value of using GFP fusion proteins for quantitative biochemistry in living cells.
The NH2‐terminal region of the active domain of sonic hedgehog is necessary for its signal transduction (1999)

The NH2-terminal domain of sonic hedgehog (residue 25-198) was expressed in both yeast and animal cells. The yeast-derived NH2-terminal domain of sonic hedgehog was less active by far than the animal cell-derived counterpart. The yeast-derived NH2-terminal domain of sonic hedgehog lacked 10 amino acids from the NH2-terminus. This cleavage of the yeast-derived NH2-terminal domain of sonic hedgehog might due to Kex 2. In contrast, a mutant yeast-derived NH2-terminal domain of sonic hedgehog (Lys-33 to Thr) retained its NH2-terminus and its activity was comparable to that of the animal cell-derived NH2-terminal domain of sonic hedgehog. The NH2-terminal deleted NH2-terminal domain of sonic hedgehog completely lost its activity, nevertheless it inhibited the alkaline phosphatase activity induced by the animal cell-derived NH2-terminal domain of sonic hedgehog in a dose-dependent manner. These data suggest that the NH2-terminal deleted NH2-terminal domain of sonic hedgehog retains a receptor-binding ability and that the NH2-terminal peptide of the NH2-terminal domain of sonic hedgehog is necessary for its signal transduction.
评保罗·肯尼迪的《展望21世纪》 (1993)

保罗·肯尼迪的《大国的兴衰》或许是80年代末期出版的、国际事务领域最值得注意的著作。这是一位杰出的外交史家和战略史家的宏篇巨著,也是被某些评论家称之为“衰落”学派的代表性著作。此书以大量事实向人们表明,美国正在走一个世纪前英国所走的那一段下坡路。而今,数年之后,保罗·肯尼迪又拿出另一部著作《展望21世纪》(美国兰多姆出版
A Flexible Mpeg2 Decoder Lsi With A Special Transport Stream Risc Processor (1998)

An MPEGZ decoder LSI which has a specially designed RISC processor for transport stream decoding is described. It realizes a good flexibility for all services from different broadcasters in the world without sacrificing the host processor ability .
Contextualizing context for synthetic biology – identifying causes of failure of synthetic biological systems (2012)

Despite the efforts that bioengineers have exerted in designing and constructing biological processes that function according to a predetermined set of rules, their operation remains fundamentally circumstantial. The contextual situation in which molecules and single-celled or multi-cellular organisms find themselves shapes the way they interact, respond to the environment and process external information. Since the birth of the field, synthetic biologists have had to grapple with contextual issues, particularly when the molecular and genetic devices inexplicably fail to function as designed when tested in vivo. In this review, we set out to identify and classify the sources of the unexpected divergences between design and actual function of synthetic systems and analyze possible methodologies aimed at controlling, if not preventing, unwanted contextual issues.
Complexity of Neutralizing Antibodies against Multiple Dengue Virus Serotypes after Heterotypic Immunization and Secondary Infection Revealed by In-Depth Analysis of Cross-Reactive Antibodies (2015)

The four serotypes of dengue virus (DENV) are the leading cause of arboviral diseases in humans. Despite the presence of neutralizing antibodies, a moderate efficacy was recently reported in phase 2b and 3 trials of a dengue vaccine; a better understanding of neutralizing antibodies in polyclonal human sera is urgently needed.We studied vaccinees who received heterotypic immunization of live-attenuated vaccines, as they were known to have received the first and second DENV serotype exposures.We found anti-envelope antibodies consist of group-reactive (GR), complex-reactive (CR), and type-specific (TS) antibodies, and that both GR and CR antibodies contribute significantly to multitypic neutralizing activities after secondary DENV immunization. These findings have implications for alternative strategies for DENV vaccination. Certain TS antibodies were recently discovered to contribute to the monotypic neutralizing activity and protection after primary DENV infection; our findings of the complexity of neutralizing activities after secondary immunization/infection provide new insights for neutralizing antibodies as surrogates of protection.
Investigations on the Antiproliferative Effects of Amino Acid Antagonists Targeting for Aminoacyl‐tRNA Synthetases Part II ‐ The Antileukemic Effect (1989)

Amino acid antagonists with proven or potentially inhibitory activities on aminoacyl-tRNA synthetases were tested for their antiproliferative effect against E. coli B. The compounds 4- and 6-fluoro-tryptophan, 5-methyltryptophan, selenocystine and beta-(2-thienyl)alanine gave strong growth inhibition in minimal medium, which disappeared after addition of structurally related natural amino acids or in an enriched broth. The inhibitory effect on amino-acyl-tRNA synthetases and the minimal inhibitory concentration for growth inhibition in minimal medium could not be correlated.
Combining Ultrasound and Biochemistry in First-Trimester Screening for Down's syndrome (1997)

Data on pregnancies with and without Down's syndrome between 10 and 14 weeks of pregnancy were used to determine the performance of combined ultrasound and biochemical markers in prenatal screening for Down's syndrome. We used three datasets: one published by Pandya et al. (1995) on nuchal translucency measurement in 86 Down's syndrome pregnancies; one published by Wald et al. (1996a) on free beta human chorionic gonadotrophin (hCG) and pregnancy-associated plasma protein A (PAPP-A) in 77 affected pregnancies and 385 unaffected pregnancies; and the third from Schuchter et al. on 561 unaffected pregnancies with nuchal translucency measurement. Combining the data from these three datasets showed that screening between 10 and 14 weeks by combining the serum markers with nuchal translucency measurement had a detection rate of 80 per cent for a 5 per cent false-positive rate, better than maternal age with two serum markers (62 per cent for 5 per cent) or maternal age with nuchal translucency measurement (63 per cent for 5 per cent). At this time in pregnancy, it appears that screening using the combined test is better than second-trimester serum screening (76 per cent for 5 per cent), though these estimates do not allow for any association between the markers and spontaneous fetal loss, an issue that needs to be clarified by further research. Meanwhile, these results provide a reasonable working estimate of screening performance using different combinations of these markers.
‘Nothing is permanent but change’†- antigenic variation in persistent bacterial pathogens (2009)

Pathogens persist in immunocompetent mammalian hosts using various strategies, including evasion of immune effectors by antigenic variation. Among highly antigenically variant bacteria, gene conversion is used to generate novel expressed variants from otherwise silent donor sequences. Recombination using oligonucleotide segments from multiple donors is a combinatorial mechanism that tremendously expands the variant repertoire, allowing thousands of variants to be generated from a relatively small donor pool. Three bacterial pathogens, each encoded by a small genome (< 1.2 Mb), illustrate this variant generating capacity and its role in persistent infection. Borrelia burgdorferi VlsE diversity is encoded and expressed on a linear plasmid required for persistence and recent experiments have demonstrated that VlsE recombination is necessary for persistence in the immunocompetent host. In contrast, both Treponema pallidum TprK and Anaplasma marginale Msp2 expression sites and donors are chromosomally encoded. Both T. pallidum and A. marginale generate antigenic variants in vivo in individual hosts and studies at the population level reveal marked strain diversity in the variant repertoire that may underlie pathogen strain structure and the capacity for re-infection and heterologous strain superinfection. Here, we review gene conversion in bacterial antigenic variation and discuss the short- and long-term selective pressures that shape the variant repertoire.
SELECTION OF POTENTIAL PROBIOTIC LACTOBACILLI FROM PIG FAECES TO BE USED AS ADDITIVES IN PELLETED FEEDING (2006)

Abstract Thirty-ﬁve isolates from pig feces were identiﬁed as Lactobacillus reuteri (12 strains), Lactobacillus mucosae (7), Lactobacillus plantarum (6), Lactobacillus kitasatonis (3), Lactobacillus rossiae (2), Lactobacillus ultunensis (2), Lactobacillus crispatus (2), and Lactobacillus intestinalis (1)by partial sequence analysis of the 16S rRNA. All isolates were detected at 8–9 log CFUg −1 . Preliminarily, strains were selected based onresistance to heat treatments (ca. 70 ◦ C for 10 s). The decrease in viability for some L. reuteri , L. mucosae , L. plantarum , L. kitasatonis ,and L. rossiae strains was lower than 1 log cycle. Selected strains were further characterized for acid and bile salt resistance, and antibacterial activity.Except for L. kitasatonis , tolerance to simulated gastric and intestinal conditions was enhanced for all strains by addition of reconstituted skimmedmilk. Antibacterial activity was found against Gram-positive and -negative potential pathogens. L. reuteri
Christlicher Hymnus (1982)

Der hier überlieferte, bisher unbekannte Christushymnus ist ein neues Beispiel für die in der frühchristlichen Poesie1 weit verbreitete alphabetische Akrostichis. In der Metrik des Hymnus zeigen sich deutliche Merkmale des Übergangs vom quantitierenden zum akzentuierenden System, einige der verwendeten Christusnamen sind wenig bekannt, die Doxologie tritt in einer bisher nicht überlieferten Form auf. Inhaltliches und Formales weisen den Hymnus in die erste Hälfte des vierten Jahrhunderts n. Chr.
Bacterial Penetration of Human Dentin in vitro (1980)

The ability of bacteria to penetrate acid-etched and unetched human dentin was examined in vitro using a split chamber. Results indicate that bacteria can grow through or be filtered by pressure through acid-etched dentin. Unetched dentin, while permitting fluid filtration, restricts bacterial penetration. Penetration of dentin tubules by bacteria reduces the rate of fluid filtration across dentin.
Update on the pathophysiology and management of idiopathic intracranial hypertension (2012)

Idiopathic intracranial hypertension is a disease of unknown aetiology, typically affecting young obese women, producing a syndrome of increased intracranial pressure without identifiable cause. Despite a large number of hypotheses and publications over the past decade, the aetiology is still unknown. Vitamin A metabolism, adipose tissue as an actively secreting endocrine tissue and cerebral venous abnormalities are areas of active study regarding the pathophysiology of idiopathic intracranial hypertension. There continues to be no evidence based consensus or formal guidelines regarding management and treatment of the disease. Treatment studies show that the diagnostic lumbar puncture is a valuable intervention beyond its diagnostic importance, and that weight management is critical. However, many questions remain regarding the efficacy of acetazolamide, CSF shunting procedures and cerebral transverse venous sinus stenting.
Analysis of the contact sites on the CD4 molecule with class II MHC molecule: co-ligand versus co-receptor function (1997)

The CD4 molecule interacts with the alpha2 and beta2 domains of the MHC class II molecules. However, the class II contact sites on CD4 are less clear. Involvement of different regions throughout D1, D2, and D3 domains have been suggested. To further delineate the class II MHC contact sites on CD4, a crystal structure-informed mutagenesis was performed. Alanine scan mutants were generated for exposed residues located throughout D1 and the FG loop of D2, and in the "hinge-like" region, a short and flexible region between D2 and D3. Mutants were tested in a co-ligand (Dd stimulation) and a co-receptor (staphylococcal enterotoxin B stimulation) assay. In the co-ligand assay, TCR and CD4 interact with two distinct ligands (Dd or HLA-DR), while in the co-receptor assay both molecules interact with the same ligand, namely HLA-DR. Results show that residues from both lateral faces of D1 and the FG loop of D2 are implicated in interaction with class II, although a bigger surface of CD4 was involved in co-receptor compared with co-ligand function. The potential involvement of residues on both the top and two side faces of CD4 is consistent with a bivalent model, which involves the interaction between a single CD4 and two class II molecules. Alternatively, our results can be interpreted with a model of a specifically organized CD4 and/or class II oligomerization event. Finally, results from the hinge region mutants revealed a very important role in maintaining the overall structural integrity of CD4, its topology, and function.
Glucagon-like peptide 1 (1–37) converts intestinal epithelial cells into insulin-producing cells (2003)

Glucagon-like peptide (GLP) 1 is produced through posttranslational processing of proglucagon and acts as a regulator of various homeostatic events. Among its analogs, however, the function of GLP-1-(1-37), synthesized in small amounts in the pancreas, has been unclear. Here, we find that GLP-1-(1-37) induces insulin production in developing and, to a lesser extent, adult intestinal epithelial cells in vitro and in vivo, a process mediated by up-regulation of the Notch-related gene ngn3 and its downstream targets, which are involved in pancreatic endocrine differentiation. These cells became responsive to glucose challenge in vitro and reverse insulin-dependent diabetes after implantation into diabetic mice. Our findings suggest that efficient induction of insulin production in intestinal epithelial cells by GLP-1-(1-37) could represent a new therapeutic approach to diabetes mellitus.
Requirement of an integrated immune response for successful neuroattenuated HSV-1 therapy in an intracranial metastatic melanoma model (2003)

Neuroattenuated herpes simplex virus ICP34.5 mutants slow progression of preformed tumors and lead to complete regression of some tumors. Although this was previously thought to be due to viral lysis of infected tumor cells, it is now understood that there is an immune component to tumor destruction. We have previously shown that no difference in survival is seen in lymphocyte-depleted mice after viral or mock therapy of syngeneic intracranial melanomas. We have also demonstrated the presence of a wide spectrum of immune cells following viral therapy, including larger percentages of CD4+ T cells and macrophages. In this paper, the contribution of the immune system to tumor destruction has been further delineated. Viral therapy of intracranial melanoma induces a tumor-specific cytotoxic and proliferative T cell response. However, there is no increase following viral therapy in either serum tumor antibody levels or viral-neutralizing antibodies. Thus specific T cell responses appear to mediate viral-elicited prolongation in survival. These data suggest that designing new viruses capable of augmenting T cell responses may induce stronger tumor destruction upon viral therapy.
N-tert-Butanesulfinyl Imines:  Versatile Intermediates for the Asymmetric Synthesis of Amines (2002)

N-tert-Butanesulfinyl aldimines 3 and ketimines 4 are exceedingly versatile intermediates for the asymmetric synthesis of amines. The N-tert-butanesulfinyl imines are prepared in high yields by condensing enantiomerically pure tert-butanesulfinamide 1, which is readily available in either configuration, with a wide range of aldehydes and ketones. The tert-butanesulfinyl group activates the imines for the addition of many different classes of nucleophiles, serves as a powerful chiral directing group, and after nucleophilic addition is readily cleaved by treatment of the product with acid. A wide range of highly enantioenriched amines, including alpha-branched and alpha,alpha-dibranched amines, alpha- and beta-amino acids, 1,2- and 1,3-amino alcohols, and alpha-trifluoromethyl amines, are efficiently synthesized using this methodology. In addition, N-tert-butanesulfinyl imine derivatives provide a new family of ligands for asymmetric catalysis.
Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent (2020)

ClinicalTrials.gov identifier: NCT03039192.
Comb-drive actuators for large displacements (1996)

The design, fabrication and experimental results of lateral-comb-drive actuators for large displacements at low driving voltages is presented. A comparison of several suspension designs is given, and the lateral large deflection behaviour of clamped-clamped beams and a folded flexure design is modelled. An expression for the axial spring constant of folded flexure designs including bending effects from lateral displacements, which reduce the axial stiffness, is also derived. The maximum deflection that can be obtained by comb-drive actuators is bounded by electromechanical side instability. Expressions for the side-instability voltage and the resulting displacement at side instability are given. The electromechanical behaviour around the resonance frequency is described by an equivalent electric circuit. Devices are fabricated by polysilicon surface micromachining techniques using a one-mask fabrication process. Static and dynamic properties are determined experimentally and are compared with theory. Static properties are determined by displacement-to-voltage, capacitance-to-voltage and pull-in voltage measurements. Using a one-port approach, dynamic properties are extracted from measured admittance plots. Typical actuator characteristics are deflections of about 30 μm at driving voltages around 20 V, a resonance frequency around 1.6 kHz and a quality factor of approximately 3.