gebhart/patrepeval huggingface dataset:
Pharmacokinetic Characteristics of Bolus‐Administered Mannitol in Patients Undergoing Elective Craniotomy (2010)

To better understand mannitol pharmacokinetics, the authors constructed and compared population models for high‐ versus low‐dose bolus infusions in humans. Patients (aged 18–75, American Society of Anesthesiologists physical status 1–3) scheduled for elective craniotomy with an anticipated need for intraoperative mannitol were randomly assigned to receive either 0.5 (n = 10) or 1.0 (n = 12) g/kg of 20% mannitol over 15 minutes. Serial blood samples were collected at the predetermined intervals over 12 hours. Plasma mannitol concentrations were measured by gas chromatography and subjected to pharmacokinetic analysis; a 3‐compartment model best described mannitol disposition characteristics. Weight and dose were the important covariates for rapid peripheral volume of distribution (V2) and central clearance (CL1), respectively. Estimated population means were 2.80, 8.86, and 12.0 L for central (V1), rapid (V2), and slow (V3) volumes of distribution, respectively. Clearances of the central compartments (CL1) were 0.07 versus 0.04 L/min in the high‐ versus low‐dose group, respectively. Thus, mannitol kinetics can be considered as nonlinear. Clearances of the rapid peripheral (CL2) and slow peripheral compartments (CL3) were identical (2.07 and 0.16 L/min) in both. The current weight‐based dosing guidelines yielded greater than expected plasma drug concentrations in obese patients.
Automated scoring of interview videos using Doc2Vec multimodal feature extraction paradigm (2016)

As the popularity of video-based job interviews rises, so does the need for automated tools to evaluate interview performance. Real world hiring decisions are based on assessments of knowledge and skills as well as holistic judgments of person-job fit. While previous research on automated scoring of interview videos shows promise, it lacks coverage of monologue-style responses to structured interview (SI) questions and content-focused interview rating. We report the development of a standardized video interview protocol as well as human rating rubrics focusing on verbal content, personality, and holistic judgment. A novel feature extraction method using ``visual words" automatically learned from video analysis outputs and the Doc2Vec paradigm is proposed. Our promising experimental results suggest that this novel method provides effective representations for the automated scoring of interview videos.
Silencing Mutant Huntingtin by Adeno-Associated Virus-Mediated RNA Interference Ameliorates Disease Manifestations in the YAC128 Mouse Model of Huntington's Disease (2014)

Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disease caused by an increase in the number of polyglutamine residues in the huntingtin (Htt) protein. With the identification of the underlying basis of HD, therapies are being developed that reduce expression of the causative mutant Htt. RNA interference (RNAi) that seeks to selectively reduce the expression of such disease-causing agents is emerging as a potential therapeutic strategy for this and similar disorders. This study examines the merits of administering a recombinant adeno-associated viral (AAV) vector designed to deliver small interfering RNA (siRNA) that targets the degradation of the Htt transcript. The aim was to lower Htt levels and to correct the behavioral, biochemical, and neuropathological deficits shown to be associated with the YAC128 mouse model of HD. Our data demonstrate that AAV-mediated RNAi is effective at transducing greater than 80% of the cells in the striatum and partially reducing the levels (~40%) of both wild-type and mutant Htt in this region. Concomitant with these reductions are significant improvements in behavioral deficits, reduction of striatal Htt aggregates, and partial correction of the aberrant striatal transcriptional profile observed in YAC128 mice. Importantly, a partial reduction of both the mutant and wild-type Htt levels is not associated with any notable overt neurotoxicity. Collectively, these results support the continued development of AAV-mediated RNAi as a therapeutic strategy for HD.
Generation of Transgenic Mice (2009)

This unit describes detailed step-by-step protocols, reagents, and equipment required for successful generation of transgenic mice using pronuclear injection. The experimental methods and practical tips given here will help guide beginners in understanding what is required and what to avoid in these standard protocols for efficiently generating transgenic mice.
Discrete elastic rods (2008)

We present a discrete treatment of adapted framed curves, parallel transport, and holonomy, thus establishing the language for a discrete geometric model of thin flexible rods with arbitrary cross section and undeformed configuration. Our approach differs from existing simulation techniques in the graphics and mechanics literature both in the kinematic description---we represent the material frame by its angular deviation from the natural Bishop frame---as well as in the dynamical treatment---we treat the centerline as dynamic and the material frame as quasistatic. Additionally, we describe a manifold projection method for coupling rods to rigid-bodies and simultaneously enforcing rod inextensibility. The use of quasistatics and constraints provides an efficient treatment for stiff twisting and stretching modes; at the same time, we retain the dynamic bending of the centerline and accurately reproduce the coupling between bending and twisting modes. We validate the discrete rod model via quantitative buckling, stability, and coupled-mode experiments, and via qualitative knot-tying comparisons.
AN UPDATE ON THE OMNITRACSR TWO-WAY SATELLITE MOBILE COMMUNICATIONS SYSTEM AND ITS APPLICATION TO THE SCHNEIDER NATIONAL TRUCK FLEET (1992)

This presentation describes the OmniTRACS two-way mobile satellite communications and vehicle position reporting system and its application to a trucking fleet.
[Chart for estimating neonatal weight]. (1993)

Estimation of neonatal weight can be used to aid management during gestation as well as to help choose the delivery method. In this study, the uterine height and abdominal circumference of 403 normal women were measured within a week before delivery. The babies were weighed immediately after birth and the data calculated by a computer and analyzed by stepwise regression analysis. A multiple linear regression equation was formed, as follows: Y gram (neonatal weight) = 101.24X1 (uterine height) +16.58X2 (abdominal circumference) -1907.64. This equation was used to construct a chart for estimating neonatal weight. Error analysis between the predicted and actual weights of 115 babies was conducted, and the results showed that the error was within +/- 300 g in 82.6%. The chart is considered a simple, convenient and accurate method for estimating fetal weight in the clinic.
Botulinum toxin injections for adults with overactive bladder syndrome (2007)

Intravesical botulinum toxin shows promise as a therapy for overactive bladder symptoms, but as yet too little controlled trial data exist on benefits and safety compared with other interventions, or with placebo. Practitioners should be aware that at present there is little more than anecdotal evidence, in the form of case reports to support the efficacy of intravesical botulinum toxin; there is not much in the way of substantial, robust safety data. Furthermore, the optimal dose of botulinum toxin for efficacy and safety has not yet been demonstrated.
Clinical description of 44 patients with acute promyelocytic leukemia who developed the retinoic acid syndrome. (2000)

We examined the incidence, clinical course, and outcome of patients with newly diagnosed acute promyelocytic leukemia (APL) who developed the retinoic acid syndrome (RAS) treated on the Intergroup Protocol 0129, which prospectively evaluated the role of alltrans retinoic acid (ATRA) alone during induction and as maintenance therapy. Forty-four of 167 (26%) patients receiving ATRA for induction developed the syndrome at a median of 11 days of ATRA (range, 2-47). The median white blood cell (WBC) count was 1,450/microL at diagnosis and was 31,000/microL (range, 6,800-72,000/microL) at the time the syndrome developed. ATRA was discontinued in 36 of the 44 patients (82%) and continued in 8 patients (18%), with subsequent resolution of the syndrome in 7 of the 8. ATRA was resumed in 19 of the 36 patients (53%) in whom ATRA was stopped and not in 17 (47%). The syndrome recurred in 3 of those 19 patients, with 1 death attributable to resumption of the drug. Ten of these 36 patients received chemotherapy without further ATRA, and 8 achieved complete remission (CR). Among 7 patients in whom ATRA was not restarted and were not treated with chemotherapy, 5 achieved CR and 2 died. Two deaths were definitely attributable to the syndrome. No patient receiving ATRA as maintenance developed the syndrome. (Blood. 2000;95:90-95)
Safety and efficacy of adjuvant anti-PD1 therapy (nivolumab) in combination with vaccine in resected high-risk metastatic melanoma. (2013)

9056^ Background: Nivolumab (BMS-936558), a fully human monoclonal antibody targeting the programmed death-1 (PD-1) receptor, has demonstrated clinical activity in advanced metastatic melanoma patients (pts). In this phase I study, the safety and activity of nivolumab plus a multipeptide vaccine was investigated as adjuvant therapy in resected stage IIIC and IV melanoma pts. Methods: HLA-A*0201 positive pts with HMB-45, NY-ESO-1, and/or MART-1 positive tumors received nivolumab (1mg/kg, 3mg/kg, or 10mg/kg IV) with a multipeptide vaccine (gp100, MART-1, NY-ESO-1, Montanide ISA 51 VG) every 2 weeks for 12 doses followed by nivolumab maintenance every 3 months (8 doses) or until disease recurrence. The primary objective was safety and determination of maximum tolerated dose (MTD). Secondary objectives were immunologic response and relapse free survival. Results: 33 pts were enrolled: 12 pts at 1mg/kg, 10 pts at 3mg/kg, and 11 pts at 10mg/kg nivolumab. Median age was 47 yrs; 55% male and 52% M1c disease (2 IIIc, 7 M1a, 7 M1b, and 17 M1c pts). As of January 16, 2012, median follow up time was 14 months and median number of doses was 12 (20 pts still receiving therapy). A MTD was not reached. Grade 2-3 related adverse events (AEs) occurred in 27 pts with the most common AEs being fatigue, rash/pruritis, and endocrinopathies. 4 pts experienced grade 3 AEs: (colitis/diarrhea (3), rash (1)). No drug related grade 4 or higher AEs occurred. 7/33 pts have relapsed to date. One pt with biopsy-proven relapse on trial had spontaneous disease regression. Non-relapsing pts had higher pre-treatment PD-1 expression on T reg and T CD4+ cells (p=0.053) and a greater increase in T reg cells after 12 weeks on treatment (p=0.027). Among all pts, treatment led to a rise in T reg cells (p=0.015) and decreased PD-1 expression on T CD4+ and T CD8+ cells (p=0.014 and p&lt;0.001, respectively). Conclusions: Nivolumab is well tolerated in combination with vaccine and preliminary data demonstrates immunologic and clinical activity as adjuvant therapy, justifying a randomized phase III study in resected high risk melanoma pts. Clinical trial information: NCT01176474.
Mixture Trees for Modeling and Fast Conditional Sampling with Applications in Vision and Graphics (2005)

We introduce mixture trees, a tree-based data-structure for modeling joint probability densities using a greedy hierarchical density estimation scheme. We show that the mixture tree models data efficiently at multiple resolutions, and present fast conditional sampling as one of many possible applications. In particular, the development of this data-structure was spurred by a multi-target tracking application, where memory-based motion modeling calls for fast conditional sampling from large empirical densities. However, it is also suited to applications such as texture synthesis, where conditional densities play a central role. Results are presented for both these applications.
Purification and characterization of natural human interferon omega 1. Two alternative cleavage sites for the signal peptidase. (1990)

Human interferon omega 1 (IFN-omega 1 = IFN-alpha II1) is a recently discovered protein structurally related to IFN-alpha and -beta; the biological activities of IFN-omega 1 and its physiological role are not known to date. We have purified IFN-omega 1 from preparations of human leukocyte IFN, derived from peripheral blood leukocytes induced with Sendai virus, by two sequential cycles of monoclonal antibody affinity chromatography. The resulting protein was at least 95% pure as determined by reverse-phase high performance liquid chromatography and showed an Mr of 24,500 upon sodium dodecyl sulfate-gel electrophoresis (theoretical Mr, 19,984). Amino acid sequence analysis revealed that only about 40% of the molecules have the NH2 terminus expected on the basis of the sequence similarity to IFN-alpha, whereas the others contain two additional amino acids. This difference probably results from variable cleavage of the pre-protein by the signal peptidase. No evidence for COOH-terminal heterogeneity was found. Essentially all IFN-omega 1 molecules are glycosylated; enzymatic deglycosylation resulted in a reduction of the Mr to 20,500. Experiments using several plant lectins indicated the presence of biantennary complex oligosaccharides containing neuraminic acid. Two major peaks were observed upon chromatofocusing, with isoelectric points of 8.1 and 8.5. The specific antiviral activity of purified IFN-omega 1 assayed on human cells was determined to be 2.7 x 10(8) IU/mg, similar to that of other human class I IFNs; potent antiviral activity was also observed on cells of bovine and ovine but not of equine or murine origin.
Electroluminescent features of oligothiophenes dispersed as a dopant in host matrices (2002)

The electroluminescent (EL) features of oligothiophenes dispersed as a dopant in the host matrices comprising tris(8-hydroxyquinoline)aluminum have been investigated. We chose the oligothiophenes that are substituted with phenyl or methyl groups at both the molecular terminals and possess various degrees of polymerization. Regarding both the phenyl- and methyl-substituted materials, the EL spectra are progressively red-shifted with the increasing number of thiophenes. Comparing these spectra with the photoluminescent spectra, we have found out that the EL arises mostly from the dopant molecules of the oligothiophenes. The emission is dominated by energy transfer from host matrices to the dopant molecules, leading to the enhanced device efficiencies. The specific effects of the phenyl- or methyl-substitution and the extension of the π-delocalization in the molecules are also discussed.
Heterogeneity of water‐soluble amyloid β‐peptide in Alzheimer's disease and Down's syndrome brains (1997)

Water-soluble amyloid beta-peptides (sA beta), ending at residue 42, precede amyloid plaques in Down's syndrome (DS). Here we report that sA beta consists of the full-length A beta(1-42) and peptides truncated and modified by cyclization of the N-terminal glutamates, A beta[3(pE)-42] and A beta[11(pE)-42]. The A beta[3(pE)-42] peptide is the most abundant form of sA beta in Alzheimer's disease (AD) brains. In DS, sA beta[3(pE)-42] concentration increases with age and the peptide becomes a dominant species in the presence of plaques. Both pyroglutamate-modified peptides and the full-length A beta form a stable aggregate that is water soluble. The findings point to a crucial role of the aggregated and modified sA beta in the plaque formation and pathogenesis of AD.
Overexpression of the Integrin-linked Kinase Promotes Anchorage-independent Cell Cycle Progression (1997)

Cell adhesion to substratum has been shown to regulate cyclin A expression as well as cyclin D- and E-dependent kinases, the latter via the up-regulation of cyclin D1 and the down-regulation of cyclin-Cdk inhibitors p21 and p27, respectively. This adhesion-dependent regulation of cell cycle is thought to be mediated by integrins. Here we demonstrate that stable transfection and overexpression of the integrin-linked kinase (ILK), which interacts with the beta1 and beta3 integrin cytoplasmic domains, induces anchorage-independent cell cycle progression but not serum-independent growth of rat intestinal epithelial cells (IEC18). ILK overexpression results in increased expression of cyclin D1, activation of Cdk4 and cyclin E-associated kinases, and hyperphosphorylation of the retinoblastoma protein. In addition, ILK overexpression results in the expression of p21 and p27 Cdk inhibitors with altered electrophoretic mobilities, with the p27 from ILK-overexpressing cells having reduced inhibitory activity. The transfer of serum-exposed IEC18 cells from adherent cultures to suspension cultures results in a rapid down-regulation of expression of cyclin D1 and cyclin A proteins as well as in retinoblastoma protein dephosphorylation. In marked contrast, transfer of ILK-overexpressing cells from adherent to suspension cultures results in continued high levels of expression of cyclin D1 and cyclin A proteins, and a substantial proportion of the retinoblastoma protein remains in a hyperphosphorylated state. These results indicate that, when overexpressed, ILK induces signaling pathways resulting in the stimulation of G1/S cyclin-Cdk activities, which are normally regulated by cell adhesion and integrin engagement.
Alterations of annexin expression in pathological neuronal and glial reactions. Immunohistochemical localization of annexins I, II (p36 and p11 subunits), IV, and VI in the human hippocampus. (1994)

Annexins are Ca(2+)-dependent membrane-binding proteins that are potentially important in Ca(2+)-induced neurotoxicity or neuroprotection. To address the possible involvement of annexins in cellular reactions to brain injury and neurodegenerative disease, we studied the immunohistochemical localization of annexins I, II (p36 and p11), IV, and VI in the adult human hippocampus. Formalin-fixed, paraffin-embedded tissue from autopsy cases representing hypoxic-ischemic injury, seizure disorders, Alzheimer's disease, and age-related controls were examined. Neurons showed cytoplasmic immunoreactivity for annexin I, whereas annexin VI was distributed in patterns suggesting plasma membrane and perisynaptic locations. The cytoarchitectural distribution of annexin VI within neurons was altered in pathological states and annexin VI was strongly associated with neuronal granulovacuolar bodies in Alzheimer's disease. Reactive astrocytes expressed annexins I, II (p36 and p11), and IV, whereas quiescent astrocytes were minimally immunoreactive. Significant annexin immunoreactivity was also detected in oligodendrocytes (annexin IV), ependymocytes (I, II, and IV), choroid plexus (I, IV, and VI), meningothelium (I, II, IV, and VI), and vascular endothelium (II and IV) and smooth muscle (I, IV, and VI). This is the first comparative study of immunoreactivities for multiple annexins in human brain. Neurons and glia display selective and different profiles of annexin protein expression and show immunohistochemical changes in pathological conditions, which suggest involvement of annexins in neuronal and glial reactions to injury.
mTOR inhibition improves immune function in the elderly (2014)

Inhibition of the mammalian target of rapamycin (mTOR) pathway extends life span in all species studied to date, and in mice delays the onset of age-related diseases and comorbidities. However, it is unknown if mTOR inhibition affects aging or its consequences in humans. To begin to assess the effects of mTOR inhibition on human aging-related conditions, we evaluated whether the mTOR inhibitor RAD001 ameliorated immunosenescence (the decline in immune function during aging) in elderly volunteers, as assessed by their response to influenza vaccination. RAD001 enhanced the response to the influenza vaccine by about 20% at doses that were relatively well tolerated. RAD001 also reduced the percentage of CD4 and CD8 T lymphocytes expressing the programmed death-1 (PD-1) receptor, which inhibits T cell signaling and is more highly expressed with age. These results raise the possibility that mTOR inhibition may have beneficial effects on immunosenescence in the elderly.
발정주기에 따른 생쥐의 선하수체내 Prolactin 및 Growth Hormone 양성 세포에 관한 면역조직화학적 연구 (1991)

성숙한 BALB/c계 자성생쥐와 웅성생쥐 및 미성숙 자성생쥐들의 선하수체에서 prolactin 및 growth hormone을 분비하는 세포들을 면역조직화학 반응으로 감별 동정하여, 자성생쥐의 발정주기에 따른 수의 변화와 분포의 변화를 조사하고, 이들과 웅성생쥐 및 미성숙자성생쥐와의 차이를 비교한 결과 다음과 같은 소견을 얻었다. 1. 생쥐의 선하수체 조직절편상에서 일부 세포들은 각각 anti-prolactin 및 anti-growth hormone에 선택적으로 염색되어 양성반응을 보였다. 2. Growth hormone 양성세포의 수는 전 실험군에서 선하수체의 중앙부와 주변부에서 고르게 관찰되었으나, prolactin 양성세포의 수는 중앙부에 비하여 주변부에서 많이 관찰되었다. 3. 자성생쥐의 발정주기에 따른 prolactin 양성세포와 growth hormone 양성세포의 수의 변화는 발정기에서 가장 많이 관찰되고 발정후기에 급격히 감소하는 주기적인 변화를 보였다. 4. 발정주기 중의 자성생쥐와 웅성생쥐 및 미성숙자성생쥐 간에 growth hormone 양성세포의 수는 차이가 없었지만, prolactin 양성세포의 수는 발정주기 중의 자성생쥐에서 많이 관찰되었다. 이상의 소견으로 볼 때 prolactin 양성세포와 growth hormone 양성세포는 자성생쥐의 생식과 밀접한 관계가 있다고 사료된다.
The antibipolar drug valproate mimics lithium in stimulating glutamate release and inositol 1,4,5-trisphosphate accumulation in brain cortex slices but not accumulation of inositol monophosphates and bisphosphates (1997)

Valproic acid and lithium are effective antibipolar drugs. We recently showed that lithium stimulated the release of glutamate in monkey and mouse cerebral cortex slices, which, through activation of the N-methyl-D-aspartate receptor, increased accumulation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. We show here that valproate behaves similarly to lithium in that at therapeutic concentrations it stimulates glutamate release and Ins(1,4,5)P3 accumulation in mouse cerebral cortex slices. The fact that these two effects are a common denominator for two structurally unrelated antibipolar drugs suggests that these effects are important in their antibipolar action. The effects of maximal concentrations of lithium and valproate on glutamate release are additive, suggesting different mechanisms for release, which are discussed. The additivity of the two drugs on glutamate release is consistent with the clinical benefit of combining the two drugs in the treatment of subsets of bipolar patients, e.g., in rapid cycling manic-depression. Unlike lithium, valproate does not increase accumulation of inositol monophosphates, inositol bisphosphates, or inositol 1,3,4-trisphosphate. This is additional evidence against the "inositol depletion" hypothesis, which states that, by trapping inositol in the form of inositol monophosphates and certain inositol polyphosphates, lithium exerts its antimanic action by inhibiting resynthesis of phosphoinositides with resultant blunting of Ins(1,4,5)P3 signaling.
Application of Temperature-Dependent Fluorescent Dyes to the Measurement of Millimeter Wave Absorption in Water Applied to Biomedical Experiments (2014)

Temperature sensitivity of the fluorescence intensity of the organic dyes solutions was used for noncontact measurement of the electromagnetic millimeter wave absorption in water. By using two different dyes with opposite temperature effects, local temperature increase in the capillary that is placed inside a rectangular waveguide in which millimeter waves propagate was defined. The application of this noncontact temperature sensing is a simple and novel method to detect temperature change in small biological objects.