gebhart/patrepeval huggingface dataset:
A Phase I Study of HGP-30, a 30 Amino Acid Subunit of the Human Immunodeficiency Virus (HIV) p17 Synthetic Peptide Analogue Sub-unit Vaccine in Seronegative Subjects (1992)

HGP-30-KLH vaccine in alum at doses of 10, 25, 50, and 100 micrograms/kg administered intramuscularly at weeks 0, 4, and 10 appear well-tolerated clinically. Local pain at the injection site, appears to be the main clinical toxicity. Laboratory parameters are not affected by administration of the vaccine candidate except for perhaps mild urinalysis abnormalities at the highest dose. This vaccine candidate has no apparent immunotoxicity and does not appear to affect lymphocyte populations or T-cell functional studies. Low levels and transient antibodies develop in a minority of subjects early after immunization with the vaccine candidate. These responses were observed in the lowest dose range. Higher doses, and longer follow-up will be needed to confirm this observation. T-cell proliferative responses to KLH and KLH-HGP-30 are consistent and may not be dose dependent, but the proliferative responses are variable and more data need to be accumulated. Preliminary, there appears to be an HGP-30-induced CTL response of HGP-30-coated EBV-transformed autologous B cell lines. This study was approved under an IND for the California Department of Health Services' Food and Drug Branch. They have provided excellent support and regulatory guidelines for this project. Future work will extend and confirm these initial observations.
Brain monoamine oxidase A inhibition in cigarette smokers (1996)

Several studies have documented a strong association between smoking and depression. Because cigarette smoke has been reported to inhibit monoamine oxidase (MAO) A in vitro and in animals and because MAO A inhibitors are effective antidepressants, we tested the hypothesis that MAO A would be reduced in the brain of cigarette smokers. We compared brain MAO A in 15 nonsmokers and 16 current smokers with [11C]clorgyline and positron emission tomography (PET). Four of the nonsmokers were also treated with the antidepressant MAO inhibitor drug, tranylcypromine (10 mg/day for 3 days) after the baseline PET scan and then rescanned to assess the sensitivity of [11C]clorgyline binding to MAO inhibition. MAO A levels were quantified by using the model term lambda k3 which is a function of brain MAO A concentration. Smokers had significantly lower brain MAO A than nonsmokers in all brain regions examined (average reduction, 28%). The mean lambda k3 values for the whole brain were 0.18 +/- 0.04 and 0.13 +/- 0.03 ccbrain (mlplasma)-1 min-1 for nonsmokers and smokers, respectively; P < 0.0003). Tranyl-cypromine treatment reduced lambda k3 by an average of 58% for the different brain regions. Our results show that tobacco smoke exposure is associated with a marked reduction in brain MAO A, and this reduction is about half of that produced by a brief treatment with tranylcypromine. This suggests that MAO A inhibition needs to be considered as a potential contributing variable in the high rate of smoking in depression and in the development of more effective strategies for smoking cessation.
Recurrent Neural Network Grammars (2016)

Chris Dyer, Adhiguna Kuncoro, Miguel Ballesteros, Noah A. Smith. Proceedings of the 2016 Conference of the North American Chapter of the Association for Computational Linguistics: Human Language Technologies. 2016.
The Mitochondrial Respiratory Chain Is Partially Organized in a Supercomplex Assembly (2004)

The model of the respiratory chain in which the enzyme complexes are independently embedded in the lipid bilayer of the inner mitochondrial membrane and connected by randomly diffusing coenzyme Q and cytochrome c is mostly favored. However, multicomplex units can be isolated from mammalian mitochondria, suggesting a model based on direct electron channeling between complexes. Kinetic testing using metabolic flux control analysis can discriminate between the two models: the former model implies that each enzyme may be rate-controlling to a different extent, whereas in the latter, the whole metabolic pathway would behave as a single supercomplex and inhibition of any one of its components would elicit the same flux control. In particular, in the absence of other components of the oxidative phosphorylation apparatus (i.e. ATP synthase, membrane potential, carriers), the existence of a supercomplex would elicit a flux control coefficient near unity for each respiratory complex, and the sum of all coefficients would be well above unity. Using bovine heart mitochondria and submitochondrial particles devoid of substrate permeability barriers, we investigated the flux control coefficients of the complexes involved in aerobic NADH oxidation (I, III, IV) and in succinate oxidation (II, III, IV). Both Complexes I and III were found to be highly rate-controlling over NADH oxidation, a strong kinetic evidence suggesting the existence of functionally relevant association between the two complexes, whereas Complex IV appears randomly distributed. Moreover, we show that Complex II is fully rate-limiting for succinate oxidation, clearly indicating the absence of substrate channeling toward Complexes III and IV.
Molecular detection and differentiation of deletions in band 13q14 in human retinoblastoma. (1986)

Five cloned DNA segments within or adjacent to human chromosome band 13q14 were mapped by a combination of in situ hybridization and DNA dosage blotting. The DNA was isolated from human retinoblastoma patients with deletions varying in size and precise location. One of these deletions occurred in mosaic form, requiring T-cell cloning to obtain cells uniformly containing the deletion and useful for blotting. Regions of overlap between the intervals on chromosome #13 deduced for each probe from the two different mapping methods permitted a more precise location for each, from which a physical ordering of these five probes could be obtained. This ordered set of probes constitutes the start of a grid spanning band 13q14 of potential use in the diagnosis and understanding of human retinoblastoma.
Involvement of Cdk5/p25 in Digoxin-triggered Prostate Cancer Cell Apoptosis (2004)

Cardiac digitalis has been considered to be a treatment for breast cancer. Our previous study indicates that digoxin, one member in digitalis, decreases the proliferation of prostate cancer cells, but the mechanisms remain unclear. In the present study, Ca(2+) proved to be an important factor in digoxin-triggered prostate cancer cell death. Because cyclin-dependent kinase (Cdk)5 and p35 cleavage (p25 formation) have been reported to be targets of intracellular Ca(2+), and subsequently correlated to apoptosis, we not only demonstrated first that Cdk5, p35, and p25 proteins were all expressed in prostate cancer cells (including lymph node carcinoma of the prostate (LNCaP) and DU-145 cells), but also showed where p25 formation and Cdk5 kinase activity were affected by treatment with digoxin. The inhibitor of p35 cleavage (calpeptin) was used to reduce p25 formation, and the result suggested that p25 accumulation might be the major cause of digoxin-triggered LNCaP cell death. Butyrolactone-I and roscovitine, two Cdk5 kinase inhibitors, were also found to prevent digoxin-triggered LNCaP cell death. In addition, treatment of siRNA-Cdk5 diminished digoxin-triggered cell death, as compared with the treatments of siRNA-Cdk1 or siRNA-Cdk2, which implies the specific involvement of Cdk5 in digoxin-triggered cell death. Caspase inhibitor set and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay were used to demonstrate that digoxin-triggered LNCaP cell apoptosis through Cdk5 activation. These results suggest that Cdk5/p35 and p25 are novel players in digoxin-triggered prostate cancer cell apoptosis and, therefore, become potential therapeutic targets.
Pteridines. Part XCVII. Synthesis and properties of 6‐thioxanthopterin and 7‐thioisoxanthopterin (1992)

Abstract 6‐Thioxanthopterin ( 13 ) was synthesized in four steps starting from 2‐amino‐4‐(penthyloxy)pteridine ( 3 ) via the 8‐oxide 4 , its subsequent interconversion to the 6‐chloro ( 7 ) and 6‐thio derivative ( 12 ) and final hydrolysis of the pentyloxy group. 7‐Thioisoxanthopterin ( 15 ) was derived analogously from 2‐amino‐4‐(pentyloxy)pteridine‐7(8 H )‐thione ( 14 ) by alkaline hydrolysis. The various 6‐ and 7‐thiopteridines were methylated to give the corresponding 6‐ ( 10, 11 ) and 7‐(methylthio) derivatives ( 16, 17 ). The newly synthesized compounds have been characterized by elemental analyses, their UV spectra, and the determination of the acidic and basic p K a values. The spectral relationships are discussed in detail.
Epidemiology of Carbapenem-Resistant Enterobacteriaceae Infections: Report from the China CRE Network (2017)

Carbapenem-resistant <i>Enterobacteriaceae</i> (CRE) infection is highly endemic in China, but estimates of the infection burden are lacking. We established the incidence of CRE infection from a multicenter study that covered 25 tertiary hospitals in 14 provinces. CRE cases defined as carbapenem-nonsusceptible <i>Citrobacter freundii</i>, <i>Escherichia coli</i>, <i>Enterobacter cloacae</i>, or <i>Klebsiella pneumoniae</i> infections during January to December 2015 were collected and reviewed from medical records. Antimicrobial susceptibility testing and carbapenemase gene identification were performed. Among 664 CRE cases, most were caused by <i>K. pneumoniae</i> (73.9%), followed by <i>E. coli</i> (16.6%) and <i>E. cloacae</i> (7.1%). The overall CRE infection incidence per 10,000 discharges was 4.0 and differed significantly by region, with the highest in Jiangsu (14.97) and the lowest in Qinghai (0.34). Underlying comorbidities were found in 83.8% of patients; the median patient age was 62 years (range, 45 to 74 years), and 450 (67.8%) patients were male. Lower respiratory tract infections (65.4%) were the most common, followed by urinary tract infection (16.6%), intra-abdominal infection (7.7%), and bacteremia (7.7%). The overall hospital mortality rate was 33.5%. All isolates showed nonsusceptibility to carbapenems and cephalosporins. The susceptibility rate of polymyxin B was >90%. Tigecycline demonstrated a higher susceptibility rate against <i>E. coli</i> than against <i>K. pneumoniae</i> (90.9% versus 40.2%). Of 155 clinical isolates analyzed, 89% produced carbapenemases, with a majority of isolates producing KPC (50%) or NDM (33.5%)-type beta-lactamases among <i>K. pneumoniae</i> and <i>E. coli</i> The incidence of CRE infection in China was 4.0 per 10,000 discharges. The patient-based disease burden in tertiary hospitals in China is severe, suggesting an urgent need to enhance infection control.
Total body water measurements using resonant cavity perturbation techniques (2004)

A recent paper proposed a novel technique for determining the total body water (TBW) of patients suffering with abnormal hydration levels, using a resonant cavity perturbation method. Current techniques to measure TBW are limited by resolution and technical constraints. However, this new method involves measuring the dielectric properties of the body, by placing a subject in a large cavity resonator and measuring the subsequent change in its resonant frequency, fres and its Q-factor. Utilizing the relationship that water content correlates to these dielectric properties, it has been shown that the measured response of these parameters enables determination of TBW. Results are presented for a preliminary study using data estimated from anthropometric measurements, where volunteers were asked to lie and stand in an electromagnetic screened room, before and after drinking between 1 and 2 l of water, and in some cases, after voiding the bladder. Notable changes in the parameters were observed; fres showed a negative shift and Q was reduced. Preliminary calibration curves using estimated values of water content have been developed from these results, showing that for each subject the measured resonant frequency is a linear function of TBW. Because the gradients of these calibration curves correlate to the mass-to-height-ratio of the volunteers, it has proved that a system in which TBW can be unequivocally obtained is possible. Measured values of TBW have been determined using this new pilot-technique, and the values obtained correlate well with theoretical values of body water (r = 0.87) and resolution is very good (750 ml). The results obtained are measurable, repeatable and statistically significant. This leads to confidence in the integrity of the proposed technique.
Solvent-driven polymeric micro beam device (2010)

The response of current hydrogel devices mainly depends on the diffusion of stimuli. However, diffusion is a slow transport mechanism compared to advection, which therefore limits the response speed of hydrogel devices. To overcome this limitation, we introduce a capillary network and elastic instability mechanism. Particularly, an open surface capillary delivers and distributes solvent, thus triggering the swelling and bending of curved polymeric beams. To demonstrate this concept, we fabricate these polymeric microstructures using projection micro-stereolithography (PμSL). Combined with instability criteria analysis based on static beam theory, this device is designed to exhibit two-way snap-through behavior. Our analysis provides the minimum dimensionless stiffness β for the beam device to snap during solvent actuation. Here, β is a well-defined dimensionless parameter in our analysis that indicates whether the device can provide sufficient axial force to trigger the snap-through of the beam. The actuation displacement can be as high as 45% of the length of the beam. We observe a maximum midpoint speed of 3.1 cm s−1 for a beam 2 mm long—20 times higher than that for a beam without an elastic instability mechanism. This device can be used in artificial muscle and as the key component for fluidic-to-mechanical signal transduction in active micro-fluidic circuits.
Melanoma cell adhesion to basement membrane mediated by integrin-related complexes. (1989)

During invasion and metastasis, tumor cells use a variety of surface adhesion receptors to attach to and invade basement membranes and interstitial stroma. We examined the role of the cell surface integrin-like complex in the attachment of the invasive murine B16-BL6 melanoma cell line to basement membrane. Polyclonal antibodies prepared against integrin-related complexes isolated from hamster BHK cells (anti-ECMR) or mouse erythroleukemia cells (anti-mouse FnR) inhibited the attachment of B16 cells to complex basement membrane matrices and to substrates coated with purified extracellular matrix components (fibronectin, laminin, and type IV collagen). The expression of integrin-like receptors on the surface of B16 cells was confirmed by selective immunoprecipitation of radiolabeled and solubilized membrane proteins with the antibodies. Both antibodies also reacted with an integrin-related fibronectin-binding receptor complex purified by ligand affinity chromatography on fibronectin-Sepharose columns. The anti-integrin antibodies failed to react with the Mr 68,000 laminin-binding protein, suggesting that their inhibition of cell attachment to laminin and complex basement membrane was not due to contaminating antibodies against the Mr 68,000 laminin receptor. The results indicate that the integrin receptor complexes on B16-BL6 cells either interact directly with a diverse set of extracellular-matrix-associated components or somehow modulate the activity and function of other receptors. Thus integrins may have an important role in tumor cell invasion of tissue barriers.
Synthesis and translation of mRNA containing 5'-terminal 7-ethylguanosine cap. (1979)

Reovirus mRNA synthesis in vitro by the virion-associated RNA polymerase was only slightly (10 to 15%) diminished in the presence of 2 mM S-adenosylethionine. However, methyl group transfer from S-adenosylmethionine (0.05 mM) to the 5'-terminal cap structure, m7GpppGm in this mRNA was markedly inhibited (80%) under these conditions. Replacement of S-adenosylmethionine by S-adenosylethionine (5 mM) yielded mRNAs containing mainly (70%) 5'-terminal e7GpppGe and e7GpppG, but some of the products were unalkylated (5'-GpppG, ppG). The ethylated mRNAs, but not the unalkylated molecules, bound to wheat germ ribosomes and were translated essentially as well as the corresponding methylated mRNAs in wheat germ extracts and in nuclease-treated rabbit reticulocyte lysates. Protein synthesis directed by ethylated mRNAs in wheat germ extract was 80% decreased by 0.1 mM m7GMP. Under conditions of limited initiation, methylated mRNA bound to wheat germ ribosomes preferentially as compared to ethylated mRNA. The results document for the first time the synthesis of ethylated mRNA and support the hypothesis that N7-alkylation of the 5'-guanosine in caps, rather than methylation itself, is important for the enhancing effect of cap on the initiation of eukaryotic protein synthesis.
Fiber laser systems shine brightly (1997)

Describes the advancements in active fiber laser systems. Outline of cladding pumping technique for enhanced power scaling; Improved energies and peak powers; Extended wavelength range; Frequency doubling with fiber sources.
In Situ Caries Models (1995)

By using in situ models, we have the potential to study both fundamental aspects of the caries process as well as more applied research problems such as the effect of food on dental caries and the role of fluoride in caries prevention in human subjects without actually causing caries in the natural dentition. The key experimental parameters that need to be considered in the development of an in situ model are the characteristics of the subject panel, the physical design of the model, the type of hard tissue substrate and the method of assessing mineral status, and the study design and clinical protocol. Each parameter must be carefully considered in relation to the objectives of the research, study design requirements, ethical considerations, impact on clinical relevance, and impact on the control of variation. The major source of variation associated with in situ models should be of biological and not experimental origin. The design and conduct of proper in situ model studies require a clear understanding of the caries process, sound analytical support, and a knowledge of how to work with research subjects to achieve a high level of compliance. Given the complex nature of caries, a combination of hard tissue substrates--including sound, surface-softened lesions and subsurface lesions--may be necessary to model all aspects of caries progression and prevention successfully. Internal validation of in situ models using fluoride dose-response controls is considered to be necessary for studies evaluating the efficacy of new fluoride dentifrice formulations.
The Insulin-like Growth Factor (IGF) Binding Site of Bovine Insulin-like Growth Factor Binding Protein-2 (bIGFBP-2) Probed by Iodination (1996)

The insulin-like growth factor (IGF) binding site of bovine insulin-like growth factor binding protein 2 (bIGFBP-2) has been probed by chemical iodination. Tyrosyl residues of bIGFBP-2 were reacted by chloramine T-mediated iodination. The modification patterns of free bIGFBP-2 and bIGFBP-2 associated with insulin-like growth factor II (IGF-II) were compared by tryptic mapping using electrospray mass spectrometry and N-terminal sequencing. The presence of bound IGF-II resulted in protection of tyrosine at position 60 from iodination measured by the relative loss of tyrosine specific fluorescence and the incorporation of the radioisotope 125I. In addition, the pattern of iodine incorporation of bIGFBP-2 was not different whether IGF-I or IGF-II was the protective ligand. bIGFBP-2, when iodinated alone sustained a 8-fold loss of binding affinity for IGF-I and a 4-fold loss in binding affinity for IGF-II. In contrast, bIGFBP-2 iodinated while complexed with either IGF-I or IGF-II retained the same binding affinity for IGF-I or IGF-II as non-iodinated bIGFBP-2. We conclude that tyrosine 60 lies either in a region of bIGFBP-2 which directly interacts with both IGF-I and IGF-II or lies in a region of bIGFBP-2 which undergoes a conformational change that is important for IGF binding. Furthermore, iodination of tyrosine residues at positions 71, 98, 213, 226, and 269 has no detectable impact on binding of bIGFBP-2 to the IGFs.
Ingestible Biosensors for Real-Time Medical Adherence Monitoring: MyTMed (2016)

Medication nonadherence complicates the management and treatment of chronic disease. Nonadherence to medications is associated with significant mortality, accelerated disease progression, and increased health care costs. My/Treatment/Medication (MyTMed) is a novel adherence monitoring system that obtains direct measures of medication adherence/nonadherence. MyTMed consists of 1) a "digital pill" with a radiofrequency emitter that activates on contact with gastric pH; 2) a relay Hub that captures the radiofrequency signal and transmits it to 3) a cloud based server that connects patient and physicians via a bidirectional interface. In our increasingly mobile world, MyTMed is able to provide medication ingestion data and deliver interventions in real time that support adherence. We describe the patient-centered design of MyTMed as well as the behavioral theory supporting the interface architecture.
Differential Effects of ADAMTS-1, -4, and -5 in the Trabecular Meshwork (2009)

These results show differential responses and expression of ADAMTS-1, -4, and -5 in human TM cells. Combined, these results suggest that ADAMTS-4 is a potential modifier of outflow facility.
Genetic Diversity among Methicillin-Resistant Staphylococcus epidermidis (MRSE) (2005)

We selected 106 methicillin-resistant Staphylococcus epidermidis (MRSE) and 22 methicillin-susceptible S. epidermidis (MSSE) hospital isolates--each with a different PFGE pattern--for more detailed documentation of genetic diversity. The 106 MRSE isolates showed extensive variation in the SmaI DNA fragments hybridizing with the DNA probe for mecA, the molecular size of which varied from as low as 20 kb up to over 500 kb. Parallel variation was also observed in the size of DNA fragments hybridizing with the chromosomal genes orfX and gyrA, and this was also observed in MSSE isolates. In contrast, SmaI fragments associated with the housekeeping genes murE and aroE, both located distantly from orfX, showed little size variation. Typing for the mec complex and ccr identified 10 different SCCmec structures and a large number of strains (21 isolates) that were non-typeable. The majority of strains studied (36%) carried a SCCmec type IV-like structure, including strains with non-related PFGE profiles. On the other hand, closely related strains often carried different types of SCCmec. The findings indicate that the acquisition and/or loss of mobile genetic elements, including various structural types of SCCmec, may occur frequently in the vicinity of the orfX gene on the S. epidermidis chromosome.
Color-converting combinations of nanocrystal emitters for warm-white light generation with high color rendering index (2008)

Warm-white light emitting diodes with high color rendering indices are required for the widespread use of solid state lighting especially indoors. To meet these requirements, we propose and demonstrate warm-white hybrid light sources that incorporate the right color-converting combinations of CdSe∕ZnS core-shell nanocrystals hybridized on InGaN∕GaN LEDs for high color rendering index. Three sets of proof-of-concept devices are developed to generate high-quality warm-white light with (1) tristimulus coordinates (x,y)=(0.37,0.30), luminous efficacy (LE)=307lm∕W, color rending index (CR)=82.4, and correlated color temperature (CCT)=3228K; (2) (x,y)=(0.38,0.31), LE=323lm∕W, CRI=81.0, and CCT=3190K; and (3) (x,y)=(0.37,0.30), LE=303lm∕W, CRI=79.6, and CCT=1982K.