gebhart/patrepeval huggingface dataset:
Towards a whole-cell modeling approach for synthetic biology (2013)

Despite rapid advances over the last decade, synthetic biology lacks the predictive tools needed to enable rational design. Unlike established engineering disciplines, the engineering of synthetic gene circuits still relies heavily on experimental trial-and-error, a time-consuming and inefficient process that slows down the biological design cycle. This reliance on experimental tuning is because current modeling approaches are unable to make reliable predictions about the in vivo behavior of synthetic circuits. A major reason for this lack of predictability is that current models view circuits in isolation, ignoring the vast number of complex cellular processes that impinge on the dynamics of the synthetic circuit and vice versa. To address this problem, we present a modeling approach for the design of synthetic circuits in the context of cellular networks. Using the recently published whole-cell model of Mycoplasma genitalium, we examined the effect of adding genes into the host genome. We also investigated how codon usage correlates with gene expression and find agreement with existing experimental results. Finally, we successfully implemented a synthetic Goodwin oscillator in the whole-cell model. We provide an updated software framework for the whole-cell model that lays the foundation for the integration of whole-cell models with synthetic gene circuit models. This software framework is made freely available to the community to enable future extensions. We envision that this approach will be critical to transforming the field of synthetic biology into a rational and predictive engineering discipline.
Modelling the spectral sensitivity of the human circadian system (2011)

It is now well established that the spectral, spatial, temporal and absolute sensitivities of the human circadian system are very different from those of the human visual system. Although qualitative comparisons between the human circadian and visual systems can be made, there still remains some uncertainty in quantitatively predicting exactly how the circadian system will respond to different light exposures reaching the retina. This paper discusses attempts to model the spectral sensitivity of the circadian system. Each of the models discussed here varies in terms of its complexity and its consideration of retinal neuroanatomy and neurophysiology. Future testing to validate or improve any of these computational models will require a targeted hypothesis, as well as a suitably high level of experimental control before one model can be rejected in favour of another. Until specific hypotheses are formulated and tested, it would be premature to recommend international acceptance of any model or system of circadian photometry.
Tinnitus outcome profile and tinnitus control. (2003)

This reports recommends the consideration of development of additional outcome measures to be used as a battery of subjective self-assessment questionnaires for patients with tinnitus. The goal is improved overall care for the tinnitus patient. Five existing outcome measurements have been incorporated into this profile, which is called the tinnitus outcome profile: the tinnitus intensity index, the tinnitus annoyance index, the tinnitus stress test, the tinnitus handicap inventory, and the measurement of depression scale. Frequently, there is an inconsistency between the self-report outcomes and the patient's subjective report to the doctor. This study reports outcomes based on the tinnitus outcome profile for 19 patients who were seen for evaluation and treatment of subjective idiopathic tinnitus of the severe disabling type and who completed a treatment protocol called receptor-targeted therapy directed to the GABAA receptor. The drugs used were gabapentin and clonazepam. Using the 0.05 significance level, the tinnitus intensity index, tinnitus annoyance index, and tinnitus stress test scores all declined significantly over time. In contrast, there was no significant change in either the tinnitus handicap inventory or the measurement of depression scale. The percent of tinnitus control reported to the doctor by the patient did not appear to be correlated with the degree of change measured on the tinnitus outcome profile.
Phosphatidylinositol 3-Kinase Regulates the Induction of Long-Term Potentiation through Extracellular Signal-Related Kinase-Independent Mechanisms (2003)

Inhibitors of both phosphatidylinositol-3-kinase (PI3-kinase) and MAPK/ERK (mitogen-activate protein kinase/extracellular signal-related kinase) activation inhibit NMDA receptor-dependent long-term potentiation (LTP). PI3-kinase inhibitors also block activation of ERK by NMDA receptor stimulation, suggesting that PI3-kinase inhibitors block LTP because PI3-kinase is an essential upstream regulator of ERK activation. To examine this hypothesis, we investigated the effects of PI3-kinase inhibitors on ERK activation and LTP induction in the CA1 region of mouse hippocampal slices. Consistent with the notion that ERK activation by NMDA receptor stimulation is PI3-kinase dependent, the PI3-kinase inhibitor wortmannin partially inhibited ERK2 activation induced by bath application of NMDA and strongly suppressed ERK2 activation by high-frequency synaptic stimulation. PI3-kinase and MEK (MAP kinase kinase) inhibitors had very different effects on LTP, however. Both types of inhibitors suppressed LTP induced by theta-frequency trains of synaptic stimulation, but only PI3-kinase inhibitors suppressed the induction of LTP by high-frequency stimulation or low-frequency stimulation paired with postsynaptic depolarization. Concentrations of PI3-kinase inhibitors that inhibited LTP when present during high-frequency stimulation had no effect on potentiated synapses when applied after high-frequency stimulation, suggesting that PI3-kinase is specifically involved in the induction of LTP. Finally, we found that LTP induced by theta-frequency stimulation was MEK inhibitor insensitive but still PI3-kinase dependent in hippocampal slices from PSD-95 (postsynaptic density-95) mutant mice. Together, our results indicate that the role of PI3-kinase in LTP is not limited to its role as an upstream regulator of MAPK signaling but also includes signaling through ERK-independent pathways that regulate LTP induction.
Thermal destruction processes in proteins involving cystine residues. (1987)

To ascertain the upper limit of protein thermostability and to evaluate the introduction of additional -S-S- bridges for the enhancement of protein thermostability by site-directed mutagenesis, the stability of cystine residues at 100 degrees C has been investigated in a number of unrelated proteins. All proteins studied (more than a dozen) undergo heat-induced beta-elimination of cystine residues in the pH range from 4 to 8. The time courses of this process closely follow first-order kinetics indicating that the stability of a cystine residue is not significantly affected by its position in the polypeptide chain. Furthermore, the first-order rate constants of beta-elimination of disulfide bonds at 100 degrees C are remarkably similar for different proteins--0.8 +/- 0.3 h-1 and 0.06 +/- 0.02 h-1 at pH 8.0 and 6.0, respectively. Thus, this process is relatively independent of both the primary structure and the elements of higher structures remaining in proteins in 100 degrees C. beta-Elimination of disulfides produces free thiols that cause yet another deleterious reaction in proteins--heat-induced disulfide interchange. This reshuffling of -S-S-bonds, which is much faster than beta-elimination, has also been quantitatively characterized.
Relative Kinetic Basicities of Organogold Compounds (2010)

The relative kinetic basicities of a series of differentially substituted and hybridized neutral organogold compounds were examined through competitive protodeauration experiments and were found to span 2.2 orders of magnitude. The effect of electron-withdrawing and electron-donating substituents on the rate of protodeauration of alkenylgold and arylgold compounds was explored. An acid counterion effect indicated the presence of a gold-mediated substrate preequilibrium before protodemetalation, and hybridization effects and a Hammett correlation with ρ+ = −0.41 indicated the involvement of the C−C π system in the protodeauration of vinylgold, alkynylgold, and arylgold complexes.
Molecular characterization of a cluster of at least two glucosyltransferase genes in Streptococcus salivarius ATCC 25975 (1991)

The oral micro-organism Streptococcus salivarius ATCC 25975 synthesizes extracellular glucosyltransferases (GTFs) which polymerize the glucose moiety of sucrose into glucan polymers. Two separate genes encoding the activities of a GTF-I (a GTF that synthesizes an insoluble product) and a GTF-S (a GTF that synthesizes soluble product) were cloned into bacteriophage lambda L47.1. The inserts in the lambda-clones were characterized by restriction mapping and Southern hybridization and were found to overlap, implying that the two genes lay very close to one another on the S. salivarius chromosome. Both genes were subcloned into phagemid vector pIBI30 where they were expressed at a high level. The GTF-I-encoding gene was named gtfJ and the GTF-S-encoding gene, gtfK. Nucleotide sequencing showed that gtfJ and most probably gtfK were closely related to the gtf genes of the mutans streptococci. Sequence alignment also indicated that gtfK lay very close to and downstream from gtfJ, and that both were transcribed in the same direction.
PLASMA ANDROSTENEDIONE AND OESTRONE LEVELS IN NORMAL AND OSTEOPOROTIC POSTMENOPAUSAL WOMEN (1978)

Plasma androstenedione and oestrone concentrations were measured in 72 postmenopasual women. The women included some who had undergone oophorectomy, some with osteoporosis, and normal controls; they were matched for years since menopause. Both hormone concentrations were significantly reduced in the women with osteoporosis. The women who had undergone oophorectomy had hormone concentrations intermediate between the normal and osteoporotic values. Oestrogen deficiency secondary to low androstenedione levels is a major risk factor in postmenopausal osteoporosis, and may be caused by failure of ovarian stromal androgen secretion or some abnormality in the pituitary-adrenal axis.
The role of discrimination and social defeat on black mental health (2021)

Black populations are diagnosed with schizophrenia at a rate that is significantly higher than white populations. This elevated diagnostic rate is often the result of misdiagnosis. This article includes a brief literature review and case presentation highlighting the importance of understanding complex racial trauma when evaluating and treating Black clients.
Acoustic sensor pad for physiological monitoring (2002)

The Army Research Laboratory has developed an acoustic sensor pad technology that is useful for combat casualty care and soldier performance monitoring. Heartbeats, breaths, motion, and other physiological sounds relating to injured and uninjured soldiers can be detected, transmitted, and analyzed for diagnostic purposes. The acoustic sensor pad is a fluid-filled bladder with a hydrophone that couples well to the soldier's torso. Since the human body is mostly water, the pad acts as a fluid extension of the body to form an acoustical conduit to a sensitive hydrophone within the pad that detects body sounds. The sensing pad can be a hand-held version for the field medic or doctor, or a torso-sized pad incorporated into casualty transport hardware such as litters or gurneys. Acoustic analysis of the sensor-pad output can provide amplitude, phase, frequency, duration, rate, and correlative information that may be useful for medical diagnosis, patient care, and research. Data collected with prototype devices show excellent signal-to-noise ratios for heart and breath sounds; such devices could be used in the field to detect conditions such as irregular heartbeats, cardiac distress, obstructed airways, sucking chest wounds, fluid in the lungs, or other respiratory and circulatory emergencies. Joint time-frequency Fourier analysis of sensor output shows that human cardiopulmonary function contains infrasonic (sounds below 20 Hz) signals, which cannot be beard with human ears, but may be useful for medical diagnostics. If soldiers were equipped with small monitoring sensor pads with transmit capability to carry in contact with the torso, squad performance level could be assessed, or those missing in action could be medically interrogated from a remote location for heart and breathing sounds. The technology can also be used to monitor operators of vehicles or aircraft, and initiate appropriate safety actions in the event of sudden incapacitation resulting from weapons fire, heart attack, or blackout.
Design Issues in Studies Evaluating Diagnostic Tests for Aspergillosis (2005)

Although invasive aspergillosis is recognized as an increased concern for immunosuppressed patients, establishing an early diagnosis remains a challenge. Current methods for diagnosis, including sensitive radiography and invasive procedures to identify organisms in affected tissues, provide an early diagnosis for only a small proportion of patients infected with Aspergillus species. The availability of a standardized assay to detect circulating Aspergillus galactomannan, the BioRad Platelia Aspergillus galactomannan enzyme immunoassay, should be considered as a valuable tool. However, at present, clinical utility is hampered by controversies surrounding the performance of the test and an apparent lack of definitive data. These controversies emphasize the complexity inherent in analyzing diagnostic tests for aspergillosis. The widespread availability of a standardized assay may now allow us to address the multiple sources of variability and bias via large, cooperative studies.
In situ Synthesis of DNA Microarray on Functionalized Cyclic Olefin Copolymer Substrate (2010)

Thermoplastic materials such as cyclic-olefin copolymers (COC) provide a versatile and cost-effective alternative to the traditional glass or silicon substrate for rapid prototyping and industrial scale fabrication of microdevices. To extend the utility of COC as an effective microarray substrate, we developed a new method that enabled for the first time in situ synthesis of DNA oligonucleotide microarrays on the COC substrate. To achieve high-quality DNA synthesis, a SiO(2) thin film array was prepatterned on the inert and hydrophobic COC surface using RF sputtering technique. The subsequent in situ DNA synthesis was confined to the surface of the prepatterned hydrophilic SiO(2) thin film features by precision delivery of the phosphoramidite chemistry using an inkjet DNA synthesizer. The in situ SiO(2)-COC DNA microarray demonstrated superior quality and stability in hybridization assays and thermal cycling reactions. Furthermore, we demonstrate that pools of high-quality mixed-oligos could be cleaved off the SiO(2)-COC microarrays and used directly for construction of DNA origami nanostructures. It is believed that this method will not only enable synthesis of high-quality and low-cost COC DNA microarrays but also provide a basis for further development of integrated microfluidics microarrays for a broad range of bioanalytical and biofabrication applications.
High-bandwidth data memory systems for superscalar processors (1991)

This paper considers the design of a data memory hierarchy, with a level 1 (L1) data cache at the top, to support the data bandwidth demands of a future-generation superscalar processor capable of issuing about ten instructions per clock cycle. It introduces the notion of cache
The nudeotide sequence of the promoter and the ammo-terminal region of alkaline phosphatase structural gene (phoA) of Escherichia coli (1981)

The promoter and the amino-terminal region of phoA, the structural gene for alkaline phosphatase of Escherichia coli K12, was cloned by using a promoter cloning vector pMC1403. The nucleotide sequence of the cloned fragment has been determined. A sequence encoding the amino-terminal portion of mature alkaline phosphatase is found and it is preceded by a sequence encoding the signal peptide. The signal peptide consists of 21 amino acids; Met-Lys-Gln-Ser-Thr-Ile-Ala-Leu-Ala-Leu-Leu-Pro-Leu-Leu-Phe-Thr-Pro-Val-Thr-Lys-Ala. The translation initiation codon is GUG, which is preceded by the Shine-Dalgarno sequence GGAG. Upstream to these sequences, there is a typical procaryotic promoter. TATAGTC for the Pribnow box. Around the Pribnow box, there are several dyad symmetrical sequences, which may probably be concerned with the regulation of this gene.
Genome engineering in large animals for agricultural and biomedical applications (2013)

University of Minnesota Ph.D. dissertation. August 2013. Major: Animal Sciences. Advisor: Scott C. Fahrenkrug. 1 computer file (PDF); vi, 226 pages.
Proteomic analysis methods for characterization of proteins from the salivary gland secretions of the medicinal leech during different seasons (2007)

Salivary gland secretion (SGS) of the medicinal leech Hirudo medicinalis in summer and winter was studied by proteomic analysis methods, and season-associated difference was found in the distribution of fractionated proteins with the same pattern of their positions. Differences were detected for proteins with molecular weights from 15 to 250 kD fractionated by two-dimensional SDS-PAGE and for 2-10- and 10-60-kD proteins analyzed by SELDI-MS. Thirty-two and 20 proteins were detected by MALDI-TOF-MS in the high-molecular-weight fraction of the summer and winter SGS, respectively, isolated from the corresponding two-dimensional electrophoregrams, and this was less than 20% of the total SGS protein. The N-terminal amino acid sequences were determined for 12 proteins. The peptide maps and N-terminal amino acid sequences of the proteins studied were identified, and no known proteins were revealed. These findings suggest a high content of newly revealed proteins in SGS of medicinal leech, and this correlates with multiple positive clinical effects of hirudotherapy realized through SGS, but the mechanisms of these effects remain unclear.
Introduction to Fungi (1971)

This new edition of the universally acclaimed and widely-used textbook on fungal biology has been completely re-written, drawing directly on the authors' research and teaching experience. The text takes account of the rapid and exciting progress that has been made in the taxonomy, cell and molecular biology, biochemistry, pathology and ecology of the fungi. Features of taxonomic relevance are integrated with natural functions, including their relevance to human affairs. Special emphasis is placed on the biology and control of human and plant pathogens, providing a vital link between fundamental and applied mycology. The book is richly illustrated throughout with specially prepared drawings and photographs, based on living material. Illustrated life-cycles are provided, and technical terms are clearly explained. Extensive reference is made to recent literature and developments, and the emphasis throughout is on whole-organism biology from an integrated, multidisciplinary perspective.
A dynamic multithreading processor (1998)

We present an architecture that features dynamic multithreading execution of a single program. Threads are created automatically by hardware at procedure and loop boundaries and executed speculatively on a simultaneous multithreading pipeline. Data prediction is used to alleviate dependency constraints and enable lookahead execution of the threads. A two-level hierarchy significantly enlarges the instruction window. Efficient selective recovery from the second level instruction window takes place after a mispredicted input to a thread is corrected. The second level is slower to access but has the advantage of large storage capacity. We show several advantages of this architecture: (1) it minimizes the impact of ICache misses and branch mispredictions by fetching and dispatching instructions out-of-order, (2) it uses a novel value prediction and recovery mechanism to reduce artificial data dependencies created by the use of a stack to manage run-time storage, and (3) it improves the execution throughput of a superscalar by 15% without increasing the execution resources or cache bandwidth, and by 30% with one additional ICache fetch port. The speedup was measured on the integer SPEC95 benchmarks, without any compiler support, using a detailed performance simulator.
Duodenal and Gastric Ulcer Prevention with Misoprostol in Arthritis Patients Taking NSAIDs (1993)

Misoprostol significantly lowers the frequency of both duodenal and gastric ulcer development in patients who require long-term therapy with NSAIDS.
Bacteriology of the Labrador dog gut: a cultural and genotypic approach (2002)

This study has shown the value of molecular-based methodologies for determining bacterial profiles in the Labrador dog gut microbiota, but has also exposed the limitations of purportedly selective agars.
Lysosomal Acid α-Glucosidase Consists of Four Different Peptides Processed from a Single Chain Precursor (2004)

Pompe's disease is caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). GAA is synthesized as a 110-kDa precursor containing N-linked carbohydrates modified with mannose 6-phosphate groups. Following trafficking to the lysosome, presumably via the mannose 6-phosphate receptor, the 110-kDa precursor undergoes a series of complex proteolytic and N-glycan processing events, yielding major species of 76 and 70 kDa. During a detailed characterization of human placental and recombinant human GAA, we found that the peptides released during proteolytic processing remained tightly associated with the major species. The 76-kDa form (amino acids (aa) 122-782) of GAA is associated with peptides of 3.9 kDa (aa 78-113) and 19.4 kDa (aa 792-952). The 70-kDa form (aa 204-782) contains the 3.9- and 19.4-kDa peptide species as well as a 10.3-kDa species (aa 122-199). A similar set of proteolytic fragments has been identified in hamster GAA, suggesting that the multicomponent character is a general phenomenon. Rabbit anti-peptide antibodies have been generated against sequences in the proteolytic fragments and used to demonstrate the time course of uptake and processing of the recombinant GAA precursor in Pompe's disease fibroblasts. The results indicate that the observed fragments are produced intracellularly in the lysosome and not as a result of nonspecific proteolysis during purification. These data demonstrate that the mature forms of GAA characterized by polypeptides of 76 or 70 kDa are in fact larger molecular mass multicomponent enzyme complexes.