gebhart/patrepeval huggingface dataset:
Prediction of Mitochondrial Targeting Signals Using Hidden Markov Model. (1997)

The mitochondrial targeting signal (MTS) is the presequence that directs nascent proteins bearing it to mitochondria. We have developed a hidden Markov model (HMM) that represents various known sequence characteristics of MTSs, such as the length variation, amino acid composition, amphiphilicity, and consensus pattern around the cleavage site. The topology and parameters of this model are automatically determined by the iterative duplication method, in which a small fully-connected HMM is gradually expanded by state splitting. The model can be used to predict the existence of MTSs for given amino acid sequences. Its prediction accuracy was estimated to be 86.9% using the cross validation test. Furthermore, a higher correlation was observed between the HMM score and the in vitro ATPase activity of MSF, which can be regarded as an experimental measure of signal strength, for various synthetic peptides than was observed with other methods.
Fabrication of monolithically integrated Mach-Zehnder asymmetric interferometer switch (2002)

We report a novel method of fabricating a compact, monolithically integrated AlInGaAs Mach-Zehnder asymmetric interferometer for use as a 40 Gbit/s demultiplexer. Instead of regrowth, the plasma process damage induced quantum well intermixing was used to modify the bandgap of passive waveguides.
Insulin release from a cloned precursor beta cell line (1987)

This paper describes the establishment in long-term tissue culture of a functional, clonal beta (B) cell line UMR 407/3 derived from neonatal rat pancreas. Immunofluorescence demonstrated specific and uniform staining for insulin. Transmission electron microscopy showed the presence of microvilli and cytoplasmic granules. The doubling time in culture was approximately 60 h in 2% (v/v) fetal calf serum with inhibition of growth at confluence. Biochemical studies demonstrated the incorporation of [3H]leucine into proinsulin and insulin, with insulin comprising 43.6% of the total radioactivity incorporated into immune complexes. When incubated at 37 degrees C for 30 min with Krebs-Ringer bicarbonate buffer (pH 7.4), the amount of insulin released on stimulation by 16.7 mmol glucose/l, 20 mmol DL-glyceraldehyde/l or 20 mmol alpha-ketoisocaproate/l was significantly higher compared with 5.6 mmol glucose/l. The mean insulin content was equivalent to 99 +/- 0.4 fmol (S.E.M.)/5 X 10(5) cells. Regulated insulin release was maintained through at least 15 passages in culture. The cells showed morphological evidence of senescence after passage 26 and this was associated with significant reduction in stimulated insulin release as well as insulin content. The ability of the cells of this clonal line to grow in soft agar suggests that it is a precursor cell line. The clonal B cell lines isolated so far may thus represent variably committed rather than fully differentiated B cells in culture. These clonal non-neoplastic cell lines will be useful models with which to study the regulation of maturation/differentiation of B cells and insulin gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)
E1 protein of human papillomavirus is a DNA helicase/ATPase (1993)

Replication of human papillomavirus (HPV) DNA requires the viral proteins E1 and E2. Amino acid similarities to SV40 large-T antigen had suggested that E1 is a DNA helicase/ATPase involved in initiating viral DNA replication, and this has recently been shown for bovine papillomavirus type 1 (BPV-1) E1 protein. However, in vitro analysis of HPV E1 has been hampered by the inability to produce purified protein using heterologous expression systems. We have succeeded in demonstrating ATPase and DNA helicase activities in purified HPV E1, expressed in E. coli as a maltose-binding protein fusion (MBP-E1), for the first time. As further confirmation that the ATPase and DNA helicase activities are due to E1 and not contaminating E. coli enzymes, we have shown that a fusion protein containing an amino acid change (E1 Pro-479 to Ser), predicted to inactivate ATP-binding, has impaired activities. We have carried out a structure prediction analysis which suggests that E1 may form two domains: a relatively open N-terminal domain (residues 1-125), and a highly structured C-terminal domain (170-649), with an intermediate region (125-170) predicted to form an inter-domain linker. This is consistent with the proteolytic susceptibility of MBP-E1 at a site 15-20 kD from the N-terminus of E1, and the accumulation of a 58 kD C-terminal fragment of E1. We speculate that the N-terminal domain is involved in DNA-binding, while the C-terminal 58 kD may constitute a distinct enzymatic domain. HPV E1 is of interest as a therapeutic target and the availability of pure enzyme will be invaluable in the search for antiviral compounds.
Effect of inducing nocturnal serum melatoninconcentrations in daytime on sleep, mood, body temperature, andperformance. (1994)

We examined effects of very low doses of melatonin (0.1-10 mg, orally) or placebo, administered at 1145 h, on sleep latency and duration, mood, performance, oral temperature, and changes in serum melatonin levels in 20 healthy male volunteers. A repeated-measure double-blind Latin square design was used. Subjects completed a battery of tests designed to assess mood and performance between 0930 and 1730 h. The sedative-like effects of melatonin were assessed by a simple sleep test: at 1330 h subjects were asked to hold a positive pressure switch in each hand and to relax with eyes closed while reclining in a quiet darkened room. Latency and duration of switch release, indicators of sleep, were measured. Areas under the time-melatonin concentration curve varied in proportion to the different melatonin doses ingested, and the 0.1- and 0.3-mg doses generated peak serum melatonin levels that were within the normal range of nocturnal melatonin levels in untreated people. All melatonin doses tested significantly increased sleep duration, as well as self-reported sleepiness and fatigue, relative to placebo. Moreover, all of the doses significantly decreased sleep-onset latency, oral temperature, and the number of correct responses on the Wilkinson auditory vigilance task. These data indicate that orally administered melatonin can be a highly potent hypnotic agent; they also suggest that the physiological increase in serum melatonin levels, which occurs around 2100 h daily, may constitute a signal initiating normal sleep onset.
Synthesis and biological evaluation of 4-purinylpyrrolidine nucleosides (1991)

The synthesis of several novel carbocyclic purine nucleosides that incorporate a nitrogen in place of carbon 3 of the cyclopentyl moiety are described. These analogues are all derived from the key stereochemically defined intermediate N-(tert-butoxycarbonyl)-O-[(4-methoxyphenyl)diphenylmethyl]-trans- 4- hydroxy-D-prolinol (19), which was accessible in 61.1% overall yield for a five-step sequence starting from cis-4-hydroxy-D-proline. The heterocyclic bases, 6-chloropurine and 2-amino-6-chloropurine, are efficiently introduced onto the pyrrolidine ring via a Mitsunobu-type coupling procedure with triphenylphosphine and diethyl azodicarboxylate. Standard transformations and removal of protecting groups gave the cis-adenine (26), hypoxanthine (27), 2,6-diaminopurine (28), and guanine (29) D-prolinol derivatives. In addition, a related sequence from trans-4-hydroxy-L-proline provided the enantiomeric L-prolinol guanine derivative (36). Lastly, the 6-(dimethylamino)purine analogue, 37, was coupled to N-(benzyl-oxycarbonyl)-p-methoxy-L-phenylalanine to provide, after deprotection, the novel puromycin-like analogue 39. The analogues 26-29, 36, and 39 were all evaluated for antitumor and, except for 39, for antiviral activity. These compounds failed to appreciably inhibit the growth of P388 mouse leukemia cells in vitro at concentrations up to 100 micrograms/mL. In addition, they did not exhibit noticeable activity against the human immunodeficiency virus or herpes simplex virus type 1 at concentrations as high as 100 microM. The adenine analogue, 26, did, however, prove to be a substrate for adenosine deaminase. It possessed an affinity for the enzyme only 50% less than that of adenosine with a Ki = 85 microM.
The kinetics of the hydrolysis of certain glucosides, part II.:—Trehalose, a-methylglucoside and tetramethyl-a-methylglucoside (1929)

E. A. Moelwyn-Hughes, Trans. Faraday Soc., 1929, 25, 81 DOI: 10.1039/TF9292500081
TCIRG1-Associated Congenital Neutropenia (2014)

Severe congenital neutropenia (SCN) is a rare hematopoietic disorder, with estimated incidence of 1 in 200,000 individuals of European descent, many cases of which are inherited in an autosomal dominant pattern. Despite the fact that several causal genes have been identified, the genetic basis for >30% of cases remains unknown. We report a five-generation family segregating a novel single nucleotide variant (SNV) in TCIRG1. There is perfect cosegregation of the SNV with congenital neutropenia in this family; all 11 affected, but none of the unaffected, individuals carry this novel SNV. Western blot analysis show reduced levels of TCIRG1 protein in affected individuals, compared to healthy controls. Two unrelated patients with SCN, identified by independent investigators, are heterozygous for different, rare, highly conserved, coding variants in TCIRG1.
A Self‐Sufficient Peroxide‐Driven Hydroxylation Biocatalyst (2003)

Directed evolution of the heme domain of cytochrome P450 BM-3 has resulted in a versatile, highly active peroxide-driven hydroxylation catalyst (see picture) that requires neither NADPH nor reductase and functions in a cell-free reaction system. This simplified, “biomimetic” catalyst is amenable to further optimization, for example, to improve stability or alter its substrate range. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2003/z51434_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Retroviral integrase functions as a multimer and can turn over catalytically. (1992)

A number of studies have demonstrated that the retroviral protein integrase (IN) alone is sufficient to carry out two discrete steps required for retroviral integration: the endonucleolytic processing of viral DNA ends and the cleavage and joining of host DNA to the processed viral DNA termini. Little is known about the biochemical and biophysical mechanisms involved in these reactions. Here, we employ in vitro assays of Rous sarcoma virus IN to demonstrate for the first time that IN is capable of multiple turnover in both the processing and joining reactions. The turnover number calculated for the processing reaction is 0.26 cleavages/min/mol of IN. Our steady state kinetic studies indicate that both the processing and joining activities require a multimeric form of IN. Ultracentrifugation analyses reveal a substrate-independent reversible equilibrium among the monomeric, dimeric, and tetrameric forms of this protein. From these results we conclude that the minimal functional unit for both the processing and joining of each viral DNA end is an IN dimer.
17β-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis (2018)

Treatment regimens with 25-μg 17β-estradiol vaginal tablets and with 1.25-mg conjugated equine estrogen vaginal cream were equivalent in relieving symptoms of atrophic vaginitis. The vaginal tablets demonstrated a localized effect without appreciable systemic estradiol increases or estrogenic side effects. Vaginal tablet therapy resulted in greater patient acceptance and lower withdrawal rates compared with vaginal cream therapy.
Plasticity in an Electrosensory System. III. Contrasting Properties of Spatially Segregated Dendritic Inputs (1998)

Efferent neurons of the first-order electrosensory processing center of the brain, the electrosensory lateral line lobe (ELL), receive electroreceptor afferent input as well as feedback inputs descending from higher centers. These ELL efferents, pyramidal cells, adaptively filter predictable patterns of sensory input while preserving sensitivity to novel stimuli. The filter mechanism involves integration of centrally generated predictive inputs with the afferent inputs being canceled. The predictive inputs, referred to as "negative image" inputs, terminate on pyramidal cell apical dendrites and generate responses that are opposite those resulting from the predictable afference, hence integration of these signals results in attenuation of pyramidal cell responses. The system also shows a robust form of plasticity; the pyramidal cells learn, with a time course of a few minutes, to cancel new patterns of repetitive inputs. This is accomplished by adjusting the strength of excitatory and inhibitory apical dendritic inputs according to an anti-Hebbian learning rule. This study focuses on the properties of two separate pathways that convey descending information to pyramidal cell apical dendrites. One pathway terminates proximally, nearer to the pyramidal cell body, whereas the other terminates distally. Recordings of ELL evoked potentials, extracellular pyramidal cell spike responses, and intracellularly recorded synaptic potentials show that the pyramidal cells respond oppositely to moderate-frequency (> approximately 8 Hz) single pulse stimulation or repeated (1/s) tetanic activation of these two pathways. Repetitive activation of the proximally terminating pathway results in highly facilitating responses due to potentiation of pyramidal cell excitatory postsynaptic potentials (EPSPs). These same stimuli applied to the distally terminating pathway result in a reduction of pyramidal cell responses due to depression of EPSPs and potentiation of inhibitatory postsynaptic potentials (IPSPs). Anti-Hebbian plasticity was demonstrated by pairing tetanic stimulation of either pathway with changes in the postsynaptic cell's membrane potential. After stabilization of the response potentiation due to tetanic stimulation of the proximally terminating pathway, paired postsynaptic hyperpolarization resulted in further increases in spike responses and additional potentiation of pyramidal cell EPSPs. Paired postsynaptic depolarization reduced subsequent responses to the tetanus, depressed EPSP amplitudes, and, in many cases, potentiated IPSPs. The same pattern of plasticity was observed when postsynaptic hyper- or depolarization was paired with tetanic stimulation of the distally terminating pathway except that the plasticity was superimposed on the depressed pyramidal cell responses resulting from stimulating this pathway alone. Modulation of a postsynaptic form of synaptic depression is proposed to account for the anti-Hebbian plasticity associated with both pathways.
Mathematical Analysis of Random Noise (1945)

In this section we use the representations of the noise currents given in section 2.8 to derive some statistical properties of I(t). The first six sections are concerned with the probability distribution of I(t) and of its zeros and maxima. Sections 3.7 and 3.8 are concerned with the statistical properties of the envelope of I(t). Fluctuations of integrals involving I <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> (t) are discussed in section 3.9. The probability distribution of a sine wave plus a noise current is given in 3.10 and in 3.11 an alternative method of deriving the results of Part III is mentioned. Prof. Uhlenbeck has pointed out that much of the material in this Part is closely connected with the theory of Markoff processes. Also S. Chandrasekhar has written a review of a class of physical problems which is related, in a general way, to the present subject. <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">22</sup>
Chemical Adaptor Immunotherapy:  Design, Synthesis, and Evaluation of Novel Integrin-Targeting Devices (2004)

A series of beta-diketone derivatives of RGD peptidomimetics that selectively bind to alphavbeta3 and alphavbeta5 integrins were synthesized and covalently docked to the reactive lysine residues of monoclonal aldolase antibody 38C2. The resulting targeting devices strongly and selectively bound to human cancer cells expressing integrins alphavbeta3 and alphavbeta5 as analyzed by flow cytometry. In vitro and in vivo studies revealed that these novel integrin-targeting devices efficiently inhibit tumor growth. Thus, the combination of beta-diketone derivatives of RGD peptidomimetics that target cell surface integrins alphavbeta3 and alphavbeta5 with monoclonal aldolase antibodies through formation of a covalent bond of defined stoichiometry holds promise as a new approach to cancer therapy.
Efficient Nonlocal Means for Denoising of Textural Patterns (2008)

This paper contributes two novel techniques in the context of image restoration by nonlocal filtering. First, we introduce an efficient implementation of the nonlocal means filter based on arranging the data in a cluster tree. The structuring of data allows for a fast and accurate preselection of similar patches. In contrast to previous approaches, the preselection is based on the same distance measure as used by the filter itself. It allows for large speedups, especially when the search for similar patches covers the whole image domain, i.e., when the filter is truly nonlocal. However, also in the windowed version of the filter, the cluster tree approach compares favorably to previous techniques in respect of quality versus computational cost. Second, we suggest an iterative version of the filter that is derived from a variational principle and is designed to yield nontrivial steady states. It reveals to be particularly useful in order to restore regular, textured patterns.
A phase I clinical trial of adoptive transfer of folate receptor-alpha redirected autologous T cells for recurrent ovarian cancer (2012)

This design involves an initial accelerated dose escalation phase of FR-α CAR-T cells followed by a standard 3 + 3 escalation phase. A split-dose approach is proposed to mitigate acute adverse events. Furthermore, infusion of bulk untransduced autologous peripheral blood lymphocytes (PBL) is proposed two days after CAR-T cell infusion at the lower dose levels of CAR-T cells, to suppress excessive expansion of CAR-T cells in vivo and mitigate toxicity.
Compact 625-channel scannerless imaging laser radar receiver (1996)

In 1995, under a USAF SBIR Phase I program, Burns Engineering Corporation investigated the application of new integrated photonics technologies and hybrid manufacturing processes to the miniaturization of an imaging laser radar receiver which has complete receiving and range counting circuitry for each pixel in a 25-by-25 element avalanche photodiode array. The `parallel multichannel' receiver (PMR) is a compact, robust, and modular laser radar subsystem which can produce high resolution 3D range imagery at 1 kHz frame rates without the use of a scanner. The modular PMR is attractive as a common module solution for a wide variety of high performance, low cost, autonomous laser-guided seeker applications. The system described illustrates one approach to integrating and packaging high-density photonic arrays and associated signal processing electronics to yield a high-performance imaging laser radar receiver using existing technology. Burns Engineering has been selected by the USAF to build a benchtop prototype, proof-of-concept demonstrator in a follow-on, SBIR Phase II program.
Saturation mutagenesis of the plasminogen activator inhibitor-1 reactive center. (1992)

Plasminogen activator inhibitor-1 (PAI-1) is a specific inhibitor of the serine proteases tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). To systematically investigate the roles of the reactive center P1 and P1' residues in PAI-1 function, saturation mutagenesis was utilized to construct a library of PAI-1 variants. Examination of 177 unique recombinant proteins indicated that a basic residue was required at P1 for significant inhibitory activity toward uPA, whereas all substitutions except proline were tolerated at P1'. P1Lys variants exhibited lower inhibition rate constants and greater sensitivity to P1' substitutions than P1Arg variants. Alterations at either P1 or P1' generally had a larger effect on the inhibition of tPA. A number of variants that were relatively specific for either uPA or tPA were identified. P1Lys-P1'Ala reacted 40-fold more rapidly with uPA than tPA, whereas P1Lys-P1'Trp showed a 6.5-fold preference for tPA. P1-P1' variants containing additional mutations near the reactive center demonstrated only minor changes in activity, suggesting that specific amino acids in this region do not contribute significantly to PAI-1 function. These findings have important implications for the role of reactive center residues in determining serine protease inhibitor (serpin) function and target specificity.
Enterprise JavaBeans (1999)

From the Publisher:
Enterprise JavaBeans was recently voted Best Java by the editors and readers of Java Developer's Journal. Readers of JavaPro named it the Best Java Book for Experts. And Amazon.com included it in the Top Computer Books for 2000. Now the best only gets better! In the new 3rd edition, Enterprise JavaBeans has been completely revised and updated with a thorough introduction to the new 2.0 version of the EJB specification. Significantly different from the earlier version, the 2.0 specification introduces three dramatic improvements: A completely new version of container-managed persistence; local interfaces; and a totally new kind of bean called the driven bean. 
The new version of container-managed persistence (CMP) beans in 2.0 is more portable and robust than in the older 1.1 version. Most significant is the introduction of the relationship fields, which allow entity beans to declare relationships with each other as natural references. In order to make this huge leap in component relationships possible, EJB 2.0 had to redesign how entity beans are defined and interact. Our new 3rd edition examines this critical CMP model in detail. 
Local interfaces are thoroughly discussed as well. Local interfaces allow beans that are co-located to interact without the overhead of remote method calls. This improves the performance of beans considerably and complements the CMP relationship fields. 
Message driven beans are a new kind of enterprise bean based on asynchronous messaging and the Java Message service (JMS). Instead of responding to Java RMI calls, message driven beans process JMS messages sent by messaging clients.An entire chapter is devoted to message-driven beans and how to use them effectively. 
In addition, the 3rd edition contains an architecture overview, information on resource management and primary services, design strategies, and XML deployment descriptors.