gebhart/patrepeval huggingface dataset:
The Role of HNF1α, HNF3γ, and Cyclic AMP in Glucose-6-phosphatase Gene Activation (1997)

The gene for glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis, is expressed in a tissue-specific manner in the liver and kidney. To understand the molecular mechanisms regulating liver-specific expression of the G6Pase gene, we characterized G6Pase promoter activity by transient expression assays. The G6Pase promoter is active in HepG2 hepatoma cells, but inactive in JEG3 choriocarcinoma or 3T3 cells. DNA elements essential for optimal and liver-specific expression of the G6Pase gene were contained within nucleotides -234 to +3. Deletion analysis revealed that the G6Pase promoter contained three activation elements (AEs) at nucleotides -234 to -212 (AE-I), -146 to -125 (AE-II), and -124 to -71 (AE-III). AE-I contains binding sites for hepatocyte nuclear factors (HNF) 1 and 4. Electromobility shift and cotransfection assays demonstrated that HNF1alpha, but not HNF4, bound to its cognate site and transactivated G6Pase gene expression. The G6Pase promoter contained five HNF3 motifs, 1 (-180/-174), 2 (-139/-133), 3 (-91/-85), 4 (-81/-75), and 5 (-72/-66), and all five sites bound HNF3gamma with high affinity. Transient expression and cotransfection assays showed that HNF3 site 1 is not required for basal promoter activity, but is essential for HNF3gamma-activated transcription from the G6Pase promoter. We further showed that HNF3 sites 3, 4, and 5 were essential for basal G6Pase promoter activity and transactivation by HNF3gamma. AE-II contains, in addition to a HNF3 motif, a cAMP-response element (CRE) and a C/EBP half-site. The G6Pase(-146/-116) DNA containing AE-II formed multiple protein-DNA complexes with HepG2 nuclear extracts, including HNF3gamma, CRE-binding protein (CREB), C/EBPalpha, and C/EBPbeta. We showed that AE-II mediated transcription activation of the G6Pase gene by cAMP.
K-Band Cryogenically Cooled Wide-Band Nondegenerate Parametric Amplifier (Correspondence) (1970)

The design and performance of a K-band cryogenically cooled wideband (600-MHz) low-noise (110/spl deg/K) parametric amplifier for use in millimeter-wavelength satellite-communication earthterminal installations is described.
Identification and Characterization of a Streptococcus pyogenes Operon Involved in Binding of Hemoproteins and Acquisition of Iron (2003)

The hemolytic Streptococcus pyogenes can use a variety of heme compounds as an iron source. In this study, we investigate hemoprotein utilization by S. pyogenes. We demonstrate that surface proteins contribute to the binding of hemoproteins to S. pyogenes. We identify an ABC transporter from the iron complex family named sia for streptococcal iron acquisition, which consists of a lipoprotein (siaA), membrane permease (siaB), and ATPase (siaC). The sia transporter is part of a highly conserved, iron regulated, 10-gene operon. SiaA, which was localized to the cell membrane, could specifically bind hemoglobin. The operon's first gene encodes a novel bacterial protein that bound hemoglobin, myoglobin, heme-albumin, and hemoglobin-haptoglobin (but not apo-haptoglobin) and therefore was named Shr, for streptococcal hemoprotein receptor. PhoZ fusion and Western blot analysis showed that Shr has a leader peptide and is found in both membrane-bound and soluble forms. An M1 SF370 strain with a polar mutation in shr was more resistant to streptonigrin and hydrogen peroxide, suggesting decreased iron uptake. The addition of hemoglobin to the culture medium increased cell resistance to hydrogen peroxide in SF370 but not in the mutant, implying the sia operon may be involved in hemoglobin-dependent resistance to oxidative stress. The shr mutant demonstrated reduced hemoglobin binding, though cell growth in iron-depleted medium supplemented with hemoglobin, whole blood, or ferric citrate was not affected, suggesting additional systems are involved in hemoglobin utilization. SiaA and Shr are the first hemoprotein receptors identified in S. pyogenes; their possible role in iron capture is discussed.
The computerized medical record in action. (1994)

Before the advent of the IPS computerized medical record at Burlington, Zallen did not own a computer. Although he learned touch-typing in high school, he emphatically states that he hated it. The average age of the physicians on staff at Burlington is about 40, but few had extensive previous experience with computers. According to Zallen, all have adapted to the CPR with few tears or tirades. The physicians continue to "tweak" the system to customize their own scrapbook and templates. Lahey physicians who work at Burlington part time are using the system, although with more staff help. The CPR is alive and well at Burlington Health Center. HCHP physicians can and do use computers in their daily work, producing quality medical records that are readable and retrievable. Nonetheless, promises that computers will make records more complete and accessible and will improve quality measurement will be mere blather if the CPR doesn't make users' lives easier. My last question to Zallen was "How has this system made your life harder?" After one pensive second, he replied, "I really can't think of anything." To me, that is potent testimony that the CPR is not a techie's fantasy, but rather, a pragmatic, workable answer to the needs of 21st century medicine.
Computer-Aided Diagnosis with an Application to Endocrinology (1978)

An interactive system for computer-assisted medical diagnosis is described. Medical experts are provided with a framework in which to translate the knowledge on which their decisions are based. The technique is based on simulating the physician's own diagnostic process. The approach taken allows consistency and completeness checks to be made, thereby achieving a high degree of reliability. Information related to a given specialty is described in terms of disorder patterns, clinical facts, and logical relationships among the clinical data. Laboratory results are processed by a subsystem which uses physician-supplied rules to establish validity and to interpret the test data with respect to their diagnostic significance. The system incorporates a dynamically generated questionnaire which provides efficient gathering of anamnestic, observational, and other clinical parameters. The physician is prompted for relevant patient data by an algorithm which assures that an almost minimal amount of information is requested. Simulation facilities allow the user to examine clustering phenomena among disorders, and an option is included that traces the logic of any decision taken to exclude candidates for a final diagnosis.
In vivo inhibition of cyclin B degradation and induction of cell-cycle arrest in mammalian cells by the neutral cysteine protease inhibitor N-acetylleucylleucylnorleucinal. (1993)

The cytotoxic neutral cysteine protease inhibitor N-acetylleucylleucylnorleucinal (ALLN) inhibits cell-cycle progression in CHO cells, affecting the G1/S and metaphase-anaphase transition points, as well as S phase. Mitotic arrest induced by ALLN is associated with the inhibition of cyclin B degradation. At mitosis-inhibiting concentrations of ALLN, cells undergo nuclear-envelope breakdown, spindle formation, chromosome condensation, and congression to the metaphase plate. However, normal anaphase events do not occur, and cells arrest in a metaphase configuration for a prolonged period. Steady-state levels of cyclin B increase to greater than normal mitotic levels, and cyclin B is not degraded for an extended period. Histone H1 kinase activity remains elevated during mitotic arrest. Duration of mitotic arrest depends on ALLN concentration; high concentrations (> 50 micrograms/ml) produce a prolonged mitotic arrest, whereas at lower concentrations, cells are transiently delayed through mitosis (up to 4-12 hr), after which they undergo aberrant cell division resulting in randomly sized daughter cells containing variable amounts of DNA. Cyclin B degradation fails to occur, and histone H1 kinase remains activated for the duration of mitotic arrest at all ALLN concentrations.
Chemical recognition of gases and gas mixtures with terahertz waves (1996)

A time-domain chemical-recognition system for classifying gases and analyzing gas mixtures is presented. We analyze the free induction decay exhibited by gases excited by far-infrared (terahertz) pulses in the time domain, using digital signal-processing techniques. A simple geometric picture is used for the classif ication of the waveforms measured for unknown gas species. We demonstrate how the recognition system can be used to determine the partial pressures of an ammonia-water gas mixture.
FBXO32 Targets c-Myc for Proteasomal Degradation and Inhibits c-Myc Activity (2015)

FBXO32 (MAFbx/Atrogin-1) is an E3 ubiquitin ligase that is markedly up-regulated in muscle atrophy. Although some data indicate that FBXO32 may play an important role in tumorigenesis, the molecular mechanism of FBXO32 in tumorigenesis has been poorly understood. Here, we present evidence that FBXO32 targets the oncogenic protein c-Myc for ubiquitination and degradation through the proteasome pathway. Phosphorylation of c-Myc at Thr-58 and Ser-62 is dispensable for FBXO32 to induce c-Myc degradation. Mutation of the lysine 326 in c-Myc reduces c-Myc ubiquitination and prevents the c-Myc degradation induced by FBXO32. Furthermore, overexpression of FBXO32 suppresses c-Myc activity and inhibits cell growth, but knockdown of FBXO32 enhances c-Myc activity and promotes cell growth. Finally, we show that FBXO32 is a direct downstream target of c-Myc, highlighting a negative feedback regulation loop between c-Myc and FBXO32. Thus, FBXO32 may function by targeting c-Myc. This work explains the function of FBXO32 and highlights its mechanisms in tumorigenesis.
Recombinant adenovirus-mediated cardiac gene transfer of superoxide dismutase and catalase attenuates postischemic contractile dysfunction. (1998)

Adenovirus-mediated cardiac gene transfer and expression of SOD and Cat augment antioxidant enzyme activity and minimize contractile dysfunction after ischemic reperfusion in the isolated perfused neonatal mouse heart.
A bacterial two-hybrid selection system for studying protein–DNA and protein–protein interactions (2000)

We have developed a bacterial "two-hybrid" system that readily allows selection from libraries larger than 10(8) in size. Our bacterial system may be used to study either protein-DNA or protein-protein interactions, and it offers a number of potentially significant advantages over existing yeast-based one-hybrid and two-hybrid methods. We tested our system by selecting zinc finger variants (from a large randomized library) that bind tightly and specifically to desired DNA target sites. Our method allows sequence-specific zinc fingers to be isolated in a single selection step, and thus it should be more rapid than phage display strategies that typically require multiple enrichment/amplification cycles. Given the large library sizes our bacterial-based selection system can handle, this method should provide a powerful tool for identifying and optimizing protein-DNA and protein-protein interactions.
Acousto-Optic Tunable Filter* (1969)

This paper proposes a new type of electronically tunable optical filter. The basic idea is to utilize collinear acousto-optic diffraction in an optically anisotropic media. Changing the driving acoustic frequency changes the band of optical frequencies that the filter passes. A LiNbO3 acousto-optic filter with a pass band approximately 1.3 cm−1 wide should be tunable from 4000 to 7000 Å by changing the acoustic frequency from 428 to 990 Mc/sec. For this case, the angular aperture will be about 1.5°, and, theoretically 100% transmittance should be attained at the filter center frequency by use of about 14 mW of acoustic power per mm2 of filter aperture.
Benefit of vitamin E, riluzole, and gababapentin in a transgenic model of familial amyotrophic lateral sclerosis (1996)

Familial amyotrophic lateral sclerosis (FALS) has been linked in some families to dominant mutations of the SOD1 gene encoding Cu,Zn superoxide dismutase (Cu,ZnSOD). We have used a transgenic model of FALS based on expression of mutant human Cu,ZnSOD to explore the etiology and therapy of the genetic disease. Expression of mutant, but not wild-type, human Cu,ZnSOD in mice places the brain and spinal cord under oxidative stress. This causes depletion of vitamin E, rather than the typical age-dependent increase in vitamin E content as occurs in nontransgenic mice and in mice expressing wild-type human Cu,ZnSOD. Dietary supplementation with vitamin E delays onset of clinical disease and slows progression in the transgenic model but does not prolong survival. In contrast, two putative inhibitors of the glutamatergic system, riluzole and gabapentin, prolong survival. However, riluzole did not delay disease onset. Thus, there was clear separation of effects on onset, progression, and survival by the three therapeutics tested. This suggests the hypothesis that oxidative damage produced by the expression of mutant Cu,ZnSOD causes slow or weak excitotoxicity that can be inhibited in part by alerting glutamate release or biosynthesis presynaptically.
Effects of Antigen and Genetic Adjuvants on Immune Responses to Human Immunodeficiency Virus DNA Vaccines in Mice (2002)

The effects of genetic adjuvants on humoral and cell-mediated immunity to two human immunodeficiency virus antigens, Env and Nef, have been examined in mice. Despite similar levels of gene expression and the same gene delivery vector, the immune responses to these two gene products differed following DNA immunization. Intramuscular immunization with a Nef expression vector plasmid generated a humoral response and antigen-specific gamma interferon (IFN-gamma) production but little cytotoxic-T-lymphocyte (CTL) immunity. In contrast, immunization with an Env vector stimulated CTL activity but did not induce a high-titer antibody response. The ability to modify these antigen-specific immune responses was investigated by coinjection of DNA plasmids encoding cytokine and/or hematopoietic growth factors, interleukin-2 (IL-2), IL-12, IL-15, Flt3 ligand (FL), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Coadministration of these genes largely altered the immune responses quantitatively but not qualitatively. IL-12 induced the greatest increase in IFN-gamma and immunoglobulin G responses to Nef, and GM-CSF induced the strongest IFN-gamma and CTL responses to Env. A dual approach of expanding innate immunity by administering the FL gene, together with a cytokine that enhances adaptive immune responses, IL-2, IL-12, or IL-15, generated the most potent immune response at the lowest doses of Nef antigen. These findings suggest that intrinsic properties of the antigen determine the character of immune reactivity for this method of immunization and that specific combination of innate and adaptive immune cytokine genes can increase the magnitude of the response to DNA vaccines.
Purging of Tumor Cells from Leukapheresis Products: Experimental and Clinical Aspects (1996)

Peripheral blood progenitor cell autografts are being used increasingly in conjunction with high-dose therapy of cancer patients, in the belief that these products have a low probability of containing tumor cells. However, recent findings demonstrate that tumor cell involvement is frequent in leukapheresis products. Although the clinical value of purging has not been clinically established by prospective randomized trials, several studies indicate that contaminating tumor cells in autografts contribute to relapse of the disease in the recipients. We describe our experimental and clinical experience in purging tumor cells from leukapheresis products. Based on our work with purging of lymphoma cells from bone marrow by the use of anti-B cell and anti-T cell antibodies and immunobeads, a purging procedure to deplete leukapheresis products of lymphoma cells has been developed. Moreover, we present data showing that breast cancer cells can be efficiently removed from leukapheresis products using antibreast cancer antibodies, either in combination with immunobeads or as immunotoxins. Our experience with enrichment of CD34 cells employing immunobeads in leukaphresis products from patients with breast cancer and lymphomas shows high purity and yield of CD34 cells. In spite of this, contaminating tumor cells can be observed, strongly suggesting that a combination of CD34 cell enrichment and a purging procedure might be warranted.
Host Ethnicity and Virus Genotype Shape the Hepatitis B Virus-Specific T-Cell Repertoire (2008)

Repertoire composition, quantity, and qualitative functional ability are the parameters that define virus-specific T-cell responses and are linked with their potential to control infection. We took advantage of the segregation of different hepatitis B virus (HBV) genotypes in geographically and genetically distinct host populations to directly analyze the impact that host and virus variables exert on these virus-specific T-cell parameters. T-cell responses against the entire HBV proteome were analyzed in a total of 109 HBV-infected subjects of distinct ethnicities (47 of Chinese origin and 62 of Caucasian origin). We demonstrate that HBV-specific T-cell quantity is determined by the virological and clinical profiles of the patients, which outweigh any influence of race or viral diversity. In contrast, HBV-specific T-cell repertoires are divergent in the two ethnic groups, with T-cell epitopes frequently found in Caucasian patients seldom detected in Chinese patients. In conclusion, we provide a direct biological evaluation of the impact that host and virus variables exert on virus-specific T-cell responses. The discordance between HBV-specific CD8 T-cell repertoires present in Caucasian and Chinese subjects shows the ability of HLA micropolymorphisms to diversify T-cell responses and has implications for the rational development of therapeutic and prophylactic vaccines for worldwide use.
Interposed request routing for scalable network storage (2002)

This paper explores interposed request routing in Slice, a new storage system architecture for high-speed networks incorporating network-attached block storage. Slice interposes a request switching filter---called a μ proxy ---along each client's network path to the storage service (e.g., in a network adapter or switch). The μproxy intercepts request traffic and distributes it across a server ensemble. We propose request routing schemes for I/O and file service traffic, and explore their effect on service structure. The Slice prototype uses a packet filter μproxy to virtualize the standard Network File System (NFS) protocol, presenting to NFS clients a unified shared file volume with scalable bandwidth and capacity. Experimental results from the industry-standard SPECsfs97 workload demonstrate that the architecture enables construction of powerful network-attached storage services by aggregating cost-effective components on a switched Gigabit Ethernet LAN.
Synthesis of Liquid‐Crystalline Colloids in Nonpolar Media and their Manipulation in Electric Fields (2009)

Abstract The first synthesis of anisotropic liquid‐crystalline colloids in silicone oil by a direct (radical) polymerization of a monomer in THF/silicone oil mixtures with the help of siloxane containing stabilizers is described. The size of the colloids is in the lower µm range and can be adjusted by varying the mixture. The resulting colloids show a bipolar director configuration if they are small (&lt;1.5 µm) and a radial configuration if they are larger. The colloids are sterically stabilized, and, due to the nonpolarity of the solvent, the disturbing effects of migrating ions are excluded and experiments in the electric field can be conducted. Both line formation in DC fields and a periodic switching of the bipolar colloids in AC fields is observed. magnified image
Identification of major tyrosine-phosphorylated proteins in Csk-deficient cells. (1994)

Csk is a non-receptor protein-tyrosine kinase that acts as a negative regulator of Src family tyrosine kinases. Csk-deficient mouse embryos exhibited developmental defects including inability to turn and impaired formation of neural tube. In these embryos, an accumulation of tyrosine phosphorylated proteins was observed as a consequence of constitutive activation of Src family kinases. In order to identify those tyrosine phosphorylated proteins, we established a Csk-deficient cell line from embryos lacking both Csk and the anti-oncogene product p53. On surveying several proteins known as Src substrates, we found that phosphorylation level of p80/85 (cortactin) was markedly elevated in the Csk-deficient cells. Enhancement of cortactin phosphorylation was also seen in Csk-deficient embryos. Furthermore, immunoprecipitated Src was able to directly phosphorylate cortactin in vitro. Thus, we suggest that cortactin is a good substrate of activated Src family kinases in vivo and may play important roles in signaling pathways mediated by Src family kinases.
Multi-step cascade of tumor cell metastasis. (1992)

The most life-threatening aspects of the oncogenic process are invasion and metastasis. Even though the clinical significance of such expression of the malignant phenotype has been well appreciated, advances in understanding the molecular mechanisms involved in metastasis have been painstakingly slow. To tackle this complex, multi-step problem, investigators have separated invasion and metastasis into a series of defined, sequential steps, and focused on one step at a time. Efforts combining the disciplines of cell biology, protein biochemistry, and molecular genetics have resulted in a surge of new information, suggesting novel strategies for prognosis and therapy of metastatic cancer.
The effect of point mutations on the free energy of transmembrane α-helix dimerization (1997)

Glycophorin A forms homodimers through interaction of the single, helical transmembrane domains of the monomers. The dimers are stable in sodium dodecylsulfate (SDS), permitting a number of studies that have identified a critical motif of residues that mediates dimer formation. We have used analytical ultracentrifugation to measure the energy of dimerization in a non-denaturing detergent solution and have observed the changes in energy arising from two of the mutants previously studied. Use of the detergent pentaoxyethylene octyl ether (C8E5) is a great advantage, since its micelles are neutrally buoyant and the detergent allows a reversible association to occur between monomer and dimer states of the glycophorin A transmembrane helices during the time-scale of sedimentation equilibrium. Use of this detergent in analytical ultracentrifugation may enable a wide range of studies of molecular association events in membrane proteins. We find that the glycophorin A transmembrane helix dimerizes with a dissociation constant of 240(+/-50) nM, corresponding to a free energy of dissociation of 9.0(+/-0.1) kcal mol-1. Point mutants that were found to be disruptive in SDS (L75A, I76A) reduced the dimer affinity in the C8E5 detergent environment (Kd=1.7(+/-0.2) microM and 4.2(+/-0.9) microM, respectively). Thus, the earlier findings are placed on a quantitative, relative energy scale of association by our measurements. Molecular modeling and simulations suggest that the energy differences can be accounted for as changes in van der Waals interactions between helices.