gebhart/patrepeval huggingface dataset:
In vivo depletion of B cells using a combination of high‐dose cytosine arabinoside/mitoxantrone and rituximab for autografting in patients with non‐Hodgkin's lymphoma (2000)

We performed a pilot study including rituximab (Mabthera; IDEC-C2B8, Hoffmann-La Roche) with a sequential high-dose therapy protocol in 15 patients with follicular and three patients with mantle cell lymphoma and studied the potential of the chemoimmunotherapy to induce depletion of malignant B cells in vivo. Our treatment protocol included induction with three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, followed by peripheral blood stem cell (PBSC) mobilization using high-dose cytosine arabinoside (2 g/m2 every 12 h, days 1 and 2) and mitoxantrone (10 mg/m2, days 2 and 3) (HAM), preceeded by rituximab (375 mg/m2). The proportion of CD19+ B cells in blood and bone marrow decreased from 1.2 +/- 0.4% to 0.13 +/- 0. 1% (P = 0.01) and from 2.7 +/- 0.8% to 0.8 +/- 0.5% (P = 0.03) respectively. The number of t(14;18)-positive cells in blood and bone marrow progressively decreased with treatment, as assessed by the quantitative real-time PCR assay in four patients. Conversion to PCR-negativity was achieved in the peripheral blood (PB) of seven informative patients. Leucaphereses were performed during the granulocyte colony-stimulating factor (G-CSF)-supported leucocyte recovery phase. In 17 of 18 patients, a median of 15.1 x 106 CD34+ cells/kg body weight (BW) could be harvested by a single procedure for enrichment by an immunomagnetic method. Leucapheresis products contained 51.3 +/- 28.8 x 104 CD19+ B cells/kg BW (mean) and were t(14;18) PCR negative in all seven informative patients. These data compare favourably with results obtained in patients treated with the same regimen without rituximab. The high-dose therapy (n = 12 patients), including total body irradiation (14.4 Gy) and cyclophosphamide (200 mg/kg BW), was also preceeded by rituximab. Recovery of neutrophils to > 0.5 x 109/l and of platelets to > 20 x 109/l required a median of 13.5 and 11.5 d (range 11-24 and 9-24 d) respectively. In conclusion, the addition of the CD20 antibody to chemotherapy ensured tumour depletion in vivo and allowed the collection of PBSCs devoid of tumour cells and with conserved engraftment capability.
Approximate nearest neighbor queries in fixed dimensions (1993)

Given a set of n points in d-dimensional Euclidean space, S ⊂ E, and a query point q ∈ E, we wish to determine the nearest neighbor of q, that is, the point of S whose Euclidean distance to q is minimum. The goal is to preprocess the point set S, such that queries can be answered as efficiently as possible. We assume that the dimension d is a constant independent of n. Although reasonably good solutions to this problem exist when d is small, as d increases the performance of these algorithms degrades rapidly. We present a randomized algorithm for approximate nearest neighbor searching. Given any set of n points S ⊂ E, and a constant ǫ > 0, we produce a data structure, such that given any query point, a point of S will be reported whose distance from the query point is at most a factor of (1 + ǫ) from that of the true nearest neighbor. Our algorithm runs in O(log n) expected time and requires O(n log n) space. The data structure can be built in O(n) expected time. The constant factors depend on d and ǫ. Because of the practical importance of nearest neighbor searching in higher dimensions, we have implemented a practical variant of this algorithm, and show empirically that for many point distributions this variant of the algorithm finds the nearest neighbor in moderately large dimension significantly faster than existing practical approaches.
Pathogenesis of Enteric Infection by Campylobacter (1997)

Microbiology Society journals contain high-quality research papers and topical review articles. We are a not-for-profit publisher and we support and invest in the microbiology community, to the benefit of everyone. This supports our principal goal to develop, expand and strengthen the networks available to our members so that they can generate new knowledge about microbes and ensure that it is shared with other communities.
Jasmonates, New Regulators of Plant Growth and Development: Many Facts and Few Hypotheses on their Actions (1991)

Abstract Jasmonates, ubiquitous cyclopentanone compounds, are reviewed as new regulators for plant growth and development. They may complement the group of well‐established “classic” phytohormones. Jasmonates influence a multiplicity of plant physiological processes by inhibition, promotion or induction. In many aspects they are similar to abscisic acid, especially in responses to stress. The review contains information on the chemical structures and metabolism of jasmonates, contributes to their biological role and describes possible mode(s) of action at the level of molecular biology and gene expression. In particular, emphasis is placed on the gene expression and accumulation of jasmonate‐induced abundant polypeptides as a stress response of the plant cells. A hypothesis is attempted in which endogenous jasmonates represent an integral part of the signal transduction chain between stress signal(s) and stress response(s).
Hypothesis about the function of membrane-buried proline residues in transport proteins. (1986)

In a survey of the bilayer-spanning regions of integral membrane proteins, membrane-buried proline residues were found in nearly all transport proteins examined, whereas membrane-buried regions of nontransport proteins were largely devoid of intramembranous proline residues. When amino acids from the complete sequences of representative sets of transport and nontransport membrane proteins were analyzed for the distribution of proline residues between aqueous vs. membranous domains, proline was shown to be selectively excluded from membranous domains of the nontransport proteins, in accord with expectation from energetic and structural considerations. In contrast, proline residues in transport proteins were evenly distributed between aqueous and membranous domains, consistent with the notion that functional membrane-buried proline residues are selectively included in transport proteins. As cis peptide bonds involving proline arise in proteins and have been implicated in protein dynamic processes, the cis-trans isomerization of an Xaa-Pro peptide bond (Xaa = unspecified amino acid) buried within the membrane--and the resulting redirection of the protein chain--is proposed to provide the reversible conformational change requisite for the regulation (opening/closing) of a transport channel. Parallel to this function, the relatively negative character of the carbonyl groups of Xaa-Pro peptide bonds may promote their participation as intramembranous liganding sites for positive species in proton/cation transport processes.
Analysis of aberrant somatic hypermutation (SHM) in non‐Hodgkin's lymphomas of patients with chronic HCV infection (2005)

Hepatitis C virus (HCV) and aberrant somatic hypermutation (SHM) have each been suggested to contribute to the development of B-cell non-Hodgkin's lymphoma (NHL). The incidence of PIM-1, PAX-5, RhoH/TTF, and c-MYC mutations in tumour biopsy specimens from 32 HCV-infected B-cell NHL patients was analysed to determine whether the extent of aberrant SHM among these patients differed from that previously reported for HCV-negative B-cell NHL patients. Mutation of PIM-1, PAX-5, RhoH/TTF, and c-MYC was detected in 4 (13%), 5 (16%), 4 (13%), and 4 (13%) of 32 samples, respectively. In HCV-positive B-cell NHL patients, the frequency of aberrant SHM was lower than that already found in HCV-negative B-cell NHL patients. This indicates that, unlike B-cell lymphomas from HCV-negative patients, aberrant SHM may not contribute significantly to malignant transformation in HCV-associated B-cell lymphomas.
Application of A‐C Techniques to the Study of Lithium Diffusion in Tungsten Trioxide Thin Films (1980)

has been measured at room temperature as a function of frequency from to at various open‐circuit voltages. The diffusion equations have been solved for the appropriate finite boundary conditions, and analysis of the impedance data by the complex plane method yields values for the chemical diffusion coefficient, the component diffusion coefficient, the partial ionic conductivity of lithium, and the thermodynamic enhancement factor for as a function of . The films of were prepared by vacuum evaporation and were largely amorphous to x‐rays. The chemical diffusion coefficient has a value of at , increasing to at . At short times the interfacial charge transfer reaction is important, but at longer times the rate of lithium injection is determined by the diffusion kinetics.
Golgi-SNARE GS28 potentiates cisplatin-induced apoptosis by forming GS28–MDM2–p53 complexes and by preventing the ubiquitination and degradation of p53 (2012)

In the present study, we observed that the Golgi-SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) GS28 forms a complex with p53 in HEK (human embryonic kidney)-293 cells. Given that p53 represents a tumour suppressor that affects the sensitivity of cancer cells to various chemotherapeutic drugs, we examined whether GS28 may influence the level of sensitivity to the DNA-damaging drug cisplatin. Indeed, knockdown of GS28 using short-hairpin RNA (shGS28) induced resistance to cisplatin in HEK-293 cells. On the other hand, overexpression of GS28 sensitized HEK-293 cells to cisplatin, whereas no sensitization effect was noted for the mitotic spindle-damaging drugs vincristine and taxol. Accordingly, we observed that knockdown of GS28 reduced the accumulation of p53 and its pro-apoptotic target Bax. Conversely, GS28 overexpression induced the accumulation of p53 and Bax as well as the pro-apoptotic phosphorylation of p53 on Ser(46). Further experiments showed that these cellular responses could be abrogated by the p53 inhibitor PFT-α (pifithrin-α), indicating that GS28 may affect the stability and activity of p53. The modulatory effects of GS28 on cisplatin sensitivity and p53 stability were absent in lung cancer H1299 cells which are p53-null. As expected, ectopic expression of p53 in H1299 cells restored the modulatory effects of GS28 on sensitivity to cisplatin. In addition, GS28 was found to form a complex with the p53 E3 ligase MDM2 (murine double minute 2) in H1299 cells. Furthermore, the ubiquitination of p53 was reduced by overexpression of GS28 in cells, confirming that GS28 enhances the stability of the p53 protein. Taken together, these results suggest that GS28 may potentiate cells to DNA-damage-induced apoptosis by inhibiting the ubiquitination and degradation of p53.
Wireless monitoring system for oral-feeding evaluation of preterm infants (2014)

Feeding and swallowing disorders are relatively common in early infancy. In Clinical, it shows negative impacts on growth and neurodevelopmental, therefore it has become a high risk of neurodevelopmental delays in preterm infants. Oral feeding that requires suckling, swallowing, and breathing coordination, and it is the most complex sensorimotor process for the newborn infant. Currently, both preterm infant's oral feeding disorders and severity are dependent on subjective clinical experience. Directly monitoring sucking-swallowing-breathing activities of oral is difficult for preterm infants. In this study, a wireless monitoring system for oral feeding of preterm infants was developed to monitor the events of sucking-swallowing-breathing activities continuously and objectively. Finally, the experimental results show that the proposed system can detect the events of sucking, swallowing, and breathing activities effectively.
An Electromagnetic Micro Power Generator for Low-Frequency Environmental Vibrations (2005)

&lt;div class="htmlview paragraph"&gt;This paper presents an electromagnetic (EM) vibration-to-electrical power generator which can efficiently scavenge energy from low-frequency external vibrations. The reported generator increases the conversion efficiency by up-converting the low-frequency environmental vibrations to a much higher frequency. Power is generated by electromagnetic induction between a magnet and coils placed on top of resonating cantilever beams. The calculated &lt;i&gt;maximum&lt;/i&gt; power from a single cantilever is 2.5μW in vacuum for vibration frequencies 1Hz to 1kHz.&lt;/div&gt;
A solid‐state electrochromic device based on polyaniline, prussian blue and an elastomeric electrolyte (1993)

Advantages of solid‐state electrochemical devices are the ease of production, no possibility of leakage, and no electrolyte evaporation. One result of the search for such a device is the electrochromic display sketched in the Figure, which uses polyaniline and Prussian Blue as the active electrochromic materials and an elastomer containing Li‐ClO 4 as the solid‐state electrolyte. magnified image
DECtalk Software: Text-to-Speech Technology and Implementation (1995)

DECtalk is a mature text-to-speech synthesis technology that Digital has sold as a series of hardware products for more than ten years. Originally developed by Digital’s Assistive Technology Group (ATG) as an alternative to a character-cell terminal and for telephony applications, today DECtalk also provides visually handicapped people access to information. DECtalk uses a digital formant synthesizer to simulate the human vocal tract. Before the advent of the Alpha processor, the computational demands of this synthesizer placed an extreme load on a workstation. DECtalk Software has an application programming interface (API) that is supported on multiple platforms and multiple operating systems. This paper describes the various text-to-speech technologies, the DECtalk Software architecture, and the API. The paper also reports our experience in porting the DECtalk code base from the previous hardware platform.
Carbon metabolism regulates expression of the pfl (pyruvate formate-lyase) gene in Escherichia coli (1991)

The anaerobic expression of pfl is reduced both in a strain mutated in the pgi gene and in a pfkA pfkB double mutant strain when cells are grown in medium supplemented with glucose. When cells are grown in medium supplemented with either fructose or pyruvate, no reduction is observed in these strains. The amount of pyruvate in the cells may be responsible for the reduced expression of pfl in the strains mutated in the genes encoding the glycolytic enzymes. Because of the lowered oxygen concentration in the medium, the expression of pfl is induced when an exponentially growing culture enters the stationary phase. This induction is increased when the Casamino Acid concentration is raised 10-fold or when the medium is supplemented with NaCl. Superhelicity of DNA is decreased in a pgi mutant strain grown in medium supplemented with glucose. The superhelicity is also changed, but the opposite way, in a wild-type strain grown in medium supplemented with Casamino Acids at a high concentration or 0.3 M sodium chloride. Our data show that changes in superhelicity do not affect the aerobic expression of pfl but might be important for the anaerobic induction of pfl.
Type beta transforming growth factor: a bifunctional regulator of cellular growth. (1985)

Type beta transforming growth factor (TGF-beta) is a two-chain polypeptide of 25,000 daltons isolated from many tissues, including bovine kidney, human placenta, and human platelets. It has been characterized by its ability to stimulate reversible transformation of nonneoplastic murine fibroblasts, as measured by the formation of colonies of these cells in soft agar (ED50 = 4 pM TGF-beta for NRK fibroblasts). We now show that the response of cells to TGF-beta is bifunctional, in that TGF-beta inhibits the anchorage-dependent growth of NRK fibroblasts and of human tumor cells by increasing cell cycle time. Moreover, the anchorage-independent growth of many human melanoma, lung carcinoma, and breast carcinoma cell lines is inhibited by TGF-beta at concentrations in the same range as those that stimulate colony formation of NRK fibroblasts (average ED50 = 10-30 pM TGF-beta for inhibition). Whereas epidermal growth factor and TGF-beta synergize to induce anchorage-independent growth of NRK fibroblasts, their effects on the growth of A-549 human lung carcinoma cells are antagonistic. The bifunctional response of cells to TGF-beta is further demonstrated in Fischer rat 3T3 fibroblasts transfected with a cellular myc gene. In these cells TGF-beta synergizes with platelet-derived growth factor to stimulate colony formation but inhibits the colony formation induced by epidermal growth factor. The data indicate that the effects of TGF-beta on cells are not a function of the peptide itself, but rather of the total set of growth factors and their receptors that is operant in the cell at a given time.
CD34+ Blood Cells Accelerate Vascularization and Healing of Diabetic Mouse Skin Wounds (2003)

Diabetes is characterized by poor circulation and impaired angiogenesis, which appear to contribute to the frequent skin lesions and poor wound healing common in diabetic patients. Therapies to improve circulation commonly improve wound healing in diabetic patients. Administration of circulating CD34+ cells, cells that can function as endothelial cell progenitors, accelerates blood flow restoration to ischemic limbs of diabetic mice. We have investigated the potential of these cells to accelerate revascularization and healing in full-thickness skin wounds of hypoinsulinemic (streptozotocin-treated) diabetic mice. Wounds were injected with human CD34+ or CD34- peripheral blood mononuclear cells or no cells, and analyzed for vascularity and healing at various times thereafter. Treatment with CD34+ enriched cells decreased wound size by 4 days after treatment, accelerated epidermal healing, and rapidly and dramatically accelerated revascularization of the wounds compared to controls. Initially increased vascularization was mediated principally by an increase in vessel diameter, but later, both an increase in vascular size and number were observed. These findings indicate that blood-derived progenitors may have therapeutic potential in the treatment of skin lesions in the setting of diabetes, and give insights into how bone marrow cells exert their effects on neovascularization.
Reconstitution of T-cell receptor repertoire diversity following T-cell depleted allogeneic bone marrow transplantation is related to hematopoietic chimerism (2000)

CDR3 spectratyping was used to analyze the complexity of the T-cell repertoire and to define the mechanisms and kinetics of the reconstitution of T-cell immunity after allogeneic bone marrow transplantation (BMT). This method, which is based on polymerase chain reaction amplification of all CDR3 regions using the T-cell receptor (TCR) Vbeta genes, was used to examine serial samples of peripheral blood lymphocytes from 11 adult patients with chronic myelogenous leukemia (CML) who underwent T-cell-depleted allogeneic BMT. In contrast to 10 normal donors who display highly diverse and polyclonal spectratypes, patient samples before and early after BMT revealed markedly skewed repertoires, consisting of absent, monoclonal, or oligoclonal profiles for the majority of Vbeta subfamilies. To quantify changes in TCR repertoire over time, we established an 8-point scoring system for each Vbeta subfamily. The mean complexity score for patient samples before transplant (130.8) was significantly lower than that for normal donors (183; P = 0. 0007). TCR repertoire complexity was abnormal in all patients at 3 months after BMT (mean score = 87). Normalization of repertoire began in 4 patients at 6 months after BMT, but the majority of patients continued to display abnormal repertoires for up to 3 years after BMT. To determine whether the reconstituted T-cell repertoire was derived from the donor or recipient, unique microsatellite loci were examined to establish chimeric status. At 3 months after BMT, 7 patients demonstrated mixed chimerism; 4 had complete donor hematopoiesis (CDH). CDH strongly correlated with likelihood of restoration of T-cell repertoire complexity (P = 0.003). In contrast, patients who demonstrated persistence of recipient hematopoiesis failed to reconstitute a diverse TCR repertoire. These findings suggest that the reconstitution of a normal T-cell repertoire from T-cell progenitors in adults is influenced by interactions between recipient and donor hematopoietic cells. (Blood. 2000;95: 352-359)
Dominant negative analogs of NF-YA. (1994)

NF-Y is a highly conserved heteromeric CCAAT-binding transcription factor involved in the function of several promoters. The NF-YA subunit contains a domain of high homology to yeast HAP2, which we show to be necessary and sufficient to mediate interactions with the NF-YB subunit and with DNA. Using protein affinity columns derivatized with amino acid substitution mutants, we further dissect this region into two functionally separable subdomains. The subunit association function resides in a 21-amino acid stretch, which is almost perfectly conserved among different species, while interaction with DNA resides in another short segment. We also show that DNA-binding mutants act as dominant repressors of NF-Y-DNA complex formation and of NF-Y-dependent transcription.
An integrated analysis of cancer genes in thyroid cancer (2015)

Cancer driver genes are commonly mutationally disrupted in cancer, which confers a growth advantage to tumor cells. Recent studies preferentially search for recurrently mutated driver genes across multiple tumor samples, leading to the neglect of low-frequency mutated cancer genes. The present study was conducted to identify cancer‑driving genes in thyroid cancer with two distinct tools, OncodriveFM and Dendrix, which aim to detect neglected driver genes with low mutation frequency. A total of 23,620 somatic mutations generated by whole‑exome sequencing of 446 tumor/normal pairs of thyroid cancer were obtained from TCGA. Variant classification was conducted with Ensembl Variant Effect Predictor (VEP). OncodriveFM and Dendrix were applied to detect driver genes and pathways with statistical evidence. In addition, we analyzed DNA‑methylation status, copy number variation, expression levels and fusion genes among these driver candidates. In total, non‑synonymous mutations accounted for over 55% (13,091/23,620) of the total variants; 53 and 3 driver genes were determined by OncodriveFM and Dendrix, respectively, including 6 recurrently mutated driver genes, such as BRAF, NRAS, HRAS, EIF1AX, KRAS and 47 new genes. A total of 75 pathways with high function impact bias were identified by OncodriveFM. Two genes, FHOD3 and SRP72, were hypomethylated, overexpressed and involved in major deletions in thyroid cancer. Moreover, we identified 91 pairs of fusion genes, 89 of which were new fusion pairs in thyroid cancer. In conclusion, we successfully identified a list of new cancer genes, pathways and fusion genes, providing better insight into the tumorigenesis of thyroid cancer.