gebhart/patrepeval huggingface dataset:
Vaccinations for Colorectal Cancer: Progress, Strategies, and Novel Adjuvants (2019)

Although cancer is a leading cause of death, significant breakthroughs have been made in its treatment in recent years. In particular, increasingly effective cancer vaccines are being developed, including some for colorectal cancer. There are also currently a variety of compounds that can act as adjuvants, such as signalling molecules called cytokines. Other adjuvants target and inhibit the specific mechanisms by which cancers evade the immune system. One of them is a galectin inhibitor, which targets galectins-proteins produced by cancer cells that can cause the death of immune cells. Likewise, immune checkpoint inhibitors affect immune checkpoints-natural host proteins that usually control inflammation but can be exploited by cancers to weaken the body's defences. Equally, regulatory T cells may contribute to the progression of cancer by inhibiting the functions of other T cells. The main advantages of cancer vaccines include their low toxicity and their ability to strengthen the immune system. Nevertheless, significant limitations include their slow effects and their inability to treat cancer at times due to immunosuppression. Ultimately, ongoing trials provide hope for the development of more effective methods of immunotherapeutic inoculation that can target a greater variety of cancers.
Nuclear grooves in fine‐needle aspiration biopsies of breast lesions: Do they have any significance? (1998)

Nuclear grooving is a recognized morphologic feature frequently seen in papillary carcinoma of the thyroid. This feature is also occasionally seen in other nonneoplastic and neoplastic conditions. Nuclear grooves have been described in tubular carcinoma of the breast. However, the significance of nuclear grooves in benign and malignant conditions of the breast has been rarely studied. In a retrospective study, we searched for the presence of nuclear grooves in Papanicolaou-stained and Diff-Quik-stained fine-needle aspiration biopsies (FNAB) of 50 cases of primary breast carcinoma, 25 cases of proliferative breast disease, and 25 cases of fibroadenoma. In addition, 10 cases of metastatic breast carcinoma diagnosed by FNAB were reviewed. Nuclear grooves were identified in 39 of 50 (78%) of the histologically confirmed primary breast carcinomas and in 9 of 10 (90%) of the cases of metastatic breast carcinoma in the Papanicolaou-stained smears. Nineteen of 50 (38%) of the cases of proliferative breast disease/fibroadenoma showed nuclear grooves in the Papanicolaou-stained smears. The difference between the percentage of cases showing nuclear grooves seen in the Papanicolaou-stained primary breast carcinomas and metastatic breast carcinomas compared with the benign breast lesions was statistically significant (P < 0.001 in the primary breast carcinoma cases and P < 0.01 in the metastatic breast cancer cases). Nuclear grooves were identified less often in the Diff-Quik-stained smears, and their presence in malignant lesions versus cases diagnosed as benign breast disease was not statistically significant. This study suggests that, although the presence of nuclear grooves is more frequently seen in malignant breast lesions, their presence cannot totally exclude the possibility of benign breast disease. The presence of nuclear grooves, however, may serve as a diagnostic clue in metastatic tumors of unknown primary. Diagn. Cytopathol. 1998;18:333–337. © 1998 Wiley-Liss, Inc.
Management Options in Triple-Negative Breast Cancer (2011)

Notorious for its poor prognosis and aggressive nature, triple-negative breast cancer (TNBC) is a heterogeneous disease entity. The nature of its biological specificity, which is similar to basal-like cancers, tumors arising in BRCA1 mutation carriers, and claudin-low cancers, is currently being explored in hopes of finding the targets for novel biologics and chemotherapeutic agents. In this review, we aim to give a broad overview of the disease's nomenclature and epidemiology, as well as the basic mechanisms of emerging targeted therapies and their performance in clinical trials to date.
The Relaxation Response: Therapeutic Effect (1997)

Irwin and Jack Tessman (Letters, [24 Oct., p. 561][1]) write that there are discrepancies between my alleged publicizing of the therapeutic claims of the relaxation response and the published data. The data that they cite are in articles that I co-authored, but they compare these data with my
Indirect coupling of phosphate release to de novo tension generation during muscle contraction. (1995)

A key question in muscle contraction is how tension generation is coupled to the chemistry of the actomyosin ATPase. Biochemical and mechanochemical experiments link tension generation to a change in structure associated with phosphate release. Length-jump and temperature-jump experiments, on the other hand, implicate phase 2slow, a significantly faster, markedly strain-sensitive kinetic process in tension generation. We use a laser temperature jump to probe the kinetics and mechanism of tension generation in skinned rabbit psoas fibers--an appropriate method since both phosphate release and phase 2slow are readily perturbed by temperature. Kinetics characteristic of the structural change associated with phosphate release are observed only when phosphate is added to fibers. When present, it causes a reduction in fiber tension; otherwise, no force is generated when it is perturbed. We therefore exclude this step from tension generation. The kinetics of de novo tension generation by the temperature-jump equivalent of phase 2slow appear unaffected by phosphate binding. We therefore propose that phosphate release is indirectly coupled to de novo tension generation via a steady-state flux through an irreversible step. We conclude that tension generation occurs in the absence of chemical change as the result of an entropy-driven transition between strongly bound crossbridges in the actomyosin-ADP state. The mechanism resembles the operation of a clock, with phosphate release providing the energy to tension the spring, and the irreversible step functions as the escapement mechanism, which is followed in turn by tension generation as the movement of the hands.
Paramunity-inducing effects of vaccinia strain MVA. (1999)

Vaccinia virus MVA is harmless for humans and animals both locally and parenterally. It offers paraspecific activities similar to those of comparable attenuated viruses of other pox genera, e.g. avipox or parapox. At the systemic level, MVA protects baby mice against lethal challenge with vesicular stomatitis virus (dose-response curve). MVA raises phagocytosis and NK-cell activity in humans and animals, whilst encouraging the induction of interferon alpha, interleukin-2 and -12 and colony-stimulating activity at the same time. The paramunity-inducing properties of MVA make it an ideal vector for the insertion of foreign genes. It is superior to other virus vectors because of its complex function. Inactivated MVA is also suitable as an inducer of paramunity.
Novel DNA vaccine based on hepatitis B virus core gene induces specific immune responses in Balb/c mice (2005)

pSW3891/HBc vaccination elicits specific anti-HBc response and induces HBc-specific CTL response in immunized Balb/c mice.
Identification of a T-cell epitope adjacent to neutralization antigenic site 1 of poliovirus type 1 (1991)

Proliferative T-cell responses to poliovirus in various strains of mice have been analyzed by using either killed purified virus or capsid protein VP1 synthetic peptides. Following immunization of mice with inactivated poliovirus type 1 (PV1), a specific proliferative response of their lymph node CD4+ T cells was obtained after in vitro stimulation with purified virus. In mice immunized with PV1, PV2, or PV3, a strong cross-reactivity of the T-cell responses was observed after in vitro stimulation with heterologous viruses. By using various strategies, a dominant T-cell epitope was identified in the amino acid 103 to 115 region of capsid polypeptide VP1, close by the C3 neutralization epitope. The T-cell response to VP1 amino acids 103 to 115 is H-2 restricted: H-2d mice are responders, whereas H-2k and H-2b mice do not respond to this T-cell epitope. Immunization of BALB/c (H-2d) mice with the uncoupled p86-115 peptide, which represents VP1 amino acids 86 to 115 and contains both the T-cell epitope and the C3 neutralization epitope, induced poliovirus-specific B- and T-cell responses. Moreover, these mice developed poliovirus neutralizing antibodies.
Photoexcited carrier recombination in wide m-plane InGaN/GaN quantum wells (2013)

Carrier recombination in single 10 nm wide m-plane homoepitaxial In0.15Ga0.85N/GaN quantum wells was examined by time-resolved photoluminescence. The radiative recombination time at 3.5 K was found to be short, about 0.5 ns. This value and the single-exponential luminescence decay show that the localized exciton recombination is not affected by the in-plane electric field. At room temperature, the nonradiative recombination was prevalent. The data indicate that the nonradiative recombination proceeds via efficient recombination centers. Complexes of Ga vacancies with oxygen and/or related interface defects are suggested to play this role and thus provide a direction for future improvements in materials' quality.
Polydimethylsiloxane (PDMS)-based spiral channel PCR chip (2005)

A novel spiral channel polymerase chain reaction (PCR) microchip was developed by using polydimethylsiloxane (PDMS) and glass. Finite element analysis was used to simulate the temperature and hydrokinetic characteristics of this PCR chip. Investigation of the spiral channel arrangement indicates that this layout can improve the productivity and efficiency effectively. An amplification of a 450 bp segment of Escherichia coli HB101 was successfully performed, which verified the ability of the microchip.
Continuous wave cavity ring-down spectroscopy measurement of NO2 mixing ratios in ambient air (2005)

The performance of a continuous wave diode laser based cavity ring-down (CRD) spectrometer is demonstrated for retrieval of NO2 mixing ratios in ambient air. Measurements are made at wavelengths around 410 nm, a region free from other spectroscopic interferences, and the instrument is shown to be capable of quantitative and precise NO2 mixing ratio determinations without any requirement for calibration. The minimum concentration of NO2 that can be measured by the spectrometer is estimated to be 0.1 ppbv (parts per billion by volume) in 50 s at atmospheric pressure. Using dynamic dilution of a standard NO2 sample, the performance of the spectrometer has been validated for NO2 measurements over the range of 0.2 to 80 ppbv. NO2 measurements performed directly on laboratory air are compared with data obtained with a calibrated chemiluminescence instrument and shown to be in excellent agreement.
Three-dimensional bioprinting of rat embryonic neural cells (2009)

We present a direct cell printing technique to pattern neural cells in a three-dimensional (3D) multilayered collagen gel. A layer of collagen precursor was printed to provide a scaffold for the cells, and the rat embryonic neurons and astrocytes were subsequently printed on the layer. A solution of sodium bicarbonate was applied to the cell containing collagen layer as nebulized aerosols, which allowed the gelation of the collagen. This process was repeated layer-by-layer to construct the 3D cell-hydrogel composites. Upon characterizing the relationship between printing resolutions and the growth of printed neural cells, single/multiple layers of neural cell-hydrogel composites were constructed and cultured. The on-demand capability to print neural cells in a multilayered hydrogel scaffold offers flexibility in generating artificial 3D neural tissue composites.
Use of multiple T cell-directed intact ricin immunotoxins for autologous bone marrow transplantation (1985)

Abstract The monoclonal antibodies (MoAb) T101, G3.7, 35.1, and TA-1 were conjugated to intact ricin using a thioether linkage. These MoAb detect, respectively, the CD5[gp67], CD7[p41], CD2[p50], and [gp95, 170] determinants that are found in the vast majority of cases of T cell acute lymphocytic leukemia (T-ALL). The resulting immunotoxins (ITs) and an equimolar mixture of these ITs were evaluated as potential purgative reagents for autologous transplantation in T-ALL. Leukemic cell lines were used to compare the kinetics of protein synthesis inactivation mediated by each IT. The cells were treated with IT in the presence of lactose in order to block the native binding of ricin. The observed rates of protein synthesis inactivation correlated with target antigen expression detected by fluorescence-activated cell sorter analysis. Of the four ITs, T101-ricin (T101-R) exhibited the fastest rate of inactivation, followed in order by G3.7-ricin, TA-1-ricin, and 35.1-ricin. At concentrations greater than 300 ng/mL, a cocktail containing an equimolar amount of all four ITs (referred to as the four- IT cocktail) exhibited kinetics that were as fast or faster than those of T101-R. The long-term cytotoxic effects of individual ITs and the four-IT cocktail were evaluated using a sensitive clonogenic assay. Each IT was specifically cytotoxic and inhibited 1 to 4 logs of clonogenic leukemic cells at doses (300 to 600 ng/mL) that can be used clinically. The four-IT cocktail was highly cytotoxic; a concentration of 300 ng/mL inhibited greater than 4 logs of leukemic cells while sparing the majority of committed (CFU-GM, CFU-E) and pluripotent (CFU- GEMM) hematopoietic stem cells. The determination of both short-term kinetics of protein synthesis inactivation and longer-term inhibition of clonogenic growth allowed new insight into cell killing by IT. Our results suggest that ITs continue to act on clonogenic target cells for a period of three to five days. Interestingly, the four-IT cocktail was not as potent against clonogenic leukemic cells as T101-R alone, although it exhibited kinetics of protein synthesis inhibition that were as fast as those of T101-R alone. This finding suggests that internalized ITs may differ in the length of time they remain active within the cell. Our results also demonstrate the importance of using several different assays to evaluate IT reagents.
Functional Similarities of Hepatic Cystic and Biliary Epithelium: Studies of Fluid Constituents And In Vivo Secretion in Response to Secretin (1990)

Hepatic cysts are a frequent manifestation of autosomal dominant polycystic kidney disease, but little is known about their functional characteristics. The goals of our study were to define the composition of hepatic cyst fluid and to determine whether hepatic cysts secrete in response to intravenously administered secretin. We percutaneously punctured five hepatic cysts and one proximal renal cyst from six subjects with autosomal dominant polycystic kidney disease and one solitary hepatic cyst from a subject without autosomal dominant polycystic kidney disease. Most fluids had an electrolyte composition similar to serum. Fluid from all hepatic cysts had glutamyltranspeptidase concentrations above those found in serum [( cyst]/[serum] = 4.93 +/- 5.92), contained secretory component (the epithelial receptor for polymeric IgA) and had glucose concentrations less than 15 mg/dl. Fluid from both hepatic and renal cysts of subjects with autosomal dominant polycystic kidney disease, but not from the subject with the solitary hepatic cyst, demonstrated extensive changes in the electrophoretic mobility of several serum proteins. Initial intracystic pressures ranged from 16 to 40 cm H2O, were reduced 57% to 97% after aspiration of a portion of cyst fluid and were held constant during the secretion study. Within 8 min of the intravenous administration of secretin, secretion of fluid increased in two of three hepatic cysts and in the renal cyst. The electrolyte composition of cyst fluids was not altered by secretin. These data suggest that hepatic cystic epithelium has functional characteristics of biliary epithelium and that secretion by both hepatic and renal cysts may be hormonally regulated.
LoRea: A Backscatter Reader for Everyone! (2016)

Computational RFID (CRFID) platforms have enabled reconfigurable, battery-free applications for close to a decade. However, several factors have impeded their wide-spread adoption: low communication range, low throughput, and expensive infrastructure - CRFID readers usually cost upwards of $1000. This paper presents LoRea, a backscatter reader that achieves an order of magnitude higher range than existing CRFID readers, while costing a fraction of their price. LoRea achieves this by diverging from existing designs of CRFID readers and more specifically, how self-interference is tackled. LoRea builds on recent work that frequency-shifts backscatter transmissions away from the carrier signal to reduce self- interference. LoRea also decouples the carrier generation from the reader, helping to further decrease self-interference. Decoupling carrier generation also enables the use of deployed infrastructure of smartphones and sensor nodes to provide the carrier signal. Together these methods reduce cost and complexity of the reader. LoRea also purposefully operates at lower bi- trates than recent backscatter systems which enables high sensitivity and longer range. We evaluate LoRea experimentally and find that it achieves a communication range of up to 225 m in line-of-sight scenarios. In indoor environments, where the signal traverses several walls separating the reader and the backscatter tag, LoRea achieves a range of 30 m. These results illustrate how LoRea outperforms state- of-art backscatter systems and CRFID platforms.
Lowered oxygen tension induces expression of the hypoxia marker MN/carbonic anhydrase IX in the absence of hypoxia-inducible factor 1 alpha stabilization: a role for phosphatidylinositol 3'-kinase. (2002)

Transcription of the gene coding for the tumor-associated antigen MN/carbonic anhydrase IX (CAIX) is regulated by hypoxia-inducible factor 1 (HIF-1). Previous studies identified CAIX expression in areas adjacent to hypoxic regions in solid tumors and suggested supplementary/alternative modes of regulation. To better understand the mechanisms activating CAIX expression, we characterized the cell density-dependent induction of CAIX in HeLa cells. This process is anchorage and serum independent and is not mediated by a soluble factor, decreased pH, or lowered glucose concentration. Stabilization of HIF-1 alpha was not observed in dense cultures. In contrast to sparse cell culture conditions, phosphatidylinositol 3'-kinase (PI3K) activity was significantly increased in dense HeLa cultures. The PI3K inhibitors LY294002 and wortmannin inhibited CAIX expression in dense cultures in a dose-dependent manner, specifically targeting the CA9 promoter (-173/+31 region) that was transactivated by constitutively active p110 PI3K subunit. The mechanism controlling CAIX expression in dense cultures is, however, dependent on lowered O(2) tension because stirring abrogates induction of CAIX expression. Hypoxia- and cell density-induced CAIX expressions were mediated by two seemingly independent mechanisms, as documented by the additive effect of increased cell density and treatment with the hypoxia-mimic CoCl(2) on levels of CAIX expression. The minimal cell density-dependent region within the CA9 promoter consists of the juxtaposed protected region 1 and hypoxia-response elements. However cell density-dependent CAIX expression was abrogated in the HIF-1 alpha-deficient Kal3.5 cells, suggesting an important role of HIF-1 in the corresponding mechanism. Thus, induction of CAIX in high-density cultures requires separate but interdependent pathways of PI3K activation and a minimal level of HIF-1 alpha. These interdependent pathways function at a lowered O(2) concentration that is, however, above that necessary for HIF-1 alpha stabilization.
Circulating bufodienolide and cardenolide sodium pump inhibitors in preeclampsia (1999)

Our observations demonstrate the coexistence of two endogenous cardiotonic steroids in preeclamptic plasma, a more polar OLC and a less polar MBG-like compound. Substantial increases in plasma OLC and MBG immunoreactivity in preeclampsia, along with the vasoconstrictor properties of authentic MBG and Na+,K+ ATPase inhibitory activity of human MBG immunoreactive factor, suggest, that in preeclampsia, plasma concentrations of MBG are enough to substantially inhibit the sodium pump in cardiovascular tissues, and are in accordance with the views attributing endogenous digitalis-like factors a pathogenic role in the preeclamptic hypertension.
Cloning and chromosomal assignment of a human cDNA encoding a T cell- and natural killer cell-specific trypsin-like serine protease. (1988)

A cDNA clone encoding a human T cell- and natural killer cell-specific serine protease was obtained by screening a phage lambda gt10 cDNA library from phytohemagglutinin-stimulated human peripheral blood lymphocytes with the mouse Hanukah factor cDNA clone. In an RNA blot-hybridization analysis, this human Hanukah factor cDNA hybridized with a 1.3-kilobase band in allogeneic-stimulated cytotoxic T cells and the Jurkat cell line, but this transcript was not detectable in normal muscle, liver, tonsil, or thymus. By dot-blot hybridization, this cDNA hybridized with RNA from three cytolytic T-cell clones and three noncytolytic T-cell clones grown in vitro as well as with purified CD16+ natural killer cells and CD3+, CD16- T-cell large granular lymphocytes from peripheral blood lymphocytes (CD = cluster designation). The nucleotide sequence of this cDNA clone encodes a predicted serine protease of 262 amino acids. The predicted protein has a 22-amino acid presegment, a 6-amino acid prosegment, and an active enzyme of 234 amino acids with a calculated unglycosylated molecular weight of 25,820. The active enzyme is 71% and 77% similar to the mouse sequence at the amino acid and DNA level, respectively. The human and mouse sequences conserve the active site residues of serine proteases--the trypsin-specific Asp-189 and all 10 cysteine residues. The gene for the human Hanukah factor serine protease is located on human chromosome 5. We propose that this trypsin-like serine protease may function as a common component necessary for lysis of target cells by cytotoxic T lymphocytes and natural killer cells.