gebhart/patrepeval huggingface dataset:
Direct Evidence on the Immune-Mediated Spontaneous Regression of Human Cancer: An Incentive for Pharmaceutical Companies to Develop a Novel Anti-Cancer Vaccine (2005)

To develop an effective pharmaceutical treatment for a disease, we need to fully understand the biological behavior of that disease, especially when dealing with cancer. The current available treatment for cancer may help in lessening the burden of the disease or, on certain occasions, in increasing the survival of the patient. However, a total eradication of cancer remains the researchers' hope. Some of the discoveries in the field of medicine relied on observations of natural events. Among these events is the spontaneous regression of cancer. It has been argued that such regression could be immunologically-mediated, but no direct evidence has been shown to support such an argument. We, hereby, provide compelling evidence that spontaneous cancer regression in humans is immunologically-mediated, hoping that the results from this study would stimulate the pharmaceutical industry to focus more on cancer vaccine immunotherapy. Our results showed that patients with >3 primary melanomas (very rare group among cancer patients) develop significant histopathological spontaneous regression of further melanomas that they could acquire during their life (P=0.0080) as compared to patients with single primary melanoma where the phenomenon of spontaneous regression is absent or minimal. It seems that such regression resulted from the repeated exposure to the tumor which mimics a self-immunization process. Analysis of the regressing tumors revealed heavy infiltration by T lymphocytes as compared to non-regressing tumors (P<0.0001), the predominant of which were T cytotoxic rather than T helper. Mature dendritic cells were also found in significant number (P<0.0001) in the regressing tumors as compared to the non regressing ones, which demonstrate an active involvement of the different arms of the immune system in the multiple primary melanoma patients in the process of tumor regression. Also, MHC expression was significantly higher in the regressing versus the non-regressing tumors (P <0.0001), which reflects a proper tumor antigen expression. Associated with tumor regression was also loss of the melanoma common tumor antigen Melan A/ MART-1 in the multiple primary melanoma patients as compared to the single primary ones (P=0.0041). Furthermore, loss of Melan A/ MART-1 in the regressing tumors significantly correlated with the presence of Melan A/ MART-1-specific CTLs in the peripheral blood of these patients (P=0.03), which adds to the evidence that the phenomenon of regression seen in these patients was immunologically-mediated and tumor-specific. Such correlation was also seen in another rare group of melanoma patients, namely those with occult primary melanoma. The lesson that we could learn from nature in this study is that inducing cancer regression using the different arms of the immune system is possible. Also, developing a novel cancer vaccine is not out of reach.
Molecular and functional characterization of mouse signaling lymphocytic activation molecule (SLAM): differential expression and responsiveness in Th1 and Th2 cells. (1999)

Optimal T cell activation and expansion require engagement of the TCR plus costimulatory signals delivered through accessory molecules. SLAM (signaling lymphocytic activation molecule), a 70-kDa costimulatory molecule belonging to the Ig superfamily, was defined as a human cell surface molecule that mediated CD28-independent proliferation of human T cells and IFN-gamma production by human Th1 and Th2 clones. In this study, we describe the cloning of mouse SLAM and the production of mAb against it which reveal its expression on primary mouse T and B cells. Mouse SLAM is expressed on highly polarized Th1 and Th2 populations, and is maintained on Th1, but not on Th2 clones. Anti-mouse SLAM mAb augmented IFN-gamma production by Th1 cells and Th1 clones stimulated through the TCR, but did not induce IFN-gamma production by Th2 cells, nor their production of IL-4 or their proliferation. Mouse SLAM is a 75-kDa glycoprotein that upon tyrosine phosphorylation associates with the src homology 2-domain-containing protein tyrosine phosphatase SHP-2, but not SHP-1. Mouse SLAM also associates with the recently described human SLAM-associated protein. These studies may provide new insights into the regulation of Th1 responses.
Controllable Soluble Protein Concentration Gradients in Hydrogel Networks (2008)

Here we report controlled formation of sustained, soluble protein concentration gradients within hydrated polymer networks. The approach involves spatially localizing proteins or biodegradable, protein-loaded microspheres within hydrogels to form a protein-releasing "depot". Soluble protein concentration gradients are then formed as the released protein diffuses away from the localized source. Control over key gradient parameters, including maximum concentration, gradient magnitude, slope, and time dynamics, is achieved by controlling the release of protein from the depot and subsequent transport through the hydrogel. Results demonstrate a direct relationship between the amount of protein released from the depot and the source concentration, gradient magnitude, and slope of the concentration gradient. In addition, an inverse relationship exists between the diffusion coefficient of protein within the hydrogel and the slope of the concentration gradient. The time dynamics of the concentration gradient profile can be directly correlated to protein release from the localized source, providing a mechanism for temporally controlling gradient characteristics. Therefore, each key, biologically relevant parameter associated with the protein concentration gradient can be controlled by defining protein release and diffusion. We anticipate that the resulting materials may be useful in three-dimensional cell culture systems, and in emerging tissue engineering approaches that aim to regenerate complex, functional tissues.
A Specific Inhibitor of TGF-β Receptor Kinase, SB-431542, as a Potent Antitumor Agent for Human Cancers (2005)

Small molecule inhibitors of signaling pathways have proven to be extremely useful for the development of therapeutic strategies for human cancers. Blocking the tumor-promoting effects of transforming growth factor-beta (TGF-beta) in advanced stage carcinogenesis provides a potentially interesting drug target for therapeutic intervention. Although very few TGF-beta receptor kinase inhibitors (TRKI) are now emerging in preclinical studies, nothing is known about how these inhibitors might regulate the tumor-suppressive or tumor-promoting effects of TGF-beta, or when these inhibitors might be useful for treatment during cancer progression. We have investigated the potential of TRKI in new therapeutic approaches in preclinical models. Here, we demonstrate that the TRKI, SB-431542, inhibits TGF-beta-induced transcription, gene expression, apoptosis, and growth suppression. We have observed that SB-431542 attenuates the tumor-promoting effects of TGF-beta, including TGF-beta-induced EMT, cell motility, migration and invasion, and vascular endothelial growth factor secretion in human cancer cell lines. Interestingly, SB-431542 induces anchorage independent growth of cells that are growth-inhibited by TGF-beta, whereas it reduces colony formation by cells that are growth-promoted by TGF-beta. However, SB-431542 has no effect on a cell line that failed to respond to TGF-beta. This represents a novel potential application of these inhibitors as therapeutic agents for human cancers with the goal of blocking tumor invasion, angiogenesis, and metastasis, when tumors are refractory to TGF-beta-induced tumor-suppressor functions but responsive to tumor-promoting effects of TGF-beta.
Genome sequence of Shigella flexneri 2a: insights into pathogenicity through comparison with genomes of Escherichia coli K12 and O157 (2002)

We have sequenced the genome of Shigella flexneri serotype 2a, the most prevalent species and serotype that causes bacillary dysentery or shigellosis in man. The whole genome is composed of a 4 607 203 bp chromosome and a 221 618 bp virulence plasmid, designated pCP301. While the plasmid shows minor divergence from that sequenced in serotype 5a, striking characteristics of the chromosome have been revealed. The S.flexneri chromosome has, astonishingly, 314 IS elements, more than 7-fold over those possessed by its close relatives, the non-pathogenic K12 strain and enterohemorrhagic O157:H7 strain of Escherichia coli. There are 13 translocations and inversions compared with the E.coli sequences, all involve a segment larger than 5 kb, and most are associated with deletions or acquired DNA sequences, of which several are likely to be bacteriophage-transmitted pathogenicity islands. Furthermore, S.flexneri, resembling another human-restricted enteric pathogen, Salmonella typhi, also has hundreds of pseudogenes compared with the E.coli strains. All of these could be subjected to investigations towards novel preventative and treatment strategies against shigellosis.
Nanofabrication by scanning probe microscope lithography: A review (2005)

In addition to its well-known capabilities in imaging and spectroscopy, scanning probe microscopy (SPM) has recently shown great potentials for patterning of material structures in nanoscales. It has drawn the attention of not only the scientific community, but also the industry. This article examines various applications of SPM in modification, deposition, removal, and manipulation of materials for nanoscale fabrication. The SPM-based nanofabrication involves two basic technologies: scanning tunneling microscopy and atomic force microscopy. Major techniques related to these two technologies are evaluated with emphasis on their abilities, efficiencies, and reliabilities to make nanostructures. The principle and specific approach underlying each technique are presented; the differences and uniqueness among these techniques are subsequently discussed. Finally, concluding remarks are provided where the strength and weakness of the techniques studied are summarized and the scopes for technology improvement and future research are recommended.
우리나라 제조산업내 기업규모에 따른 소득양극화 및 불균형에 관한 연구 (2012)

본 연구는 산업내 양극화 및 불균형 현상이 존재하는지 여부를 분석하기 위해 약 20년간의 356개 제조업에 속한 기업의 재무제표 자료를 토대로 소득양극화 지수인 Wolfson지수 및 ER지수, 소득불균형지수인 GINI계수와 5분위 분배율을 제조산업내 기업규모별 수치를 산출, 실증분석을 하였다. 또한 소득5분위 배율은 기업규모별 매출액 기준 상위 20%인 대기업과 하위 20%인 중소기업으로 분류하여 두 계층간 매출격차를 비교하였다. 분석결과에 따르면, 우리나라 제조산업내 기업규모별 양극화 및 불균형을 비롯한 제조업에 속한 중소기업은 다음과 같은 특징을 보이고 있다. 먼저, 우리나라 제조산업 내에서 기업규모에 따른 대기업과 중소기업간의 소득양극화 심화현상을 제조업 Wolfson지수, ER지수를 산출하여 그 추이를 분석해보면, 1997년 전후를 제외하고는 지속적으로 상승하는 점과 시간이 경과될수록 기울기가 더 가파른 추세로 이어지는 현상을 볼 수 있다. 이는 국민소득의 양극화와는 다른 추세로 감소 없이 지속적으로 증가한다는 점에서 더 심각하다고 판단할 수 있다. 다음으로 소득불균등 수준을 나타내는 GINI계수와 소득 5분위 배율을 통한 제조산업내 소득불균등의 현황은 소득양극화지수와 동일하게 외환위기 이후부터 급격하게 상승한 것을 볼 수 있다. 마지막으로 이러한 산업내 불균형 및 양극화가 존재함에 따라 기업규모별 특징을 중소기업과 대기업으로 구분하여 매출액 이익률, 매출액경상이익률, 총자산회전율, ROA, EBIT, NOPAT, NI측면에서 분석 결과 중소기업이 대기업에 비하여 자산의 규모가 상대적으로 작기 때문에 총자산을 효율적으로 활용하고 있는 것처럼 볼 수 있지만 실제로 자산의 수익성 측면에서는 오히려 떨어지는 것으로 볼 수 있다. 이와 같은 결과는 매출액이익률과 매출액 경상이익률의 결과와도 일치한다.
A Highly Restricted Antigen for Renal Cell Carcinoma Defined by a Monoclonal Antibody (1985)

Monoclonal antibodies against renal cell carcinoma (RCC) antigens were generated by immunizing Balb/c mice with the human RCC cell line 7860. After cloning many RCC reactive monoclonal antibodies, one antibody (D5D), was of special interest. Specificity testing against 33 human tumor cell lines revealed D5D to have no specific reactivity with 17 specimens of normal adult or fetal kidney. Reactivity with 67 specimens of nonrenal tissue demonstrated no reactivity. The reactivity of D5D with 15 different RCC tissues has been variable, being present in 60% of cases. Preliminary data, however, suggest that the antigen may be reexpressed for some of the remaining 40% during in vitro propagation.
Lateral opening of a translocon upon entry of protein suggests the mechanism of insertion into membranes (2010)

The structure of the protein-translocating channel SecYEβ from Pyrococcus furiosus at 3.1-Å resolution suggests a mechanism for chaperoning transmembrane regions of a protein substrate during its lateral delivery into the lipid bilayer. Cytoplasmic segments of SecY orient the C-terminal α-helical region of another molecule, suggesting a general binding mode and a promiscuous guiding surface capable of accommodating diverse nascent chains at the exit of the ribosomal tunnel. To accommodate this putative nascent chain mimic, the cytoplasmic vestibule widens, and a lateral exit portal is opened throughout its entire length for partition of transmembrane helical segments to the lipid bilayer. In this primed channel, the central plug still occludes the pore while the lateral gate is opened, enabling topological arbitration during early protein insertion. In vivo, a 15 amino acid truncation of the cytoplasmic C-terminal helix of SecY fails to rescue a secY-deficient strain, supporting the essential role of this helix as suggested from the structure.
Chromosome 11 translocation breakpoints at the PRAD1/cyclin D1 gene locus in centrocytic lymphoma. (1993)

Centrocytic lymphoma is a CD5-positive B-cell neoplasm. Rearrangements at the chromosome 11q13 bcl-1 breakpoint loci are present in the majority of these lymphomas, as a result of reciprocal translocation with the 14q32 immunoglobulin heavy chain joining genes. Recently, a gene lying approximately 110 kb telomeric of the bcl-1 major translocation cluster breakpoint locus, designated PRAD1, was proposed as a candidate bcl-1 oncogene. Accumulated evidence now indicates that this gene is the postulated bcl-1 oncogene. It encodes a protein with homology to cyclin family proteins designated cyclin D1 (CCND1). In order to determine whether 11q13 translocation breakpoints were present near the PRAD1 coding region in addition to the previously defined bcl-1 sites, we analyzed 27 centrocytic lymphomas by Southern blot using genomic and cDNA probes flanking the first exon of PRAD1. Five samples showed rearrangement at PRAD1 sites. In four of these, the breakpoints could be mapped from approximately one to 25 kb upstream of the first PRAD1 exon; each showed comigration of rearranged PRAD1 and immunoglobulin heavy-chain joining gene bands consistent with the t(11;14)(q13;q32). The fifth case was rearranged with PRAD1 probes only on BamHI-digested DNA, indicating either a point mutation or a polymorphism at this site. This sample also had rearrangement on multiple enzyme digests with the bcl-1 p94PS probe. None of 80 non-centrocytic B-cell neoplasms showed PRAD1 rearrangement. Thus, rearrangement at both bcl-1 and PRAD1 loci is strongly associated with centrocytic lymphoma, and provides a useful molecular marker for classifying this subtype of lymphoma. Furthermore, translocation-induced aberrant expression of the PRAD1 cyclin may lead to deregulated cell cycle control and play an important role in the pathogenesis of centrocytic lymphoma.
Regulation and Functional Involvement of Distinct Determinants of Leucocyte Function‐Associated Antigen 1 (LFA‐1) in T‐Cell Activation In Vitro (1991)

The expression of leucocyte function-associated antigen 1 (LFA-1) was studied by immunofluorescence method on human peripheral blood mononuclear cells (PBMC) stimulated by the phytohaemagglutinin lectin (PHA). Monoclonal antibodies (MoAb) Mas 191c, IOT18 (directed against the beta-chain, 95 kDa, CD18) and IOT16, SPVL7, MHM24 (identificating the alpha-chain, 180 kDa, CD11a) were used, defining the 'CD11a/CD18' antibody panel. By means of cross-linking or competitive experiments, we showed that these antibodies recognized at least four distinct and spatially distant domains on the LFA-1 molecule. Immunofluorescence analysis revealed that the up-regulation of LFA-1 expression was a late event, similar to the expression kinetics of the HLA DR and CD38 molecules, and followed the appearance of CD25 and CD71 molecules. Moreover, it was established that the LFA-1 up-regulation required mRNA and protein synthesis. Functional activity comparison of the different anti LFA-1 MoAb showed that the CD11a MoAb significantly inhibited the proliferation of lymphocytes stimulated by the phytohaemagglutinin to various extents, as the LFA-1 alpha determinant identified. By contrast, the CD18 MoAb did not influence strongly this cell process. We observed only a dim inhibitory effect with the CD18 MoAb recognizing an epitope common or very close to an LFA-1 alpha determinant. These results suggested that the LFA-1 antigen was important, at a molecular level, in the regulation of T-cell activation.
Impact of Polymer Tether Length on Multiple Ligand-Receptor Bond Formation (2001)

The promoters of cell adhesion are ligands, which are often attached to flexible tethers that bind to surface receptors on adjacent cells. Using a combination of Monte Carlo simulations, diffusion reaction theory, and direct experiments (surface force measurements) of the biotin-streptavidin system, we have quantified polymer chain dynamics and the kinetics and spatial range of tethered ligand-receptor binding. The results show that the efficiency of strong binding does not depend solely on the molecular architecture or binding energy of the receptor-ligand pair, nor on the equilibrium configuration of the polymer tether, but rather on its "rare" extended conformations.
Neuron Activity Related to Short-Term Memory (1971)

Nerve cells in the monkey's prefrontal cortex and nucleus medialis dorsalis of the thalamus show changes of firing frequency associated with the performance of a delayed response test. Most cells increase firing during the cue presentation period or at the beginning of the ensuing delay; spike discharge highler than that in intertrial periods is present in some cells throughout the delay. These changes are interpreted as suggestive evidence of a role of frontothalamic circuits in the attentive process involved in short-term memory
Are you comfortable doing that? (2014)

Several research groups have demonstrated advantages of extending a mobile device's input vocabulary with in-air gestures. Such gestures show promise but are not yet being integrated onto commercial devices. One reason for this might be the uncertainty about users' perceptions regarding the social acceptance of such around-device gestures. In three studies, performed in public settings, we explore users' and spectators' attitudes about using around-device gestures in public. The results show that people are concerned about others' reactions. They are also sensitive and selective regarding where and in front of whom they would feel comfortable using around-device gestures. However, acceptance and comfort are strongly linked to gesture characteristics, such as, gesture size, duration and in-air position. Based on our findings we present recommendations for around-device input designers and suggest new approaches for evaluating the social acceptability of novel input methods.
Phase change and the regulation of trichome distribution in Arabidopsis thaliana (1997)

Higher plants pass through several phases of shoot growth during which they may produce morphologically distinct vegetative structures. In Arabidopsis thaliana this phenomenon is apparent in the distribution of trichomes on the leaf surface. Leaves produced early in rosette development lack trichomes on their abaxial (lower) surface, leaves produced later have trichomes on both surfaces, and leaves in the inflorescence (bracts) may have few or no trichomes on their adaxial (upper) surface. Here we describe some of the factors that regulate this distribution pattern. We found that the timing of abaxial trichome production and the extent to which bracts lack adaxial trichomes varies in different ecotypes. The production of abaxial trichomes appears to be regulated by the age, rather than the size of the plant. This conclusion is based on the observation that mutations that affect either the rate (altered meristem programming1) or onset (paused) of leaf initiation respectively increase or decrease the number of leaves that lack abaxial trichomes, but have only a minor effect on the time at which the first leaf with abaxial trichomes is produced. The production of abaxial trichomes is coordinated with the reproductive development of the shoot as this trait is delayed by photoperiodic conditions and some mutations that delay flowering. The loss of adaxial trichomes is likely to be a consequence of floral induction, and is accelerated by terminal flower1-10, a mutation that accelerates inflorescence development. We demonstrate that gibberellins promote trichome production in Arabidopsis and present evidence indicating that abaxial trichome production is regulated by both the level of a trichome inducer and the competence of the abaxial epidermis to respond to this inducer.
César Vallejo: "El acento me pende del zapato" (1992)

Quiero comenzar declarando que la unica lectura de que me siento capaz cuando se trata de textos regionales, es la lectura diferencial. Es decir, la que busca en nuestros textos eso que los distingue de los producidos en otras regiones culturales. He escogido reiterar ante ustedes la lectura de un texto de Vallejo perteneciente a Poemas humanos, porque me parece ser de las mas violentamente capaces de presentar el caso diferencial. En efecto, espero que haciendo explicitos los intertextos vulgares que permiten leer acento me pende del zapato, quede claro que, por lo menos para este poema es verdadera la siguiente afirmacion: la poesia de Vallejo puede ser todo lo universal que se quiera, pero antes de acceder a eso universal que ella sin duda tiene, hay que leerla siguiendo los codigos regionales. El poema dice lo siguiente:
Adaptive motion-compensated filtering of noisy image sequences (1993)

The authors propose a novel adaptive spatiotemporal filter, called the adaptive weighted averaging (AWA) filter, for effective noise suppression in image sequences without introducing visually disturbing blurring artifacts. Filtering is performed by computing the weighted average of image values within a spatiotemporal support along the estimated motion trajectory at each pixel. The weights are determined by optimizing a well defined mathematical criterion, which provides an implicit mechanism for deemphasizing the contribution of the outlier pixels within the spatiotemporal filter support to avoid blurring. The AWA filter is therefore particularly well suited for filtering sequences that contain segments with abruptly changing scene content due to, for example, rapid zooming and changes in the view of the camera. The performance of the proposed AWA filter is compared with that of the spatiotemporal, local linear minimum mean square error (LMMSE) filtering. The results demonstrate that the proposed AWA filter-outperforms the LMMSE filter, especially in the cases of low signal-to-noise ratios and abruptly varying scene content.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Association of Single-Nucleotide Polymorphisms in Age-Related Macular Degeneration With Pseudodrusen (2018)

Among patients with neovascular AMD, the AMD risk alleles ARMS2 and HTRA1 were associated with an increased risk of pseudodrusen and the risk allele CFH Y402H was associated with lower risk of pseudodrusen, supporting findings from previous studies. Understanding the role of these SNPs in the development of pseudodrusen might improve our understanding of the pathogenesis of AMD and help develop future therapies.