Miracle-dz/UniFAR-FTUs huggingface dataset:
Shaping the repertoire of tumor‐infiltrating effector and regulatory T cells

Many tumors express antigens that can be specifically or selectively recognized by T lymphocytes, suggesting that T‐cell‐mediated immunity may be harnessed for the immunotherapy of cancer. However, since tumors originate from normal cells and evolve within the context of self‐tissues, the immune mechanisms that prevent the autoimmune attack of normal tissues function in parallel to restrict anti‐tumor immunity. In particular, the purging of autoreactive T cells and the development of immune‐suppressive regulatory T cells (Tregs) are thought to be major barriers impeding anti‐tumor immune responses. Here, we discuss current understanding regarding the antigens recognized by tumor‐infiltrating T‐cell populations, the mechanisms that shape the repertoire of these cells, and the role of the transcription factor autoimmune regulator (Aire) in these processes. Further elucidation of these principles is likely to be critical for optimizing emerging cancer immunotherapies, and for the rational design of novel therapies exhibiting robust anti‐tumor activity with limited toxicity.
Immune CD4+ T cells promote the clearance of influenza virus from major histocompatibility complex class II -/- respiratory epithelium

The experiments described establish that CD4+ T-cell-dependent effector mechanisms can eliminate an H3N2 influenza A virus from lung cells that are unable to express class II major histocompatibility complex (MHC) glycoproteins. Radiation chimeras were made by using CD4+ T cells and bone marrow from CD8-depleted, MHC class II +/+ mice and irradiated (950 rads) MHC class II -/- recipients. The influenza virus-specific CD4+ T-cell responses in these +/+-->-/- mice were not obviously different from those in the +/+-->+/+ controls: the cytokine profiles, the spectra of plasma cells producing the various immunoglobulin isotypes, and the frequencies of virus-specific CD4+ T cells were similar for the two groups. Expression of class II MHC glycoproteins on stimulator cells, B lymphocytes, and monocytes/macrophages is apparently sufficient for CD4+ T cells to terminate influenza virus infection of MHC class II -/- respiratory epithelium. A possible explanation is that the local spread of this lytic virus in the lung is limited by cytokines and/or antibody.
Confronting the social debate: A study of the distribution of Russian recreational properties in Eastern Finland

ABSTRACT Transborder property ownership is a growing trend in different parts of the world. In Finland, Russians make up the biggest group of foreign buyers. The article examines Russian recreational property purchases in Eastern Finland, where South Savo Region is subject to the heaviest flow of Russian purchasers. Russian purchases of second homes have been the subject of a broad social debate dominated by negative attitudes towards the phenomenon. Fears of place change and displacement have been among the main concerns. The authors reveal how arguments presented in the social debate on Russian ownership correspond to the distribution of Russian properties in South Savo. Statistics for the period 2003–2012 and GIS methods were used to analyse the distribution and density of Russian recreational properties in the region. Statistical modelling uncovered some factors that affected the location of the properties. The findings indicate that the arguments presented within the social debate have only partially derived from the distribution patterns of Russian properties. The authors conclude that a combination of factors, including distances from the border and services as well as preferences for waterside locations, have influenced the choice of location of Russian properties and led to concentrations in certain areas.
Age‐Related Changes in Ploidy Levels and Biochemical Parameters in Cardiac Myocytes Isolated from Spontaneously Hypertensive Rats

Postnatal growth of the mammalian ventricular myocyte is characterized by a brief period of hyperplasia followed by an extensive period of physiological hypertrophy. Using myocytes isolated from both Wistar-Kyoto and spontaneously hypertensive rats from fetus to 10 months old, we analyzed morphological, biochemical, and ploidy changes. Fetal myocytes from both spontaneously hypertensive and Wistar-Kyoto rats were mononuclear, diploid cells. By 4 weeks, adult binucleation levels (84% binuclear) were found, and myocytes pooled from both ventricles demonstrated nuclear ploidy shifts to tetraploid levels. However, analysis of myocytes isolated from left ventricle, right ventricle, and septum showed that nuclear polyploidation was confined to the right ventricle and septum, with few polyploid nuclei detected in the left ventricle. This pattern remained relatively constant through 10 months of age, although spontaneously hypertensive myocytes showed significantly more polyploidation than Wistar-Kyoto in all regions. Biochemical analysis of isolated myocytes substantiated the nuclear ploidy changes and demon-strated elevated protein and ribonucleic acid content in left ventricular myocytes without extensive polyploidation. Since cardiac hypertrophy, both physiological and pathological, is associated primarily with the left ventricle and occurs in the absence of significant ploidy changes, these findings suggest that a unique pattern of gene regulation may be ongoing in the left ventricle myocytes that is not present in the septum and right ventricle. These variations may be essential for cellular hypertrophy under normal and pathological conditions.
Metabolic and Morphologic Studies in Intraportal-Islet-Transplanted Rats

The intraportal injection of 350 to 1,000 isolated islets into streptozotocin-diabetic rats immediately normalized (∼ 24 hours) fasting plasma glucose and insulin levels. Polyuria, polydipsia, and hyperglucagonemia disappeared more gradually over a 2-to-12-week period—the time required for normalization varying with the severity of the diabetes and the number of islets transplanted. In long-term islet-transplanted rats (> five months), the hepatic insulin and glucagon reserves averaged 50 per cent and 25 per cent, respectively, of the corresponding normal pancreatic hormone content. Glucagon was increased slightly in the pancreas of streptozotocin-diabetic rats and decreased considerably in transplanted animals. However, total pancreatic glucagon (i.e. pancreatic and hepatic reserves) in transplanted animals was the same as the pancreatic content of normal control rats, indicating the presence of feedback control mechanism(s) in the regulation of pancreatic glucagon reserves. Long-term transplanted islets demonstrated well-granulated A-, B-, and D-cell movement out of the vascular space and the formation of narrow intercellular spaces and junctional complexes with surrounding hepatocytes.
Perioperative systemic chemotherapy in peritoneal carcinomatosis of lymph node positive colorectal cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the preferred treatment of peritoneal carcinomatosis (PC) of colorectal carcinoma. Patients with positive lymph node status have worse survival after CRS-HIPEC, which is probably due to higher rates of systemic failure. In this study, we analysed the effect of administration and timing of systemic chemotherapy on the outcome of lymph node positive colorectal carcinoma patients treated with CRS-HIPEC. PATIENTS AND METHODS A prospective database was reviewed to identify lymph node positive patients with PC treated with CRS-HIPEC within 1 year after primary tumour diagnosis between 2004 and 2012. Medical history of the patients was studied for the administration of perioperative systemic chemotherapy and follow-up. Outcome parameters were progression-free survival (PFS), overall survival (OS) and pattern of recurrence. RESULTS Seventy-three patients treated with CRS-HIPEC for PC from lymph node positive colorectal carcinoma were identified. Fourteen patients received pre-CRS-HIPEC chemotherapy only, 32 patients underwent post-CRS-HIPEC chemotherapy only, 9 patients received chemotherapy both pre- and post-CRS-HIPEC and 16 patients did not receive any systemic chemotherapy. Of the 47 patients who did not receive pre-CRS-HIPEC chemotherapy, 11 (23%) did not receive any chemotherapy due to major postoperative complications. PFS and OS were significantly higher in patients who received systemic chemotherapy (PFS: median 15 versus 4 months, P = 0.024; OS: median 30 versus 14 months, P = 0.015), although this difference was attenuated after adjustment for major complications. Different chemotherapy timings did not differ significantly in either survival or recurrence patterns. CONCLUSIONS In patients with PC from lymph node positive colorectal carcinoma, perioperative systemic chemotherapy is associated with increased OS and PFS, although this difference may be partly explained by the occurrence of major postoperative complication; with no evidence of difference in PFS, OS and systemic recurrence rate by timing of systemic chemotherapy.
Lessons on Ethnic Data Disaggregation from the "Count Me In" Campaign

Jude Paul Matias Dizon is a first-year HESA student. He received his B.A. in Development Studies with a minor in Asian American Studies from UC Berkeley in 2009. Jude’s experiences in community organizing greatly shape his interests in higher education. He would like to especially acknowledge and thank Erin Pangilinan and Oiyan Poon for their support and feedback on this article. Jude is inspired by the student leaders involved in the “Count Me In” campaign for their work to increase the visibility of Asian American and Pacific Islander students. Lessons on Ethnic Data Disaggregation from the “Count Me In” Campaign
Executive functions among individuals with methamphetamine or alcohol as drugs of choice: Preliminary observations

Substance dependent individuals (SDIs) are frequently, but not invariably, impaired on tasks of executive functions. In this study, we examine patterns of executive performance among subjects with different self-reported “drug of choice” (defined as substance used >80% of the time prior to abstinence). Subjects were 33 abstinent SDIs receiving inpatient treatment and 19 non-SDI normal controls (NC) well-matched on age, sex, ethnicity, and VIQ, who were assessed using the Iowa Gambling Task (GT) and a delayed non-match to sample task (DNM): measures of decision making and working memory, respectively. Seventeen SDIs identified alcohol (AL group) and 16 SDIs identified methamphetamine (METH group) as their drug of choice. Overall, the METH group performed more poorly than the NC and AL groups on both tasks, with the largest differences observed in working memory. The AL group was not significantly impaired overall compared to NCs on either task, but showed subtle abnormalities of GT performance similar to the METH group. These preliminary findings suggest that self-reported drug of choice on admission to treatment may be associated with different patterns of executive performance during early recovery.
Tuberculosis in Hospital Personnel

Abstract Tuberculosis (TB) skin testing practices and the prevalence and inherent risk of TB infection among hospital employees in 167 North Carolina (NC) hospitals were determined from a 79% (132/167) response to a tuberculosis screening questionnaire. Preemployment TB skin testing was performed by 98% of responding hospitals, primarily (87%) by the Mantoux method. TB skin test reactions of ≥ 10 mm were interpreted as significant by 72% and at the appropriate time interval of 48 to 72 hours after administration by 80%. The booster test was routinely performed in 12% of the hospitals. TB infection prevalence among new employees during 1983 was 6.3% (260/4137) in 30 hospitals supplying these data. A positive correlation was noted between employee infection prevalence and county TB case rates (P = .014). Skin test conversion data from 56 hospitals across the state revealed a five year mean conversion rate of 1.14% among 71,253 personnel. There was an association between the incidence of TB in the general population and the frequency of conversions among hospital employees in corresponding geographical regions. Similarly, the incidence of TB among approximately 100,000 NC hospital employees in 1983 and 1984 was less than the incidence in the general population. These associations suggest that the incidence of TB infection among hospital personnel may reflect the prevalence of tuberculosis in the community rather than an occupational hazard. Annual TB skin testing of hospital employees may be justified in eastern North Carolina where the incidence of tuberculosis (22-30 cases/ 100,000) is greater than the national average and where the risk of new TB infection among hospital employees is relatively common (≥1.5%).
Selection of Test Chemicals for the ECVAM International Validation Study on In Vitro Embryotoxicity Tests

The European Centre for the Validation of Alternative Methods (ECVAM) has sponsored a large international prevalidation and validation study of three embryotoxicity tests, involving embryonic stem cells, limb bud micromass cultures, and postimplantation whole-embryo cultures. The main objective of the study was to assess the performance of these in vitro tests in discriminating between non-embryo-toxic, weakly embryotoxic and strongly embryotoxic compounds. An initial part of the study was to select 20 test substances for the formal validation trial, conducted under blind conditions. A database of in vivo and in vitro developmental toxicity test results was compiled on 309 chemicals that had been used in previous validation studies, or suggested for such use, or that had good quality “segment II”-type in vivo data, or for which there were human data. From this database, a shortlist of about 30 candidates was constructed. Because the ECVAM study would not include metabolic activation, chemicals known to require activation for their developmental effects were excluded as candidates, although some known stable metabolites were included. Attempts were made: to include substances of diverse mechanism; to avoid overemphasis on pharmaceuticals; to avoid biologically inert substances as non-embryotoxicants; and to make the list different from those used previously. The candidates were of three categories: Class 3, strongly embryotoxic, was defined as developmentally toxic in all species tested, inducing multiple developmental effects, and with a high A/D ratio. Class 1, non-embryotoxic, was defined as not developmentally toxic at maternally toxic exposures, but which may show some minor embryo/fetal toxicity, which cannot be separated from maternal toxicity. Class 2, weakly embryotoxic, were chemicals of intermediate activity. From this candidate list, chemicals of known receptor (androgen, oestrogen, glucocorticoid, aryl hydrocarbon) mechanisms were excluded, on the basis that simple tests for such activity are already available. In addition, chemicals not freely available were excluded, and an emphasis on human data was applied. The final list of 20 chemicals was: Class 3 — 6-aminonicotinamide, 5-bromo-2′-deoxyuridine, hydroxyurea, methylmercury chloride, methotrexate, all-trans-retinoic acid; Class 2 — boric acid, dimethadione, lithium chloride, methoxyacetic acid, valproic acid (VPA), 2-propyl-4-pentynoic acid (4-yn-VPA), salicylic acid sodium salt; and Class 1 — acrylamide, D-(+)-camphor, dimethyl phthalate, diphenhydramine hydrochloride, 2-ethyl-4-methylpentanoic acid (isobutyl-ethyl-VPA), Penicillin G sodium salt, saccharin sodium hydrate.
Survival Strategy of Obligately IntracellularEhrlichia chaffeensis: Novel Modulation of Immune Response andHost CellCycles

ABSTRACT Ehrlichia chaffeensis is an obligatory intracellular bacterium which resides in an early endosome in monocytes. E. chaffeensis infection in a human monocyte cell line (THP1) significantly altered the transcriptional levels of 4.5% of host genes, including those coding for apoptosis inhibitors, proteins regulating cell differentiation, signal transduction, proinflammatory cytokines, biosynthetic and metabolic proteins, and membrane trafficking proteins. The transcriptional profile of the host cell revealed key themes in the pathogenesis of Ehrlichia. First, E. chaffeensis avoided stimulation of or repressed the transcription of cytokines involved in the early innate immune response and cell-mediated immune response to intracellular microbes, such as the interleukin-12 (IL-12), IL-15, and IL-18 genes, which might make Ehrlichia a stealth organism for the macrophage. Second, E. chaffeensis up-regulated NF-κB and apoptosis inhibitors and differentially regulated cell cyclins and CDK expression, which may enhance host cell survival. Third, E. chaffeensis also inhibited the gene transcription of RAB5A, SNAP23, and STX16, which are involved in membrane trafficking. By comparing the transcriptional response of macrophages infected with other bacteria and that of macrophages infected with E. chaffeensis, we have identified few genes that are commonly induced and no commonly repressed genes. These results illustrate the stereotyped macrophage response to other pathogens, in contrast with the novel host response to obligate intracellular Ehrlichia, whose survival depends entirely on a long evolutionary process of outmaneuvering macrophages.
Echocardiographic diagnosis of pulmonary artery occlusion pressure elevation during weaning from mechanical ventilation*

Objective:Weaning-induced pulmonary edema is a cause of weaning failure in high-risk patients. The diagnosis may require pulmonary artery catheterization to demonstrate increased pulmonary artery occlusion pressure (PAOP) during weaning. Transthoracic echocardiography can estimate left ventricular filling pressures using early (E) and late (A) peak diastolic velocities measured with Doppler transmitral flow, and tissue Doppler imaging of mitral annulus velocities including early (Ea) peak diastolic velocity. We tested the hypothesis that E/A and E/Ea could be used to detect weaning-induced PAOP elevation defined by a PAOP ≥18 mm Hg during a spontaneous breathing trial (SBT). Measurements and Main Results:We included 39 patients who previously failed two consecutive SBTs. A third SBT was performed over a maximum 1-hour period using a T-piece. The PAOP, E/A, and E/Ea were measured before and during this SBT. Receiver operating characteristic curves were constructed to determine the optimal sensitivity and specificity values of E/A and E/Ea obtained at the end of the SBT for predicting a weaning-induced PAOP elevation. Weaning-induced PAOP elevation occurred in 17 patients. A value of E/A >0.95 at the end of the SBT predicted weaning-induced PAOP elevation with a sensitivity of 88% and a specificity of 68%. A value of E/Ea >8.5 at the end of the SBT predicted weaning-induced PAOP elevation with a sensitivity of 94% and a specificity of 73%. The combination of E/A >0.95 and E/Ea >8.5 predicted a weaning-induced PAOP elevation with a sensitivity of 82% and a specificity of 91%. Conclusion:At the end of an SBT, the combination of E/A >0.95 and E/Ea >8.5 measured with transthoracic echocardiography allowed an accurate noninvasive detection of weaning-induced PAOP elevation.
Free dimensions-an effective approach to achieving fault tolerance in hypercube

In the n-dimensional hypercube, Q/sub n/, for large n, faults can occur with relatively high probability. How to use the inherent redundancy present in the hypercube to obtain fault tolerance is discussed, along with computing in faulty hypercubes. The authors study the fault tolerance independently present in hypercubes by defining and using the concept of free dimensions. Briefly, in Q/sub n/, a dimension is said to be free if no pair of nodes across the dimension link are both faulty. Efficient algorithms are presented for finding free dimensions, given a set of faulty nodes, and it is shown that at least n-f+1 free dimensions exist with f<or=n faulty nodes. Free dimensions can be used to partition Q/sub n/ into subcubes such that each subcube contains at most one fault. Such a partitioning helps in achieving fault tolerance via emulation, embedding, and reconfiguration. It also helps in designing efficient routing and broadcasting algorithms in faulty hypercubes. <<ETX>>
Factors associated with HIV/AIDS high-risk behaviours among female injection drug users

Abstract This study examined factors associated with reporting engaging in HIV/AIDS high-risk behaviours at two different time points spaced one year apart for a sample of 185 women who were active injection drug users (IDUs). The high-risk behaviours included injecting drugs in the past six months, having shared needles in the past six months and having engaged in unprotected sexual activity in the past thirty days. Through logistic regression modelling it was identified that living with a spouse at year one was significantly and positively associated with high-risk behaviours at both time points. Being prescribed medications for psychological or emotional problems as well as testing positive for the HIV/AIDS virus were significantly and negatively associated with reporting high-risk behaviours at both time points. These results suggest that spousal relationships may play an important role in HIV/AIDS high-risk behaviours of women drug users. An implication of this study is the need to focus on how spousal relationships and issues such as gender and empowerment should be incorporated into the design and implementation of HIV/AIDS prevention and treatment programs. The benefits of comprehensive mental health diagnosis and treatment services as well as HIV testing in reducing harm to female IDUs and their partners are also discussed.
Differential responsiveness of cultured suckling and adult rat hepatocytes to growth‐promoting factors: Entry into s phase and mitosis

The capacity of suckling and adult rat hepatocytes in culture to enter into S phase and mitosis in response to EGF, insulin, and glucagon was measured. Both cell types were isolated in high yield and purity and cultured in the absence of serum under identical conditions. At the time of isolation, suckling rat hepatocytes were all diploid and in the G1 phase of the cell cycle. Adult rat hepatocytes constituted a population of mixed ploidy level, as shown by flow cytometry. Upon stimulation, both suckling and adult rate hepatocytes entered S phase after a minimum lag period of 24 h. For suckling rat hepatocytes EGF was required, but its stimulating action was dependent on insulin and/or glucagon. In contrast, adult rat hepatocytes entered into S phase in response to EGF alone; insulin and glucagon did not significantly potentiate its effect. Under optimal hormonal stimulation for entry into S phase a large proportion of suckling rat hepatocytes underwent mitosis, whereas only a few mitoses were observed in the case of adult rat hepatocytes. Therefore, there is a differential response of suckling and adult rat hepatocytes to growth factors which correlates with ploidy level, and this difference may be associated with the degree of maturation.